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      The 33 rd Great Wall International Congress of Cardiology Asian Heart Society Congress 2022

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      Cardiovascular Innovations and Applications
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            BASIC AND TRANSLATIONAL MEDICINE

            BASIC RESEARCH OF CARDIOVASCULAR DISEASE
            GW33-e0014
            Intensive exercise induces atrial fibrillation in an autophagy- necroptosis-inflammation dependent manner

            Yuping Fu1, Yudi Zhang1, Haoyu Gong1, Xinghua Qin2, Qiangsun Zheng1

            1The Second Affiliate Hospital of Xi’an Jiaotong University

            2Northwestern Polytechnical University

            OBJECTIVES The role of exercise in atrial fibrillation (AF) is complicated, presenting a J-shaped phenomenon which means intensive exercise raises the risk of AF, whereas the underlying mechanisms haven’t been fully illustrated. Emerging evidence reveals altered autophagy in AF patients but the role of autophagy in AF genesis is still controversial, thus requiring further exploration.

            METHODS Male C57BL/6J mice were divided into sedentary group (Sed), moderate-intensity exercise group (MIE) and high-intensity exercise group (HIE) to investigate the role of exercise intensity and time on AF and underlying mechanisms. Then verifying in AF patients and using 3-methyladenine (3-MA) to inhibit autophagy in mice, we explored the relationship between autophagy and AF. AF inducibility test was performed by transesophageal atrial pacing. Atrial electrical remodeling was evaluated by ion channel genes and connexins expression. And atrial structural remodeling was assessed by echocardiographic measurement of left atrial diameter, Masson trichrome and Sirius red staining of atrial fibrosis, respectively. Western blot, real-time PCR, TUNEL staining and histological staining were performed to reveal molecular mechanisms.

            RESULTS AF frequency and duration increased in a swim time course-dependent manner in HIE group and the differences were most significant at the 8th week, while in MIE group, swim training protected mice against AF at the 3rd week yet this effect gradually disappeared as swim time increasing. Thus, we established an intensive exercise-induced AF mouse model by 8 weeks of high-intensity swim training. Real-time PCR results showed altered ion channels expression, especially K+-related ion channels in intensively exercised mice and western blot analysis showed downregulated connexin 40 and 43, indicating obvious atrial electrical remodeling. Besides, we observed left atrial enlargement and atrial fibrosis in HIE group, consistent with AF-related atrial structural remodeling. Furthermore, to investigate the mechanisms, we found upregulated atrial pro-inflammatory cytokines especially IL-18 but decreased ventricular inflammation, apoptosis and oxidative stress after swim training, suggesting a reserved cardioprotective effect on the ventricles of intensive exercise despite atrial inflammation. Of note, apparently activated atrial autophagy was demonstrated both in AF patients and intensively exercised mice. Accordingly, inhibiting autophagy via 3-MA partially reversed exercise-induced AF susceptibility and atrial fibrosis, meanwhile blocking necroptotic signaling and downregulating pro-inflammatory cytokines activated by excessive exercise, suggesting a critical role of autophagy in AF genesis, probably via activating necroptosis-inflammation signaling.

            CONCLUSIONS Our results identify autophagy as a novel potential therapeutic target for AF in endurance athletes or even other AF population and highlight autophagy-necroptosis-inflammation axis as the underlying regulate mechanism in this process.

            GW33-e0056
            Endothelial Foxp1 restricts tumor angiogenesis and protects against tumor growth through Hif1α-Hk2 glycolysis signal pathway

            Jingjiang Pi

            Shanghai East Hospital, Tongji University School of Medicine

            OBJECTIVES Angiogenesis is critical for physiological and pathological processes, Endothelial cells (ECs) rely on glycolysis for energy production to maintain vascular homeostasis and normalization of hyperglycolysis.

            METHODS We analyzed the TCGA database of the NIH Cancer Genome Atlas Program and found reduced Foxp1 expression in lung carcinoma. Immunostaining demonstrated that the reduced expression was more restricted at tumor vascular ECs, and EC-Foxp1 deletion mice exhibited a significant increase of xenograft tumor angiogenesis for tumor growth. Through data mining of ECs-Foxp1 Chip sequence results and confirmed by ChIP and luciferase assays, we identified hypoxia-inducible factor 1 (Hif1α) as the Foxp1 target gene, for the regulation of EC glycolytic metabolism to govern tumor angiogenesis.

            RESULTS Moreover, we identified Hk2 as the Hif1α target gene for regulation of tumor EC metabolism. RGD-peptide magnetic nanoparticles EC target delivery of Hif1α-siRNAs or Hk2-siRNAs reduced the hyperglycolysis to suppress ECs growth. Finally, simvastatin, a strong inducer of EC-Klf2-Foxp1, as well as EC-Foxp1 gain-of-function, significantly reduced the hyperglycolysis of ECs and inhibited the pro-angiogenic activity to protect against tumor growth.

            CONCLUSIONS Foxp1 regulation of a Hif1α-Hk2 pathway in the endothelium advances our understanding of EC metabolism for tumor angiogenesis, and meanwhile provides evidence for future therapeutic intervention of hyperglycolysis in tumor ECs for suppression of tumor growth.

            GW33-e0059
            CB1R-stabilized NLRP3 inflammasome drives antipsychotics cardiotoxicity

            Liliang Li1, Yunzeng Zou2

            1Department of Forensic Medicine, School of Basic Medical Sciences, Fudan University

            2Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University

            OBJECTIVES Long-term use of antipsychotics is a common cause of myocardial injury and even sudden cardiac deaths. The mechanisms underlying antipsychotics cardiotoxicity remain largely unknown. The present study aimed to investigate the toxic effects of common antipsychotics on hearts and designed a cell-based small-molecule compound screen to identify cardioprotectants during antipsychotics use.

            METHODS Representative antipsychotics including clozapine (Clz) and olanzapine (Olz) were intraperitoneally injected into mice for 7, 14, and 21 days, respectively, with doses comparable to clinical use. Analysis of left-ventricle function, QT interval, heart histopathology and myocardial injury markers were conducted. Transcriptomic and proteomic analyses were conducted to identify enriched molecular pathways.

            RESULTS Olz and Clz time-dependently concentrated in hearts and induced cardiotoxicity preceding development of glycolipid metabolic disorder and other solid organs dysfunction. NLRP3 inflammasome-mediated pyroptotic cell death, but not other types of programmed cell death, predominantly contributed to multiple antipsychotics cardiotoxicity. Pyroptosis-based small-molecule compound screening identified antagonists of cannabinoid receptor 1 (CB1R) as potent inhibitors of the NLRP3 inflammasome activity. Mechanistically, antipsychotics competitively bond to the CB1R and led to CB1R translocation to plasma via its sites S426/S430. Internalized CB1R physically interacted with the NLRP3 inflammasome via amino acid residues 177–209, rendering stabilization of the inflammasome. Knockout of Cb1r or specific antagonists of CB1R significantly alleviated antipsychotic-induced cell pyroptosis and cardiotoxicity. In turn, adeno associated virus-delivered Cb1r overexpression promoted pyroptosis in wild-type mice but not in Gsdmd-knockout mice. Multi-organ based investigation revealed no additional toxicity of newer-generation CB1R antagonists. In human heart samples, the expression of CB1R and NLRP3 inflammasome components positively correlated with the extent of antipsychotics-induced myocardial injuries.

            CONCLUSIONS Antipsychotics prominently induce NLRP3 inflammasome-dependent pyroptotic myocyte death by directly targeting CB1R. Small-molecule inhibitors targeting the CB1R/NLRP3 signaling represent attractive approaches to rescue cardiac side effects of antipsychotics.

            GW33-e0060
            Nesfatin-1 protects cardiac damages in a streptozotocin-induced diabetes mice

            Zhenhuan Chen, Gulao Zhang, Fanzhi Zhang, Yu Tao, Hengli Lai

            Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College

            OBJECTIVES Nesfatin-1 is a novel anorexigenic peptide that has been recently found to possess an antihyperglycemic effect. However, the role of nesfatin-1 in diabetic cardiomyopathy (DC) has not been fully investigated.

            METHODS The aim of this article was to bring a different perspective on the effect of nesfatin-1 on diabetes-associated cardiac dysfunction in a mice model.

            RESULTS In this study, we found that nesfatin-1 expression was significantly downregulated in a high-fat diet (HFD) reptozotocin (STZ)-induced diabetic mice. Nesfatin-1 treatment elevated the insulin sensitivity and attenuated the diabetic dyslipidemia with the reduced levels of total cholesterol (TC), triglycerides (TAG), low-density lipoprotein (LDL) in diabetic mice. Nesfatin-1 improved the diabetes-caused alternations in cardiac function and structure, as proved by reduced heart rate and mean arterial pressure (MAP), decreased creatine kinase (CK)-MB and aspartate aminotransferase (AST) levels, as well as mitigated myocardial hypertrophy. Nesfatin-1 exerted an antioxidant activity in STZ-induced diabetic mice with decreased ROS and MDA levels, as well as increased SOD and GSH levels in heart tissues. Nesfatin-1 also attenuated the cardiac inflammation, as shown by decreased cardiac and plasma IL-1β and TNF-α levels. In addition, we also found that p38 MAPK was markedly activated in diabetic mice, while nesfatin-1 significantly inhibited its activation.

            CONCLUSIONS Collectively, nesfatin-1 exerted protective effects against diabetes-mediated cardiac damages via regulating p38 MAPK. These results indicated that targeting nesfatin-1 might be a good approach for therapeutic intervention of DC.

            GW33-e0071
            Single-cell RNA sequencing of the rat carotid arteries uncovers potential cellular targets of NIH

            Xiao-Fei Gao, Ai-Qun Chen, Zhen Ge, Jun-Jie Zhang

            Nanjing First Hospital

            OBJECTIVES In-stent restenosis (ISR) remains an Achilles heel of drug-eluting stents despite technical advances in devices and procedural techniques. Neointimal hyperplasia (NIH) is the most important pathophysiological process of ISR. The present study mapped normal arteries and stenotic arteries to uncover potential cellular targets of neointimal hyperplasia.

            METHODS By comparing the left (control) and right (balloon injury) carotid arteries of rats, we mapped 11 clusters in normal arteries and 11 mutual clusters in both the control and experimental groups. Different clusters were categorized into 6 cell types, including vascular smooth muscle cells (VSMCs), fibroblasts, endothelial cells (ECs), macrophages, unknown cells and others. An abnormal cell type expressing both VSMC and fibroblast markers at the same time was termed a transitional cell via pseudotime analysis.

            RESULTS Due to the high proportion of VSMCs, we divided them into 6 clusters and analyzed their relationship with VSMC phenotype switching. Moreover, N-myristoyltransferase 1 (NMT1) was verified as a credible VSMC synthetic phenotype marker. Finally, we proposed several novel target genes by disease susceptibility gene analysis, such as Cyp7a1 and Cdk4, which should be validated in future studies.

            CONCLUSIONS Maps of the heterogeneous cellular landscape in the carotid artery were defined by single-cell RNA sequencing and revealed several cell types with their internal relations in the ISR model. This study highlights the crucial role of VSMC phenotype switching in the progression of neointimal hyperplasia and provides clues regarding the underlying mechanism of NIH.

            GW33-e0072
            Therapeutic exosomes in prognosis and developments of coronary artery disease

            Ai-Qun Chen, Xiao-Fei Gao

            Nanjing First Hospital

            OBJECTIVES Exosomes, with an diameter of 30∼150 nm, could be released from almost all types of cells, which contain diverse effective constituent, such as RNAs, proteins, lipids, and so on. In recent years, exosomes have been verified to play an important role in mechanism, diagnosis, treatment, and prognosis of cardiovascular disease, especially coronary artery disease (CAD).

            CONCLUSIONS Moreover, it has also been shown that exosomes derived from different cell types have various biological functions based on the cell stimulation and microenvironment. However, therapeutic exosomes are currently far away from clinical translation, despite it is full of hope. In this review, we summarize an update of the recent studies and systematic knowledge of therapeutic exosomes in atherosclerosis, myocardial infarction, and in-stent restenosis, which might provide a novel insight into the treatment of CAD and promote the potential clinical application of therapeutic exosomes.

            In recent years, the therapeutic effect of exosomes on heart diseases has been gradually discovered. We have summarized the progress in studying exosomes as drug delivery vehicles. Before entering the clinical transformation, a perfect therapeutic concept of exosomes is essential, and pioneering in the field of exosomes is tumor-related studies. We can draw on tumor-related studies to optimize treatment regimens. Certainly, CAD-targeted treatment options also need to take notice of the cardiovascular lineage specificity.

            Exosomes, as natural drug delivery vehicles, have excellent biocompatibility and targeting properties. We have discovered the potential of exosomes in the treatment of CAD based on existing research. However, exosomes still face huge resistance in clinical transformation. Moreover, we hope that the optimization of therapeutic exosomes is getting better and enter the clinical application stage as soon as possible.

            GW33-e0086
            TRIM21 aggravates cardiac injury after myocardial infarction via polarizing macrophages into M1 phenotype

            Zhiqiang Li, Xiangdong Liu, Mengmeng Gong, Xingxu Zhang, Xiaoming Qin, Wenming Zhang, Jiachen Luo, Baoxin Liu, Yidong Wei

            Shanghai Tenth People’s Hospital

            OBJECTIVES Macrophage polarization followed by myocardial infarction (MI) is essential for the regulation of inflammation and scar formation. Tripartite motif-containing protein 21 (TRIM21), a member of E3 ubiquitin ligases, is a crucial mediator in the process of inflammation and heart failure. However, the functions of TRIM21 in modulating post-MI inflammation and macrophage polarization remain elusive.

            METHODS We generated global knockout mice to investigate the effects of TRIM21 after MI. The role of TRIM21 on macrophage polarization was tested with a lentivirus system. Moreover, we conducted RNA-sequencing to identify the underlying molecular mechanism contributing to TRIM21 effects.

            RESULTS The levels of TRIM21 were significantly reduced in mice after MI. After TRIM21 knockout (KO), we discovered mice with improved cardiac remodeling, as determined by a markedly decrease in mortality, increased wall thickness, and improved cardiac function compared with wild-type (WT) MI mice. TRIM21 depletion also decreased the post-MI apoptosis and DNA damage in the hearts of mice. Moreover, the accumulation of M1 phenotype macrophages in KO infarcted hearts decreased more than that of WT mice. Mechanistically, TRIM21 depletion orchestrates the process of macrophage polarization via PI3K/Akt signaling pathway.

            CONCLUSIONS TRIM21 mediates the inflammatory response and cardiac remodeling after MI by regulating macrophage polarization to the M1 phenotype through PI3K/Akt signaling pathway.

            GW33-e0090
            Protective effect of MG53 combined with BMSC transplantation on myocardial infarction

            Xuewei Xia, Chunyu Zeng

            Department of Cardiology, Chongqing Institute of Cadiology & Chongqing Cardiovascular Clinical Research Center, Daping Hospital, Third Military Medical University

            OBJECTIVES Stem cell transplantation in the treatment of myocardial infarction has had modest success. However, the hypoxic-ischemic microenvironment post myocardial infarction is not conducive to the survival of stem cells, resulting in a large number of apoptosis of transplanted stem cells, which seriously limits its therapeutic effect. Studies showed that MG53 has protective effect on cardiac injury by improving cardiomyocytes survival, repressing inflammation and apoptosis. We investigated the effect of MG53 over-expressing in mouse bone marrow mesenchymal stem cells (BMSCs) on the transplantation of BMSCs into the infarcted myocardium.

            METHODS MG53 and vector lentivirus were transfected into BMSC. BMSC apoptosis was observed after hypoxia and H2O2 stimulation in vitro. MG53 over-expressing or control BMSC were transplanted into mice post myocardial infarction.

            RESULTS Apoptosis in both BMSCs and myocardium transplanted with BMSCs were significantly reduced in MG53 over-expressing group than in control group. The scar size was limited, while the cardiac function was improved by transplantation of MG53 over-expressing BMSCs, as compared with control group. The expression of PHD3 was increased by hypoxia treatment but reduced by MG53 over-expression. MG53 binds to PHD3, promotes PHD3 ubiquitination and degradation, resulting in increased Hif2α levels and decreased apoptosis of BMSC. In addition, the paracrine effect of BMSCs was enhanced by MG53 over-expression, among these paracrine factors, the MG53 are with higher levels. Moreover, the culture supernatant of MG53 over-expression BMSC also had protective effect on myocardial infarction, and the protective effect was weakened after neutralization of MG53.

            CONCLUSIONS MG53 transfection can promote the survival of BMSC, enhance its paracrine secretion, and protect the function of myocardial cells in mice with myocardial infarction. MG53 promotes the survival of BMSC by degrading PHD3 and increasing the expression of Hif2α. Over-expression of MG53 in stem cells may be a novel strategy to enhance the efficacy of stem cell therapy after myocardial infarction.

            GW33-e0093
            LncRNA FGD5-AS1 aggravates myocardial ischemia-reperfusion injury by sponging miR-129-5p

            Ming Lou1, Peng Wei2, Zhi Feng Dong2

            1Department of Cardiology, Xuzhou Central Hospital, The Affiliated Xuzhou Hospital of Medical School of Southeast University

            2Department of Cardiology, Shanghai Jiao Tong University Affliated Sixth People’s Hospital

            OBJECTIVES LncRNA FGD5-AS1 has been found to regulate the pathogenesis of many human diseases. This study aims to elucidate the function of lncRNA FGD5-AS1 and the regulatory mechanism of lncRNA FGD5-AS1/miR-129-5p in myocardial ischemia-reperfusion (I/R) injury.

            METHODS Myocardial I/R injury mice model and H/R treated H9c2 cells were established. RT-qPCR and Western blot analysis were used to detect the mRNA and protein expression. Cell viability was detected by MTT assay. Dual luciferase reporter assay was applied to confirm the relationship between lncRNA FGD5-AS1 and miR-129-5p. Data were analyzed SPSS 19.0 and expressed as mean±SD. Graphs are made by Graphpad Prism 6. Student t-test was adopted to compare the difference between two groups, and multiple comparison was performed by one-way analysis of variance followed by Tukey’s post hoc test. P<0.05 indicates statistically significant difference.

            RESULTS LncRNA FGD5-AS1 was upregulated in myocardial I/R injury mice models and H/R treated H9c2 cells. Functionally, knockdown of lncRNA FGD5-AS1 promoted cell viability and inhibited apoptosis in H/R treated H9c2 cells. In addition, lncRNA FGD5-AS1 directly targets miR-129-5p. And upregulation of lncRNA FGD5-AS1 weakened the protective effect of miR-129-5p on myocardial I/R injury.

            CONCLUSIONS LncRNA FGD5-AS1 aggravates myocardial I/R injury by downregulating miR-129-5p.

            GW33-e0128
            Biomimetic mineralization of nanoceria alleviates isoproterenol- induced myocardial impairment by regulating mitochondrial oxidative stress

            Yunpeng Zhang1, Shifeng Cheng2, Qingling Zhang1, Jing Peng2, Yang Zhao2, Tong Liu1

            1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, People’s Republic of China

            2Department of Radiology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin 300211, People’s Republic of China

            OBJECTIVES The exact evidence has indicated that concentrations of catecholamines are elevated in the development of chronic heart failure (CHF). Isoproterenol (ISO), one of the catecholamine adrenergic receptor agonists, has been proved to cause myocardial necrosis, cardiac hypertrophy, fibroblast proliferation and abnormality of cardiac function. Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of ISO-induced CHF. Cerium oxide nanoparticles (NPs) recently have received extensive attention in biomedical applications due to their excellent antioxidation performance. The biomineralization-based synthesis method is green, environmentally friendly, simple and efficient compared to traditional methods. Herein, we develop a novel therapeutic nanoparticle via the biomineralization process and assessed its effectiveness for ISO-induced CHF.

            METHODS We synthesized albumin-based cerium oxide nanoparticles (CeO2@BSA) via a biomineralization process and polyethylene glycol (PEG) modified hydrophobic cerium oxide NPs (CeO2@PEG) as a comparison. Then the physicochemical and biological properties of NPs were characterized. The Ce content in the purified solution was determined by an X Series quadrupole inductively coupled plasma mass spectrometry (ICP-MS) instrument. Cellular uptake, cytotoxicity test, intracellular mitochondrial membrane potential (MMP) and reactive oxygen species (ROS), were verified with H9c2 cell lines. Thereafter the distribution of CeO2@BSA in C57BL/6J mouse ventricular tissue cells were observed by transmission electron microscope (TEM) and optical in vivo Imaging. The cardiac function of C57BL/6J male mice was evaluated. Fibrosis for assessment of myocardial structural remodeling was stained by Masson. Finally, the histocompatibility of CeO2@BSA was evaluated.

            RESULTS TEM revealed the CeO2@BSA are ≈2–4 nm in diameter and remain stable in deionized water. X-ray diffraction and X-ray photoelectron spectroscopy characterized the other properties successfully. MTT assay show that H9c2 cell viabilities were not influenced by CeO2@BSA even at high doses of Ce of up to 200 μM and CeO2@BSA had better efficacy and better biocompatibility compared to CeO2@PEG. H2O2 treatment led to increased ROS and decreased intracellular MMP in H9c2 cells. CeO2@BSA and CeO2@PEG improved the above changes. TEM found CeO2@BSA both in cytoplasm and mitochondrion in mice ventricular at 12 hours after injection through the tail vein and lasting ≈24 hours by optical in vivo Imaging. ISO mice showed increased myocardial fibrosis, abnormality of diastolic and systolic functions. All these abnormal changes were improved in the ISO+CeO2@BSA group but none significant improvement was observed in group ISO+CeO2@PEG however. Finally, CeO2@BSA show excellent biosafety after 14 days treatment.

            CONCLUSIONS These consistent biochemical and histopathological results suggest that, biomimetic mineralization of CeO2@BSA could be used as effective antioxidant in prophylactic protocols for management of cardiac disorders associated with oxidative stress. Compared with PEG modification, biomimetic mineralization shows advantages such as narrow size distribution, good biocompatibility, high stability and ability to control drug release.

            GW33-e0151
            Quercetin protects endothelial function from inflammation induced by localized disturbed flow by inhibiting NRP2

            Feng Wang, Junjie Zhang

            Nanjing First Hospital

            OBJECTIVES The present research aims to elucidate the mechanism underlying the regulation of Neuropilin (NRP) 2 under DF in endothelial cells (ECs) in an inflammatory state.

            METHODS The mRNA and protein levels of NRP family members were observed by shear stress stimulation, and were verified in animal and human tissue samples. Possible transcription factors were predicted using a database and verified by luciferase reporting assay and chip-QPCR assay. The model of deranged flow in mice was established by carotid artery ligation. Quercetin and NRP2 adeno-associated virus were used to observe the inflammatory level of endothelial cells in the disturbed flow area.

            RESULTS We observed that NRP2 expression was significantly upregulated in DF-stimulated human umbilical vein endothelial cells (HUVECs). Knockdown of NRP2 in HUVECs significantly ameliorated cell inflammation induced by DF. In addition, quercetin inhibited NRP2 expression as well as endothelial inflammation. Animal experiments suggested that NRP2 knockdown or intraperitoneal injection of quercetin affected the expression of inflammation-related genes. Moreover, the upstream transcription factor GATA2 was found to regulate NRP2 transcription by binding to the −1100 to +100 bp region of the NRP2 promoter.

            CONCLUSIONS These findings suggest that NRP2 plays an essential proinflammatory role and that NRP2 is a promising therapeutic target for the treatment of atherosclerotic disorders.

            GW33-e0157
            Endothelial PHACTR1 promotes endothelial activation and atherosclerosis by repressing PPARγ activity under disturbed flow

            Dongyang Jiang1, Hao Liu1, Guofu Zhu1, Xiankai Li1, Linlin Fan1, Faxue Zhao1, Chong Xu1, Shumin Wang2, Xiangbin Xu2, Edward A. Fisher3, Junbo Ge1, Yawei Xu1, Jinjiang Pang2

            1Department of Cardiology, Pan-Vascular Research Institute, Shanghai Tenth People’s Hospital, Tongji University School of Medicine

            2Aab Cardiovascular Research Institute, Department of Medicine and Dentistry, University of Rochester, Rochester

            3Division of Cardiology, Department of Medicine, New York University School of Medicine

            OBJECTIVES Numerous genome-wide association studies revealed that SNPs at phosphatase and actin regulator 1 (PHACTR1) locus are strongly correlated with coronary artery disease (CAD). However, the mechanism linking these variants to CAD remains uncertain. Here, we identified PHACTR1 as the causal gene and demonstrated biological functions and molecular mechanisms of endothelial PHACTR1 in atherosclerosis.

            METHODS We generated global (Phactr1 −/− ) and endothelial cell (EC)-specific (Phactr1ECKO ) Phactr1 knockout mice and crossed these mice with apolipoprotein E-deficient (Apoe −/− ) mice. Atherosclerosis models were built by feeding the high-fat/high-cholesterol (HF-HC) diet for 12 weeks or partially ligating carotid arteries combined with a 2-week HF-HC diet. Atherosclerotic lesions were analyzed in whole aorta, aortic sinus or ligated carotid arteries. PHACTR1 localization was identified by immunostaining of overexpressed PHACTR1 in human umbilical vein endothelial cells (HUVECs) exposed to different types of flow. The molecular function of endothelial PHACTR1 was explored by RNA-seq using EC-enriched mRNA from global or EC-specific Phactr1 knockout mice. Endothelial activation was evaluated in HUVECs transfected with siRNA targeting PHACTR1 and in Phactr1ECKO mice after partial carotid ligation.

            RESULTS Global or EC-specific Phactr1 deficiency significantly inhibited atherosclerosis in regions of disturbed flow. PHACTR1 was enriched in ECs and located in the nucleus of disturbed flow area but shuttled to cytoplasm under laminar flow in vitro. RNA-seq using EC-enriched RNA showed that Phactr1 depletion affected vascular function and peroxisome proliferator-activated receptor gamma (PPARγ) was the top transcription factor regulating differentially expressed genes. PHACTR1 functioned as a PPARγ transcriptional corepressor by binding to PPARγ through the corepressor motifs. PPARγ activation protects against atherosclerosis by inhibiting endothelial activation. Consistently, PHACTR1 deficiency remarkably reduced endothelial activation induced by disturbed flow in vivo and in vitro. PPARγ antagonist GW9662 abolished the effects of Phactr1 knockout on EC activation and atherosclerosis in vivo.

            CONCLUSIONS Our results identified endothelial PHACTR1 as a novel PPARγ corepressor to promote atherosclerosis in disturbed flow region. Endothelial PHACTR1 is a potential therapeutic target for atherosclerosis treatment.

            GW33-e0159
            A lymph node-targeted drug delivery system for effective immunomodulation to prolong the long-term survival of heart transplantation

            Yanjia Che

            Renmin Hospital of Wuhan University

            OBJECTIVES Despite scientific and clinical advances in cardiac transplant surgery and immune regulation, the chronic rejection response and the ensuing side effects of systematic administration of immunosuppressant have been the main obstacles for heart allograft and patient survival. In addition, the development of xenotransplantation also urgently requires more efficient immune regulation strategies with minimized effects of immunosuppression. To develop more effective immune regulation strategies and minimize the side effects associated with long-term use of immunosuppressive drugs are of critical importance for improved prognosis and prolongation of survival time. The purpose of this study is to develop an aptamer functionalized lymph node (LN) targeted drug delivery system with high targeting efficiency and ideal biocompatibility to effectively prolong the long-term survival after heart transplantation.

            METHODS First, we synthesized the FTY720 loaded nanoparticles-FTY720@NP and lymph node targeted FTY720 loaded nanoparticles-FTY720@TNP using the biotin-avidin interaction connected the CCL21-aptamer with the particles. In vivo fluorescence imaging was used to verify the ability of FTY720@TNP to target lymph nodes. We designed the hybrid nanoparticles loading the novel immunosuppressant-FTY720 in the model of full-MHC mismatch acute heart transplantation and analyzed the immune infiltration of allografts. Then we transplanted the hearts of C57/Bm12 mice were transplanted into C57BL/6 mice, in this chronic heart transplantation model, we explored the role of FTY720@TNP in preventing CAV, and we analyzed the CD4+Teff cells, CD8+Teff cells and CD4+Tregs cells of draining the lymph nodes and spleens derived from recipients by FCM.

            RESULTS In vivo live flurorescence imaging studies confirmed the lymph-targeting capability of the targeting drug delivery system (FTY720@TNP) using the MHCII fully mismatch heart transplantation model. FTY720@ NP suppressed acute allografts response and significantly reduced the frequency the effector/memory T cells but increased the generation of Treg cells and in chronic heart transplantation model, LN-targeted FTY720@TNP prolongs allograft survival and improve the CAV. Prolongation of chronic graft survival treated by FTY720@TNP relies primarily on increasing the Treg/Teff ratio in draining LNs.

            CONCLUSIONS In this experiment, we developed a new draining lymph node targeted drug delivery system that targets CCL21 expressed by high endothelial venules and fibroblastic reticular cells of the lymphoid T cell rich zones of lymph nodes. The application of CCL21 aptamer can drive the nanoparticles into the T cell rich area of lymph nodes. We demonstrate that FTY720@TNP can efficiently deliver the novel immunosuppressant FTY720 to draining lymph nodes, thereby alleviating CAV in chronic transplant rejection. Our aptamer functionalized lymph node targeted drug delivery system can effectively deliver the immunotherapeutic drug to the draining lymph nodes to relieve immune rejection locally and thereby minimize the side effects associated the immunosuppressant. This study provides a promising strategy to overcome the key difficulties encountered in heart transplantation, which is also applicable for other organ transplantations.

            GW33-e0185
            The molecular mechanisms of catecholaminergic polymorphic ventricular tachycardia

            Tingting Lv, Siyuan Li, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal inherited arrhythmia with an estimated population prevalence of 1:10,000. CPVT is characterized by polymorphic ventricular arrhythmias that are triggered by catecholamines released during exercise, stress or sudden emotion in individuals with structurally normal hearts.

            METHODS By consulting the literature, we reviewed the molecular mechanism of CPVT.

            RESULTS Six different genes have been identified in CPVT disease, which account for 60–75% of CPVT cases. All six CPVT genes including RYR2, CASQ2, TRDN, CALM1, CALM2, and CALM3, encode proteins that are directly involved in regulating SR calcium release during excitation-contraction (EC) coupling. Membrane depolarization during the cardiac action potential opens L-type calcium channel which brings calcium into the cell. Calcium binds to and opens RyR2 located in the terminal cisternae of the SR, the junctional SR, a process known as calcium-induced calcium release (CICR). During systole, cytosolic calcium initiates myofilament contraction before being taken back up into the SR or pumped out into extracellular space during diastole. It has been reported that RyR2 mutations are found in 65% of patients with CPVT. RYR2 encodes the cardiac ryanodine receptor (RyR2), a 565 kD protein that forms a homotetrameric, high-conductance, cationselective channel that releases calcium from the SR. The most widely hypothesis is that CPVT mutations sensitize RyR2 channels to SR luminal calcium, causing them to open at a lower intra-SR calcium concentration, termed store overload-induced calcium release (SOICR). Another theory is that mutations in RYR2 affect the ability of FKBP 12.6 to interact with RyR2, leading to dissociation of FKBP 12.6 and the opening of RyR2 during diastole. And the third hypothesis pays attention to the interactions within the structure of RyR2. When RyR2 is activated during the EC coupling cycle, the intramolecular interactions are weakened, ‘unzipping’ the domains, opening the channel, and causing the calcium release.

            CONCLUSIONS While it is still debated which hypothesis is correct, common to all of them is that CPVT-linked RYR2 mutations increase the likelihood of spontaneous RyR2 openings and pathological calcium release during diastole. However, further study is needed as to how exactly mutations in CPVT genes cause functional alterations in the SR calcium release machinery that leads to pathological calcium release during diastole.

            GW33-e0204
            Allicin regulates P-PERK through SHP2 to inhibit the oxidative stress of I/R mice

            Tong Gao1, Dongliang Fu2, Peng Yang2, Yajun Xue1, Boda Zhou1, Mengru Liu2, Xianlun Li2

            1Beijing Tsinghua Changgung Hospital

            2China-Japan Friendship Hospital

            OBJECTIVES This study aims to explore the specific mechanism of allicin regulating the expression of Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) in mouse ischemia/reperfusion (I/R)-induced oxidative stress.

            METHODS The mouse model of myocardial I/R injury (MIRI) was established using macrophage-specific conditional SHP2-knockout (cSHP2-KO) and wild-type (WT) mice, followed by animal experiments and cell experiments. The mice were divided into three groups (control group, model group and allicin group) in animal experiments, and divided into five groups (control group, model group, allicin group, SHP2 KO group and SHP2 KO+allicin group) in cell experiments. The changes in myocardial fibrosis and the expressions of oxidative stress pathway-related proteins in tissues and macrophages were detected through Masson staining and Western blotting, respectively.

            RESULTS The results of in vivo experiments showed that allicin significantly reduced the area of myocardial infarction and myocardial fibrosis after myocardial injury, and up-regulated the protein expression of SHP2 in the myocardium in I/R mice, and the expressions of other proteins phosphorylated protein kinase R-like ER kinase (p-PERK), mitofusin-1 (MFN1), NLR family pyrin domain containing 3 (NLRP3), NADPH oxidase 2 (NOX2) and NOX3 also significantly declined. The results of in vitro experiments revealed that the protein expression of SHP2 was significantly lower, while the expressions of other proteins (p-PERK, MFN1, NLRP3, MFN2, NOX4, p47, gp91, NOX2 and NOX3) were significantly higher in WT mouse-derived macrophages in model group than those in control group. However, the expressions of these proteins were reversed by allicin, consistent with the results of in vivo experiments. There were no obvious changes in the expressions of these proteins in cSHP2-KO mouse-derived macrophages between SHP2 KO+allicin group and SHP2 KO group. It can be seen that the deficiency of SHP2 deprives allicin of the regulatory effect on p-PERK and NLRP3, suggesting that allicin acts on the expressions of oxidative stress-related proteins in I/R mice through promoting the expression of SHP2, and that the activation of p-PERK is involved in the occurrence of oxidative stress after I/R in mice.

            CONCLUSIONS In conclusion, allicin can regulate the activation of p-PERK through enhancing the expression of SHP2, thereby inhibiting the mouse I/R-induced oxidative stress.

            GW33-e0213
            Silencing mas-related G protein-coupled receptor member D (MrgD) improved hypertension and ameliorated hypertension- induced vascular remodeling via mediating Cav1.2-CamkII gamma axis

            Kun Zhao, Peng Li, Xiangqing Kong

            The First Affiliated Hospital of Nanjing Medical University

            OBJECTIVES Cardiac fibrosis and hypertrophy, as the major hallmarks of cardiac remodeling involved in the pathophysiological process of hypertensive heart diseases, can result in disturbed function and structure of the myocardium. Alamandine (Ala), a ligand of Mas-related G protein-coupled receptor, member D (MrgD), was reported to improve hypertension. However, the specific physiological and pathological role of MrgD in hypertension is not yet elucidated.

            METHODS The recombinant adenovirus-MrgD (AD-MrgD) or adenovirus-shRNA-MrgD (shRNA-MrgD) was intravenously injected in Wistar-Kyoto rats (WKY) or Spontaneous Hypertension rats (SHR), respectively. The vascular smooth muscle cells (VSMCs) was induced by AngII to mimic the cell culture model of hypertension in vitro. Then, low-intensity pulsed ultrasound (LIPUS) irradiation (0.5 MHz, 77.20 mW/cm2) was applied for 20 minutes every other day in mice received chronic AngII infusion in vivo.

            RESULTS We found that MrgD overexpression increased blood pressure and induced mesenteric vascular remodeling in WKY rats, while silencing MrgD alleviated hypertension and mesenteric vascular remodeling in SHR rats. The same trends were observed in AngII-induced VSMCs. Moreover, the vasopressor effects of AngII were weaked in MrgD-KO mice. Further results indicated that shRNA-MrgD, like Ala, downregulated AngII-induced protein and mRNA expression of Cav1.2 in vitro, while Cav1.2 activator Bay-K-8644 could reversed the protective effects of silencing MrgD. Meanwhile, COIP-MS mass spectrometry showed that the expression of CamkII gamma, which is related to Cav1.2 function, was significantly increased in AngII-induced VSMCs compared with the control group. In vitro functional experiments also showed that AngII induction promoted the binding of CamkII gamma to MrgD and CamkII Gamma to Cav1.2, respectively, thus promoting the phenotypic transformation of VSMCs. Moreover, LIPUS, a novel and safe apparatus, improved AngII-induced vascular remodeling in vivo and VSMCs phenotypic switch in vitro via inhibiting MrgD expression.

            CONCLUSIONS Taken together, our current study unveiled the promising protective effects of silencing MrgD expression on improving hypertension and ameliorating hypertension-associated mesenteric vascular remodeling by mediating Cav1.2-CamkII gamma axis, paving the way to develop novel therapeutic apparatus, LIPUS, in the clinical practice of lowering hypertension in the future.

            GW33-e0232
            OSMR deficiency aggravates pressure overload-induced cardiac hypertrophy by modulating macrophages and OSM/LIFR/STAT3 signaling

            Yizhou Feng1,2,3, Yuan Yuan1,2,3, Hongxia Xia1,2,3, Zhaopeng Wang1,2,3, Yan Che1,2,3, Fangfang Li1,2,3, Qingqing Wu1,2,3, Heng Zhou1,2,3, Zhouyan Bian1,2,3, Difei Shen1,2,3, Qizhu Tang1,2,3

            1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China

            2Cardiovascular Research Institute of Wuhan University, Wuhan 430060, China

            3Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan 430060, China

            OBJECTIVES Oncostatin M (OSM) is a member of interleukin (IL)-6 family mainly involved in inflammatory and cardiovascular diseases through binding to the functional receptor complexes of common signal transducing component glycoprotein 130 (gp130) and OSM receptor β (OSMR) or leukemia inhibitory factor receptor (LIFR). The effect and underlying mechanism of OSM/OSMR/LIFR on the development of cardiac hypertrophy remains unclear. This study aims to investigate the effect of OSMR deficiency on murine cardiac hypertrophy induced by pressure overload.

            METHODS C57BL/6 wild-type (WT) and OSMR-knockout (OSMR-KO) mice underwent aortic banding (AB) followed by the assessment of echocardiographic, histological, biochemical and immunological analyses in the myocardium. Bone marrow-derived macrophage (BMDM) was isolated and cultured followed by stimulating with Lipopolysaccharide (LPS) for vitro study. Furthermore, WT mice were subjected to bone marrow transplantation (BMT) of OSMR-KO hematopoietic cells.

            RESULTS It was found that OSMR deficiency aggravated cardiac hypertrophy, fibrotic remodeling and cardiac dysfunction after aortic banding (AB) in mice. The expression of glycoprotein 130 (gp130) receptor cytokine family was detected and LIFR level was remarkably up-regulated in the hypertrophic mouse myocardium which was mainly located in macrophages. In addition, we observed a relatively increased level of OSM and signal transducer and activator of transcription (STAT) 3 in the heart tissue of OSMR-KO mice after AB surgery. Moreover, OSMR deletion enhanced macrophage accumulation and adherence in the hypertrophic mouse myocardium and increased numbers of infiltrating leukocytes and inflammatory monocytes/macrophages instead of reparative macrophage subsets both in heart and peripheral blood. Additionally, bone marrow transplantation of OSMR-KO hematopoietic cells to WT mice after AB surgery displayed a consistent phenotype. However, silencing of LIFR expression with siLIFR ameliorated OSMR deletion effects on the phenotype and STAT3 activation.

            CONCLUSIONS This study uniquely revealed that OSMR deficiency aggravated pressure overload-induced cardiac hypertrophy by modulating macrophages and OSM/LIFR/STAT3 signaling, which provided evidence that OSMR might represent an attractive target for treating pathological cardiac hypertrophy and heart failure.

            GW33-e0241
            USP36 mediates doxorubicin-induced cardiomyopathy through inhibiting ubiquitination and degradation of PARP1

            Dongchen Wang, Zihao Jiang, Yue Gu, Shaoliang Chen

            Nanjing First Hospital, Nanjing Medical University, Nanjing, China

            OBJECTIVES The molecular mechanism underlying doxorubicin (DOX)-induced cardiotoxicity is yet to be fully elucidated. Our current study sought to determine the role of ubiquitin specific proteases 36 (USP36), a nucleolar deubiquitinating enzyme (DUB), in the progress of DIC and its mechanism.

            METHODS Neonatal rat cardiomyocytes and H9c2 cells were used to construct a doxorubicin-induced cardiomyocyte injury model. The expression levels of USP36 and its downstream PARP1 were analyzed by western blotting and the binding of USP36 and PARP1 was verified by co-IP experiments. DHE staining, LDH content analysis and western blotting were performed to evaluate cell oxidative stress injury and apoptosis. We also established a DIC model in mice, specifically knocked down USP36 by injecting AAV9 (adeno-associated virus serotype 9) – associated virus into the tail vein of mice, and analyzed mouse heart function, myocardial structural cell survival status by echocardiography, HE staining and Masson staining.

            RESULTS We identified an increased expression of USP36 both in neonatal rat cardiomyocytes and H9c2 cells exposed to DOX, and USP36 silencing significantly ameliorated DOX-induced oxidative stress injury and apoptosis in vitro. Mechanistically, USP36 knockdown resulted in reduction of PARP1 levels, and its overexpression was observed to positively correlate with PARP1 expression. Further investigation showed that USP36 could bind to and mediate the deubiquitination of PARP1 and increase its protein stability in cardiomyocytes upon DOX exposure. Moreover, overexpression of wild-type (WT) USP36, but not its catalytic-inactive mutant (C131A), stabilizes PARP1 in HEK293T cells. Herein, we also established DIC model in mice and observed a significant upregulation of USP36 in the heart. USP36 cardiomyocyte-specific knockdown mice showed preserved cardiac function after chronic low-dose DOX treatment and were protected against DOX-induced in terms of structural changes within the myocardium.

            CONCLUSIONS DOX promotes DIC progression by activating USP36-mediated PARP1 deubiquitination. USP36/PARP1 axis may play an important regulatory mechanism in the pathogenesis of DIC.

            GW33-e0254
            CDK9 combined with SGK3 regulates cardiomyocyte regeneration and cardiac repair in the mouse infarcted heart by activating GSK-3β/β-catenin pathway

            Tianwen Wei, Liansheng Wang

            Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University

            OBJECTIVES The neonatal heart maintains entire regeneration capacity in a transient regeneration window, but the adult heart loses this function. The loss of the proliferative capacity of cardiomyocytes (CMs) involves numerous core hubs regulation of gene expression and activities. SGK3 is a functional kinase we identified previously, with the capacity of promoting cardiomyocyte proliferation and cardiac repair after myocardial infarction (MI). The present study further elucidated the direct combination relationship of cyclin-dependent kinase 9-serine (CDK9) and threonine-protein kinase 3(SGK3), and explored the role and mechanism of CDK9 in cardiac regeneration after myocardial infarction.

            METHODS We used quantitative phosphoproteomics data of infarct border zone in newborn hearts after MI to identify CM regeneration-associated kinases. Gain- and loss-of-function experiments were performed to determine the effect of CDK9 in CM proliferation and cardiac repair after apical resection (AR) or MI. Pulldown assay and co-immunoprecipitation (Co-IP) experiments were conducted to investigate the direct binding target proteins.

            RESULTS CDK9 and SGK3 protein expression was highly expressed at postnatal day 1 (P1), reduced at P7 until adult. In, CM proliferation ratio was elevated by CDK9 overexpression, while it was decreased by CDK9 knockdown in newborn mice cardiomyocytes. In vivo, inhibition of CDK9 shortened the time window of cardiac regeneration after AR in neonatal mice, and overexpression of CDK9 significantly promoted CM proliferation and cardiac repair after MI in adult mice. Mechanistically, CDK9 could be directly combined with and activated the phosphorylation of SGK3, and the activated SGK3 further promotes CM regeneration through the GSK-3β/β-catenin signal pathway. Inhibition of SGK3 partially blunted CM proliferation induced by CDK9 overexpression in vitro.

            CONCLUSIONS Our study revealed the direct combination relationship of CDK9 and SGK3. As an upstream of SGK3, CDK9 plays a greater role in promoting myocardial regeneration after cardiac injury such as MI, which may reopen a novel therapeutic avenue for MI.

            GW33-e0257
            miR-455-5p promotes pathological cardiac remodeling via inhibition of PRMT1-mediated Notch1 activation

            Sidong Cai1, Cong Chen1, Mengqi Su1, Yinxia Wei2, Haoran Sun3, Junlei Chang4, Kai-hang Yiu1,5

            1Division of Cardiology, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

            2School of Public Health, Southern Medical University, Guangzhou 510515, China

            3Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

            4Centre for Protein and Cell-based Drugs, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, No. 1068, Xueyuan Blvd, Xili Nanshan, Shenzhen 518055, China

            5Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences; Division of Cardiology, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Room 1929B/K1931, Block K, Hong Kong, China

            OBJECTIVES Although microRNAs have been reported to participate in the regulation of cardiovascular diseases, the potential role of miR-455-5p on pathological cardiac remodeling remains to be elucidated. The present study focused on clarifying the function and searching the direct target of miR-455-5p, as well as exploring its underlying mechanisms in pathological cardiac remodeling.

            METHODS To clarify the function of miR-455-5p in pathological cardiac remodeling, miR-455-5p mimic and inhibitor were transfected into cardiomyocytes in vitro, miR-455-5p agomir and miR-455-5p antagomir were injected to caudal vein of mice; To exploring which echocardiographic parameter was significantly correlated to miR-455-5p level, quantitative primer chain reaction (Q-PCR) was utilized to measure the miR-455-5p level in patients with hypertention; To find out the direct target of miR-455-5p, luciferase binding assay was employed; Co-imuunoprecipitation assay (Co-IP) was used to testify asymmetric dimethylation of Notch1 was regulated by PRMT1 and influenced by miR-455-5p level.

            RESULTS miR-455-5p participated in inducing pathological cardiac remodeling suppressed both in vivo and in vitro; By exploring the correlation of miR-455-5p level and echocardiograhy results in hypertensive patients, miR-455-5p mainly regulated in left ventricular wall thickening via inhibition of Notch signaling pathway; By luciferase binding assay, PRMT1 was confirmed to be a direct target of miR-455-5p; By co-immunoprecipitation, miR-455-5p was proved to impede asymmetric dimethylaiton of Notch1 and subsequent Notch1 activation.

            CONCLUSIONS The present study reveals that miR-455-5p provokes pathological cardiac remodeling by impediment of PRMT1 transcription and subsequent inhibition of Notch1 asymmetric dimethylation. Downregulation of Notch1 asymmetric level mediated by PRMT1 inhibition results in suppression of Notch signaling pathway. Thus, targeting the miR-455-5p/PRMT1/Notch1 signaling axis may suggest a novel therapeutic approach against pathological cardiac remodeling.

            GW33-e0266
            CHK1 pathway inhibition with gemcitabine treatment results in cardiotoxicity and worsens cardiac remodeling after myocardial infarction

            Jiawen Chen, Liansheng Wang

            Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University

            OBJECTIVES CHK1 is the core component of DNA damage response pathway and regulates multiple downstream factors, controlling cell proliferation and survival. CHK1 inhibitor AZD7762 is now in clinical trials, whereas it will potentially cause cardiotoxicity especially combined with gemcitabine. The adverse impact of CHK1 inhibition and gemcitabine on the heart is unclear. This research aims to determine whether CHK1 inhibition combined with gemcitabine affects cardiac physiology and ventricular remodeling post-MI and to elucidate the underlying molecular mechanisms.

            METHODS Healthy mice were treated with AZD7762 combined with gemcitabine for 21 days and mice with MI were treated for 10 days to construct a cardiotoxicity model. Echocardiography and cardiac MRI were conducted to detect the functional and structural changes with the anti-neoplastic treatment. H&E and Masson’s trichrome staining were used to identify the histological alterations. Proteomics analysis was taken to determine the cardiotoxicity-related pathways. Western blot and RT-qPCR were used to verify the gene expression changes.

            RESULTS In vivo, both chk1 inhibition and gemcitabine therapy induced weight loss, heart atrophy, exaggerated blood pressure, systolic dysfunction and myocardial inflammation in mice. After myocardial infarction, mice with the anti-neoplastic treatment showed aggravated cardiac dysfunction, adverse post-MI remodeling and greater infarct area. Proteomics analysis revealed changes in the level of multiple proteins, which were further enriched in acute inflammation response-related pathways. Both AZD7762 and gemcitabine treatment resulted in DNA damage response pathway activation and worsened ventricular remodeling with reduced blood vessel density, activated inflammatory response and endothelial apoptosis. In vitro, AZD7762 and gemcitabine suppressed CHK1 activation, cell viability, proliferation, and increased cell apoptosis in human umbilical vein endothelial cells.

            CONCLUSIONS The CHK1 pathway is associated with heart atrophy, cell survival and angiogenesis in mice and CHK1 inhibition with gemcitabine worsens cardiac remodeling post-MI. The promising anti-neoplastic therapy is potentially cardiotoxic, especially in patients with myocardial infarction.

            GW33-e0274
            Pex3 KO activates NLRC5 via inhibiting AKT/GSK3β pathway to impair cardiac regeneration after injury

            Jiateng Sun1, Zimu Wang1, Liuhua Zhou1, Jiahao Sha2, Liansheng Wang1

            1The First Affiliated Hospital of Nanjing Medical University

            2State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology

            OBJECTIVES Peroxisomes are versatile organelles in the performance of different metabolic functions, such as fatty acid oxidation and redox homeostasis maintenance. PEX3, a peroxisomal membrane protein, is verified to be responsible for the biogenesis of peroxisomes and the import of their matrix protein machinery. Given the cardiac protective role of peroxisomes, the effect of Pex3 in cardiomyocyte proliferation remains to be elucidated. Here we report the position of Pex3 on cardiomyocyte proliferation and provide a better understanding of its mechanism. Pex3 KO mice exhibit impaired heart regeneration capacity compared with wide-type (WT) littermates after cardiac injury. Ex vivo data shows that downregulated Pex3 leads to a lower proliferation ratio of primary cardiomyocytes. RNA-seq profiling reveals the increased level of NLRC5. Loss-of-function experiments show a restored proliferation capacity of Pex3KO myocardial cells. The AKT activator SC79 and GSK3β specific inhibitor TDZD8 could attenuate the upregulated NLRC5 and jeopardize proliferation ability.

            METHODS We generated Pex3/KO mice from mice with a C57BL/6 background, and the effect of Pex3 on cardiac regeneration was tested on neonatal and adult mice who underwent apical resection or myocardial infarction and on the cardiomyocytes harvested from P1 mice. Immunofluorescent staining was used to detect proliferation signals (Edu, Ki67) and apoptosis (Tunel). RNA-seq was performed on the infarct border zone of the neonatal myocardium. Bioinformatic analyzed 510 upregulated genes and 116 down-regulated genes enriched. KEGG pathway analysis and GO analysis showed the enrichment in the AKT pathway.

            RESULTS Pex3 KO mice showed a decreased abundance of peroxisomes and jeopardized proliferation capacity of neonatal CMs in the first week of life. Notably, after induction of myocardial infarction, adult Pex3/KO mice prohibit impaired heart function with increased myocardial fibrosis, declined left ventricular systolic function, and higher apoptosis on infarct border zone compared with adult WT mice. Treatment with 4-PBA in CMs, which results in peroxisome proliferation, resulted in more proliferation and DNA oxidative damage, but not in Pex3-overexpression CMs. For further research on the potential molecular mechanism of Pex3, we conducted High-throughput sequencing on the infarct border zone of neonatal KO and WT myocardium and locked the downstream of Pex3 in the AKT/GSK3β pathway. In Pex3 KO CMs, we observed decreased AKT Ser473 and increased levels of GSK3βTyr216 phosphorylation, and reduced levels of GSK3βSer9 phosphorylation. When the AKT activator SC79 was added to the Pex3 KO CMs, the phosphorylation level of GSK Ser9 was higher, and the phosphorylation level of GSK3βTyr216 was decreased, accompanied by an increase in the proliferation signal of CMs. Similar findings were obtained when Pex3/KO CMs were treated with TDZD-8, a particular inhibitor of GSK3β.

            CONCLUSIONS Pex3 knockout leads to the abnormal abundance and biological function of peroxisomes, which inhibits the AKT/GSK3β signaling pathway, resulting in the impaired regenerative capacity of cardiomyocytes. Overall, our data reveal the role of Pex3 in regulating CM regeneration, emphasizing the effect of Peroxins mutations on myocardial regeneration.

            GW33-e0292
            METTL3 improves cardiomyocyte proliferation by mediating m6A modification of miR-17-3p/Ank2 after myocardial infarction

            Kun Zhao1,2, Bin Zhou2, Jing Shi1

            1The First Affiliated Hospital of Nanjing Medical University

            2Albert Einstein College of Medicine

            OBJECTIVES Myocardial infarction (MI) leads to heart failure by causing a massive and rapid loss of cardiomyocytes. However, MI injury-induced proliferation of adult mammalian cardiomyocytes is insufficient to restore impaired cardiac function. Therefore, research on revealing the mechanism of endogenous cardiomyocyte proliferation has become crucial locally and abroad. As the most abundant internal modification in eukaryotic genome, N6-methyladenosine (m6A) modification plays an irreplaceable role in organ development. This study aimed to investigate the role of m6A modification and m6A methyltransferase-like protein 3 (METTL3) in physiological and pathological changes of cardiomyocyte proliferative capacity; and then to explore the underlying molecular mechanisms.

            METHODS The genome-wide profiling of methylation-modified transcripts was conducted with methylation-modified RNA immunoprecipitation sequencing (m6A-RIP-seq) and RNA sequencing (RNA-seq). Then, the effects of METTL3 on cardiomyocyte proliferation and apoptosis were investigated in an in vivo rat model of MI and in an in vitro model of NRCMs exposed to hypoxia.

            RESULTS (1) The heart tissues or cultured NRCMs of rats at P7 showed significant lower proliferation ability and m6A modification levels than those of rats at P0. The results of m6A-RIP-seq and RNA-seq systematically constructed the m6A modification profile of neonatal rat heart regeneration, and showed that the potential hub genes with differentially expressed hypermethylated or hypomethylated m6A levels were involved in the regulation of cardiomyocyte proliferation. (2) Besides, WB and RT-PCR results indicated that the decrease of METTL3 levels was closely related to the decrease of m6A modification levels. Further in vitro experiments showed that METTL3 overexpression enhanced cardiomyocyte proliferation, while silencing METTL3 downregulated cardiomyocyte proliferation. METTL3 also regulated the expression of these newly identified hub genes. (3) Then, we found that METTL3 expression was downregulated in hypoxia-exposed NRCMs and MI-induced rats. METTL3 overexpression enhanced cardiomyocyte proliferation and inhibited cardiomyocyte apoptosis under hypoxic or MI conditions. (4) Also, METTL3 overexpression upregulated miR-17-3p expression. The miR-17-3p antagomir blocked the pro-proliferative and anti-apoptotic effects of METTL3 overexpression in hypoxia-exposed cells or rats with MI, while the miR-17-3p agomir hindered the inhibitory effects of silencing METTL3 on cardiomyocyte proliferation. (5) Further, we found that METTL3 overexpression could increase m6A modification in pri-miR-17-3p, which promoted miR-17-3p processing by recognizing and binding DGCR8 to pri-miR-17-3p. Finally, bioinformatics analysis, luciferase reporter assays and the reversal experiments demonstrated that miR-17-3p was involved in the protective effects of METTL3 overexpression in hypoxia-exposed cells via binding and silencing Ank2.

            CONCLUSIONS The current study suggested that METTL3 overexpression upregulated miR-17-3p expression in a DGCR8/m6A-dependent pri-miRNA-processing manner, and then silenced Ank2 expression, thereby improving cardiomyocyte proliferation and inhibiting cardiomyocyte apoptosis, which ultimately ameliorated cardiac dysfunction in MI-induced rats.

            GW33-e0296
            Magnoflorine protects against cardiac remodeling induced by pressure overload through enhancing the Keap-1/Nrf-2/HO-1 signaling pathway

            Zhefu Hu, Yizhou Feng, Qingqing Wu, Yuan Yuan, Qizhu Tang

            Renmin Hospital of Wuhan University

            OBJECTIVES Magnoflorine (MAG), a well-known quaternary alkaloid isolated from Chinese herb Magnolia or Aristolochia, has been reported to possess anti-inflammatory and antioxidant activities, but the effect of MAG on pressure overload-induced cardiac remodeling remains inconclusive. In this study, we investigated the effect of MAG on cardiac remodeling in in vivo and in vitro models, and to clarify the underlying mechanisms.

            METHODS C57BL/6 mice were subjected to aortic banding (AB), and treated with MAG (10 mg/kg/day, ig) 1 week after AB surgery (and continued for further 7 weeks). Eight weeks after AB surgery, the mice were subjected to echocardiography, and then sacrificed to harvest the hearts for analysis. For in vitro study, neonatal rat cardiomyocytes and cardiac fibroblasts were used to validate the protective effects of MAG in response to angiotensin II (Ang II) and transforming growth factor-β (TGF-β) challenge.

            RESULTS We showed that MAG administration protected against pressure overload-induced cardiac hypertrophy, fibrosis, inflammation, and dysfunction in AB mice. In the in-vitro study, we showed that treatment with MAG (50 μM) blocked Ang II-induced-cardiomyocyte hypertrophy and TGF-β-induced cardiac fibroblast activation. Furthermore, MAG treatment significantly enhanced the activation of the Keap-1/Nrf-2/HO-1 signaling pathway in response to pressure overload in vivo and extracellular stimuli in vitro. Moreover, adenoviruses infections by siRNA-mediated silencing of Nrf-2 abolished the protective effects of MAG in both in vitro and in vivo models.

            CONCLUSIONS MAG improves cardiac function and alleviates cardiac remodeling induced by pressure overload through enhancing the Keap-1/Nrf-2/HO-1 signaling pathway, and provide a reference for the development and utilization of natural products in the intervention of pathological cardiac remodeling.

            GW33-e0302
            Checkpoint kinase 1 alleviates myocardial ischemia/reperfusion injury by restoring blocked autophagic flux in cardiomyocyte

            Tongtong Yang, Liuhua Zhou, Lingfeng Gu, Tiankai Shan, Jiateng Sun, Liansheng Wang

            Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University

            OBJECTIVES Myocardial ischemia/reperfusion (I/R) injury remains a leading cause of mortality worldwide. The role and mechanism of autophagy in myocardial I/R remains controversial and largely unknown. CHK1 (Checkpoint Kinase 1) was indicated to promote cardiomyocyte proliferation and cardiac repair after myocardial infarction but its role in reperfusion injury remains unknown. Here, we aim to explore the role of CHK1 in regulation of myocardial autophagy and I/R injury.

            METHODS In this study, we used both an in vivo and in vitro I/R model to investigate whether CHK1 regulates myocardial I/R injury and autophagy in cardiomyocyte, by subjecting mice to I/R and by exposing NMCMs (neonatal mouse cardiomyocytes) to OGD/R (oxygen glucose deprivation/reperfusion) models. The I/R model was established by ligation of LAD (left anterior descending) of coronary for 45 minutes, followed by removal of occlusion. We constructed cardiomyocyte-specific CHK1-knockin (CHK1-cKI) or knockout (CHK1-cKO) mouse to determine the role of CHK1 in myocardial I/R injury. We used echocardiography (LVEF, left ventricular ejection fraction. LVFS, left ventricular fractional shortening) and Evans Blue-TTC staining to evaluate cardiac injury. In addition, we used Ad5: cTNT-CHK1/Ad5: cTNT-CHK1sh and mCherry-GFP-LC3 puncta to monitor CHK1-mediated dynamics of autophagic flux in NMCMs. The expression levels of autophagy-related proteins (ATG5, LC3, p62) were also employed to reflect autophagic levels in vivo. We used autophagy inhibitors 3-MA (3-methyladenine) and CQ (chloroquine) to confirm the function of CHK1-mediated autophagy in myocardial I/R injury.

            RESULTS The phosphorylation activity of CHK1 decreased in myocardium with I/R injury, while the total expression level of which remained unchanged. During myocardial reperfusion, CHK1-cKI mice had a significantly relieved infarct size and moderate cardiac function (LVEF and LVFS) deterioration. Compared with the blocked autophagic flux in wider type-I/R mice, CHK1-cKI-I/R mice showed enhanced activity of autophagy flux, manifested by higher levels of beclin, ATG5 and LC3, together with downregulated autophagy substrate, p62. In vitro, NMCMs exposed to OGD/R and transfected Ad5: cTNT-CHK1sh showed decreased autolysosome-to-autophagosome ratio. Moreover, CHK1-induced cardio-protection was partially weakened in CHK1-cKI-I/R mice subjected with intraperitoneal injection of 3-MA and CQ. Conversely, CHK1-cKO mice showed worse cardiac function and further aggravated by 3-MA and CQ.

            CONCLUSIONS Our study revealed a key cardioprotective role of CHK1 after myocardial I/R injury through restoring impaired autophagic flux.

            GW33-e0334
            Repolarization heterogeneity in heart failure with preserved ejection fraction and its relation to ventricular tachyarrhythmias

            Cong Xue, Mengfei Wang, Fang Jia, Ling Yang

            Department of Cardiology, The Third Affiliated Hospital of Soochow University

            OBJECTIVES Heart failure with preserved ejection fraction (HFpEF) has a unique pathophysiological mechanism, and its mechanism of ventricular arrhythmia is in urgent need of further study. The purpose of this study was to investigate the repolarization heterogeneity in heart failure with preserved ejection fraction and its relation to ventricular tachyarrhythmias.

            METHODS Twenty SD rats were randomly divided into HFpEF group (n=12) and control group (n=8). The HFpEF group was treated with abdominal aortic constriction to establish HFpEF model, and the control group was treated with sham operation. The heart rate, PR interval, QRS interval, QTc interval, TpTe interval and so on were recorded in all SD rats before and every 2 weeks after operation. After successful modeling, MAP recording electrode was attached to left subatrial myocardium and ventricular septum in body, MAP and limb lead electrocardiogram were recorded, sinus heart rate, repolarization 90% action potential duration (MAPD90) and effective response period (ERP) were measured, and ERP/MAPD90 were calculated. After that, the pacing electrode was attached to the middle part of the left ventricular free wall to induce ventricular arrhythmia.

            RESULTS Routine ECG: The post-operation PR interval in HFpEF group was gradually prolonged, and reached the peak at the 12th week (57±2.33 ms), and then decreased slightly, which was statistically significant compared with the baseline (49±2.28 ms) (P<0.05). The QTc interval was significantly longer at 6 weeks (188±18.44 ms), 10 weeks (200±18.05 ms) and 16 weeks (186±17.98 ms) than the baseline level (166±18.10 ms) (all P<0.05). The duration of TpTe was significantly longer than baseline (31±10.57 ms) at 2 weeks (40±10.77 ms), 6 weeks (48±10.16 ms), 8 weeks (39±9.88 ms), 10 weeks (48±10.35 ms), and 16 weeks (49±10.55 ms) (all P<0.05). There were no significant differences in PR interphase, QTc interphase and TpTe interphase in the control group compared with baseline. ERP: HFpEF group (72±9.87 ms) was significantly shorter than control group (90±8.51) (P<0.05). Induction of ventricular arrhythmia: persistent ventricular tachycardia was found in 2 cases and paroxysmal ventricular tachycardia was found in 8 cases in HFpEF group.

            CONCLUSIONS HFpEF has delayed cardiac repolarization, increased heterogeneity of ventricular repolarization, and shortened ventricular effective refractory period, leading to increased sensitivity to arrhythmias and laying a foundation for the onset of HFpEF ventricular arrhythmias.

            GW33-e0344
            Acetylation of PTPN1 mRNA mediates the SMCs proliferation in PAH

            Deng Yunfei, Chen Shaoliang

            Department of Cardiology, Nanjing First Hospital

            OBJECTIVES The uncontrolled proliferation of SMCs (smooth muscle cells) is the major pathophysiological trait of PAH (pulmonary arterial hypertension). Previous evidence showed that mRNAs acetylation is associated with cell proliferation, leading us to explore the relationship between them.

            METHODS Immunoblot, Immunohistochemistry and qRT-PCR were used to measure the protein and RNA expression level. Dot blot was used to estimate the RNA acetylation level in vivo and in vitro. EdU and CCK-8 were utilized to test the cell proliferation. Viral vector (SM22-Cre+AAV2-flex) and Crispr-cas 9 were employed to specifically knock down the NAT10 (the mRNAs acetylation enzyme) in vivo. acRIP-seq and RIP-seq were used to predict the downstream target gene.

            RESULTS RNA acetylation level decreased obviously in SMC from lung of mice (Hypoxia+su5416 for 4 weeks) or PAH patients, in consistent with NAT10 expression. Decreased NAT10 could accelerate the SMC proliferation in vitro. Specifically knocking down the NAT10 in SMC could elevate the pulmonary arterial pressure and narrow the lumen of pulmonary artery in vivo. Bioinformatic analysis of acRIP-seq and RIP-seq results showed that PTPN1 might be the downstream target of RNA acetylation, which is negatively related to the cell proliferation.

            CONCLUSIONS Our above results showed that mRNA acetylation is related to the SMC proliferation in vivo and in vitro, in turn being associated with the development of PAH. PTPN1 was the main downstream target, might be a potential therapeutic agent for PAH.

            GW33-e0345
            Circular RNA Fbxl5 regulates cardiomyocyte apoptosis during ischemia reperfusion injury via sponging microRNA-146a

            Dongjiu Li, Jiayin You, Changqian Wang

            Shanghai Ninth People’s Hospital, Shanghai JIao Tong University School of Medicine

            OBJECTIVES Cardiomyocyte apoptosis critically contributes to ischemia reperfusion injury (IRI), which lacks effective therapeutic strategies. Circular RNAs (circRNAs) serve as novel diagnostic and therapeutic targets in various cardiovascular diseases. CircRNA Fbxl5 is one of the abundantly expressed circRNAs in the heart and its role in myocardial IRI remains elusive.

            METHODS Wild-type (WT) mice and neonatal mice ventricular myocytes (NMVMs) were used and subjected to myocardial IRI and anoxia reoxygenation (AR), respectively. Molecular and histological analyses and echocardiography were used to determine the extent of apoptosis, infarct size, and cardiac function.

            RESULTS We found that circRNA Fbxl5 was significantly upregulated in the myocardium, as well as in NMVMs subjected to AR. Knockdown of circRNA Fbxl5 ameliorated cardiomyocyte apoptosis, thereby decreasing infarct size and preserving cardiac function. Additionally, in vitro knockdown of circRNA Fbxl5 in NMVMs subjected to AR recapitulated the in vivo findings. Mechanistically, we identified that circRNA Fbxl5 directly sponged and suppressed the endogenous microRNA-146a (miR-146a), thereby weakening its inhibitory effect on MED1, which could further promote the apoptosis of cardiomyocytes.

            CONCLUSIONS Our findings revealed a novel and critical role for circRNA Fbxl5 in regulating cardiomyocyte apoptosis, and added additional insight into circRNAs mediated during myocardial IRI. The underlying miR-146a-MED1 signaling serves as an important cascade in regulating the apoptosis of cardiomyocytes.

            GW33-e0349
            Reg3γ-dependent accumulation of macrophages in aging related atrial fibrillation

            Zhaojia Wang, Guangping Li, Qiankun Bao, Tong Liu

            Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China

            OBJECTIVES Atrial fibrillation (AF) is the most common persistent arrhythmia and significantly increases the risk of stroke, heart failure and mortality in patients. Aging, however, is an independent risk factor for AF, significantly increasing its incidence. However, the mechanisms underlying the high prevalence of AF in the elderly population are not well understood. Inflammation is an important pathogenesis of AF, and the mechanisms that inflammation induced aging related AF need to be further elucidated. The aim of this study was to explore new mechanisms that inflammation induced aging related AF and to provide new directions for the clinical management of the occurrence, development and recurrence of AF in the elderly.

            METHODS SD rats fed normally until 20 months of age were constructed as the aging group. The young group (control) was SD rats fed normally until 3 months of age. The atrioventricular conduction circumference (AVWCL), sinus node recovery time (SNRT), atrial expiration period (AERP) and AF induction rate were observed by electrophysiological examination. The aging rats were also divided into aging-prone and non-prone AF according to the induction of AF. RNA-seq analysis was performed on the atrial tissues. Bone marrow-derived macrophages (BMDM) were isolated and induced. Migration assays were performed to observe whether Regenerating Islet-Derived Protein3 gamma (Reg3γ) could recruit BMDMs. qPCR and cytokine array panel were performed to observe the effect of Reg3γ on production and secretion of inflammatory factors of BMDMs. RNA-seq was performed on BMDM with or without Reg3γ.

            RESULTS AVWCL, SNRT, AERP, and AF inducibility were increased in aging rats compared with young controls. We performed RNA-seq analysis of AF-prone atrial tissues in the aging group compared with those in the young group and found that the differential genes were mainly concentrated in inflammation-related pathways. The most significant change in the differential genes was Reg3γ, and the expression of Reg3γ was higher in aging atrial tissues prone to AF than in those less prone to AF. And we found an increase in macrophages and associated inflammatory in aging atria. We also found that Reg3γ promoted the recruitment of BMDMs and inflammatory factor production. Using cytokine array panel, we screened that Reg3γ could promote the secretion of CCL3, CCL4, CXCL9, CXCL10, CXCL13, IL17 by macrophages. We also determined that Reg3γ activates STAT3-JAK1 through the gp-130 receptor and then enables macrophages to function. In addition, we performed RNA-seq assays on Reg3γ-acting macrophages and control cells, and analyzed the differential genes by GO enrichment and KEGG pathway annotation and enrichment, and found that the differential genes mainly focused on MAPK pathway, IL17 signaling pathway, and protein metabolism pathway. It is suggested that Reg3γ may also affect macrophages through the non-classical gp130-STAT3-JAK1 pathway.

            CONCLUSIONS Reg3γ recruits macrophages and activates them through the gp130-STAT3-JAK1 pathway to promote inflammatory factor production and release, ultimately contributing to the development of aging related AF. The present study provides a new experimental basis for the prevention and treatment of elderly patients with AF from the perspective of Reg3γ-induced macrophage-associated inflammation.

            GW33-e0352
            Protective effects of nicotinamide mononucleotide on radiation-related cardiac injury

            Zhaojia Wang1, Xiaotong Zhao2, Zandong Zhou1, Feng Wang3, Xu Zhang4, Gary Tse1,5,6, Guangping Li1, Yang Liu2, Tong Liu1

            1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China

            2Institute of Radiation Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300192, China

            3Department of Genetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China

            4Tianjin Key Laboratory of Metabolic Diseases, Collaborative Innovation Center of Tianjin for Medical Epigenetics, Center for Cardiovascular Diseases, Research Center of Basic Medical Sciences, Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin 300070, China

            5Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK

            6Kent and Medway Medical School, Canterbury CT2 7NZ, UK

            OBJECTIVES Radiation therapy for cancer treatment can cause damage to the heart. There are numerous possible mechanisms related to radiation-related cardiac dysfunction, among which increased oxidative stress is an important factor. However, the detailed mechanisms remain unclear and effective treatments on radiation-related cardiac dysfunction are still lacking. Nicotinamide mononucleotide (NMN), the most direct precursor of nicotinamide adenine dinucleotide (NAD+), can effectively reduce reactive oxygen species (ROS) production and thus could be a candidate to alleviate radiation-induced damage. However, the protective effects and the underlying mechanisms of NMN on radiation-related cardiac injury remain to be elucidated.

            METHODS Wild-type c57 mice were divided into radiation exposure (7.2 Gy radiation) and non-exposure groups. Wild-type C57BL6/J mice supplied with NMN for 12 months before radiation. Echocardiography to detect mice cardiac function. Epicardial electrical mapping technique to detect cardiac electrical conduction. Non-targeted metabolomics was used to detect cardiac different metabolites. In parallel, we observed the effect of radiation on survival and mitochondrial function of H9c2 cells with or without NMN.

            RESULTS In the radiation exposure group, echocardiography showed that the left ventricular ejection fraction (LVEF) and fractional shortening (FS) were reduced, whilst epicardial mapping demonstrated slowed conduction velocity and change in the direction of propagation. Non-targeted metabolomics showed the different metabolites between the radiation group and the control group were mainly in nucleotide and amino acid metabolism. Metabolic pathway enrichment analysis showed that different metabolites were implicated in the metabolism of pyrimidine, folate, arginine and proline, and tryptophan. Mice with NMN before radiation showed reduced mechanical and electrical dysfunction, with non-targeted metabolomic results showed NMN rescued the radiation-induced down-regulation of 1-(4-aminobutyl)urea, 4-aminobenzoic acid, 3-hydroxyanthranilic acid, which ultimately exerted cardioprotective effects. We also found that radiation can reduce the survival, increase ROS production, and reduce ATP content of H9c2 cells in vitro, and these harmful effects can be partially reversed by NMN.

            CONCLUSIONS The mechanical and electrical dysfunction caused by radiation were associated with altered nucleotide and amino acid metabolism in the myocardium, and these harmful effects could be partially mitigated by NMN supplement.

            GW33-e0355
            The influence of diabetes duration on ischemic postconditioning

            Nazila Yaliqin, Qianru Yuan, Yitong Ma, Aibibanmu Aizeze

            Heart Center, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES It has been demonstrated that Ischemic postconditioning (IPC) seems a largely efficient approach to enhance the myocardial resistance to the reperfusion injury. Yet the cardio-effectiveness of IPC in a diabetic state is controversial, we established an experimental model of diabetes mellitus with different disease stages and evaluated the effect of the duration of diabetes on IPC.

            METHODS Seventy-two healthy male C57BL/6J mice were selected to establish a diabetes model with high glucose diet combined with multiple low-dose intraperitoneal injections of STZ. After the establishment of the experimental model, the mice were randomly divided into eight groups: non-diabetic (2 weeks) ischemia-reperfusion group (2NIR), non-diabetic (2 weeks) ischemia-postconditioning group (2NPost), non-diabetic (8 weeks) ischemia-reperfusion group (8NIR), non-diabetic (8 weeks) ischemia postconditioning group (8NPost), diabetic (2 weeks) ischemia-perfusion group (2DIR), diabetic (2 weeks) ischemia postconditioning group (2DPost), diabetic (8 weeks) ischemia-perfusion group (8DIR), and diabetic (8 weeks) ischemia postconditioning group (8DPost). After all, hearts underwent 30 mins of prolonged ischemia, 2NIR, 8NIR, 2DIR, and 8DIR groups received 60 minutes of continuous reperfusion. 2NPost group, 8NPost group, 2DPost group, and 8DPost group were given three cycles of 10 s reperfusions and 10 s ischemia followed by 60 mins continuous reperfusion. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary outflow fluid at 60 min of reperfusion were measured, the left ventricular myocardium was isolated and the infarct area was measured, and immunohistochemical staining of the myocardium was performed to determine the expression of ERK1/2 to evaluate the effect of different stage of diabetes on the protective effect of ischemic postconditioning after myocardial ischemia.

            RESULTS Compare to the 2NIR group, the 2DIR group had displayed higher LDH and CK levels (P<0.05), with larger infarct size (P<0.05), and downregulation of ERK1/2 level (P<0.05) however between 2NPost and 2DPost group, there was no significant difference (P>0.05) compare to 8 weeks normoglycemic IR group and IPost group, the 8DIR group, and 8DPost group showed increased LDH and CK levels, larger infarct size, and decreased ERK1/2 level (P<0.05). Yet there is no statistical significance between the 8DIR group and 8DPost group.

            CONCLUSIONS Preclinical studies and some clinical trials demonstrated that IPC is associated with attenuation of ischemic reperfusion injury, however, previous studies suggested that the cardioprotective effect of IPC fails in the diabetic state, but our results showed that IPC still has a cardioprotective effect in the early phase of diabetes. Yet further experiments and clinical trials will need to be performed to confirm the results of the studies reviewed here.

            GW33-e0374
            Mechanism of hepatic lipoprotein Perilipin4 on metabolic fatty liver induced by CGI-58 deficiency

            Xinyu Bao, Rongfeng Huang, Mindian Li, Zhihui Zhang

            Department of Cardiology, Southwest Hospital, Third Military Medical University (Army Medical University)

            OBJECTIVES Nonalcoholic fatty liver disease (NAFLD) is an important risk factor for cardiovascular diseases such as coronary heart disease (CHD). The global prevalence rate of NAFLD is up to 24.4%, and lipid metabolism disorder is the key mechanism of its pathogenesis. How to effectively improve liver lipid metabolism will become a key link to protect liver function and reduce long-term cardiovascular and cerebrovascular events. Lipid droplet associated protein CGI-58 is a rate-limiting enzyme that activates triglyceride hydrolysis, promotes lipid droplet decomposition, and is a key inhibitor of liver lipid metabolism disorders. Liver specific knockout of CGI-58 leads to the formation of hyperlipide-induced fatty liver. However, its regulatory mechanism remains unclear. Lipid droplet coated protein Perilipin4 (PLIN4) promotes lipid droplet formation and abnormal lipid accumulation under the regulation of overnutrition. Therefore, this study investigated whether PLIN4 interacts with CGI58 to participate in the formation and pathological progress of NAFLD.

            METHODS CGI58Flox/Flox homozygtic mice aged 6 weeks from the same nest were divided into experimental group (miR-Plin4) and control group (miR-NC) according to the principle of randomization. AAV virus expressing Cre was injected into the experimental group by micro-RNA interference of Plin4 gene expression, and the control group was injected with micro-RNA control fragment. After 6 weeks of high fat diet (60% KCAL) feeding, the liver weight of the mice was weighed to calculate the hepatosomatic weight, liver samples were collected for qPCR and WB detection of virus knockout efficiency, serum was collected to detect liver function and other indicators, liver HE staining and oil red staining were used to observe the tissue morphology and lipid drop size.

            RESULTS The mRNA and protein levels of CGI58 in liver of mice were detected by qPCR and WB. Taking wild-type mice as the baseline, the mRNA levels of liver in miR-Plin4 group and miR-NC group decreased by 94 and 90%, respectively (P<0.0001; P<0.0001), the level of CGI58 protein detected by WB was significantly reduced. Liver weight of mice in miR-PLin4 group was 1.488±0.192 g, and liver weight of mice in miR-NC group was 3.130±0.121 g, P<0.0001; Hepatosomatic proportion of miR-plin4 (5.18±0.92)% and that of miR-NC group (12.33±1.35)%, P<0.0001; Serum alanine aminotransferase was 206.3±49.59(IU/L) in the experimental group, and 926.6±109.2(IU/L) in the miR-NC group, P<0.0001; Serum aspartate aminotransferase was 432.3±106.4(IU/L) in the miR-PLin4 group and 1709±190.8(IU/L) in the miR-NC group, P<0.0001; Liver HE staining and oil red staining indicated that the volume of liver lipid droplets decreased and the lipid change was alleviated in miR-PLin4 group.

            CONCLUSIONS Reducing PLIN4 in liver of mice with CGI58 liver deficiency can significantly improve liver dysfunction, reduce the volume of liver lipid droplets, reduce liver weight, delay or even reverse the occurrence and development of NAFLD induced by high fat diet.

            GW33-e0376
            Low shear stress promotes atherosclerosis via IKKε/STAT1/ NLRP3 mediated endothelial cell pyroptosis

            Yifei Lv, Linlin Zhu, Xiaomin Jiang

            Nanjing First Hospital, Nanjing Medical University

            OBJECTIVES The initiation and progression of atherosclerosis is characterized by vascular endothelial dysfunction, and low shear stress (LSS) of blood flow is a key factor leading to endothelial dysfunction. Caspase-dependent pyroptosis is a novel type of inflammatory programmed cell death characterized by the activation of inflammasomes, especially NOD-like receptor protein 3 (NLRP3). Growing evidence suggests that endothelial cell pyroptosis plays an important role in the development of atherosclerosis. However, the exact mechanism by which low shear stress induces endothelial cell pyroptosis remains unclear.

            METHODS At the cellular level, we investigated the effect of IKKε on the scorching of endothelial cells under LSS and the specific mechanism using molecular biology and immunofluorescence, and at the animal level, we used RT-qPCR and enface staining to detect the expression of scorching-related molecules in different blood flow patterns in the aortic arch and descending aorta.

            RESULTS Our cellular experiments demonstrate that low shear stress induces endothelial cell pyroptosis and promotes the phosphorylation of IκB kinase ε (IKKε). Knockdown of IKKε can significantly reduce low shear stress-induced endothelial cell pyroptosis, and vice versa promotes pyroptosis. Concomitant knockdown of IKKε attenuated low shear stress-induced reactive oxygen species (ROS) accumulation in endothelial cells. IKKε promotes the expression of NLRP3 by activating its downstream signal transducer and activator of transcription 1 (STAT1) activation and nuclear translocation rather than leading to endothelial cell pyroptosis through the ROS pathway. The above results were verified by animal experiments. The phosphorylation level of IKKε in the medial curvature of the aortic arch (AA) of mice was significantly higher than that in the descending aorta (DA). IKKε knockdown significantly reduces the level of NLRP3 in the medial aortic arch and attenuates atherosclerosis in high cholesterol diet-induced ApoE−/− mice.

            CONCLUSIONS These results suggest that low shear stress can play a pro-atherosclerotic role by causing endothelial cell pyroptosis through the IKKε/STAT1/NLRP3 pathway and provide new insights into the formation of atherosclerosis.

            GW33-e0382
            Soluble RAGE attenuates myocardial I/R injury by suppressing monocytes /macrophages-produced interleukin-6

            Jie Zhang1, Xuejie Han1, Jian Liu1, Fenghe Du2, Xiangjun Zeng3, Caixia Guo1

            1Beijing Tongren Hospital Affiliated to Capital Medical University

            2Beijing Tiantan Hospital Affiliated to Capital Medical University

            3Capital Medical University

            OBJECTIVES Inflammation plays a central role during myocardial ischemia/reperfusion (I/R) injury. Previous studies have demonstrated that the receptor for advanced glycation end-products (RAGE) is involved in the pro-inflammatory process of myocardial I/R injury by binding to diverse ligands. Soluble RAGE (sRAGE) is a decoy receptor for RAGE, inhibiting inflammation response. This study aimed to investigate whether the effects of sRAGE on myocardial I/R injury was associated with a reduced inflammatory state.

            METHODS Plasma levels of sRAGE and several inflammatory mediators were measured in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and control subjects (negative coronary arteriographic findings). Myocardial I/R surgeries were operated on cardiomyocyte-specific sRAGE knock-in (sRAGE-CKI) mice and littermate control (sRAGE KIfl/fl) mice by ligation of the left anterior descending coronary artery. Cardiac function and infarct size were evaluated by echocardiography and TTC staining, respectively. Plasma levels of inflammatory mediators in the mice were measured by ELISA. Mouse peripheral blood monocytes were assessed by flow cytometry. The phenotypes of macrophages in the mouse heart were detected by immunohistochemistry.

            RESULTS sRAGE levels in STEMI patients were significantly increased compared with that in the control subjects. There was a negative correlation between the plasma sRAGE level before PCI with interleukin (IL)-1, IL-6 and IL-10. Cardiac overexpression of sRAGE dramatically improved cardiac function and decreased infarct size during myocardial I/R. Furthermore, sRAGE decreased IL-6 level, but did not affect the plasma IL-1 and IL-10 levels compared with the sham group in mice. Mechanistically, sRAGE decreased the numbers of proinflammatory CD14++CD16 monocytes in the mice. In addition, cardiac-specific overexpression of sRAGE increased CD206+ M2-macrophages, and decreased pro-inflammatory iNOS+ M1-macrophages in the heart.

            CONCLUSIONS Our data suggested that sRAGE protected the heart from myocardial I/R injuries. The process might be mediated by inhibiting the numbers of proinflammatory monocytes and infiltration of M1-macrophages, leading to decreased secretion of IL-6.

            GW33-e0383
            Ibrutinib induced connexins degradation contributed to atrial arrhythmia through the activation of autophagy by off-target inhibiting PI3K-AKT-mTOR signaling pathway

            Huiyuan Qin

            The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

            OBJECTIVES Ibrutinib is a Bruton tyrosine inhibitor that has remarkable efficacy against B-Cell cancers. However, according to pivotal trial research, almost 5–9% of the Chronic lymphocytic leukemia (CLL) patients developed atrial fibrillation compared to 0.5–2.4% in the comparator arms. Why ibrutinib could increase the occurrences of atrial fibrillation remained poorly understood. This study aimed to investigate the ibrutinib-related proarrhythmic mechanism in atrial.

            METHODS We performed optical mapping using calcium and action potential dye to explore the intracellular calcium activity and conduction of HL-1 cells with or without ibrutinib treatment. Fluorescence imaging was used to determine the Cx43 distribution and structure of ibrutinib treated HL-1 cells. We also conducted a western blot to analyze the expression of connexins, ibrutinib targets, and autophagy-regulated proteins. The virus- Monomeric cherry (mCherry)-green fluorescent protein (GFP)-LC3 was transfected into cells to display autophagic flux. The structure of autophagosome and autophagolysosome was shown with electron microscopy results.

            RESULTS Our results showed that Ibrutinib enhanced susceptibility to atrial arrhythmia by decreasing the conduction velocity. Compared to the control group, Ibrutinib significantly reduced the expression of connexin 43 and connexin 40 at the protein level. However, the total levels of connexin 43 and connexin 40 were not different between the two groups at the gene transcription level. The autophagy activity was enhanced in the ibrutinib intervention group, and autophagy inhibitors could reverse the degradation of Cx43. Thus, Ibrutinib could induce the connexins degradation contributing to atrial arrhythmia through the activation of autophagy by its off-target effect on the PI3K-AKT-mTOR Signaling Pathway.

            CONCLUSIONS In the present study, we discovered that the concentration of 100 μm ibrutinib could increase susceptibility to AF in HL-1 cells. To further investigate the possible arrhythmogenic mechanism, we demonstrated that the underlying effect was associated with the degradation of Connexin 43. Besides, we found that the decreased expression of Connexin 43 was due to enhanced autophagic activity, and the degradation process was significantly slowed down. At the same time, the autophagy was inhibited in HL-1 cells, suggesting that inhibiting autophagy could be a promising preventative for ibrutinib-related atrial arrhythmia.

            GW33-e0391
            Gut permeability promotes aortic dissection via low-grade endotoxemia

            Gulinazi Yesitayi, Qianru Yuan

            The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES Aortic Dissection (AD) is a severe life-threatening cardiovascular emergency with rapid onset, rapid progress, and high mortality. In recent years, with the continuous in-depth research on the Gut microbiome (GM), the potential role of GM in cardiovascular disease has been revealed. However, it is still unknown whether GM disorders are involved in AD development. This study explored the role of the innate immune inflammatory response caused by the damage of the intestinal barrier in the pathogenesis of aortic dissection.

            METHODS 1. Use proteomics technology to detect the blood samples and tissue of the healthy control group, screening the differential genes and proteins when AD occurs, and through the gene ontology On (Gene Ontology, GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases carry out enrichment analysis of the essential biological processes and critical signal pathways involved in differential genes and proteins in the occurrence of AD, revealing The critical mechanism of AD occurrence. 2. We collected blood samples from 50 healthy controls, 50 hypertensive patients, and 50 AD patients and tested lipopolysaccharide (LPS), which is the component of the outer wall of gram-negative bacteria, also known as endotoxin;interleukin-6 (Interleukin-6, IL-6), a marker protein of inflammation; serum lipopolysaccharide-binding protein (LBP) and soluble CD14 (soluble-CD14, s-CD14). 3. In order to study the potential role of intestinal microbial disorders in AD, fecal samples from the above population were collected, and 16S amplicon sequencing was used for bacterial diversity analysis (including α -diversity, and β -diversity) to screen the differential flora further, analyze the species composition and abundance comparison, and predict the function of the flora.

            RESULTS 1. Proteomics analysis results show that differential proteins are enriched in the Toll-like receptor signaling pathway. 2. Compared with healthy controls and hypertensive patients, AD patients have higher levels of serum LPS, IL-6, LBP, and sCD14; the difference is statistically significant (P<0.05). 3. The composition of the intestinal microbiome was analyzed, and α-diversity and β-multiplicity were evaluated. The results show that compared with healthy controls and hypertensive patients, the intestinal flora of AD patients tends to be more inclined. It produces LPS type.

            CONCLUSIONS After the intestinal barrier function is impaired, LPS-mediated low-grade endotoxemia causes the activation of immune inflammation in the blood vessels and participates in the occurrence and development of aortic dissection.

            GW33-e0398
            The impact of lymphangiogenesis in transplant arteriosclerosis

            Kai Chen1, Rong Mou1, Pengwei Zhu1, Xiaodong Xu1, Han Wang2, Liujun Jiang1, Yanhua Hu1, Xiaosheng Hu1, Qingzhong Xiao2, Qingbo Xu1

            1Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine

            2Centre for Clinical Pharmacology, William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of London

            OBJECTIVES Transplant arteriosclerosis is a major limitation to long-term survival of patients with solid organ transplantation. Although lymphatic vessels have been recently reported to possess organ-specific features in allograft transplantation, the relationship between lymphangiogensis and transplant arteriosclerosis remains unknown.

            METHODS Vascular allografts were performed among wild type (BALB/c, C57BL/6), Lyve1-CreERT2; R26-tdTomato, CAG-Cre-tdTomato, severe combined immune deficiency (SCID), Ccr2 KO, Foxn1 KO and lghm/lghd KO mice. Whole-mount staining and three-dimensional reconstruction depicted the lymphatic vessel regeneration within transparent grafted arteries. Multiple lineage tracing strategies were performed to delineate the cellular origin of lymphangiogenesis within grafts. Single-cell RNA sequencing, Western blotting, quantitative polymerase chain reaction and immunohistochemical staining were used to identify the characteristics of lymphatic endothelial cells and evaluate cellular contributions of related lymphangiogenic factors. AAV.VEGFC, AAV.sVEGFR3-Ig and VEGFR3 inhibitor, MAZ51, were separately applied to explore the possible therapeutic effect.

            RESULTS Lymphangiogenesis within allografted vessels was initiated in the anastomotic sites and primarily derived from recipient pre-existing lymphatic vessels but not bone marrow derived cells. Coexistence of initial and two distinct Foxp2 hi and Icam1 hi collecting lymphatic endothelial cells demonstrated the heterogeneity of lymphatic vessels in vascular allografts. CCL21-expressing lymphatic vessels had a close relationship with tertiary lymphatic organ formation in grafted arteries. Most critically, a positive feedback was revealed between cellular immunity and lymphangiogenesis mediated by VEGFC released from fibroblasts. Taking advantages of a unique recipient replacement phenomenon, early inhibition of lymphangiogenesis in vascular allografts could break this vicious circle and led to a long-term alleviation of transplant arteriosclerosis.

            CONCLUSIONS Our results substantiated the importance of lymphatic vessels serving as a key immunosuppressive target in the treatment of transplant arteriosclerosis.

            GW33-e0401
            Newly-synthesized proteomic analyisis of mesenchymal stem cells under OGD condition

            Dunzheng Han, Dingli Xu

            Nanfang Hospital

            OBJECTIVES Mesenchymal stem cell (MSC) is an attractive choice of regenerative medicine for possible development of clinical applications. The aim of this study was to understand the biochemical and metabolic mechanisms and feedback associated with response to hypoxia and ischemia in MSCs using a metabolic labeling method for cell-selective analysis of newly synthesized proteins.

            METHODS After culturing and identification, murine MSCs were transduced with lentivirus MetRSL274G and supplemented with azidonorleucine (ANL); targeting of a mutant methionyl-tRNA synthetase (MetRS) from MSCs permits ANL charged to initiator tRNAMet and subsequently allows ANL labeling of their nascent proteins. Bio-orthogonal non-canonical amino-acid tagging (BONCAT) and fluorescent non-canonical amino-acid tagging (FUNCAT) were performed to detect the efficiency and specificity of this labeling method. Results showed that MetRSL274G mutant MSCs with ANL treated showed fluorescent protein bands in the gel and strong green signal in cell culture, indicating efficient and specific incorporation of ANL in nascent protein synthesis. MetRSL274G-transduced MSCs were then cultured in glucose/serum-free and ANL supplemented medium under hypoxia (5% CO2 and 95% N2) for 12 h. Newly synthesized proteins were isolated by click chemistry reaction eliminating preexisting proteins and identified by LC/MS.

            RESULTS As results, we found totally 1326 and 1323 of ANL-labeled proteins respectively in Sham and Oxygen and glucose deprivation (OGD) group; 1219 proteins were shared among two groups, accounting for 92±0.2% of all identified proteins in individual group. Notably, 50 proteins were significantly up-regulated whereas 29 proteins were significantly down-regulated in OGD vs. Sham group. These differentially expressed proteins were more pronounced in the pathways of actin cytoskeleton, oxidative phosphorylation and apoptotic process. Some factors like gelsolin and moesin may serve as a crucial role in survival of MSCs under OGD condition.

            CONCLUSIONS Our results showed that mutant MetRSL274G brought about an efficient and specific labeling method of dynamic proteome in MSCs cell line. By this approach, we investigate functional and adaptive changes of MSCs in hypoxic and ischemic environment that help us better understanding how to improve stem cell therapy.

            GW33-e0407
            Knock down of PCSK9 can improve myocardial ischemia/ reperfusion injury by inhibiting autophagy

            Guangwei Huang1,2,3, Xiyang Lu1,2, Xinlin Xiong1,2, Haiyan Zhou1,2, Zhenhua Luo4, Lei Xu3, Wei Li1,2

            1Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, Guizhou, China

            2Guizhou Medical University, Guiyang 550004, Guizhou, China

            3Department of Cardiovascular Medicine, Anshun City People’s Hospital, Anshun 561000, Guizhou, China

            4Department of Central Lab, Guizhou Provincial People’s Hospital, Guiyang 550002, Guizhou, China

            OBJECTIVES To investigate the effect and mechanism of proprotein convertase subtilisin/Kexin type 9 (PCSK9) on myocardial ischemia-reperfusion injury (MIRI) and to provide a reference for clinical prevention and treatment of acute myocardial infarction (AMI).

            METHODS We established a rat myocardial ischemia/reperfusion (I/R) model and AC16 hypoxia/reoxygenation (H/R) model. A total of 48 adult male Sprague-Dawley rats were randomly assigned into 3 groups.

            RESULTS PCSK9 mRNA and protein levels were significantly upregulated during cardiomyocyte hypoxia in vitro and in vivo. Immunohistochemistry confirmed that PCSK9 expression was increased in rat hearts 3 days after anterior descending branch ligation. In vitro and in vivo experimental studies revealed that siRNA knockdown of PCSK9 resulted in reduced expression of the autophagic protein Beclin-1, light chain 3 (LC3) compared to control-treated cells and sham-operated groups, at the same time, the presentation of the autophagic pathway BNIP3 was also downregulated. Furthermore, the PCSK9-mediated small interfering RNA (siRNA) group injected into the left ventricular wall significantly improved cardiac function and myocardial infarct size, as well as the expression of mRNA of Recombinant Human Interleukin-1β (IL-1β) and Nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) was significantly downregulated and reduced the inflammatory response compared with the I/R group.

            CONCLUSIONS In ischemic/hypoxic circumstances, PCSK9 expression was dramatically increased. PCSK9 knockdown alleviated MIRI via the BNIP3-mediated autophagic pathway, and improved myocardial infarct size and cardiac function.

            GW33-e0424
            Novel insights of ANGPTL-3 on modulating cholesterol efflux capacity induced by HDL particle

            Su Xin, Chen Xiang, Wang Bin

            Xiamen Cardiovascular Hospital of Xiamen University

            OBJECTIVES Angiopoietin-like protein 3 (ANGPTL-3) modulates lipid metabolism and the risk of acute coronary syndrome (ACS) via suppressing lipoprotein lipase (LPL). Whether there are other mechanisms are still not elucidated. The current research explored the modulatory roles of ANGPTL-3 on high-density lipoprotein (HDL) particle which further affects the atherosclerotic development.

            METHODS Two hundred individuals were enrolled in the present study. Serum ANGPTL-3 levels were detected via enzyme-linked immunosorbent assays (ELISA). Cholesterol efflux capacity induced by HDL particles was detected through H3-cholesterol loading THP-1 cells.

            RESULTS As shown, the serum ANGPTL-3 levels presented no significant discordance between ACS group with non-ACS group, whereas the serum ANGPTL-3 levels in type 2 diabetes mellitus (T2DM) group was significantly elevated compared with those in the non-T2DM group [428.3 (306.2 to 736.8) ng/mL vs. 298.2 (156.8 to 555.6) ng/mL, P<0.05]. Additionally, the serum ANGPTL-3 levels exhibited elevated in patients with low TG levels compared to those in patients with high TG levels [519.9 (377.6 to 809.0) ng/mL vs. 438.7 (329.2 to 681.0) ng/mL, P<0.05]. By comparison, the individuals in ACS group and DM group presented decreased cholesterol efflux induced by HDL particles [ACS: (12.21±2.11)% vs. (15.51±2.76)%, P<0.05; T2DM: (11.24±2.13)% vs. (14.65±3.27)%, P<0.05]. In addition, the serum concentrations of ANGPTL-3 were inversely associated with the cholesterol efflux capacity of HDL particles (r=-0.184, P<0.05). Via regression analysis, it is shown that that the serum concentrations of ANGPTL-3 were an independent modulator to cholesterol efflux capacity of HDL particle (standardized β=-0.172, P<0.05).

            CONCLUSIONS Conclusively, ANGPTL-3 exhibited a negative modulatory function on cholesterol efflux capacity induced by HDL particles.

            GW33-e0431
            KDM3A attenuate myocardial ischemic and reperfusion injury by ameliorating cardiac microvascular endothelial cells pyroptosis

            Bofang Zhang, Jing Chen

            Department of Cardiology, Renmin Hospital of Wuhan University; Cardiovascular Research Institute, Wuhan University; Hubei Key Laboratory of Cardiology, Wuhan 430000, China.

            OBJECTIVES Even though subjected to successful revascularization therapy, microvascular endothelial cell ischemia-reperfusion (CMEC I/R) injury occurs in approximately 50% of acute myocardial infarction patients, leading to the dysfunction of the cardiac microcirculatory system. Our prior studies have characterized the participation of histone demethylase KDM3A in protecting cardiomyocytes from I/R injury, while its roles in CMEC I/R injury remain to be illustrated.

            METHODS CMEC hypoxia and reoxygenation (H/R) model was established to mimic the ischemia-reperfusion process in vitro. The proliferative and migration abilities of CMEC were measured by the CCK-8 and wound healing assay. Tube formation assay and sprouting assay were performed to determine the angiogenesis ability of CMEC. Also, CMEC death were detected by Hoechst 33342/PI double fluorescent staining. Besides, the rat ischemia-reperfusion injury model was established in vivo. Myocardial infarct size, cardiac function, and cell death were measured by Evans blue and TTC staining, echocardiography assay and TUNEL staining, respectively. In addition, the no-reflow area and capillary density were detected by thioflavin-S and CD31 fluorescent staining. Moreover, the expression of pyroptosis-associated proteins and PI3K/Akt signaling pathway-related molecules were analyzed by Western blot assay.

            RESULTS Here we show that H/R treatment significantly impaired CMEC function and induced CMEC pyroptosis accompanied by the obvious downregulation of KDM3A. Subsequently, gain- and loss-of-function experiments were performed to investigate the effects of KDM3A in the settings of CMEC H/R injury in vitro. KDM3A knockout further aggravated CMEC malfunction and accelerated the expression of pyroptosis-associated proteins including NLRP3, ASC, cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18. Conversely, KDM3A overexpression developed the ameliorated alternations in CMEC H/R injury. Additionally, in vivo experiments also confirmed KDM3A knockout further deterioration of heart function as well as decreased no-reflow area and capillary density. Mechanistically, our data uncovered that KDM3A could activate the PI3K/Akt signaling pathway and mitigate I/R induced CMEC pyroptosis.

            CONCLUSIONS Our present study suggests that KDM3A is a potential therapeutic target for alleviating CMEC I/R injury by activating PI3K/Akt signaling pathway.

            GW33-e0448
            Global phosphoproteomic profiling reveals perturbed signaling in a sheep model of atrial fibrillation

            Qiqiang Jie1,2, Lin Wu1

            1Peking University First Hospital

            2Nanjing First Hospital

            OBJECTIVES Atrial fibrillation (AF) is a common arrhythmia, but the detailed mechanism and underlying signaling networks are unclear. To fully understand the intricate pathogenesis, there are still challenges to overcome. Thus, identifying the fundamental mechanisms and targets of AF progression, then exploring possible treatments, is critically important.

            METHODS In this work, precision mass spectrometry-based proteomics and phosphoproteomics were constructed to depict the pivotal abnormalities of AF, and quantified 2799 proteins and 10,746 phosphorylation sites were mapped to 2886 proteins in AF- and sham-sheep left atrial tissues. Signaling pathways of AF-associated remodeling were evaluated via global statistical enrichment analysis of differential phosphoprotein patterns. The signaling pathway alterations were confirmed via Western blotting and immunohistochemistry.

            RESULTS Deep phosphoproteomic analysis of atrial tissue from sham- and AF-sheep atrial tissue demonstrated a prominent role of adrenergic signaling- and autophagy-regulating roles in AF pathophysiology. Notably, the considerably perturbed pathways included the Hippo signaling pathway, ErbB signaling pathway and spliceosome pathways, which have never been reported to be AF-associated. Alternations in components of these AF development-associated signaling pathway were verified via Western blotting or immunohistochemistry.

            CONCLUSIONS These data reveal the unexpected relationships between cell signaling networks and AF, paving the way for investigation of AF mechanisms and drug targets.

            GW33-e0458
            HSP70 improves coronary microcirculation disturbance in neonatal rat with hypoxia-induced pulmonary arterial hypertension

            Lingjie Yang, Yuming Mu

            Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, and Xinjiang Key Laboratory of Ultrasound Medicine, Urmuqi 830011, China

            OBJECTIVES Right ventricular (RV) heart failure is the main cause of death in pulmonary hypertension (PH), while there is an unmet need for RV-targeted therapies to improve mortality. Heat shock protein 70 (HSP70) acts as a vasoprotective regulator in pulmonary smooth muscle and endothelial cells, while its role in the heart is unclear. This study investigated the effect of HSP70 on RV injury in HPH.

            METHODS HPH model was induced using 10% hypoxia, and a single intratracheal injection of adenoviral vectors carrying HSP70 or luciferase gene was administered. The animals were euthanized 7 or 14 days after gene delivery to assess cardiac structure, function and myocardial perfusion. Also we measured RV microcirculation relevant measures of histology, protein, and gene expression.

            RESULTS Hypoxia induced progressive RV dysfunction, fibrosis, and inflammation. HSP70 prevented hypoxia-induced RV dysfunction and remodeling, improved myocardial perfusion; Besides, HSP70 promoted myocardial microvascular neovascularization by up regulating VEGF; and promoted vasodilation by upregulating eNOS and reducing ET-1; Also, HSP70 reduced the expression of E-selectin and ICAM-1, inhibited the adhesion and aggregation of inflammatory cells in myocardium and the release of inflammatory factors IL-6 and TNF-α (P<0.05), to inhibit microcirculation inflammatory response.

            CONCLUSIONS Together, HSP70 gene transduction can improve myocardial microcirculation and induce the cardioprotective effect of HPH, by promoting myocardial neovascularization and vasodilation, and attenuating microcirculation inflammation, representing a therapeutic approach for PAH and other cardiovascular/pulmonary diseases.

            GW33-e0488
            Deficiency of NLRC5 in macrophages promotes chronic heart failure

            Qing Yu, Ju Peinan, Zhuang Jianhui, Peng Wenhui

            Department of Cardiology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai

            OBJECTIVES Macrophages play an important role in tissue repair and inflammatory response during the process of myocardial infarction. However, the role of macrophages in the microenvironment of chronic cardiac remodeling has not been clearly elucidated. Among NOD-like receptor family members, NOD-like receptor family caspase recruitment domain family domain containing 5 (NLRC5) was an innate immunologic protein and play important roles in chronic inflammation. However, the role of NLRC5 in heart failure (HF) remains unclear. In this study, we determine the role of macrophage NLRC5 in pressure overload-induced HF and dissect the underlying mechanisms.

            METHODS Peripheral blood samples from 20 patients with hypertrophic cardiomyopathy and 20 healthy subjects and heart tissue samples from patients with heart failure were collected to explore the significantly different genes of NLRs family members in peripheral blood monocytes and cardiac macrophages. Then, male C57BL/6J wild-type (WT) and NLRC5 knockout (Nlrc5−/− ) mice were subjected to pressure overload induced heart failure using transverse aortic constriction (TAC). The numbers of macrophages, monocytes and T cells in mice with TAC was determined by flow cytometry. The myeloid conditioned knockout mice and bone marrow transplantation mice were also used to identify myeloid-specific cells NLRC5 plays a major role. The difference cytokine secretion between NLRC5 KO and WT bone marrow derived macrophages (BMDM) was detected by cytokine array and Enzyme linked immunosorbent assay. High performance liquid chromatography mass spectrometry, co-immunoprecipitation and immunofluorescence were used to investigate the target protein that interacted with NLRC5, and western blot and RNA sequencing was used to reveal the underlying mechanism of NLRC5 influencing cardiomyocytes and fibrotic cells in heart failure through macrophage.

            RESULTS NLRC5 was markedly increased in circulating monocytes and cardiac macrophages from patients with hypertrophic cardiomyopathy and mice with pressure overload induced by transverse aortic constriction (TAC). Both global and myeloid-specific NLRC5 knockout significantly aggravated TAC-induced pathological cardiac hypertrophy and fibrosis, as shown by a series of morphological experiments in mice. More importantly, NLRC5-null mice exhibited increased infiltration of macrophages, neutrophils and T lymphocytes in failing hearts. Mechanically, we identified that NLRC5 suppressed the phosphorylation of IKKβ and p38 via interaction with chaperone protein HSPA8 in bone marrow-derived macrophages (BMDMs). In addition, depletion of NLRC5 in BMDMs enhanced the expression and secretion of proinflammatory cytokines such as IL-6, ICAM-1 and CXCL1, while blockade of IL-6 receptor by Tocilizumab alleviated cardiomyocyte hypertrophy and cardiac fibroblast activation induced by conditioned medium from NLRC5-deficient BMDMs. Furthermore, specific IL-6 receptor antagonist Tocilizumab reversed cardiac remodeling and dysfunction caused by NLRC5 deficiency in vivo.

            CONCLUSIONS Our findings suggest that NLRC5 in macrophages positively impacts on cardiac remodeling via interaction with HSPA8, thereby providing a strong pre-clinical foundation that the NLRC5-HSPA8-IL-6 signaling axis may serve as complementary immunomodulatory target for HF.

            GW33-e0508
            Exogenous rDLK1 improves neovascularization after hindlimb ischemia by modulating endothelial progenitor cells mitochondrial function

            Yayu You1,2, Ning Zhang1,2, Zhuo Wang1,2, Zhehui Yin1,2, Xiaojie Xie1,2

            1Department of Cardiology, Second Affiliated Hospital, College of Medicine, Zhejiang University

            2Cardiovascular Key Laboratory of Zhejiang Province

            OBJECTIVES Peripheral arterial disease (PAD) is an atherosclerosis disease characterized by impaired circulation to the lower extremities, commonly results from vascular occlusion or narrowing. Noteworthy, severe PAD leads to critical limb ischemia (CLI), characterized by high mortality and significant amputation rates. Currently, interventions aimed at enhancing angiogenesis and restoring blood flow in CLI are essential. Bone marrow-derived endothelial progenitor cells (EPCs) are a subset of circulating endothelial cells responsible for vascular and tissue repair processes after ischemia, and mitochondria regulate energy balance, and cell fate determination of EPCs. Delta-like non-canonical Notch ligand 1 (DLK1) is a member of the epidermal growth factor-like family of homeotic proteins, typically involved in endothelial cell function. However, its role in angiogenesis remains controversial. Therefore, the present study aimed to determine whether DLK1 could affect angiogenesis and blood flow recovery after CLI.

            METHODS Mouse model of hindlimb ischemia (HLI) created by femoral artery ligation was performed on 6–8 weeks old male C57BL/6 mice. From Day 0, Mice were injected intravenously with recombinant DLK1 (rDLK1) (0.1 mg/kg) or vehicle every 3 days for 14 days. Hindlimb blood flow was sequentially measured before and at 0, 3, 7, and 14 days after surgery. Angiogenesis was detected by CD31 staining, and mature blood vessel was assessed by α-SMA staining. In addition, flow cytometry was used to evaluate the EPC (CD34+/KDR+) mobilization from bone marrow to ischemic muscles. ROS, Δψ m and ATP measurement were further performed in EPCs under oxygen glucose deprivation condition.

            RESULTS rDLK1-treated mice showed better recovery than vehicle control-treated mice at days 3 and 7 post-surgery. This result was further supported by increased CD31+ and a-SMA+ vessels in the ischemic muscles of rDLK1-treated mice compared to the vehicle group. In addition, The rDLK1 group exhibited significantly enhanced EPC mobilization from bone marrow to ischaemic tissue during the progression of hindlimb ischemia. rDLK1 reduced ROS production, Δψ m decrease of EPC mitochondrial and increased ATP levels.

            CONCLUSIONS These findings suggested that rDLK1 repletion may inhibit ischemia-induced damage by promoting EPC mobilization, thus improve angiogenesis and tissue repair. This benefit of rDLK1 may lead to a new therapeutic approach for critical hindlimb ischemia. Under oxygen glucose deprivation condition, mitochondria shift their function from ATP synthesis to reactive oxygen species (ROS) production causing decrease of Δψ m, which could be reversed by rDLK1.

            GW33-e0512
            Human antigen R regulates autophagic flux by stabilizing autophagy-associated mRNA in calcific aortic valve disease

            Juan Fang1,2, Yi Qian1,2,3, Jinyong Chen1,2, Dilin Xu1,2, Naifang Cao1,2, Gangjie Zhu1,2, Wangxing Hu1,2, Haochang Hu1,2, Ningjing Qian1,2, Shuangshuang Yang1,2, Xianbao Liu1,2, Jian’an Wang1,2

            1Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Zhejiang University

            2Key Laboratory of Cardiovascular Disease of Zhejiang Province

            3Department of Cardiology, The Fourth Affiliated Hospital, International Institutes of Medicine

            OBJECTIVES The incidence of calcific aortic valve disease (CAVD) has risen over the last decade and is expected to continue rising. Currently, surgical and transcatheter aortic valve replacements (TAVR) remain the most effective interventions for patients with late-stage CAVD, however, pharmacological approaches have proven ineffective. In this study, we evaluated the role and underlying mechanisms of human antigen R (HuR)-mediated post-transcriptional regulation in CAVD.

            METHODS We performed quantitative real-time polymerase chain reaction and western blot to evaluate the expression of HuR in human calcific aortic valves and human aortic valvular interstitial cells upon osteogenic induction. Then we investigated the role of HuR in osteogenic differentiation and CAVD progression by silencing HuR in vitro and in vivo. Furthermore, we conducted RNA immunoprecipitation and pull-down assay to explored the interaction between HuR and its target mRNA phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A). And more functional studies proven the roles of HuR and PIP4K2A played on autophagy and associated pathway.

            RESULTS We found that HuR was significantly upregulated in human calcified aortic valves and primary aortic valvular interstitial cells (VICs) following osteogenic stimulation. Subsequent functional studies revealed that HuR silencing ameliorated calcification both in vitro and in vivo. For the first time, we demonstrated that HuR directly interacted with the transcript of phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP4K2A), which mediates phosphatidylinositol signaling, facilitates autophagy, and act as an mRNA stabilizer. HuR positively modulated PIP4K2A expression at the post-transcriptional level, and consequently influenced the AKT/mTOR/ATG13 pathway to regulate autophagy and CAVD progression.

            CONCLUSIONS Our study provides new insights into the post-transcriptional regulatory role of HuR in modulating autophagy-positive factors to regulate the pathogenesis of CAVD. Our findings highlight the potential of HuR as an innovative therapeutic target in CAVD treatment.

            GW33-e0530
            Dapagliflozin attenuates cardiac fibrosis by suppressing cardiac fibroblasts STAT3-Grb2 signaling axis in diabetic cardiomyopathy

            Guangfeng Zuo, Liguo Wang, Zhen Ge, Junjie Zhang

            Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006

            OBJECTIVES Cardiac fibroblast (CF) proliferation and activation drive extracellular matrix (ECM) remodeling, leading to fibrosis and diastolic dysfunction (DD) eventually heart failure (HF). Previous study showed that dapaglifozin (DAPA), a sodium glucose transporter 2 inhibitors (SGLT2i), decreased cardiac fibrosis and improved cardiac function in diabetic cardiomyopathy (DCM), which is characterized by DD and/or systolic dysfunction. Herein, we attempt to determine whether DAPA exerts antifibrotic effects on DCM by directly suppressing CF proliferation and activation.

            METHODS High-glucose (HG) cultured adult mouse cardiac fibroblasts (AMCFs) and streptozotocin (STZ) -induced diabetic mice were administrated with or without DAPA. Signaling pathway was verified through gene silencing and western blot in both vivo and vitro. The cardiac structures were determined by histopathological analysis.

            RESULTS Knockdown of signal transducer and activator of transcription 3 (STAT3) or pretreatment with DAPA markedly inactivated STAT3, leading to inhibit Grb2 (growth factor receptor bound protein 2), with subsequently attenuated CF proliferation and activation and cardiac fibrosis in high glucose (HG)-treated AMCFs. These properties of DAPA were dampened when cells were pretreated with colivelin TFA, a potent activator of STAT3. In CF isolated from hearts of db/db mice, DAPA treatment significantly mitigated diabetes induced STAT3 activation, Grb2 phosphorylation and cell proliferation and activation. Additionally, administration of DAPA significantly improved cardiac fibrosis in db/db mice. However, these effects were weakened when diabetic mice pre-subjected to intraperitoneal injection of colivelin TFA.

            CONCLUSIONS DAPA-induced improvement of cardiac fibrosis in diabetic mice, may be at least in part attributable to the suppression of STAT3-Grb2 signaling axis-mediated CF proliferation and activation.

            GW33-e0535
            Dual GIP/GLP-1 receptor activation by tirzepatide promotes BCAA catabolism to prevent myocardial infarction

            Mengya Chen, Saiyang Xie, Wei Deng

            Department of Cardiology, Renmin Hospital of Wuhan University

            OBJECTIVES Adverse cardiac remodeling is an important cause of heart failure. Patients with Type 2 diabetes mellitus (T2DM) have an increased risk of developing heart failure. Controlling blood glucose can reduce the incidence of cardiovascular events in diabetic patients. Tirzepatide (LY3298176, TZP), a novel dual GIPR and GLP-1R agonist, has shown superior efficacy in glycemic control and weight loss. The biological functions in myocardial infarction, however, are still unknown. We wanted to explore the role of tirzepatide in myocardial infarction and the potential mechanism.

            METHODS C57/BL/6J mice underwent permanent coronary artery ligation to induce MI, or sham surgery. A week later, mice received a daily injection of vehicle (n=30) or tirzepatide (10 nmol/kg, n=30) for 7 days. Cardiac function was assessed by using echocardiography and histological and molecular indicators of cardiac remodeling and metabolism were detected. Downstream effectors were screened through Untargeted Metabolomics analysis. In addition, we used Molecular Docking to determine the combining sites of tirzepatide and downstream molecules. In vitro, H9c2 were exposed to hypoxia (5%O2, 24 h) to simulate cardiac hypoxia and ischemic situation and then tirzepatide (100 nmol/L, 24 h). Molecular markers of cardiac remodeling and metabolism were tested.

            RESULTS We found that the mortality of post-MI mice decreased by 36.58% and MI size and incidence of cardiac rupture largely diminished. Cardiac function of MI-tirzepatide group had significantly improved, accompanied by an increase in the left ventricular ejection fraction, fraction shortening, and a decrease in cardiac fibrosis and myocardial inflammation. Mechanistically, tirzepatide was associated with branched chain amino acid (BCAA) catabolism by attenuating BCAA accumulation, ultimately contributing toward the improvement of cardiac function.

            CONCLUSIONS Taken together, these findings provide new insights into the previously unrecognized role of tirzepatide in cardiac protection via enhancing BCAA catabolism. Consequently, these findings may provide new therapeutic options for patients with heart failure.

            GW33-e0540
            The role of SGLT2 inhibitor dapagliflozin in renal protection in diabetic nephropathy use and mechanism research

            Qiu-Min Yang, Jiayin Li, Yi Cai, Zhu Mei, Yan Zhang, Jing Liu, Cheng-Hui Yan

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang 110016, China; phone: (0086)-24-23951988, email: yanch1029@163.com;

            BACKGROUND AND AIMS Dapagliflozin is a new hypoglycemic drug, which not only has a low risk of hypoglycemia, but also has good cardio-renal protection. Dapagliflozin can inhibit SGLT2, a sodium-glucose co-transporter, increasing urine glucose, reducing blood glucose, and achieving the purpose of blood glucose control. However, the protective effect and mechanism of dapagliflozin on diabetic nephropathy is still unclear.

            METHODS db/db diabetic nephropathy animal model were used to investigate the effect of dapagliflozin on diabetic nephropathy. Eight-week-old diabetic mice were randomly divided into two groups: normal control group and drug-treated group, fed for 12 weeks, during which body weight and blood glucose were monitored regularly. After 12 weeks, the mice were sacrificed, and kidney tissue and serum were collected. The kidney tissue was isolated and observed at the serological and tissue levels, and the inflammatory response of diabetic mice was observed at the protein level. At the same time, AD293 cells were stimulated with hydrogen peroxide to simulate the inflammatory response in diabetic mice. Furthermore, overexpression or knockdown of SGLT2 detected the anti-inflammatory effect in AD293 with or without Dapagliflozin.

            RESULTS Dapagliflozin increases the survival rate of diabetic mice, reduce the fasting blood glucose level of diabetic mice, alleviate the expansion of the mesangial matrix and fibrosis in the kidney tissue of diabetic mice, and improve the diabetic mice decreased renal function in db/db mice. Furthermore, dapagliflozin can reduce the inflammatory response in the kidney tissue of diabetic mice, and at the protein and tissue levels. It also can be observed that dapagliflozin can reduce the protein expression level of SGLT2. In vitro experiments, dapagliflozin can reduce the inflammatory response stimulated by hydrogen peroxide and the expression level of SGLT2. When the protein expression level of P65 was inhibited, the protein expression level of SGLT2 in the cells was also reduced. When the expression level of SGLT2 was inhibited, the protein expression level of p-P65 in the cells was also decreased. When SGLT2 was overexpressed, the expression level of p-P65 in the cells also decreased rise.

            CONCLUSION Dapagliflozin may reduce the expression of SGLT2 by reducing the inflammatory response. The reduced expression of SGLT2 also inhibits the production of some inflammatory responses, thus forming a good cycle and better exerting the kidney protection of Dapagliflozin effect.

            GW33-e0544
            Empagliflozin ameliorates cardiac dysfunction through suppressing macrophage recruitment via NLRP3/IL1β signaling in murine models of heart failure

            Guiquan Zhou1,2,3, Ying Wang1,2,3, Wenxu Pan1,2, Meiling Hu1,2, Gaoshan Li1,2, Jun Jin1,2

            1Institute of Cardiovascular Diseases of PLA, Xinqiao Hospital, Army Medical University, Chongqing, China

            2Department of Cardiology, Xinqiao Hospital, Army Medical University, Chongqing, China

            3These authors equally contributed to this work

            BACKGROUND Recent studies have shown that inhibitors of sodium-glucose cotransporter 2 (SGLT2is) can reduce the risk of heart failure and cardiovascular deaths in patients irrespective of the presence or absence of diabetes. However, its cardioprotective effects and related mechanisms in non-diabetic heart failure remain ambiguous.

            OBJECTIVES This study sought to explore whether Empagliflozin (Empa) can ameliorate cardiac outcomes in murine models of ischemic and non-ischemic heart failure and potential mechanisms.

            METHODS 12-week-old male C57BL6/J mice underwent treatment of Empa (10 mg/kg) or isotype control by oral gavage every day for 3 weeks. Heart failure was induced by permanent ligation of the left anterior descending artery (LAD) or Angiotensin II infusion by osmotic pump implantation. Echocardiography was applied weekly to evaluate cardiac function. Plasma BNP and supernatant cleaved IL-1β level was detected by ELISA kit. Myocardial hypertrophy was evaluated by wheat germ agglutinin (WGA) staining, and the fibrosis area was analyzed by Masson-trichrome staining or picro-sirius red staining on paraffin sections. Flow cytometry was employed to analyze the recruitment of immune cells into the myocardium. The expression of IL1β by macrophages in tissue was investigated by immunofluorescence. Primary peritoneal macrophage cells (Pmacs) were induced by 3% thioglycolate (2 mL/mouse) for 4 days. After pre-treatment with Empa (200 μM) for 30 min, Pmac were primed by LPS (10 ng/mL) and interferon-γ (2 ng/mL) stimulation for 6 hours and treated with ATP (5 μM) at last 30 min for NLRP3 inflammasome activation. Gene and protein expression of inflammation-related genes in cells were analyzed by qPCR and western blot.

            RESULTS In both experimental heart failure models, Empa treatment abolished the worsening of cardiac remodeling and cardiac function, as demonstrated by significant reduction of plasma BNP levels, decrease of cardiac hypertrophy and myocardial fibrosis, and restoration of cardiac function. Flow cytometrical analysis showed that Empa treatment significantly reduced the recruitment of inflammatory bone marrow-derived MHCII+CCR2+ macrophages into myocardium. Mechanistically, Empa treatment significantly attenuated NLRP3 inflammasome activation and thereby decreased the expression of downstream pro-inflammatory cytokines (Il6, Il1β etc.) and chemokines (Ccl2, TNFα etc.) in Pmac ex vivo.

            CONCLUSIONS These findings collectively suggest that Empa administration can significantly ameliorate the cardiac outcomes of non-diabetic heart failure, possibly by regulating AMPK phosphorylation, in turn suppressing the over-activation of NLRP3 inflammasome and downstream inflammation response in macrophages.

            GW33-e0546
            Cardiac overexpression of PHD3 can alleviate the cardiac function impairment of chronic intermittent hypoxia in mice with cardiac pressure overload

            Xuan Xu1,2, Fuchao Yu1, Penghao Zhen2, Tao Wang2, Jiayi Tong1

            1Department of Cardiology, Zhongda Hospital Affiliated to Southeast University

            2Southeast University

            OBJECTIVES Obstructive sleep apnoea (OSA) accelerates the development and progression of heart failure (HF). However, the underlying molecular mechanism has not been elucidated, and effective treatments are also lacking. This study explored the chronic intermittent hypoxia (CIH) accelerates the occurrence and development of HF and identify new therapeutic directions based on the corresponding mechanisms.

            METHODS Mice were modeled by transverse aortic constriction (TAC) surgery or/and CIH exposure. Tail vein injection injection of an adeno-associated virus 9 (AAV9) expressing prolyl hydroxylase 3 (PHD3) (AAV9-PHD3) for drug treatment. Echocardiography analysis, histopathology, western blotting, and Real-time PCR methods were performed to elucidate the mechanism.

            RESULTS CIH exposure promotes long-term abnormal expression of hypoxia-inducible factor 1α (HIF-1α) in mice subjected to TAC, further inducing continuous upregulation of miR-29c expression. Together, HIF-1α and miR-29c inhibit the expression of sarco/endoplasmic reticulum calcium ATPase 2a (SERCA2a) in the nucleus and cytoplasm in cardiomyocytes, Synergistically accelerate cardiomyocyte hypertrophy and cardiac dysfunction. Treatment with AAV9-PHD3 inhibited CIH-induced HIF-1α activation in the mouse heart while decreasing miR-29c expression, stabilizing the level of SERCA2A in the mouse heart, alleviates cardiac dysfunction and cardiomyocyte hypertrophy.

            CONCLUSIONS CIH exposure in combination with TAC can cause further hypertrophy of mouse cardiomyocytes and promote cardiac dysfunction. Overexpression of PHD3 may be its potential therapeutic approach.

            GW33-e0557
            E3 ubiquitin-ligase Trim69 prevents D-galactose-induced cardiac aging in rats by suppressing oxidative stress and apoptosis

            Yifan Huang1,2,3, Jian Yang1,2,3, Jing Zhang1,2,3, Jingyi Wu1,2,3

            1Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University

            2Institute of Cardiovascular Disease, China Three Gorges University

            3HuBei Clinical Research Center for Ischemic Cardiovascular Disease

            OBJECTIVES Cardiac aging manifests as a progressive deterioration in cardiac structure and function, resulting in subsequent heart failure. The main purpose of our study is to investigate whether the altered expression of Trim69 affects cardiac aging.

            METHODS The aging model was constructed in SD rats by subcutaneous injection of D-gal (150 mg kg−1 d−1) for 8 weeks. Echocardiography was used to evaluate the cardiac function. Transmission electron microscope was used to observe the ultrastructure of cardiomyocyte. SA-β-galactosidase staining was performed to assess cardiac aging. Western-blotting was applied to detect the expression of age-associated proteins (P53, P21), and Trim69. Reactive oxygen species (ROS) was evaluated through measuring 3-Nitrotyrosine by immunohistochemistry. Tunnel staining was used to measure apoptosis. Masson trichrome staining was used to assess cardiac fibrosis and WGA staining was used to assess cardiac hypertrophy.

            RESULTS In present study, our results revealed that the expression of Trim69 was decreased while the expression of age-associated proteins (P53, P21), ROS level, and apoptosis activity was significantly increased in the heart tissue from aging rats induced by D-gal. Overexpression of Trim69 alleviates cardiac aging induced by D-gal (SA-β-galactosidase, P21, P53), as well as the accompanied cardiac hypertrophy, fibrosis, and myocardial ultrastructural derangement. Echocardiography also indicated that the compromised cardiac function induced by D-gal was reversed in rats from Trim69-overexpression group. In addition, the reduced ROS level and apoptosis activity suggested that Trim69 might prevent cardiac aging through oxidative stress and apoptosis pathway.

            CONCLUSIONS Trim69 might play a protective role on cardiac aging via the suppression of oxidative stress and apoptosis.

            GW33-e0561
            mir-3154 regulates phenotypic conversion of vascular smooth muscle cells by targeting Pax7

            Yisi Liu, Xiaoxiang Tian, Dan Liu, Xiaolin Zhang, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, The General Hospital of Northern Theater Command

            OBJECTIVES Vascular smooth muscle cells transform from differentiated phenotype to synthetic phenotype can lead to many cardiovascular diseases, such as abdominal aortic aneurysm and vascular remodeling. Finding the regulatory molecules of smooth muscle cell phenotype transformation is crucial for the discovery of therapeutic targets for vascular injury. Currently, there are 5 literatures about mir-3154 searched on PubMed. As a prognostic biomarker of cervical cancer and leukemia, there are no literatures about the biological function of mir-3154 at present. This study is the first to find the regulatory role of mir-3154 in vascular smooth muscle cells. The purpose of this study was to explore the regulatory role of mir-3154 in phenotypic transformation of vascular smooth muscle cells.

            METHODS Primary vascular smooth muscle cells were cultured and treated by angiotensin II (1 μmol/L) with mimic-NC or miR-3154 mimic transfection. After angiotensin II (1 μmol/L) stimulation, real-time quantitative PCR (RT-QPCR) detected a slight increase in mir-3154 expression. Cell proliferation was detected by EDU immunostaining. CCK8 was used to detect cell proliferation activity. Cell migration was detected by Transwell Chamber analysis. The expressions of PCNA, cyclinD1, α-smooth Muscle actin and trans-coagulant protein (SM22α), MMP2 and Pax7 were detected by Western blot.

            RESULTS Compared with the control group, the expression level of miR-3154 in miR-3154 mimic group increased (P<0.05), the positive proportion of EDU increased, the expression of PCNA and CyclinD1 increased, the expression of SMA and SM22 decreased, the OD value of cells increased, and the number of migratory cells increased. However, this regulation is reversed by Pax7. MiR-3154 was identified as the upstream of PAX7 by luciferase assay and investigated by gain/loss-of-function approaches.

            CONCLUSIONS mir-3154 regulates phenotypic conversion of vascular smooth muscle cells through Pax7.

            GW33-e0562
            miR-193a-5p and its target genes CCND1, CCNE1 and CXCR4 modulate proliferation and migration of vascular smooth muscle cells in angiotensin II-induced the abdominal aortic aneurysm mice model

            Yisi Liu, Xiaoxiang Tian, Dan Liu, Xiaolin Zhang, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES AAA refers to the abdominal aortic aneurysm with a diameter greater than 3 cm and dilation of more than 50%, and its incidence is increasing year by year. Its treatment usually includes surgery and interventional vascular stents, but there is no effective drug treatment at present, so it is particularly important to find regulatory targets for abdominal aortic aneurysm. The purpose of this study is to explore the role and mechanism of mir-193a-5p in abdominal aortic aneurysm, and strive to provide a new target for the treatment of abdominal aortic aneurysm.

            METHODS qRT-PCR were detected the expressions of mir-193a-5p in abdominal aortic aneurysm vascular tissue and AngII treated vascular smooth muscle cells. Western blot was used to detect the effects of mir-193a-5p on PCNA, CCND1, CCNE1, CCNE1, CXCR4. CCK-8 method, EdU staining method, flow cytometry, wound healing and Transwell method were used for detection effects of mir-193a-5p on proliferation and migration of vascular smooth muscle cells.

            RESULTS In AAA patients, vascular tissue and AngII treated cells vascular smooth muscle cells, mir-193a-5p expression was significantly decreased, while CCND1, CCNE1, CXCR4 expression was significantly up-regulated. mir-193a-5p overexpression can inhibit the proliferation and migration of vascular smooth muscle cells.

            CONCLUSIONS mir-193a-5p inhibits proliferation and migration of vascular smooth muscle cells by targeting CCND1, CCNE1 and CXCR4, thus providing an effective target for the treatment of AAA.

            GW33-e0563
            FGF21 deficiency promotes heart failure by impairing mitochondrial dynamics and inhibiting mitophagy

            Bing Yan, Mei Zhu, Yi Cai, Yan Zhang, Jing Liu, Xiaojie Zhao, Haixu Song, Dan Liu, Xiaoxiang Tian, Xiaolin Zhang, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Fibroblast growth factor 21 (FGF21) is a pleiotropic hormone, secreted mainly by the liver, considered as a major regulator of energy homeostasis. Cardiovascular disease is a serious threat to human health and life, and has become the number one killer of human health. Common cardiovascular diseases include hypertension, coronary heart disease, etc. An important cause for heart failure is cardiac remodeling. Therefore, slowing or reversing cardiac remodeling in patients is the focus of clinical treatment of cardiovascular disease. Studies have found that mitochondrial dysfunction may lead to myocardial hypertrophy, causing heart failure. Under normal circumstances, the adult heart is mainly powered by fatty acid oxidation. Studies have found that before the occurrence of left ventricular hypertrophy and heart failure, the increase of pressure load will lead to changes in the energy metabolism of myocardial mitochondria, and the myocardial energy supply from fatty acids is converted into glucose energy. This alteration in energy metabolism plays an important role in protecting the heart from irreversible damage during the early stages of cardiac remodeling. Recent research revealed that FGF21 could play an important role in cardiac pathological remodeling effects and preventing cardiomyopathy, but the underlying mechanism remained largely unknown. The aim of this study was to clarify the mechanism of FGF21 cardiac protective effects.

            METHODS We assessed plasma FGF21 levels in patients with severe symptomatic heart failure (ejection fraction ≤35%, n=18) and control subjects (n=22) by ELISA analysis. Furthermore, we engineered FGF21 knock out mice and used the high-fat diet to produce a cardiac dysfunction model. The effects of FGF21 and its downstream mediators were subsequently elucidated using western blot, qRT-PCR, and mitochondrial morphological, functional analysis.

            RESULTS The plasma FGF21 levels were lower in patients with severe symptomatic heart failure compared with the control subjects (331.4±188.9 vs 496.2±274.7 pg/mL, P<0.05). FGF21 knock out mice resulted in cardiac dysfunction accompanied by a decline in global longitudinal strain and ejection fraction which was independently of obesity. Mitochondrial quality, quantity and functions were abnormal accompanied with the decreased levels of OPA1 (optic atrophy-1)/MFN2 (mitofusin-2) in FGF21−/− mice. In contrast to FGF21 knockdown, the overexpression of FGF21 can alleviate high fat diet-induced cardiac dysfunction. In vitro study FGF21 siRNA can inhibit the cardiomyocytes mitophagy and deteriorate mitochondrial dynamics, functions impairment induced by PA. Both recombinant FGF21 and adeno virus mediated FGF21 expression can alleviate PA induced mitochondrial impairment by restoring mitochondrial dynamics.

            CONCLUSIONS FGF21 is essential for maintaining mitochondrial dynamics and functions in cardiomyocytes. FGF21, as an important target in regulating cardiomyocytes mitophagy under oxidative stress, will provide new therapeutic options for heart failure patients.

            GW33-e0564
            AMPKγ2 regulated macrophage migration after myocardial infarction via YY1/CXCL16/CXCR6 axis

            Ziping Song, Dan Liu, Haixu Song, Yan Zhang, Xiaojie Zhao, Xiaoxiang Tian, Chenghui Yan, Yaling Han

            Department of Cardiology and Cardiovascular Research Institute of PLA, General Hospital of Northern Theater Command, Shenyang 110016, China

            OBJECTIVES Recent years myocardial infraction (MI) has got developed therapeutic strategy, however, cardiac remodeling and dysfunction post- myocardial infraction remain common and remain keep high mortality. In the early stage after MI, Th1 lymphocyte secretes amounts of IFN-γ, which stimulates monocyte and macrophage activation. Therefore inhibiting excessive inflammatory reaction may repress cardiac necrosis and benefit cardiac dysfunction post-MI. However, how to regulate and target macrophage migration to restrain cardiac inflammation is still needed to be elucidated.

            METHODS Firstly, AMPKγ2 level in plasma of myocardial infarction patients was tested by Elisa assays. Experimental LAD surgery was conducted to establish myocardial infraction model in vivo. IFN-γ was employed to simulate inflammatory conditions in macrophage. To identify the mechanism by which AMPKγ2 deletion promoted migration, we performed transcriptome sequencing (RNA-Seq) based on silencing AMPKγ2 and corresponding control. LyZ2 specific knockout of AMPKγ2 mice were employed to test the role of AMPKγ2 in macrophage in vivo. Adeno-associated virus (AAV) carrying CMV and F4/80 promoter injection was performed to simulate AMPKγ2 specifically overexpression of macrophage in vivo.

            RESULTS Elisa assays were performed to find AMPKγ2 was declined in myocardial infarction patients. Besides, AMPKγ2 was downregulated by inflammatory stimuli such as IFN-γ, TNFα and CoCl2 in RAW264.3 cell line, AMPKγ2 was declined as well as in bone marrow derived macrophage (BMDM) extracted from mice subjected to MI. AMPKγ2 repressed macrophage migration and inflammatory factor expression in vivo and in vitro. Besides, CXCL16/CXCR6 axis was the key contributor for macrophage migration involved in MI, which was alleviated by AMPKγ2 administration via transcriptional regulation. CXCL16 secretion in plasm of mice subjected to MI reached two folds of sham group at 7 D post-MI, which was rescued by global overexpression of AMPKγ2 using AAV carrying CMV promoter. Meanwhile, AAV-CMV-AMPKγ2 group repressed CXCL16 expression in BMDM when MI-7 D. AMPKγ2-KO showed increased CXCL16 expression in BMDM under physiological condition. AMPKγ2-KO aggravated MI-induced inflammation activation, shown as elevated inflammation factor, even facilitated CXCL16 and CXCR6 expression in BMDM derived from mice post-MI 7 D. AMPKγ2 repressed CXCL16/CXCR6 axis via restraining YY1 expression to rescue cardiac dysfunction after myocardial infarction. IFN-γ induced HOXA5 downregulated, which repressed AMPKγ2 transcriptional activity. Overexpression of HOXA5 repressed IFN-γ mediated YY1/CXCL16/CXCR6 expression and following macrophage migration, instead. Finally, AMPKγ2 mediated the regulation of migration and inflammation in macrophage involved in MI via the YY1/CXCL16/CXCR6 pathway was dependent on AMPK activity, our current data supported AMPKγ2 maintain the stability of AMPK complex composed of α1-β1-γ2 subunits in macrophage.

            CONCLUSIONS In our current study, IFN-γ induced HOXA5-AMPKγ2-YY1-CXCL16-CXCR6 pathway played an important role in cardiac dysfunction following myocardial infarction, AMPKγ2 can be developed as a potential therapeutic target to ameliorate cardiac remodeling post-myocardial infarction.

            GW33-e0565
            Endogenous S100A12 transcriptional activation of annexin A5-RAGE aggravates acute myocardial infarction injury through excessive neutrophil extracellular trap formation

            Xi Zhang, Dan Liu, Yujie Zhang, Yi Cai, Xiaoxiang Tian, Xiaolin Zhang, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Members of the S100 protein family have been reported to function as endogenous danger signals (alarmins) playing an active role in tissue inflammation and repair when released from myeloid cells. However, the role of S100A12 in the etiology of Acute Myocardial Infarction (AMI) is not well understood. Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of AMI and in the externalization of some S100 family members. Here, we investigated the effect of S100A12 on neutrophils’ function and myocardial injury after AMI.

            METHODS Since S100A12 is a human specific molecule and not expressed in mice, we constructed transgenic (TG) mice expressing S100A12 in myeloid cells. Myocardial infarction was induced by ligating the left anterior descending coronary artery (LAD). Cardiac function was assessed by echocardiography. Primary neutrophils from TG and WT mice bone marrow were isolated and cultured. In vitro experiments we used the overexpressing plasmid to increase the expression of S100A12 and small interfering RNA (siRNA) to inhibit the expression of S100A12. Western blotting, quantitative RT-PCR, immunofluorescence (IF), immune-histochemistry (IHC) and Masson’s trichrome staining were used to explore the function of S100A12. The levels of NETosis- and apoptosis-associated proteins were analyzed by Western blotting, TUNEL and IF staining. The formation of NETs was visualized using differential interference contrast (DIC) method. Intracellular Ca2+ uptake was detected by the Rhod-2 probe using confocal imaging.

            RESULTS We found significant increase of S100A12 level after AMI in vitro and in vivo. Moreover, S100A12 markedly increased neutrophil infiltration and exacerbated the damage of myocardial injury in TG mice compared to WT mice. Within the infarct zone, more markers of NETs were observed in TG mice, whereas intraperitoneal injection of DNase I decreased the damage effect of NETs. By dual-luciferase reporter assay we found that Hypoxia-inducible factor-1α (HIF1α) directly bound to the promoter of the S100A12 gene and regulated S100A12 expression. Whereas, siRNA-mediated S100A12 silencing reduced the production of NETs. We next used tandem mass tag (TMT) labeling quantitative proteomic technology and discovered that annexin a5 (ANXA5) was a receptor with significantly different expression level in TG compared with WT mice. In vitro experiments demonstrated that there existed a direct interaction between ANXA5 and S100A12. Furthermore, ANXA5 increased the expression of receptor for advanced glycation end products (RAGE) by up regulating STAT3 and promoted NETs formation through ERK-ROS-neutrophil elastase (NE) pathway.

            CONCLUSIONS Our findings reveal a critical role of S100A12 in regulating neutrophil activation and NETs formation, resulting in aggravated myocardial injury after AMI. In such a process, S100A12 regulates NETosis via the Hif1α-S100A12-ANXA5/RAGE pathway. S100A12 is a useful molecular marker and possible target for treatment for AMI.

            GW33-e0566
            CREG1 attenuates abdominal aortic aneurysm formation through modulating vascular smooth muscle cell phenotype

            Yaohan Tang, Shuo Wang, Xiaoxiang Tian, Dan Liu, Chenghui Yan, Yalin Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Vascular smooth muscle cell (VSMC) phenotypic switch from a contractile to a synthetic phenotype plays a significant role in abdominal aortic aneurysm (AAA). CREG1 (Cellular Repressor Of E1A-Stimulated Genes 1) is a glycoprotein that antagonizes transcriptional activation of E1A and may contribute to the transcriptional control of cell growth and differentiation. It has been reported that CREG1 promotes smooth muscle cell contractile phenotype, however, the role of CREG1 in angiotensin II (Ang II)-induced AAA remains unclear. The purpose of this article is to clarify the role of CREG1 in AAA.

            METHODS To investigate the function of CREG1 in AAA formation, mice deficient in Apoe (Apoe-/-) or both CREG1 systemic overexpression and Apoe-/- were subjected to an angiotensin II infusion model of AAA formation. To further clarify the therapeutic effect of CREG1, Apoe-/- mice were injected with the CREG1 recombinant protein subcutaneously using micropumps. Aortas were harvested at different time points and the diameter of the aortas were measured. Dissection of mice aortas for biological and functional determination. Masson staining was used to assess collagen deposition. Verhoeff’s Van Gieson (EVG) staining was used to assess elastic fiber breakage. Western blot, immunofluorescence, immunohistochemistry, and quantitative polymerase chain reaction were used to assess protein and gene expression. Vascular smooth muscle cells were isolated and CREG1 was overexpressed by adenovirus.

            RESULTS The expression of CREG1 decreased with Ang II stimulation in a time dependent manner in vivo and in vitro. Compared with AAA model group, CREG1 overexpressed mice significantly attenuated Ang II-induced AAA incidence, aortic dilation and severity, accompanied by preserved α-SMA expression and reduced elastin degradation, MMP2 activity, deposition of collagen and blood pressure. The CREG1 recombinant protein group had consistent results. In VSMC, Ang II leads to a transition from contractile to synthetized, which can be reversed by overexpression of CREG1. Overexpression of CREG1 significantly increased the expression of systolic markers SM22 and α-SMA, while decreased the expression of MMP9 and MMP2.

            CONCLUSIONS Our results indicate that in response to Ang II stimulation, CREG1 maintains aortic VSMC phenotype, ECM homeostasis, structural integrity and reduces AAA formation. Thus, targeting CREG1 provides a potential therapeutic strategy for AAA.

            GW33-e0567
            Role of apamin-sensitive small conductance calcium-activated potassium currents in regional repolarization reserve in pacing rabbit hearts

            Hongpeng Yin, Bin Li, Dechun Yin

            Department of Cardiology, The First Affiliated Hospital of Harbin Medical University

            OBJECTIVES Long-term right ventricular pacing leads to an increased risk of sudden death. Apamin-sensitive small conductance calcium-activated K current (IKAS) is up-regulated during ventricular pacing. The purpose of this study was to determine the role of IKAS in repolarization reserve that leads to the regional distribution of Action potential duration (APD).

            METHODS There were 24 female New Zealand rabbits, including 10 for acute experiment and 14 for chronic experiment. Epicardial optical mapping was performed in both paced and normal ventricles in two groups. Action potential duration (APD80) was determined during right atrial and ventricle pacing. AT-APD correlation and ventricular stability was tested before and after IKAS blockade.

            RESULTS There were 24 female New Zealand rabbits, including 10 for acute experiment and 14 for chronic experiment. Epicardial optical mapping was performed in both paced and normal ventricles in two groups. Action potential duration (APD80) was determined during right atrial and ventricle pacing. AT-APD correlation and ventricular stability was tested before and after IKAS blockade.

            CONCLUSIONS Long-term ventricular pacing leads to an increase in the intracellular Ca2+ concentration in the paced far-point cardiomyocytes, which activates IKAS, shortens APD, and maintains uniform ventricular repolarization. APD in the paced heart has regional adaptability, IKAS participates in the repolarization reserve of APD regional distribution, and blocking IKAS increases the susceptibility of ventricular arrhythmia.

            GW33-e0572
            miR-22 regulates AngII-induced hypertension

            Shanquan Gao, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES Hypertension and its complications are the primary risk factor of cardiovascular diseases. Although extensive and sustained efforts have been made to understand the pathogenesis of essential hypertension, its potential cellular and molecular mechanisms are still elusive, which need to be further clarified. Hypertension is associated with vascular changes, and the disturbance of vascular smooth muscle cell signal pathway and the change of its function play a basic and core role in the occurrence and development of hypertension. MicroRNA has been proved to regulate the level of key genes controlling contraction, remodeling, and phenotypic regulation in vascular smooth muscle cells, and plays an important role in controlling the development and function of vascular smooth muscle cells, including proliferation, differentiation, and phenotypic transformation. Among the miRNAs that can regulate smooth muscle function, which can also play an important role in systemic hypertension is not clear. Therefore, to identify miRNAs that can directly regulate blood pressure is a problem that needs to be solved in the research field. The aim of our study was to identify miRNA that directly regulates vascular smooth muscle function and blood pressure.

            METHODS A mouse model of hypertension was established by subcutaneously implanting a micro-osmotic pump into the back of the mouse and continuously pumping AngII. We use the isolated vascular ring experiment to evaluate the changes of vascular ring tension and study the vasomotor function. We isolated vascular smooth muscle cells from mouse aorta and cultured them in vitro. We used cre/flox technique to construct smooth muscle specific miR-22 overexpression mice. We used luciferase reporter gene experiment to verify the target gene of miR-22. We used miR-22 minic to transfect vascular smooth muscle cells to overexpress miR-22 in the cells.

            RESULTS Through the screening and comparison of online databases, we found that miR-22 may play an important role in the regulation of hypertension. We found that the expression of miR-22 in aorta of AngII-induced hypertensive mice was down regulated. We used mice with smooth muscle specific miR-22 overexpression and wild-type mice to construct AngII- induced hypertensive mice and found that overexpression of miR-22 in smooth muscle may elevate hypertension. In isolated vascular rings, we found that overexpression of miR-22 in smooth muscle could promote vasoconstriction. After screening, we believe that PTGS1 and PLA2G6, two important enzymes in arachidonic acid metabolic pathway, may be potential target genes of miR-22 to regulate hypertension. Finally, luciferase reporter gene experiment was used to verify the target genes.

            CONCLUSIONS miR-22 plays a regulatory role in AngII induced hypertension by regulating the expression of arachidonic acid metabolism related genes PLA2G6 and PTGS1.

            GW33-e0578
            FABP5 deficiency aggravates pathological cardiac remodeling and dysfunction by impairing mitochondrial function

            Shanquan Gao, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES Heart failure (HF) is one of the leading causes of death worldwide. Although its therapeutic strategies and drugs have made significant progress, its current therapeutic methods are still limited, so it is necessary to continue to study the pathogenesis of HF. HF evolves from pathological cardiac remodeling and homeostasis of energy metabolism is the basis of normal heart function. Energy metabolism disorders are associated with cardiac dysfunction. Fatty acids (FA) represent the main energy substrate of the heart. The water solubility of FA is low, and their transport into specific cells and organelles require the help of fatty acid-binding proteins (FABP). Fatty acid-binding protein 5 (FABP5) is an important member of the FABP family. The role of FABP5 in pathological cardiac remodeling and dysfunction remains unknown. We aimed to investigate the role of FABP5 in pathological cardiac remodeling and HF.

            METHODS We performed TAC to establish the pressure-overload pathological cardiac remodeling and HF model in mice. Heart tissues were prepared for Single-cell sequencing and the transcriptome data of single cells were obtained by 10× single-cell sequencer and analyzed by R Studio. CRISPR/cas9 technology was used to generate FABP5-deficient mice. The small animal ultrasound imaging system was used to evaluate cardiac function. Histopathological examination, transmission electron microscopy, and ATP content assay were used to investigate the role of FABP5 in pathological cardiac remodeling and HF. We used small interfering RNA (siRNA) to downregulate FABP5 mRNA expression in cardiac fibroblasts (CFs) in vitro. Dihydroethidium (DHE) staining was performed to detect oxidative stress in CFs. The oxygen consumption rate (OCR) of adherent living cells was measured by seahorse XFe 24 extracellular flux analyzer to evaluate the mitochondrial respiratory function in vitro.

            RESULTS FABP5 expression was increased in pressure-overloaded hearts and mainly expressed in endothelium and cardiac fibroblasts (CFs). FABP5 deficiency aggravated pressure-overload-induced cardiac dysfunction, cardiac hypertrophy and fibrosis. FABP5 deficiency aggravated structural and functional damage of mitochondria in myocardial and cardiac fibroblasts after TAC and TGF-β treatment.

            CONCLUSIONS FABP5 deficiency aggravates pressure-overload-induced pathological cardiac remodeling and dysfunction. Mechanically, FABP5 deficiency mediate structural and functional impairment of mitochondria in myocardial and cardiac fibroblasts.

            GW33-e0584
            Plexin D1 mediates disturbed flow-induced macrophage polarization in murine carotid bifurcation lesions

            Zhang Suhui1, Zhang Yingqian2, Zhang Peng3, Wei Zechen4, Hui Hui4, Tian Jie4, Chen Yundai2

            1Medical School of Chinese PLA, Chinese PLA General Hospital

            2Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital

            3School of Computer and Information Technology, Beijing Jiaotong University

            4CAS Key Laboratory of Molecular Imaging, Beijing Key Laboratory of Molecular Imaging, The State Key Laboratory of Management and Control for Complex Systems, Institute of Automation, Chinese Academy of Sciences

            OBJECTIVES Atherosclerosis preferentially develops at bifurcations exposed to disturbed flow. Plexin D1 (PLXND1) responds to mechanical forces and drives macrophage accumulation. However, the distribution of PLXND1 in bifurcation lesions and its role in the process of macrophage polarization remains unelucidated. In this study, we investigated the relationship between PLXND1 and bifurcation lesion progression.

            METHODS ApoE–/– mice fed a high-fat diet (0-week, 10-week and 20-week) were used as models of different stages of atherosclerosis. Computational fluid dynamics (CFD) were applied to verify different hemodynamic modes of straight segment and bifurcation of carotid artery. Histological analysis was used to reveal the occurrence and progression of atherosclerotic plaques. Immunohistochemistry analysis was applied to observe the distribution and expression of M1 macrophage and PLXND1 by detecting induced nitric oxide synthase (iNOS; M1 marker). Tissue clearing in combination with fluorescent labelling and light-sheet fluorescence-microscopy technology were used to provide data of the entire vessel and further reveal quantitative and spatial evidence for distribution of PLXND1 via three-dimensional reconstruction imaging. We used a PLXND1-specific molecular fluorescent probe to examine whether it could quantitate and visualize the atherosclerotic lesions in vivo. We also applied THP-1 derived macrophage polarization model to detect the expression of PLXND1 in M0, M1 and M2 macrophages. Besides, we established models in different shear stress patterns with oxLDL of human umbilical vein endothelial cells (HUVECs) and THP-1 derived macrophages to evaluate the changes during polarization of macrophage. We also applied PLXND1 knock-down macrophage to explore the role of PLXND1 in polarization of macrophage.

            RESULTS CFD showed that low disturbed flow predominates at carotid bifurcations in high-fat fed mice. Histological analysis revealed that atherosclerotic plaques initiated and progressed predominantly at the lateral walls of carotid bifurcations. Immunohistochemistry analysis revealed highly expressed PLXND1 in M1 macrophages at these bifurcation plaques. Light-sheet fluorescence-microscopy via three-dimensional reconstruction imaging analysis confirmed consistent colocalization of PLXND1 and M1 macrophage and the distribution of PLXND1 in plaques which were on the lateral walls of bifurcation influenced by disturbed flow. Quantitative analysis confirmed that PLXND1 expression increased in M1 macrophages as lesions progressed. PLXND1-specific molecular fluorescent probe visually showed PLXND1 in intact arterial trees and confirmed that PLXND1 levels were higher at bifurcations than at common carotid arteries. In vitro experiments demonstrated that disturbed flow increased M1 macrophage polarization and that PLXND1 expression level was substantially elevated in THP-1-derived M1 macrophages. Disturbed flow with oxLDL was detected to promote M1 macrophage polarization in the in vitro experiments. And after knock-down of PLXND1, the polarization to M1 macrophage was weakened.

            CONCLUSIONS Disturbed flow-induced atherosclerotic plaques at the lateral walls of bifurcations. PLXND1 predominates in M1 macrophage at the bifurcation lesions and its level increased with the progression of atherosclerosis. PLXND1 mediates disturbed flow-induced M1 macrophage polarization. Thus, PLXND1 may be a potential target for monitoring and treatment for bifurcation lesions.

            GW33-e0602
            Natriuretic peptide receptor C protects vascular endothelial cells and macrophage against high glucose-induced injury by inhibiting the pyroptosis pathway

            Luyan Zheng, Meixia Ren, Fan Lin

            Fujian Provincial Hospital

            OBJECTIVES The aim was to investigate the effect of high glucose on human umbilical vein endothelial cells (HUVECs) and macrophage, and to explore whether NPR-C signaling could alleviate HUVECs and macrophages injury induced by high glucose via regulating pyrolysis pathway.

            METHODS HUVECs and macrophages were treated with high glucose, together with c-ANF (NPR-C agonists). The cell viability were detected by cell counting kit-8 (CCK-8). The toxicity of high glucose was subjected with LDH assay and Hoechst/Propidium Iodide (PI) staining. The scratch assay was utilized to detect the cell migration ability. RT-PCR and western blot were carried out to compare the levels of gene expressions and protein synthesis involved in pyrolysis.

            RESULTS 1. Result of HUVECs.

            (1) CCK-8 indicate that cell viability decrease in a concentrations-dependant manner as glucose concentrations rise when HUVECs treated by high-glucose with various concentrations (P<0.05). In conditions of using 33 mM high-glucose, c-ANF can inhibit the decline viability of HUVEC cell induced by high-glucose in a concentrations-dependant manner when using various concentrations of c-ANF to activate NPR-C.

            (2) LDH detection: Compared with the control group, the secretion of lactate dehydrogenase in the cell supernatant was increased in the high glucose group, showing high-glucose toxicity to cells, and this could be alleviated by c-ANF with a lower level of the lactate dehydrogenase in the c-ANF+ high glucose group (P<0.05).

            (3) Hoechst/PI staining: Compared with the control group, the PI stained cells increased in the high glucose group, while compared with the high glucose group, the PI stained cells in the c-ANF + high glucose group decreased (P<0.001).

            (4) RT-PCR: Compared with the control group, the mRNA expressions levels involved in pyrolysis were augmented by high glucose (P<0.05), and c-ANF could reduce the increase by high glucose (P<0.05).

            (5) Western blot: Compared with the control group, the protein synthesis levels involved in pyrolysis were augmented by high glucose, and c-ANF could reduce the increase by high glucose. It needs to be further verified.

            (6) Scratch test: After scratch injury, the migratory distance of HUVECs in the high glucose group decreased compared with the control group, while in the c-ANF+ high glucose group, the migratory distance increased compared with the high glucose group.

            2. Result of macrophages.

            (1) CCK-8 indicate that micro phage viability will be inhibited by 33 mM high glucose (P<0.05), the cell viability of group high glucose and lipopolysaccharide is significantly lower than group high glucose (P<0.05). c-ANF take a certain effects to the survival of micro phage treated with high-glucose or lipopolysaccharide (P<0.05), but without obvious concentration dependent manner.

            (2) RT-PCR: Compared with the control group, the mRNA expressions levels involved in pyrolysis were augmented by high glucose, and c-ANF could reduce the increase by high glucose. This needs to be further verified.

            CONCLUSIONS High glucose could cause the damage of HUVECs and macrophages. NPR-C might protect HUVECs and macrophages against high glucose-induced injury by inhibiting the pyroptosis pathway.

            GW33-e0603
            CREG1 attenuates doxorubicin-induced cardiotoxicity via inhibiting the ferroptosis of cardiomyocytes

            Dan Liu, Xiaoli Cheng, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Cardiovascular diseases and cancers are two important causes of human death. Doxorubicin (DOX) is currently one of the most commonly used broad-spectrum anti-tumor drugs, it is widely used in the treatment of patients with leukemia, breast cancer and ovarian cancer. However, some cancer patients may experience obvious cardiotoxicity after the use of DOX. Cellular repressor of E1A-stimulated genes (CREG1) is an important cardioprotective factor, which plays an important role in maintaining cardiomyocyte differentiation and homeostasis regulation. However, the roles and mechanisms of CREG1 in DOX-induced cardiotoxicity have not been reported.

            METHODS In vivo, the intraperitoneal injection of DOX was used to establish a mouse DOX-induced cardiotoxicity model, the mRNA and protein expression of CREG1 in the DOX-treated myocardium was examined using real-time PCR and western blot. To clarify the role of CREG1 in the development of DOX-induced cardiotoxicity, CREG1 transgenic mice, cardiac-specific CREG knockout mice and its littermate controls were used to establish DOX-induced cardiotoxicity model, HE staining, Masson staining, WGA staining and western blot were applied to examine fibrosis, myocardial hypertrophy and ferroptosis of myocardium. In vitro, neonatal mouse cardiomyocytes (NMCMs) were cultured and stimulated with DOX, CREG1 overexpression adenovirus and small interfering RNA was used to examine the role of CREG1 on the ferroptosis of NMCMs.

            RESULTS In vivo, the mRNA and protein expression of CREG1 were significantly reduced in DOX-treated myocardium. CREG1 transgenic mice significantly alleviated the myocardial damage induced by DOX, and CREG1 deficiency in heart aggravated the DOX-induced cardiotoxicity. In vitro, the mRNA and protein expression of CREG1 was also obviously reduced in DOX-treated NMCMs. Under DOX stimulation, CREG1 overexpression inhibited the ferroptosis of cardiomyocytes, and CREG1 knockdown aggravated the ferroptosis of cardiomyocyte. Mechanically, CREG1 inhibited the mRNA and protein expression of pyruvate dehydrogenase kinase 4 (PDK4). The effect of CREG1 overexpression on ferroptosis of cardiomyocytes was reversed by PDK4 overexpression.

            CONCLUSIONS CREG alleviated DOX-induced cardiotoxicity by inhibiting ferroptosis of cardiomyocytes. Our findings might help clarify new roles of CREG1 in the development of DOX-induced cardiotoxicity.

            GW33-e0605
            Pentamethylquercetin protects against angiotensin II-induced abdominal aortic aneurysm formation in mice

            Hanlin Wu, Jia Li, Yuxin Bu, Jing Wang, Dan Liu, Chenghui Yan, Yalin Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command, Shenyang

            OBJECTIVES Pentamethylquercetin (PMQ) is a kind of natural polymethyl flavonoids with many biological activities, such as anti-oxidation and anti-inflammatory. The purpose of this study was to investigate the role and mechanism of PMQ in the development of abdominal aortic aneurysm (AAA).

            METHODS AAA model was established by continuous infusion of angiotensin II (Ang II) in ApoE−/− mice for 4 weeks. PMQ (5 mg/kg/day or 12.5 mg/kg/day) was intraperitoneally administered to mice for 5 days before administration of Ang II and continued for 4 weeks. Experimental animals were divided into four groups: control group, AAA group, PMQ low-dose group and PMQ high-dose group. Blood pressure and body weight were measured. Real-time PCR, western blot and immunohistochemical staining was used to measure mRNA and protein levels of matrix metalloproteinases (MMP2 and MMP9), apoptosis-related proteins (Bax, Bcl-2, and active caspase-3), oxidative stress associated protein (SOD and CAT). HE, Masson staining and Verhoeff staining were used to examine the morphology of abdominal aorta. Mouse vascular smooth muscle cells (VSMCs) were used to clarify the role of PMQ in cell apoptosis and oxidative stress. Tunel staining was used to evaluate the apoptosis of vascular smooth muscle cells in vitro and in vivo. Proteomic analysis was used to screen the difference proteins between AAA group and PMQ treatment group. Real-time PCR and western blot was used to measure mRNA and protein levels of Gsk-3β and p-Gsk-3β in vitro and in vivo.

            RESULTS We found that administration of PMQ dose-dependently reduced the incidence of Ang II-induced AAA, aneurysm diameter enlargement, elastatin degradation, matrix metalloproteinase production, and the apoptosis of VSMCs. The oxidative stress injury was improved in PMQ-treated mice. In Ang II-stimulated VSMCs, PMQ dose-dependently reduced the apoptosis and improved oxidative stress injury. Gsk-3β was found to be the most significant difference protein between the AAA group and the PMQ treatment group using by proteomics analysis. PMQ could increase the phosphorylation of Gsk-3β. The therapeutic effect of PMQ was disappeared after the application of Gsk-3β phosphorylation inhibitor.

            CONCLUSIONS In our study, PMQ alleviates Ang II-induced AAA by enhancing antioxidant capacity and reducing the apoptosis of VSMCs, through regulating the phosphorylation of Gsk-3β. PMQ may be a potential treatment agent for AAA.

            GW33-e0607
            UBC9 alleviates diabetic cardiomyopathy by inhibiting oxidative stress and mitochondrial damage in cardiomyocytes

            Hanlin Wu, Jia Li, Yuxin Bu, Jing Wang, Dan Liu, Chenghui Yan, Yalin Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Oxidative stress injury is one of the important pathogenic factors of diabetic cardiomyopathy. Ubiquitin conjugating enzyme E2 I (UBC9) is the only SUMO-E2 enzyme and plays a key role in oxidative stress. However, the role of UBC9 in the development of diabetic cardiomyopathy is poorly understood. The aim of this study is to clarify the role and mechanism of UBC9 in the development of diabetic cardiomyopathy.

            METHODS Male C57BL/6J mice were injected with UBC9 overexpressed adeno associated virus (AAV-UBC9) and control virus (AAV-GFP) by tail vein injection for 21 days. Mouse diabetic cardiomyopathy model was established by high fat diet (HFD) and low-dose streptozotocin injection. Body weight, fasting glucose, glucose tolerance, insulin tolerance, cardiac function of were measured. Real-time PCR, western blot and immunohistochemical staining was used to measure mRNA and protein levels of UBC9, oxidative stress associated proteins (SirT3, SOD2 and NOX4) and mitochondrial autophagy related proteins (PINK1, PARKIN, LC3B and P62). H&E, WGA and Masson staining were used to detect myocardial hypertrophy and fibrosis. DHE staining was used to evaluate the ROS of cardiomyocytes. In vitro, cultured cardiomyocytes were stimulated with palmitic acid (PA). UBC9-overexpressed adenovirus or small interfering RNA was used to examine the effect and mechanism of UBC9 on the oxidative stress and mitochondrial function of cardiomyocytes using by Real-time PCR, western blot, DHE staining.

            RESULTS In vivo, the mRNA and protein of UBC9 was significantly decreased in the myocardium of diabetic cardiomyopathy. UBC9 overexpression could improve cardiac dysfunction, decrease myocardial fibrosis and hypertrophy, and inhibit oxidative stress injury and mitochondrial damage. In vitro, PA obviously inhibited the mRNA and protein expression of UBC, accompanied by mitochondrial dysfunction and oxidative stress damage. UBC9 overexpression improved mitochondrial function and oxidative stress of cardiomyocytes induced by PA stimulation. In contrast, UBC9 knockdown aggravated mitochondrial dysfunction and oxidative stress damage of cardiomyocytes. Moreover, SirT3 was a downstream of UBC9, the effect of UBC9 on the mitochondrial function and oxidative stress was reversed by SirT3 knockdown.

            CONCLUSIONS In our study, UBC9 alleviates the development of diabetic cardiomyopathy by protects inhibiting oxidative stress and improving mitochondrial function of cardiomyocytes. This study provides new perspectives for the use of UBC9 as a therapeutic target for diabetic cardiomyopathy.

            GW33-e0609
            CREG inhibits vascular calcification by regulating FHL2 expression

            Jing Wang, Dan Liu, Xiaoxiang Tian, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Vascular calcification (VC) is a common pathological feature of atherosclerosis, chronic kidney disease, vascular injury and aging. VC is characterized by different mineral deposits accumulating in blood vessels and valves. Cellular repressor of E1A-stimulated genes (CREG) is a small molecule secreted glycoprotein and is consisted by 220 amino acids. Studies have shown that CREG is involved in regulating cell growth and differentiation. The aim of this study is to clarify the role of CREG participates in the development of VC.

            METHODS Male C57BL/6J, CREG transgenic (CREGTG), and CREG smooth muscle cell-specific knockout (CREGSMKO) mice were used to establish a VC model induced by VitD3 injection. Alizarin red staining, Von Kossa staining, and western blotting were used to assess the severity of VC. In vitro, mouse primary vascular smooth muscle cells (VSMCs) were isolated and cultured, VSMCs were infected with CREG overexpressing adenovirus or CREG small interfering RNA, followed by phosphate (Pi) stimulation, real-time PCR, western blotting, Alizarin red staining were used to assess the severity of VSMCs calcification.

            RESULTS In vivo, the mRNA and protein levels of CREG were significantly decreased in VitD3-induced VC. CREGSMKO mice aggravated VC by increasing the expressions of the osteogenic markers runt-related transcription factor 2 (Runx2) and osteopontin (OPN), and inhibiting SMA expression. In contrast, CREGTG mice inhibit VC by inhibiting the expressions of Runx2 and OPN, and increasing SMA expression. In vitro, CREG expression was significantly decreased in Pi-induced VSMCs. CREG knockdown exacerbated Pi-induced VSMCs differentiation and calcification, CREG overexpression inhibited VSMCs differentiation and calcification induced by Pi stimulation. Mass spectrum and western blotting revealed that FHL2 was a downstream molecular of CREG, and was involved in the regulation of CREG in VC. Moreover, CREG could regulate FHL2 protein expression in lysosome-dependent pathway.

            CONCLUSIONS Our study identified that CREG was a novel endogenous inhibitor of VC by regulating FHL2 protein expression. This study could provide a promising target for VC therapy.

            GW33-e0610
            Untargeted metabolomics identifies tryptophan/kynurenine metabolic pathway as a reliable plasm metabolic markers in ST-segment elevated myocardial infarction

            Xiaolin Zhang, Minghui Cheng, Xiaoxiang Tian, Dan Liu, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES The tryptophan/kynurenine pathway plays a key role in the increase of cardiovascular disease incidence by regulating inflammation, oxidative stress and immune activation. We evaluated the predictive value of Kynurenine/Tryptophan (KTR) for the major adverse cardiac and cerebral events (MACCE) in STEMI patients.

            METHODS In order to clarify the characteristics of plasm metabolism in the STEMI patients, plasm metabolite profiling of STEMI and healthy controls was analysed using nuclear magnetic resonance (1H-NMR). Ultraperformance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC/Q-TOF) was used to analyze the concentration of metabolites of tryptophan/kynurenine pathway among the 504 participants. Major adverse cardiac and cerebral events were assessed in the STEMI patients followed for 1 year.

            RESULTS 1H-NMR revealed 15 differential kinds of metabolites markers identified were related to the plasm of STEMI patients compared with the control subjects. Targeted metabolomics results showed that serum concentration of tryptophan in STEMI group were significantly lower than those in the control group (P=0.001); the expression levels of IDO, kynurenine, kynurenic acid, 3-hydroxykynurenine were increased in the STEMI group (P<0.05). The serum KTR of STEMI patients was significantly higher than that of the control group (12.8±5.4 vs 27.0±12.1), and the difference was statistically significant (P<0.000). The incidence of MACCE in 280 patients with STEMI was 6.4% (17/266) after one-year follow-up. The KTR level of STEMI patients with MACCE events was significantly higher than that those without MACCE events, the difference was statistically significant (40.6±17.0 vs 25.7±11.1, P=0.002).

            CONCLUSIONS A total of 15 different metabolic markers were identified in the serum of STEMI patients compared with the control group (P<0.05). The serum tryptophan level was significantly decreased in STEMI patients, while the level of IDO, KTR and kynurenines (kynurenine, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and xanthene acid) were significantly increased in STEMI patients. The higher the expression level of serum KTR, the higher the risk of MACCE in STEMI patients within one year.

            GW33-e0612
            S100A12 aggravates abdominal aortic aneurysm by promoting MMP9 expression in macrophages via activating JAK2/STAT3 signaling pathway

            Jinping Jiang, Xiaolin Zhang, Xiaoxiang Tian, Dan Liu, Chenghui Yan, Yaling Han

            Cardiovascular Research Institute and Department of Cardiology, General Hospital of Northern Theater Command

            OBJECTIVES Abdominal aortic aneurysm (AAA) is recognized as a chronic vascular inflammatory disease with no effective drug therapy. So, exploring new target to prevent AAA is crucial. S100A12 is a calcium-, zinc- and copper-binding protein which plays a significant role in the regulation of inflammatory processes and immune response. However, whether S100A12 participates in the pathological process of AAA has not been identified yet. In this study, we identified the effect of S100A12 on AAA formation and its underlying mechanisms.

            METHODS The enzyme-linked immunosorbent assay was used to detect the level of S100A12 in AAA and normal control group. For in vivo experiment, we constructed lysozyme M promoter S100A12 transgenic mice (S100A12-Tg) to overexpress S100A12 and the S100A12-Tg mice received angiotensin II for 4 weeks, together with its control group. PCR, Western blotting and gelatin zymography were used to access the expression and the activity of MMP9 in the aortas of each group. In vitro, to clarify the specific signaling pathway, RAW264.7 cells were stimulated by exogenous S100A12 protein and RNA interference, respectively.

            RESULTS The level of serum S100A12 in AAA patients was significantly higher than that in normal group. Interestingly, the incidence of AAA in S100A12-Tg mice was higher under AngII stimulation. Besides, loss of medial smooth muscle cells (SMCs) was severe and more elastin fragmentation, vascular inflammation and degradation of the extracellular matrix was observed in S100A12-Tg mice stimulated with Ang II. In addition, matrix metalloproteinase 9 (MMP9) expression greatly increased in the abdominal aortic tissue and spleen tissue in S100A12-Tg group. Similarly, the expression and activity of MMP9 increased in RAW264.7 cells after they were treated with S100A12. Moreover, exogenous S100A12 protein could active JAK2 and increase the downstream STAT3 expression. Furthermore, overexpression of STAT3 increased MMP9 expression while inhibition of STATS elicited the opposite change.

            CONCLUSIONS S100A12 aggravated AAA formation under AngII stimulation in mice. By activating JAK2/STAT3 signaling pathway, S100A12 promoted inflammatory and MMP9 expression in macrophages. These data suggested that S100A12/JAK2/STAT3 signaling pathway could be a potential target to treat AAA.

            GW33-e0616
            Ginsenoside-Rg1 ameliorates heart failure by activating Nrf2-mediated anti-ferroptosis

            Jiabin Zhou, Qi Lu, Tao Yu, Chu Chen, Jiayu Shi

            Affiliated Hospital of Nantong University

            OBJECTIVES Evidence suggests that ferroptosis plays a key role in the occurrence and development of heart failure, while the Nrf2 signaling pathway regulates oxidative stress and lipid peroxidation, but its effects with ginsenoside-Rg1 on heart failure and ferroptosis remain unclear. In the present study, we aimed to investigate the functional role of ginsenoside-Rg1 in heart failure and to elucidate its potential mechanisms of action.

            METHODS We established an in vivo model with C57BL/6 mice using transverse aortic constriction (TAC) and stimulated neonatal mouse cardiomyocytes with phenylephrine (PE) to establish an in vitro model to determine the effect of ginsenoside-Rg1 on heart failure and to assess the anti-ferroptosis death effect of Nrf2.

            RESULTS In this study, we observed that ginsenoside-Rg1 treatment significantly attenuated heart failure in TAC mice, including changes in cardiac ultrasound, morphologic changes in the heart and elevated expression of heart failure markers (ANP, BNP and β-MHC). Ginsenoside Rg1 also inhibited ferroptosis in the myocardium of TAC mice in vivo, including changes in mitochondrial morphology, iron accumulation, and expression associated with lipid peroxidation (increased ROS, elevated MDA levels, SOD and GSH depletion, as well as decreased GPX4 expression). Meanwhile, Nrf2 KO mice were more susceptible to ferroptosis after TAC-induced heart failure than control mice. The protective effect of ginsenoside-Rg1 against heart failure and ferroptosis was largely abolished in Nrf2 KO mice. Experiments in vitro showed that ginsenoside-Rg1 treatment remarkably ameliorated PE-induced hypertrophy in primary mouse cardiomyocytes and activated Nrf2 to inhibit ferroptosis. In addition, we down-regulated the expression level of Nrf2 in vitro using a gene-specific siRNA targeting Nrf2. The results showed that suppression of Nrf2 eliminated the protective effect of ginsenoside-Rg1 against ferroptosis in heart failure.

            CONCLUSIONS Ginsenoside-Rg1 can play a regulatory role in heart failure, and its mechanism of action involves Nrf2-mediated anti-ferroptosis, suggesting that ginsenoside-Rg1 can be used as a potential therapeutic agent in heart failure.

            GW33-e0666
            Rosuvastatin enhances lymphangiogenesis after myocardial infarction by regulating the miRNAs/VEGFR3 pathway

            Zheng Lian1,2,3,4, Hong Chen2,3,4

            1Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China

            2Department of Cardiology, Peking University People’s Hospital, Beijing, China

            3Beijing Key Laboratory of Early Prediction and Intervention of Acute Myocardial Infarction, Peking University People’s Hospital, Beijing, China

            4Center for Cardiovascular Translational Research, Peking University People’s Hospital, Beijing, China

            OBJECTIVES Several clinical studies have suggested that early administration of statins could reduce the risk of in-hospital mortality in acute myocardial infarction (AMI) patients. Recently, some studies have identified that stimulating lymphangiogenesis after AMI could improve cardiac function by reducing myocardial oedema and inflammation. This study aimed to identify the effect of rosuvastatin on postinfarct lymphangiogenesis, especially the epigenetic regulation of lymphangiogenesis, and to identify the underlying mechanism of this effect.

            METHODS Myocardial infarction (MI) was induced by ligation of the left anterior descending coronary artery in mice orally administered rosuvastatin for 7 days. The changes in cardiac function, pathology, and lymphangiogenesis following MI were measured by echocardiography and immunostaining. EdU, Matrigel tube formation and scratch wound assays were used to evaluate the effect of rosuvastatin on the proliferation, tube formation and migration of the lymphatic endothelial cell line SVEC4-10. The expression of miR-107-3p, miR-491-5p, and VEGFR3 was measured by PCR and western blotting. A gain-of-function study was performed using miR-107-3p and miR-491-5p mimics.

            RESULTS The rosuvastatin-treated mice had a significantly improved ejection fraction and increased lymphatic plexus density 7 days after MI. Rosuvastatin also reduced myocardial oedema and inflammatory infiltration after MI. We used a VEGFR3 inhibitor to partially reverse these effects. Rosuvastatin promoted the proliferation, migration and tube formation of SVEC4-10 cells. PCR and Western blot analysis revealed that rosuvastatin intervention downregulated miR-107-3p and miR-491-5p and promoted VEGFR3 expression. The gain-of-function study showed that miR-107-3p and miR-491-5p could inhibit the proliferation, migration and tube formation of SVEC4-10 cells.

            CONCLUSIONS Rosuvastatin could improve heart function by promoting lymphangiogenesis after MI by regulating the miRNAs/VEGFR3 pathway.

            GW33-e0679
            Interleukin 29 accelerates vascular calcification via JAK2/STAT3/ BMP2 signaling

            Nannan Hao, Feifei Zhang, Rui Hu, Fang Wang

            The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital)

            OBJECTIVES Vascular calcification (VC), associated with enhanced cardiovascular morbidity and mortality, is characterized by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). Inflammation promotes the initiation and progress of VC. Interleukin 29 (IL-29), a newly discovered member of type III interferon, has recently been implicated in the pathogenesis of autoimmune diseases. Therefore, we evaluated the role of IL-29 on VC process and the underlying inflammatory mechanisms.

            METHODS We detected the mRNA expression of IL-29 in calcified carotid arteries from patients with coronary artery disease (CAD) or chronic kidney disease (CKD) by real-time quantitative PCR. We also investigated the effects of IL-29 on VC process and the underlying inflammatory mechanisms. In vitro, VSMCs calcification was induced by the the CaP or osteogenic medium, while in vivo VC was triggered by intraperitoneally injection with vitamin D3. Alizarin red and calcium were performed to test VC. Cell proliferation, invasion were detected by CCK-8 assay and transwell assays, and the cell apoptosis was examined by flow cytometry analysis. Western blot was employed to analyze the expression of proteins associated with IL-29, VSMCs osteoblastic transformation and JAK2/STAT3/BMP2 signaling.

            RESULTS The mRNA expression of IL-29 was significantly increased and positively associated with an increased BMP2 mRNA level in calcified carotid arteries from patients with CAD or CKD. IL-29 and BMP2 proteins were co-localized in the human calcified arteries. IL-29 binding to its specific receptor IL-28Rα (IL-29/IL-28Rα) inhibited the proliferation of rat VSMCs without changes in cell apoptosis or migration. IL-29 promoted the calcification of rat VSMCs and their osteogenic transdifferentiation in vitro as well as the rat aortic ring calcification ex vivo, induced by the CaP or osteogenic medium. The pro-calcification effect of IL-29 was reduced by pharmacological inhibition of the binding of IL-29/IL-28Rα as well as suppressing JAK2/STAT3 pathway activation that were accompanied by the decreased expression of BMP2 in the cultured rat VSMCs.

            CONCLUSIONS These results suggest an important role for IL-29 in the development of VC, at least partly, via activating the JAK2/STAT3 signaling. Inhibition of IL-29 or its specific receptor IL-28Rα may provide a novel strategy to reduce the VC in patients with vascular diseases.

            GW33-e0690
            PCSK9 up regulates T lymphocyte subsets TNF-α aggravating hepatic steatosis in mice

            Yu Xiao-Lin1,2,3, Yang Yi-Ning1,3

            1Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region

            2Institute of Clinical Medicine, The First Affiliated Hospital of Xinjiang Medical University

            3Xinjiang Key Laboratory of Cardiovascular Medicine

            OBJECTIVES To investigate the mechanism of proprotein convertase subtilisin 9 (PCSK9) on hepatic steatosis in mice.

            METHODS C57BL / 6 mice were recruited, transfected with PCSK9 of human origin as an experimental group, GFP as a control group, and fed with a high fat diet for 24 W. ELISA, WB, immunohistochemical staining, flow cytometry were used for validation.

            RESULTS (1) In the GFP group, liver oil red O showed the total amount of lipid droplets, and H&E staining showed that steatosis and vacuolization were significantly lower than in the PCSK9 group; (2) Flow cytometry showed that GFP group vs PCSK9 group, ①CD4+-IL-2% (3.35±0.92 vs 13.72±2.99, P<0.05); CD8+-IL-2% (1.38±0.37 vs. 4.54±0.99, P<0.05); NK- IL-2% (1.45±0.34 VS 0.59±0.13, P<0.05); ②CD4+-TNF- α% (9.25±2.7 vs 24.78±4.66, P<0.05); CD8+-TNF- α% (7.65±1.85 vs 21.18±3.82, P<0.01), NK- TNF- α% (0.65±0.09 VS 1.63±0.35, P<0.05).

            CONCLUSIONS PCSK9 accelerates hepatic steatosis by upgrading TNF -α in hepatic lymphocyte subsets in mice.

            GW33-e0699
            Recipient circulating non-bone marrow CD34+ fibroblast progenitor cells promote fibrosis in cardiac allograft

            Xiaotong Sun, Ting Chen, Hui Gong

            Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China

            OBJECTIVES Fibrosis is one of the major causes leading to cardiac allograft malfunction, and is mainly characterized by excessive extracellular matrix deposition secreted by activated fibroblasts. Extracardiac cells play a critical role in repopulating most cellular components in cardiac allografts. However, the role of recipient-derived cells in generating allograft FCs and the mechanisms underlying this process remain to be studied.

            METHODS Heterotopic cervical heart transplantation was performed by transplanting hearts from female BALB/c mice to male C57BL/6J mice. Single-cell RNA sequencing (scRNA-seq) were introduced to delineate the allograft cell atlas. Y chromosomes analyses and genetic lineage tracing technique were applied to identify cells from different origins. The contribution of recipient CD34+ cells in allograft fibrosis were investigated using CD34-CreERT2; Rosa26-tdTomato mice. The exact source of recipient fibrogenic CD34+ cells were confirmed by constructing the bone marrow transplantation and parabiotic models. The CD34+ fibroblast progenitor cells were also isolated from human peripheral blood to verify its potential to differentiate into activated fibroblasts both in vivo and in vitro.

            RESULTS In our study, the allograft fibroblasts expanded and exhibited a diffuse activated phenotype. The majority of activated fibroblasts comes from recipient and showed high expression of Cd34. Recipient Cd34+ cells were proved to prefer to generate activated fibroblasts after transplantation. In addition, recipient Cd34+ cells, which possessed fibrogenic potential, mainly originated from non-bone marrow circulation. The circulating Cd34+ fibroblast progenitor cells were recruited to the allograft via Cxcl12-Ackr3 interaction. Once located in the allograft tissue, Cd34+ fibroblast progenitor cells differentiated into activated fibroblasts in response to various pro-fibrotic pathways, including TGFb and TNFa signaling pathway.

            CONCLUSIONS These results show that recipient-derived FCs were crucial contributors to allograft fibrosis, in which circulating non-BM CD34+ cells play a vital role in generating activated FCs both in vivo and in vitro. Thus, targeting recipient CD34+ cells would be a novel therapy for cardiac allograft fibrosis.

            GW33-e0715
            Endothelial GATA5 positively regulates angiogenesis via cathepsin S-mediated Angpt2/Flk1 and MMP2/9 signaling pathways

            Anmin Ren, Xinkai Qu

            Huadong Hospital

            OBJECTIVES Although GATA5 is vital in maintaining the function of endothelial cells, the relationship between GATA5 and angiogenesis, however, remains unclear. Our study aims to determine how endothelial GATA5 mediates angiogenesis.

            METHODS 1. C57BL/6 mice were injected with endothelial cell-specific GATA5-overexpressing adeno-associated virus. One week after virus infection, the hindlimb ischemia model was established by ligating the femoral artery of mice, and the blood perfusion ratio of the operated limb/healthy limb was detected by a blood perfusion imager. CD31 staining of mouse gastrocnemius muscle showed the number of new capillaries per unit area. Western Blot and qPCR were used to detect the expression of GATA5 and related angiogenesis factors. 2. On human umbilical vein endothelial cells, transfected lentivirus to knock down the expression of GATA5 and/or administered vascular endothelial growth factor-165 intervention, through CCK-8 experiments were used to detect cell proliferation, scratch experiments to detect cell migration, and endothelial tube formation experiments to detect the ability of cells to form tubes. Western blot and qPCR assays were used to detect the protein and mRNA levels of GATA5, cathepsin S, Angpt2 and Flk1, and MMP2/MMP9. The direct binding of GATA5 to cathepsin S was verified by co-immunoprecipitation experiments. 3. GATA5 knockdown human umbilical vein endothelial cells were transfected with plasmids overexpressing GATA5 or cathepsin S to increase the expression levels of GATA5 or cathepsin S. Cell function and expression of related factors were detected.

            RESULTS 1. The blood perfusion ratio and CD31 immunofluorescence expression of the mice in the endothelium-specific overexpression GATA5 group were significantly higher than those of the negative control mice, and the mRNA and protein levels of angiogenesis factors Angpt2 and Flk1 were increased as well. 2. Cell experiments showed that the knockdown of GATA5 could inhibit cell proliferation, migration and endothelial tube formation stimulated by VEGF-165, and at the same time, reducing the expression of cathepsin S, Angpt2, Flk1 and MMP2/MMP2. Co-immunoprecipitation experiments showed that GATA5 had a direct binding relationship with cathepsin S. 3. Overexpression of GATA5 or cathepsin S reversed the decline in cell migration and tube formation caused by GATA5 knockdown, and up-regulated the expressions of Angpt2/Flk1 and MMP2/MMP9.

            CONCLUSIONS Endothelial GATA5 regulates angiogenesis by regulating endothelial cell proliferation, migration and tube formation through the cathepsin S-Angpt2/Flk1 and MMP2/MMP9 signaling pathways.

            GW33-e0719
            Cardiomyocyte peroxisome proliferator-activated receptor α prevents against septic cardiac dysfunction via improving mitochondrial function

            Xinxin Zhu, Xia Wang, Shiyu Jiao, Ye Liu, Li Shi, Yun’er Chen, Ming Wei, Baoqi Yu, Aijuan Qu

            Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University; Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education; Beijing Key Laboratory of Metabolic Disorder-Related Cardiovascular Diseases, Beijing 100069, P.R. China

            OBJECTIVES Cardiac dysfunction is an identified serious component of the sepsis-induced multi-organ failure in intensive care units. Mitochondrial function and dynamic control are extremely essential for cardiomyocyte homeostasis and disturbed mitochondrial dynamics enhances mitophagy and apoptosis. However, the therapies targeted to mitochondrial function in septic patients have not been explored.

            METHODS A published transcriptome data (SRA at the NCBI under the accession number SRP00123) associated with septic cardiomyopathy and male WT mice, Ppara fl/fl, cardiomyocyte-specific Ppara-deficient (Ppara fl/fl;Myh6-ERT2Cre, Ppara DCM), myeloid-specific Ppara-deficient mice (Ppara DMac) were injected intraperitoneally with LPS to induce septic cardiac dysfunction. Echocardiography, morphology, LDH level and analyses of gene and protein expression were used to evaluate septic dysfunction. Mitochondrial function, dynamics and mitophagy were investigated by transmission electron microscopy, ATP content detection, mitochondrial complex and Western blot analysis. For 3-MA treatment, Ppara fl/fl and Ppara ∆CM mice were intraperitoneally injected with 3-MA (15 mg/kg) 6 hours before LPS treatment. For WY-14643 treatment, WY-14643 (0.1%) were diet to WT mice two days before LPS administration.

            RESULTS PPARα and its target genes expression were the most significantly decreased in septic cardiac dysfunction which was shown by a transcriptomic data analysis and quantitative analysis of LPS treated heart (Ppara mRNA level: WT PBS vs. WT LPS 5 mg/kg: 1.000±0.1070 vs. 0.9578±0.009897, P<0.0001; PPARα protein level: WT PBS vs. WT LPS 5 mg/kg: 1.196±0.6073 vs. 0.1429±0.04652, P<0.05). Then, PPARα in which cell plays a crucial role were identified in septic cardiac dysfunction. Cardiomyocytes-specific PPARα deficiency but not myeloid PPARα knock out resulted in an exacerbation of LPS-induced cardiac dysfunction which were does-dependent. (EF%: Ppara fl/fl LPS 5 mg/kg vs. Ppara ∆CM LPS 5 mg/kg: 54.54±2.162 vs. 50.98±5.718, P<0.05; Ppara fl/fl PBS vs. Ppara ∆CM PBS: 65.10±5.531 vs. 54.54±2.162; Ppara fl/fl LPS 10 mg/kg vs. Ppara ∆CM LPS 10 mg/kg: 51.55 ± 2.637 vs. 45.45±4.247, P<0.05; Ppara fl/fl PBS vs. Ppara ∆CM PBS: 65.65±2.901 vs. 63.81±2.715). Mechanically, PPARα disruption in cardiomyocytes augmented mitochondrial dysfunction and dynamic disturbance, which was shown by ATP contents (Ppara fl/fl LPS vs. Ppara ∆CM LPS: 0.2624±0.03903 vs. 0.09674±0.04057, P<0.0001), mitochondrial complexes level decreased and DRP1, MFN1 protein expression increased. Mitochondrial dynamics disturbance resulted in an increasing of mitophagy and mitochondrial dependent apoptosis, excessive mitophagy and apoptosis leads to the aggravation of heart injury. Moreover, mitochondrial dysfunction caused a ROS (Ppara fl/fl LPS vs. Ppara ∆CM LPS: 7.22551×106 ±1.9310×106 vs. 8.80478×106±1.06617×106, P<0.0001) production increasing, which resulted in an increasing of IL-6/STAT3/NF-κB signaling pathway activation. For further verified, 3-MA (an autophagosome formation inhibitor) was used and found that 3-MA alleviated cardiomyocytes PPARα disruption induced cardiac and mitochondrial dysfunction. Finally, WY14643 pre-treatment for activating PPARα ameliorated LC3II/I protein level and mitochondrial dysfunction-induced cardiomyopathy in septic heart.

            CONCLUSIONS Cardiomyocytes PPARα but not myeloid PPARα could protect against septic cardiac dysfunction by ameliorating mitochondrial dysfunction. Our study highlights that cardiomyocytes PPARα could be a preventive and therapeutic targeted to mitochondrial function in septic cardiac dysfunction.

            GW33-e0730
            The association of genetic polymorphism of DAB2 gene with type 2 diabetes mellitus in Chinese Uyghur population

            Yanpeng Li, Dilare Adi, Aibibanmu Aizezi, Yitong Ma

            Department of Cardiology the First Affiliated Hospital of Xinjiang Medical University, Urumqi

            OBJECTIVES Human Disabled-2 (DAB2) plays an indispensable role in clathrin-mediated endocytosis of selected cargo proteins including LDLR. As hyperlipidemia is a major risk factor for Type 2 diabetes mellitus (T2DM), In the present study, we focused on exploring whether genetic variants of the Dab2 gene were associated with T2DM and the risk factors for T2DM in Uygur population in Xinjiang, China.

            METHODS A total of 2157 subjects were recruited in this case–control study, involved 458 T2DM patients and 1699 age- and sex-matched individuals. Four SNPs (rs1050903, rs2255280, rs2855512 and rs11959928) were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method.

            RESULTS In Uygur people, for rs2255280, the distribution of genotypes, recessive model (CC vs CA+AA), additive model (CA vs CC+AA) showed significant differences between the T2DM patients and the controls (P=0.003, P=0.005 and P=0.026, respectively). For rs2855512, meanwhile, the distribution of genotypes, recessive model (CC vs CA+AA), additive model (CA vs CC+AA) also showed significant differences between the T2DM patients and the controls (P=0.005, P=0.007 and P=0.033, respectively). The recessive model (CC vs CA+AA) of rs2255280 and rs2855512 remain significantly associated with the T2DM after adjustment for confounders (OR=1.241, 95% CI=1.047–1.506, P=0.029; OR=1.245, 95% CI=1.059–1.523, P=0.031).

            CONCLUSIONS Rs2255280 and rs2855512 of Dab2 gene are associated with T2DM in Uygur subjects. Subjects with CA/CC genotype or C allele of rs2255280 and rs2855512 were associated with a significantly increased risk of the T2DM.

            GW33-e0745
            Whole-exome sequencing of 41K CAD cases and 217K controls identifies perturbation in nitric oxide signaling as a non-lipid molecular subtype of coronary artery disease

            Minxian Wang1,2

            1Beijing Institute of Genomics, Chinese Academy of Sciences and China National Center for Bioinformation

            2Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA

            OBJECTIVES A key goal of precision medicine is to disaggregate common, complex diseases into discrete molecular subtypes. Rare coding variants in the low-density lipoprotein receptor gene (LDLR) are identified in 1–2% of coronary artery disease (CAD) patients, defining a molecular subtype with risk driven by hypercholesterolemia.

            METHODS To search for additional subtypes, we compared the frequency of rare, predicted loss-of-function and damaging missense variants aggregated within a given gene in 41,081 CAD cases versus 217,115 controls.

            RESULTS Rare variants in LDLR were most strongly associated with CAD, present in 1% of cases and associated with 4.4-fold increased CAD risk. A second subtype was characterized by variants in endothelial nitric oxide synthase gene (NOS3), a key enzyme regulating vascular tone, endothelial function, and platelet aggregation. A rare predicted loss-of-function or damaging missense variants in NOS3 was present in 0.6% of cases and associated with 2.42-fold increased risk of CAD (95% CI 1.80 to 3.26; P=5.5×10−9). These variants were associated with higher systolic blood pressure (+3.25mmHg; 95% CI 1.86 to 4.65; P=5.0×10−6) and increased risk of hypertension (adjusted odds ratio 1.31; 95% CI 1.14 to 1.51; P=0.0002) but not circulating cholesterol concentrations, suggesting that – beyond lipid pathways – nitric oxide synthesis is a key nonlipid driver of CAD risk.

            CONCLUSIONS Beyond LDLR, we identified an additional nonlipid molecular subtype of CAD characterized by rare variants in the NOS3 gene.

            GW33-e0747
            Assessment of intestinal microbiota metabolome in patients with metabolic syndrome

            Maria Lyapina1,2, Tatiana Petelina2, Liana Valeeva2, Elena Dorodneva1, O Schmidt1

            1Tyumen State Medical University of the Ministry of Health of Russia

            2Tyumen Cardiology Research Center – Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES Accumulated data on participation of intestinal microbiota (IM) in metabolic processes of human body suggest the existence of relationship between changes in IM and development of pathological conditions, including metabolic syndrome (MS). The objective was to study the relationship of IM functional activity and factors of cardiovascular risk in patients with MS.

            METHODS Eighty-four patients with MS were examined (mean age 49.74±5.62 years). Examination included a questionnaire on actual nutrition (method of general semi-quantitative assessment of food groups, nutrients and energy intake) and anthropometric analysis. Explanation of carbohydrate, lipid metabolism and severity of inflammation were carried out in compliance with plasma glucose concentration, total cholesterol, LDL cholesterol, CRP. Assessment of intestinal microbial metabolites was performed by chromatographic analysis of short-chain fatty acids (SCFA) level in coprofiltrate. Control group (CG) consisted of 20 apparently healthy individuals aged 18–62 years old. Statistical analysis of results was carried out using SPSS software package.

            RESULTS Daily intake of dietary fibers (DF) was lower in all groups with MS (15.4±6.1 g) than the reference range (31.6±4.9 g), with detection of maximum differences in individuals with MS and class III obesity (P<0.001). It was revealed reduced daily DF intake as part of the diet increased BMI (r=-0.283; P<0.01), dietary energy supply (r=-0.188; P<0.05) and consumption of simple carbohydrates (r=-0.228; P<0.05) in MS individuals. CRP level in individuals with MS was significantly different from CG, regardless of BMI level, at the same time moderate positive correlation was registered between BMI and CRP levels (r=0.486, P<0.001). Glucose levels reasonably increased with elevation of BMI (r=0.418, P<0.001), reaching 6.3 [5.8–6.8] mmol/L in the cohort with MS. Lipid parameters in MS (BMI≥30 kg/m2) individuals were manifested by increase in TC, HDL, LDL, TG (P<0.05). Significant correlation of BMI values could be found only with HDL (r=-0.198, P<0.05), triglycerides (TG) (r=0.255, P<0.01) and atherogenic index (AI) (r=0.259, P<0.01). In the course of chromatographic analysis of microbal metabolites in feces, it was possible to register significant differences in the profile and concentration of SCFAs in individuals with MS in comparison with CG and groups with different BMI values.

            Analysis of relative concentrations of individual SCFAs (C2, C3, C4) showed changes in acid profile of CG and MS individuals with class III obesity (P<0.05) and class II obesity (P<0.001). Reductive-oxidative potential of intraluminal intestinal milieu in MS individuals with class II obesity (−0.502±0.11 U) and with class III obesity (−0.426±0.10 U) was shifted towards slightly negative values. Those changes in concentration of both total and individual SCFAs were associated with combined changes in IM.

            CONCLUSIONS Investigation of persistent metabolites of microorganisms, among which SCFAs had a special place, provided new opportunities for quantitative and qualitative assessment of IM. Early detection of IM metabolome disorders in patients with MS and enrichment of the diet with dietary fibers, including nutraceuticals, offered new opportunities of non-drug correction for functional activity of IM and over and above for MS components. Managing IM represented new approach to reduce the risk of CVD and obesity.

            GW33-e0752
            Inhibition of the P2X7 receptor prevents atrial proarrhythmic remodeling in experimental depression

            Tianxin Ye1, Jinxiu Yang1, Bo Yang2, Xingxiang Wang1

            1Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine

            2Department of Cardiology, Renmin Hospital of Wuhan University

            OBJECTIVES Atrial fibrillation (AF) is the most common sustained arrhythmia; fibrosis and inflammation are critical factors in the pathogenesis of atrial fibrillation (AF). Depression is associated with chronic inflammation, and can also promote cardiac arrhythmias, but the mechanisms has not been fully elucidated. The purinergic receptor P2X7 (P2X7R), a ligand-gated cation channel, predominately mediates inflammation and cellular death, whereas its effect on AF is unclear. Thus, this study was to assess the effect of the P2X7R antagonist Brilliant Blue G (BBG) on atrial arrhythmogcnic remodeling in experimental depression model and explore its potential mechniasms.

            METHODS Myocardial infarction (MI) was induced by permanent ligation of LAD, and Depression (DEP) was established by chronic unpredictable mild stress (CUMS). In vitro, fibroblasts seperated from LA in adult rats were subjected to IL-1b in the presence or absence of BBG and A740003, two selective P2X7R antagonists. Atrial electrophysiology, Masson staining, Immunofluorescence, Immunohistochemistry, Western blot, RNA sequencing, RT-qPCR were conducted.

            RESULTS The P2X7R was significantly upregulated in LA both in the MI and DEP rats, along with the increased risk of AF. Burst pacing induced atrial tachyarrhythmias in 10% CTL rats vs. 80% DEP-only rats, and only 20% BBG-treated DEP rats. Activation latency (AL) was significantly prolonged by DEP, whereas atrial effective refractory period (ERP) and ERP/APD90 ratio were reduced (all P<0.01). The above-mentioned electrophysiological parameters were attenuated by BBG. DEP caused atrial fibrosis. BBG strongly attenuated atrial fibrosis. DEP increased atrium expression of inflammation- and fibrosis-related mRNA and protein expression; however, BBG-treatment suppressed all these DEP-induced alterations. IL-1b induced inflammation in atrial fibroblasts, which was inhibited by BBG and A740003.

            CONCLUSIONS The P2X7R antagonist BBG prevents DEP-induced atrial proarrhythmic remodeling, while suppressing inflammatory changes and fibrotic/electrical remodeling, thus providing new insights into the relationship between P2X7R and atrial arrhythmias.

            GW33-e0757
            Loss of BTK ameliorates the pathological cardiac fibrosis and dysfunction

            Wang Bo1, Liu Xingguang2, Zhan Zhenzhen1

            1Institute of Heart Failure & Key Laboratory of Arrhythmias of the Ministry of Education of China, Tongji University Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, China

            2Department of Pathogen Biology, Naval Medical University, Shanghai 200433, China

            OBJECTIVES Cardiac fibrosis is a common irreversible pathological feature of diverse heart disorders. Uncontrolled cardiac fibrosis contributes to maladaptive cardiac remodeling and eventually heart failure. However, the molecular determinants of ischemic and non-ischemic cardiac fibrosis remain largely unknown. Here, we investigated the role of Bruton’s tyrosine kinase (BTK) in cardiac fibrosis and remodeling of mice under various pathological conditions.

            METHODS BTK-deficient mice following myocardial infarction (MI) or pressure overload model were used to investigate the role of BTK in pathological cardiac fibrosis and heart dysfunction. We further utilized primary cardiac fibroblasts with BTK deficiency or inhibitor treatment to explore potential mechanism.

            RESULTS BTK expression was increased in myocardium of mice after pressure overload or MI. BTK was mainly located in cardiac fibroblasts of myocardium, and its expression in isolated cardiac fibroblasts was upregulated following TGF-β treatment. BTK-deficient mice or the small molecule inhibitor of BTK were introduced to explore BTK function. The deficiency or pharmacological inhibition of BTK attenuated cardiac fibrosis, preserved cardiac function, prevented adverse cardiac remodeling and protected against heart failure in mice subjected to pressure overload or MI. BTK deficiency or inhibitor treatment significantly decreased the expression of fibrosis-related molecules in isolated cardiac fibroblasts and inhibited the transition of fibroblasts to myofibroblasts in response to diverse pathological stresses. BTK directly bound and phosphorylated TGF-β receptor I (TβR I), and then promoted the activation of downstream SMAD-dependent or -independent TGF-β signaling, leading to the enhanced transition of fibroblasts toward pro-fibrotic myofibroblasts and the excessive extracellular matrix gene expression.

            CONCLUSIONS Our finding uncovers a driving role of BTK in cardiac fibrosis and dysfunction following pressure overload and MI stress conditions, and highlights novel pathogenic mechanisms in ischemic and non-ischemic maladaptive cardiac remodeling, which presents as a promising target for the development of anti-fibrotic therapy.

            GW33-e0788
            Effect of rapamycin on the expression of origin recognition complex 1 on vascular smooth muscle cells of rats

            Qian Wang1, Maoqin Shu2, Xianxian Zhao1, Zhifu Guo1

            1Department of Cardiology, Changhai Hospital, Naval Medical University, Shanghai 200433, China

            2Department of Cardiology, Southwest Hospital, Army Medical University, Chongqing 400038, China

            OBJECTIVES To explore the effect of rapamycin on the expression of origin recognition complex 1 (ORC1) on vascular smooth muscle cells (VSMCs) of rats in vitro.

            METHODS Growth curves of VSMCs were drawn by methyl-thiazolyl-tetrazolium (MTT) colorimetric assay. VSMCs were divided randomly into two groups. Control group (CG) cells were cultured in DMEM with 10% FBS, and experimental group (EG) cells were cultured in DMEM with 10% FBS plus different concentrations of rapamycin (0.1 μmol/L, 1 μmol/L, 10 μmol/L and 100 μmol/L) to find the optimal concentration. Expression of ORC1 at transcriptional and protein levels were displayed respectively by RT-PCR and Western Blot during VSMCs were cultured with the optimal concentration of rapamycin at 0 h, 12 h, 24 h, and 48 h.

            RESULTS MTT showed that VSMCs were proliferative and in the exponential grow phase during cultured for 1–3 d. The optimal concentration of rapamycin was 10 μmol/L. The expression levels of ORC1mRNA in EG decreased gradually from 0 h to 12 h and reduced significantly from 24 h to 48 h compared with those of CG. The expression changes of ORC1 protein by Western Blot were similar to those of ORC1mRNA.

            CONCLUSIONS Rapamycin inhibits the expression of ORC1, indicating that the target of rapamycin (mTOR) is on the upstream of ORC1 in cell cycle, which shed light on novel strategies that can be used to prevent and treat vascular proliferative disease.

            TRANSLATIONAL RESEARCH OF CARDIOVASCULAR DISEASE
            GW33-e0013
            Efficacy and safety of a polytetrafluoroethylene membrane wrapped a single layer of sirolimus -eluting stent in a porcine coronary perforation model

            Rutao Wang, Yi Liu, Jingyu Zhou, Xiaoming Wang, Chao Gao, Fangjun Mou, Wangwei Yang, Ling Tao

            Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, China

            OBJECTIVES Covered stents are effective in treating coronary artery perforation (CAP), however, the high rate of immediate device deployment failure and in-stent restenosis have limited the application of the currently covered stents.

            METHODS We designed a balloon-expandable covered stent system consist of a single layer of drug-eluting stent and a layer of polytetrafluoroethylene (PTFE) membrane wrapped at the outer layer of the stent. The immediate sealing effect of our novel covered stent was observed by using an Ellis type III CAP model. The device’s success was defined as its ability to seal the perforation, assessed by visual estimation and final thrombolysis in myocardial infarction (TIMI) 3 flow. The antiproliferative effect was evaluated in 12 swine, which were randomly assigned to treatment (sirolimus-eluting covered stents) and control (bare metal covered stents) groups. Coronary angiography and optical coherence tomography (OCT) were performed at index procedure, 1- and 6-month after stent implantation. All swine were sacrificed for histopathological analyses at 6-month.

            RESULTS The device success rate was 100%. All swine were alive at 6-month follow-up. At 1-month, the treatment group had a larger minimal luminal diameter (MLD) (1.89±0.29 vs. 0.63±0.26, P=0.004) and lower late luminal loss (LLL) (0.47±0.15 vs. 1.80±0.34, P<0.001) compared with control group. At 6-month, the treatment group had a numerically higher MLD (0.94±0.75 vs 0.26±0.75 mm; P=0.230) and lower LLL (1.43±0.85 mm vs 2.17±0.28 mm; P=0.215) compared with control group. Histological analyses revealed the mean plaque area was lower in the treatment group (2.99±0.81 mm2 vs 4.29±0.77 mm2, P=0.035) than in the control group. No in-stent thrombosis was observed in either group.

            CONCLUSIONS In the porcine model of coronary perforation, the PTFE membrane wrapped sirolimus-eluting stent showed a high device success rate in sealing the perforation. The drug-eluting covered stent demonstrated a relatively sustained antiproliferative effect up to 6 months post-implantation.

            GW33-e0057
            Identification and characterization of novel loss-of-function mutations in the PCSK9 gene associated with low-density lipoprotein cholesterol in a Uyghur population in Xinjiang, China

            Fanhua Meng1,2

            1The First Affiliated Hospital of Xinjiang Medical University

            2Affiliated Hospital of Jining Medical College

            OBJECTIVES Dyslipidemia, represented by elevated serum LDL-C, is an important risk factor for ASCVD and reducing serum LDL-C levels can significantly reduce the risk of ASCVD morbidity and mortality. A loss-of-function mutation in the PCSK9 gene associated with low serum LDL-C levels reduces the risk of ASCVD morbidity and mortality.

            METHODS We screened for non-synonymous mutations in the PCSK9 gene by whole-exome sequencing of subjects with very low LDL-C levels and normal in a healthy population of young Uyghurs in the Xinjiang region of China. The effects of mutations on PCSK9 maturation and secretion, and on LDLR degradation were determined. Functional validation was performed at the cellular, animal and expanded population levels, respectively, to explore the molecular mechanisms by which novel mutations in the PCSK9 gene affect cholesterol metabolism.

            RESULTS By whole-exome sequencing, we identified two PCSK9 nonsynonymous mutations in a healthy population of young Chinese Uyghurs. Expanded population validation revealed that PCSK9 E144K and C378W carriers displayed lower LDL-C levels. PCSK9 E144K and C378W mutations are loss-of-function mutations that are unable to perform self-catalytic splicing and translocation out of the endoplasmic reticulum, respectively. PCSK9 E144K and C378W mutations have a reduced ability to degrade hepatic LDLR. Adeno-associated viral-mediated expression of PCSK9 (E144K and C378W) in mouse liver reduced hepatic LDLR degradation and lowered serum LDL-C, total cholesterol and triglycerides.

            CONCLUSIONS Our study shows that PCSK9 E144K and C378W are loss-of-function mutations. They have an effect on serum LDL-C levels in both humans and mice.

            GW33-e0058
            Serum SELENBP1 and VCL are effective biomarkers for clinical and forensic diagnosis of coronary artery spasm

            Liliang Li

            School of Basic Medical Sciences, Fudan University

            OBJECTIVES Coronary artery spasm (CAS) plays an important role in the pathogenesis of ischemic heart diseases, including stable angina, unstable angina, myocardial infarction, and sudden death. Currently there are no established diagnostic biomarkers for CAS in clinical and forensic settings. The present study aimed to identify biomarkers using serum quantitative proteome and machine learning methods, and validate their effectiveness in both clinical and forensic serum samples.

            METHODS A rabbit CAS provocation model was established to screen potential diagnostic biomarkers using quantitative serum proteomics, followed by parallel reaction monitoring/mass spectrometry (PRM/MS)-based targeted proteomics and machine learning analysis. Clinical and forensic serum samples were used for validation studies. Logistic regression analysis and receiver operating characteristics (ROC) curves were used to assess the diagnostic efficacy.

            RESULTS A total of 67 (18.3%) serum proteins were identified as differentially expressed proteins from the rabbit CAS model. Cross-analysis of PRM/MS-based targeted proteome and machine learning results suggested that SELENBP1 and VCL were the potential candidate biomarkers for CAS. Genome-wide association study and phenome-wide association study indicated that a variation in the SELENBP1 or VCL was significantly associated with blood monocyte aggregates and left-ventricle contractility, respectively. SELENBP1 and VCL were more concentrated in extracellular vesicles (EVs)-free serum samples. In the clinical samples, serum SELENBP1 and VCL levels were significantly lower in CAS patients than in controls. The areas under curve were 0.9064 for SELENBP1 and 0.8679 for VCL when diagnosing CAS. Logistic regression analysis showed the CAS risk decreased by 30.4 and 54.8% for every 10 units increase of serum SELENBP1and VCL, respectively. In collected forensic CAS samples, postmortem serum SELENBP1 level alone diagnosed the CAS-induced deaths at a sensitivity of 100.0% and specificity of 72.73%, which was superior to traditional biomarkers cTnI and CK-MB. A combination of serum SELENBP1 and VCL yielded a diagnostic specificity of 100.0%.

            CONCLUSIONS Serum SELENBP1 and VCL are effective biomarkers for both clinical and forensic diagnosis of CAS.

            GW33-e0073
            Plasma small extracellular vesicle-carried miRNA-501-5p promotes vascular smooth muscle cell phenotypic modulation-mediated in-stent restenosis

            Xiao-Fei Gao, Ai-Qun Chen, Zhen Ge, Jun-Jie Zhang

            Nanjing First Hospital

            OBJECTIVES Vascular smooth muscle cell (VSMC) phenotypic modulation plays an important role in the occurrence and development of in-stent restenosis (ISR), the underlying mechanism of which remains a key issue needing to be urgently addressed. This study is designed to investigate the role of plasma small extracellular vesicles (sEV) in VSMC phenotypic modulation.

            METHODS sEV were isolated from the plasma of patients with ISR (ISR-sEV) or not (Ctl-sEV) 1 year after coronary stent implantation using differential ultracentrifugation. Plasma sEV in ISR patients are elevated markedly and decrease the expression of VSMC contractile markers α-SMA and calponin and increase VSMC proliferation. miRNA sequencing and qRT-PCR validation identified that miRNA-501-5p was the highest expressed miRNA in the plasma ISR-sEV compared with Ctl-sEV.

            RESULTS We found that sEV-carried miRNA-501-5p level was significantly higher in ISR patients, and the level of plasma sEV-carried miRNA-501-5p linearly correlated with the degree of restenosis (R2=0.62). Moreover, miRNA-501-5p inhibition significantly increased the expression of VSMC contractile markers α-SMA and calponin and suppressed VSMC proliferation and migration; in vivo inhibition of miRNA-501-5p could also blunt carotid artery balloon injury induced VSMC phenotypic modulation in rats. Mechanically, miRNA-501-5p promoted plasma sEV-induced VSMC proliferation by targeting Smad3.

            CONCLUSIONS Notably, endothelial cells might be the major origins of miRNA-501-5p. Collectively, these findings showed that plasma sEV-carried miRNA-501-5p promotes VSMC phenotypic modulation-mediated ISR through targeting Smad3.

            GW33-e0094
            Adeno-associated viral gene therapy targeting cardiomyocyte with ubiquitin-specific protease 28 prevents diabetes-induced cardiac dysfunction

            Saiyang Xie1,2,3, Wei Deng1,2,3, Tang Qizhu1,2,3

            1Department of Cardiology, Renmin Hospital of Wuhan University

            2Hubei Key Laboratory of Metabolic and Chronic Diseases

            3Cardiovascular Research Institute of Wuhan University

            OBJECTIVES Diabetic heart failure is a leading complication and the cause of high mortality in type 2 diabetes mellitus (T2DM) patients. Most diabetics with genetic expression defects are susceptible to cardiac dysfunction, and conventional drug therapy cannot correct progression of diabetic cardiomyopathy.

            METHODS We first profiled the expression of ubiquitin-proteasome system (UPS) in db/db mice, and identified ubiquitin-specific protease 28 (USP28) as the key gene associated with diabetic heart phenotype. We next established the clinical relevance of this finding by showing the down-regulation of USP28 in the failing heart of diabetes patients. We used db/db mice (a mouse model of spontaneous type 2 diabetes) and mice with high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes as our models. Cardiac-specific USP28 deficient, cardiac-specific USP28 transgenic, wild type (WT) mice were fed HFD/STZ diet or standard diet. Subsequently, heart characteristics, cardiometabolic profile, transcriptomics and mitochondrial morphology and function were evaluated. Adeno-associated viral vector serotype 9 encoding Usp28 (AAV9-USP28) and AAV9-USP28 (C171S) in cardiomyocytes, and CRISPR-Cas9 gene edited induced pluripotent stem cells (iPSCs) was used to investigate the role of USP28. Transmission electron microscopy (TEM), oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and protein truncation test were used to explore the effect of USP28 upon mitochondrial homeostasis and the underlying mechanism.

            RESULTS USP28 level was substantial reduction in diabetic myocardium from patients and in spontaneously T2DM mice and mice fed with HFD/STZ diet. The level of USP28 also increased in high glucose plus palmitic acid (HG+PA)-treated iPSCs. Firstly. USP28 presented limited influence upon blood glucose, gain of body weight, insulin resistance and glucose tolerance in the myocardium. Cardiac-specific USP28 deficient mice presented deteriorated cardiac dysfunction following T2DM. Conversely, cardiac-specific USP28 transgenic mice showed improved diabetic heart phenotype. Importantly, Treatment of db/db mice with adeno-associated viral vector serotype 9 encoding Usp28 (AAV9-USP28) in cardiomyocytes counteracted T2DM induced systolic and diastolic dysfunction, cardiac hypertrophy, cardiac fibrosis and mitochondrial defects. Mechanistically, USP28 directly bound, deubiquitinated and stabilized peroxisome proliferators-activated receptor α (PPARα), and led to PPARα-mediated Mitofusin2 (Mfn2) transcription and improved mitochondrial fission in iPS induced cardiomyocytes. Further investigation uncovered that the UCH domain of USP28 directly interacted with the DBD domain of PPARα, while inactivation of USP28 (C171S) impeded the deubiquitination of PPARα. In addition, cardiac-specific knockdown of PPARα abolished AAV9-USP28 induced cardioprotection in db/db mice. Consistently, AAV9-USP28(C171S) showed no impact on diabetic heart.

            CONCLUSIONS We demonstrated the potential of AAV mediated-USP28 gene therapy to correct the diabetic heart pathology, providing strong rationale for future clinical translation.

            GW33-e0132
            Mechanism of differential response to propranolol and mexiletine in LQT2 patient with hERG_G604C mutation

            Ying Yang

            School of Clinical Medicine, Tsinghua University

            OBJECTIVES β-blockers have been recommended as first-line therapy in long QT syndrome (LQTS) patients. In our center, a LQT2 patient with hERG_G604C mutation showed prolonged QTc and increased cardiac events (CEs) with propranolol treatment, while QTc was shortened and CEs were controlled after switching to mexiletine, but the mechanism remains unclear.

            METHODS hERG_WT (WT), hERG_G604C (G604C) and heterozygous (WT/M) monoclonal stable cells were constructed in HEK293 cells. Western Blot and RT-qPCR were used to confirm the levels of hERG protein and mRNA, membrane protein Western Blot and immunofluorescence to evaluate protein trafficking, whole-cell patch-clamp to detect IKr current, and molecular docking to predict interaction between propranolol/mexiletine and hERG channel.

            RESULTS The expression of hERG mRNA and protein were comparable in WT and G604C group. G604C group presented with hERG trafficking deficiency. WT group induced strong IKr current, IKr current were disappeared in G604C group, and IKr current decreased over 50% in WT/M group. hERG mRNA and protein didn’t change significantly with increased concentration of propranolol, while propranolol inhibited IKr current with a concentration-dependent manner. Mexiletine rescued hERG protein trafficking deficiency, while transient effect of mexiletine on IKr current was a concentration-dependent inhibition, chronic effect of mexiletine on G604C mutant hERG channel was promotion. G604C mutation enhanced the interaction between hERG channel and propranolol, while not in mexiletine.

            CONCLUSIONS The combined effect of propranolol and mexiletine in LQT2 patients depends on the composite effect of rescuing mutant hERG protein trafficking deficiency, inhibition of β-receptor, INa,L current, and IKr current.

            GW33-e0265
            Sonodynamic therapy reduces inflammation and fibrosis of epicardial adipose tissue in pacing induced atrial fibrillation rabbit model

            Dechun Yin, Weifa Wang, Yanfeng Tian, Wei Wang, Hongpeng Yin, Ye Tian

            Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

            OBJECTIVES Epicardial adipose tissue (EAT) is an important risk factor for the occurrence and development of atrial fibrillation. There are active pro-inflammatory macrophages in EAT. The previous research of our research group found that sonodynamic therapy (SDT) could make macrophages died in atherosclerotic plaque and reduce atherosclerotic plaque inflammation. But the effect of SDT on EAT in AF is not clear. We plan to use pacing atrial fibrillation rabbits as a model to explore the effect and mechanism of SDT intervention in EAT. Then we maybe provide a new theoretical basis for the treatment of AF.

            METHODS The experiment was divided into sham operation group (Sham group), paced group and paced +SDT treatment group (+SDT group). (1) New Zealand white rabbits were installed pacemaker, pacing 600 times/min for 4 weeks to establish the rabbit model of atrial fibrillation. The +SDT group was given 4 hours of light avoidance and SDT intervention after intravenous injection of sinoporphyrin sodium (DVDMS). The three experimental models groups were taken after 2 weeks. (2) The number of macrophages in EAT insham group, paced group and +SDT group were detected by immunohistochemistry. (3) The level of EAT fibrosis in three groups were detected by Masson staining. (4) The differentially expressed genes and enrichment pathways in EAT were analyzed by transcriptome sequencing. (5) The mRNA level of inflammation and fibrosis related genes were detected by Real-time PCR. (6) The level of inflammation and fibrosis related proteins were detected by Western blot.

            RESULTS (1) Immunohistochemical results showed that the number of macrophages in EAT in paced group were higher than that in Sham group. The number of macrophages in EAT decreased after SDT. (2) Masson staining showed that the collagen content in EAT in paced group were higher than that in Sham group. The collagen content decreased after SDT. (3) Enrichment analysis of differentially expressed gene KEGG showed NF-κB signaling pathway and Toll like receptor signaling pathway changed. There were significant differences in the mRNA of Nacht, LRR and PYD domains containing protein 3 (NLRP3), C-C ligand 2 (CCL2), cysteine-x-cysteine ligand 8 (CXCL8) and matrix metalloproteinase 2 (MMP2). (4) The results of Real-time PCR showed that the mRNA levels of NLRP3, CCL2, CXCL8 and MMP2 in EAT were up-regulated after pacing. The mRNA level of these genes were down-regulated after SDT. (5) Western blot showed the protein levels of TLR4, NLRP3, NF- κB p50, NF-κB p65 and MMP2 were significantly up-regulated after pacing and significantly decreased after SDT.

            CONCLUSIONS SDT reduce inflammation and fibrosis in EAT of atrial fibrillation rabbits through inhibiting the expression of macrophage inflammatory factors and MMP2.

            GW33-e0347
            HIF-1α overexpression in mesenchymal stem cell-derived exosome-encapsulated arginine-glycine-aspartate (RGD) hydrogels boost therapeutic efficacy of cardiac repair after myocardial infarction

            Qingjie Wang

            Department of Cardiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China

            OBJECTIVES Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1α engineered mesenchymal stem cells (MSCs) in a rat model of AMI.

            METHODS EVs isolated from HIF-1α engineered MSCs (HIF-1α-EVs) and control MSCs (MSCs-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats.

            RESULTS Compared with MSCs-EVs, HIF-1α-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1α-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1α-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221-3p was highly expressed in HIF-1α-EVs. After miR-221-3p was inhibited in HIF-1α-EVs, the biological effects of HIF-1α EVs on apoptosis and angiogenesis were attenuated.

            CONCLUSIONS EVs released by MSCs with HIF-1α overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1α engineered MSCs-derived EVs.

            GW33-e0348
            Predicting acute kidney injury risk in acute myocardial infarction patients: an artificial intelligence model using MIMIC databases

            Ling Sun

            Department of Cardiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China

            OBJECTIVES Accurate estimation of the risk of acute kidney injury (AKI) is critical and essential for acute myocardial infarction (AMI). The aim of this study was to develop a machine learning model for improving the estimation of AKI risk in patients with AMI.

            METHODS Patients data in the training group were extracted from Medical Information Mart for Intensive Care-III (MIMIC-III) database, and adult patients diagnosed with AMI were selected. Several common machine learning algorithms were conducted to select the best pridiction model. Recursive feature elimination was used to select the best prediction features. The final model was validated using an external validation set from AMI patients in Medical Information Mart for Intensive Care-IV (MIMIC-IV) database database. The area under the receiver operating characteristic curve (AUROC) and calibration curve were used to evaluate the performance of each prediction model. Finally, an online predictive program was developed on WeChat (a mobile messaging App commonly used in China), which could evaluate the probability of AKI in AMI patients timely.

            RESULTS A total of 3882 patients with AMI were included, and among whom 1098 patients were diagnosed with AKI. The random forest model showed the best prediction performance (AUROC=0.912) among five machine learning models. Creatinine, urea nitrogen, platelet count, creatine kinase isoenzyme (CK-MB) and arterial blood systolic pressure were considered as the top five important features for developing the model. The enrolled patients were divided into low-risk and high-risk group for AKI, survival analysis showed an significant higher short-term mortality in high-risk group patients (P<0.001).

            CONCLUSIONS The results revealed that the prediction performance of random forest was superior to other machine models. Random forest classifier displayed a reliable performance in assessing AKI risk in AMI patients.

            GW33-e0406
            PCSK9 inhibition protects against myocardial ischemia- reperfusion injury via suppressing autophagy

            Guangwei Huang1,2,3, Xiyang Lu1,2, Haiyan Zhou1,2, Runhong Li1,2, Qing Huang3, Xinlin Xiong1,2, Zhenhua Luo4, Wei Li1,2

            1Guizhou Medical University, 550004 Guiyang, China

            2Department of Cardiovascular Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, 550004 Guizhou, China

            3Department of Cardiovascular Medicine, Anshun city People’s Hospital, Anshun, 561000 Guizhou, China

            4Department of Central Lab, Guizhou Provincial People’s Hospital, Guiyang 550002, China

            OBJECTIVES Autophagy is critical for myocardial ischemia-reperfusion (I/R) injury. However, there is still considerable debate over its protective and deleterious effects. The purpose of this study was to determine the involvement of the proprotein convertase subtilisin/Kexin type 9(PCSK9) and its inhibitor in myocardial ischemia-reperfusion injury autophagy (MRI).

            METHODS Nine groups of eighty rats were used: sham, I/R2 h, I/R4 h, I/R6 h, I/R8 h, I/R1 d, and I/R2 d. A 30-minute coronary artery blockage was used to produce myocardial IR. The time required for reperfusion rose linearly with the time gradient, from 2 hours to 2 days. Following the determination of the best reperfusion period, three groups were formed: sham, I/R, and I/R+P (PCSK9 inhibitor (evolocumab) 10 mg/kg diluted in 2 mL sterile injection water was administered subcutaneously 1 week and half an hour before to surgery. Each group’s infarction area was determined by electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) /Evan Blue (EB) staining. To detect morphological alterations in myocardial cells in each group, hematoxylin and eosin (HE) staining was used. Meanwhile, western blotting, immunohistochemistry, and Masson trichrome staining were utilized to quantify myocardial fibrosis and PCSK9 and autophagy protein expression.

            RESULTS The results indicated that PCSK9 expression levels increased significantly in MRI, as indicated by increased levels of the autophagy regulatory protein light chain 3 (LC3) and Beclin-1, which activated autophagy in cardiomyocytes, exacerbated myocardial injury, and increased the size of myocardial infarcts. Meanwhile, PCSK9 regulates mitophagy via the Bcl-2/adenovirus E1B 19-kDa interacting protein (BNIP3) pathway, which controls myocardial infarction MRI throughout. Additionally, the PCSK9 inhibitor significantly decreased autophagy, enhanced cardiac function, and reduced the extent of reperfusion injury, consequently reducing myocardial infarct size expansion.

            CONCLUSIONS PCSK9 is upregulated in the myocardial ischemia-reperfusion injury hearts and regulates mitophagy via the BNIP3 pathway, which in turn contributes to reperfusion injury after myocardial infarction. PCSK9 inhibition protects against myocardial ischemia-reperfusion injury via suppressing autophagy.

            GW33-e0433
            Rare-variant based linkage analysis and nanopore sequencing enable diagnosis of familial facioscapulohumeral dystrophy 1

            Kun Li, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies. Over 95% of FSHD cases are caused by deletion of the subtelomeric macrosatellite repeats (D4Z4) on human chromosome 4q35. Directly sequencing these repetitive regions is difficult owing to the high similarity among repeat units and high GC content. We aim to develop an efficient and accurate procedure for the diagnosis of FSHD.

            METHODS Whole genome sequencing was performed for ten individuals from a large FSHD family. Parametric linkage analysis was performed via Merlin (v1.1.2) with the following parameters: dominant model, an estimated population allele frequency of 1E-5, and penetrance of 90%. 4q and 10q haplotypes were characterized by alignment to the chm13 reference genome. A BLAT of the pLAM sequence were performed to identify the A/B haplotypes. Nanopore sequencing was used to obtain the whole D4Z4 repeat sequence and the methylation status, including the DUX4 in the last D4Z4 repeat.

            RESULTS Rare variants-based linkage analysis identified one single 1.7 MB haplotype on chromosome 4q35.2, presenting in affected individuals and absent from unaffected family members. Parametric linkage analysis resulted in a LOD score of 3.228 for the region. All pedigree samples contained 4q-pLAM sequence suggesting at least one copy of an 4qA permissive haplotype. Normalized counts of reads containing 4q-specific pLAM sequence were comparable between the FSHD patients, while 4q-specific D4Z4 repeat sequence demonstrated fewer reads in pedigree samples.

            CONCLUSIONS Family WGS and rare variants-based linkage analyses, combined with read depth analysis, provide the possibility of detecting the D4Z4 repeat contraction for FSHD1 patients. 4q pLAM specific sequence could be detected by matching to T2T-CHM13 reference. We verified Nanopore-based ultra-long read sequencer could obtain the whole D4Z4 repeat sequence and the methylation status in real cases for the first time in the world.

            GW33-e0452
            Rare variant based linkage analysis and nanopore sequencing enable diagnosis of familial facioscapulohumeral dystrophy 1

            Kun Li1, Ping Zhang1, Daniel Quiat2, Jonathan G Seidman2

            1Beijing Tsinghua Changgung Hospital

            2Harvard University Genetic Center

            OBJECTIVES Over 95% of FSHD cases are caused by deletion of the subtelomeric macrosatellite repeats (D4Z4) on human chromosome 4q35. Directly sequencing these repetitive regions is difficult owing to the high similarity among repeat units and high GC content. We aim to develop an efficient and accurate procedure for the diagnosis of FSHD.

            METHODS Whole genome sequencing was performed for ten individuals from a large FSHD family. Parametric linkage analysis was performed via Merlin (v1.1.2) with the following parameters: dominant model, an estimated population allele frequency of 1E-5, and penetrance of 90%. We realigned the 250-bp paired end whole genome sequencing reads to the chm13 reference genome using BWA-MEM and then measured the read count for reads containing either the 4q-specific D4Z4 sequence of 4q-specific pLAM sequence and normalized counts to the read depth of the p-arm of chromosome 4. Nanopore sequencing was used to obtain the whole D4Z4 repeat sequence and the methylation status, including the DUX4 in the last D4Z4 repeat.

            RESULTS Rare variants-based linkage analysis identified one single 1.7 MB haplotype on chromosome 4q35.2, presenting in affected individuals and absent from unaffected family members. Parametric linkage analysis resulted in a LOD score of 3.228 for the region. All pedigree samples contained 4q-pLAM sequence suggesting at least one copy of an 4qA permissive haplotype. Normalized counts of reads containing 4q-specific pLAM sequence were comparable between the FSHD patients, while 4q-specific D4Z4 repeat sequence demonstrated fewer reads in pedigree samples. Nanopore obtained the whole D4Z4 repeat sequence and the methylation status, including the DUX4 in the last D4Z4 repeat.

            CONCLUSIONS Family WGS and rare variants-based linkage analyses, combined with read depth analysis, provide the possibility of detecting the D4Z4 repeat contraction for FSHD1 patients. 4q pLAM specific sequence could be detected by matching to T2T-CHM13 reference. We verified Nanopore-based ultra-long read sequencer could obtain the whole D4Z4 repeat sequence and the methylation status in real cases for the first time in the world.

            GW33-e0457
            Mesenchymal stromal cells overexpressing farnesoid X receptor exert cardioprotective effects against acute ischemic heart injury by binding endogenous bile acids

            Yunlong Xia, Xiaoming Xu, Tingting Qi, Lu Peng, Yongzhen Guo, Wenjun Yan, Ling Tao

            Fourth Military Medical University

            OBJECTIVES Bile acid metabolites have been increasingly recognized as pleiotropic signaling molecules that regulate multiple cardiovascular functions, but their role in mesenchymal stromal cells (MSC)-based therapy has never been investigated. This study clarifies whether and how farnesoid X receptor (FXR), a main receptor for bile acids, improves the retention and cardioprotection of MSC against myocardial infarction (MI) injury.

            METHODS The targeted metabonomics was determined to detect the types and levels of bile acids in myocardial tissue after MI. Adenovirus harboring FXR was used to modify adipose tissue-derived MSC (ADSC-FXR). Eight-week-old male C57BL/6J mice were used for in vivo study. CM-DiI- or tdTomato-labeled ADSC were intramyocardially injected into the peri-infarct area at 3 sites immediately after MI surgery. The ADSC retention rate was detected by quantifying CM-DiI- or tdTomato-positive cells in heart sections. TUNEL and CD31 immunofluorescence staining were determined to detect cardiomyocyte apoptosis and capillary density. Echocardiography was determined to detect the cardiac structure and function. The myocardial fibrosis area was detected by Masson trichrome staining. At the cellular level, the paracrine proangiogenic capacity of ADSC was detected by tube formation assay and the antiapoptotic capacity was detected by Western blot and Flow cytometry. Moreover, the downstream molecules mechanism was investigated and verified by RNA sequencing, LC-MS/MS analysis, loss-of-function studies, ChIP and dual-luciferase reporter assay.

            RESULTS In vivo, FXR overexpression significantly increased the ADSC survival rate at 3 and 7 days after intramyocardial injection compared to ADSC-con. Moreover, ADSC-FXR significantly improved cardiac remodeling and function of MI mice, and increased the capillary density and ameliorated the cardiomyocyte apoptosis in the peri-infarcted area. In vitro, FXR overexpression promoted ADSC paracrine angiogenesis via angiopoietin-like protein 4 (Angptl4), but failed to improve ADSC survival. By performing bile acid-targeted metabolomics, we found that there was a bile acid pool in the myocardial microenvironment. ADSC-FXR showed significantly lower apoptosis by upregulating NADPH quinone oxidoreductase-1 (Nqo-1) expression in the presence of FXR ligands. In addition, knockdown of retinoid X receptor α (RXRα), a coactivator of FXR, largely reduced ADSC-FXR retention in the ischemic heart and their cardioprotection.

            CONCLUSIONS We first demonstrate that there is a bile acid pool in the myocardial microenvironment. Bile acid-FXR signaling enhances the cardioprotection of MSC against IHD via Nqo-1-mediated survival/retention and Angptl4-mediated paracrine angiogenesis directly.

            GW33-e0504
            MTP-131 modification alleviates superparamagnetic iron oxide nanoparticles induced ferroptosis in hypoxia/reoxygenation H9c2 cells

            Qizheng Lu, Jinbo Ou, Xiaobo Yao, Yunli Shen

            Department of Cardiology, Shanghai East Hospital, Tongji University School of Medicine

            OBJECTIVES Superparamagnetic iron oxide nanoparticles (SPION) as target carriers and cell tracers have been widely applied in the cardiovascular field. However, SPION may provoke a risk of ferroptosis in myocardial cells of ischemia reperfusion, which could be a potential obstacle for clinical transformation. Here, we explored the underlying mechanisms of SPION induced myocardial toxicity and whether MTP-131 modification could reverse the cardiotoxicity.

            METHODS MTP-131 was physically adsorbed on SPION in order to construct mitochondrial targeted antioxidant peptides modifying SPION (SPION@MTP-131). H9c2 cells following hypoxia/reoxygenation (H/R) procedure were treated with SPION or SPION@MTP-131 to evaluate the dose- and time-dependent toxic potential, as well as investigate the effect of MTP-131 on improving SPION induced cytotoxicity. The mitochondrial ROS levels and MMP were respectively measured by Mito-sox and JC-1. The lipid peroxidation product (MDA), ATP, GSH and GPX4 were tested by ELISA. The mitochondrial structure was observed by TEM. Cellular iron metabolic homeostasis was detected by WB or ELISA. The ferroptosis markers were detected by WB analysis or RT-PCR. To explore the main form of SPION-induced cell death, cardiomyocytes were exposed to SPION combined with Fer-1, 3-MA, Nec-1 or zVAD for 24 h, respectively.

            RESULTS SPION induced time- and concentration- dependent cardiotoxicity, evidence by significant loss of cell viability and elevated the level of LDH, whereas SPION@MTP-131 demonstrated similar results relative to the H/R group, suggesting that MTP-131 can significantly alleviate SPION induced cell damage. SPION seriously disturbed cellular iron homeostasis, characterized by increased expression of FtH and level of FtMt, and decreased expression of FPN1 and ABCB8, leading to mitochondrial iron overload. The mitochondrial iron metabolism disorder caused mitochondrial integrity damage and dysfunction, accompanied by MMP loss, ATP depletion, down-regulation of GSH and GPX4 expression and dramatically elevated mitochondrial MDA. The mitochondrial lipid peroxidation burst eventually led to ferroptosis of H/R cardiomyocytes, evidenced by up-regulated protein expression of NRF2 and ACSL4 and the increase of mRNA levels of ACSL4 and Ptgs2. MTP-131 significantly mitigated SPION-induced ferroptosis through reducing production of mitochondrial MDA and preserving concentrations of GSH and GPX4, indicating that MTP-131 holds a potential to reverse SPION-induced cytotoxicity by exerting mitochondrial targeted antioxidant effect. Compared with the H/R cardiomyocytes, there was no significant difference in cell viability of H9c2 cells co-incubated with SPION and Fer-1. Conversely, co-incubation of H9c2 cells with SPION by inhibitors of 3-MA, zVAD or Nec-1 respectively, these three inhibitors caused remarkable loss of H9c2 cell viability, indicating that ferroptosis could be main mechanism of SPION induced myocardial cytotoxicity.

            CONCLUSIONS SPION promote mitochondrial lipid peroxidation by inducing mitochondrial iron overload, thereby leading to ferroptosis of H/R cardiomyocytes. MTP-131 may inhibit SPION-induced ferroptosis of H/R cardiomyocytes, suggesting the modification of mitochondrial targeted antioxidant peptide could be a promising strategy.

            GW33-e0558
            The protective value of angiopoietin-like protein 8 in the prediction of myocardial infarction

            Yuanshu Peng, Chunming Han, Jian Zhou, Yuhao Zhao, Pixiong Su, Lei Zhao

            Beijing Chaoyang Hospital, Capital Medical University

            OBJECTIVES Angiopoietin-like protein 8 (ANGPTL8) is closely related to lipoprotein, blood glucose metabolism and atherosclerosis. The relationship between ANGPTL8 and coronary heart disease (CHD), especially myocardial infarction (MI), needs to be further explored. This study aimed to clarify the potential association between ANGPTL8 and myocardial infarction, and attempted to establish a MI prediction model with ANGPTL8 as the core.

            METHODS A total of 160 patients with CHD were included in this study, with 100 patients in the myocardial infarction group and 60 patients in the non-myocardial infarction group (non-MI group). In addition, patients were divided into the diabetic group (T2DM group) and the non-diabetic group (non-T2DM group) according to whether or not they had type 2 diabetes mellitus (T2DM). The levels of serum lipoprotein, blood glucose and related clinical variables were measured. The concentration of serum ANGPTL8 was detected by enzyme-linked immunosorbent assay (ELISA). The severity of coronary artery stenosis was evaluated by Gensini and Syntax scores. The prediction model of MI was established by logistic regression and visualized by nomogram.

            RESULTS Serum ANGPTL8 level in the non-MI group was significantly higher than that in the MI group (4.070[2.329–6.531] vs. 5.968[4.105–10.310], P=0.002). After adjusting the risk factors, ANGPTL8 was found to be an independent protective factor for the occurrence of MI (OR=0.864, [95% CI 0.759–0.982], P=0.026). The model based on the three variables of ANGPTL8, Gensini score and total cholesterol had a good predictive effect for MI (optimism-corrected c-statistic=0.864). Different from the non-T2DM group (4.885[2.543–8.296] vs. 5.184[4.066–7.045], P=0.337), there was a significant difference in the level of ANGPTL8 between patients with or without MI in the T2DM group (3.429[1.867–5.716] vs. 7.327[5.232–10.950], P<0.001). In the T2DM group, the addition of ANGPTL8 significantly improved the prediction efficiency of the model for MI by 46.2% (NRI (Categorical)=0.462, P<0.001; IDI=0.260, P<0.001), while the difference was not observed in the non-T2DM group (NRI (Categorical)=0, P=NaN; IDI<0.001, P=0.718).

            CONCLUSIONS ANGPTL8 is an independent protective factor of MI. ANGPTL 8 and diabetes may jointly affect the occurrence of MI. It would be helpful to improve the prediction accuracy of MI by stratification analysis and establish prediction models based on diabetes.

            GW33-e0648
            CD51+bMSCs exosomes coated with macrophage membrane migrated to infarcted myocardium and reconstructed coronary microcirculation via SOX17-VEGFR signaling pathway

            Dongmei Xie, Chaoquan Peng

            Department of Cardiology, The Third Affiliated Hospital, Sun Yat-Sen University

            OBJECTIVES Bone marrow-derived CD51-positive cells (CD51+bMSCs) were candidate progenitor cells for transplantation into acute myocardial infarction (AMI) mice, which could reduce death of cardiomyocytes and promote recovery of cardiac function. However, practical applications were limited by short survival time of resident cells in the injured myocardium and ball-like proliferation potential.

            METHODS Considering exosomes can mimic the biological effects of mother cells, we have discovered that the transplantation of exosomes secreted by CD51+bMSCs (abbreviation: CD51+bMSCs-Exo) to mice with AMI avoided the above problems, and effectively improved heart function via intramyocardial injection but not intravenous injection. The unequal effects were contributed to the different number of exosomes that attached to the injured tissues. Based on the chemotactic characteristics of macrophages to inflammatory tissues, we supposed that the chemotactic capacity of CD51+bMSCs-Exo could be improved when they encapsulated with macrophage membrane expressing multiple receptors (abbreviation: ME complex).

            RESULTS The experimental results show that: 1) ME complex migrated to the injured myocardium after intravenous delivery and promoted the recovery of infarcted myocardium. 2) Plenty of new blood vessels were emerged in the injured myocardium, which reconstructed coronary microcirculation. 3) Single-cell sequencing data found that sox17 may be an important factor to reconstruct coronary microcirculation in myocardial infarction tissue. We assessed the hypothesis that sox17 can form a positive feedback loop with VEGFR on endothelial cells. +bMSCs-Exo promotes angiogenesis.

            CONCLUSIONS In conclusion, ME complex activates SOX17/VEGFR of endothelial cells to promote angiogenesis in AMI mice.

            GW33-e0651
            A pH/H2O2/MMP9 time-response gel system with Sparchigh Tregs derived exosomes promote recovery after acute myocardial infarction

            Panke Cheng

            Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China

            OBJECTIVES Regulatory T cells overexpressing SPARC (Sparchigh Tregs) can help repair infarct tissues after acute myocardial infarction (AMI), but there is currently no effective strategy to mobilize large numbers of cells to sites of infarction, and the effect of Sparchigh Tregs derived exosomes on AMI also unknow.

            METHODS Sparchigh Treg-derived exosomes were directly injected into myocardium around the infarct border zone in AMI. An in situ gel forming system was designed based on Sparchigh Treg-derived exosomes overexpressing CXCR2, distearoyl phosphoethanolamine-acylhydrazone-polyethylene glycol, MMP9 enzyme substrate peptides and Co2+-modified 4-arm-polyethylene glycol, finally, the composite system was used to promote recovery after AMI.

            RESULTS Exosomes derived from Sparchigh Tregs can effectively promote the repair of AMI. Under the guidance of CXCR2 based on the inflammatory response, pH<6.8 triggered the release of the exosomes due to the acid sensitivity of the acylhydrazone bonds, while reactive oxygen species triggered gel formation in situ based on the oxidation of Co2+ by H2O2 to capture the released exosomes. Then, enzyme-triggered gel degradation based on the hydrolysis of substrate peptides by MMP9 slowly released the exosomes.

            CONCLUSIONS The synthetic composite system can quickly target infarcted areas, release and capture the exosomes to enhance the recovery of cardiac function in AMI.

            CLINICAL RESEARCH ON CARDIOVASCULAR DISEASES

            CORONARY HEART DISEASE
            GW33-e0035
            The relationship between serum ionized calcium and acute coronary syndrome

            Yong Hu, Xue Liang

            903 Hospital

            OBJECTIVES It is not totally clear what are the factors determine acute coronary syndrome (ACS) to be non-ST-segment elevated ACS (NSTE-ACS) or ST-segment elevated myocardial infarction (STEMI). This study aimed to evaluate the relationship between serum ionized calcium (i-Ca) and ACS.

            METHODS Patients with STEMI and NSTE-ACS in the eICU database were selected for retrospective analysis, excluding those with cardiac arrest, kidney dysfunction, parathyroid dysfunction and the history of atrial fibrillation/flutter, stroke and coronary atherosclerotic diseases (including myocardial infarction, percutaneous coronary intervention and coronary artery bridge grafting). Logistic regression models were fitted for STEMI risk compared with NSTE-ACS. i-Ca was initially fitted in 1 mg/dL, and in its quartiles (Q1–Q4), then as a restricted cubic spline, and finally in several subgroups. Multi-variable adjustments including: age, gender, body mass index, creatinine and albumin, type-2 diabetes and hypertension.

            RESULTS There were 863 ACS patients with 365 STEMI and 471 NSTE-ACS included. There was no difference in gender, BMI, ethnicity between STEMI and NSTE-ACS. Patients with STEMI were younger (61 vs 67, P<0.001) and their i-Ca were slightly but significantly higher (4.6 mg/dL vs 4.4 mg/dL, P=0.003). There were more diabetes and hypertension in NSTE-ACS (32.5 vs 18.9%, P<0.001, 61.4 vs 46.9%, P<0.001, respectively). Approximately 90% patients discharged alive from hospital in both groups. According to the restricted cubic spline, the risk of STEMI was equivalent to NSTE-ACS when i-Ca were 1.6 mg/dL-2.9 mg/dL, and that was slightly increased when i-Ca<1.6 mg/dL, the risk of STEMI was parabola-like when i-Ca;2.9 mg/dL, the highest risk of STEMI was four times of NSTE-ACS when i-Ca was around 4.5 mg/dL. Compared with Q1 of i-Ca, the OR (95% CI) of STEMI for Q2–Q4 were 1.66 (1.09–2.51, P=0.017), 1.61 (1.06–2.46, P=0.025) and 1.83 (1.19–2.80, P=0.006), respectively. The risk of STEMI increased by 14% for 1 mg/dL increase of i-Ca for all the patients and that was 74% for patients with concomitant hypertension.

            CONCLUSIONS Elevated i-Ca increased the risk of STEMI for ACS patients, especially for those with concomitant hypertension.

            GW33-e0037
            Analysis of optical coherence tomography of recurrent in-stent restenosis

            Yue Ma, Lei Song, Yunfei Huang, Jiansong Yuan, Jingang Cui, Fenghuan Hu, Weixian Yang, Shubin Qiao

            Research Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, CAMS & PUMC

            OBJECTIVES To clarify the similarities and differences in the mechanisms of of R-ISR and non-R-ISR by OCT characteristics analysis.

            METHODS A total of 52 patients with ISR after DES implantation who underwent OCT in Chinese Academy of Medical Sciences Fuwai Hospital from January 2015 to December 2019 were retrospectively enrolled, and the patients were divided into R-ISR group (16 patients) and non-R-ISR group (36 patients). The data on patient demographics, cardiovascular risk factors, ancillary tests, previous interventional treatments, and other medical history were collected. The coronary angiography and OCT images were analyzed qualitatively and quantitatively. To compare the differences between R-ISR and non-R-ISR patients.

            RESULTS There were no significant differences between R-ISR and non-R-ISR patients with cardiovascular risk factors such as hypertension, hyperlipidemia, diabetes mellitus, smoking history, family history of coronary heart disease, and coronary angiographic characteristics such as lesion location, ISR classification, reference vessel diameter, target lesion length (all P>0.05). The proportion of homogeneous neointima in R-ISR (43.8%) was significantly higher than that in non-R-ISR (19.4%), and the proportion of neoatherosclerosis (43.8%) was significantly lower than that in non-R-ISR (75%) (P<0.05).

            CONCLUSIONS As no difference in cardiovascular risk factors, patients with R-ISR showed a higher proportion of homogeneous neointimal, revealed fibroplasia was an important mechanism for R-ISR.

            GW33-e0038
            Long term prognosis and risk factors of intravascular imaging guided intervention for in-stent restenosis of coronary artery

            Yue Ma, Lei Song, Xiaojin Gao, Juan Wang, Chao Guo, Xiaoliang Luo, Jiansong Yuan, Weixian Yang, Shubin Qiao

            Research Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, CAMS & PUMC

            OBJECTIVES To analyze the clinical characteristics, compare the differences in long-term prognosis, and clarify the predictors of the occurrence of long-term adverse events in patients who underwent coronary in stent restenosis intervention guided by optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary angiography (CAG).

            METHODS A total of 79 patients with ISR underwent drug-eluting stent (DES) intervention guided by OCT in Chinese Academy of Medical Sciences Fuwai Hospital from January 2015 to December 2019 were retrospectively enrolled and matched by age, sex and admission date in a 1:1 ratio to the patients guided by IVUS and CAG guidance. The data on patient demographics, cardiovascular risk factors, ancillary tests, and other medical history were collected, patients were followed up by telephone or outpatient clinic, and the primary outcome (MACE) and secondary outcomes were used as study endpoints to compare the differences in long-term prognosis among the three groups and to analyze their predictive factors.

            RESULTS During a mean follow-up of 3.2±1.4 years, the primary endpoint (log rank P=0.033) and secondary endpoint (log rank P=0.027) were significantly more frequent in the CAG group than in the other 2 groups, the differences in the incidence of primary endpoint (log rank P=0.453) and secondary endpoint (log rank P=0.313) between OCT and IVUS groups were not statistically significant. Cox hazard proportional model analysis showed that intravascular imaging guided intervention remained an independent protective factor for reducing the occurrence of long-term MACE (hazard ratio=0.447, 95% confidence interval: 0.200–0.998, P=0.049).

            CONCLUSIONS The intravascular imaging guided PCI in patients with ISR is an independent protective factor for the occurrence of long-term MACE, and the long-term prognosis of PCI guided by OCT and IVUS is similar.

            GW33-e0043
            Compaired sacubitril/valsartan with benalapril on the left ventricular remordeling of AMI after PPCI: a case-control study

            Yanmin Xu

            The Second Hospital of Tianjin Medical University, Tianjin, China

            OBJECTIVES To compare the effect of sacubitril/valsartan with benalapril on left ventricular remodeling in patients with acute myocardial infarction.

            METHODS Eighty-five patients with acute ST segment elevation myocardial infarction who were treated with PCI in the Second Affiliated Hospital of Tianjin Medical University. The patients were randomly divided into two groups: the experimental group (sacubitril/valsartan, 25–100 mg/d, BID) and the control group (benalapril, 5–10 mg, QD).

            RESULTS One month after the treatment of sacubitril/valsartan or benalapril, only the left ventricular end systolic diameter was statistically different between the two groups (P<0.05), and the other indexes were not statistically different three months after treatment with sacubitril/valsartan or benalapril, there were statistical differences in the indexes related to myocardial remodeling between the two groups (P<0.05). The results of multivariate logistic analysis showed that the index of left ventricular end systolic diameter was statistically significant (or=0.006, 95% CI: 0.733–0.981). acute myocardial infarction whose LVEF is less than 50%, show sacubitril/valsartan is better than traditional ACEI.

            CONCLUSIONS Sacubitril/valsartan compared with benalapril is better on left ventricular remodeling in patients with ST segment elevation acute myocardial infarction.

            GW33-e0074
            3-Year outcomes of the ULTIMATE trial comparing intravascular ultrasound versus angiography-guided drug-eluting stent implantation

            Xiao-Fei Gao, Zhen Ge, Jun-Jie Zhang, Shao-Liang Chen

            Nanjing First Hospital

            OBJECTIVES The multicenter randomized ULTIMATE (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions) trial showed a lower incidence of 1-year TVF after IVUS-guided DES implantation among all comers compared with angiographic guidance. However, the 3-year clinical outcomes of the ULTIMATE trial remain unknown.

            METHODS A total of 1448 all comers undergoing DES implantation who were randomly assigned to either IVUS guidance or angiographic guidance in the ULTIMATE trial were followed for 3 years. The primary endpoint was the risk for TVF at 3 years. The safety endpoint was definite or probable stent thrombosis (ST).

            RESULTS At 3 years, TVF occurred in 47 patients (6.6%) in the IVUS-guided group and in 76 patients (10.7%) in the angiography-guided group (P=0.01), driven mainly by the decrease in clinically driven target vessel revascularization (4.5 vs. 6.9%; P=0.05). The rate of definite or probable ST was 0.1% in the IVUS-guided group and 1.1% in the angiography-guided group (P=0.02). Notably, the IVUS-defined optimal procedure was associated with a significant reduction in 3-year TVF relative to that with the suboptimal procedure.

            CONCLUSIONS IVUS-guided DES implantation was associated with significantly lower rates of TVF and ST during 3-year follow-up among all comers, particularly those who underwent the IVUS-defined optimal procedure compared with those with angiographic guidance. (Intravascular Ultrasound Guided Drug Eluting Stents Implantation in “All-Comers” Coronary Lesions; NCT02215915).

            GW33-e0100
            Bivalirudin versus heparin on a background of ticagrelor and aspirin in ST-segment elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: a multicenter prospective cohort study

            Xiao-Fan Yu1, Hong-Wu Chen1, Jie Xu1, Qi-Zhi Xu1, Xiao-Hong Zhang2, Bin-Bin Li2, Bang-Long Xu3, Li-Kun Ma1

            1Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China

            2Department of Cardiology, The First People’s Hospital of Hefei City

            3Department of Cardiology, The Second Affiliated Hospital of Anhui Medical University

            OBJECTIVES Current guidelines recommend potent P2Y12 inhibitors such as ticagrelor over clopidogrel as part of the dual antiplatelet therapy (DAPT) after ST-segment elevation myocardial infarction (STEMI), irrespective of final management strategy. The aim of this multicenter prospective cohort study was to examine the efficacy and safety of bivalirudin with background ticagrelor and aspirin therapy in STEMI patients undergoing primary percutaneous coronary intervention (PPCI).

            METHODS A total of 800 STEMI patients who were undergoing PPCI and receiving treatment with aspirin and ticagrelor from 3 Hospitals between April 2019 and September 2021 were included in this study. The patients were assigned, according to the perioperative anticoagulant, to the bivalirudin group (n=456) or the heparin group (n=344). In this study, the primary endpoint was 30-day net adverse clinical events (NACE), a composite of major adverse cardiac or cerebral events (MACCE, a composite of cardiac death, recurrent myocardial infarction, ischemia-driven target vessel revascularization, or stroke), or any bleeding as defined by the Bleeding Academic Research Consortium (BARC) definition (grades 1–5).

            RESULTS The patients were followed up for 30 days after PPCI. The incidence of NACE was significantly lower in the bivalirudin group than in the heparin group (11.2 vs 16.0%, P=0.042), and this significance was mainly a consequence of the reduction in BARC 1 bleeding events in the bivalirudin group compared to the heparin group (3.2 vs. 7.1%, P=0.010). Results from multivariate Cox regression analysis showed that bivalirudin significantly reduced 30-day NACE (HR: 0.676, 95% CI: 0.462–0.990, P=0.042) and BARC1 bleeding events (HR: 0.429, 95% CI: 0.222–0.830, P=0.010). No significant between-group differences were observed for MACCE, all-cause mortality, cardiac death, recurrent myocardial infarction, stroke, target vessel revascularization, stent thrombosis, and BARC2-5 bleeding events at 30 days.

            CONCLUSION In patients with STEMI who were undergoing primary PCI and receiving treatment with aspirin and ticagrelor, bivalirudin was associated with decreased rates in NACE and minimal bleeding events without significant differences in the rates of MACCE or stent thrombosis when compared with heparin. Nevertheless, large randomized trials are warranted to confirm these observations.

            GW33-e0101
            HDL-C/ApoA-I ratio is an important indicator predicting in-hospital death in patients with acute coronary syndrome

            Ji Zhenjun1, Liu Guiren2, Zhang Rui1, Carvalho Abdlay1, Guo Jiaqi1, Zuo Wenjie1, Zhang Xiaoguo1, Qu Yangyang1, Lin Jie3, Gu Ziran1, Yao Yuyu1, Ma Genshan1

            1Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China

            2Department of Epidemiology and Health Statistics, School of Public Health, Southeast University, Nanjing 210009, Jiangsu, China

            3Department of Cardiology, Jiangsu Taizhou People’s Hospital, The Fifth Affiliated Hospital of Nantong University, Taizhou 225300, Jiangsu, China

            OBJECTIVES Dyslipidemia plays a pivotal role in the pathogenesis of acute coronary syndrome (ACS). This study aims to investigate the value of two indices associated with lipid metabolism, low-density lipoprotein cholesterol to apolioprotein B ratio (LBR) and high-density lipoprotein cholesterol to apolioprotein A-1 ratio (HAR), to predict in-hospital death in patients with ACS.

            METHODS This single-center, retrospective, observational study included consecutive 3366 ACS patients in Zhongda Hospital, Southeast University from Jul 2013 to Jan 2018. The clinical and laboratory data were extracted, and the in-hospital death and hospitalization days were also recorded. Shapiro-Wilk test was used for judging normality. For continuous numerical variables conforming to the normal distribution, one-way ANOVA analysis was used for comparison among multiple groups. Data following the non-normal distribution was described as median (interquartile range), and Mann-Whitney U test was used for comparison between multiple groups. Chi-square test was used for comparison of binary variables. Pearson analysis was used for correlation analysis between HAR and other variables. Logistic regression analyses were used for adjusting potential confounding factors to determine indepdent factors of in-hospital death.

            RESULTS (1) All patients were equally divided into four groups according to quartiles of HAR: Q1 (HAR<1.0283), Q2 (1.0283≤HAR<1.0860), Q3 (1.0860≤HAR<1.1798), and Q4 (HAR≥1.1798). Overall, HAR was positively associated with the counts of neutrophils and monocytes whereas negatively correlated to lymphocyte counts. HAR was negatively correlated to left ventricular ejection fraction (LVEF). Compared to other three groups, in-hospital mortality (vs. [Q1], [Q2], and [Q3], P<0.001) and hospitalization length (vs. [Q1], [Q2], and [Q3], P<0.001) were significantly higher in the Q4 group. When grouped by LBR, however, there was no significant difference in LVEF, in-hospital mortality, and hospitalization length among groups. (2) HAR was positively correlated to age (r=0.073, P<0.001), BUN (r=0.161, P<0.001), Cr (r=0.122, P<0.001). HAR was negatively related to SBP (r=-0.055, P=0.001) and ALB (r=-0.169, P<0.001). Regarding inflammatory markers, HAR was positively associated with high sensitivity C reactive protein (hsCRP) (r=0.297, P<0.001), neutrophils (r=0.138, P<0.001), and WBC (r=0.119, P<0.001), while it was negatively correlated to lymphocytes counts (r=-0.130, P<0.001). HAR was not associated with diabetes related indicators, such as HbA1C (r=-0.024, P=0.163) and GLU (r=-0.008, P=0.655). By contrast, LBR was negatively related to age (r=-0.085, P<0.001), BUN (r=-0.080, P<0.001), ALB (r=0.134, P<0.001), Cr (r=-0.055, P=0.001) and hsCRP (r=-0.103, P<0.001), and positively associated with SBP (r=0.039, P=0.023) and lymphocyte count (r=0.075, P<0.001). (3) After adjusting potential impact from age, systolic blood pressure, creatine, lactate dehydrogenase, albumin, glucose, and uric acid, multivariate analysis indicated that HAR was an independent factor predicting in-hospital death among ACS patients.

            CONCLUSIONS HAR had good predictive value for patients’ in-hospital death after the occurrence of acute coronary events, but LBR, which represents the size of the LDL particle size, was not related to in-hospital adverse events.

            GW33-e0111
            Association of sagittal abdominal diameter with cardiovascular disease and cardiometabolic risk factors among US adults: results from the NHANES (2011–2016)

            Haitao Huang1, Hemanyun Bai1,2, Kangling Ke1,2, Xiao Liang1,2, Linyan Fang1, Weize Xu1,2, Fanji Meng1, Can Chen1

            1Department of Cardiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China

            2Guangdong Medical University, Zhanjiang, Guangdong 524001, China

            OBJECTIVES Obesity is a significant risk factor of cardiovascular diseases (CVD), posing a serious threat to global health. The study regarding sagittal abdominal diameter (SAD), a proxy for visceral fat, and CVD is scarce and its association remains uncertain. The aim of current study was to evaluate the association between SAD and CVD in adults.

            METHODS We included 11,477 adults from the National Health and Nutrition Examination Survey (NHANES) 2011–2016. Multivariable logistic regression analysis and restricted cubic spline were used to assess the relationship between SAD and CVD. Then, the receiver operating characteristic (ROC) curve was established and the area under curve (AUC) was calculated to compare the predictive ability of SAD, body mass index (BMI) and waist circumference (WC) on CVD.

            RESULTS The weighted mean (95% CI) of SAD was 22.6 (22.4, 22.8) cm, and prevalence of CVD was 6.81%. Higher SAD levels were significantly with higher levels of glucose, insulin, HOMA of insulin resistance, HbA1c, and triglyceride, and lower levels of high-density lipoprotein cholesterol (all Ptrend<0.001). After multivariate adjustment, higher SAD levels were significantly and linearly associated with higher prevalence of CVD, congestive heart failure (CHF), coronary heart disease (CHD), and myocardial infarction (MI): augment of risk were 10, 16, 11, and 7%, respectively, per one-unit increment of SAD (all P<0.05). Compared with participants with SAD<19.2 cm, the multivariate-adjusted ORs (95% CI) for participants with SAD>25.3 cm were 3.26 (1.72, 6.18) for CVD, 3.94 (1.51, 10.29) for CHF, 6.31 (2.59, 15.37) for CHD, and 5.21 (1.62, 16.76) for MI (all Ptrend<0.05). The area under the ROC curve of SAD [0.639 (95% CI, 0.622–0.655)] was more than BMI [0.564 (95% CI, 0.547–0.582)] and WC [0.566 (95% CI, 0.550–0.582)].

            CONCLUSIONS Higher level of SAD were closely related to the risk of cardiovascular disease. With the increase of SAD, the incidence of CVD increased gradually. SAD is better than BMI and WC in predicting CVD. These findings suggest that SAD should be evaluated to assess visceral fat and CVD risk during physical examination.

            GW33-e0133
            Impact of subclinical hypothyroidism on prognosis after percutaneous coronary intervention for chronic total occlusion

            Yu Yang, Lei Zhang, Dingxin Zhang, Mengqing Ma, Xianhe Lin

            Cardiology Department, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China

            OBJECTIVES The influence of subclinical hypothyroidism (SCH) on clinical outcomes following percutaneous coronary intervention (PCI) for Chronic Total Occlusion (CTO) remains unclear. To investigate the effect of SCH on the prognosis of patients with chronic total coronary artery occlusion after Interventional therapy.

            METHODS From August 2018 to October 2019, a total of 120 patients who were diagnosed with CTO and successfully treated with PCI in the Cardiac Catheterization Room of the first affiliated Hospital of Anhui Medical University were included. According to the level of (TSH), the patients were divided into two groups: euthyroidism group (ET group, n=98) and subclinical hypothyroidism group (SCH group, n=22). The clinical and angiographic conditions of the two groups were compared, and multivariate Cox survival analysis was used to compare the differences of major adverse cardiovascular and cerebrovascular events (MACCE) between the two groups during follow-up, and multivariate Cox regression analysis was used to evaluate the independent correlation between SCH and adverse clinical outcomes.

            RESULTS The average follow-up was 18 months. The incidence of MACCE in the SCH group was higher than that in the ET group (22.7 vs 5.1%). Multivariate Cox regression analysis showed that SCH was independently associated with the risk of MACCE (HR=4.56, 95% CI: 1.32∼15.77, P=0.017).

            CONCLUSIONS SCH negatively impacted clinical outcomes following CTO-PCI. Therefore, patients with SCH should be carefully observed after CTO-PCI.

            GW33-e0140
            Correlation between bilirubin levels and PCI-related death after surgery in diabetic patients with coronary heart disease

            Linqing Li1, Mingkang Li1, Yuhan Qin1, Yong Qiao2, Dong Wang2, Gaoliang Yan2, Chengchun Tang2

            1School of Medicine, Southeast University

            2ZhongDa Hospital, Southeast University, Cardiology

            BACKGROUND Bilirubin is a natural endogenous antioxidant, which has important physiological functions, including anti-free radicals, anti-inflammatory, anti-complement, anti-immune and anti-vascular smooth muscle proliferation, can protect vascular endothelial function, and can inhibit platelet activation. Recent studies have found that bilirubin levels may be closely related to coronary heart disease. This study mainly explores the relationship between serum bilirubin levels and long-term cardiopathic death after epithelial coronary artery intervention therapy (PCI) in diabetic patients with coronary heart disease.

            METHODS Retrospective analysis of 1952 patients receiving PCI coronary heart disease combined diabetes. Patients were divided into four groups according to serum bilirubin (BIL) levels: < =6.10 (group 1, n=485), 6.11–8.70 (group 2, n=471), 8.71–12.0 (group 3, n=458) and ;12.01 (group 4, n=445). Follow-up of patients after PCI surgery, Cox regression model was used to analyze whether bilirubin levels were an independent risk factor for PCI-derived death after surgery in patients with coronary heart disease combined diabetes.

            RESULTS Of the 1952 patients followed, 93 (4.76%), had a heart-derived death. There were 18, 19, 19 and 37 patients with heart-derived deaths at different bilirubin levels. Lower or higher bilirubin levels were significantly associated with an increased risk of heart-derived death after PCI, independent of mixed factors. Kaplan-Meier shows survival in patients with different serum bilirubin levels, suggesting that lower aor higher bilirubin levels may be higher in patients with a higher risk of cardiogenic death, the difference in incidence between groups is statistically significant (P<0.005). According to Cox regression analysis, it is suggested that age, AMI history, stroke history, LVEF, right coronary lesions, CTO, ST segment elevation are risk factors for survival in patients with high bilirubin levels; Revascularization may be a protective factor for heart-derived death after PCI.

            CONCLUSIONS There is a correlation between higher or lower bilirubin levels and the occurrence of heart-derived death in patients with coronary heart disease combined diabetes, and too low or too high bilirubin may be an independent risk factor for clinical heart-derived death in patients with coronary heart disease combined diabetes treated with PCI.

            GW33-e0156
            High sensitivity C-reactive protein, body mass index and long-term outcomes in patients after percutaneous coronary intervention: a large cohort study from China

            Zeng Guyu, Yuan Deshan, Wang Peizhi, Jia Sida, Li Tianyu, Yuan Jinqing

            Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Science and Peking Union Medical College

            OBJECTIVES Residual inflammatory risk contributes to the occurrence of cardiovascular (CV) events. As obesity is considered as a state of chronic low-graded inflammation, we hypothesized that body mass index (BMI) might modify the prognostic value of elevated high-sensitivity C-reactive protein (hsCRP) for CV risk in patients with coronary artery disease.

            METHODS This study included 7396 patients undergoing percutaneous coronary intervention (PCI) from January to December 2013. Patients were divided into three groups according to the BMI criteria for Chinese adults: normal weight (18.5 to <24 kg/m2, n=1870), overweight (24 to <28 kg/m2, n=3762) or obese (≥28 kg/m2, n=1764). Elevated hsCRP was defined as ;3 mg/L. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality, myocardial infarction, revascularization, and stroke. The secondary endpoint was all-cause mortality.

            RESULTS During a mean follow-up of 5.1 years, 1620 (21.9%) and 276 (3.7%) patients experienced MACCE and mortality, respectively. After multivariable adjustment, elevated hsCRP was significantly associated with an increased risk of MACCE (HR: 1.19, 95% CI: 1.05–1.34, P=0.006). Significant association between hsCRP and risk of MACCE and all-cause mortality was only observed in the normal-weight group (HR: 1.37, 95% CI: 1.07–1.75, P=0.01; HR: 2.20, 95% CI: 1.34–3.60, P=0.002) and diminished in the obese group. There was a significant interaction for all-cause mortality between BMI categories and hsCRP (P=0.04).

            CONCLUSIONS In patients undergoing PCI, hsCRP-associated cardiovascular risk may be modified by BMI levels, which could help identify specific individuals who may benefit the most from further anti-inflammation treatment.

            GW33-e0176
            Clinical study of two dimensional speckle tracking to evaluate myocardial abnormal movement caused by coronary artery disease

            Shaoqing Sun, Shihui Wang, Linwen Zeng, Lin Sun, Jingjie Li

            First Affiliated Hospital of Harbin Medical University

            OBJECTIVES By exploring the global longitudinal strain (GLS) reflecting myocardial contractility in STE and the mechanical dispersion reflecting the synchrony of myocardial motion in predicting coronary stenosis, this topic provides more reliable early diagnosis for patients with coronary heart disease. non-invasive testing methods.

            METHODS (1) Sixty-seven patients were enrolled. According to their coronary angiography results as diagnostic criteria, patients with coronary artery stenosis greater than 50% were included in the experimental group, and the rest were included in the control group. (2) Echocardiography of apical second, third and fourth cavities was taken, and the duration of echocardiography was ≥3 cardiac cycles. GLS and longitudinal strain of each cavity were analyzed and the myocardial movement of the patients was assessed by mechanical discrete analysis. (3) The myocardial movement of patients with coronary stenosis was statistically analyzed, and P<0.05 was considered statistically significant. STE results, patients’ age, blood pressure, heart rate, BMI and past medical history were taken as input variables, and the outcome variables were CTCA coronary stenosis ;50%. A diagnostic prediction support vector machine model was constructed to observe the diagnostic value of the model for coronary stenosis prediction.

            RESULTS The results showed that both GLS and mechanical dispersion were positively correlated with the degree of coronary stenosis (r=0.383, 0.342, P<0.05), and GLS was also positively correlated with mechanical dispersion (R=0.327, P<0.05). The results showed that reduced GLS (P=0.007, OR=1.354, OR 95% confidence interval 1.100, 1.722) and reduced mechanical dispersion (P=0.030, OR=1.005, OR 95% confidence interval 1.001, 1.010) were independent risk factors for predicting coronary stenosis.

            CONCLUSIONS STE can identify abnormal myocardial movement caused by coronary stenosis at an early stage, and can be evaluated from two aspects of myocardial contractility and coordination of myocardial movement, providing a new clinical idea for non-invasive prediction of coronary vessel conditions. The combination of GLS and mechanical dispersion can supplement the diagnostic basis of echocardiography to observe patients with inadequate myocardial movement, and the PREDICTION of LS in each cavity is significant, which can rapidly evaluate the coronary situation in a very short time, providing a simple and feasible new method and new idea for clinical practice.

            GW33-e0178
            P2Y12 inhibitor reloading for patients with Non-ST-segment Elevation Acute Coronary Syndrome already on chronic P2Y12 inhibitor therapy in China: findings from the CCC-ACS (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) project

            Yu Geng, Yintang Wang, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES The safety and efficacy of an additional clopidogrel load in non-ST-segment elevation acute coronary syndrome (NSTEACS) patients whilst on chronic maintenance clopidogrel therapy have not yet been well characterized in China. This study was designed to evaluate whether P2Y12 receptor inhibitor reloading is associated with in-hospital major adverse cardiac events and major bleeding for these patients.

            METHODS The Improving Care for Cardiovascular Disease in China–Acute Coronary Syndrome (CCC-ACS project) is a novel national quality enhancement registry of the Chinese Society of Cardiology. A total of 4790 patients with a definitive diagnosis of NSTEACS on chronic P2Y12 receptor inhibitor therapy were included at 104 hospitals in China from November 2014 to December 2019. Univariable and multivariable Cox proportional hazard model were performed to examine the association between reloading of P2Y12 inhibitor and in-hospital outcomes. Survival curves of MACE and major bleeding were illustrated using Kaplan–Meier curves and compared employing log-rank tests.

            RESULTS Among the NSTACS patients on long-term P2Y12 receptor inhibitor therapy who were received P2Y12 receptor inhibitor reloading were younger and had fewer comorbid conditions. Reloading P2Y12 receptor inhibitors had lower risk of MACE (0.51 vs. 1.42%, P=0.007), as well as all-cause death (0.36 vs. 0.99%, P=0.028) and myocardial infarction (0.15 vs. 0.50%, P=0.028), however the risks of major bleeding (0.15 vs. 0.35%, P=0.234) were not significantly different between patients with and without reloading. In Kaplan–Meier curves, the lower cumulative hazard of MACE could be identified (Log-rank test, P=0.007) in reloading group patients. In the unadjusted Cox regression model, reloading P2Y12 receptor inhibitors was associated with a decreased risk of MACE (HR, 0.35; 95% CI, 0.16–0.78; [P=0.010]) and all-cause death (HR, 0.37; 95% CI, 0.14–0.94; [P=0.036]). Reloading of P2Y12 receptor inhibitors was associated with a decreased risk of MACE in most of the subgroups.

            CONCLUSIONS The NSTEACS patients receiving long-term P2Y12 receptor inhibitors therapy was associated with decreased risk of in-hospital major adverse cardiac events or all-cause mortality, and did not increase the risk of major bleeding with P2Y12 receptor inhibitors reloading, therefore reloading could be effective and safe for NSTE-ACS patient.

            GW33-e0183
            The staged revascularization for chronic total occlusion in the non-IRA in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: an updated systematic review and meta-analysis

            Yintang Wang, Yu Geng, Ping Zhang

            Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing, China

            OBJECTIVES Patients with ST-segment elevation myocardial infarction (STEMI) concomitant with chronic total occlusion (CTO) in the non- infarct-related artery (non-IRA) were associated with an increased mortality. Successful revascularization for CTO lesion in the non-IRA could improve clinical outcomes. The meta-analysis was performed to evaluate the effect of the staged revascularization for the CTO in the non-IRA of patients with STEMI treated with primary percutaneous coronary intervention (p-PCI).

            METHODS Studies were searched in electronic databases from inception to June, 2021. The primary endpoint was the all-cause death, and the secondary endpoint was a composite of major adverse cardiac events (MACEs). Odds ratio (OR) was pooled with 95% confidence interval (CI) for dichotomous data.

            RESULTS Seven studies involving 1540 participants were included into the final analysis. Pooled analyses revealed that patients with successful staged revascularization for a CTO in non-IRA with STEMI treated with p-PCI had overall lower all-cause death (OR, 0.46; 95% CI, 0.23–0.95), cardiac death (OR, 0.43; 95% CI, 0.20–0.91), MACEs (OR, 0.43; 95% CI, 0.20–0.91) and heart failure (OR, 0.57; 95% CI, 0.37–0.89). No significant differences were observed between the two groups with regard to myocardial infarction and repeated revascularization.

            CONCLUSIONS Successful revascularization of CTO in the non-IRA was associated with improved outcomes in patients with STEMI treated with p-PCI.

            GW33-e0235
            A novel predictor of the outcomes in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention: random blood glucose to albumin ratio

            Cien Zhen1,2,3, Hualin Fan1,2,3, Weibin He2, Zehuo Lin4, Zijing Lin5, Yuanhui Liu2,3, Pengcheng He2,3,6

            1Department of Cardiology, School of Medicine, South China University of Technology, Guangzhou 510006, China

            2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            3Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            4Shantou University Medical College, Shantou 515041, China

            5The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China

            6Department of Cardiology, Heyuan People’s Hospital, Heyuan 517000, China

            OBJECTIVES Random blood glucose and albumin are easily accessible, both of which are indicators of diabetes mellitus and malnutrition, respectively. However, the predictive value of random blood glucose to albumin ratio (RAR) for clinical adverse outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains unclear.

            METHODS Patients with STEMI undergoing PCI were enrolled from 2010 to 2019. These patients were categorized into 3 groups according to the RAR value quantiles (Q1, Q2 and Q3). The primary outcome was in-hospital all-cause mortality. The secondary outcomes were in-hospital major adverse cardiac events (MACEs).

            RESULTS Of the 3324 enrolled patients, in-hospital all-cause mortality occurred in 130 patients (3.9%) and in-hospital MACEs in 181 patients (5.4%). Patients with higher RAR value had higher incidences of in-hospital all-cause mortality and in-hospital MACEs (P<0.001). Multivariate logistic regression showed that the higher RAR was associated with a higher risk of in-hospital all-cause mortality [adjusted odds ratio (OR) 2.72, 95% confidence interval (CI) 1.47–5.03, P=0.001] and in-hospital MACEs (adjusted OR 1.91, 95% CI 1.18–3.10, P=0.009). Receiver operating characteristic curve analysis indicated that RAR could accurately predict in-hospital all-cause mortality [area under the curve (AUC) 0.718, 95% CI 0.675–0.761] and the in-hospital MACEs (AUC=0.672, 95% CI=0.631–0.712). The optimal statistical cutoff point of RAR was 4.429 by using the Youden index.

            CONCLUSIONS RAR, as a novel and convenient predictor, was an independent predictor of in-hospital all-cause mortality and in-hospital MACEs in patients with STEMI undergoing PCI.

            GW33-e0236
            No myocardial ischemia induced by myocardial bridge in resting-state confirmed by fractional flow reserve

            He Lv, Youfa Zeng, Aijie Hou, Yunqi Shi, Qiang Fu

            Department of Cardiology, The People’s Hospital of China Medical University, The People’s Hospital of Liaoning Province, Shenyang City, Liaoning Province

            OBJECTIVES Studies have found that myocardial bridge (MB) is associated with atherosclerosis and myocardial ischemia. However, the vast majority of patients may have no symptom.

            METHODS Thirty-nine patients with MB in the left anterior descending coronary artery confirmed by coronary computed tomography angioplasty were recruited. Hyperemic proximal FFR (FFRp) and distal FFR (FFRd) of MCA were measured by pressure wire, and then the decline degree of FFR (FFRp–FFRd, ΔFFR) was calculated. Quantitative coronary angiography (QCA) was used to identify the MSSD and MCAL. By comparing FFRp with FFRd, the effect of MB on FFR was analyzed. “FFR=0.8” (i.e. ΔFFR=0.2 (1–0.8)) was taken as the cutoff of myocardial ischemia to explore the correlation between MB and myocardial ischemia. In addition, we further observed the influence of MCAL and MSSD on ΔFFR and the correlation between MCAL and MSSD.

            RESULTS FFRd is significantly lower than FFRp (P<0.01). However, ΔFFR was distinctly lower than 0.20 (P<0.01). Neither MCAL (P>0.05) nor MSSD (P>0.05) has correlation with ΔFFR. There is a significant positive correlation between MSSD and MCAL.

            CONCLUSIONS Although MB causes a significant decrease in FFR, no ischemia is induced. ΔFFR is independent of both MCAL and MSSD. So it can be got the conclusion that maybe no treatment is necessary for MB itself.

            GW33-e0247
            Predictive value of a naive bayesian classifier for the diagnostic of stable coronary artery disease

            Xinliang Zou1, Min Jiang1, Weiyi Han1, Li Nie2, Tao Jing1

            1Department of Cardiology, Southwest Hospital, Third Military Medical University (Army Medical University)

            2Department of Internal Medicine, Wandong Town Central Hospital, Wansheng Economic Development Zone

            OBJECTIVES Based on the naive Bayesian classification algorithm in machine learning, a predictive model for the diagnosis of stable coronary artery disease (SCAD) was constructed for patients with chest pain symptoms to assist in the initial diagnosis and screening of clinical SCAD. It aims to identify high-risk patients early, accurately guide the formulation of clinical examinations and treatment plans, assist clinicians in judging the indications for coronary angiography, and reduce the burden of medical and health resources.

            METHODS A cross-sectional study was designed. We selected patients aged 18–85 who visited the Department of Cardiology, the First Affiliated Hospital of Army Military Medical University, from January 2020 to December 2021 due to chest pain symptoms. Results at least one artery with more than 50% stenosis was diagnosed with SCAD and used as the case group (429 cases). According to the ratio of 1:1, the patients who did not support the diagnosis of coronary artery disease by the angiography results were used as the control group, and patients with the acute coronary syndrome were excluded. The variable information of the research subjects was collected from the baseline time of the visit, combined with general information, past medical history, auxiliary examination results, etc. A total of 18 variables were collected. Data analysis and machine learning algorithm implementation were performed using R software. Based on the naive Bayesian classification algorithm in machine learning, this research prunes and optimizes the model according to the prediction performance of each variable, simplifying the model structure and improving the prediction performance. We used the ROC curve and AUC to evaluate the model prediction performance.

            RESULTS The naive Bayesian classifier calculates the corresponding AUC of a single variable. And then, we removed the variable from the model one by one from low to high to find the model structure with the best performance. Finally, we choose “age”, “the number of mixed carotid plaques”, “glycated hemoglobin (HbA1C)”, “gender”, and “(high-density lipoprotein cholesterol) HDL-C”. The ROC curve AUC of the internally validated model was 0.662. The AUC of the naive Bayesian classifier after only retaining “the number of mixed carotid plaques”, “age” and “gender” was 0.640.

            CONCLUSIONS The naive Bayesian classifier has a simple structure, and the corresponding variables are the most common indicators in clinical work. Among them, the number of mixed plaques in the carotid artery results showed good performance in the model.

            GW33-e0260
            Prognostic implications of noninvasive myocardial work and microvascular perfusion in acute myocardial infarction patients who underwent primary percutaneous coronary intervention

            Siyao Sun, Tao Cong, Qiqi Chen, Na Chen, Qiaobing Sun, Hong Wei, Tingting Fu, Zhijuan Shang, Yinghui Sun

            The First Affiliated Hospital of Dalian Medical University

            OBJECTIVES Predicting left ventricular recovery (LVR) after acute ST-elevation myocardial infarction (STEMI) is of prognostic importance. This study aims to explore the predictive value of noninvasive myocardial work (niMW) and microvascular perfusion in predicting LVR after STEMI.

            METHODS A total of 112 patients with STEMI who successfully underwent emergent PCI with thrombolysis in myocardial infarction (TIMI) 3 were enrolled and underwent transthoracic Doppler echocardiography within 72 h after PCI and at a 3 month follow-up. Microvascular perfusion (MVP) was analyzed by low mechanical index ultrasound imaging, and segmental myocardial work was analyzed by noninvasive pressure-strain loops (PSLs). At the three-month follow-up, segmental function was reassessed, and the ability of the niMW and MVP to predict segmental LVR (normalization of wall thickening within the risk area) was assessed.

            RESULTS A total of 671 segments with abnormal function at baseline were analyzed. The segments were divided into 3 groups according to the MVP: Group 1 (normal MVP, n=70), Group 2 (delayed MVP or dMVP, n=236), and Group 3 (microvascular obstruction or MVO, n=365). sMW and segmental longitudinal strain (sLS) were significantly worse in Group 3 patients (P<0.001) compared with those in Group 1 and Group 2. The sMW indices were independently correlated with MVP. Of the 671 segments, segmental recovery at the 3-month follow-up was observed in 244 segments, whereas nonrecovery was observed in 427 segments. Segments with LVR had higher (more negative) baseline sLS and sMW indices and lower baseline MVP rates than those in nonrecovery segments (all P<0.001). Segmental myocardial work efficiency (sMWE) and MVP were independent predictors for LVR (P<0.05). sMWE provided incremental prognostic information over MVP (P<0.001).

            CONCLUSIONS Segmental niMW is correlated with segmental MVP in STEMI patients who underwent primary PCI. Furthermore, sMWE and MVP have independent prognostic value in predicting segmental recovery, and sMWEs provide incremental prognostic value over MVP. These noninvasive echocardiography parameters may improve the evaluation of myocardial viability and prognosis in these patients.

            GW33-e0263
            Construction and verification of the nomogram model for major adverse cardiovascular events risk after PCI in patients with NSTEMI

            Qianru Yuan, Yitong Ma, Baozhu Wang, Aibibanmu Aizeze, Gulinazi Yesitayi, Nazila Yaliqin

            Heart Center, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES Clinically, patients with NSTEMI have a higher risk of major adverse cardiovascular events (MACE) after PCI. Therefore, we construct a nomogram model for MACE risk after PCI in patients with NSTEMI, and evaluate its discrimination and consistency.

            METHODS This study included 655 patients with NSTEMI who underwent PCI in the First Affiliated Hospital of Xinjiang Medical University from June 2017 to April 2021. MACE was defined as cardiovascular death, cardiovascular readmission, heart failure, acute myocardial infarction, stroke and all-cause death. According to the occurrence of MACE after PCI, the patients were divided into MACE group (79 cases) and non-MACE group (576 cases). The clinical data of patients were collected, and univariate analysis and multivariate Logistic regression analysis were used to explore the related influencing factors of MACE in NSTEMI patients. The determined influencing factors were introduced into R4.1.3 software to build a nomogram model to predict the risk of postoperative MACE in NSTEMI patients. Receiver operating characteristic curve (ROC) was used to analyze the discrimination of the nomogram model, and the calibration curve and the Hosmer-Lemeshow goodness-of-fit test were used to evaluate the consistency.

            RESULTS Multivariate Logistic regression analysis showed that age [OR=4.432, 95% CI (3.661, 5.827)], Kiliip score [OR=3.894, 95% CI (3.366, 5.131)], Gensini score [OR=6.014, 95% CI (6.010, 6.019)], Grace score [OR=3.444, 95% CI (3.172, 4.099)], Timi score [OR=3.894, 95% CI (3.366, 5.131)] were the influencing factors of MACE after PCI in patients with NSTEMI (P<0.05). Based on the results of multivariate Logistic regression analysis, a nomogram model was constructed to predict the risk of MACE after PCI in patients with NSTEMI. The area under curve of nomogram model in predicting the MACE after PCI in patients with NSTEMI was 0.896 [95% CI (0.837, 0.934)]. The calibration curve of the nomogram model for predicting the risk of MACE after PCI in patients with NSTEMI was basically consistent with the actual curve, and the Hosmer-Lemeshow goodness of fit test showed that χ2=8.778, P=0.336.

            CONCLUSIONS Age, Kiliip score, Gensini score, Grace score and Timi score are the influencing factors of MACE after PCI in patients with NSTEMI. In this study, the nomogram model for MACE risk after PCI in patients with NSTEMI constructed based on the above 5 factors has good discrimination and consistency.

            GW33-e0271
            Observation of acute and chronic injury of radial artery after transradial intervention

            Senhu Wang

            Department of Cardiology, Beijing Luhe Hospital, Capital Medical University, Beijing, China

            OBJECTIVES Used OCT to observe acute and chronic injury of radial artery after first and repeat transradial intervention in the same patient.

            METHODS A total of 51 patients who underwent repeat OCT guided transradial intervention from January 2016 to March 2022 were divided into a first-time group and a repeat group according to the number of treatments. The differences of acute injuries (Intimal tear, dissection, perforation, thrombosis and spasm) and chronic injuries (LN%, IER, ITI) between the two groups and the differences between each segment after two operations were compared.

            RESULTS There was no statistically significant difference in the incidence of acute injury between the first and repeated group (21.1 vs 31.6%, 12.3 vs 21.1%, 7 vs 10.5%, 61.4 vs 43.9%, 80.7 vs 75.4%), and there is no significant difference between the paragraphs. The repeated group LN%, IER, ITI were higher than the first group. Moreover, the luminal stenosis in the sheath free area was significantly higher than that in the sheath area.

            CONCLUSIONS Repeat transradial interventions had no significant effect on the occurrence of acute damage, and there was no significant difference in the incidence of acute injury between segments transradial intervention leads to intimal thickening and luminal narrowing of the radial artery with a more prominent sheath free zone.

            GW33-e0276
            Digital therapy for rest heart rate control in coronary artery disease: a parallel-group, single-blind, randomised controlled trial

            Ou Zhang, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES The mobility and mortality of coronary artery disease (CAD) is rapidly increasing in China but access to secondary prevention remains low. Rest heart rate (RHT) is closely relatively with mortality in patients with CAD. In this study, we aimed to assess the digital therapy for rest heart rate in CAD (DIRECT-CAD) from a smartphone-based secondary prevention mini-program delivered via the social media platform WeChat.

            METHODS In this parallel-group, single-blind, randomised controlled trial, we recruited patients aged 18 years or older with coronary artery disease who had received percutaneous coronary interventions from Beijing Tsinghua Changgung Hospital in Beijing, China. Participants were randomly assigned (1:1) by block randomisation to either a digital therapy programme or to usual care. In the DIRECT-CAD group, participants received comprehensive secondary prevention via WeChat. The usual care group received standard outpatient cardiology follow-up but without formal secondary prevention. Assessments were done at baseline, 1 month, 3 months, and 6 months. The primary outcome was a change in rest heart rate baseline, measured by office and family rest heart rate at 6 months.

            RESULTS Between October 1, 2020, and Feb 1, 2021, 302 patients (mean age 60⋅1 years, of whom 52 (17.2%) were female and 250 (82.8%) were male, were recruited and subsequently randomly assigned to DIRECT-CAD (n=151) or usual care (n=151). The improvement in rest heart rate at 6 months was significantly greater in the DIRECT-CAD group (from 72 b/m at baseline to 64 b/m than in the control group (from 72.4 b/m at baseline to 70.8 b/m).

            CONCLUSIONS DIRECT-CAD was found to be a secondary prevention service model with high efficacy and accessibility and to be easy to use. These results justify the implementation of similar models of care on a broader scale.

            GW33-e0278
            Clinical characteristics and outcomes for STEMI patients treated with primary PCI in low risk area during the pandemic of COVID-19: a retrospective cohort study

            Ou Zhang, Ping Zhang

            Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University

            OBJECTIVES The pandemic of COVID-19 has affected millions of patients and changed management strategies of various diseases. There is no large-scale data reporting clinical characteristics and outcomes of STEMI patients in low risk area during COVID-19 pandemic. To determine whether the pandemic of coronavirus disease 2019 (COVID-19) may affect clinical outcome of ST segment elevation myocardial infarction infarction (STEMI) patients in North of Beijing, China, the epidemiological low risk area.

            METHODS It was a single center retrospective observational study. Clinical characteristics and outcomes of all STEMI patients treated with primary percutaneous coronary intervention (PPCI) from January 24, 2020 to April 24, 2020 (group 2020) and in the same period in 2019 (group 2019) were compared.

            RESULTS Totally 90 STEMI patients were included in our study (group 2020, n=51 vs. group 2019, n=39). No confirmed COVID-19 case in our study. Of note, group 2020 tended to have longer door-to-balloon (DTB) time (135 (90, 184) vs. 76 (59, 102), P<0.0001), system delay time (from first medical contact to wire crossing time (206.5 (118, 313) vs. 92 (73, 114), P=0.003) and total delay time (from symptoms to wire crossing time) (333 (204, 581) vs. 173 (150, 362), P<0.0001)). There was no significant difference in the incidence of composite outcome of in-hospital death, cardiogenic shock, heart failure and use of mechanical circulatory support between group 2020 and 2019 (17 (33.33%) vs. 11 (28.21%), P=0.60). However, the rate of left ventricular aneurysm was significantly increased in group 2020 (27.45 vs. 5.13%, P=0.006) compared with 2019.

            CONCLUSIONS COVID-19 may delay the treatment time of PPCI for STEMI patients, but no significant difference was observed on clinical outcome.

            GW33-e0289
            Changes in HMGB1/RAGE signaling pathway expression in the middle-aged patients with acute myocardial infarction and its correlation with the degree of coronary stenosis

            Ruoyu Cui, Juan Zhao

            First Affiliated Hospital of Harbin Medical University

            OBJECTIVES Recent studies have found that high mobility group box 1 protein (HMGB1) interacts with receptor for advanced glycation end-products (RAGE) in the extracellular environment. In combination, it can regulate the release of inflammatory factors, participate in inflammatory responses, and play a role in the occurrence and progression of various cardiovascular diseases. This study observed the expression of HMGB1 and RAGE signaling pathways and downstream cytokines in serum of middle-aged patients with AMI changes and their relationship with the degree of coronary stenosis.

            METHODS From September 2021 to December 2021, 304 middle-aged patients who were admitted to the First Affiliated Hospital of Harbin Medical University due to “chest pain” and were hospitalized in the cardiovascular department were collected. Symptoms, electrocardiogram, myocardial enzymes and other examination results required for a clear clinical diagnosis divided them into three groups: the control group (Con group, n=152) and the acute myocardial infarction group (AMI group, n=152). The medical records of the enrolled patients were collected, including: age, gender, smoking history, drinking history, body mass index (BMI), hypertension history, diabetes history, etc. Then, according to the patient’s condition, coronary angiography or coronary CTA was selected to determine the coronary stenosis, and the Gensini calculation score was performed. HMGB1, RAGE, ICAM-1, VE-cad, TNF-α, MMP-9 and other levels. Finally, SPSS26.0 was used for statistical analysis of the above indicators.

            RESULTS The levels of ICAM-1, VE-cad, TNF-α and MMP-9 in the AMI group were significantly higher than those in the Con group (P<0.05). In the short-term follow-up observation, compared with the Con group, the AMI group had significantly higher levels of HMGB1 and RAGE at the time of enrollment (P<0.05), significantly decreased on the 3rd day, and almost dropped on the 7th day. to baseline levels (P=NS) but still above baseline levels. The results of correlation analysis confirmed that serum HMGB1/RAGE protein levels were positively correlated with the levels of sICAM-1, VE-cad, and TNF-α, but had no significant correlation with the levels of MMP-9 in the AMI group. The expression of HMGB1/RAGE protein was positively correlated with the degree of coronary stenosis (r=0.522, P=0.015 and r=0.506, P=0.019), and was positively correlated with Gensini score (r=0.765, P=0.000 and r =0.718, P=0.000).

            CONCLUSIONS The expression levels of HMGB1 and RAGE proteins are significantly increased in middle-aged patients at the onset of AMI, which may accelerate coronary vasospasm and plaque progression by promoting the release of cytokines such as ICAM-1, VE-cad and TNF-α. form. The level of HMGB1/RAGE protein is closely related to the degree of coronary stenosis and may be a clinical indicator for predicting the degree of coronary damage.

            GW33-e0295
            Prognostic impact of stress hyperglycemia ratio in acute myocardial infarction patients with and without diabetes mellitus: insights from the NOAFCAMI-SH registry

            Jiachen Luo

            Shanghai Tenth People’s Hospital

            OBJECTIVES

            Stress hyperglycemia ratio (SHR) is associated with increased in-hospital morbidity and mortality in patients with acute myocardial infarction (AMI). We aimed to investigate the impact of stress hyperglycemia on long-term mortality after AMI in patients with and without diabetes mellitus (DM).

            METHODS We included 2089 patients with AMI between February 2014 and March 2018. SHR was measured with the fasting glucose divided by the estimated average glucose derived from glycosylated hemoglobin (HbA1c). The primary endpoint was all-cause death.

            RESULTS Of 2089 patients (mean age: 65.7±12.4, 76.7% were men) analyzed, 796 (38.1%) had DM. Over a median follow-up of 2.7 years, 141 (6.7%) and 150 (7.2%) all-cause deaths occurred in the diabetic and nondiabetic cohorts, respectively. Compared with participants with low SHR (<1.24 in DM; <1.14 in non-DM), the hazard ratios and 95% confidence intervals for those with high SHR (≥1.24 in DM; ≥1.14 in non-DM) for all-cause mortality were 2.23 (1.54–3.23) and 1.79 (1.15–2.78); for cardiovascular mortality were 2.42 (1.63–3.59) and 2.10 (1.32–3.35) in DM and non-DM subjects, respectively. The mortality prediction was improved in the diabetic individuals with the incorporation of SHR into the Global Registry of Acute Coronary Events (GRACE) score, showing an increase in a continuous net reclassification index of 0.184 (95% CI: 0.003–0.365) and an absolute integrated discrimination improvement of 0.014 (95% CI: 0.002–0.025).

            CONCLUSIONS The improvement in the prediction of long-term mortality beyond the GRACE score indicates the potential of SHR as a biomarker for post-MI risk stratification among patients with DM.

            GW33-e0303
            Smoking and outcomes following personalized antiplatelet therapy in stable coronary artery disease patients: a substudy from the randomized PATH-PCI trial

            Ying Pan, Ying-Ying Zheng, Ting-Ting Wu, Chang-Jiang Deng, Xiang Xie

            Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, P.R. China

            OBJECTIVES Prior studies have suggested better outcomes in stable coronary artery disease (SCAD) patients undergoing PCI who received personalized antiplatelet therapy (PAT). Smoking is a high-risk factor for poor prognosis in CAD. However, it is unknown whether smoking affects the safety and efficacy of PAT.

            METHODS The PATH-PCI was a prospective, randomized, open-label trial. SCAD patients after PCI were randomized to either a standard group or a personalized group guided by a novel platelet function test. We evaluated net adverse clinical events (NACEs) 180 days after PCI as the primary endpoint.

            RESULTS Of 2285 randomized SCAD patients, 1170 (51.2%) patients were smokers. For NACEs and major bleeding, we found no difference between the groups in smokers or nonsmokers (P>0.05). Compared with SAT, PAT reduced the percentage of MACCEs in smokers (HR=0.513, P=0.022) and nonsmokers (HR=0.485, P=0.011). We only find PAT reduced the percentage of MACEs in nonsmokers (HR=0.365, P=0.006). The Cox hazard model suggested that PAT was an independent protective factor against MACCEs.

            CONCLUSIONS PAT is effective in SCAD patients who have undergone PCI, regardless of smoking status. PAT may be an independent protective factor against MACCEs. Smoking weakens the efficacy of PAT and has no impact on the safety of PAT.

            GW33-e0333
            Polymorphisms of rs55796634 in the CD74 gene are associated with myocardial infarction

            Mintao Gai1, Xiaocui Chen1, Fen Liu1, Xiang Xie1,2, Yining Yang 1, Xiang Ma1,2, Zhenyan Fu1,2, Xiaomei Li1,2, Bangdang Chen1, Yitong Ma1,2

            1Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University

            2Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES CD74 is involved in innate immunity, and it is a receptor of macrophage migration inhibition factor. Basic studies show that CD74 participates in myocardial infarction (MI) in mice. However, whether the CD74 gene is associated with MI in clinics is still unclear.

            METHODS A case-control study was designed to investigate the relationships between the tag single nucleotide polymorphisms (tagSNPs) of the CD74 gene and MI in the Xinjiang population, China. Two tag SNPs (rs55796634, rs1056400) of the CD74 gene were genotyped in 996 MI patients and 998 healthy controls by an improved multiplex ligation detection reaction (iMLDR) technique.

            RESULTS Comparing the differences in baseline characteristics between the MI and control groups, no significant differences were observed in age, sex, waist circumference, and systolic blood pressure (all P>0.05). And blood glucose, diastolic blood pressure, and body mass index (BMI) had differences between the two groups (all P<0.05). The distributions of rs55796634 genotype in each genotype and dominant model were significantly different between the groups (all P<0.05). The CT+TT genotype of rs55796634 was associated with MI [odds ratio (OR) 1.29, confidence interval (CI) 1.06–1.57, P=0.011]. Further, the CT+TT genotype of rs55796634 was still an independent risk factor for MI after adjusting for age, BMI, hypertension, and diabetes [odds ratio (OR) 1.30, confidence interval (CI) 1.01–1.67, P=0.045]. In addition, we observed that the number of monocytes in blood was higher in the CT+TT genotype than the CC genotype [0.52±0.43(×109/L) vs. 0.47±0.32(×109/L), P<0.05].

            CONCLUSIONS The CT+TT genotype of rs55796634 in the CD74 gene was a novel independent risk factor for MI.

            GW33-e0337
            Prognostic value of malnutrition using geriatric nutritional risk index in patients with NSTEMI after percutaneous coronary intervention

            Gulinazi Yesitayi, Qi Wang, Xiang Ma

            The First Affiliated Hospital of Xinjiang Medical University

            METHODS Baseline malnutrition risk was determined in 756 patients with NSTEMI after PCI in this study. All patients were divided into three groups according to 3 categories of the geriatric nutritional risk index (GNRI): moderate to severe, GNRI of <92 (n=179); low, GNRI of 92∼98 (n=233); and absence of risk, GNRI of ;98 (n=344). The primary outcome is in-hospital major adverse cardiac events (MACE: all-cause death, heart failure, nonfatal recurrent myocardial infarction, and stroke). Long-term MACE were cardiac death, stent restenosis, and target vessel revascularization during the 1-year follow-up period.

            RESULTS Average age in this study was 64.25±14.80 years old. More than half of patients were at risk of malnutrition (moderate to severe: 23.7; low: 30.8; and absence of risk: 45.5%). Compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for in-hospital MACE (hazard ratio [HR]: 2.70, 95% confidence interval [CI]: 1.78 to 4.97, P=0.0020) after adjustment for baseline variables. Moreover, over a median follow-up of 1 year, addition of the GNRI score significantly raised the predictive value for the all-cause death (0.313, P=0.003 and 0.0042, P=0.011, NRI and IDI respectively), Long-term MACE (0.478, P<0.001 and 0.004, P=0.008, NRI and IDI respectively) as compared to traditional factors.

            CONCLUSIONS Malnutrition assessed by the GNRI score on admission was an independent predictor for MACE in NSTEMI patients after PCI during the hospitalization. Addition of the GNRI score to the existing risk prediction model significantly increased the predictive ability for long-term MACE in NSTEMI patients after PCI.

            GW33-e0350
            Geriatric nutritional risk index: a new index for predicting the clinical outcomes in patients with non-ST-elevation myocardial infarction after percutaneous coronary intervention

            Qianru Yuan, Yitong Ma, Baozhu Wang, Aibibanmu Aizeze, Nazila Yaliqin, Gulinazi Yesitayi

            Heart Center, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES Malnutrition is associated with poor prognosis in a wide range of chronic illnesses, however, the impact of malnutrition on long-term outcomes of patients with non-ST-elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention, is not known. The purpose of the study was to assess the geriatric nutritional risk index in predicting clinical outcomes in NSTEMI patients after percutaneous coronary intervention (PCI).

            METHODS Baseline malnutrition risk was determined in 655 patients with NSTEMI after PCI in this study. All patients were divided into 3 groups according to 3 categories of the GNRI: moderate to severe, GNRI of <92 (n=83); low, GNRI of 92–98 (n=167); and absence of risk, GNRI of ≥98 (n=405). The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE).

            RESULTS Average age in this study was 65.32±9.97 years old. More than one-third of patients were at risk of malnutrition (moderate to severe: 12.7%; low: 25.5%; and absence of risk: 61.8%). Over a median follow-up of 3.2 years, compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for the all-cause death (HR 2.79, 95% CI 1.43–3.87, P<0.05), cardiovascular death (HR: 3.99, 95% CI 2.42–6.77, P<0.01) and MACE (HR: 1.46, 95% CI 1.09–2.93, P<0.05) after adjustment for baseline variables.

            CONCLUSIONS Malnutrition assessed by the GNRI score on admission was an independent predictor for adverse cardiovascular events in NSTEMI patients after PCI.

            GW33-e0356
            Predictive value of SYNTAX score II and triglyceride glucose index for long-term prognosis in patients with acute ST segment elevation myocardial infarction with multivessel disease

            Aibibanmu Aizeze, Yitong Ma, Dilare Adi, Qianru Yuan, Nazila Yaliqin

            Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

            OBJECTIVES The purpose of this study is to explore the predictive value of SYNTAX-II score combined with TyG index for adverse cardiovascular events in patients with acute ST segment elevation myocardial infarction with multi vessel disease after percutaneous coronary intervention (PCI).

            METHODS A retrospective cohort study was conducted on 3215 patients who underwent coronary intervention in the heart center of the First Affiliated Hospital of Xinjiang Medical University from January 2014 to January 2020. The primary endpoint was target lesion failure (TLF), including cardiac death, target vessel myocardial infarction, and ischemia driven target lesion revascularization. Secondary endpoints included stent thrombosis and major adverse cardiac events (MACE), defined as all-cause death, myocardial infarction, and all revascularization.

            RESULTS During the 24-month follow-up period, the incidence of primary endpoint events increased significantly with the increase of SYNTAX-II score and TyG index (P<0.05). Kaplan Meier analysis showed that patients with high TyG index had the lowest survival rate of events (P<0.001). Multivariate analysis showed that age, left ventricular ejection fraction, creatinine clearance, TyG index and SYNTAX-II score were independent predictors of all-cause mortality, and TyG index and SYNTAX-II score were independent predictors of TLF (HR=1.616 and 1.165, 95% CI: 1.201–2.176 and 1.020–1.046, P<0.05). The predictive value of TyG index combined with SYNTAX-II score for all-cause death was higher than that of SYNTAX-II score (AUC 0.612 vs. 0.729, P=0.001). Hosmer lemeshow goodness of fit test was used to show that χ2=5.364, P=0.718. After TyG index was included, the net reclassification index and overall difference index increased significantly (NRI=0.319, P<0.001; IDI=0.034, P<0.001).

            CONCLUSIONS SYNTAX-II score and TyG index are independent predictors of long-term adverse cardiovascular events in patients with acute STEMI with multi vessel disease after PCI.

            GW33-e0357
            Stress hyperglycemia ratio combined with plaque characteristics as a novel biomarker for cardiovascular outcomes after percutaneous coronary intervention in ST-elevated myocardial infarction patients: an intravascular optical coherence tomography study

            Aibibanmu Aizezi, Yitong Ma, Dilare Adi, Yuan Qianru, Nazila Yaliqin

            Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

            OBJECTIVES Stress hyperglycemia is a powerful predictor of adverse outcomes in patients with acute myocardial infarction (AMI). However, the relationship between SHR and the morphology and characteristics of vulnerable plaques in patients with acute myocardial infarction (AMI) has not been fully studied.

            METHODS Nine hundred forty-six patients with acute myocardial infarction diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2017 to January 2019 were included in the retrospective study. Optical coherence tomography was performed before intervention. All patients were divided into three groups according to the third quartile of SHR (SHR1, SHR2 and SHR3). Patients with plaque rupture (PR) and plaque erosion (PE) were divided into three groups across the SHR tertiles. Baseline clinical data and culprit plaque characteristics were compared between the three groups, and all patients were followed up for major adverse cardiovascular events (MACE) and all-cause mortality, MACEs were defned as a composite of all-cause death, myocardial infarction (MI) recurrence, and ischaemic stroke.

            RESULTS In fully adjusted analyses, the middle tertile of SHR was signifcantly associated with greater rates of MACEs in patients with PR but not in those with PE (SHR1, HR: 2.01, 95% CI: 1.25–1.88, P=0.015). Cox regression models indicated a signifcantly higher HR for MACEs in patients in the middle tertile of SHR than in those in the low tertile of SHR after full additional adjustment (HR: 2.31, 95% CI: 1.10–1.29, P=0.018). However, being in the high tertile of SHR independently and signifcantly increased the risk of major bleeding events among patients with PE (HR: 1.65, 95% CI: 1.21–1.65, P=0.016). The area under the receiver operating characteristic curve for predicting MACEs to evaluate the diagnostic value of the SHR index combined with the morphologica characteristics of plaque after full adjustment was 0.881 (sensitivity=81.74%, specifcity=78.04%, cut-of level=0.70). Kaplan–Meier curves were generated for the cumulative incidence of MACEs for up to a median of 2 years stratifed by tertiles of SHR among the PR and PE subgroups. Among patients with PR, there were signifcant diferences among the tertiles of SHR (P=0.015).

            CONCLUSIONS Microstructural OCT features of culprit lesions in combination with the SHR, can be used in clinical practice to support risk stratifcation and predict adverse events in patients with STEMI.

            GW33-e0358
            IVUS combined with SYNTAX score to guide revascularization of multi vessel coronary artery lesions

            Aibibanmu Aizezi, Yitong Ma, Dilare Adi, Qianru Yuan, Nazila Yaliqin

            Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

            OBJECTIVES This study applied IVUS calculated by machine learning algorithm to explore the predictive effect of functional SYNTAX score calculated based on IVUS algorithm on the clinical prognosis of patients with three branches of disease.

            METHODS Nine hundred forty-six patients with coronary heart disease diagnosed by invasive coronary angiography (defined as three vessel stenosis >50%) from a single center were included retrospectively, excluding patients with previous revascularization, previous coronary occlusion and left main artery disease. Two independent clinicians calculated the SYNTAX score of the above patients, and according to the SYNTAX score, the patients were divided into low SS group (0∼22, n=490), medium SS group (23∼32, n=371) and high SS group (≥33, n=85). IVUS is calculated by machine learning algorithm, and the minimum lumen area of each diseased vessel is recorded. The SYNTAX score was calculated only for lesions with a minimum lumen area <4.0 mm2. The primary clinical endpoint mace was defined as a composite endpoint composed of all-cause death, nonfatal myocardial infarction and emergency revascularization.

            RESULTS After calculating the IVUS threshold by machine learning, 8.4% (79/946) of the patients were reclassified to the low-risk group. During the median follow-up period of 24 months, the overall MACE rate of the study patients was 30.3%. Compared with the low SS group, the incidence of MACE in the medium and high SS group was significantly higher (18.0 (88/490) vs. 6.2 (23/371) vs. 85.9% (73/85), P<0.001). Meanwhile, ROC analysis showed that the SYNTAX score included in IVUS could better predict mace than that based on a single SYNTAX score (IVUS+SS:AUC: 0.72 vs. SS:AUC: 0.61, P=0.01).

            CONCLUSIONS Using machine learning algorithm to calculate IVUS and apply it to SYNTAX score calculation is a better predictor of mace incidence in patients with three vessel lesions. It was found that compared with the traditional SYNTAX score, it can better predict the occurrence of MACE events, and may change the revascularization strategy of these patients.

            GW33-e0393
            Feasibility exploration of different anti-angina regimens using electronic Patient Reported Outcomes (ePRO) tool: a multicenter, prospective study (GREAT)

            Yong Zeng

            Beijing Anzhen Hospital, Capital Medical University

            OBJECTIVES Angina pectoris (AP) is typically associated with myocardial ischemia. Patients with AP present with chest discomfort, or discomfort in the neck, shoulders or arms after physical activities or emotional stress. Insufficient reporting of angina symptoms is common in clinical practice, which may lead to under treatment and decreased quality of life for patients with AP. The registry study (GREAT) is an ongoing study that aims to evaluate the feasibility of using the electronic Patient-Reported Outcome (ePRO) tool via Wexin to monitor the efficacy and safety of different antianginal regimens in patients with AP in real-world clinical practice.

            METHODS GREAT is a multicenter, prospective, observational study to explore the Chinese angina disease cohort and compare the efficacy of different anti-angina regimens in patients with AP. Two natural cohorts, the nicorandil group and non-nicorandil group, will be formed based on the data of Chinese patients with AP registered in 10 hospitals. The baseline information of patients will be record and patients will be followed up every 3 months during the 12 months after enrollment. The visits at 3, 6 and 9 months will be conducted in the form of ePRO and telephone, and the visit at 12 months will be conducted on site. Patients are required to fill in the patient diary records (weekly) during the course of the study. Statistical analysis of efficacy and safety is based on the full analysis set and safety analysis set. Other statistical analyses, quality control and bias control are also to be conducted. Trial registration number: NCT05050773.

            RESULTS Our study has enrolled 628 patients between September 2021 and February 2022 in 10 hospitals and the enrollment is ongoing at the time. The baseline data at present showed that the average Seattle Angina Questionnaire Summary Score (SAQ-SS) was 61.2±12.9. The Canadian Cardiovascular Society classification of AP were 67.4%I, 24%II, 3.5%III, 4.8%IV, respectively. The ROSE angina questionnaire positive was in 5.6% (n=35). The follow-up data will be gathered through the ePRO tool. The primary endpoint is the changes of SAQ-SS at 12 months from baseline. The secondary endpoint includes changes in SAQ-SS at 3,6, and 9 months, changes in the retest results of vascular stenosis imaging at 12 months, and medication compliance evaluated by proportion of days covered.

            CONCLUSIONS This will be the first research exploring the efficacy and safety of AP regimen in real-world settings via ePRO in China. The results from this study may provide new perspective and potential of ePRO in clinical practice.

            GW33-e0413
            The predictive value of D-dimer for hospital death in patients with acute myocardial infarction

            Yupeng Wang, Wenyue Wang, Zhaoping Li

            Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital

            OBJECTIVES To evaluate the predictive value of D-dimer for hospital death in patients admitted with acute myocardial infarction (AMI).

            METHODS We summarized 167 cases admitted to the Department of Cardiology of our hospital from January 2012 to April 2018, who were diagnosed and died due to AMI. Six hundred seventy-four patients discharged with similar ages and gender ratios at the same time were selected as the control group. Basic characteristics were collected, including age, gender, grade of cardiac function (Killip classification), the application of aortic balloon counter pulsation, and the results of the examination at baseline, which included white blood cells, fasting blood glucose, D-dimer, creatinine, uric acid, blood lipid, high-sensitivity c-reactive protein, creatine kinase isoenzyme and myocardial troponin, peak value of N terminal brain natriuretic peptide precursor, left ventricular ejection fraction (2-D), and other indicators. The receiver operating characteristic (ROC) curves were plotted according to the results of multivariate logistic regression analyses, and the correlation between D-dimer and hospital death of AMI was analyzed.

            RESULTS Creatine kinase isoenzyme, D-dimer, white blood cells, fasting blood glucose, creatinine, uric acid, myocardial troponin and N terminal brain natriuretic peptide precursor were all significantly higher in the death group than the control group (P<0.01). Yet left ventricular ejection fraction (2-D) decreased significantly in the death group (P<0.01). The level of D-dimer was predictive for hospital death with higher accuracy (AUC=0.811) in AMI than the level of creatine kinase isoenzyme (AUC=0.644).

            CONCLUSIONS The level of D-dimer can predict in-hospital mortality among patients admitted with AMI.

            GW33-e0418
            Predictive value of the fibrinogen to gamma-glutamine transferase ratio in long-term outcome in patients with coronary heart disease: a retrospective cohort study

            Ju Yan, Xiang Xie, Yi-Tong Ma

            The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES The ratio of fibrinogen to γ-glutamine transferase (FGR) was used to predict long-term prognoses in patients with coronary heart disease (CHD).

            METHODS A total of 5638 patients with CHD who were hospitalised from January 2008 to December 2016 were retrospectively enrolled as the study subjects. With a mean follow-up time of 35.9±22.5 months, the follow-up endpoints was the major cardiac and cerebrovascular adverse events (MACCEs). According to the ROC curve, the optimal FGR cut-off value was determined and divided into high- and low-FGR groups. Statistical methods were used to compare the differences between the two groups and their prognoses to determine whether FGR can be used as a predictor of prognosis in patients with CHD.

            RESULTS The optimal cut-off value was determined via a ROC analysis (FGR=1.22, AUC=0.554, P=0.002, 95% CI [0.520–0.588]), and subjects were divided into high- and low-FGR groups. The follow-up found that the incidence of MACCEs in the high FGR group was higher than that in the low FGR group. The Cox multivariate regression model showed that high FGR was independently correlated with the occurrence of MACCEs. In addition, the Kaplan–Meier survival curve showed that the risk of events was significantly increased in the group with high FGR. With the increase in the FGR ratio, the risk of MACCEs was increased.

            CONCLUSIONS High FGR can increase the risk of MACCEs in patients with CHD; additionally, it can be used as a new biomarker for long-term prognosis in CHD patients.

            GW33-e0465
            Left atrial function index predicts poor outcome in STEMI patients treated with percutaneous coronary intervention

            Yi Tang

            Hunan Provincial People’s Hospital, The First Affiliated Hospital of Hunan Normal University

            OBJECTIVES The prognostic value of left atrial function index (LAFI) in acute ST segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary intervention (PCI) is unknown. This study sought to determine whether LAFI predicts cardiovascular events in STEMI patients treated with PCI.

            METHODS Patients with newly diagnosed STEMI and treated with PCI in Hunan Provincial people’s Hospital from March 2020 to October 2020 were prospectively enrolled. All patients underwent transthoracic echocardiography at baseline and follow-up. The endpoint cardiovascular events include re-hospitalization due to unstable angina, nonfatal myocardial infarction, re-hospitalization due to heart failure and cardiovascular death.

            RESULTS A total of 156 STEMI patients treated with PCI were studied with a median follow-up of 14 months. Forty-eight patients had endpoint cardiovascular events. The univariate analysis revealed that Type 2 diabetes mellitus (T2DM), White Blood Cells (WBC), N-terminal prohormone brain natriuretic peptide (NT-proBNP), Killp Classification, and variables obtained from echocardiography were significant predictors of events (all P<0.05). However, Multivariate Cox analysis demonstrated that only LAFI (HR, 0.90, 95% CI, 0.86–0.95, P<0.0001) was independently predictive of cardiovascular events in patients with STEMI. Furthermore, LAFI owned the highest area under the receiver operating characteristic curve (AUC) predicting the end point cardiovascular events, with AUC of 0.90 (95% CI 0.84 to 0.94).

            CONCLUSIONS LAFI is a strong and independent predictor of cardiovascular events in STEMI patients treated with PCI.

            GW33-e0509
            A novel simply calculated nutritional index for adverse outcomes in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

            Enmin Xie1,2, Qing Li1, Yike Li1,2, Zixiang Ye1, Jingyi Ren1, Jingang Zheng1

            1Department of Cardiology, China-Japan Friendship Hospital, Beijing 100029, China

            2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100029, China

            OBJECTIVES Malnutrition is a well-known risk factor for adverse outcomes in patients with cardiovascular disease. Few studies have applied the triglycerides, cholesterol, and body weight index (TCBI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). This study aimed to assess the association between admission TCBI and long-term adverse outcomes in patients with STEMI undergoing pPCI.

            METHODS Six hundred fifty-seven patients with STEMI undergoing pPCI at the China-Japan Friendship Hospital from January 2015 to December 2018 were enrolled. The TCBI was calculated using serum total cholesterol (TC), triglycerides (TG), and body weight (BW) using the following formula: TCBI=TG (mg/dL)×TC (mg/dL)×BW (kg)/1000. Patients were divided into four groups according to quartile levels of the admission TCBI: TCBI≤969.8 (quartile 1), 966.5–1566.3 (quartile 2), 1566.3–2650.2 (quartile 3), and TCBI;2650.2 (quartile 4). The primary outcome was long-term major clinical adverse events (MACE), including cardiac death, non-fatal myocardial infarction, non-fatal ischemic stroke, and peripheral artery revascularization. Multivariable Cox regression analyses were conducted to assess the relationship between admission TCBI and MACE.

            RESULTS Among 657 enrolled patients, the mean age was 60.1±13.2 years, and 514 (78.1%) were male. During a median follow-up of 4.5 years, 105 (16.0%) MACEs were recorded. The incidence of MACE increased from the highest quartile of TCBI to the lowest quartile of TCBI (3.6 vs. 14.5 vs. 20.1 vs. 25.6%, P<0.001). The receiver operating characteristic curve analysis revealed that TCBI possessed excellent discrimination for predicting MACE (AUC 0.675, 95% confidence interval [CI] 0.624–0.726, P<0.001). Multivariable Cox analyses revealed that the lowest quartile of TCBI (compared with the highest quartile of TCBI) was independently associated with a significantly increased risk of MACE (hazard ratio 1.284, 95% CI 1.041–1.585, P=0.020).

            CONCLUSIONS Our results demonstrated that TCBI might be useful for predicting adverse outcomes in patients with STEMI undergoing pPCI.

            GW33-e0511
            The prognostic value of admission mean platelet volume/ platelet count ratio in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

            Enmin Xie1,2, Qing Li1, Yike Li1,2, Zixiang Ye1, Jingyi Ren1, Jingang Zheng1

            1Department of Cardiology, China-Japan Friendship Hospital, Beijing 100029, China

            2Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100029, China

            OBJECTIVES Elevated mean platelet volume/platelet count ratio (MPR) has been demonstrated to be associated with short-term outcomes in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI). This study aimed to assess the association between MPR and long-term adverse outcomes in patients with STEMI undergoing pPCI.

            METHODS We retrospectively evaluated 683 patients with STEMI undergoing pPCI at the China-Japan Friendship Hospital from January 2015 to December 2018. Patients were divided into two groups according to the admission MPR values with the optimal cutoff evaluated by receiver operator characteristic curve: MPR<0.048 (n=339) and MPR≥0.048 (n=344). The primary outcome was long-term major clinical adverse events (MACE) consisting of cardiac death, non-fatal myocardial infarction, and non-fatal ischemic stroke. Patients were further categorized into three groups by the tertile of MPR to enhance clinical utility: ≤0.422 (tertile 1), 0.422–0.567 (tertile 2), and ;0.567 (tertile 3).

            RESULTS Mean age was 60.2 (±13.3) years, and 78.5% (536/683) were male. During a median follow-up of 4.5 years, 94 (13.8%) MACEs were recorded. Multivariable Cox analyses revealed that MPR≥0.048 was independently associated with either MACE [hazard ratio (HR) 1.787, 95% confidence interval (CI) 1.129–2.828, P=0.013] or non-fatal reinfarction (HR 1.980, 95% CI 1.003–3.907, P=0.049), but not cardiac mortality (P=0.508) nor non-fatal ischemic stroke (P=0.258). The association was further confirmed when MPR was categorized into three groups by the tertile.

            CONCLUSIONS While MPR is found to increase the risk of long-term MACE and non-fatal re-infarction, it is not related to long-term cardiac mortality nor non-fatal ischemic stroke in patients with STEMI undergoing pPCI.

            GW33-e0518
            Establishment and evaluation of risk prediction model and nomogram in ACS patients with PCI

            Bing Zhu, Yi-Tong Ma

            Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

            OBJECTIVES The main purpose of this study is to analyze the relevant factors affecting the long-term prognosis of patients in acute coronary syndrome (ACS) with percutaneous coronary intervention (PCI), and to construct a nomogram for predicting the prognosis of ACS patients with PCI.

            METHODS Patients with acute coronary syndrome who were hospitalized in the Department of Cardiology of our hospital from October 2008 to September 2019 and underwent percutaneous coronary stent implantation were included in the study. They were divided into 1010 cases in the modeling group and 316 cases in the validation group. The incidence of composite end points was followed up. Univariate analysis, Pearson correlation analysis and Cox proportional hazards regression model were used to screen the independent predictors of poor prognosis of ACS patients after PCI, and the nomogram was established according to these factors.

            RESULTS After telephone follow-up, 164 ACS patients with PCI had adverse cardiac event (MACE) and 74 ACS patients with PCI had all cause mortality (ACM). The results of multivariate Cox regression analysis with MACE as the endpoint showed that age, Creatine Kinase-MB (CKMB), left ventricular ejection fraction (LVEF) and neutrophil to lymphocyte ratio (NLR) were independent predictors of MACE in ACS patients with PCI (P<0.05). The nomogram model had high predictive value for MACE in ACS patients with PCI (C-Index:0.78). The results of multivariate Cox regression analysis with ACM as the endpoint showed that age, CKMB, LVEF, NLR and monocyte count were independent predictors of ACM in ACS patients with PCI (P<0.05). The nomogram is established with these five variables. The nomogram model had high predictive value for ACM in ACS patients with PCI (C-Index:0.81).

            CONCLUSIONS The nomogram of ACS patients with PCI constructed in this study can individually predict the risk of MACE, ACM, and provides an effective tool for predicting the long-term prognosis of ACS patients with PCI.

            GW33-e0529
            Coenzyme Q10 improves cardiac remodeling and prognosis after myocardial infarction by regulating ROS-NLRP3/IL-1β mediated macrophage inflammation

            Wen Xu Pan, Ying Wang, Jun Jin

            Department of Cardiology, Institute of Cardiovascular Diseases of People’s Liberation Army, Xinqiao Hospital, Army Medical University (Third Military Medical University)

            OBJECTIVES Many studies have shown that coenzyme Q10 (CoQ10) protects against cardiac damage from myocardial infarction (MI). Macrophage mediated inflammation plays a critical role in determining the prognosis post MI. However, the effect of CoQ10 on macrophage and its potential role in MI prognosis remains unknown. This study sought to determine whether CoQ10 has an impact on macrophage by regulating ROS-NLRP3/IL-1β pathway mediated inflammatory response and thereby improves the prognosis of heart post-MI.

            METHODS The patients with MI and healthy volunteers were randomly enrolled according to the age and gender matched. Then the blood plasma were obtained to determine the CoQ10 levels by LC-MS/MS. In addition, we recruited 39 MI patients and randomly treated with or without CoQ10, echocardiography was detected at 1 and 3 months post PCI to evaluate the heart function. MI in C57BL6/J male mice (8–12-week-old) was induced by permanent ligation of left anterior descending artery (LAD). All the mice were randomly assigned to MI or sham groups and treated with either CoQ10 (600 mg/kg/day) or coin oil (isotype control) by oral gavage. Echocardiography was applied at designated time points to evaluate the cardiac function and the serum levels of BNP were analyzed by ELISA. Triphenyl tetrazolium chloride (TTC) and immunohistochemical staining were used to assess the myocardial infarction area, myocardial fibrosis and immune cells. Flow cytometry was employed to analyze the recruitment of immune cells into heart tissue. RNA sequence was performed on PMACs stimulated by LPS and INF-γ either treated with CoQ10 or Vehicle. Western blot and qRT-PCR were used to assess the expression of inflammatory factors.

            RESULTS We found that CoQ10 level was significantly lower in MI patients than healthy volunteers. CoQ10 treatment significantly improve heart function and attenuated myocardial infarction injury and cardiac remodeling, consequently, patients with MI treated with CoQ10 significantly improved ejection fraction compared with control group post PCI, and the survival rate of CoQ10-treated mice was significantly higher than that of control mice post-MI. Mechanistically, flow cytometrical analysis showed that CoQ10 treatment suppressed recruitment of inflammatory neutrophils and macrophages into infarct myocardium post MI. Specifically, bone marrow derived inflammatory macrophage subtype (MHCII+CCR2+) was significantly suppressed by CoQ10. Additionally, we observed the level of IL-1β and ROS positive macrophages were remarkblely decreased in the myocardium of CoQ10-treated mice. In vitro, CoQ10 significantly reduced the the levels of IL-1β and ROS in PMACs after inflammatory stimulated. RNA sequence on PMACs stimulated by LPS and INF-γ showed that inflammatory response related genes and oxidative stress related genes were downregulated by CoQ10 treatment. Moreover, Western blotting and qRT-PCR shown the expression levels of NLRP3/IL-1β inflammasome pathway was significantly suppressed by CoQ10.

            CONCLUSIONS CoQ10 could significantly improve cardiac function and survival rate and attenuate cardiac remodeling after MI partially by regulating oxidative stress response in macrophages and its downstream inflammatory response.

            GW33-e0538
            Critical left ventricular ejection fraction and its possible pathogenesis in STEMI patients with supra-normal ejection fraction after primary PCI

            Hao Xiao, Zhao Mei, Li Shuren

            Hebei General Hospital

            OBJECTIVES Left ventricular ejection fraction (LVEF) is often used as an assessment indicator for left ventricular systolic function. As adverse events occur in some patients with preserved LVEF, other phenotypes based on LVEF may exist in the population with LVEF≥50%, affecting the prognosis.

            METHODS A total of 272 STEMI patients with initial LVEF≥50% by transthoracic echocardiographic measurement after primary PCI were selected from Heart Center, Hebei General Hospital from November 2016 to June 2018. All patients were admitted to the cardiovascular care unit. Data were collected, including baseline characteristics (gender, smoking history, drinking history, family history of cardiovascular disease, angina in the past one month, diabetes history, hypertension history, stroke history, old myocardial infarction, age, body mass index, pulse rate, and mean arterial pressure), time of onset of chest pain [including time from symptom onset to first medical contact, time from symptom onset to first antiplatelet therapy, time from symptom onset to first anticoagulation, symptom onset to balloon time (SBT), door-to-balloon (D-to-B) time], periprocedural data [pre-procedural TIMI flow grade, collateral circulation, treatment of non-infarct related artery (NIRA), thrombus aspiration, IABP application, anticoagulant medication, pre-procedural use of β-blockers, renin-angiotensin-aldosterone system inhibitors (RAASi), or statins, intra-procedural application of tirofiban and pro-urokinase, post-procedure TIMI flow grade], laboratory test results (leukocyte count, neutrophil count, lymphocyte count, hemoglobin, hematocrit, platelet count, potassium ion, urea nitrogen, creatinine, random blood glucose, eGFR, total cholesterol, triacylglycerol, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, non-high density lipoprotein, creatine kinase, creatine kinase isozyme) and transthoracic echocardiographic data. The correlation between LVEF and in-hospital death was analyzed. By ROC analysis, the optimal threshold of LVEF predicting in-hospital death was obtained, and patients with LVEF greater and less than the optimal threshold were compared in terms of clinical indictors.

            RESULTS The area under the ROC curve of LVEF predicting in-hospital death was 0.846 [95% CI (0.628, 0.999), P=0.018], and the optimal threshold was 67.5% with a sensitivity of 75.0% and a specificity of 95.1%. Compared with those with LVEF<67.5%, patients with LVEF;67.5% had higher in-hospital mortality [18.8% (3/16) vs 0.4% (1/256)], with a statistical difference (P<0.05). Moreover, they also showed a statistical difference in Kaplan-Meier survival curve (χ2=36.526, P<0.001). Furthermore, patients with LVEF;67.5% showed higher female ratio and rate of IABP application, lower mean pulse rate as well as lower rate of post-procedure TIMI grade 2–3 flow (P<0.05). They also demonstrated lower mean left ventricular end-systolic diameter (P<0.001).

            CONCLUSION There may be a subgroup in STEMI patients with preserved ejection fraction after primary PCI, who presented higher LVEF (supra-normal LVEF) and higher in-hospital mortality than those with normal LVEF. The optimal threshold of LVEF for predicting in-hospital death in these STEMI patients was 67.5%. Being female and coronary microcirculation disorder may contribute to the development of supra-normal ejection fraction.

            GW33-e0548
            Real-world observational study of nicorandil combined with beta-blocker in Chinese patients with coronary heart disease

            Hongyang Shu, Na Li, Ning Zhou

            Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology

            OBJECTIVES Although coronary heart disease (CHD) remains the leading cause of mortality in China, the treatment strategies are still far from satisfactory. This study was aimed to evaluate the long-term potential of nicorandil combined with beta-blocker in Chinese patients with CHD.

            METHODS The data of the CHD patients from three tertiary hospitals in central China was retrospectively reviewed between October 2009 and March 2020. The primary outcome was the rate of major adverse cardiovascular event (MACE) at 2.5 years, which was a composite outcome of stroke, myocardial infarction (MI), and all-cause mortality. The secondary outcomes were the rate of the separate events at 2.5 years. Inverse probability of treatment weighting (IPTW) method based on the propensity score was used to balance intergroup differences and the relationship between the treatment and events was further assessed by Cox proportional-hazards regression analysis.

            RESULTS A total of 4669 patients treated with the combination of nicorandil and beta-blocker and 12,243 patients treated with beta-blocker alone were included in the study, respectively. The median follow-up time was 0.87 and 0.81 year for the combination and beta-blocker alone group, respectively. After IPTW for propensity score, the primary outcome showed that the cumulative MACE-free survival rate at 2.5 years was higher in the nicorandil and beta-blocker combination group compared to beta-blocker alone group (77 vs. 68%). Cox regression analysis showed that the combination group was associated with a higher MACE-free survival (HR=0.80, 95% CI: 0.73–0.88; P<0.0001). The secondary outcome showed a higher stroke-free survival rates in the combination group (89 vs. 77%) at 2.5 years, while the other two events (MI and all-cause mortality) showed no difference between the two groups. Cox regression analysis also showed that the combination group was significantly associated with higher stroke-free survival (HR=0.49, 95% CI: 0.43–0.56; P<0.0001). Interaction analyses were performed for the following subgroups: age (<65 or 65 years), gender, acute coronary syndrome (ACS), smoking, drinking, revascularization, diabetes and hypertension, and showed a favorable consistency with the primary outcome.

            CONCLUSIONS Treatment of nicorandil combined with beta-blocker is associated with less MACE and stroke in patients with CHD in the Chinese population.

            GW33-e0569
            Obstructive sleep apnea affects heart rate variability in patients with coronary artery disease: a cross-sectional study

            Xiexiong Zhao1, Xueli Yang1, Ziming Li1, Shengya Xu1, Yue Liu1, Min Zhang2, Wenjuan Wang2, Weihong Jiang1, Chunyan Weng1

            1Department of Cardiology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China

            2Department of Electrocardiograph, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, China

            OBJECTIVES It is unknown how obstructive sleep apnea (OSA) affect coronary artery disease (CAD) in dynamic electrocardiogram, especially heart rate variability (HRV). We aimed to determine the association of OSA and HRV in patients with CAD.

            METHODS Consecutive CAD patients from the Third Xiangya Hospital of Central South University were recruited. Patients were divided into two groups according to apnea-hypopnea index (AHI): OSA group (AHI>15) and control group (5<AHI<=15). Parameters of HRV from dynamic electrocardiogram including SDNN, rMSSD, pNN50, VLF, LF, HF, LF/HF were analysed in different types of CAD and different period of time like wakefulness and sleep.

            RESULTS Sixty-three eligible participants were enrolled finally, including forty-three in OSA and twenty in control. There were no significant differences between OSA and con-trol group in parameters of HRV. While taking period of time into consideration, we found all parameters in OSA group were higher at night than in the daytime (SDNN 104.6 vs. 103.1, P=0.731; rMSSD 60.2 vs. 57.1, P=0.666; pNN50 12.1 vs. 9.8, P=0.157; TF 3544.5 vs. 2562.0, P=0.082; VLF 2692.1 vs. 1475.4, P<0.001; LF 557.5 vs. 384.5, P=0.005; HF 259.9 vs. 179.5, P=0.006; respectively) while in control group, the results were some kind of different even opposite. In different type of CAD, parameters of HRV were different in two groups. In angina patients, HRV was decreased in OSA group in most parameters (SDNN 130.80 vs. 123.17; rMSSD 65.40 vs. 55.29; pNN50 13.90 vs. 9.29; VLF 1509.96 vs. 1841.50; LF 484.87 vs. 353.26; HF 329.77 vs. 131.92), while in myocardial infarction patients, HRV was increased in OSA group in all parameters (SDNN 104.40 vs. 110.79; rMSSD 45.20 vs. 46.53; pNN50 6.80 vs. 12.26; VLF 1973.25 vs. 2553.27; LF 373.65 vs. 557.91; HF 168.99 vs. 302.55), even though there were no statistic significance.

            CONCLUSIONS In CAD patients, OSA would influence the change of HRV from daytime to night and different types of CAD would be different in HRV when OSA happened.

            GW33-e0597
            Short-term exposure to traffic-related air pollution and STEMI events: insights into STEMI onset and related cardiac impairment

            Yuanyuan Fan1, Lingyun Zu1, Wei Huang2, Yutong ZHU2, Yuan Xu1

            1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research

            2Department of Occupational and Environmental Health, Peking University School of Public Health, Peking University Institute of Environmental Medicine

            OBJECTIVES Evidence on the impacts of traffic-related air pollution (TRAP) on ST-segment elevation myocardial infarction (STEMI) events is limited. We aimed to assess the acute effects of TRAP exposure on the clinical onset of STEMI and related cardiac impairments.

            METHODS We recruited patients who were admitted for STEMI and underwent primary percutaneous coronary intervention at Peking University Third Hospital between 2014 and 2020. Indicators relevant to cardiac impairments were measured. Concomitantly, hourly concentrations of traffic pollutants were monitored throughout the study period, including fine particulate matter, black carbon (BC), particles in size ranges of 5–560 nm, oxides of nitrogen (NOX), nitrogen dioxide, and carbon monoxide.

            RESULTS The mean (SD) age of participants was 62.4 (12.5) years. Daily average (range) concentrations of ambient BC and NOX were 3.9 (0.1–25.0) μg/m3 and 90.8 (16.6–371.7) μg/m3. Significant increases in STEMI risks of 5.9 (95% CI: 0.1, 12.0) to 21.9% (95% CI: 6.0, 40.2) were associated with interquartile range increases in exposure to TRAP within a few hours. These changes were accompanied by significant elevations in cardiac troponin T levels of 6.9 (95% CI: 0.2, 14.1) to 41.7% (95% CI: 21.2, 65.6), as well as reductions in left ventricular ejection fraction of 1.5 (95% CI: 0.1, 2.9) to 3.7% (95% CI: 0.8, 6.4). Furthermore, the associations were attenuated in participants living in areas with higher residential greenness levels.

            CONCLUSIONS Our findings extend current understanding that short-term exposure to higher levels of traffic pollution was associated with increased STEMI risks and exacerbated cardiac impairments, and provide evidence on traffic pollution control priority for protecting vulnerable populations who are at greater risks of cardiovascular events.

            GW33-e0617
            Reverse J-shaped association between estimated glomerular filtration rate and contrast-associated acute kidney injury in patients undergoing elective percutaneous coronary intervention

            Man-Qing Luo, Li-Wei Zhang, Li-Chuan Chen, Kai-Yang Lin, Yan-Song Guo

            Shengli Clinical Medical College of Fujian Medical University

            OBJECTIVES Estimated glomerular filtration rate (eGFR) remains to be used routinely to assess glomerular filtration function in clinical practice. A decline in eGFR is confirmed as a significantly independent risk factor with contrast-associated acute kidney injury (CA-AKI), and closely associated with chronic kidney disease (CKD) progression and poor prognosis. Recent evidence has indicated that glomerular hyperfiltration increased the risk of kidney disease, however, the association between glomerular hyperfiltration and the risk of CA-AKI as well as long-term prognosis in patients undergoing elective percutaneous coronary intervention (PCI) remains unclear.

            METHODS We retrospectively observed 6227 consenting patients undergoing elective PCI from January 2012 to December 2018 in a tertiary center. Serum creatinine was measured at admission and within 48 to 72 hours after contrast exposure. The eGFR was calculated by 2021 CKD Epidemiology Collaboration (CKD-EPI) equation. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure. The relationships between eGFR levels and CA-AKI as well as prognosis, were explored using restricted cubic splines to allow for non-linearity.

            RESULTS The incident of CA-AKI was 5.89% (n=367). A inversely ‘J-shaped’ relation of eGFR levels with CA-AKI was presented in a restricted cubic spline logistic regression model, with two threshold values of <60 mL/min/1.73 m2 and >110 mL/min/1.73 m2 that were associated with increased risk for CA-AKI. All patients were divided into normal eGFR (60≤eGFR≤110 mL/min/1.73 m2, n=5337), low eGFR (eGFR<60 mL/min/1.73 m2, n=573), and high eGFR (eGFR;110 mL/min/1.73 m2, n=317). Unadjusted logistics regression analysis revealed that both low and high eGFR were significantly correlated with increased risk of CA-AKI as compared to normal eGFR (OR=2.57, 95% CI: 1.92–3.40, P<0.001; OR=2.66, 95% CI: 1.829–3.783, P<0.001, respectively). After adjustment of potential confounding factors, the significant difference was still observed (OR (95% CI): 1.89 (1.37–2.59), P<0.001; OR (95% CI): 3.19 (2.13–4.68), P<0.001, respectively). Furthermore, the patients with high eGFR had a greater risk of CA-AKI than those with low eGFR (OR=1.685, 95% CI: 1.031–2.73, P=0.03). Nevertheless, the restricted cubic spline in a Cox proportional hazards model showed that the lower eGFR, the higher the long-term mortality. In multivariable Cox analysis, there was no statistically difference between high and normal eGFR in long-term mortality.

            CONCLUSIONS Glomerular hyperfiltration was independently associated with CA-AKI in patients undergoing elective PCI, and the risk was higher than low eGFR level. Whereas the adverse effect cannot directly reflect on the long-term prognosis. The definition of CA-AKI may need to be optimized further to recognize the patients developing CA-AKI associated with poor prognosis.

            GW33-e0621
            Association of between arterial-ventricular coupling and late left ventricular remodeling in patients with acute myocardial infarction undergoing percutaneous coronary intervention

            Man-Qing Luo, Li-Wei Zhang, Li-Chuan Chen, Kai-Yang Lin, Yan-Song Guo

            Shengli Clinical Medical College of Fujian Medical University

            OBJECTIVES The ventricle after acute myocardial infarction (AMI) will undergo a process of remodeling characterized by continuous changes in ventricular size, shape, structure and function. However, onset of cardiac remodeling can delay after the initial 3 months and has a detrimental impact on long-term outcomes. Therefore, it is pivotal to recognize the potential change of cardiac function at the early stage. Arterial-ventricular coupling (AVC) is an important determinant of cardiovascular function, which can well reflect arterial stiffness and cardiac function and their relation. Moreover, alterations in AVC may be more sensitive than ejection fraction. In previous studies, the association between AVC and late left ventricular (LV) remodeling has not been explored. The present study aims to investigate the relationship between AVC and late LV remodeling and the impact of LV remodeling on long-term prognosis in patients with AMI undergoing percutaneous coronary intervention (PCI).

            METHODS We prospectively observed 767 consenting new-onset AMI patients without early LV remodeling after PCI from January 2012 to December 2020. The patients received echocardiography during admission and 3 to 12 months after admission. Late LV remodeling is defined as a >15% increase in left ventricular end-systolic volume (LVESV). AVC was calculated as the ratio of effective arterial elastance (Ea) to LV end-systolic elastance (Ees). The association of AVC with late LV remodeling was investigated by logistic regression analysis. Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with late LV remodeling.

            RESULTS The incident of LLVR is 27.5% (211/767). The best cutoff value of baseline AVC for predicting late LV remodeling was 0.696 (AUC=0.630, 95% CI: 0.5836–0.6762, P<0.001). After multivariate adjustment of clinical and laboratory variables, AVC<0.696 remained a significant independent risk predictor of late LV remodeling in AMI patients undergoing PCI (OR: 3.32, 95% CI: 2.24–4.95, P<0.001). In the multivariable cox analysis, after adjusting for the potential confounders, late LV remodeling can increase the risk rate of long-term mortality, rehospitalization or an urgent visit for heart failure (HR: 2.56, 95% CI: 1.63, 4.02, P<0.001) during the median follow-up of 2 years.

            CONCLUSIONS In patients with AMI treated with PCI, baseline AVC assessed by the non-invasive measurement of the Ea/Ees ratio has a significant role in predicting late LV remodeling. Furthermore, late LV remodeling is significantly correlated to poor outcome. The ratio may be a useful and simple tool to guide follow-up of AMI patients and prevention of adverse late LV remodeling.

            GW33-e0636
            A new predictor of post-contrast acute kidney injury after percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction: serum uric acid/albumin ratio

            Yeshen Zhang1, Yuming Huang2, Zehuo Lin1, Zijing Lin1, Pengcheng He1, Yuanhui Liu1, Ning Tan1

            1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences

            2Department of Catheterization Lab, Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of South China Structural Heart Disease, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences

            OBJECTIVES The serum uric acid/albumin ratio (sUAR), a novel inflammatory marker, has been demonstrated to effectively predict acute kidney injury and cardiovascular outcomes. However, whether the sUAR predicts post-contrast acute kidney injury (PC-AKI) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) remains uncertain. This study aimed to evaluate the predictive value of sUAR for PC-AKI in STEMI patients undergoing PCI.

            METHODS We consecutively recruited STEMI patients undergoing PCI between January 2010 and February 2020. Patients were stratified into three groups in accordance with the tercile of the sUAR. The primary outcome was the development of PC-AKI, defined as an increase in serum creatinine level ≥0.5 mg/dL (44.2 μmol/L) from baseline within 72 h after administration of contrast media. The association between the sUAR and PC-AKI was assessed by multivariate logistic regression analysis, and the predictive value was evaluated by receiver operating characteristic (ROC) curve analysis.

            RESULTS A total of 2861 STEMI patients were finally included. The incidence of PC-AKI increased stepwise with the increasing tercile of the sUAR (16.6 vs 18.8 vs 22.3%, P=0.006), and both the incidence of in hospital death and MACEs were highest among patients in the tercile 3 group. Multivariate logistic regression analysis revealed that the sUAR was also an independent predictor of PC-AKI (continuous sUAR, per 1-unit increase, the OR (95% CI) values: 1.06 (1.02∼1.10), P=0.005; tercile of sUAR, the OR (95% CI) values for Q2 and Q3 were 1.18 (0.69∼2.01) and 1.85 (1.12∼3.06), respectively, with Q1 as a reference). In the ROC analysis, the area under the curve (AUC) of the sUAR for predicting PC-AKI was 0.708 (95% CI: 0.666–0.751), and the AUC of the sUAR for predicting in hospital MACEs was 0.624 (95% CI: 0.572–0.677). Meanwhile, ROC analysis also showed that the sUAR was superior to the uric acid and albumin alone in predicting PC-AKI.

            CONCLUSIONS The increasing sUAR was significantly associated with a higher risk of PC-AKI in STEMI patients underwent PCI, and had a good predictive value for PC-AKI after PCI in STEMI patients. Future studies are needed to confirm the predictive value of sUAR in PC-AKI.

            GW33-e0637
            Estimation of predicted 10-year survival and risk of cardiovascular complications in an unorganized population of men and women

            Mekhman Mamedov

            National Research Center for Therapy and Preventive Medicine

            OBJECTIVES Estimation of the predicted 10-year survival rate and the risk of cardiovascular complications in an unorganized population of men and women of working age in the cities of the Golden Ring.

            METHODS The cross-sectional population study included 1200 men and women aged 30–69 years from 5 cities of the Vladimir region (Vladimir, Kovrov, Murom, Yuryev-Polsky and Vyazniki). The response to the study was at least 80%. Overall, 1004 people completed the study. Of these, 346 men (34.5%) and 658 women (65.5%). Respondents were interviewed according to a standard questionnaire, including information on socio-demographic indicators, behavioral risk factors, the presence of somatic diseases, records of medications taken, and an assessment of psychosomatic status. Instrumental and laboratory studies included in the standard dispensary examination were performed. The European SCORE scale was used to assess the risk of cardiovascular complications. To assess the 10-year survival of individuals, the Charlesson comorbidity index was used.

            RESULTS Hypertension was detected in 38% of men and 43% of women. IHD among men was registered three times more often than in women: 15 and 5% (P<0.0001). Other NCDs, such as diabetes mellitus, COPD and malignant tumors, were detected separately in no more than 5% of cases. 67% of women had low to moderate cardiovascular risk. 19% of men had a high and 10% very high cardiovascular risk, which was higher than that of women (6 and 0%). The prevalence of the combination of two diseases was 32.6%. Among men, this figure is 36.7%, while among women it is 10% less, it was found in every fourth participant in the study (27%) (P=0.002). The combination of three diseases among men was detected in 12%, and among women it was detected in 5.9% of cases (P<0.001). Short 10-year survival (21 and <5%) by Charleson index was determined in less than 10% of men and women. The largest number of respondents had 90 and 77% 10-year survival.

            CONCLUSIONS In an unorganized population of adults, high and very high cardiovascular risk is found in one in four men and only one in 16 women. A short 10-year survival rate according to the Charlson index was found in every tenth respondent, while at the same time, every second participant had an average 10-year survival rate. Thus, the comorbidity of somatic diseases with low and average 10-year survival requires complex preventive interventions.

            GW33-e0638
            Comprehensive analysis of clinical and instrumental parameters and coronary blood flow in patients with acute forms of coronary artery disease on the background of type 2 diabetes mellitus

            Mekhman Mamedov

            National Research Center for Therapy and Preventive Medicine

            OBJECTIVES To study the features of clinical and instrumental parameters and lesions of the coronary bed in patients with acute forms of coronary artery disease on the background of type 2 diabetes mellitus (DM).

            METHODS The study included 102 patients of both sexes with acute forms of coronary artery disease. The patients were analyzed in two groups: the 1st (mean age 56.6±0.96 years, male/female 34/16) consisted of 50 patients with ACS (acute coronary syndrome) and type 2 diabetes, the 2nd (58.7±1.01 years, male/female 37/15), without diabetes –52 patients. Along with the assessment of behavioral and biological risk factors, clinical and hemodynamic parameters were analyzed, and coronary angiography was performed.

            RESULTS In the group of persons with ACS and diabetes mellitus, the duration of diabetes mellitus was 5.6±3.7 years. Comorbidity of somatic diseases was registered in 74% in the first group, and in the group without diabetes 53.8%. According to echocardiography data, in the group of people with ACS and diabetes mellitus, the left ventricular ejection fraction was lower, and the mean pulmonary artery pressure was higher compared to the group without diabetes mellitus. Stenosis of the distal third of the coronary artery in patients with diabetes occurred in 78% of cases, and in patients without diabetes −42%, these differences were statistically significant (P<0.001). Diffuse lesion of the coronary artery also prevailed in the first group and amounted to 58%, and in the second −27%. The calculation of the total risk value according to the anatomical scale SYNTAX Score showed a higher value compared to the group without diabetes mellitus 29.2 and 22%, P<0.001, respectively.

            CONCLUSIONS In patients with ACS and diabetes, the prevalence of cases of pulmonary hypertension and systolic dysfunction of the LV myocardium is revealed. The features of coronary blood flow in patients with DM and ACS were predominantly the distal type of lesion, as well as an increased risk of complications of angioplasty procedures, assessed using the SYNTAX score scale.

            GW33-e0662
            Prognostic analysis of medical interventional therapy and surgical bypass grafting in patients with chronic total occlusion

            Hai-Lin Li, Yi-Tong Ma

            Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical

            OBJECTIVES To compare the prognosis between interventional therapy and coronary artery bypass grafting in patients with chronic total occlusion.

            METHODS This study was a single center retrospective cohort study. From July 2015 to June 2020, 409 patients with CTO revascularization were continuously treated in the first affiliated Hospital of Xinjiang Medical University through stent therapy or surgical bypass graft. According to the inclusion criteria and exclusion criteria, 320 patients were enrolled in the study. According to the different ways of revascularization, the patients were divided into two groups: interventional therapy group (PCI group, n=153) and surgical bypass transplantation group (CABG group, n=167). The clinical baseline data and coronary artery lesion characteristics of the patients in the study group were collected. The main end point of the study was all-cause death, and the secondary end point was major cardio-cerebrovascular adverse events (MACCE), including all-cause death, acute myocardial infarction, repeated revascularization, stroke and CTO target vessel reocclusion. All the patients were followed up. The mortality and cumulative incidence of end-point events between the two groups were described by Kaplan-Meier survival curve, and the differences between the two groups were compared by log-rank test. COX proportional hazard model and propensity score matching method were used to analyze the difference between interventional therapy and surgical bypass transplantation on the long-term prognosis of patients.

            RESULTS The median follow-up period was 35 months. There was no significant difference in the risk ratio of all-cause death (HR=0.54, 95% CI 0.22–1.31, P=0.173) and the risk ratio of MACCE (HR=1.33, 95% CI 0.79–2.25, P=0.286) between the PCI group and the CABG group. After the tendency scores were matched, there was no significant difference in the risk ratio of all-cause death (HR=0.40, 95% CI 0.11–7.50, P=0.172) and the risk ratio of MACCE (HR=1.07, 95% CI 0.51–2.23, P=0.862) between the two groups. According to the characteristics of age, complications and vascular lesions, it was found that there was no significant difference in the risk ratio of all-cause death and the risk ratio of MACCE between PCI treatment and CABG treatment.

            CONCLUSIONS There is no significant difference in long-term prognosis between PCI and CABG revascularization of CTO target vessels in patients with CTO.

            GW33-e0667
            Timing of angiography and outcomes in patients with non-ST-segment elevation myocardial infarction

            Yu Han, Shujian Wei

            Qilu Hospital of Shandong University

            OBJECTIVES Although guidelines have been recommended the invasive strategy for non-ST-segment elevation myocardial infarction (NSTEMI) patients within 24 hours, the optimal timing of the invasive strategy remains controversial. We sought to investigate the association between the timing of different invasive strategies and clinical outcomes in patients with NSTEMI.

            METHODS Using data from the Evaluation and Management of Patients with Acute ChesT pain in China (EMPACT) database, we retrospectively analyzed 969 patients. They were stratified into 3 groups according to timing of coronary angiography (CAG) from admission: no, early (<24 hours), or delayed (≥24 hours) CAG. The primary outcomes were major adverse cardiac events (MACEs) within 30 days.

            RESULTS Nine hundred sixty-nine patients with NSTEMI from the EMPACT database were eligible for this study. Five hundred one NSTEMI patients (51.7%) underwent CAG. Among them, 150 (23.3%) had early CAG and 351 (34.5%) had delayed CAG. The rate of MACEs at 30 days in overall patients was 9.2%, including 54 (5.6%) deaths. Patients who underwent CAG had a lower rate of 30-day MACEs and mortality than those who did not receive CAG (MACEs: 5.6 versus 13%, P<0.001; mortality: 1.6 versus 9.8%, P<0.001). Nonetheless, there was no statistically significant difference in the rates of MACEs and mortality between the early and delayed CAG groups. Independent predictors of the rate of MACEs included whether to undergo CAG (OR=0.385, 95% CI: 0.200, 0.744, P=0.004) or PCI (OR=2.910, 95% CI: 1.273,6.651, P=0.011), age (OR=1.043, 95% CI: 1.015, 1.017, P=0.002), acute HF (OR=2.962, 95% CI: 1.612, 5.442, P<0.001), and systolic blood pressure (OR=0.985, 95% CI: 0.976, 0.994, P=0.001). The independent predictors of whether to underwent CAG revealed the age (OR=0.947, 95% CI: 0.935, 0.96, P<0.000), cardiogenic shock (OR=0.164, 95% CI: 0.05, 0.534, P=0.003), pulmonary moist rales (OR=0.401, 95% CI: 0.213, 0.756, P=0.005), and CKD (OR=0.064, 95% CI: 0.016, 0.251, P<0.001).

            CONCLUSIONS This real-world cohort of NSTEMI patients confirmed that early invasive strategies did not reduce the incidence of MACEs and mortality within 30 days compared with delayed invasive strategies in patients with NSTEMI.

            GW33-e0671
            Neutrophil-to-lymphocyte ratio (NLR) and mean platelet volume-to-lymphocyte ratio (MPVLR) are diagnostic and predictive indicators of functionally significant coronary artery stenosis

            Xuehe Zhang, Fen Liu, Xiaomei Li

            Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

            OBJECTIVES For borderline coronary lesions, due to the limited information provided by coronary angiography, the severity of coronary stenosis cannot be correctly evaluated, let alone the coronary ischemia. At present, the results of a number of studies have confirmed that Fractional Flow Reserve (FFR) is the gold standard for evaluating coronary function. FFR is a useful functional index for judging whether the stenosis of the coronary artery does cause the ischemia of the distal myocardial tissue. There are many reasons for patients with insufficient coronary blood flow reserve, and inflammation may have an important influence on the coronary blood flow reserve. Neutrophil to lymphocyte ratio (NLR) and Mean platelet volume to lymphocyte ratio (MPVLR) are used as indicators to reflect the level of inflammation and physiological stress. Numerous studies have clarified its relationship with cardiovascular disease. The purpose of this study is to clarify the diagnostic and predictive effects of NLR and MPVLR indicators on insufficient blood flow reserve in patients with stable angina.

            METHODS This study was continuously selected from August 2017 to October 2020 in the First Affiliated Hospital of Xinjiang Medical University. Coronary angiography was performed to indicate coronary artery borderline disease (coronary artery stenosis diameter 50∼70%) and the reference diameter of the diseased vessel is greater than 2.5 mm. There were 395 patients with chronic stable angina. Collect subjects’ venous blood samples for blood routine, biochemical, cardiac ultrasound and other related examinations.

            RESULTS In 395 patients with stable angina, FFR≤0.8 group had higher levels of NLR, MPVLR and other inflammatory markers than FFR;0.8 group (P<0.05). After adjusting for confounders, NLR (OR=1.439, 95% 1.205–1.718, P<0.001) MPVLR (OR=1.312, 95% 1.163–1.480, P<0.001) was independently associated with functional significant coronary artery stenosis. After a follow-up of 12 months for patients with FFR or less than 0.8 groups, COX regression analysis adjusted for confounders showed that NLR and MPVLR were independent predictors of adverse cardiovascular events in patients with FFR≤0.8. When NLR was greater than 2.44 and MPVLR was greater than 5.59, the survival rate of patients with hemodynamically significant stable angina decreased significantly.

            CONCLUSIONS NLR and MPVLR have an independent predictive effect on whether patients with stable angina are associated with insufficient blood flow reserve, and can be further used to evaluate the prognosis of patients with insufficient blood flow reserve.

            GW33-e0673
            Shrunken pore syndrome: a new and more powerful phenotype of renal dysfunction than chronic kidney disease for predicting contrast-associated acute kidney injury

            Li-Wei Zhang1,2,3, Man-Qing Luo1,2,3, Wen-Jia Liang1,2,3, Kai-Yang Lin1,2,3, Yan-Song Guo1,2,3

            1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China

            2Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular Diseases, Fuzhou, China

            3Fujian Heart Failure Center Alliance, Fuzhou, China

            OBJECTIVES Shrunken pore syndrome (SPS) as a novel phenotype of renal dysfunction is characterized by a difference in renal filtration between cystatin C and creatinine. The manifestation of SPS was defined as cystatin C-based eGFR (eGFRcys) less than 60% of creatinine-based eGFR (eGFRcr). SPS has been shown to be associated with the progression and adverse prognosis of various cardiovascular and renal diseases. However, the predictive value of SPS for contrast-associated acute kidney injury (CA-AKI) and long-term outcomes in patients undergoing elective PCI remains unclear.

            METHODS We retrospectively observed 5050 consenting patients from January 2012 to December 2018. Serum cystatin C and creatinine were measured and applied to corresponding 2012 and 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, respectively, to calculate eGFR. Chronic kidney disease (CKD) was defined as eGFRcr<60 mL/min/ 1.73 m2 without dialysis. CA-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure.

            RESULTS Overall, 649 (12.85%) patients had Shrunken pore syndrome and 324 (6.42%) patients developed CA-AKI. Multivariate logistic regression analysis indicated that SPS was an independent predictor of CA-AKI [adjusted odds ratio (OR): 4.485, 95% confidence interval (CI): 3.396–5.906, P<0.001]. After adjusting for potential confounding factors, COX regression analysis showed that SPS was associated with an increased risk of long-term mortality [hazard ratio (HR)=1.45, 95% CI: 1.13–1.85, P=0.004]. Further comparing eGFRcys/eGFRcr and eGFRcr, The eGFRcys/eGFRcr showed a better performance and stronger predictive power for CA-AKI than eGFRcr (AUC: 0.707 vs. 0.557, P<0.001), while eGFRcr showed a much stronger association with death (AUC: 0.673 vs. 0.568, P<0.001). Subgroup analysis found that compared to those without CKD and SPS simultaneously, patients with CKD and non-SPS, non-CKD and SPS, CKD and SPS had increased risk of CA-AKI (adjusted OR: 2.038, 95% CI: 1.342–3.028, P<0.001; adjusted OR: 4.158, 95% CI: 3.093–5.563, P<0.001; adjusted OR: 11.574, 95% CI: 6.371–20.728, P<0.001; respectively). Notably, Patients with CKD only had higher all-cause mortality risk than those with SPS but without CKD (HR: 2.007, 95% CI: 1.469–2.743, P<0.001). Patients with both SPS and CKD appeared to present the highest risk of long-term mortality compared to those without both (HR=5.546, 95% CI: 3.375–8.849, P<0.001).

            CONCLUSIONS SPS is a new and more powerful phenotype of renal dysfunction for predicting CA-AKI than CKD, while CKD shows a more prognostic-related clinical predictive value.

            GW33-e0674
            Association of intraindividual difference between cystatin C- and creatinine-based estimated GFR and contrast-induced acute kidney injury and mortality

            Li-Wei Zhang1,2,3, Man-Qing Luo1,2,3, Ji-Lang Zeng1,2,3, Kai-Yang Lin1,2,3, Yan-Song Guo1,2,3

            1Department of Cardiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China

            2Fujian Provincial Key Laboratory of Cardiovascular Disease, Fujian Cardiovascular Institute, Fujian Provincial Center for Geriatrics, Fujian Provincial Clinical Research Center for Severe Acute Cardiovascular Diseases, Fuzhou, China

            3Fujian Heart Failure Center Alliance, Fuzhou, China

            OBJECTIVES Creatinine-based estimated glomerular filtration rate (eGFR) is an important indicator for contrast-induced acute kidney injury (CI-AKI). As cystatin C is increasingly adopted to estimate GFR, The difference between cystatin C-based eGFR (eGFRcys) and creatinine-based eGFR (eGFRcr) has been observed widely. Assessing risk of CI-AKI may be difficult Because of this difference. We hypothesized that eGFRdiff (eGFRcys-eGFRcr) might provide predictive utility for CI-AKI and long-term mortality in patients undergoing elective percutaneous coronary intervention (PCI).

            METHODS We retrospectively observed 4591 consenting patients with CKD stages 1 to 2 (eGFRcr≥60 mL/min/1.73 m2) from January 2012 to December 2018. Serum cystatin C and creatinine were measured and applied to corresponding 2012 and 2021 CKD Epidemiology Collaboration (CKD-EPI) equations, respectively, to calculate eGFR. CI-AKI was defined as an increase in serum creatinine ≥50% or 0.3 mg/dL within 48 h after contrast medium exposure. Because 15 mL/min/1.73 m2 represents a clinically meaningful difference in eGFR that also distinguishes CKD stages, eGFRdiff was categorized as: less than −15 mL/min/1.73 m2 (negative-eGFRdiff group), −15 to 15 mL/min/1.73 m2 (reference group), and 15 mL/min/1.73 m2 or greater (positive-eGFRdiff group).

            RESULTS Approximately half of participants had a baseline eGFRdiff between −15 and 15 mL/min/1.73 m2 (2230, 48.5%). Compared with the other 2 eGFRdiff groups, participants in the negative-eGFRdiff group were generally older and had the higher baseline NT-proBNP. Multivariate logistic regression analysis indicated that compared with participants with similar baseline eGFRcys and eGFRcr (reference group), those in whom eGFRcys was substantially lower than eGFRcr (negative-eGFRdiff group) had a higher risk of CI-AKI (odds ratio [OR]: 3.422; 95% CI: 2.403–4.952). Furthermore, After adjusting for potential confounding factors, COX regression analysis showed that eGFRdiff<-15 mL/min/1.73 m2 was associated with an increased risk of long-term mortality during a mean follow-up period of 16 months (hazard ratio [HR]=1.52, 95% CI: 1.20–1.93, P<0.001).

            CONCLUSIONS A large negative difference between eGFRcys and eGFRcr was associated with a higher risk of CI-AKI and long-term mortality in patients with CKD stages 1 to 2. Therefore, careful monitoring of renal function is needed for patients with a lower eGFRdiff.

            GW33-e0675
            Machine learning algorithms for acute kidney injury prediction in patients with acute myocardial infarction

            Dabei Cai1,2, Tingting Xiao1, Ailin Zou1, Lipeng Mao1,2, Boyu Chi1,2, Yu Wang1, Qingjie Wang1,2, Yuan Ji1, Ling Sun1,2

            1Department of Cardiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu 213000, China

            2Dalian Medical University, Dalian, Liaoning 116000, China

            OBJECTIVES Predictive models based on machine learning have been widely used in clinical practice. Patients with acute myocardial infarction (AMI) are prone to the risk of acute kidney injury (AKI), which results in a poor prognosis for the patient. The aim of this study was to develop a machine learning predictive model for the identification of AKI in AMI patients.

            METHODS Patients with AMI who had been registered in the Medical Information Mart for Intensive Care (MIMIC) III and IV database were enrolled. The primary outcome was the occurrence of AKI during hospitalization. We developed Random Forests (RF) model, Naive Bayes (NB) model, Support Vector Machine (SVM) model, eXtreme Gradient Boosting (xGBoost) model, Decision Trees (DT) model and Logistic Regression (LR) models with AMI patients in MIMIC-IV database. The importance ranking of all variables was obtained by the SHapley Additive exPlanations (SHAP) method. AMI patients in MIMIC-III databases were used for model evaluation. The area under the receiver operating characteristic curve (AUC) was used to compare the performance of each model.

            RESULTS A total of 3882 subjects with AMI were enrolled through screening of the MIMIC database, of which 1098 patients (28.2%) developed AKI. We randomly assigned 70% of the patients in the MIMIC-IV data to the training cohort, which is used to develop models in the training cohort. The remaining 30% is allocated to the testing cohort. Meanwhile, MIMIC-III patient data performs the external validation function of the model. Three thousand eight hundred eighty-two patients and 37 predictors were included in the analysis for model construction. The top 5 predictors were serum creatinine, blood urea nitrogen, atrial fibrillation, blood glucose concentration, and hemoglobin concentration (SHAP values are 0.730, 0.348, 0.310, 0.306 and 0.287, respectively). In the testing cohort, using top 20 important features, the models of RF, NB, SVM, xGBoost, DT model and LR obtained AUC of 0.961, 0.709, 0.775, 0.780, 0.714 and 0.692, respectively. Placing RF models of number of different variables on the external validation cohort yielded their AUC of 0.725, 0.779, 0.773, 0.781 and 0.788, respectively.

            CONCLUSIONS Machine learning algorithms, particularly the random forest algorithm, have improved the accuracy of risk stratification for AKI in AMI patients and are applied to accurately identify the risk of AKI in AMI patients.

            GW33-e0685
            The relation between urinary 8-iso-prostaglandin F2α level and culprit plaque rupture in the diabetic patients with acute coronary syndrome

            Gong Su1, Lili Zhang1, Tao Zhang2

            1Center of Cardiovascular Medicine, Aerospace Central Hospital, Peking University, Beijing 100049, China

            2Center of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100029, China

            OBJECTIVES Enhanced isoprostanes-related oxidative stress was reported to play a key role in cardiovascular complications in patients with type 2 diabetes melitus (T2DM). The spontaneous plaque rupture and subsequent thrombosis is the most common cause of ischemic cardiovascular events. The relationship between urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) and coronary plaque rupture has not been fully elucidated. The aim of this study was to evaluate the assessment of rupture of culprit lesions in diabetic patients with acute coronary syndrome (ACS) by the use of urinary 8-iso-PGF2α.

            METHODS A total of 136 diabetic patients with ACS were included in this observational and case-control study. Sixty-eight patients with plaque rupture were matched by age and gender with other 68 patients without plaque rupture. The characteristics of ruptured culprit plaque were identified by intravascular ultrasound. Urinary 8-iso-PGF2α level was measured before coronary angiography and corrected by creatinine clearance.

            RESULTS Under the same age and gender conditions, patients with ruptured plaque had greater plasma hemoglobin A1c (HbA1c, 7.6±1.2 vs. 7.2±1.2%, P=0.038), high sensitive C reactive protein [hs-CRP, 3.9 (1.1, 5.9) vs. 2.3 (0.6, 4.4) mg/dL, P=0.043], urinary 8-iso-PGF2α levels [147.5 (68.6, 217.9) vs. 108.9 (59.5, 182.3) pmol/mmolCr, P=0.009], and more positive remodeling plaques (remodeling index, 1.04±0.15 vs. 0.97±0.17, P=0.018) than patients with non-ruptured plaque. In multivariate analysis, high urinary 8-iso-PGF2α, plasma hs-CRP and positive remodeling index were significantly associated with incidence of plaque rupture, but HbA1c was not. Urinary 8-iso-PGF2α also displayed a significant value in predicting ruptured plaques in diabetic patients with ACS by constructing the receiver-operating characteristic (ROC) curve (Area under the ROC curve: 0.803, P=0.001).

            CONCLUSIONS High urinary 8-iso-PGF2α levels appeared to be correlated with plaque rupture in diabetic patients with ACS, which indicated that urinary 8-iso-PGF2α may be an important predictor for the cardiovascular outcomes in diabetic patients with coronary heart disease. The study suggests therapies aimed at reducing oxidative stress would benefit diabetic patients at risk of developing adverse cardiac events.

            GW33-e0688
            Prognostic value of malnutrition using geriatric nutritional risk index in patients with non-ST-elevation myocardial infarction after percutaneous coronary intervention

            Qian-Ru Yuan, Yi-Tong Ma

            Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES Malnutrition is associated with poor prognosis in a wide range of chronic illnesses, however, the impact of malnutrition on long-term outcomes of patients at advanced stages of atherosclerosis, non-ST-elevation myocardial infarction (NSTEMI), is not known. This study aims to investigate the relationship between malnutrition and adverse cardiovascular events in patients with NSTEMI after percutaneous coronary intervention (PCI).

            METHODS Baseline malnutrition risk was determined in 754 patients with NSTEMI after PCI in this study. All patients were divided into 3 groups according to 3 categories of the geriatric nutritional risk index (GNRI): moderate to severe, GNRI of<92 (n=102); low GNRI of 92–98 (n=222); and absence of risk, GNRI of;98 (n=430). The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE).

            RESULTS Average age in this study was 60.37±10.92 years old. More than two-fifth of patients were at risk of malnutrition (moderate to severe: 13.5%; low: 29.4%; and absence of risk: 57.1%). Over a median follow-up of 40 months, compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for the all-cause death, cardiovascular death and MACE (HR: 2.91, 95% CI: 1.49–4.80, P=0.002; HR: 3.12, 95% CI: 1.42–7.25, P=0.010; HR: 1.46, 95% CI: 1.02–3.09, P=0.040; respectively) after adjustment for baseline variables. Moreover, addition of the GNRI score significantly raised the predictive value for the all-cause death (0.398, P=0.004 and 0.022, P=0.011, NRI and IDI respectively), cardiovascular death (0.439, P<0.001 and 0.013, P=0.014, NRI and IDI respectively) and MACE (0.372, P=0.004 and 0.014, P=0.008, NRI and IDI respectively) as compared to traditional factors.

            CONCLUSIONS Malnutrition assessed by the NSTEMI score on admission was an independent predictor for adverse cardiovascular events in NSTEMI patients after PCI. Addition of the GNRI score to the existing risk prediction model significantly increased the predictive ability for cardiovascular events in NSTEMI patients after PCI.

            GW33-e0693
            Optical coherence tomography findings of the braid-like coronary artery: case series

            Ting Tian1, Yining Yang1,2

            1Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

            2People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

            OBJECTIVES In coronary angiography (CAG), woven coronary artery and thrombus recanalization both show the braided hair like coronary arteries, which is difficult to distinguish. We aimed to analyze the characteristics of woven coronary artery and thrombus recanalization by optical coherence tomography (OCT), and make a detailed differential diagnosis between these two diseases.

            METHODS Six patients with braided hair like coronary arteries in CAG underwent OCT tests including two-dimensional (2D) images and three-dimensional (3D) reconstruction. Detailed clinical and imaging characteristics were analyzed.

            RESULTS Through the implementation of OCT, three patients were diagnosed as woven coronary artery, three patients were diagnosed as thrombus recanalization. The lesion of woven coronary artery was characterized by multiple, separated small vessels, which do not communicate with each other, showed by OCT. These separated channels had a complete arterial wall structure of intima and media, indicating that they were intact and independent. However, the lesion of thrombus recanalization displayed many microchannels without layered structure of arterial wall. These microchannels communicated with each other, showing a typical lobulated structure protruding to the lumen, and the larger one passed through the whole lesion.

            CONCLUSIONS OCT makes a better differential diagnosis between woven coronary artery and thrombus recanalization than CAG. Using OCT after CAG can improve the accuracy of woven coronary artery diagnosis. In addition, OCT-3D vascular reconstruction accurately locates the lesion segments and helps to describe the morphological characteristics.

            GW33-e0694
            Coronary artery calcium and cystatin C for risk stratification of MACCEs and all-cause death in symptomatic patients

            Fan Luo1, Yining Yang1,2

            1Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China

            2Department of Cardiology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China

            OBJECTIVES The risk stratification and event prediction capabilities of coronary artery calcium score (CACS) and Cystatin C (Cys-C) alone for major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death have been well described, but the combination has not been studied. The aim of this study was to examine the independent and joint associations of baseline CACS and Cys-C with the risk of MACCEs and all-cause death in symptomatic populations.

            METHODS The study included 7140 patients with symptom of chest pain who underwent cardiac CT examinations to measure CACS. All of them had serum Cys-C results. Endpoints were set for MACCEs and all-cause death events.

            RESULTS Seven thousand one hundred forty participants were followed for a median of 1106 days. At the end of the follow-up period, 305 patients had experienced MACCEs and 191 patients had experienced all-cause death. CACS≥100 and Cys-C≥0.995 mg/L were independently associated with an increased risk of MACCEs (adjusted hazard ratio [HR]: 1.46; 95% confidence interval [CI]: 1.15 to 1.85; P=0.002 and adjusted HR: 1.57; 95%CI: 1.24 to 2.00; P<0.001, respectively). Cys-C≥0.995 mg/L was independently associated with an increased risk of all-cause death (adjusted HR: 2.26; 95%CI: 1.64 to 3.13; P<0.001), but CACS≥100 was only nominally associated with an increased risk of all-cause death (adjusted HR: 1.31; 95%CI: 0.97 to 1.78; P=0.077). Compared with CACS<100 and Cys-C<0.995 mg/L patients, CACS≥100 and Cys-C≥0.995 mg/L patients had the highest risk of MACCEs and all-cause death (adjusted HR: 2.33; 95% CI: 1.64 to 3.29; P<0.001 and adjusted HR: 2.85; 95% CI: 1.79 to 4.55; P<0.001, respectively). Even in patients with CACS <100, Cys-C≥0.995 mg/L was also associated with a higher risk of MACCEs and all-cause death than Cys-C<0.995 mg/L (adjusted HR: 1.76; 95% CI: 1.21 to 2.56; P=0.003 and adjusted HR: 2.02; 95%CI: 1.21 to 3.37; P=0.007, respectively).

            CONCLUSIONS The combined stratification of CACS and Cys-C showed an incremental risk of MACCEs and all-cause death, reflecting complementary prognostic value. Our results support the combination of the two indicators for risk stratification and event prediction.

            GW33-e0700
            Prognostic impacts of the dynamic evolution of renal function in patients undergoing elective percutaneous coronary intervention

            Yifei Xiang1,2,3, Xueqin Lin1,2,3, Xiaoling Cai1,2,3, Kaiyang Lin1,2,3

            1Fujian Provincial College of Clinical Medicine

            2Fujian Provincial Hospital

            3Fujian Medical University

            OBJECTIVES Previous studies have shown that chronic kidney disease (CKD) affected the long-term prognosis of patients underwent the elective percutaneous coronary intervention (EPCI). However, the prognostic impact in patients with the development of the contrast-associated acute kidney injury (CA-AKI) or the onset of the acute kidne disease (AKD) were controversial. For the moment, little attention has been paid to the relationship between the dynamic evolution of renal function and its prognosis.

            METHODS We used three stages to characterize the dynamic evolution of renal function, namely the occurrence of CKD at baseline, the occurrence of CA-AKI in the postoperative period and the occurrence of AKD at 3 months postoperatively. All-cause mortality was used as the primary endpoint of the study. The five-year survival rate of each group was analyzed using Kaplan-Meier curve. The relationships between each group and long-term prognosis were analysed by multifactorial Cox regression analysis.

            RESULTS We prospectively enrolled 2951 patients who underwent EPCI from 2012 to 2018. They were divided into three groups according to baseline CKD and CA-AKI: STAGE I [Unimpaired renal function group, CKD(-)/CA-AKI(-) (n=1247)], STAGE II [Partially impaired renal function group, IIa: CKD(-)/CA-AKI(+) (n=91) and IIb: CKD(+)/CA-AKI(-) (n=1472)] and STAGE III [severely impaired renal function group, CKD(+)/CA-AKI(+) (n=141)]. Subsequently, based on the occurrence of AKD, they were divided into six groups: STAGE I/AKD(-) (n=1212), STAGE I/AKD(+) (n=35), STAGE II/AKD(-) (n=1508), STAGE II/AKD(+) (n=55), STAGE III/AKD(-) (n=108), STAGE III/AKD(+) (n=33). In a mean follow-up period of 3.33±1.39 years, we found that the occurrence of both CKD and CA-AKI affected the long-term prognosis of patients. The occurrence of AKD did not affect the prognosis of patients in the STAGE I group (hazard ratio [HR]=1.10, 95% CI: 0.15–8.11, P=0.928) and the STAGE III group (hazard ratio [HR]=1.12, 95% CI: 0.46–2.68, P=0.806). However, for the STAGE II group, the development of AKD would lead to a poor prognosis for patients.

            CONCLUSIONS In patients undergoing EPCI, the occurrence of CKD and CA-AKI affected the long-term prognosis of patients. The prognostic impact of the occurrence of AKD depended on the renal function of patients. In patients with unimpaired renal function and severely impaired renal function, the prognostic impact of AKD was negligible. However, in patients with partial abnormal avoidance of AKD could benefit the patient.

            GW33-e0705
            Malnutrition increases the risk of left ventricular remodeling

            Xiaozhao Lu1,2, Qiang Li1,2, Haozhang Huang1,2, Shiqun Chen1,2, Guoxiao Liang1,2, Siqi Su1,2, Ning Tan1,2, Jiyan Chen1,2, Jin Liu1,2, Yong Liu1,2

            1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            OBJECTIVES Malnutrition is associated with increased incidence of heart failure (HF). Left ventricular (LV) remodelling is one of the most important processes in the occurrence and evolution of HF. However, the relationship between nutritional status and LV remodelling is not well known. The study aims to investigate the association between malnutrition and LV remodeling.

            METHODS We enrolled 16,149 patients from January 2007 to December 2018 at Guangdong Provincial People’s Hospital (NCT04407936). The primary endpoint was LV remodeling, defined as an absolute decrease in LV ejection fraction ≥10% after discharge compared with baseline. Nutritional status was assessed by the Controlling Nutritional Status (CONUT) score. Eligible patients were divided into absent-mild malnutrition group (CONUT score ≤4) and moderate-severe malnutrition group (CONUT score ;4). Univariable and multivariable logistic regression was performed to verify the association between malnutrition and LV remodeling.

            RESULTS A total of 7217 patients (mean age 61.3±10.5 years, 71.7% male) were included in the final analysis, among which 712 (9.9%) had LV remodeling. The incidence of LV remodelling in moderate-severe malnutrition group was significantly higher than that in absent-mild malnutrition group (12.9 vs. 9.5%, P=0.002). In multivariable logistic regression, moderate-severe malnutrition group was significantly associated with 1.69-fold increased risk of LV remodeling after adjusting confounders (OR: 1.69, CI: 1.32–2.16). Similar results were observed in subgroup stratified by age, gender, and coronary artery disease.

            CONCLUSIONS Nearly one eighth of patients were classified as moderate-severe malnutrition, 12% of whom had LV remodeling. Moderate-severe malnutrition was associated with 69% increased risk of LV remodeling. Further studies are needed to prospectively evaluate the nutrition-oriented managements on outcomes in LV remodeling.

            GW33-e0721
            Effect of kidney disease on all-cause and cardiovascular-specific mortality in patients undergoing coronary angiography

            Qiang Li1,2, Shanshan Shi3,4, Haozhang Huang1,2, Jingru Deng1,2, Weihua Chen3,4, Jin Liu1,2, Yong Liu1,2,5

            1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            2Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            3Longyan First Affiliated Hospital of Fujian Medical University, Longyan 364000, China

            4The Third Clinical Medical College, Fujian Medical University, Fuzhou 350000, China

            5Guangdong Provincial People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510100, China

            OBJECTIVES Acute kidney injury (AKI) occurred in 12.8% of patients undergoing surgery and is linked to a 22.2% increase in mortality. Chronic kidney disease (CKD) is a well-known risk for death and cardiovascular events. Effects of AKI and CKD on patients undergoing coronary angiography (CAG) remain incompletely defined. We aim to investigate the associations of kidney disease with risk of death among patients received CAG.

            METHODS This multi-center study was conducted from Cardiorenal Improvement II (CIN-II) cohort with the mean follow-up of 5.92 years (final date of follow-up, September 1, 2021). Patients aged >18 years with diagnostic information of AKI and CKD in 5 tertiary hospitals in South China between January, 2007 and December, 2018 were included, excluding those lacking follow-up records or with outlying values of estimated glomerular filtration rate (eGFR). Ultimately, 37,377 patients were included in this study. All-cause and cardiovascular-specific mortality. We used Cox regression analyses and Fine-Gray proportional subdistribution risk regression analysis to test the association between kidney disease and all-cause mortality and cardiovascular-specific mortality, respectively.

            RESULTS In present study, 12,454 (33.3%) patients had kidney disease. During a mean follow-up of 5.92 years, 7921 patients died, of which 3496 (44.1%) were due to cardiovascular disease. Multivariate Cox proportional risk analysis showed that AKI without CKD (HR: 1.32, 95% CI: 1.18–1.47), CKD without AKI (HR: 1.71, 95% CI: 1.60–1.82), AKI with CKD (HR: 2.60, 95% CI: 2.33–2.89), and end-stage renal disease (ESRD; HR: 5.36, 95% CI: 4.84–5.93) were significantly associated with long-term all-cause mortality. Adjusted hazard ratios (95% CIs) for cardiovascular-specific mortality were significantly elevated among patients with AKI without CKD (1.58[1.34–1.87]), CKD without AKI (2.34[2.12–2.59]), AKI with CKD (3.67[3.13–4.31]) and ESRD (8.74[7.49–10.2]).

            CONCLUSIONS This large multi-center study shows that acute and chronic kidney disease is present in up to one third of patients undergoing CAG and is associated with a substantially increased mortality. These findings highlight the importance of perioperative management of kidney function, especially in patients with CKD.

            GW33-e0724
            Clinical heterogenity of acute coronary syndrom causes and its angiographic profile in young patients

            Daria Nedbaeva, Galina Kukharchik

            Almazov National Medical Research Centre

            OBJECTIVES Prevalence of coronary artery disease is increasing in young adults. This group has different mechanisms of myocardial ischemia and less traditional cardiovascular risk factors.

            METHODS We retrospectively studied 114 patients ≤45 years of age admitted for ACS. 97% of patients underwent coronary angiography. Primary in-hospital endpoints were cardiovascular death, nonfatal myocardial infarction, unstable angina, stent thrombosis and arrythmias.

            RESULTS The most common etiology of ACS remains atherosclerosis. Nearly quarter of patients (24%, n=27) had multivessel disease, 17% (n=19) - complex lesion: left main stem lesion (n=5), bifurcation lesion (n=6), chronic total occlusion (n=8). High proportion (18%, n=20) of young patients showed no atherosclerotic lesions. This finding suggests a different mechanism of ACS, like type II MI (n=7). Another cause may be spontaneous coronary artery dissection (SCAD), found in 4 patients. Type II MI and SCAD were prevalent among women (P<0.05). ACS in young patients may be the first manifestation of congenital coronary artery abnormalities: myocardial bridge (n=3), or vasculitis, such as Takayasu arteritis (n=2). Therefore, heterogeneity of ACS causes, clinical and angiographic features determined the treatment strategy.

            CONCLUSIONS ST-segment elevation, low ejection fraction, history of MI and complex coronary lesions were predictors of in-hospital adverse outcomes. Identification of the ACS causes was necessary for personalized treatment and sometimes led to the choice of an invasive strategy.

            GW33-e0726
            Benefits of successful percutaneous coronary intervention in chronic total occlusion patients with diabetes

            Shuai Zhao1, Boda Zhu2, Qingyi Wang3, Zhihong Wei2, Jiayi Wang2, Yan Chen4, Yiming Zou2, Wentao Hu2, Cheng Liu2, Tiantong Yu1, Suining Xu5, Peng Han6, Feng Tao7, Qing Yang1, Tongtong Li1, Li Yang1, Qiling Liu8, Wei Wang9, Haokao Gao1, Chengxiang Li1, Kun Lian1

            1Department of Cardiology, Xijing Hospital, The Fourth Military Medical University

            2Cadet Brigade, School of Basic Medicine, The Fourth Military Medical University

            3Department of Foreign Languages, School of Basic Medicine, Fourth Military Medical University

            4Department of Cardiology, No. 971 Hospital of the PLA Navy

            5Department of Cardiology, The First Affiliated Hospital of Xi’an Medical University

            6Department of Cardiology, 981 Hospital of Joint Logistics Support Force

            7Department of Naval Medicine, Naval Medical University

            8Department of Epidemiology and Medical Statistical, School of Public Health, Shannxi University of Chinese Medicine

            9Department of Pharmaceutics and Pharmacy Administration, School of Pharmacy, The Fourth Military Medical University

            OBJECTIVES Diabetes was commonly seen in chronic total occlusion (CTO) patients but data regarding the impact of successful percutaneous coronary intervention (PCI) on clinical outcome of CTO patients with diabetes was controversial. And importantly, no studies have compared quality of life (QOL) after CTO-PCI in patients with and without diabetes.

            METHODS Consecutive patients undergoing elective CTO-PCI were prospectively enrolled at Xijing Hospital from Apr 2018 to Apr 2021. Patients were subdivided into 2 groups: Diabetes and No Diabetes. Detailed baseline characteristics, assessment of symptom and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. Accordingly, data were analyzed for risk predictors of clinical outcome in patients with diabetes underwent successful revascularization.

            RESULTS A total of 995 patients underwent CTO-PCI attempts. Diabetes was present in 346 (36.23%) patients, who had more hypertension, previous stroke, chronic kidney disease, multi-CTO lesion and higher J-CTO score (P<0.05), and their procedural success rate did not significantly reduce compared to without diabetes (91.33 vs. 91.68%, respectively; P=0.850). In-hospital major adverse cardiac cerebrovascular event (MACCE) (3.76 vs. 3.39%; P=0.764) was similar in the two groups. At 1 month and 1 year follow-up after successful CTO-PCI, major adverse cardiac event (MACE) and all-cause mortality were also similar in the two groups (P>0.05). LVEF<40% was independent risk factor of MACE (OR=6.212, 95% CI 3.170–12.174; P<0.001) and all-cause mortality (OR=12.637, 95% CI 3.992–40.001; P<0.001) 1 year after successful revascularization. Symptom and QOL were markedly improved regardless of diabetes both at 1 month and 1 year follow-up, and importantly, the improvement degree of patients with diabetes was similar with those without diabetes (P;0.05).

            CONCLUSIONS Successful CTO-PCI could represent an effective strategy improving clinical outcome, symptom and QOL in CTO patients with diabetes.

            GW33-e0727
            Benefits of successful percutaneous coronary intervention in Chinese CTO patients with low LVEF

            Shuai Zhao1, Boda Zhu2, Yan Chen3, Haokao Gao1, Zhihong Wei2, Qingyi Wang4, Yiming Zou2, Wentao Hu2, Cheng Liu2, Jiayi Wang2, Tiantong Yu1, Suining Xu5, Peng Han6, Feng Tao7, Qing Yang1, Tongtong Li1, Li Yang1, Qiling Liu8, Wei Wang9, Kun Lian1, Chengxiang Li1

            1Department of Cardiology, Xijing Hospital, The Fourth Military Medical University

            2Cadet Brigade, School of Basic Medicine, The Fourth Military Medical University

            3Department of Cardiology, No. 971 Hospital of the PLA Navy, Qingdao

            4Department of Foreign Languages, School of Basic Medicine, Fourth Military Medical University

            5Department of Cardiology, The First Affiliated Hospital of Xi’an Medical University

            6Department of Cardiology, 981 Hospital of Joint Logistics Support Force

            7Department of Naval Medicine, Naval Medical University

            8Department of Epidemiology and Medical Statistical, School of Public Health, Shannxi University of Chinese Medicine

            9Department of Pharmaceutics and Pharmacy Administration, School of Pharmacy, The Fourth Military Medical University

            OBJECTIVES Low LVEF was commonly seen in CTO patients and was considered as an independent risk factor of poor prognosis of those patients. Yet, data regarding the clinical outcome, symptom and QOL of successful recanalization of CTO in low LVEF patients were scarcely reported. This study set out to assess the clinical outcome, symptoms and quality of life (QOL) of chronic total occlusion treated with percutaneous coronary intervention (CTO-PCI) in Chinese patients with low left ventricular ejection fraction (LVEF) (<40%).

            METHODS Patients consecutively undergoing elective CTO-PCI at Xijing Hospital from Apr. 2018 to Apr. 2021 were included in this study. Patients were subdivided into 3 groups: LVEF≥50%, 50%;LVEF≥40%, and LVEF<40%. Detailed baseline characteristics, assessment of symptoms and QOL, angiographic and procedural details, in-hospital complications, and 1 month and 1 year follow-up data were collected. Accordingly, data were analyzed for its risk predictors of procedural success and clinical outcome in patients with low LVEF.

            RESULTS Of 995 CTO patients, LVEF<40% was present in 172 (17.29%), who had more previous MI, multi-CTO lesion, LCX-CTO lesion, application of MCS and higher SYNTAX score (P<0.001), and their procedural success rate did not drop significantly compared with the other two groups (93.95 vs. 92.31 vs. 88.95%; P=0.078). In-hospital major adverse cardiac and cerebrovascular event (MACCE) (2.55 vs. 2.56 vs. 8.14%; P=0.001) and other complications (6.05 vs. 5.13 vs. 19.76%; P<0.001) were the highest in patients with LVEF<40%. At 1 month and 1 year follow-up, major adverse cardiac event (MACE) and all-cause mortality were also the highest in patients with LVEF<40% after successful CTO-PCI (P<0.001), while they were markedly lower than those with failed CTO-PCI (P<0.001). LVEF<40% was an independent risk factor of MACE (OR=2.905, 95% CI 1.930–4.372, P<0.001) and all-cause mortality (OR=5.833, 95% CI 3.240–10.501, P<0.001) 1 year after successful revascularization. Symptoms and QOL were markedly improved regardless of LVEF both at 1 month and 1 year follow-up, notably at a similar degree between patients with LVEF<40% and the other two groups (P;0.05).

            CONCLUSIONS PCI could represent an effective revascularization strategy improving clinical outcome, symptoms and QOL in CTO patients with low LVEF.

            GW33-e0728
            Predictive value of the TC/HDL-C for chronic total occlusion of coronary heart disease

            Shuai Zhao1, Boda Zhu2, Yan Chen3, Zhihong Wei2, Jiayi Wang2, Peng Han4, Tiantong Yu1, Wentao Hu2, Yiming Zou2, Ziwei Wang2, Cheng Liu2, Qing Yang1, Li Yang1, Yamin Zhang1, Haokao Gao1, Qingyi Wang5, Chengxiang Li1, Kun Lian1

            1Department of Cardiology, Xijing Hospital, The Fourth Military Medical University

            2Cadet Brigade, School of Basic Medicine, The Fourth Military Medical University

            3Department of Cardiology, No. 971 Hospital of the PLA Navy

            4Department of Cardiology, 981 Hospital of Joint Logistics Support Force

            5Department of Foreign Languages, School of Basic Medicine, Fourth Military Medical University

            OBJECTIVES Dyslipidemia has been well-recognized as critical risk factor of coronary heart disease (CHD). Recently, studies reported that the ratio of total cholesterol and high-density lipoprotein cholesterol (TC/HDL-C) was associated with cardiovascular diseases, but its association with chronic total occlusion (CTO), the most severe coronary lesion of CHD, requires elucidation.

            METHODS A total of 6260 CHD inpatients were consecutively enrolled between November 2012 and July 2020 at Xijing Hospital. Data on baseline and coronary angiography characteristics were collected and Gensini score (GS) was calculated by coronary artery stenosis. TC/HDL-C value was evaluated by the ratio of TC and HDL-C levels. The prognostic ability of several blood lipid indicators including total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) or TC/HDL-C to discriminate CTO from non-CTO was investigated using binary logistic regression and receiver operating characteristic (ROC) curve analysis. Additionally, the discrimination value of TC/HDL-C for multi-CTO or GS was also investigated.

            RESULTS Among the 6260 CHD patients, CTO and non-CTO were evaluated in 2437 and 3823 patients, respectively. CTO patient showed higher levels of baseline TC, TG, LDL-C, while baseline HDL-C was higher in non-CTO patient, and TC/HDL-C was significantly higher in CTO patient. Binary logistic regression analyses revealed that the TC/HDL-C, TC, TG and LDL-C were independent risk factors for CTO while HDL-C was protective factor. The area under the receiver operating curve (AUC) for the diagnosis of CTO was higher for TC/HDL-C (0.703) than for TC (0.578), TG (0.542), LDL-C (0.520), and HDL-C (0.602) and the optimal cutoff value was 3.753 with 63.4% sensitivity at 71.9% specificity. Meanwhile, compared with TC, TG, LDL-C or HDL-C, TC/HDL-C also showed the highest AUC in discriminating multi-CTO (0.674) or GS (0.639).

            CONCLUSIONS TC/HDL-C has a favorable predictive accuracy in the diagnosis of CTO patients, thus providing evidence for the earlier clinical decisions and intervention.

            GW33-e0732
            CAC for risk stratification among hypertriglyceridemia patients with extreme atherosclerotic cardiovascular disease

            Qianru Yuan, Yitong Ma

            Department of Coronarry Heart Disease, The First Affiliated Hospital of Xinjiang Mediacal University

            OBJECTIVES It is extremely important to identify those at extreme ASCVD risk and intervene effectively. In this study, we sought to evaluate whether the coronary artery calcium (CAC) score can enhance current paradigms for risk stratification among hypertriglyceridemia in primary prevention of patients with extreme atherosclerotic cardiovascular disease risk.

            METHODS We concluded 1478 participants with extreme ASCVD risk from the First Affiliated Hospital of Xinjiang Medical University from June 2017 to April 2021. We evaluated the incidence of MACE overall and further stratified by CAC scores (0, >0–100, >100) and triglycerides level (<2.6 mmol/L, 2.6∼5.54 mmol/L, >5.54 mmol/L). The number needed to treat for 5 years (NNT5) to prevent 1 event was estimated among patients with extreme ASCVD risk. We used Kaplan-Meier survival functions to generate cumulative incidence estimates of MACE. Cox proportional hazards regression models were used to evaluate the independent associations between CAC>0 to 100 and CAC;100 (compared with CAC 0) and MACE, adjusting for demographics, traditional cardiovascular risk factors, statin use and level of triglycerides.

            RESULTS The study population comprised 1478 patients with extreme ASCVD risk. Median age was 57 years, and 45% of patients were women. There was marked heterogeneity in CAC burden overall and different triglycerides level. Overall, the incidence of MACE was 60.0% and there was a marked increase with higher CAC scores. 69% of patients were hypertriglyceridemia and 39% had MACE within 40 months. Among participants with hypertriglyceridemia, 62% had CAC>100, and their event rates were markedly higher (38.4 vs 21.2%) and the NNT5 lower (14 vs 54) than those of the 3% patients with CAC 0. The incidence of MACE of severe hypertriglyceridemia was higher than that of mild to moderate hypertriglyceridemia. Among the 31% patients without hyperlipidemia, 39% had CAC>100, their 40-months incidence of MACE (15.9%) was lower than the overall incidence among patients were hypertriglyceridemia.

            CONCLUSIONS CAC can improve current risk stratification and therapy allocation paradigms among individuals with hypertriglyceridemia with extreme ASCVD risk. Future trials of risk-reduction therapies in hypertriglyceridemia could use CAC>100 to enroll a high-risk study sample, with implications for a larger target population.

            GW33-e0751
            Lung ultrasound combined with ACEF score to predict the risk of in-hospital adverse events in acute myocardial infarction

            Ziheng Lun1,2, Jiexin He1,2, Ying Zhang1,2

            1Guangdong Cardiovascular Institute

            2Guangdong Provincial People’s Hospital

            OBJECTIVES The prognosis of acute myocardial infarction complicated with pulmonary edema is poor. The ACEF (age, creatinine, and ejection fraction) Score and the number of B-lines detected by lung ultrasonography (LUS) have been shown to predict poor prognosis in acute coronary syndrome (ACS). However, whether lung ultrasound combined with ACEF score has incremental value in predicting the prognosis of patients with acute myocardial infarction (AMI) is still unclear. The purpose of this study is to explore the value of ACEF Score and LUS in predicting the occurrence of in-hospital adverse events in AMI.

            METHODS We performed preoperative echocardiography and lung ultrasonography (LUS) in patients with AMI who underwent emergency percutaneous coronary intervention (PCI) in Guangdong Provincial People’s Hospital from February to December 2021, collected clinical data from all patients and conducted ACEF score [ACEF score formula: age/ejection fraction +1 (if creatinine;176 μmol/L)]. LUS used the 8-zones method to detect B-lines and calculate the sum of B-lines. Definition of pulmonary edema severity was according to number of B-lines. The classification was as follows: normal (B-line numbers <5), mild (B-line numbers ≥5 and <15), moderate (B-line numbers ≥15 and <30), and severe (B-line numbers ≥30). The adverse events were defined as all-cause death, recurrent myocardial infarction, and heart failure.

            RESULTS Eighty-five patients were enrolled, and the average hospital stay was 9.05±7.35 days. The ACEF score during hospitalization was positively correlated with the number of B-lines (r=0.427, P<0.001) and NT-proBNP (r=0.282, P=0.009). In the multivariate logistic regression analysis, B-lines number (OR 1.148[95% CI: 1.040–1.305], P=0.035) and ACEF Score (OR 61.559[95% CI: 1.468–2580.693], P=0.031) were independent predictors of adverse events during hospitalization in AMI patients. The area under the receiver operating characteristic curves (AUCs) were 0.753(P=0.002), 0.828(P<0.001) and 0.862(P<0.001) for ACEF Score, LUS and their combination, respectively.

            CONCLUSIONS Both the number of B-lines and the ACEF Score can be used as independent predictors of adverse events in AMI patients during hospitalization. The number of B-lines combined with ACEF Score provides incremental value in predicting the risk of adverse events and is important for risk stratification during hospitalization.

            GW33-e0758
            Non-traditional risk factors predict coronary artery disease in patients with chronic kidney disease

            Qingbo Xu1, Guode Li1, Jingru Deng2,3, Qiang Li2,3, Zhining Li1, Xiaozhao Lu2,3, Guoxiao Liang2,3, Shi Wang2,3, Siqi Su2,3, Jin Liu2,3, Bo Wang2,3, Yongquan Yang2,3, Ning Tan2,3,4,5, Jiyan Chen2,3,4,5, Yong Liu2,3,4,5, Yan Liang2,3,4,5, Shiqun Chen6

            1Department of Cardiology, Maoming People’s Hospital, Maoming 525099, China

            2Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            3Department of Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China

            4The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China

            5Guangdong Provincial People’s Hospital, School of Medicine, South China University of Technology, Guangzhou 510100, China

            6Global Health Research Center, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Science, Guangzhou 510100, China

            OBJECTIVES Identifying coronary artery disease (CAD) early in patients with chronic kidney disease (CKD) is of primary importance for its subsequent treatment. However, the risk factors for diagnosis of CAD in patients with CKD are needed to investigated. We aimed to assess the non-traditional risk factors for the diagnosis of CAD in patients with CKD based on routine clinical variables.

            METHODS We enrolled 14,273 patients with CKD from the Cardiorenal Improvement II (CIN-II) Study and then classified them into two groups as moderate CKD (estimated glomerular filtration rate (eGFR) from 30 to 60 mL/min/1.73 m2, n=12,576) and severe CKD (eGFR<30 mL/min/1.73 m2, n=1697). Logistic regression was used to evaluate the association between non-traditional factors and CAD.

            RESULTS Of 14,273 CKD patients (31.9% female), nearly three quarters had CAD. Univariate analysis showed that the traditional and most non-traditional risk factors were significantly associated with CAD. After adjusting for traditional risk factors, severe CKD (adjusted odds ratio [aOR] 1.43, 95% CI 1.24–1.66), congestive hearts failure (aOR 1.55, 95% CI 1.39–1.73) and other 9 non-traditional risk factors were independent risk factors for CAD. In addition, adding the non-traditional risk factors into a model with traditional CAD risk factors, c-statistics was increased significantly.

            CONCLUSIONS Our study identified that not only traditional risk factors but also several non-traditional risk factors contribute to the identification of CAD in CKD patients. Identification of risk factors help in the management of CAD among CKD patients.

            GW33-e0767
            Development and validation of a nomogram predicting the survival of diabetic patients with three-vessel disease: insights from three large Asian cohorts

            Peizhi Wang, Ce Zhang, Deshan Yuan, Jinqing Yuan

            Department of Cardiology, Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

            OBJECTIVES In the real-world clinical practice, multivessel percutaneous coronary intervention (PCI) remains a common revascularization strategy for patients with three-vessel disease (3VD). However, risk assessment for 3VD patients undergoing PCI is still challenging, especially for those with diabetes mellitus. The study aims to build and validate a nomogram for estimating the short-term and long-term survival probabilities of diabetic patients with 3VD from three large Asian cohorts.

            METHODS A total of 1263 patients from the derivation cohort were included in the current analysis of nomogram development. LASSO regression analysis was employed for the development of the prediction model. The model was internally validated using bootstrap resampling and externally validated in two independent and large real-world cohorts, including validation cohort 1 (containing 2562 consecutive subjects from a multicenter cohort) and validation cohort 2 (containing 1461 consecutive subjects with long-term follow-up). The model performance was assessed by Harrell’s C-index, calibration curves and clinical usefulness analysis.

            RESULTS The proposed nomogram finally included 9 variables. The 1-, 2-, 5- and 10-year area under the receiver operating characteristic curve (AUC) of the nomogram were 0.70, 0.71, 0.73 and 0.73, respectively, showing the good discrimination of the model. The calibration was acceptable considering that optimism-corrected slopes of 1-, 2-, 5- and 10-year calibration plots were 0.93, 0.94, 0.93 and 0.94, respectively. Application of the nomogram in two validation cohorts still revealed good discrimination (1-, 2- and 5-year AUC were 0.80, 0.79 and 0.73, respectively) and good calibration (1-, 2- and 5-year optimism-corrected slopes were 1.01, 1.01 and 1.02, respectively). Decision curve analysis demonstrated that the prediction nomogram was clinically useful.

            CONCLUSIONS The individualized prediction nomogram was a useful risk stratification tool that could help identify high-risk patients with convenience where more precise treatment should be performed.

            GW33-e0771
            Higher HbA1c variability is associated with higher risk of cardiovascular diseases: insights from pooled results among patients with diabetes mellitus

            Li Feng, Wang Ru-Xing

            Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China

            OBJECTIVES HbA1c variability is a key parameter of glucose fluctuation. The relationship between glucose fluctuation and cardiovascular diseases (CVDs) in patients with diabetes mellitus (DM) remains elusive.

            METHODS PubMed, Cochrane Library, Web of Science and Embase were searched up to 1 July 2022. Studies reporting the association of HbA1c variability [standard deviation of HbA1c (HbA1c-SD), coefficient of variation of HbA1c (HbA1c-CV), and HbA1c variability score (HVS)] and the CVDs risk in DM patients were included. We used three different insights (a high-low dose meta-analysis, a study-specific meta-analysis, and a non-linear dose-response meta-analysis) to explore the relationship of HbA1c variability and the CVDs risk. Subgroup analysis was also performed to screen the potential confounding factors.

            RESULTS A total of 14 studies with 254,017 DM patients were eligible. The highest HbA1c variability was significantly associated with the increased CVDs risk (HbA1c-SD, RR 1.45; HbA1c-CV, RR 1.74; HVS, RR 2.46; all P=0.000) compared to the lowest HbA1c variability. The RRs of CVDs for per HbA1c variability were significantly more than 1 (P=0.000). Subgroup analysis for per HbA1c-SD showed that a significant exposure-covariate interaction was identified in the DM type subgroup (P=0.003 for interaction). Dose-response analysis showed a positive association between HbA1c-CV and the CVDs risk (P for non-linearity<0.001).

            CONCLUSIONS Our study suggests that the higher HbA1c variability might be significantly associated with the higher CVDs risk among T2DM patients. The CVDs risk might be higher among T1DM patients than T2DM patients.

            GW33-e0787
            Effect of early revascularization on major adverse cardiovascular events with different severity of myocardial ischemia in patients with chronic coronary syndrome

            Shuang Zhang1, Yihan Zhou2, Jingjing Meng2, Xiang Li3, Xiaoli Zhang2

            1Department of General Ultrasonography, Capital Medical University Affiliated Beijing Anzhen Hospital

            2Department of Nuclear Medicine, Capital Medical University Affiliated Beijing Anzhen Hospital

            3Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna

            OBJECTIVES Based on several large studies patients with stable ischemic heart disease may not benefit from an invasive therapeutic strategy, particularly the optimal choice may be different according to the severity of myocardial ischemia. Therefore, the purpose of the present study is to evaluate whether or not the effects of revascularization on the prognosis of patients with chronic coronary syndromes (CCS) are associated with the amount of ischemic myocardium detected by nuclear stress imaging.

            METHODS This retrospective study analyzed data from 617 patients with suspected or known CCS who underwent 99mTc-MIBI MPI and CAG (the interval was less than three months) between October 2016 and December 2019. According to the MPI imaging all patients were divided into two groups as None-Moderate ischemia (<15% ischemic myocardium) and Severe ischemia (≥15% ischemic myocardium). For assessment of outcome of treatment, patients further classified into three subgroups, complete coronary revascularization (CCR) or incomplete coronary revascularization (ICR) and no coronary revascularization (NCR), and early revascularization was defined as revascularization with PCI or CABG within 90 days of the MPI test. The primary outcome was major adverse cardiac events (MACE) (death, myocardial infarction and coronary revascularization). Cumulative incidence of MACE was estimated by Kaplan–Meier method and compared by the log-rank test. Cox proportional hazard regression analysis was used to determine independent predictors for MACE.

            RESULTS During the follow-up of 35.6±7.9 months, 68 (11.0%) MACE were recorded. MPI imaging indicated 429 (69.5%) patients with None-Moderate ischemia and 188 (30.5%) patients with Severe ischemia. In patients with None-Moderate ischemia, the cumulative incidence of MACE of CCR+ICR (7.2±4.5%) and NCR (4.2±2.7%) was significantly different (P=0.033). The subgroup analyses revealed ICR group (12.6±6.7%) has a worse prognosis than NCR or CR group (5.1±3.4%) (P=0.005). However, there was no significant difference among the NCR (7.1±4.7%), CCR (9.8±5.5%) and ICR (10.9±6.4%) group (P=0.372). Multivariate regression Cox analysis revealed revascularization surgery itself increase a risk of MACE among patients with None-Moderate ischemia (adjusted hazard ratio [HR] 1.93[95% CI 1.021–3.621]), but no increased risk was found among those with severe ischemia (adjusted hazard ratio [HR] 1.902[95% CI 0.873–4.145]) (P=0.003 for interaction), after adjusting for age, sex, previous infarction, and previous revascularization.

            CONCLUSIONS In patients with none-moderate ischemia, conservative strategy for CCS has a better prognosis compared with coronary revascularization, particularly incomplete revascularization.

            HYPERTENSION
            GW33-e0009
            Integrating waist circumference and body mass index to predict all-cause death for patients with hypertension: a population-based cohort study

            Jin-Yu Sun, Yang Hua, Qiang Qu, Hui Shen, Shun Xu, Ze-Zhong Cao, Wei Sun, Xiang-Qing Kong

            Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

            OBJECTIVES This study aims to investigate the integration of both waist circumference and body mass index (BMI) to predict all-cause and cardiovascular-specific death in patients with hypertension.

            METHODS This prospective cohort study included 12,386 participants with a median follow-up of 6.2 years. Waist circumference-to-BMI ratio (WtBR) was used to integrate waist circumference and BMI, defined as a ratio of waist circumference to BMI. We applied adjusted Cox regression models, restricted cubic spline, Kaplan-Meier curves, random forest analysis, and sensitivity analysis to evaluate the association between WtBR and all-cause mortality. Then, to assess the discriminative ability of WtBR for cardiovascular-specific death, we used Fine-Gray competing risk regression models setting non-cardiovascular death as a competing risk. Additionally, a prediction model was created based on WtBR to evaluate the risk of all-cause mortality in patients with hypertension.

            RESULTS The adjusted model showed a significant association of waist circumference and BMI with all-cause death with hazard ratios (95% confidence interval) of 1.44 (1.33–1.57) and 0.42 (0.34–0.51), respectively. When analyzed as a continuous variable, WtBR was consistently associated with an increased risk of death in a linear pattern with an adjusted HR of 2.42 (2.06–2.85). Patients in the highest quintile showed a 2.24-fold risk of death than the lowest quintile. Sensitivity analysis demonstrated the robustness of the association. However, no significant association was observed between WtBR and cardiovascular-specific death. In the testing set, the predictive model showed a reliable performance with an area under the curve of 0.803, sensitivity of 0.72, specificity of 0.76, and negative predictive value of 0.84. The visualized nomogram can be easily accessed at https://data15651725761.shinyapps.io/ACM-for-HP/.

            CONCLUSIONS WtBR provides an additional opportunity to predict all-cause death in patients with hypertension. Waist circumference should be routinely examined in patients with hypertension regardless of BMI to better manage obesity-related health risks.

            GW33-e0049
            High waist circumference is a risk factor for hypertension in normal-weight or overweight individuals with normal metabolic profiles

            Chen Cheng1,2, Jinyu Sun1,2, Ying Zhou1,2, Qiyang Xie1,2, Liyuan Wang1,2, Xiangqing Kong1,2, Wei Sun1,2

            1Cardiovascular Research Center, The Affiliated Suzhou Hospital of Nanjing Medical University

            2Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University

            OBJECTIVES This study aims to investigate the relationship between waist circumference and hypertension risk in normal-weight and overweight individuals with normal cardiometabolic profiles.

            METHODS This study included 7217 normal-weight and overweight individuals with normal cardiometabolic profiles from the 2001–2014 US National Health and Nutrition Examination Survey. We first summed up their demographic characteristics, cardiometabolic profiles, and behavioral factors across waist circumference quartiles. Then, we analyzed the relationship between waist circumference and hypertension prevalence using multivariate logistic regression models and restricted cubic spline. Finally, we applied multivariate Cox regression analysis and Kaplan-Meier curve analysis to explore the association of waist circumference with all-cause mortality in individuals with hypertension.

            RESULTS In multivariate logistic regression analysis, we observed a positive and significant association of waist circumference (as a continuous variable) with hypertension prevalence in all three models (non-adjusted, minimally-adjusted, and fully-adjusted), with odds ratios (95% confidence intervals) of 1.76 (1.65–1.86), 1.28 (1.19–1.38), and 1.22 (1.08–1.38), respectively. And when analyzed as a categorical variable, individuals in the highest waist circumference group had a 1.44-fold increased risk of hypertension than those in the lowest group in the fully-adjusted model. In multivariate Cox regression analysis, waist circumference had a positive and significant association with all-cause mortality in individuals with hypertension in the non-adjusted model (HR, 1.27; 95% CI, 1.10–1.47) and the fully-adjusted model (HR, 1.59; 95% CI, 1.22–2.06), while no significant difference was observed in the minimally-adjusted model.

            CONCLUSIONS We found waist circumference had a positive and significant association with hypertension prevalence in normal-weight/overweight individuals with normal cardiometabolic profiles and all-cause mortality once hypertension has been established. This study suggested that waist circumference may well be a causal risk factor for the occurrence and development of hypertension independently of cardiometabolic factors.

            GW33-e0360
            Application of roy adaptation model in treatment adherence of patients with hypertension

            Li Wang1,2, Lian Zhou2, Xiaomei Chen1, Yanni Yang1

            1School of Nursing, Third Military Medical University (Army Medical University)

            2Department of Cardiology, Southwest Hospital, Third Military Medical University (Army Medical University)

            OBJECTIVES To explore the effect of Roy adaptation model in predicting treatment adherence in hypertensive patients.

            METHODS A total of 182 hospitalized hypertensive patients in the cardiovascular department of a level A tertiary hospital in Chongqing from May to November 2021 were selected by convenience sampling method. The personal information questionnaire, Therapeutic adherence scale for hypertensive patients, Coping and Adaptation Processing Scale-Short Form, Beijing Montreal Cognitive Assessment and Self-Rating Depression Scale were used for investigation. Logistic regression was used to analyze the predictive factors of treatment adherence in hypertensive patients, and the predictive efficacy was evaluated by receiver operating characteristic (ROC) curve.

            RESULTS The proportion of low treatment adherence in 182 hypertensive patients was 67%, and the score of daily life management dimension was the lowest 3.20 (2.80, 3.60). Logistic regression analysis showed that the ability of coping and adaptation, age, residence and economic stress were predictors of treatment adherence in hypertensive patients. The area under the ROC curve of Logistic regression prediction model and Coping and Adaptation Processing Scale-Short Form was 0.785 and 0.698, respectively. The sensitivity was 70.49 and 47.54%, respectively. The specificity was 81.67 and 85.00%, respectively. The cut-off value of Coping and Adaptation Processing Scale-Short Form was 41 points.

            CONCLUSIONS Roy adaptation model can be used to understand and predict the treatment adherence of hypertensive patients. Coping and Adaptation Processing Scale-Short Form can effectively and efficiently screen hypertensive patients with poor treatment adherence, and provide the basis for intervention framework.

            GW33-e0379
            A survey of emergency hospitalized patients due to poorly controlled hypertension

            Zhongxing Zhou1, Lixia Chen2

            1Jining Institute of Cardiovascular Disease

            2Jining Number one People’s Hospital

            OBJECTIVES Analyzing clinical date of emergency hospitalized patients due to poor blood pressure control.

            METHODS The medical records of inpatients were collected.

            RESULTS One hundred forty five patients included 63 males (43.4%). Sixty-six patients were admitted by ED (45.5%), OPD (54.5%). No significant difference of stay days between OPD and ED [(4.88±1.91) vs (5.05±1.97), P=0.629]/d. The female age was significantly higher than that of male patients [(63.4±13.1) vs (55.3±13.0), P=0.002]/years; the age of patients were older admitted by ED compared with OPD [(63.4±13.7) vs (55.8±12.4), P=0.001]; all patients have recorded the instantaneous blood pressure when they were hospitalized, of which SBP (178.6±25.6) mmHg, and DBP (99.8±15.4) mmHg, there was no significant difference in SBP between male and female at admission [(177.5±25.2) vs (179.6±25.9) P=0.64] mmHg, while male patients had higher DBP at admission [(104.5±14.2) vs (96.2±15.3) P=0.001] mmHg. Similarly, ED patients had higher SBP [(191.1±23.6) vs (168.3±22.4) P=0.003] mmHg. Including SBP (134±15.9) mmHg, DBP (81.9±11.9) mmHg, there were no significant difference in SBP between male and female [(136.3±16.8) vs (132.3±15.1) P=0.13] mmHg, while male patients had higher DBP at discharge [(84.7±12.5) vs (79.8±10.8) P=0.012] mmHg. With discharge baseline BP≤140/90 mmHg, 83 (57.2%) patients reached the target. There was no significant difference between male and female (P=0.086, X2=2.938). 38 (57.6%) cases admitted to the ED met the standard at the time of discharge, and 45 (57.0%) of the 79 OPD met the standard, no difference (P=0.94, X2=0.006). A total of 131 patients with echocardiography results, including EF:(62.6±3.5)%, LVEDD (45.3±4.2) mm, LA (34.3±5.1) mm, IVS (11.6±1.9) mm, LVPW (10.1±1.0) mm, mitral valve E/e′ (12.7±4.0). Comparative analysis of date between male and female: LV [(59.6±2.0) vs (65.2±2.4) P=0.92]%, LVEDD [(45.6±5.0) vs (45.0±3.3) P=0.47] mm, LA [(34.0±4.9) vs (34.5±5.3) P=0.51] mm, E/e′ [(13.4±4.2) vs (12.2±3.9) P=0.15] had no significant difference, while the male IVS and LVPW were higher than female patients [(12.0±2.0) vs (11.2±1.8) P=0.02] mm, [(10.4±1.1) vs (9.9±0.9) P=0.002] mm. Totally, 22 (15.2%) patients take one HTN drug; 48 (33.1%) take two HTN drugs, 35 (72.9%) were freely combined, and 14 (27.1%) in the SPC group; 39 (26.9%) take 3 HTN drugs, and 13 (33.3%) were freely combined, 26 (66.7%) in the SPC group; 34 (23.4%) applied 4 HTN drugs, 2 (5.9%) in the free combination, and 32 (94.1%) in SPC; 1 (0.7%) take 5 kinds of HTN drugs. Overall 74 (51.0%) cases take SPC, CCB in 99 (68.3%) cases, beta-blockers in 91 (62.8%) cases, and diuretics in 67 cases (46.2%). The A+D combination in SPC was 63 cases (43.4%). 36 cases (24.8%) were freely combined with A+C, A+B, or B+C. 106 (73.1%) patients taken ACEi/ARB. No significant difference of stay days between the discharged patients who met the standard and not met [(4.8±1.7) vs (5.1±2.2), P=0.61 W=2448.5]. When more kinds of drugs, the compliance rate is gradually decreasing. The compliance rate with one or two kinds of HTN drugs compared with four kinds of HTN drugs was significantly different (P1, 4=0.024 X2=5.64) (P2, 4=0.006 X2=8.73). Considering patients who were treated with 4 HTN drugs had higher blood pressure levels on admission [SBP1, 4 (175.9±21.4) vs (189.7±23.2) P=0.002 T=0.96], [SBP2, 4 (176.4±26.9) vs (189.7±23.2) P=0.02 T=2.89] mmHg. The compliance rate in SPC group 71 (38) and 70 (44) in the non-SPC group had no significant difference at the time of discharge (P=0.26 X2=1.26).

            CONCLUSIONS The compliance rate of patients with blood pressure at discharge was still low, early compliance and early benefits.

            GW33-e0384
            Value of monocyte/high-density lipoprotein cholesterol ratio in screening of early renal damage

            Wanyue Sang

            The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES This study aim to explore the association between MHR and early renal damage in young and middle-aged Chinese participants with hypertension (EH) and determine whether MHR can be a new screening indicator of hypertensive renal damage.

            METHODS Two hundred ninety-four eligible participants (age: 18–65 years) from northwest China were enrolled and divided into two groups according to the eGFR: a normal renal function group and a abnormal renal function group. Clinical and laboratory data as well as calculated MHR were collected.

            RESULTS MHR levels were significantly higher in abnormal renal function group (P<0.0001). Spearman rank correlation analysis showed negative correlation between the level of MHR and eGFR (r 2=0.1832, P<0.001). A multivariate logistic regression analysis of the data showed that elevated MHR was a risk factor for hypertensive renal damage (P<0.001). Finally, a cutoff value of MHR>0.37 measured in young and middle-aged Participants was associated with a specificity of 74.60% and a sensitivity of 84.3% for hypertensive early renal damage (area under the curve [AUC]: 0.819, 95% CI: 0.768, 0.870; P<0.0001).

            CONCLUSIONS MHR is associated with eGFR and has a high screening value in early renal damage in young and middle-aged Chinese Participants with essential hypertension.

            GW33-e0414
            Obstructive sleep apnea in middle-aged and elderly patients with hypertension

            Tao Wang

            Department of Cardiology, Zhongda Hospital, Southeast University

            OBJECTIVES This paper intended to explore the prevalence of obstructive sleep apnea (OSA) in middle-aged and elderly hypertension patients and the relationship between OSA and nocturnal blood pressure.

            METHODS Middle-aged and elderly hypertension patients were enrolled consecutively. All patients underwent portable overnight cardiorespiratory polygraphy and 24-hour ambulatory blood pressure monitor measurement on the same day. According to whether the nocturnal blood pressure drop rate was normal, the patients were divided into dippers and nondippers groups, and the clinical data of the two groups were compared.

            RESULTS The prevalence of OSA in middle-aged and elderly hypertension patients was 78.8%, and the prevalence of moderate-to-severe OSA was 43.8%. The proportion of moderate-to-severe OSA in nondippers was significantly higher than that in dippers (51.0 vs 32.3%, P=0.023). The 24-hour mean systolic blood pressure, nighttime mean systolic blood pressure, nighttime mean diastolic blood pressure, morning systolic blood pressure and morning diastolic blood pressure in nondippers were significantly higher than those in dippers (P<0.05). Logistic regression analysis showed that apnea-hypopnea index (AHI) was a risk factor for nondipping nocturnal blood pressure. The ROC curve showed that AHI had certain predictive value for the occurrence of nondipping nocturnal blood pressure, with AUC=0.620 (95% CI: 0.533–0.706, P=0.011).

            CONCLUSIONS Middle-aged and elderly hypertension patients have a high prevalence of OSA, especially moderate-to-severe OSA, which more likely to lead to abnormal nocturnal blood pressure drop rate, nocturnal hypertension and morning hypertension. AHI is a risk factor for nondipping nocturnal blood pressure and can predict the occurrence of nondipping nocturnal blood pressure to some extent.

            GW33-e0441
            Relationship between vascular ageing and left ventricular geometry in newly diagnosed primary aldosteronism

            Miao Huang, Jiaying Li, Xiaogang Li, Weihong Jiang

            Department of Cardiology, The Third Xiangya Hospital, Central South University

            OBJECTIVES Changes in left ventricular (LV) geometry is early manifestations of cardiac damage. The relationship between vascular aging and LV geometry has been reported. However, in primary aldosteronism (PA), with more severe target organ damage than essential hypertension, the relationship between vascular aging and LV geometry is unclear. The aim of our study was to investigate the association of vascular ageing parameter and LV geometry in newly diagnosed PA.

            METHODS We conducted a retrospective study among patients with newly diagnosed PA from January 1st 2017 to September 30th 2021 at the Third Xiangya Hospital. The data of vascular aging parameters were collected, including ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT). Echocardiography date were collected to assess LV geometry patterns.

            RESULTS A total of 146 patients with newly diagnosed PA were included. Mean age was 44.77±9.79 years and 46.58% participants were female. Linear regression analysis adjusting all potential confounders showed cIMT was significantly associated with LV mass index (LVMI) (β=44.240, P=0.001) and baPWV was significantly associated with relative wall thickness (RWT) (β=0.00005, P=0.025). Multifactorial adjusted logistic regression analysis demonstrated that cIMT was significantly associated with LV hypertrophy (LVH) (OR=7.421, 95% CI: 1.717–815.688, P=0.021) and baPWV was significantly associated with LV concentric geometry (LVCG) (OR=1.003, 95% CI: 1.001–1.006, P=0.017).

            CONCLUSIONS baPWV was significantly associated with LVCG and cIMT was significantly associated with LVH in newly diagnosed PA. This study provides insights on the importance of baPWV measurement and cIMT measurement in early assessment of cardiac damage in newly diagnosed PA.

            GW33-e0622
            Association between hypertension and metabolic associated fatty liver disease among U.S. adults

            Xiao Liang1,2, Haitao Huang1

            1Department of Cardiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, China

            2Guangdong Medical University, Zhanjiang, Guangdong 524001, China

            OBJECTIVES Data are limited on the association between hypertension and metabolic associated fatty liver disease (MAFLD). The aim of current study was to evaluate the association between hypertension and MAFLD in adults.

            METHODS This population-based cross-sectional study used data on U.S. adults aged 20 to 80 years from the National Health and Nutrition Examination Survey 2017–2018. Multivariable logistic regression analyses were performed to assess the relationship between hypertension and MAFLD.

            RESULTS Among 4658 (weighted N=209,971,629) adults included in this study (mean age, 46.6 years [95% CI, 45.5–47.6 years]; 2376[50.7%] female), 2100 (38.0%) had hypertension and 2558 (62.0%) did not have hypertension. A total of 2003 participants (42.2%) were classified as having MAFLD. Compared with participants without hypertension, those with hypertension had a higher prevalence of MAFLD (58.3[1107] vs 41.7%[993]). In a multivariable logistic regression model adjusted for age, sex, race/ethnicity, education level, marital status, family income to poverty, smoking status, alcohol consumption, leisure time physical activity, eGFR, BMI category, the history of metabolic syndrome, cardiovascular disease and diabetes, and current drug (anti-diabetes, anti-hyperlipidemic, anti-hypertension, and aspirin), hypertension was associated with MAFLD (odds ratio [OR], 1.67; 95% CI, 1.03–2.70). In subgroup analyses, hypertension was associated with MAFLD among male (OR, 2.10; 95% CI, 1.52–2.89), among those aged 20 to 59 years (OR, 1.68; 95% CI, 1.32–2.14), and among Non-Hispanic White (1.92; 95% CI, 1.47–2.51).

            CONCLUSIONS In this cross-sectional study, hypertension was associated with MAFLD in U.S. adult and the associations remained robust after adjusted for a variety of potential confounding.

            GW33-e0646
            Combined association of triglyceride-glucose index and intensive or standard blood pressure control with all-cause and cardiovascular mortality in the general population

            Yu Yu, Wei Hua

            Department of Cardiology, Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Triglyceride-glucose (TyG) index and uncontrolled blood pressure (BP) are risk factors for all-cause and cardiovascular mortality. However, the combined association of TyG index and different BP control targets with all-cause and cardiovascular mortality remains unclear.

            METHODS In this study, 6245 individuals were from the National Health and Nutrition Examination Survey (1999–2002). The study endpoints were all-cause and cardiovascular mortality. Systolic BP (SBP) was classified into three categories based on intensive BP control (<120 mmHg), ACC/AHA guidelines recommended BP control target (<130 mmHg), and standard BP control (<140 mmHg). Multivariate Cox proportional hazards regression models were used to explore the combined association of TyG index and different BP control targets with all-cause and cardiovascular mortality.

            RESULTS A total of 284 all-cause deaths (3.31/1000 person-years) and 61 cardiovascular deaths (0.66/1000 person-years) were recorded during a mean follow-up period of 66.8 months. Compared with the combined group with high TyG index and SBP ≥120 mmHg, the combined group with low TyG index and intensive BP control had a significantly lower risk of all-cause and cardiovascular mortality [all-cause mortality: adjusted hazard ratio (HR): 0.29, 95% confidence interval (CI) 0.18–0.46; cardiovascular mortality: adjusted HR: 0.16, 95% CI 0.05–0.46]. Similarly, the combined group with low TyG index and ACC/AHA guideline-recommended BP control had a significantly lower risk of all-cause and cardiovascular mortality compared with the other groups (all-cause mortality: adjusted HR: 0.36, 95% CI: 0.22–0.60; cardiovascular mortality: adjusted HR: 0.32, 95% CI: 0.13–0.77). However, the combined group with low TyG index and standard BP control did not differ from the other groups in terms of all-cause and cardiovascular mortality. Adding the TyG index and SBP to the established risk factors significantly improved the predictive value of all-cause and cardiovascular mortality.

            CONCLUSIONS The lower TyG index combined with intensive BP control or ACC/AHA guideline-recommended BP control was associated with a significantly reduced risk of all-cause and cardiovascular mortality.

            GW33-e0682
            High waist circumference increases the risk of new-onset hypertension: an integrated study

            Jin-Yu Sun, Wei Sun, Xiang-Qing Kong

            Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

            OBJECTIVES This study aims to investigate whether high waist circumference increases the risk of hypertension based on the nationwide US and China population.

            METHODS Multiple data sources were analyzed in this study, including the National Health and Nutrition Examination Survey (NHANES), China Health and Retirement Longitudinal Study (CHARLS), China Health and Nutrition Survey (CHNS), and Gene Expression Omnibus (GEO), and UK Biobank databases. This study used the TwoSampleMR package to estimate the casual link of waist circumference and BMI with the development of hypertension. GWAS summary data were acquired from the IEU GWAS database (https://gwas.mrcieu.ac.uk/)1, which integrates a curated database including a summary originated from thousands of GWAS summary datasets. Waist circumference (ukb-b-9405) was used as exposure, whereas hypertension (ukb-b-12493) was used as outcomes. The expression profile of GSE703532 and GSE1559603 were acquired from the GEO database. GSE70353 collected abdominal subcutaneous adipose tissue gene expression by the Affymetrix Human Genome U219 Array. We performed weighted gene co-expression network analysis (WGCNA) on the top 25% most variant genes by the ‘WGCNA’ package. GSE155960 recorded single-cell RNA sequencing on stromal vascular fraction. We analyzed single-cell RNA-seq data by the ‘Seurat’ package.

            RESULTS After a mean follow-up of 3.82 years, 2604 individuals (38.1%) developed hypertension. When analyzed as a continuous variable, waist circumference significantly contributed to hypertension in all three models with HRs of 1.38 (1.33–1.43), 1.29 (1.23–1.34), and 1.15 (1.09–1.22), respectively. Consistently, when analyzed as categories, the risk of new-onset hypertension increased with the elevated categories from Q1 to Q4. In the fully adjusted model, individuals in the highest waist circumference quartile (Q4) showed a 1.32-fold risk of hypertension compared with the lowest quartile (Q1). The results remained stable in the sensitivty ananlysis. The restricted cubic spline showed that the risk of hypertension increased with waist circumference. Mendelian randomization analysis found that the increased waist circumference could contribute the risk of hypertension. The enriched biological processes of the key module identified by the WGCNA were involved in Neutrophil activation, T cell activation, Lymphocyte proliferation, and so forth. A higher percentage of macrophage was observed in the obese group and the lean group. The top 20 biological processes were identified by the GO enrichment on the DEGs, including positive regulation of cell adhesion, extracellular matrix organization, regulation of cell-cell adhesion, and so forth. Among the many enriched KEGG pathways, PI3K-Akt signaling pathway showed the highest gene ratio. The cell communication analysis suggested a strong interaction between macrophages and T cells.

            CONCLUSIONS This study demonstrated high waist circumference is a risk factor for hypertension. We provided the expression profiles of abdominal subcutaneous adipose tissue based on array and single cell sequence.

            GW33-e0734
            Differences in risk factors for cardiovascular diseases in men and women in rotational shift work in the Arctic

            Nina Shurkevich1, Alexander Vetoshkin1,2, Ani Simonyan1, Lyidmila Gapon1, Maria Kareva1

            1Tyumen Cardiology Research Center, Branch of Tomsk National Research Medical Center of the Russian Academy of Sciences

            2Medical Unit “Gazprom dobycha Yamburg” LLC

            OBJECTIVES To study factors associated with the risk of cardiovascular diseases (CVD) in men (M) and women (F) in rotational shift work in the Arctic.

            METHODS In Yamburg polar settlement (68 N), 99 M and 81 F comparable in age (mean 48 years, 41.5; 58.5, P=0.441) and office systolic BP 149.4 mmHg (119.1; 180.2, P=0.250) were examined. Ultrasound examination of carotid arteries (CA) was performed; cardio-ankle vascular index (CAVI), pulse wave velocity (PWV) was studied. Ambulatory blood pressure monitoring (ABPM), EchoCG with calculation of heart failure with preserved ejection fraction (HFpEF) probability using H2FPEF score (Heavy; Hypertensive; Atrial Fibrillation; Pulmonary Hypertension; Elder; Filling Pressure) were carried out. Biochemical blood test was performed; such risk factors (RF) as smoking, overweight, physical activity (PA), perceived stress level were studied.

            RESULTS In M overweight (P=0.039), smoking (P=0.013), increased stress level (P<0.0001) were detected more frequently; atherosclerotic plaques (ASP) in CA were more often found in connection with increased CAVI (P=0.043) and PWV (P=0.012). Multivariate analysis in M revealed higher values of Peterson’s Ep (CA) elastic modulus (OR=1.003; 95% CI [1.001; 1.005], P=0.009); homocysteine (OR=1.191; 95% CI [1.067; 1.341], P=0.003), mean daily DBP24 (OR=1.136; 95% CI [1.044; 1.244], P=0.004); MMI (OR=1.038; 95% CI [1.014; 1.066], P=0.003) and lower HDL-C (OR=0.115; 95% CI [0.029; 0.392] P=0.001); hs-CRP (OR=0.894; 95% CI [0.815; 0.958], P=0.005); NT-proBNP (OR=0.989; 95% CI [0.982; 0.995], P=0.001). M and W did not differ significantly (P=0.303) in the risk of HFpEF development assessed by H2EPEF scale, which does not exclude differences in the mechanisms of LV remodeling and functional changes in M and F.

            CONCLUSIONS RF for CVD development in M are overweight, smoking, increased stress levels, homocysteine as a predictor of vascular damage, increased thickness and stiffness of the vascular wall with subsequent atherosclerotic remodeling and higher frequency of ASP detection in CA; in W - increased markers of systemic inflammation and neurohumoral activation, determining high risk of structural and functional disorders of LV myocardium. Differences in RF should be aimed at personalized prevention and early diagnosis of CVD in rotational shift work in the Arctic.

            GW33-e0735
            Factors associated with the risk of heart failure in asymptomatic patients with arterial hypertension in the conditions of rotational shift work in the Arctic

            Alexander Vetoshkin1,2, Nina Shurkevich1, Ani Simonyan1, Lyidmila Gapon1, Maria Kareva1

            1Tyumen Cardiology Research Center, Branch of Tomsk National Research Medical Center of the Russian Academy of Sciences

            2Medical Unit “Gazprom dobycha Yamburg” LLC

            OBJECTIVES To study factors associated with the risk of heart failure (HF) in asymptomatic patients with arterial hypertension (AH) in the conditions of rotational shift work in the Arctic.

            METHODS In Yamburg polar settlement (68 N) 100 males (M) and 80 females (F) with grade 1–2 AH and normotensive individuals were examined. EchoCG was performed. The H2FPEF (Heavy; Hypertensive; Atrial Fibrillation; Pulmonary Hypertension; Elder; Filling Pressure) scale was used to calculate the probability of HF with preserved ejection fraction (HFpEF). A treadmill test was carried out according to the Bruce method.

            RESULTS Group 1 (gr.1) included 95 M and F patients with zero HF probability (the sum of H2EPEF scores from 0 to 1 points), group 2 (gr.2) - 85 persons of both sexes with an intermediate HF probability (the sum of H2EPEF points from 2 to 5). Patients of gr.2 were older (P=0.038), worked longer in rotational shifts (P=0.0143), had higher ambulatory SBP (P=0.0001) and DBP (P=0.0013) associated with greater body mass index (BMI) (P=0.0001). Based on odds ratio (OR) analysis, the factor that most influenced on intermediate HF probability in patients was the Quetelet index (OR=1.261, 95% CI 1.140; 1.393). In the logistic regression model, the appearance of dyspnea during the treadmill test occupied a leading position (OR 0.113, 95% CI 0.044; 0.292, P<0.0001). The value of the inotropic reserve (OR 1.020, 95% CI 1.006; 1.035, P=0.005). Analysis of EchoCG revealed in gr.2 significant differences in LVMM and LVMMI (P=0.0002 and P=0.072, respectively), LV internal area (P=0.0002), isovolumic relaxation time (P=0.003) and E/Em lat. ratio (P=0.0001) indicating signs of LV diastolic dysfunction.

            CONCLUSIONS The factors associated with the risk of HFpEF at an early stage with an intermediate HF probability according to the H2FPEF scale in asymptomatic patients with AH are BMI, duration of rotational shift work, dyspnea and increased inotropic reserve during physical activity, decreased adaptive potential and impaired LV diastolic dysfunction. Identified factors associated with the risk of HF, including asymptomatic LV diastolic dysfunction, can be included in the definition of the initial stage of HF, which refers to individuals at risk of developing symptomatic HF. Initiation of management strategies targeting identified risk factors in patients with asymptomatic HF may slow symptomatic disease progression in rotational shift workers in the Arctic region.

            GW33-e0780
            Insight on efficacy of renal artery denervation for refractory hypertension with chronic renal failure: a long-term study outcome

            Zhoufei Fang

            The First Affiliated Hospital of Fujian Medical University

            OBJECTIVES To explore the long-term safety and efficacy of renal denervation in patients with RHT and CKD, a post hoc analysis of eGFR subgroups was completed.

            METHODS Fifty-four patients with uncontrolled hypertension associated with sympathetic nervous system activation underwent RDN and were included in the study. The patients were divided into three groups according to eGFR: eGFR 46–90 mL/min group, eGFR 15–45 mL/min group and eGFR<15 mL/min group. The planned follow-up period is 48 months to assess office blood pressure, renal function, type of antihypertensive medication, and RDN complications.

            RESULTS The ablation sites of GFR 46–90 mL/min group and GFR 15–45 mL/min group were 32.57±2.99 mmHg and 29.53±5.47, respectively. No complications occurred in the GFR 46–90 mL/min group. The GFR<15 mL/min group was treated with 27.07±5.59 mmHg ablation. Renal artery dissection occurred in each group of GFR 15–45 mL/min and GFR<15 mL/min. And renal stent implantation artery was performed on these two patients. No severe renal artery stenosis occurred. There were no significant differences in Scr and eGFR between the three groups at each follow-up point. Compared with baseline, the SBP was significantly of each group decreased to varying degrees at each follow-up time point. SBP decreased most in GFR 46–90 mL/min group. Compared with baseline, the type of antihypertensive drugs used in GFR 46–90 mL/min group decreased significantly except for 36 and 48 months. The type of antihypertensive drugs used in GFR 15–45 mL/min group decreased significantly at 48 months’ post-enrolment. The types of antihypertensive drugs taken by the GFR<15 mL/min group did not decrease significantly.

            CONCLUSIONS RDN can safely reduce SBP in CKD patients combined with RHT for 48 months, with the most significant reduction in GFR 15–45 mL/min group. The type of antihypertensive drugs was significantly decreased after RDN. This was especially pronounced in patients with GFR 15–45 mL/min.

            ARRHYTHMIAS
            GW33-e0011
            Assessing the mC2HEST score as a pragmatic risk prediction model for incident atrial fibrillation: Insights from the Multi-Ethnic Study of Atherosclerosis (MESA)

            Yan-Guang Li, M.D1, Jin Bai1, Philip Greenland, M.D.2, Gregory Y. H. Lip, M.D.3, Shu-Wang Liu, M.D.1, Yi-Da Tang, M.D.1

            1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, China

            2Department of Preventive Medicine, Feinberg School of Medicine, Northwest University, Chicago, USA

            3Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart & Chest Hospital, Liverpool, United Kingdom

            Conflicts of interests

            None directly related to this paper.

            BACKGROUND The comparative performance of the mC2HEST (Coronary artery disease/Chronic obstructive pulmonary disease, Hypertension, Elderly [65–74: 1 point; over 75: 2 points], Systolic and diastolic heart failure [2 points], Thyroidism) scores with other published comprehensive (CHARGE-AF, Framingham and ARIC scores) and simple (C2HEST, CHA2DS2-VASc, HATCH and HAVOC scores) risk scores for incident AF have never been evaluated, especially in a multiethnic population cohort.

            METHODS The Multi-Ethnic Study of Atherosclerosis (MESA) was designed for observing the progression of subclinical cardiovascular situations into overt cardiovascular diseases, involving more than 6000 men and women aged between 45–84 from six communities in the United States. The performance of the various risk score models (CHA2DS2-VASc, HATCH and HAVOC scores) were compared for predicting incident AF.

            RESULTS A total of 4524 subjects (aged 60.2±9.5 years) were enrolled with 565 developed AF during 13.6±2.5 years of follow-up, with an incidence of 0.93%/y. The mC2HEST score has modest predictive accuracy at 5-year (c-index of 0.697), 10-year (0.727) and 15-year (0.773) follow-up time points. Positive net reclassification indexes and integrated discriminative improvement were evident for the mC2HEST score compared with other simple scores. Optimal calibration was seen in the mC2HEST score (PHosmer-Lemeshow=0.413), while the comprehensive models did not show good calibration (PHosmer-Lemeshow: CHARGE-AF=0.001, Framingham=0.037 and ARIC=0.008). The risk of incident AF increased with higher mC2HEST score points and risk-groups (Log-rank P<0.0001). The mC2HEST score showed moderate capability in identifying a real high-risk population for developing incident AF.

            CONCLUSIONS In the MESA cohort, the mC2HEST score could be used as a simple, practical model, allowing a swift and on-site evaluation of individuals’ risk of incident AF.

            GW33-e0036
            Influence of obesity on atrial fibrillation incident in patients with heart failure with preserved ejection fraction: obesity paradox remained?

            Xinyi Huang1,2, Xiao Liu1, Yuling Zhang3, Jingfeng Wang4

            1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou 510120, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, China

            2Department of Cardiology (W.M., Z.C., X.Z., D.M., J.P., X.Z., G.W.), The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, People’s Republic of China

            3Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: zzhangyuling@126.com

            4Department of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China; Guangzhou Key Laboratory of Molecular Mechanism and Translation in Major Cardiovascular Disease, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: wjingf@mail.sysu.edu.cn

            OBJECTIVES There exists argument for “obesity paradox” in heart failure with preserved ejection fraction (HFpEF). However, the influence of obesity on atrial fibrillation (AF) incident in patients with HFpEF is unclear.

            METHODS We included 2138 subjects with HFpEF from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Kaplan-Meier curves and Cox regression with hazard ratios (HRs) and confidence intervals (CIs) were used to assess the incidence of AF with and without obesity. Obesity is defined as body mass index (BMI) ≥30 kg/m2. We also performed a sensitive analysis by using competing risk regression to confirm the relationship with different BMI groups and AF, death was defined as competing events. Overweight (BMI from 25.0 to 29.9 kg/m2) had the lowest BMI incidence, thus we set the overweight group as the reference.

            RESULTS Of 2138 patients with HFpEF without baseline AF, there are 1165 obese, 708 overweight and 265 normal weight. With a median follow up of 3.3±1.7 years, 103 patients developed new on-set AF. The incident rate of AF in patients with obesity, overweight and normal weight was 1.79, 1.01 and 1.19 per 100 person-years, respectively. Group with obesity experienced the higher new on-set AF incidence than those with overweight (log-rank test=0.035) compared with the overweight in HFpEF, with no significant association with normal BMI (18.5–24.9 kg/m2). In the cox regression analysis, the positive association remained in HFpEF with obesity (adjusted HR: 1.68; 95% CI: 1.04–2.71, P=0.034) after adjustment for age, sex, current smoking, eGFR, ethnicity, alcohol intake, NYHA class, spironolactone randomization, history of DM, PCI, hypertension, thyroid diseases and usage of aspirin. When BMI was analyzed as a continuous variable, the occurrence of AF increases by 3% every kg/m2 increase (HR: 1.03; 95% CI: 1.00–1.06, P=0.04) after adjustments. Sensitivity analysis by competing risk model and subgroups analysis generated consistent results, either BMI was analyzed as category or continuous variable.

            CONCLUSIONS Obesity increases the risk of new on-set AF in patients with HFpEF. “Obesity Paradox” for AF did not remain in patients with HFpEF.

            GW33-e0052
            The long-term outcomes of ablation with vein of Marshall ethanol infusion versus ablation alone in patients with atrial fibrillation: a meta-analysis

            Feng Li, Jin-Yu Sun, Li-Da Wu, Lei Zhang, Qiang Qu, Chao Wang, Ling-Ling Qian, Ru-Xing Wang

            Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China

            OBJECTIVES The long-term outcomes of ablation with vein of Marshall ethanol infusion (VOM-ABL) compared with ablation alone in patients with atrial fibrillation (AF) remains elusive. We aimed to explore whether VOM-ABL showed better long-term benefits and screen the potential determinants of outcome impact of VOM-ABL procedure.

            METHODS PubMed, Cochrane Library, Web of Science, and Embase were searched up to 1 September 2021. Studies comparing the long-term (one-year or longer) outcomes between VOM-ABL and ablation alone were included. Subgroup analysis identified potential determinants for VOM-ABL procedure.

            RESULTS Compared with ablation alone, VOM-ABL was associated with a significantly higher rate of long-term freedom from AF/atrial tachycardia (AT) (risk ratio [RR], 1.28; 95% confidence interval [CI], 1.12–1.47; P=0.00), and successful mitral isthmus (MI) block (RR 1.52; 95% CI, 1.16–1.99; P=0.00); whereas, no significant difference in pericardial effusion, stroke/transient ischemic attack (TIA), and all-cause death. Subgroup analysis identified two significant treatment-covariate interactions: one was ablation strategy subgroup (PVI+; RR 1.41; 95% CI, 1.27–1.56 vs PVI; RR 1.05; 95% CI, 0.92–1.19, P=0.00 for interaction) for freedom from AF/AT, while the other was VOM-ABL group sample size subgroup (≥100; RR 1.98; 95% CI, 1.24–3.17 vs <100; RR 1.20; 95% CI, 1.10–1.30, P=0.04 for interaction) for MI block.

            CONCLUSIONS This meta-analysis demonstrates that VOM-ABL has superior efficacy and comparable safety over ablation alone in AF patients with long-term follow-up. Moreover, PVI+ and VOM-ABL group sample size ≥100 may be associated with a great impact on freedom from AF/AT and MI block, respectively.

            GW33-e0106
            Utility of provocative tests in the diagnosis and genotyping of congenital long QT syndrome: a systematic review and meta-analysis

            Tingting Lv1, Ying Yang2, Siyuan Li1, Peng Liu2, Qinggele Gao2, Ping Zhang1,2

            1Department of Cardiology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University

            2School of Clinical Medicine, Tsinghua University

            OBJECTIVES Diagnosis is particularly challenging in concealed or asymptomatic long QT syndrome (LQTS). Provocative testing, unmasking the characterization of LQTS, is a promising alternative method for the diagnosis of LQTS, but without uniform standards.

            METHODS A comprehensive search was conducted in PubMed, Embase and the Cochrane Library through Oct. 14, 2021. Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was used for all data analyses. A fixed-effects model was used to pool data and differences of QTc between groups were expressed as mean difference (MD) with a 95% confidence interval (CI).

            RESULTS A total of 22 studies with 1137 LQTS patients were included in our study. At baseline, QTc interval was 40 ms longer in LQTS patients than in control (MD 40.54, 95% CI 37.43–43.65, P<0.001). Compared to control group, LQTS patients had 28 ms longer ΔQTc upon standing (MD 28.82, 95% CI 23.05–34.58, P<0.001), nearly 30 ms longer both at peak exercise (MD 27.31, 95% CI 21.51–33.11, P<0.001) and recovery 4–5 min (MD 29.85, 95% CI 24.36–35.35, P<0.001). With epinephrine infusion, QTc interval was prolonged both in control and LQTS patients, most obviously in LQT1 (MD 68.26, 95% CI 58.91–77.60, P<0.001) and LQT2 (MD 60.17, 95% CI 50.18–70.16, P<0.001). Subgroup analysis showed QTc interval response to abrupt stand testing and exercise testing varied between LQT1, LQT2 and LQT3, named Type I, Type II and Type III.

            CONCLUSIONS QTc trend Type I and Type III during abrupt stand test and exercise test can be used to propose a prospective evaluation of LQT1 and LQT3, respectively. Type II QTc trend combined epinephrine infusion test could distinguish LQT2 from control. A preliminary diagnostic workflow was proposed but deserves further evaluation.

            GW33-e0117
            Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy

            Chang Cui1, Xiaokai Zhou2, Weizhu Ju1, Hongwu Chen1, Kai Gu1, Mingfang Li1, Minglong Chen1

            1Division of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

            2Department of Pain Management, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

            OBJECTIVES The sympathetic nervous system plays a key role in both initiation and persistence of ventricular arrhythmias (VA). This study sought to describe our institutional experience with providing repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM).

            METHODS This study included 8 consecutive patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021, and January 31, 2022. Lidocaine (10 mL, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data were collected for patient clinical characteristics, immediate and long-term outcomes, and procedure related complications.

            RESULTS Totally, five patients with dilated cardiomyopathy, two patients with arrhythmogenic right ventricular cardiomyopathy and one patient with hypertrophic cardiomyopathy were enrolled. Clinical characteristics included age, 51.5±13.6 years; men, 100%; and left ventricular ejection fraction, 37.8±6.6%. After the treatment of R-SGB, 75% of patients were free of electrical storm. Twenty-four hour Holter monitoring showed a significant 97% reduction in ventricular tachycardia (VT) episodes from 43±17.75 vs. 1±0.75 after R-SGB (P<0.01). There were no procedure-related major complications. The mean follow-up was 4.7±1.2 months, and the median time to recurrent VT was 60 days.

            CONCLUSIONS Minimally invasive R-SGB was a safe and effective method to attenuate electrical storm in patients with NICM. Half of patients were free of VT episode in 2 months. Hence R-SGB could serve as bridge therapy to stabilize ventricular rhythm in patients with VT storm.

            GW33-e0131
            The effect of mexiletine in patients with type 2 long QT syndrome

            Ying Yang

            School of Clinical Medicine, Tsinghua University

            OBJECTIVES Long QT syndrome (LQTS) is caused by gene mutations encoding cardiac ion channels or ion channel regulatory proteins, resulting in prolonged cardiac repolarization and prolonged QT/QTc interval on electrocardiogram. Currently, β-blockers are recommended as first-line therapy for LQTS. As a gene-specific therapy, mexiletine has been proven efficacy in LQT3 patients, but its role in LQT2 patients remains controversial.

            METHODS Patients admitted to the Department of Cardiology of Beijing Tsinghua Changgung Hospital, which met the diagnostic criteria of LQTS, and were treated with mexiletine. Genetic testing has been completed, and The American College of Medical Genetics and Gemonics (ACMG) has been assessed. The pathogenicity as pathogenic or possibly pathogenic mutation. Exclude acquired LQTS due to electrolyte disturbances, medications, and other factors.

            RESULTS In our center, 14 patients from 12 families have been treated with mexiletine. All 14 patients had a history of syncope, and 1 patient was complicated with deafness. 11 patients were female, with mean age of 23.5±17.2 years and a mean QTc of 551 (509–569) ms. The baseline QTc interval of 1 patient was not available, and the baseline QTc interval of the other 13 patients was greater than 500 ms, with an average of 551 (509–569) ms. Of the 14 patients, 9 had a family history of LQTS and 11 had a family history of sudden death. LQTS classification showed 9 cases with LQT2, 2 cases with LQT3, LQT5, LQT7 and JLNS both with 1 case. β-blockers were used in 10 patients. In 9 LQT2 patients, the QTc intervals was 551 (524–600) ms before mexiletine, and shortened to 503 (474–520) ms after mexiletine, with an average shortening of 62.4±52.4 ms (P<0.05).

            CONCLUSIONS Although, in current guidelines, mexiletine has been recommended as a gene-specific therapy in LQT3 patients, our experience confirmed that mexiletine also shortens the QTc significantly in most LQT2 patients.

            GW33-e0163
            Heart rate variability as a predictor of sustained ventricular tachycardia in patients with arrhythmogenic cardiomyopathy

            Baowei Zhang1, Chunjiang Zhou1, Jiaxi Xie2, Yizhang Wu1, Xin Xie1, Xiaorong Li1, Jinbo Yu1, Aibin Tao3, Bing Yang1

            1Shanghai East Hospital, Tongji University School of Medicine

            2The First Affiliated Hospital of Nanjing Medical University

            3The Affiliated People’s Hospital of Jiangsu University

            OBJECTIVES Arrhythmogenic cardiomyopathy (ACM) is an inherent cardiomyopathy with high risk of ventricular arrhythmias (VAs). Cardiac sympathetic nerve system (SNS) might play important roles in arrhythmogenesis of ACM. This study aims to assess the activity of cardiac ANS in ACM patients by heart rate variability (HRV), and to investigate its value in risk stratification for VAs.

            METHODS A total of 88 ACM patients and 65 sex- and age- matched healthy participants were enrolled. The time domain measures, which were calculated based on statistical and mathematical analysis on RR intervals, were used to evaluate the HRV.

            RESULTS Patients in the ACM group had comparable age (41.8±12.9 vs 42.0±15.1 years old) and proportion of male (76.1 vs 64.6%) to those in the HC group. In addition, there were similar comorbidities between ACM and HC groups. As variables reflected greater sympathetic nervous contribution to HRV, the levels of SDNN and SDANN were significantly lower in ACM group compared with those in HC group (115.97±32.83 vs 155.03±35.57 ms, P<0.001 for SDNN; 98.08±31.28 vs 139.92±35.47 ms, P<0.001 for SDANN). There were also decreased levels of rMSSD (32.90±14.72 vs 36.63±13.10, P=0.02) and pNN50 (10.41±9.64 vs 14.62±10.63%, P=0.004) in the ACM group. To investigate the role of HRV in risk stratification of sVT in patients with ACM, patients with ACM were divided into sVT group (52 patients) and non-sVT group (36 patients) according to the presence of sVT in their history. Comparing the HRV variables between sVT group and non-sVT group showed that the levels of SDNN and SDANN in patients with sVT were lower significantly than those in patients without sVT (105.0±28.1 vs 131.8±33.1 ms, P<0.001 for SDNN; 88.4±25.7 vs 112.1±33.6 ms, P<0.001 for SDANN). However, the difference of neither rMSSD nor pNN50 was significant between the two groups (31.5±14.7 vs 34.9±14.7, P=0.17 for rMSSD; 9.1±8.3 vs 12.3±11.2%, P=0.13 for pNN50). Multivariate logistic regression analysis showed SDNN was independently associated with sVT in ACM patients (odds ratio [OR] 0.59, 95% confidence interval [CI] [0.45–0.78], P<0.001). Receiver operating characteristics curve demonstrated SDNN had clinical values in differentiating ACM patients with sVT from those without sVT (aera under the curve [AUC]=0.73, 95% CI 0.63–0.84, P<0.001). The cutoff value of the SDNN level for predicting sVT in ACM patients was 126.5 ms based on the optimal balance between sensitivity and specificity. The level of SDNN<126.5 ms predicted sVT with 76.9% sensitivity and 66.7% specificity. The positive and negative predictive value for sVT in ACM patients were also 76.9 and 66.7%, respectively.

            CONCLUSIONS The present study suggests that HRV is impaired in patients with ACM, and the impaired HRV is independently associated with the ventricular arrhythmogenesis. In addition, the SDNN level has a moderate value in risk stratification for VAs in ACM patients.

            GW33-e0252
            Left bundle branch area pacing combined with atrioventricular node ablation in persistent atrial fibrillation patients with heart failure

            Mengna Chen, Yimin Zhang, Zhiqin Guo, Haiju Liu, Xiaozhen Ge, Wenbin Fan, Xu Zhang, Shuo Wang, Junmeng Zhang

            Department of Cardiology, Heart Center, The First Hospital of Tsinghua University

            OBJECTIVES Biventricular pacing (BVP) combined with atrioventricular node ablation (AVNA) is the traditional treatment strategy for persistent atrial fibrillation patients with heart failure, whose ventricular rate is not well controlled and catheter ablation is not appropriate. Left bundle branch area pacing (LBBaP) is one of the physiological pacing methods proposed in recent years; Studies have shown that it is similar to biventricular pacing and can also achieve cardiac resynchronization.

            METHODS Six patients with heart failure and persistent atrial fibrillation were included in this study, and the duration of atrial fibrillation was greater than 12 months. The average age of the patients was 60.8±14.9 years, 2 cases were ischemic cardiomyopathy and 4 cases were dilated cardiomyopathy. After optimized drug therapy, the ventricular rate of atrial fibrillation was not well controlled, and they were admitted to hospital for worsening heart failure. All 6 patients received LBBaP combined with atrioventricular node ablation, and the average follow-up was 3 months after operation. The changes of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, NYHA class, and 6-minute walking distance were compared before and after operation.

            RESULTS The results showed that the LVEF of 6 patients at 3 months after operation was significantly improved compared with the baseline (24.6±5.4% vs 47.8±12.6%, P<0.05); the NYHA classification was significantly improved (baseline 1.4±0.5 vs post operation 2.6±0.5, P<0.05); the 6-minute walking distance was significantly increased (baseline 138.8±51.9 m vs post operation 650.0±53.4 m, P<0.05); the left ventricular end-diastolic diameter at 3 months after surgery decreased compared with the baseline (post operation 67.0±7.4 mm vs baseline 56.6±7.5 mm, P=0.059), but the difference was not statistically significant; no patient was hospitalized for heart failure during the follow-up period.

            CONCLUSIONS For long-term persistent atrial fibrillation patients with heart failure, LBBaP combined with AVNA can improve left ventricular ejection fraction, increase the 6-minute walking distance, reduced left ventricular remodeling, and improve the prognosis of such patients.

            GW33-e0293
            Identifying optimal metrics of atrial fibrillation burden for the risk stratification in acute myocardial infarction patients developing new-onset atrial fibrillation

            Jiachen Luo

            Shanghai Tenth People’s Hospital

            OBJECTIVES The optimal metrics of new-onset atrial fibrillation (NOAF) burden in acute myocardial infarction (AMI) individuals have not been evaluated. We aimed to assess the relation between post-MI NOAF burden metrics and major adverse cardiac events (MACEs) and to determine which one added most to the predictive power of the Global Registry of Acute Coronary Events (GRACE) score.

            METHODS The post-MI NOAF burden metrics including longest NOAF duration, total NOAF duration, and NOAF proportion (percentage of time in NOAF) were collected from the NOAFCAMI-SH registry. All-cause death and heart failure hospitalization were recorded as MACEs. Time-dependent ROC analyses were used to explore the discriminative ability of prediction models. The continuous net reclassification index (cNRI) and integrated discrimination improvement (IDI) were also calculated to evaluate the added value of NOAF burden metric on top of the GRACE score.

            RESULTS A total of 278 patients (mean age: 74.3±10.5 years, 66.9% man) with post-MI NOAF were included. MACEs occurred in 146 patients (52.5%) during a median follow-up of 30.6 (IQR: 18.4–45.2) months. Multivariable Cox regression analyses showed that it was the NOAF proportion (hazard ratio for per 1 SD increment: 1.306, 95% confidence interval [CI]: 1.115–1.528, P=0.001) rather than the longest and total NOAF durations that was an independent predictor of MACEs. Comparison of predictive performance demonstrated that adding NOAF proportion, but not NOAF durations, to the GRACE score significantly improve its reclassification ability, as evidenced by continuous net reclassification indexes and 95% CIs of 0.202 (0.089–0.294), 0.223 (0.086–0.336), and 0.214 (0.068–0.329); integrated discrimination improvements and 95% CIs of 0.030 (0.006–0.058), 0.034 (0.008–0.060), and 0.032 (0.004–0.066), at 1-, 2-, and 3-year follow-up, respectively.

            CONCLUSIONS Post-MI NOAF burden measured by NOAF proportion has the greatest prognostic impact and may add to risk stratification beyond the GRACE score.

            GW33-e0369
            Role of skin nerve activity in transesophageal atrial pacing of paroxysmal supraventricular tachycardia

            Jiaxin Wang1, Liuyu Xu1, Zhengqiang Chen1, Jia Zeng1, Mingge Zhao1, Huiling Tao1, Bin Li1, Mbabazi Nadine2, Mingyu Shi3, Dechun Yin1

            1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

            2Department of Cardiology, King Faisal Hospital, Kigali, Rwanda

            3Department of Cardiac Electrophysiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

            OBJECTIVES Paroxysmal supraventricular tachycardia (PSVT) is one of the most common cardiac emergencies seen in clinic. The functional status of cardiac autonomic nervous system is closely related to the occurrence and progression of PSVT. PSVT occurs under a specific threshold of autonomic nervous tension, and autonomic nervous activity is closely related to cardiac refractory period and cardiac conduction function. Transesophageal atrial pacing can make a non-invasive diagnosis of PSVT. If we can quantify the onset window of autonomic nervous activity of PSVT, we can detect and regulate the functional status of autonomic nervous system in advance, and reduce or terminate the occurrence of PSVT. neuECG is a non-invasive method to simultaneously measure skin sympathetic nerve activity (SKNA) and electrocardiogram (ECG). The purpose of this study was to quantify the onset window of autonomic nervous activity of PSVT by neuECG during transesophageal atrial pacing in PSVT patients, as well as to provide a new intervention strategy for the treatment of PSVT.

            METHODS A total of 60 palpitation patients and 10 healthy people were enrolled in this study. According to the results of transesophageal atrial pacing, palpitation patients were divided into PSVT group (30 cases) and non-PSVT group (30 cases). NeuECG was recorded by non-invasive SKNA recorder ME6000. The baseline data, SKNA data and ECG data of all patients were collected, and the differences and correlations of SKNA, heart rate, electrocardiogram indexes and atrioventricular node effective refractory period were compared in each group.

            RESULTS NeuECG was correlated with the acceleration of heart rate. SKNA and heart rate increased sharply during esophageal electrode intubation. In non-PSVT group, SKNA increased significantly when transesophageal atrial pacing, which was positively correlated with heart rate. After atropine administration, the SKNA increased, presenting a temporary peak, and then heart rate increased. SKNA was significantly enhanced and heart rate was accelerated in PSVT group at the onset of PSVT. The baseline of SKNA in PSVT group was significantly higher than that in non-PSVT group and healthy subjects, and the difference was statistically significant (P<0.05). The increase of SKNA increased heart rate and shortened QT interval and Tp-Te interval. Correlation analysis showed that integrated SKNA was negatively correlated with QT interval, but positively correlated with QTc interval (P<0.05). SKNA was still higher than baseline at the end of transesophageal atrial pacing and atrioventricular node refractory period was shortened after atropine administration.

            CONCLUSIONS The baseline of SKNA in PSVT group was higher than that in non-PSVT group and healthy people. SKNA at the onset of PSVT is higher than baseline, suggesting that quantification of the onset window of PSVT by neuECG can provide a new strategy for the diagnosis and treatment of PSVT.

            GW33-e0419
            Latest incidence and electrocardiographic predictors of atrial fibrillation: a prospective study from China

            Yong Wei

            Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

            OBJECTIVES China bears the biggest atrial fibrillation (AF) burden in the world. However, little is known about the incidence and precursors of AF. This study aimed to investigate the current incidence of AF and its electrocardiographic predictors in general community individuals aged over 60 years in China.

            METHODS This was a prospective cohort study, recruiting a consecutive series of subjects who underwent annual health checkups from 2015 to 2019 in four community health centers in Songjiang Area, Shanghai, China.

            RESULTS Of 18,738 subjects, AF developed in 351 (1.87%). The overall incidence rate of AF was 5.2/1000 person-years during an observation period of 67,704 person-years. Multivariate cox regression indicated age [hazard ratios (HR)=1.07, 95% confidence intervals (CI): 1.06–1.09, P<0.001], male sex (HR=1.29, 95% CI: 1.04–1.61, P=0.023), previous hypertension (HR=1.57, 95% CI: 1.25–1.97, P<0.001), a history of cardiac diseases (HR: 3.21, 95% CI: 2.33–4.44, P<0.001), atrial premature complex (APC) (HR=2.80, 95% CI: 2.15–3.66, P<0.001), atrial flutter (HR=19.36, 95% CI: 7.63–49.09, P<0.001), junctional premature complex (JPC) (HR=3.60, 95% CI: 1.60–8.09, P=0.002), junctional rhythm (HR=17.21, 95% CI: 5.38–55.08, P<0.001), ventricular premature complex (VPC) (HR=1.72, 95% CI: 1.09–2.69, P=0.019), short PR interval (HR=5.55, 95% CI: 1.37–22.42, P=0.016), second-degree atrioventricular block (AVB) Mobitz type I (HR=10.02, 95% CI: 1.35–74.18, P=0.024), second-degree AVB Mobitz type II (HR=89.26, 95% CI: 11.57–688.87, P<0.001), right atrial enlargement (HR=6.22, 95% CI: 1.54–25.17, P=0.010) and pacing rhythm (HR=3.68, 95% CI: 1.40–9.66, P=0.008) were independently associated with the incidence of AF.

            CONCLUSIONS The present incidence of AF was 5.2/1000 person-years in the studied population aged over 60 years in China. Among various ECG abnormalities, only APC, atrial flutter, JPC, junctional rhythm, short PR interval, second-degree AVB Mobitz type I, second-degree AVB Mobitz type II, VPC, right atrial enlargement and pacing rhythm were independently associated with AF incidence.

            GW33-e0420
            Contemporary survival and anticoagulation of patients with atrial fibrillation: a community based cohort study in China

            Yong Wei, Shaowen Liu

            Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

            OBJECTIVES The understanding of death in patients with atrial fibrillation (AF) in China is limited. This study aimed to assess the contemporary survival of AF patients in China and to explore risk factors for deaths.

            METHODS This was a prospective community-based cohort study including 559 AF patients, who were followed-up from July 2015 to December 2020.

            RESULTS During 66-month follow-up, there were 200 deaths (56.5% cardiovascular, 40.0% non-cardiovascular, and 3.5% unknown causes) among 559 AF patients with the median age of 76 years. The top three causes of death were heart failure (33.0%), ischemic stroke (17.0%) and cancer (16.5%). Multivariate Cox regression analysis indicated baseline variables positively associated with all-cause death were age (HR: 1.10, 95% CI: 1.08–1.13), AF subtype (HR: 1.37, 95% CI: 1.08–1.73), prior myocardial infarction (HR: 3.40, 95% CI: 1.48–7.78), previous tumor (HR: 2.61, 95% CI: 1.37–4.98), hypoglycemic therapy at baseline (HR: 1.81, 95% CI: 1.13–2.91), but body weight (HR: 0.98, 95% CI: 0.97–1.00) and use of calcium channel blocker (CCB) (HR: 0.62, 95% CI: 0.41–0.95) played a protective role to all-cause death. Of patients who were alive at the end of follow-up, 24.0% were on oral anticoagulants (OAC) alone, 4.5% on dual antithrombotic therapy, 33.1% on antiplatelet agents alone and 38.4% weren’t on any antithrombotic medication.

            CONCLUSIONS Ischemic stroke still remains one of the leading causes of death and OAC is seriously underused in AF patients in China. Independent risk factors for death are age, AF subtype, previous tumor, prior myocardial infarction, hypoglycemic therapy, low body weight and no CCB use.

            GW33-e0421
            Pattern of atrial fibrillation is associated with cancer death

            Yong Wei, Shaowen Liu

            Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

            OBJECTIVES Limited data are available on the association between atrial fibrillation (AF) and cancer. This study aimed to investigate the association between patterns of AF and cancer mortality.

            METHODS This is a community-based cohort study including 559 AF patients aged over 60 years old with a 66-month follow-up.

            RESULTS AF was paroxysmal in 18.4% (n=103), persistent in 61.2% (n=342) and permanent in 20.4% (n=114) of the 559 AF patients with the median age of 76 (70–81) years. A total of 33 cancer deaths were adjudicated. The majority of cancer deaths were attributed to digestive tumors (accounting for 54.5%) and respiratory tumors (accounting for 24.2%). With the follow-up of 2562 patient-years, cancer mortality was 1.29 per 100 person-years (%/P-Y) regardless of AF patterns. The rates of cancer mortality were 0.79%/P-Y for paroxysmal AF, 0.96%/P-Y for persistent AF and 2.80%/P-Y for permanent AF, showing permanent AF was associated with higher risk of cancer mortality compared with paroxysmal AF and persistent AF (P=0.004). Multivariate Cox regression analysis indicated baseline variables independently associated with cancer death were AF pattern (HR: 1.62, 95% CI: 1.10–2.38), age (HR: 1.12, 95% CI: 1.08–1.16), diabetes mellitus (HR: 2.06, 95% CI: 1.16–3.67), symptom pattern of AF (HR: 1.41, 95% CI: 1.01–1.99), previous tumor (HR: 5.04, 95% CI: 2.28–11.15), and liver disease (HR: 5.57, 95% CI: 1.99–15.58).

            CONCLUSIONS Permanent AF conferred higher risk of cancer death than paroxysmal AF and persistent AF. AF pattern was independently associated with cancer mortality.

            GW33-e0426
            Characteristics and ablation outcomes of atrial tachycardias in patients with prior cardiac surgery or with spontaneous scars: where are the differences?

            Sainan Li, Ming Liang, Zulu Wang

            General Hospital of Northern Theater Command

            OBJECTIVES Myocardial scar is usually found in patients after invasive procedure, such as cardiac surgery and catheter ablation, while it is also observed in some patients without prior invasive procedure, which is thought spontaneous scar. Atrial scars can be related to atrial tachycardia (AT), but whether the incisional scars caused by prior cardiac surgery (PCS) and spontaneous scars (SS) play the same roles in arrhythmia mechanisms has not been clearly clarified. This study was to analyze the characteristics, mechanisms and ablation outcomes of ATs in patients with PCS and patients with SS.

            METHODS Forty-six patients with PCS and 18 patients with SS who underwent catheter ablation for right atrial AT from September 2013 to April 2019 in General Hospital of Northern Theater Command were retrospectively reviewed. Baseline information, recordings of electrophysiological study and radiofrequency ablation, and acute and long-term ablation outcomes were collected and analyzed.

            RESULTS There were average 1.52 ATs in patient with PCS and 2.33 ATs in patient with SS (P<0.01). In PCS group, cavo-tricuspid isthmus (CTI)-dependent atrial flutter (AFL) was the most common, found in 43 (93.5%) patients, and the scar-mediated intra-atrial reentrant AT (IART) was presented in 18 (39.1%) patients; in SS group, AFL and IART were both presented in high proportion of patients (77.8 and 88.9%, separately), and the focal AT was found in 22.2% patients. Incidence of IART and FAT in patients with SS were significantly higher than those with PCS (88.9 vs. 39.1%, P<0.01; 22.2 vs. 2.2%, P<0.05). CTI ablation was performed in most patients in both groups (89.1 vs. 77.8%, P=0.44), while the scar-related ablation was more frequently performed in patients with SS (39.1 vs. 83.3%, P<0.01). There were no significant differences on acute success rate between two groups (93.5 vs. 83.3%; P=0.44). While the long-term success rate was lower in the SS group after the follow-up of average 66.8 months (87.0 vs. 61.1%; P<0.05). Patients with SS had significantly higher occurrence of bradyarrhythmia (8.7 vs. 33.3%, P<0.05), mainly the SSS.

            CONCLUSIONS CTI-dependent AFL is prevalent in both patients with PCS and patients with SS. Routine CTI ablation was recommended in these two conditions. Compared with patients with PCS, patients with SS have more ATs, especially with higher occurrence of IART and FAT, and more ablation is needed. Patients with SS have lower long-term success rate and higher incidence of brady-arrhythmias, mainly the SSS.

            GW33-e0429
            Radiofrequency catheter ablation of ventricular tachycardia after repaired congenital heart disease

            Sainan Li, Ming Liang, Zulu Wang

            General Hospital of Northern Theater Command

            OBJECTIVES Though surgical repair of congenital heart disease has improved the prognosis and prolonged the longevity greatly, arrhythmia after cardiac surgical repair is common in the long term. This study aims to clarify the clinical characteristics and long-term ablation outcomes of ventricular tachycardia (VT) in patients with surgical repaired congenital heart disease.

            METHODS Nineteen patients with surgical repaired congenital heart disease who underwent radiofrequency catheter ablation for VT were enrolled. The baseline characteristics, recordings of electrophysiologic study and catheter ablation, and the outcomes of long-term follow-up of each patient were collected and analyzed.

            RESULTS There were 17 patients with tetralogy of Fallot (TOF), one patient with trilogy of Fallot and 1 with congenital pulmonary stenosis in this research. Scars in right ventricular outflow tract (RVOT) and ventricular septum were mapped in all patients, consistent with RVOT incision and ventricular septal defect patch, while non-surgery related scars were found in three patients (two patients in RV apex and one patient in RV anterior wall). The acute success rate of the first ablation was 94.7% (18/19), and nine patients had VT recurrence during follow-up. After one or more ablation, the long-term success rate was 73.7%. Patients with non-surgery related scar had older surgical age, larger RA and LA dimension, more VT, and lower long-term success rate (P<0.05).

            CONCLUSIONS The scar of RVOT incision and ventricular septum defect patch can be found in patients with TOF, trilogy of Fallot or congenital pulmonary stenosis, but some patients may also present non-surgery related scar, who often undergo surgery at older age. Those patients with older age of surgery have lower long-term success rate of VT ablation.

            GW33-e0440
            Impact of pericoronary adipose tissue attenuation on recurrence after radiofrequency catheter ablation in patients with atrial fibrillation

            Wang Zhe1, Wang Yijia2, Chen Jiawei3, Reng Lichen3, Guo Hehe3, Chen Yingwei3, Dong Jianzeng3, Sun Yihong2

            1China-Japan Friendship Hospital

            2Beijing Hospital

            3The First Affiliated Hospital of Zhengzhou University

            OBJECTIVES

            Posterior left atrial (LA) adipose tissue attenuation is an independent predictor for AF patients recurrence. Pericoronary adipose tissue (PCAT) inflammation may be directly related to coronary inflammation and play an important role in the pathophysiology of AF. This study aimed to evaluate the association between pericoronary adipose tissue attenuation (PCATA), as a marker of inflammation, and atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA).

            METHODS This was a retrospective study of 299 AF patients with coronary computed tomography angiography (CCTA) before ablation who underwent the first RFCA were included between 2018 and 2021 in the First Affiliated Hospital of Zhengzhou University. We investigated the association between the risk of AF recurrence and PCATA. Multivariate Cox regression analysis and restricted cubic splines were performed to explore the relationship between PCATA and AF recurrence. The area under the receiver operating characteristic curve (AUC), relative integrated discrimination improvement (IDI) and categorical free net reclassification (NRI) were used to assess the discrimination ability of the models.

            RESULTS Overall, 299 patients were enrolled with a mean age of 60.5±11.0 years. Our analysis showed excellent intra-reader and inter-reader reliability in PCATA measurement performed by 50 random AF patients. During 1 year follow up, 34.1% of patients experienced recurrence. All patients were divided into two groups according to with AF recurrence (102/299) and without AF recurrence (197/299). In multivariable analysis, RCA-PCATA (HR: 1.04, 95% CI: 1.02∼1.06, P=0.001) remained an independent factor for AF recurrence. The association between higher RCA-PCATA levels and AF recurrence remained consistent using the cut-off value of ROC (−77.45 HU). The risk of AF recurrence increased with the rising of RCA-PCATA (P for non-linearity=0.489). RCA-PCATA as a categorical variable remained as an independently predictor for AF recurrence after multivariable adjustment (HR: 2.22, 95% CI: 1.45∼3.40, P<0.001). The model efficacy for predicting AF recurrence was significantly improved by adding RCA-PCATA (AUC, 0.731 vs. 0.690, P=0.023; relative EDI, 0.047, P=0.002; categorical NRI, 0.154, P=0.004).

            CONCLUSIONS RCA-PCATA was independently associated with the recurrence of AF after ablation. The PCATA is a novel marker to quantify the degree of inflammation and to identify optimal candidates and guide the treatment after catheter ablation. PCATA in standard CCTA reporting could be more meaningful for assessing AF patients’ risk classification.

            GW33-e0477
            Advancing the second-generation 28-mm cryoballoon in different bifurcations of pulmonary vein as a conventional approach during atrial fibrillation cryoablation

            Mingyu Sun, Zulu Wang

            Department of Cardiology, General Hospital of Northern Theater Command, Shenyang

            OBJECTIVES Cryoballoon (CB) based ablation for pulmonary vein isolation (PVI) has demonstrated high procedural success rates and a promising clinical outcome for patients with paroxysmal and persistent AF. How to expand the ablation area of antrum and lead to better outcomes is still a challenging topic.

            METHODS A total of 89 consecutive patients who underwent CB ablation in different bifurcations of each PV as a routine approach were consented and enrolled. The nadir temperatures were all moderately correlated with the bifurcation diameters and the temperature difference was positively correlated with the diameter difference in various bifurcations of each PV.

            RESULTS The CB catheter advanced in different bifurcations of each PV could achieve different force directions to the antrum and the orientation difference was negatively correlated with the ostium-bifurcation distance. After the first application in one bifurcation of each PV, PV potentials could still be recorded in the other bifurcation in 13 patients, and the PV foci could trigger AF in 2 of them. The total isolated antral surface areas after the application in a second bifurcation were larger than those after the first application whether in left PVs [(40.88±15.10) cm2 vs (26.73±12.61) cm2, P<0.001] or in right PVs [(43.26±21.85) cm2 vs (29.06±13.95) cm2, P=0.001].

            CONCLUSIONS Applications performed in different bifurcations of each PV might create a wide area antral ablation lesion especially in those with small diameter or early branching. CB catheter advanced in different bifurcations would contribute to eliminate PV foci adequately.

            GW33-e0537
            The three-dimensional spatial relationship among the coronary artery, pulmonary sinus and right ventricular outflow tract: shadowed by the trivial

            Ruikun Jia, Kaijun Cui

            Department of Cardiovascular Medicine, West China Hospital, Sichuan University

            OBJECTIVES Coronary artery (CA) injury during radiofrequency ablation (RFA) is a fatal complication, and ablation catheter and CA distances are not routinely evaluated during routine right ventricular outflow tract (RVOT) ablation. CA injury has been increasingly reported during RVOT ablation in recent years. Recently, ablation on the pulmonary valve is considered to be at greater risk of CA injury. The aim of this study was to investigate the anatomical relationship between the catheter and coronary artery during ablation of RVOT-originated arrhythmias.

            METHODS The right ventricular, pulmonary and coronary arteries were reconstructed using CartoSegmentation in cardiac enhanced CT segmentation and fused with the electroanatomical model to measure the distance from the effective ablation target to the nearest CA and from the nearest ablation target to the CA, respectively.

            RESULTS Twenty-four patients each with ventricular arrhythmias ablated in the RVOT supravalvular and subvalvular were retrospectively enrolled consecutively. There was no significant difference in the minimum distance from the effective ablation target to the CA between the supra- and subvalvular groups (10.29±7.09 vs. 13.65±7.35, P=0.114), with a total of three patients (8.3%) in the supra-valvular group and 2 (12.5%) in the subvalvular group having an ablation site to CA distance of less than 5 mm (P=1.00). There was no significant difference in the distance from the nearest ablation target to the CA (8.93±6.62 vs. 10.59±6.87, P=0.396), and the distance from the ablation point to the CA was less than 5 mm in seven patients (29.2%) in the suprapulmonary group and 5 (20.8%) in the subpulmonary group (P=0.505).

            CONCLUSIONS There was no significant difference in the distance from the ablation point to the CA between the suprapulmonary and subvalvular ablation points, but the distance to the CA needs to be evaluated at the time of ablation in both cases.

            GW33-e0542
            The mean pulmonary artery pressure as a predictor of the outflow tract ventricular arrhythmias origin

            Yixuan Bai, Ruikun Jia, Kaijun Cui

            Department of Cardiovascular Medicine, West China Hospital, Sichuan University

            OBJECTIVES Chronic pressure overload plays an important role in the induction of the outflow tract (OT) ventricular arrhythmias (VAs). The diameters of the main pulmonary artery (dMPA), ascending aorta (dAA), and the Cobb angle were associated with the pulmonary artery pressure. We hypothesized that the mean pulmonary artery pressure (MPAP) could be associated with the right ventricular OT (RVOT) VAs and differentiate the RVOT VAs from the left ventricular OT (LVOT) VAs.

            METHODS Sixty-seven consecutive patients who underwent the cardiac multidetector CT examination and the OT-VAs ablation were included. They were retrospectively classified into two groups, the RVOT group (n=47) and the LVOT group (n=20). The MPAP was estimated using the following formula: MPAP=9.011+34.195*dMPA/dAA-0.319*systolic blood pressure+0.4023 Cobb angle.

            RESULTS No significant difference in baseline data between the two groups. The patients with the RVOT VAs have a higher dMPA/dAA (0.84±0.11 vs. 0.75±0.11, P=0.006) and Cobb angle (47.57±5.99 vs. 40.55±8.66, P<0.001), compared to the LVOT VAs patients. The MPAP was higher in the RVOT VAs patients (18.58±5.38 vs. 11.18±5.36, P<0.001). Multivariable analysis showed that the MPAP was an independent predictor of the RVOT VAs (P=0.001, 95% CI: 0.116 to 1.486).

            CONCLUSIONS The RVOT origin is associated with the higher dMPA/dAA, Cobb angle and MPAP. MPAP is a useful predictor for differentiating the RVOT VAs from the LVOT VAs.

            GW33-e0574
            Effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) for atrial fibrillation in patients with heart failure with reduced ejection fraction: a meta-analysis

            Zhenyu Dong, Baopeng Tang, Yanmei Lu, Muyassar Yusup

            Department of Pacing and Electrophysiology, Department of Cardiac Electrophysiology and Remodeling, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES It is reported that Angiotensin receptor-neprilysin inhibitor (ARNI) can work in the treatment of atrial fibrillation in patients with heart failure with reduced ejection fraction (HFrEF), but it is ambiguous.

            METHODS The databases of PubMed, MEDLINE, EMbase, The Cochrane Library, CNKI, Wanfang, Weipu and China Biomedical Literature Service System were searched respectively, and related clinical researches on ARNI in the treatment of heart failure were searched. The retrieved documents were all distributed in January 1, 2015 to December 12, 2021. Two reviewers independently screened the literature, extracted the data, and evaluated the quality of the included literature. The Review manage 5.4 software was used for meta-analysis.

            RESULTS A total of four studies were included, with a total of 9205 patients. The meta-analysis showed that compared with the ACEI/ARB group, the incidence of atrial arrhythmia was reduced in the ARNI treatment group, and the difference was statistically significant (P<0.05). While, the difference between the groups in inappropriate shock was not statistically significant (P>0.05).

            CONCLUSIONS ARNI can reduce the occurrence of atrial arrhythmia in patients with HFrEF, while not shown the improvement in inappropriate shock.

            GW33-e0575
            Deformation pattern changes in left atrium are related to paroxysmal atrial fibrillation: nested case control study from the single center CMR reservoir strain cohort

            Huan Sun, Yanjing Wang, Lin Liu, Yue Yang, Yuquan He, Ping Yang

            China-Japan Union Hospital of Jilin University

            OBJECTIVES Atrial fibrillation (AF) is associated with decreased atrial mechanic function and deformation parameters such as strain measured by cardiac magnetic resonance imaging (CMR). However, whether further analysis of atrial deformation helps identify function disorders associated with AF renders under-detected.

            METHODS One thousand twenty-three consecutive patients who completed CMR exam were screened, and nested case control was performed to include AF cases and control individuals. CMR images were analyzed to obtain left atrial (LA) strain and comparison of strain values between different segments of LA. The ratios of non-valve segments Versus valval segments (N:V), anterior segments Versus posterior segments (A:P) and free wall segments versus septal segments (F:S) were selected to illustrate deformation pattern changes in patients. The relationship between these parameters and AF were explored.

            RESULTS Thirty-six AF patients and 36 control cases without patients were finally included in our cohort. The global strain (Es) was shown to be significantly decreased in AF patients compared with control ones (30.82±15.02% Vs 52.83±12.69%, P<0.001). And the N:V value also shows a significant decline in AF patients (1.34±0.49 Vs 1.95±0.63, P<0.001). Further Logistic regression shows Es and N:V are independently related to AF, and the ROC curves also show that combination of Es and N:V may improve the prediction value for AF.

            CONCLUSIONS In AF patients, the deformation pattern acquired by CMR changes along with global mechanic function injury. N:V value provides a new insight during understanding the mechanic function change in AF patients, and this may also help predicting AF, which renders further detection through large prospective clinical observation.

            GW33-e0592
            Waist circumference, body mass index and risk of arrhythmias in patients with type 2 diabetes

            Wu Meizhen1,2, Ren Qingwen1,2, Huang Jiayi1,2, Tse Yi-Kei1,2, Li Hang-Long1,2, Yu Shuk-Yin2, Tse Hung-Fat1,2, Yiu Kai-Hang1,2

            1The University of Hong Kong-Shenzhen Hospital

            2The University of Hong Kong

            OBJECTIVES Obesity and increased body mass index (BMI) were associated with increased risk of atrial fibrillation. We thought to investigate the association between BMI and waist circumference with arrhythmias in patients with type 2 diabetes.

            METHODS Type 2 diabetic patients aged over 18 years without atrial fibrillation, bradycardia and ventricular arrhythmias were identified from the territory-wide Clinical-Data-Analysis-Reporting System from 2000 to 2015. Patients were followed-up until 31 December, 2020 for incident atrial fibrillation, bradycardia or ventricular arrhythmias. Cox proportional hazards model was used to assess the association of BMI or waist circumference with atrial fibrillation, bradycardia and ventricular arrhythmias.

            RESULTS A total of 64,787 patients were included. Higher BMI was associated with incident atrial fibrillation (HR 1.05[95% CI 1.04, 1.06]), and incident bradycardia (HR 1.03[95% CI 1.01, 1.05]), but not ventricular arrhythmias. Compared to patients with BMI <25.0kg/m2, patients with BMI ≥25.0kg/m2 had a 27 and 26% higher risk of developing AF and bradycardia. Similarly, patients with higher waist circumference had increased risk of atrial fibrillation (HR 1.02[95% CI 1.01, 1.02]), and bradycardia (HR 1.01[95% CI 1.00, 1.02]), but not ventricular arrhythmias. In analyses according to waist circumferential categories. Patients in the 4th quartile indicated a higher risk of AF (HR 1.45[95% CI 1.33, 1.58]) and bradycardia (HR 1.30[95% CI 1.09, 1.56]).

            CONCLUSIONS In patients with type 2 diabetes, BMI and waist circumference were independently associated with incident bradycardia and AF.

            GW33-e0601
            U-shaped association between the triglyceride-glucose index and the atrial fibrillation incidence in individuals without known cardiovascular disease: the atherosclerosis risk in communities (ARIC) study

            Ayiguli Abudukeremu, Xiao Liu, Yuling Zhang, Jingfeng Wang

            Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

            OBJECTIVES Triglyceride-glucose (TyG) index has shown as a new alternative measure for insulin resistance. However, no study attempts to investigate the association of TyG index with risk of incident atrial fibrillation (AF).

            METHODS A total of 11,851 individuals without known cardiovascular disease (heart failure, coronary heart disease, or stroke) from the prospective Atherosclerosis Risk in Communities (ARIC) cohort were recruited. The baseline TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. The association between levels of baseline TyG index and sex-specific incident AF was examined using Cox regression. The potential dose-response were fitted by restricted cubic spline curve.

            RESULTS Of 11,851 participants, median age was 54.04±5.74 years; 6586 (55.6%) were female. During a mean follow-up of 20.8 years, 1925 incident cases of AF (0.78/per 100 person years) occurred. A U-shape association between the TyG index and AF incidence in the overall population was observed. In category analysis, both of low (hazard ratio [HR]=1.19, 95% confidence interval [CI] 1.04, 1.37) and high levels (HR 1.21, 95% CI 1.02, 1.43) of TyG index were associated with increased risk of AF compared with the middle TyG category (8.80–9.20). Further sex-specific analysis showed that the U-shaped association trend between TyG index and incident AF was still existed in male, rather than in females.

            CONCLUSIONS A U-shaped association between TyG index and risk of AF was observed in Americans people without known cardiovascular disease. Sex may a modifier in the association between TyG index and AF incidence.

            GW33-e0628
            Temporary pacemaker reference for left bundle branch pacing site guidance analysis

            Yuying Liu, Xitian Hu

            Shijiazhuang People’s Hospital

            OBJECTIVES In 2017, Huang et al. proposed the left bundle branch pacing, which attracted much attention because of its relatively easy implantation technology and more stable pacing parameters. At present, there are two difficult problems in left bundle branch pacing: choosing the proper implantation site and determining the proper implantation depth. This study is to explore the effectiveness of left bundle branch pacing with temporary pacemaker as reference.

            METHODS A total of 30 patients with pacing indications will be selected for left bundle branch pacing in Shijiazhuang People’s Hospital from August 2021 to August 2022. The radian of the temporary pacemaker across the tricuspid ring and the apex of the heart was used to confirm the implantation site of the left bundle branch. DSA was used to measure the depth of electrode wire implantation. Compared with traditional positioning of left bundle branch pacing, the success rate of surgery, operation time, X-ray exposure time, times of electrode implantation, pacing parameters of left bundle branch during operation and follow-up, pacing characteristics, and surgery-related complications were evaluated.

            RESULTS As of May 27, 2022, a total of 30 cases of left bundle branch pacing were successfully completed, with a total success rate of 93.3% 28/30. The comparison of the number of patients in the two groups (10:20), the operation time of the two groups (120 min: 75 min), and the X-ray exposure time of the two groups (17 min: 12 min), the number of electrode implantation (5 times: 2.5 times), the intraoperative operation parameters were stable, and the postoperative follow-up parameters were stable.

            CONCLUSIONS Temporary pacemakers for targeting area reference can improve surgical success, reduce surgical time, reduce X-ray exposure time, and shorten the learning curve for beginners. Intraoperative full use of the inherent measurement means of DSA can provide the position of the electrode into the interval, which helps to judge the depth of the left bundle branch electrode.

            GW33-e0639
            Orthostatic hypotension and intensive blood pressure control on cognitive outcomes: insights from the SPRINT trial

            Manlin Zhao, Chao Jiang, Yiwei Lai, Yufeng Wang, Sitong Li, Liu He, Ribo Tang, Caihua Sang, Deyong Long, Jianzeng Dong, Xin Du, Changsheng Ma

            Beijing Anzhen Hospital

            OBJECTIVES Orthostatic hypotension (OH) is common among patients with hypertension. The potential benefits or harms of intensive blood pressure (BP) control on cognitive outcomes in patients with OH is unclear. We evaluated the association between OH and cognitive outcomes and the effects of intensive BP control on cognitive outcomes in patients with OH.

            METHODS We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial (SPRINT) who had completed at least one follow-up cognitive assessment. OH was defined as a drop in systolic BP of at least 20 mmHg or diastolic BP of at least 10 mmHg from sitting to standing. The cognitive outcomes, including probable dementia (PD), mild cognitive impairment (MCI), and the composite outcomes of PD or MCI, were evaluated biennially. The multivariable Cox proportional hazards regression was applied to assess the relationship between the baseline OH and incident cognitive outcomes. A product term of OH and treatment group was additionally included in the model to quantify the interaction effect. In sensitivity analyses, we repeated all the analyses stratified by severity of OH.

            RESULTS Among 8547 participants, 615 (7.2%) participants had baseline OH (OH vs. No OH 69.7 [9.5] years vs. 67.8 [9.3] years). Baseline Montreal Cognitive Assessment scores for participants with and without OH did not show significant differences. Baseline OH was not significantly associated with cognitive dysfunction, as adjusted hazard ratios (HR) was 0.98 for PD (95% CI 0.66–1.47, P=.93), 1.12 for MCI (95% CI 0.83–1.51, P=.46), and 1.09 for the composite outcomes of PD or MCI (95% CI 0.85–1.41, P=.49). The presence of OH did not significantly modify the effect of intensive BP control on PD (P for interaction 0.186), MCI (P for interaction 0.374), and the composite outcomes of PD or MCI (P for interaction 0.939).

            CONCLUSIONS In this post-hoc analysis of the SPRINT trial, OH was not independently associated with an increased risk of cognitive impairment. The presence of OH did not modify the effects of intensive BP control on cognitive outcomes. OH should not be a barrier to adopting a strict BP control strategy considering the cognitive outcomes among hypertensive patients.

            GW33-e0640
            Dose elderly patients with atrial fibrillation have a comparable ablation outcome with younger ones? Evidence from the pooled clinical studies

            Li Feng, Wang Ru-Xing

            Department of Cardiology, Wuxi People’s Hospital Affiliated to Nanjing Medical University, Wuxi 214023, China

            OBJECTIVES Age is an independent risk factor for the progress and prognosis of atrial fibrillation (AF). However, the ablation outcomes between elderly and younger patients with AF remain elusive.

            METHODS Cochrane Library, Embase, PubMed, and Web of Science were systematically searched up to 1 April 2022. Studies comparing the AF ablation outcomes between elderly and younger patients and comprising the outcomes of AF ablation for elderly patients were included. Trial sequential analysis (TSA) was performed to adjust the random error and lower statistical power in our meta-analysis. Subgroup analysis identified possible determinants of outcome impact for elderly patients after ablation. Moreover, linear and quadratic prediction fit plots with confidence interval were performed, as appropriate.

            RESULTS A total of 27 studies with 113,106 AF patients were eligible. Compared with younger group, elderly group was significantly associated with a lower rate of freedom from AF (risk ratio [RR], 0.95; P=0.011), as well as a higher incidence of safety outcomes (cerebrovascular events: RR, 1.64; P=0.001; serious hemorrhage complications: RR, 1.60; P=0.019; all-cause death: RR, 2.61; P=0.003). Subgroup analysis and quadratic prediction fit analysis revealed the follow-up time was the potential determinant on freedom from AF for elderly patients after AF ablation.

            CONCLUSIONS Our meta-analysis suggests that elderly patients may have inferior efficacy and safety outcomes to younger patients with AF ablation. Moreover, the follow-up time may be a potential determinant of outcome impact on freedom from AF for elderly patients after AF ablation.

            GW33-e0663
            Clinical analysis of delayed cardiac tamponade in atrial fibrillation patients with left atrial appendage closure

            Zhihong Zhao

            Department of Cardiology, Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China

            OBJECTIVES To investigate the relationship of delayed cardiac tamponade (CT) after left atrial appendage closure (LAAC) in atrial fibrillation (AF) patients and the effects of implanted occluders and adjacent anatomical structures.

            METHODS This study is a retrospective and cross-sectional study. AF patients with LAAC whom complicated with delayed CT and with concurrent emergency pericardiocentesis drainage in Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from August 2016 to June 2021 were selected, the mean follow-up time was 16±12 months. The clinical data including the relationship between the left atrial appendage and pulmonary artery, vein anatomy by left atrium computed tomography angiography (CTA) before and after LAAC were retrospectively analyzed.

            RESULTS Thirteen patients whom delayed CT treated by pericardiocentesis and drainage after LAAC, of whom 7 males, average 72.1±8.3 years, including 11 delayed CT patients, and 6 patients LAAC with simultaneous cryoablation, the classification types of left atrial appendage including cauliflower and chicken wing types. The incidence of CT: LACbes 6.6% (6/91 cases), Watchman 0.71% (4/562 cases), LAmbre 0.93% (2/216 cases) and Laager 6.25% (1/16 cases) respectively. The average diameter of the seal plate was 29.5±2.8 mm; 10 patients have cardiac CTA reviewed, 8 of whom the occluder were attached to pulmonary artery, 1 patient attached to left superior pulmonary vein only, and 1 patient attached to pulmonary artery and left superior pulmonary vein, except one patient died 2 days after LAAC, other patients have a good prognosis.

            CONCLUSIONS Anatomic relationship of the left atrial appendage, pulmonary artery and left superior pulmonary vein related to delayed CT after LAAC, and which more closely related to larger occluder and anchor hook.

            GW33-e0686
            Length of hospitalization-related differences and associated long-term prognosis of patients with cardiac resynchronization therapy: a propensity score matched cohort

            Yu Yu, Wei Hua

            Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Previous studies indicated that prolonged lengths of hospitalization (LOH) during cardiac resynchronization therapy (CRT) implantation are associated with poorer physical status and higher in-hospital mortality. However, evidence on the impact of LOH on the long-term prognosis of CRT patients is limited. The purpose of this study was to assess LOH-related prognostic differences in CRT patients.

            METHODS In the propensity score-matched cohort, patients with standard LOH (≤7 days, n=172) were compared with those with prolonged LOH (;7 days, n=172) for cardiac function and study outcomes during follow-up. The study outcome were all-cause death and heart failure (HF) hospitalization. In addition, cardiac function and changes in cardiac function at the follow-up period were used for comparison.

            RESULTS At a mean follow-up of 3.36 years, patients with prolonged LOH, as compared with those with standard LOH, were associated with a significantly higher risk of all-cause death (hazard ratio [HR] 1.87, 95% confidence interval [CI] 1.18–2.96, P=0.007), and a higher risk of HF hospitalization (HR 1.68, 95% CI 1.08–2.63, P=0.023). Moreover, patients with standard LOH had a more significant improvement in cardiac function and a pronounced reduction in QRS duration during follow-up than those with prolonged LOH.

            CONCLUSIONS LOH-associated differences were found in the long-term prognosis of CRT patients. Patients with prolonged LOH had a worse prognosis than those with standard LOH.

            GW33-e0711
            Serum biomarkers of fibrosis as predictors of left atrial appendage thrombosis in patients with non-valvular atrial fibrillation

            Tatiana P. Gizatulina, Natalia Yu. Khorkova, Tatiana I. Petelina, Alexandra V. Mamarina, Leysan U. Martyanova, Alfira V. Belokurova

            Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia

            BACKGROUND Left atrial appendage (LAA) thrombosis is known to occur in approximately 10% of patients (pts) with atrial fibrillation (AF) and is associated with a 3.5-fold increased risk of stroke/systemic embolism. Since LA fibrosis determines the development and maintenance of AF, and is associated with an increased risk of stroke, we hypothesized that levels of circulating fibrosis biomarkers may be predictors of LAA thrombosis in pts with non-valvular AF (NVAF). The objective was to conduct a comparative analysis of clinical, echocardiography (EchoCG) indicators and serum biomarker levels in pts with NVAF, depending on the presence of LAA thrombus, followed by the identification of independent predictors of LAA thrombosis.

            METHODS The study included 142 pts (90 men and 52 women) with NVAF hospitalized for catheter ablation or cardioversion, aged 34–72 years, divided into 2 groups comparable in gender and age: gr. 1 (n=45) – with LAA thrombosis, gr. 2 (n=97) – without LAA thrombosis. Patients underwent transthoracic and transesophageal EchoCG, determination of biomarkers in the blood: NT-proBNP (pg/mL), GDF-15 (pg/mL), TGF-β1 (pg/mL), PIIINP (ng/mL), ST2 (ng/mL), highly sensitive (hs) CRP (mg/L), cystatin C (mg/L).

            RESULTS The groups did not differ in the mean CHA2DS2-VASc score (2.2±1.0 in gr. 1 and 1.9±1.0 in gr. 2), as well as in the proportion of low-risk pts (0–1 point): 29 and 37% respectively (P=0.15). In gr. 1, persistent AF, coronary artery disease, congestive heart failure f.c. 2–3 were more common, higher volumes of both atria, left ventricular myocardial mass index and systolic pressure in the pulmonary artery were noted, lower left ventricular ejection fraction and blood flow rate in LAA. There were no differences in the proportion of pts taking oral anticoagulants (OAC), as well as in the spectrum of OAC taken. Pts in gr. 1 showed higher levels of NT-proBNP (281.0 [126.0; 674.0] and 97.6 [44.4; 208.0], respectively, P=0.0001), GDF-15 (1039.5 [838.0; 1461.0] and 810.8 [630.0; 988.0], P=0.0001) and PIIINP (80.0 [64.0; 104.0] and 64.9 [59.6; 68.6], P=0.0002), while the levels of TGF-β1, hs CRP, ST2 and cystatin C did not differ. The cut-off values of biomarkers calculated using ROC analysis, clinical data and EchoCG indicators that differ between groups are included in the stepwise multivariate regression analysis. The following independent predictors of LAA thrombosis were identified: LA volume index (mL/m2) – odds ratio (OR)=1.084, (95% confidence interval (CI) 1.028–1.143, P=0.003), GDF-15≥933 pg/mL – OR=3.054, 95% CI 1.260–7.403, P=0.013, PIIINP≥68 pg/mL – OR=5.865, 95% CI 2.404–14.308, P<0.001). When evaluating the model using ROC analysis, the area of the curve AUC=0.815 (P<0.001), specificity - 74.4%, sensitivity - 72.7%.

            CONCLUSION According to our study, in pts with NVAF taking OAC, higher levels of serum biomarkers PIIINP≥68 pg/mL and GDF-15≥933 pg/mL, along with the LA volume index, can be independent predictors of LAA thrombosis.

            HEART FAILURE
            GW33-e0006
            Preoperative leukocyte count as a useful predictor for unplanned heart failure readmission in elderly diabetic patients with newly implanted cardiac pacemakers: a 5-year cohort study

            Yu Yu

            Cardiac Arrhythmia Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Long-term incidence of heart failure (HF) remained higher in diabetic patients with right ventricular pacing. Early high leukocyte count plays an essential role in the development processes of HF. However, studies exploring associations between early leukocyte count and the incidence of HF in elderly diabetic patients with newly implanted pacemakers are lacking. This study examined whether higher leukocyte count is a risk factor for HF in elderly diabetic patients with newly implanted pacemakers.

            METHODS From January 2017 to January 2018, 233 consecutive diabetic patients were older than 65 years undergoing newly implanted cardiac pacemakers were enrolled in this study, and information on demographic characteristics, disease and medication history, and laboratory test were collected. The study endpoint was the first readmission for HF.

            RESULTS The mean leukocyte count was 6.73±1.77 (109/L), and 47 (20.17%) incident HF readmission occurred during the 5-year follow up. Multivariate cox regression models were used to reveal the positive association between preoperative leukocyte count and incidence of HF readmission (hazard ratio [HR] 1.34, 95% confidence interval [CI] 1.09, 1.64). The HR (95% CI) for HF readmission in the high-level leukocyte group (tertile 3) was 3.21 (1.17, 8.79) compared with the lower leukocyte group (tertile1). Further subgroup analyses showed that the relationship between leukocyte count and HF readmission was more robust in the presence of hypertension (P for interaction<0.001).

            CONCLUSIONS The higher preoperative leukocyte count is an independent risk factor for HF readmission in elderly diabetic patients with newly implanted pacemakers, especially in the presence of hypertension.

            GW33-e0026
            Expression of serum endoplasmic reticulum stress protein XBP-1S in patients with acute myocardial infarction in different cardiac function grades

            Ni-Ni Tian1, Guang-Ping Ruan2, Feng Xu1, Pin Wang1, Huixian Duan1, Qiangyao Jiang3, Hong-Jian Li4, Xing-Hua Pan2

            1Department of Cardiology, Kunming First People’s Hospital, Kunming Yunnan 650011, China

            2Basic Medical Laboratory of the 920th Hospital of the Chinese People’s Liberation Army, Kunming Yunnan 650032, China

            3Director of Laboratory Medicine, Kunming First People’s Hospital, Kunming Yunnan 650011, China

            4Department of Surgery, Affiliated Medical College of Kunming University of Science and Technology, Kunming Yunnan 650034, China

            AIM To investigate the expression of endoplasmic reticulum stress protein XBP-1S in peripheral venous blood of patients with different levels of cardiac function caused by acute myocardial infarction (AMI) within 24 hours.

            METHODS 1.58 patients with normal physical examination were selected as the control group. AMI patients in the 230 case group were divided into the acute cardiac function classification (Killip classification) method after the onset: 122 cases were included in the cardiac function classification 1 group; the cardiac function classification 2 group was included 36 cases; 14 cases were included in the 3-level cardiac function group; 58 cases were included in the 4-level cardiac function group. ELISA method was used to detect the XBP-1S and BNP content in the patient’s serum within 24 hours.

            RESULTS 1. Analysis by non-parametric rank sum test: the concentration of XBP-1S in the control group is 142.26 (125.62–155.5) ng/mL; the level 1 group of cardiac function is: 151.79 (131.01–178.84) ng/mL; the level of cardiac function is 2 The group is: 158.09 (152–163.15); the 3-level cardiac function group is: 171.5 (148.72–195); the 4-level cardiac function group is: 295.13 (263.64–365.76); and P<0.05, the difference is statistically significant. 2. Serum BNP content is analyzed by non-parametric rank sum test: the BNP concentration of the control group is 49 (32–65) ng/mL; the cardiac function grade 1 group is: 144.6 (130.2–3498) ng/mL; the cardiac function grade 2 The grade group is 611.2 (161.1–1192) ng/mL; the cardiac function grade 3 group is: 1584 (557–14569) ng/mL; the cardiac function grade 4 group is: 1599 (1019–3212) ng/mL; and P<0.05.

            CONCLUSION The response in UPR’s IRE1α/XBP-1 signaling pathway is one of the three classic pathways that participate in the ER response. Under normal circumstances, the expression of XBP-1S is very low, but patients with IRI and heart failure caused by AMI may be significantly induced.

            GW33-e0051
            Insulin resistance is associated with heart failure with recovered ejection fraction in non-diabetic patients

            Chendie Yang, Xiaoqun Wang

            Department of Cardiovascular Medicine, Ruijin Hospital, Shanghai Jiao-Tong University School of Medicine

            OBJECTIVES Due to advances in medical treatments, a substantial proportion of heart failure (HF) patients have experienced recovery of ejection fraction (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in non-diabetic patients.

            METHODS A total of 262 non-diabetic HF patients with reduced EF (HFrEF) were consecutively enrolled. Patients were classified into HFrecEF (follow-up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiogram after 12 months. IR was estimated by an updated homeostasis model assessment (HOMA2-IR).

            RESULTS The median HOMA2-IR level was 1.05 (IQR 0.67∼1.63) in our cohort of non-diabetic HF patients. During follow-up, 121 (46.18% [95% CI 40.15%∼52.22%]) patients developed HFrecEF. Compared with HFrEF patients, HFrecEF patients had significantly lower HOMA2-IR levels (0.92 [IQR 0.61∼1.37] vs. 1.14 [IQR 0.75∼1.78], P=0.007), especially in HF of non-ischemic etiology. Log-transformed HOMA2-IR was inversely correlated to improvements in EF (Pearson’s r=-0.25, P<0.001). After multivariate adjustment, a doubling of HOMA2-IR was associated with a 41.2% decreased likelihood of HFrecEF (OR 0.588 [95% CI 0.402∼0.838]).

            CONCLUSIONS This study reveals that IR is independently associated with compromised development of HFrecEF in non-diabetic patients.

            GW33-e0124
            Characteristics of patients undergoing pericardiocentesis and safety of pericardiocentesis under anticoagulation or antiplatelet therapy

            Yuansong Zhu, Bi Huang, Chengxiang Zhang, Yuqiao Xie, Suxin Luo

            The First Affiliated Hospital of Chongqing Medical University

            OBJECTIVES Pericardial effusions can be caused by a variety of diseases. The safety of urgent pericardiocentesis for large pericardial effusion in some patients without the cessation of anticoagulants or antiplatelet agents is uncertain. This study aimed to analyze the characteristics of patients undergoing pericardiocentesis, and the safety of pericardiocentesis under anticoagulants or antiplatelet agents at a regional medical center in southwest China.

            METHODS We performed a retrospective observational study of 347 consecutive patients undergoing pericardiocentesis at our hospital between 2012 and 2022. The baseline characteristics, medications and procedural details were collected through the electronic medical records. Patients were divided into Groups of Antithrombotic (use of any antiplatelet agents or anticoagulants at the day of procedure) or Non-antithrombotic. Comparisons between groups were achieved using Mann-Whitney test or chi-square test. All procedures were performed by experienced cardiologists. Bleeding events were defined using the National Institutes of Health scale of adverse events (CTCAE).

            RESULTS Among the 347 patients included, 51 patients (14.7%) were under usage of antithrombotic agents. They were older, had more comorbidities of hypertension, diabetes, chronic kidney disease, coronary artery disease and atrial fibrillation (all P<0.001). They also had lower platelet count (Antithrombotic vs Non-antithrombotic, 205*109/L vs 230*109/L, P=0.011) and prolonged APTT (30.6s vs 28.8s, P=0.002) but comparable INR (1.17 vs 1.15, P=0.554). In Non-antithrombotic Group, malignancy represents the most frequent etiology for pericardial effusion (19.6 vs 45.3%, P=0.001), while procedure-related pericardial effusion was most frequently seen in Antithrombotic (23.5 vs 3.0%, P=0.001). Dark red was the most common color of pericardial effusion and was similar between groups (75.5 vs 64.5%, P=0.133), while Non-antithrombotic had higher volume of drainage (600 mL vs 800 mL, P=0.045). Two patients in Antithrombotic Group had minor oozing at the puncture site that did not require intervention (3.9 vs 0%, P=0.021), while all patients did not experience any bleeding events higher than Grade 1.

            CONCLUSIONS Although patients with pericardial effusions under antiplatelet agents or anticoagulants were older, had more comorbidities and altered coagulopathy, pericardiocentesis may still be performed safely without increasing major complications.

            GW33-e0177
            Pulmonary hemodynamic and prognostic value of cardiopulmonary exercise score in patients with left heart failure

            Hang Zhang

            Nanjing First Hospital

            OBJECTIVES Secondary pulmonary hypertension in left heart failure (PH-LHF) is associated with abnormal ventilatory response on exercise and poor prognosis. Our study sought to develop an algorithm, using cardiopulmonary exercise testing (CPET) data, to assess pulmonary hemodynamic severity and predict clinical worsening and mortality in heart failure (HF) patients.

            METHODS A total of 102 HF patients prospectively participated in the study underwent CPET and invasive right heart catheterization (RHC). Using CPET data, including VO2 peak/Kg, the minute ventilation/carbon dioxide production (VE/VCO2) slope, resting end-tidal CO2 (PET CO2), VO2/WR flattening, exercise oscillatory ventilation (EOV), Oxygen Uptake Efficiency Slope (OUES), a Heart Failure Cardiopulmonary Exercise (HFCE) Score was developed. Patients were tracked for composed clinical events (all-course death and rehospitalization for HF) for at least 1 years.

            RESULTS The high HFCE score group of 26 (25%) patients had a higher prevalence of NYHA class III-IV, higher NT-proBNP level, lower 6-mimute-walk-distance (6-MWD). The high HFCE score group had worsening hemodynamic parameters including higher prevalence of combined post- and pre-capillary PH (Cpc-PH), higher mean pulmonary artery pressure (mPAP), higher pulmonary artery wedge pressure (PAWP), higher pulmonary vascular resistance (PVR) and lower cardiac output (CO). The high HFCE score correlated well with the high level of PVR, PAWP and mPAP, and the low level of CO. There were 54 composed clinical events (12 all-cause death, 43 HF rehospitalization) in 46 (45%) patients during the mean follow-up period of 477 days, which were increased corresponded with the HFCE score. In the multivariate model, the HFCE Score was an independent predictor of composed clinical events (P=0.007). Kaplan–Meier analysis showed a significantly higher probability of composed clinical events in the patients with a higher HFCE score (8–14 points) (P=0.004).

            CONCLUSIONS The HFCE score, obtained from cardiopulmonary exercise testing, indicates hemodynamic severity and provides prognostic information for predicting clinical worsening and mortality in patients with PH-LHF.

            GW33-e0291
            Hba1c variability is associated with long term outcome of heart failure patients with and without diabetes

            Xin Xu1,2, Qingwen Ren1,2, Kaihang Yiu1,2

            1Cardiology Division, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, Shen Zhen, China

            2Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China

            OBJECTIVES Glycemic control is an important clinical issue in the management of patients with heart failure (HF), but the effect of long-term glycemic variability on clinical outcomes in HF patients remains unclear. This study aims to evaluate the association of HbA1c variability and clinical outcomes for patients with HF.

            METHODS By using a previously validated territory-wide clinical information registry, HF patients who had more than 3 times HbA1c measurements after the diagnose of HF were included (N=77,006) from 2004–2018. Average successive variability (ASV) (average absolute difference between successive values), standard deviation (SD) and mean of HbA1c were calculated. Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of rehospitalization and all-cause mortality associated with HbA1c variability.

            RESULTS Of all eligible patients, the mean age was 67.5±12.2 years and 39,409 (51.2%) were male. During a mean follow-up of 7.7±5.2 years, 63,032 (81.9%) patients had an incidence of HF rehospitalization, while 40,743 (52.3%) experienced the endpoint of death. Greater long-term HbA1c variability was significantly associate with higher risk of HF rehospitalization (HR=1.25, 95% CI, 1.23 to 1.27, P<0.01) and all-cause mortality (HR=1.538, 95% CI, 1.507 to 1.570, P<0.01). Interestingly, for patients without DM, higher HbA1c variability had an even stronger impact on HF resocialization than DM patients (DM patients: HR: 1.22, 95% CI: 1.20 to 1.25; Non-DM patients: HR: 1.86, 95% CI: 1.70 to 2.04). High HbA1c mean was associated with higher risk of HF rehospitalization in DM patients while in Non-DM patients the effect was opposite (DM patients: HR: 1.04, 95% CI: 1.04 to 1.05; Non-DM patients: HR: 0.88, 95% CI: 0.85 to 0.92).

            CONCLUSIONS This study suggests that for patients with HF, substantial variability was associated with a higher risk of HF rehospitalization, this effect existed in both patients with and without diabetes.

            GW33-e0437
            Performance of the heart failure risk scores in predicting 1-year mortality and short-term readmission of patients

            Xiangwei Bo1, Lijuan Chen1,2

            1Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China

            2Department of Cardiology, Nanjing Lishui People’s Hospital, Zhongda Hospital Lishui Branch, Southeast University, Nanjing, China

            OBJECTIVES Many risk scores for predicting the risk of death in patients with heart failure have been established and existing studies have shown that while these scores can stratify patients by risk, they still differ from clinical reality in assessing individual patient mortality. The aim of this study was to externally validate the performance of these major scores in predicting prognosis in patients with heart failure.

            METHODS A total of 2008 patients who were admitted to the Fourth People’s Hospital of Zigong, Sichuan, from 2016.12 to 2019.6 and diagnosed with heart failure were included in the study. We compared the prognostic accuracy of Seattle Heart Failure Model (SHFM), Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC-HF) risk score, Get With the Guidelines-Heart Failure program (GWTG-HF), Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND) risk scores, the Acute Decompensated Heart Failure National Registry (ADHERE) model, Barcelona Bio-Heart Failure (BCN-Bio-HF) risk calculator and Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico-Heart Failure (GISSI-HF) for the endpoints. The primary endpoint was 1-year all-cause mortality and the secondary endpoint was the incidence of 28-day readmission postdischarge. The accuracy and clinical applicability were tested by the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses (DCA).

            RESULTS At 1 year follow-up, 44 (2.21%) patients with heart failure died. Discrimination analyses showed all risk scores performed reasonably well in predicting 1-year mortality, with AUCs fluctuating between 0.757–0.822. GISI-HF showed the best discrimination with the AUC of 0.822 (0.768–0.876), followed by MAGGIC-HF, BCN-Bio-HF, ASCEND, SHFM, GTWG-HF and ADHERE with AUCs of 0.819 (0.756–0.883), 0.812 (0.758–0.865), 0.802 (0.742–0.862), 0.787 (0.725–0.849), 0.762 (0.684–0.840) and 0.757 (0.681–0.833), respectively. All risk scores were similarly predictive of 28-day emergency readmissions, with an AUC fluctuating between 0.609–0.680. The calibration plot suggested some overestimation of mortality by all scores except the ASCEND. The ADHERE and GWTG scores showed the best calibration and had the greatest net benefit, with net benefit thresholds ranging from 1 to 45%. The DCA showed benefits for all risk scores where used, and better calibration for lower risk groups.

            CONCLUSIONS Currently assessed risk scores have limited clinical utility, with fair accuracy and calibration in assessing patients’ 1-year risk of death, and poor accuracy in assessing patients’ risk of readmission. There is a need to incorporate more patient-level information and use more advanced technology to achieve a more practical, innovative and accurate risk assessment tool.

            GW33-e0446
            Analysis of etiological heterogeneity in hospitalized elderly patients with ejection fraction preserved heart failure

            Jian Zhu1, Suyan Bian1, Shanshan Liu1, Binhua Wang2, Hongli Xu3, Kunlun He3

            1Cardiology Department, The Second Medical Center, & National Clinical Research Center of Geriatric Disease, Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, PLA General Hospital

            2Disaster Medical Research Center, Medical Innovation Research Department, PLA General Hospital

            3Medical Big Data Research Center, Medical Innovation Research Department, PLA General Hospital

            OBJECTIVES To analyze the etiological heterogeneity of elderly patients hospitalized with ejection fraction preserved heart failure (HFpEF) and its difference with the other two types of chronic heart failure.

            METHODS The clinical data of 4650 elderly patients (aged ≥ 60 years) hospitalized with chronic heart failure (CHF) in the first medical center of the PLA General Hospital from February 2008 to December 2019 were analyzed retrospectively. According to left ventricular ejection fraction (LVEF), the study population was divided into heart failure with reduced ejection fraction (HFrEF), heart failure with mildly reduced ejection fraction (HFmrEF) and HFpEF group. The differences in cardiac and extra-cardiac comorbidities were compared among the three groups. Furthermore, the burden and spectrum of comorbidites in HFpEF were also investigated.

            RESULTS HFpEF accounted for 49.46% of the elderly inpatients with CHF. Among the three types of CHF, HFpEF patients were the oldest (mean age 73.96 years), with the highest proportion of women (49.35%), the highest systolic blood pressure, relatively mild symptoms of heart failure with 36.09% of NYHA II (P<0.001). There were significant differences in cardiac and extra-cardiac causes of the three types of CHF. Among them, hypertension, arrhythmia (atrial flutter/atrial fibrillation) and valvular heart disease were the most common cardiac reasons, meanwhile, anemia, peripheral vascular disease and malignant tumor were the most prominent extra-cardiac comorbidities in HFpEF patients. HFpEF and HFmrEF had the largest number of extra-cardiac comorbidities with the median of 3, both of which were significantly higher than that of HFpEF (P<0.001). Moreover, with the adding of extra-cardiac comorbidities, the proportion of HFpEF gradually increased. 25.78% of HFPEF patients sufferd from three comorbidities and 11.82% were attacked by more than five illness, which were significantly higher than the other two types of CHD (P<0.001). Dyslipidemia, chronic kidney disease and type 2 diabetes were the most common combination of extra-cardiac comobidities.

            CONCLUSIONS The cardiac and extra-cardiac causes of HFpEF are significantly different from the other types of CHF, and its burden of extra-cardiac comorbidity is heavier and more heterogeneous, which may be the main reason for the clinical heterogeneity of HFPEF.

            GW33-e0585
            Association between triglyceride and all-cause and cause-specific mortality in heart failure patients: a territory-wide study in Hong Kong

            Qing-Wen Ren, MD1,2, Yi-Kei Tse2, Kai-Hang Yiu, MD, PhD1,2

            1Cardiology Division, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, Shen Zhen, China

            2Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China

            BACKGROUND To determine the association between levels of triglyceride (TG) and all-cause mortality, cardiovascular death (CVD) or non-cardiovascular death (non-CVD), and the concentration of TG associated with the lowest risk of adverse outcomes in heart failure (HF) patients.

            METHODS Using a previously validated territory-wide clinical information registry, all eligible patients with HF (N=147,396) from 1996 to 2020 were enrolled. Baseline levels of time-weighted TG associated with risk of mortality were evaluated on a continuous scale using restricted cubic splines and by categories with Cox proportional hazards regression models. The main outcomes were all-cause mortality, CVD and non-CVD. Secondary outcomes were cause-specific mortality (HF-related death, myocardial infarction-related death, pneumonia-related death and other mortality).

            RESULTS Among 147,396 individuals, the mean age was 70.0±12.5 years and 73,571 (49.9%) were male. The association between levels of time-weighted TG and the risk of all-cause mortality was J shaped, with low and high levels associated with an increased risk of all-cause mortality, CVD and non-CVD. Compared with individuals with concentrations of TG of 1.14–2.85 mmol/L, the multivariable-adjusted hazard ratio for all-cause mortality was 1.39 (95% confidence interval 1.35 to 1.44) for individuals with TG concentrations of less than 0.71 mmol/L and 1.97 (1.67 to 2.32) for TG concentrations of more than 5.70 mmol/L. The concentration of TG associated with the lowest risk of all-cause mortality was 1.84 mmol/L. Similar results were seen in men and women, in patients with or without lipid-lowering treatment, and for cause-specific mortality.

            CONCLUSION In the HF population, low and high levels of TG were associated with an increased risk of all-cause mortality, CVD and non-CVD. The lowest risk of all-cause mortality was found at a TG concentration of 1.84 mmol/L.

            GW33-e0587
            Hemodynamic monitoring improved the clinical outcomes of the patients with acute myocardial infarction complicated by cardiogenic shock

            You Jieyun, Geng Li, Shen Yunli, Huang Jing, Guo Wei, Zhang Qi

            Department of Cardiovascular Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China

            OBJECTIVES Acute myocardial infarction with cardiogenic shock (AMICS) often leads to a poor prognosis. Prompt and accurate monitoring of hemodynamic changes is crucial to the condition. Pulse index continuous cardiac output (PiCCO) provides precise hemodynamic parameters. However, there is scanty utilization of PiCCO in the management of AMICS. In this study, PiCCO is evaluated for its potential utility in improving management and clinical outcomes among AMICS patients.

            METHODS A total of 100 patients with AMICS were prospectively assigned to the PiCCO group and the control group by a 1:1 ratio in Shanghai East hospital from 2018 to 2021. The major adverse cardiovascular and cerebrovascular events (MACCEs) and parameters related to cardiac function were compared during follow-up.

            RESULTS PiCCO-guided intensive care reduced MACCEs and all-cause death 8 weeks after admission (P<0.05). The duration of hospitalization was appreciably shortened in the PiCCO group (P<0.05). The levels of hs-TnT, NT-proBNP, LVEF and Scr were improved more immediately and significantly in the PiCCO group accompanied by optimizing hemodynamic parameters (P<0.05).

            CONCLUSIONS Hemodynamic monitoring optimized the therapy for AMICS patients and improved their clinical outcomes.

            GW33-e0590
            Statin associated lower risk of incident dementia in heart failure patients: a territory-wide cohort study in Hong Kong

            Qing-Wen Ren, Yi-Kei Tse, Kai-Hang Yiu

            The University of Hong Kong

            OBJECTIVES The number of heart failure (HF) patients who develop dementia has grown rapidly due to improved treatment and aging populations. Data relating to the association of statin use on the risk of dementia incidence among patients with HF are sparse.

            METHODS Using a previously validated territory-wide clinical information registry, statin use was ascertained among all eligible patients with HF (N=104,295) from 2004 to 2018. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates between statin users (N=54,004) and statin non-users (N=50,291). Competing risk regression with Cox proportional-hazard models was performed to estimate the risk of incident dementia associated with statin use.

            RESULTS Of all eligible subjects, the mean age was 74.2±13.6 years and 52,511 (50.3%) were male. Over a median follow-up of 9.9 years (interquartile range [IQR]: 6.4–13.0), 10,031 (9.6%) patients were diagnosed with dementia including Alzheimer’s disease (N=2250), vascular dementia (N=1831), and unspecified dementia (N=5950). After IPTW, statin use was associated with a 20% lower risk of incident dementia compared with non-use (multivariable-adjusted sub-distribution hazard ratio [SHR]=0.80; 95% Confidence Interval [CI], 0.76–0.84). Furthermore, statin use was associated with a 27% lower risk of Alzheimer’s disease (SHR=0.72, 95% CI, 0.63–0.82), 18% lower risk of vascular dementia (SHR=0.82, 95% CI, 0.70–0.95), 20% lower risk of unspecified dementia (SHR=0.80, 95% CI, 0.75–0.85).

            CONCLUSIONS Our study suggests that in patients with HF, statin use was associated with a significantly lower risk of incident dementia, including Alzheimer’s disease, vascular dementia, and unspecified dementia.

            GW33-e0591
            Efficacy of cardiac contractility modulation in patients with heart failure: a meta-analysis

            Zhenyu Dong, Baopeng Tang, Yanmei Lu, Yusup Muyassar

            Department of Pacing and Electrophysiology, Department of Cardiac Electrophysiology and Remodeling, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES To investigate the effectiveness of cardiac contractility modulation (CCM) in patients with heart failure.

            METHODS We searched Wanfang, CNKI, VIP, Cochrane Trial Center, MEDLINE, and EMBASE from January 2001 to March 2022 to identify eligible clinical studies, which were systematically reviewed and meta-analysed. The primary endpoints were all-cause mortality, all-cause hospitalizations, heart failure hospitalizations, peak oxygen consumption, 6-minute walk test distance, quality of life scores, and incidence of arrhythmias.

            RESULTS A total of six trials were included, four of which were randomised controlled studies, recruiting a total of 935 patients. The analysis showed that compared with controls, CCM failed to improve all-cause mortality, all-cause hospitalizations, and heart failure hospitalizations, but significantly improved peak oxygen consumption (Mean Difference+0.91, 95% CI 0.44 −1.307, P=0.0001), 6-minute walk test distance (Mean Difference +20.36 m, 95% CI 6.06 −34.66, P=0.005) and quality of life as measured by MLWHFQ (Mean Difference −7.85, 95% CI 10.76 to 4.94, P<0.00001).

            CONCLUSIONS CCM failed to improve mortality and hospitalization in heart failure patients with short-term follow-up, but it had a statistically significant effect on patients’ quality of life. Larger randomized controlled trials may be needed to determine whether CCM treatment is beneficial in long-term follow-up.

            GW33-e0595
            Clinical characteristics of elderly chronic heart failure inpatients complicated with atrial fibrillation and its relationship with left atrial enlargement

            Shanshan Liu1, Suyan Bian1, Jian Zhu1, Binhua Wang2, Hongli Xu3, Kunlun He3

            1Cardiology Department, The Second Medical Center, & National Clinical Research Center of Geriatric Disease, Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, PLA General Hospital

            2Disaster Medical Research Center, Medical Innovation Research Department, PLA General Hospital

            3Medical Big Data Research Center, Medical Innovation Research Department, PLA General Hospital

            OBJECTIVES To analyze the clinical characteristics and risk factors of elderly patients hospitalized with chronic heart failure (CHF) combined with atrial fibrillation (AF) and their relationship with left atrial enlargement (LAE).

            METHODS Through the hospital information system and inpatient electronic medical record system, the gender, age, past medical history, discharge diagnosis and echocardiographic indexes of elderly patients (≥60 years old) hospitalized with CHF in our hospital from 2008 to 2020 were collected. The CHF patients were divided into two groups according to whether they were combined with AF. The differences in clinical characteristics, risk factors for AF, and the correlation between AF, CHF and LAE were analyzed.

            RESULTS Among the 4650 elderly CHF inpatients, 1411 (30.34%) were complicated with AF, of which 56.48% were heart failure with preserved ejection fraction (HFpEF). Compared with the CHF/AF- group (n=3239), patients in the CHF/AF+ group were older (73.79±7.90 years vs 72.12±7.64 years, P<0.05), women predominant (44.15 vs 39.12%, P<0.001), with more severe heart failure symptoms, a higher proportion of patients in New York Heart Association (NYHA) class III and above (74.99 vs. 68.42%), higher prevalence of valvular heart disease (348 cases, 24.66%) and primary cardiomyopathy (164 cases, 11.62%). Parameters reflecting left atrial size in cardiac ultrasound [left atrial anterior-posterior diameter (LAD-AP), medio-lateral diameter, supero-inferior diameter and left atrial volume index (LAVI)] and relative wall thickness in the CHF/AF+ group were significantly higher than those in the CHF/AF-group. The incidence of LAE was also significantly higher in the CHF/AF+ group than in the CHF/AF- group when LAVI and LAD-AP were used for the defining of LAE. Multifactorial logistic regression analysis showed that LAVI (OR=1.06) and high left ventricular mass index (defined as ;115g/m2 in men and >95g/m2 in women, OR=2.08) were independent risk factors for the development of AF in the elderly CHF patients.

            CONCLUSIONS Elderly patients with CHF have a higher comorbidity prevalence of AF, and those with AF may have more severe heart failure symptoms, more significant LAE, and worse left ventricular diastolic function. LAE is an independent risk factor for the development of AF in the elderly patients with CHF.

            GW33-e0600
            Clinical characteristics of different types of elderly patients hospitalized with chronic heart failure

            Shanshan Liu1, Suyan Bian1, Jian Zhu1, Binhua Wang2, Hongli Xu3, Kunlun He3

            1Cardiology Department, The Second Medical Center & National Clinical Research Center of Geriatric Disease, Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, PLA General Hospital

            2Disaster Medical Research Center, Medical Innovation Research Department, PLA General Hospital

            3Medical Big Data Research Center, Medical Innovation Research Department, PLA General Hospital

            OBJECTIVES To investigate and compare the clinical characteristics of elderly patients hospitalized with different types of chronic heart failure (CHF) in our hospital.

            METHODS Through the hospital information system and inpatient electronic medical record system, the gender, age, past medical history, discharge diagnosis and echocardiographic indexes of elderly patients (≥60 years old) hospitalized with CHF in our hospital from 2008 to 2020 were collected. Then the study population were divided into three groups according to left ventricular ejection fraction (LVEF): heart failure with preserved ejection fraction (HFpEF), heart failure with mildly reduced ejection fraction (HFmrEF) and heart failure with reduced ejection fraction (HFrEF). Clinical characteristics were compared among the above three CHF categories.

            RESULTS A total of 4650 valid data were included in the analysis, of which 59.35% were males with an average age of 72.63±7.76 years. HFpEF accounts for 49.46% and was the oldest in all elderly CHF inpatients, with an average age of 73.96±7.86 years. The top 5 underlying causes of CHF were ischemic heart disease (3375 cases, 72.58%), primary hypertension (2945 cases, 63.33%), arrhythmia (1986 cases, 42.71%), valvular heart disease (724 cases, 15.57%), and primary cardiomyopathy (457 cases, 9.83%). Among these, the prevalence of primary cardiomyopathy (354 cases, 21.76%) and ischemic heart disease (580 cases, 80.22%) was the highest in HFrEF and HFmrEF group, respectively. However, the prevalence of primary hypertension (1592 cases, 69.22%) and arrhythmia (1012 cases, 44.00%) were the highest in HFpEF group. The top 5 co-morbidities of CHF were dyslipidemia (3946 cases, 84.86%), chronic kidney disease (2190 cases, 47.10%), type 2 diabetes mellitus (1693 cases, 36.41%), anemia (1606 cases, 34.54%) and ischemic cerebrovascular disease (840 cases, 18.06%). The prevalence of dyslipidemia (635 cases, 87.83%) and type 2 diabetes (293 cases, 40.53%) was the highest in HFmrEF group, while anemia (949 cases, 41.26%) and ischemic cerebrovascular disease (470 cases, 20.46%) were more common in HFpEF group. There were significant differences in cardiac structural and functional ultrasound indices among the three types of CHF. Among them, left ventricular diastolic dimension, left ventricular mass index, left atrial anterior–posterior diameter, and left atrial volume index were the highest in HFrEF group, while the relative wall thickness, LVEF, and fractional shortening were the highest in HFpEF group (all P<0.05).

            CONCLUSIONS There are significant differences in the underlying etiology, co-morbidities and ultrasound indices among different types of elderly CHF inpatients. It is of great importance to carry out targeted comprehensive management and conduct clinical studies according to clinical characteristics.

            GW33-e0606
            Autonomic nervous system in hypertension and heart failure

            Ying Guo

            Beijing Tongren Hospital Afflicted Capital Medical University

            OBJECTIVES Left ventricular hypertrophy (LVH) is a clinically relevant sequela of elevated blood pressure (BP), then essential hypertension (EH) acts as a chief risk factor of congestive heart failure (CHF). Autonomic nervous system (ANS) plays a pivotal role in EH and LVH. Heart rate variability (HRV) is currently used as a noninvasive evaluation of ANS. Blood pressure and its variability (BPV) is also considered to be a marker of ANS in some reports. To explore the difference of autonomic nerve in patients with normal blood pressure, hypertension and heart failure and its correlation with left ventricular hypertrophy.

            METHODS One hundred ninety-two patients with essential hypertension, 40 patients with hypertension and heart failure, and 72 patients without hypertension or heart failure were enrolled. The general data of three groups were collected, 24-hour holter, ambulatory blood pressure measurement and echocardiography were performed. Heart rate variability (HRV), blood pressure variability (BPV) and left ventricular mass index (LVMI) calculated.

            RESULTS Gender distribution, history of diabetes, smoking and drinking, body mass index, triglyceride and glycosylated hemoglobin were similar among the groups. The age, cholesterol, BNP, albumin, LVMI, standard deviation of all normal sinus R–R intervals over 24 h (SDNN), high-frequency normalized units (HFnu), 24 h, day and night mean systolic blood pressure, diastolic blood pressure, pulse pressure, standard deviation of systolic blood pressure and systolic blood pressure decline rate among the three groups were statistically significant (P<0.05, P<0.01). In each pairwise comparison between groups, pulse pressure was significantly different (47.9±5.8, 55.8±11.7, 66.18±14.8, all P<0.01). There was a positive correlation between pulse pressure and LVH (r=0.2, P<0.01).

            CONCLUSIONS Pulse pressure may be a more sensitive index for left ventricular hypertrophy.

            GW33-e0632
            Analysis of cardiac structure and function in 2281 elderly patients with ejection fraction preserved heart failure complicated with anemia

            Jian Zhu1, Suyan Bian1, Shanshan Liu1, Binhua Wang2, Hongli Xu3, Kunlun He3

            1Cardiology Department, The Second Medical Center & National Clinical Research Center of Geriatric Disease, Beijing Key Laboratory of Chronic Heart Failure Precision Medicine, PLA General Hospital

            2Disaster Medical Research Center, Medical Innovation Research Department, PLA General Hospital

            3Medical Big Data Research Center, Medical Innovation Research Department, PLA General Hospital

            Objectives To analyze the characteristics of cardiac structure and function in elderly patients with ejection fraction preserved heart failure (HFpEF) complicated with anemia.

            METHODS A total of 2281 elderly HFpEF patients (≥60 years old) hospitalized in our hospital from February 2008 to December 2019 were enrolled and divided into anemia group or control group according to whether they had anemia or not. The clinical data of the patients were collected and the differences of cardiac ultrasound structure and function between the two groups were compared and analyzed.

            RESULTS There were 949 elderly HFpEF inpatients complicated with anemia, accounting for 41.6%. Compared with the control group, the anemia group had a higher proportion of male (54.69 vs 45.31%), older age (74.79±7.99 vs 73.40±7.72 years old), lower body mass index (24.34±4.10 vs 24.87±4.05 kg/m2), higher systolic and diastolic blood pressure (140.06/70.58 vs 136.77/74.89 mmHg), worse heart failure symptoms. Among them, the proportion of of New York Heart function above grade III was higher (27.25 vs 13.44%). The renal function was worse in the anemia group and the proportion of chronic kidney disease above grade 4 (55.11 vs 16.26%) was much higher than that of the control group. The all-cause mortality in hospital (3.58 vs 1.50%) was also higher (P<0.05) in the anemia group. Echocardiographic results showed that left heart enlargement was more obvious in the anemia group, including left atrial anteroposterior diameter (41.43±8.13 vs 40.64±7.62 mm), left atrial volume index (35.74±27.29 vs 33.22±21.79 mL/m2), left ventricular end-systolic volume (44.98±23.97 vs 41.15±15.75 mm), left ventricular end-diastolic volume (103.69±30.07 vs 97.36±31.03 mm), left ventricular end-systolic diameter (32.63±4.48 vs 31.64±4.89 mm), and left ventricular end-diastolic diameter (46.87±5.78 vs 45.75±6.47 mm), when compared with the control group. Moreover, the indexes of left ventricular hypertrophy, such as left ventricular posterior wall thickness (10.68±1.47 vs 10.47±1.52 mm) and left ventricular mass index (120.24±39.99 vs 110.14±36.91 g/m2) were also significantly higher than those in the control group (P<0.05). In addition, the diameter of the inferior vena cava (16.89±4.18 vs 16.15±3.93 mm), the maximum diameter of the right ventricle (35.90±7.42 vs 36.74±7.12 mm) and the main pulmonary artery diameter (22.93±3.40 vs 22.51±3.63 mm) in the anemia group were also larger than those in the control group.

            CONCLUSIONS The elderly HFpEF patients with anemia are male predominant, with a higher prevalence of hypertension and chronic kidney disease. The cardiac structure of HFpEF patients with anemia is characterized by left heart enlargement, left ventricular hypertrophy, right heart and inferior vena cava dilation. The heart and renal function and prognosis are poor.

            GW33-e0664
            Prognostic value of high-sensitivity modified Glasgow prognostic score in patients hospitalized for heart failure

            Guangda He, Lihua Zhang, Runqing Ji, Aoxi Tian

            National Clinical Research Center for Cardiovascular Diseases, NHC Key Laboratory of Clinical Research for Cardiovascular Medications, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular Diseases

            OBJECTIVES Inflammation plays a key role in the progression of heart failure (HF). High-sensitivity modified Glasgow prognostic score (Hs-mGPS) is a sensitive indictor of systemic inflammation which has been validated in cancer. It is unknown whether Hs-mGPS can assess the prognosis in patients hospitalized for HF. We sought to determine whether Hs-mGPS is independently associated with long-term mortality in patients hospitalized for HF.

            METHODS We enrolled patients hospitalized for HF from 52 hospitals in China. We calculated Hs-mGPS according to previous literature: patients with high-sensitivity C-reactive protein (hsCRP) ≤3 mg/L were defined as 0 score, those with hsCRP>3 mg/L and albumin ≥35 g/L as 1 score, and those with hsCRP;3 mg/L and albumin<35 g/L as 2 scores. The level of hsCRP were centrally analyzed with blood samples, and the level of albumin at admission were obtained from medical charts of the index hospitalization. The outcome was all-cause death after discharge. Unadjusted death rates were displayed with Kaplan–Meier plots and tested. Multi-variable Cox proportional regression models were performed to assess the association of Hs-mGPS with mortality, and the candidate covariates were selected based on literature review and clinical knowledge. We evaluated the incremental prognostic value of Hs-mGPS and established risk scores by C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) when adding it to Get With the Guidelines (GWTG) HF score.

            RESULTS Of the 4486 patients included in this analysis, the median (interquartile range, IQR) age was 67 (57, 75) years old and 37.5% were female. The median (IQR) levels of hsCRP and albumin at admission were 4.3 (1.7, 13.5) mg/L and 38.8 (35.7, 41.9) g/L. There were 1770 (39.5%) patients with 0 Hs-mGPS score, 2012 (44.9%) with 1 score, and 704 (15.7%) with 2 scores. Within 2-year of discharge, 1231 patients died. Patients with increasing Hs-mGPS had significantly higher risk of mortality in unadjusted analysis (P for log-rank<0.0001). Using multi-variable Cox models, compared with 0 Hs-mGPS score, the adjusted hazard ratios (HRs) were 1.22 (95% confidential interval [CI], 1.06–1.39) for 1 score and 1.78 (95% CI, 1.52–2.09) for 2 scores. When adding Hs-mGPS to GWTG HF score, the C-index was 0.66 (95% CI, 0.64–0.67), the NRI was 0.04 (95% CI, 0.00–0.09), and the IDI was 0.02 (95% CI, 0.01–0.03).

            CONCLUSIONS In this first report of Hs-mGPS among patients with HF, Hs-mGPS is a strong predictor for long-term mortality, and it could serve as a convenient inflammation-based tool for rapid risk stratification.

            GW33-e0708
            Factors associated with early left ventricular systolic dysfunction in post-COVID-19 patients

            Natalia Musikhina, Tatiana Petelina, Elena Yaroslavskaya, Nikita Shirokov, Elena Gorbatenko, Alina Valeeva

            Tyumen Cardiology Research Center - Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES Currently, it is not known what factors negatively affect the parameters of the global longitudinal strain of the left ventricle (GLS LV), which is considered the earliest marker of left ventricular systolic dysfunction. The objective was to study the factors associated with impaired GLS LV in persons without cardiovascular pathology and in patients with arterial hypertension.

            METHODS Two hundred forty-two patients included in the register “One-year cardiological follow-up of patients with COVID-19 associated pneumonia” were examined. All patients underwent blood sampling and echocardiography with speckle tracking analysis 3 months after COVID-19. The patients were divided into 2 groups. Group 1 (n=78) included individuals without cardiovascular pathology, 13 of them had a decrease in GLS LV (<-18%); group 2 (n=164) consisted of patients with arterial hypertension, of which GLS LV impairment was detected in 44 people.

            RESULTS Decrease in GLS LV in both groups was more often recorded in men (group 1 - 84.6.1%, P=0.006; group 2 - 68.2%, P=0.003), in group 1 in patients with increased body mass index (BMI) (30.41±vs 25.64±4.39, P=0.001). In both groups, there was a relationship between GLS LV impairment and erythrocytes level (group 1 r=−0.381, P=0.001; group 2 r=−0.232, P=0.003), hemoglobin (group 1 r=−0.381, P=0.001; group 2 r=−0.248, P=0.001), hematocrit (group 1 r=−0.407, P=0.000; group 2 r=−0.285, P=0.000), highly sensitive C-reactive protein (group 1 r=−0.293, P=0.009; group 2 r=−0.258, P=0.001) and with BMI (group 1 r=−0.293, P=0.010; group 2 r=−0.248, P=0.001). Additionally, in patients of group 1, relationship between GLS LV disturbance and HDL-C (r=0.405, P=0.000) and ferritin (r=−0.316, P=0.021) was established.

            CONCLUSIONS In patients who recovered from COVID-19, the factors associated with impaired GLS LV in both groups were laboratory parameters of blood viscosity, immune inflammation, and elevated BMI. In the group without cardiovascular pathology, a relationship between decrease in GLS LV and impaired lipid profile and ferritin was revealed, possibly as an indicator of oxidative stress.

            GW33-e0737
            Hidden myocardial systolic dysfunction one year after COVID-19 pneumonia by left ventricular global longitudinal strain

            Elena Yaroslavskaya, Dmitriy Krinochkin, Nikita Shirokov, Elena Gorbatenko, Elena Gultyaeva, Nadezhda Osokina, Anastasia Migacheva

            Tyumen Cardiology Research Center, Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES To study the influence of a new coronavirus infection complicated course on the patient’s cardiovascular system in the long term after discharge is important now. The bjective was to compare the clinical and echocardiographic parameters of survivors one year after COVID-19 pneumonia, depending on the value of the left ventricular global longitudinal strain (LV GLS).

            METHODS One hundred sixteen patients were examined one year ± 3 weeks after discharge after proven COVID-19 pneumonia, mean age 49.0±14.4 years (from 19 to 84 years); 50.4% men. The LV GLS were studied in 80 patients with optimal visualization quality in echocardiography. Patients were divided into groups depending on the LV GLS value: group 1 with normal LV GLS (−20% or less) - 35 patients, group 2 with impaired LV GLS (more than −20%) - 45 patients.

            RESULTS The groups did not differ in age (P=0.145), severity of lung injury during hospitalization (P=0.691), duration of hospitalization (P=0.626) and frequency of stay in intensive care units (P=0.420). LV GLS one year after discharge was impaired in 57.5% of patients with optimal visualization quality, while the LV ejection fraction (EF) was normal in all patients. The majority of group 2 were men (71.1 vs 28.6%, P<0.001), a combination of coronary artery disease (CAD) and arterial hypertension (AH) was more often diagnosed in this group (22 vs 6%, P=0.040). There were no differences in LV EF between the groups. However, LV GLS was impaired in group 2 (−17.6±1.9 vs −21.8±1.2%, P<0.001), as were the parameters of diastolic function - lower left atrial emptying volume index (1.3±0.3 mL/m2 vs 1.4±0.3 mL/m2, P=0.052), lower velocity of the lateral part of the mitral ring e′ (10.8±4.4 cm/s vs 12.8±4.0 cm/s, P=0.045).

            CONCLUSIONS LV GLS was impaired in 57.5% with normal LV EF one year after COVID-19 pneumonia. In the group with impaired LV GLS, men predominated, CAD was more often detected in combination with AH, and parameters of LV diastolic function were worse compared to the group with normal LV GLS.

            GW33-e0755
            The mediation effect of blood pressure in association of obesity and arterial stiffness in heart failure preserved ejection fraction patients

            Min Sun1, Hongmei Bai1, Xiaowei Tan1, Linna You1, Xiaofang Zhang1, Jin Xiao1, Xiangliang Deng1, Hanwen Yi1, Hongmei Tao1, Pin Ge2, Yuhong Qin1, Dongying Zhang1

            1Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

            2Department of Cardiovascular Medicine, The First Branch of the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China

            OBJECTIVES Long-term increased blood pressure partly mediated the association between increased childhood-body mass index (BMI) and adult-aortic-femoral pulse wave velocity in common population. However, no study has revealed blood pressure mediates the association between obesity and arterial stiffness in HFpEF patients. Thus, we conducted this study to explore the role of blood pressure in the relationship between obesity and arterial stiffness in HFpEF population.

            METHODS Ninety-four patients with HFpEF were recruited in the present study. Obesity indexes included BMI, waist circumference (WC), hip circumference (HC), waist-hip ratio (WC/HC), abdominal circumference (AC), body fat mass, fat percentage and visceral fat area (VFA). Blood pressure came from the upper limbs. Brachial–ankle pulse wave velocity (baPWV) was used to estimate arterial stiffness. Mediation analysis was performed to reveal whether the effect of obesity on arterial stiffness can be explained by BP in a population with HFpEF.

            RESULTS 93.6% of HFpEF patients were accompanied with abdominal obesity. Among all the detected indicators of obesity including BMI, WC, HC, WC/HC, AC, VFA, body fat mass and fat percentage, only VFA was positively associated with baPWV (β=5.898, 95% CI 2.226–9.569, P=0.002). SBP, DBP and PP were all related to baPWV (P<0.05). SBP and PP, but not DBP, were associated with VFA. The mediation effect of SBP and PP on the VFA-baPWV association were 35.1% (indirect effect was 2.070, P<0.05) and 35.2% (indirect effect was 2.074, P<0.05), respectively. DBP failed to mediated the association between VFA and baPWV.

            CONCLUSIONS The systolic blood pressure and pulse pressure might be mediators of VFA-induced arterial stiffening in HFpEF patients.

            GW33-e0782
            Tricuspid regurgitation as an independent predictor of cardiogenic shock among hospitalized patients with heart failure

            Huayuan Zeng, Ying Shi, Yuyan Zhang, Yu Liu, Qili Huang, Ning Wu, Ling Liu, Qingwei Ji

            Department of Cardiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Institute of Cardiovascular Diseases, Guangxi Academy of Medical Sciences, Nanning, China

            OBJECTIVES The presence of Cardiogenic shock (CS) is associated with poor prognosis in patients with heart failure (HF). The relationship between transthoracic echocardiography (TTE) parameters and the development of CS in patients with HF is less known. Our study aims to evaluate the predictive value of TTE parameters for the development of CS among hospitalized patients with HF.

            METHODS Adult patients who received TTE measurements and were discharged with a diagnosis of HF from October 2018 to December 2021 were included in this retrospective study. Multivariate logistic regression was used to evaluate predictors of CS. Patients with CS were divided into 4 groups according to quartiles of the duration of vasoactive therapy. Ordinal logistic regression was used to assess predictors of vasopressor dependency.

            RESULTS A total of 2064 patients were included, among which 338 (16.4%) were identified as having CS and were treated with vasopressors for a median duration of 4 (2–7) days. Multivariate analysis showed that lower weight, lower systolic blood pressure at admission, higher New York Heart Association (NYHA) class, revascularization therapy, dialysis, history of hypertension, as well as a higher level of serum makers including leukocytes, C-reactive protein, and troponin were independent predictors of CS (all P-value<0.05). TTE variables such as left atrial diameter and tricuspid regurgitation were independently associated with CS (adjusted OR 0.97, 95% CI 0.94–0.99, P=0.003; adjusted OR 1.5, 95% CI 1.09–2.06, P=0.012; respectively) but were unrelated to vasopressor dependency. Patients who had severe HF symptoms (NYHA class IV) were more likely to experience a longer duration of vasoactive therapy compared with those who had mild HF symptoms (NYHA class II) (OR 3.09, 95% CI 1.64–5.83, P<0.001). A similar trend was observed in dialysis-dependent patients compared with non-dialysis-dependent patients (OR 4.58, 95% CI 1.94–10.82, P=0.001).

            CONCLUSIONS Our data suggest that TR is an independent predictor of CS in hospitalized patients with HF but is not associated with the duration of vasoactive therapy.

            GW33-e0789
            Heart failure with preserved ejection fraction and regional adiposity: vicious twins

            Jin Zhao, Xi Wang, Yi Hanwen, Deng Xiangliang, Liu Zhiqiang, Zhang Xiaofang, Xiao Jin, Sun Min, Zhang Dongying, Gao Lei

            Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

            OBJECTIVES Recent research reports that regional adiposity, notably epicardial and visceral fat, may serve a pivotal pathophysiologic role in HFpEF. We aimed to describe the role of regional adiposity and obese related indicators on predicting all-cause death in patients with HFpEF.

            METHODS This was a prospective cohort study included 172 patients with HFpEF who were recruited in the First Affiliated Hospital of Chongqing Medical University from September 2020 to January 2022. The primary outcome of this study was all-cause mortality in patients with HFpEF.

            RESULTS A total of 172 patients whose mean age was 72 years were included in this study, of which 40.1% (n=69) were males and 59.9% (n=103) were females, 66% had hypertension and 40% had atrial fibrillation. A total of 7 patients died after a median follow-up time of 395.5 days (interquartile range: 207.5 to 535.5 days). Patients with higher VFA were older, had higher BMI, and more frequently had pre-existing hypertension and AF. Age, Smoking, BMI and VFA were significantly associated with higher mortality in HFpEF by cox univariable analysis. However, pericardial adipose tissue (PAT) thickness, epicardial adipose tissue (EAT) thickness, abdominal obesity, waist/hip ratio and body fat mass failed to predicting outcomes of HFpEF. After adjusting for cofounders of other underlining risk factors, VFA could independently predict all-cause mortality in patients with HFpEF.

            CONCLUSIONS VFA might be an independent prognostic risk factor for all-cause mortality in patients with HFpEF.

            BLOOD LIPIDS AND ATHEROSCLEROSIS
            GW33-e0105
            The associations among carotid plaque progression, cerebrovascular/cardiovascular diseases and LDL-C/ non-HDL-C goal achievement in diabetic patients: a retrospective cohort study

            Li Hongwei1, Guo Qi1, Xie Wei2, Zhan Xiaoying2, Chen Qian1, Xie Xiangkun1, Zhang Jie1, Sun Runlu1, Cao Zhengyu1, Jiang Yuan1, Xu Xiaolin2, Zhang Yuling1

            1Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou 510120, China

            2Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou 510120, China

            OBJECTIVES Impaired glycolipid metabolism can induce vascular injury and plaque formation. Carotid ultrasonography is an important examination to assess carotid plaque, the presence of which is correlated with increased cardiovascular risk. Current recommendations provide no instruction for repeated carotid ultrasound examinations to guide lipid-lowering therapeutic decisions. It is important to investigate the associations between carotid plaque progression and lipid-lowering goal achievement and cardiovascular disease.

            METHODS Diabetic patients who underwent at least 2 carotid ultrasound scans with intervals ≥0.5 years and were hospitalized in the Department of Endocrinology at Sun Yat-sen Memorial Hospital were included. Patients were divided into 3 groups based on carotid plaque progression: the persistent plaque absence, new-onset plaque and persistent plaque presence groups. The primary outcomes were low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal achievement. Carotid arterial parameters, lipids and other clinical variables were recorded. Logistic regression analysis and linear regression analysis were performed for the association between carotid plaque progression and lipid-lowering goal achievement.

            RESULTS There were 304 diabetic patients included, with a median follow-up period of 2.15 years. In multivariable logistic regression analysis, persistent plaque presence was positively associated with the prevalence of coronary heart disease (CHD) and stroke, while new-onset plaque was positively associated with the prevalence of stroke compared to persistent plaque absence in patients with follow-up periods ≥0.5 years, ≥1 year and ≥2 years. Categorical variables of carotid plaque progression were not significantly associated with LDL-C/non-HDL-C goal achievement. The velocity of the average plaque length change was independently associated with increased ΔLDL-C (last – goal).

            CONCLUSIONS Carotid plaque progression was independently associated with the prevalence of CHD and stroke, while the velocity of the average plaque length was associated with increased ΔLDL-C (last – goal). Repeated carotid plaque measurement might guide lipid-lowering therapy, but this requires further validation.

            GW33-e0224
            Identification and validation of candidate gene module along with immune cells infiltration patterns in atherosclerosis progression to plaque rupture via transcriptome analysis

            Cheng Chen, Jing Xu, Yuejin Yang

            Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Atherosclerosis is the major cause of a global cardiovascular disease, ischemic stroke, as well as peripheral arterial disease. The inflammatory nature of atherosclerosis remains a predominant reason for plaque vulnerability, and the interplay between immune cells and genetic modulations in atherosclerosis formation, progression, and plaque rupture is still vastly under-investigated.

            METHODS In this study, three atherosclerosis-related microarray datasets were downloaded from the NCBI-GEO database. Gene set enrichment analysis (GSEA) was performed for interpreting the biological insights of gene expression data. CIBERSORTx algorithm was applied to infer the relative proportions of infiltrating immune cells of the atherosclerotic samples. DEGs of the datasets were screened using R. The protein interaction network was constructed via STRING. The cluster genes were analyzed by Cytoscape software. Gene ontology (GO) enrichment was performed via geneontology.org. The least absolute shrinkage and selection operator (LASSO) logistic regression algorithm and receiver operating characteristics (ROC) analyses were performed to build machine learning models for differentiating atherosclerosis status. The Pearson correlation analysis was carried out to illustrate the relationship between cluster genes and immune cells. The expression levels of the cluster genes were validated in two external cohorts. Transcriptional factors and drug-gene interaction analysis were performed to investigate the promising targets for atherosclerosis intervention.

            RESULTS Pathways related to immunoinflammatory responses were identified according to GSEA analysis, and the detailed fractions infiltrating immune cells were compared between the early and advanced atherosclerosis. Additionally, we identified 170 DEGs in atherosclerosis progression (|log2FC|≥1 and adjusted P<0.05). They were mainly enriched in GO terms relating to inflammatory response and innate immune response. A cluster of nine genes including ITGB2, C1QC, LY86, CTSS, C1QA, CSF1R, LAPTM5, VSIG4, and CD163 was found to be significant, and their correlations with infiltrating immune cells were calculated. The cluster genes were also validated to be up-regulated in two external cohorts. Moreover, C1QA and ITGB2 may exert pathogenic functions in the entire process of atherogenesis.

            CONCLUSIONS We reanalyzed the transcriptomic signature of atherosclerosis development from onset to plaque rupture along with immune cells landscape, as well as revealed new insights and specific prospective DEGs for the investigation of disease-associated dynamic molecular processes and their regulations with immune cells.

            GW33-e0365
            Remnant cholesterol and joint arteriosclerosis and atherosclerosis progression beyond LDL cholesterol in the general population

            Zhiyuan Wu1,2, Jinqi Wang1, Lixin Tao1, Xiuhua Guo1,2

            1Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China

            2Centre for Precision Health, Edith Cowan University, Perth, Australia

            OBJECTIVES Remnant cholesterol could predict cardiovascular events, while its effect on joint arteriosclerosis and atherosclerosis progression remains unclear. This study aims to evaluate the association of remnant cholesterol with arteriosclerosis and atherosclerosis progression trajectories in the general population, and evaluate its effect beyond low density lipoprotein (LDL) cholesterol.

            METHODS This longitudinal study collected data across five biennial surveys of the Beijing Health Management Cohort from 2010 to 2019. We used the multi-trajectory model to cluster the joint arteriosclerosis and atherosclerosis progression groups measured by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). Remnant cholesterol was both calculated by Martin-Hopkins method and Friedewald equation. Then, the ordinal logistics model was performed to assess the effect of baseline lipid profiles on progression trajectories. We also performed discordance analyses for remnant cholesterol vs. LDL cholesterol according to the percentile distance (ten percents) and clinical cut-off points.

            RESULTS A total of 3186 participants were included, with three clusters following distinct arteriosclerosis and atherosclerosis progression patterns identified using a multi-trajectory model. In the multivariable-adjusted ordinal logistics analyses, remnant cholesterol was significantly associated with baPWV and ABI progression (OR: 1.20; 95% CI: 1.13–1.28, per 10 mg/dL). We also performed discordance analyses for remnant cholesterol vs. LDL cholesterol, and the discordant low remnant cholesterol group was associated with decreased risk compared to the concordant group (OR: 0.73; 95% CI: 0.60–0.89). People with a high remnant cholesterol level were at an increased risk of joint arteriosclerosis and atherosclerosis progression, even with optimal LDL cholesterol.

            CONCLUSIONS Remnant cholesterol is independently associated with joint arteriosclerosis and atherosclerosis progression beyond LDL cholesterol. Remnant cholesterol could be an earlier risk factor than LDL cholesterol of arteriosclerosis and atherosclerosis in the general population. Future studies are needed to assess whether Remnant cholesterol is a potential intervention target for arteriosclerosis and atherosclerosis, and cardiovascular events, even in people with an optimal LDL cholesterol level.

            GW33-e0460
            Liver damage of xuezhikang compared with statin in patients with hypercholesterolemia: results from a multicenter, retrospective real-world study in China

            Zeya Li1, Min Wang2, Qi Chen1, Guosheng Fu2, Rongchong Huang1

            1Beijing Friendship Hospital, Capital Medical University

            2Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University

            OBJECTIVES Both Xuezhikang and statins could effectively decrease cholesterol levels. However, the potential harmful effect of statin therapy on liver has become a concern in clinical practice. Thus, we conducted a large multicenter, retrospective cohort study to investigate the safety of xuezhikang compared with statin in patients with hypercholesterolemia, especially liver damage.

            METHODS A total of 1746 patients with hypercholesterolemia were enrolled from 3 centers in China. Five hundred eighty-three patients received 1200 mg/d of Xuezhikang while 1163 patients received moderate statin. The primary outcome was defined as the changes of liver transaminases from baseline to the study end-point (90 days from the baseline). Secondary outcomes included the incidences of liver transaminases > 3 upper limit of normal (ULN), the absolute value of liver transaminases, creatine kinase (CK), HbA1c, fasting glucose at the study end-point, and the changes of low-density lipoprotein cholesterol (LDL-C), cholesterol and non-high-density lipoprotein cholesterol (non-HDL-C) from baseline to end-point.

            RESULTS Mean baseline aspartate transaminase (AST) for the two treatment groups were 22.27 and 21.93 mmol/L while the mean alanine transaminase (ALT) was 21.07 and 20.3 mmol/L for the xuezhikang and statin groups respectively. After a follow-up duration of 90 days, the changes of AST/ALT from baseline to end-point were lower in xuezhikang group than in statin group (xuezhikang vs. statin for AST: 1.34±5.77 vs 3.86±11.61, P<0.001; xuezhikang vs. statin for ALT: 5.24±16.19 vs. 2.93±10.37, P=0.002). After adjusted for age and gender, the changes of AST/ALT were still lower in xuezhikang group than in statin group (AST P=0.001, ALT P=0.004, respectively). Similar effects were observed on the absolute value of AST (xuezhikang vs. statin: 23.61±6.83 vs 25.76±11.99, P<0.001). The incidences of ALT/AST ; 3 ULN were low in both groups and no difference was observed (xuezhikang vs. statin: 0.2 vs 0.3%, P=0.670). No significant difference was observed in terms of the CK, HbA1c, and fasting glucose at the end-point between the groups (P<0.05). In addition, both treatments produced significant efficacy on LDL-C (xuezhikang: 3.26 vs. 2.44 mmol/L, P<0.001; statin: 3.34 vs. 2.10 mmol/L, P<0.001), cholesterol (xuezhikang: 5.72 vs. 4.58 mmol/L, P<0.001; statin: 5.69 vs. 4.18 mmol/L, P<0.001) and non-HDL-C (xuezhikang: 4.41 vs. 2.91 mmol/L, P<0.001; statin: 4.36 vs. 3.29 mmol/L, P<0.001) from baseline to end-point. However, significantly more patients achieved LDL-C levels < 2.6 mmol/L (80 vs. 60%), < 1.8 mmol/L (41 vs. 22%) and < 1.4 mmol/L (17 vs. 5%) with statin than xuezhikang (all P<0.001).

            CONCLUSIONS In patients with hypercholesterolemia, xuezhikang treatment was much safer on liver function compared with moderate statin, but also produced significant efficacy on lipid reduction compared with baseline.

            GW33-e0552
            Effects of rosuvastatin for delaying progression of atherosclerosis in people living with HIV

            Jingyi Wu1,2, Jian Yang1,2, Jing Zhang1,2, Yifan Huang1,2

            1Department of cardiology, The First College of Clinical Medicine Science, China Three Gorges University

            2Institute of cardiovascular disease< Chinese Three Gorges University

            OBJECTIVES People with HIV are more susceptible to atherosclerosis due to immune disorder, chronic inflammatory state, and highly active antiretroviral therapy. Present research are design to evaluate the efficacy and safety of rosuvastatin for delaying progression of atherosclerosis in people living with HIV.

            METHODS Randomized controlled trials (RCTs) were searched from MEDLINE (1980–July 2021), the Cochrane Controlled Trials Register, EMBASE (1985–July 2021), Science Citation Index and PUBMED (updated through July 2021). The change of unilateral or bilateral carotid intima-media thickness from baseline was defined as the primary outcome while the variation of LDL-c, IL-6 and hsCRP as the second. Statistical analyses were performed using Review Manager software (version 5.4; The Cochrane Collaboration). The analysis was stratified by the difference of control group: placebo or rosuvastatin therapy. The weighted mean difference (WMD) of continuous variables was calculated with 95% confidence interval (CI).Heterogeneity was assessed by the I2 measure of inconsistency, statistically significant if I2 was ;50%. For all the outcomes a P value of less than 0.05 was considered statistically significant.

            RESULTS Three eligible trials of rosuvastatin therapy involving a total of 273 patients were included after reviewing by two independent reviewers. (137 subjects received rosuvastatin, while 136 subjects were in the placebo) All of three studies showed that the change of mean carotid IMT progression from baseline were significantly different between rosuvastatin and placebo, the Z score for overall effect of IMT was 6.03(P<0.00001), Total 95% CI of weighted mean difference (WMD) between two groups was −0.01 [−0.01, −0.01]. Three studies provided information regarding variation of hsCRP and IL-6. There was a significant difference between two groups in hsCRP [Z score 4.03(P<0.00001); 95% CI (−2.27)–(−0.78)] but not in IL-6 [Z score 1.03 (P=0.30); 95% CI −1.16–0.36]. A significant difference was also found in the change of LDL-c from baseline. [Z score 3.43(P=0.0006); 95% CI (−36.05)–(−29.13)]. Rosuvastatin was not significantly different of serious adverse events and withdrawal than placebo (P;0.05).

            CONCLUSIONS Rosuvastatin is an accessible, safe and effective drug that could be utilized for delaying progression of atherosclerosis in people living with HIV. The tolerability, benefits, and safety should be confirmed in in-depth clinical trials.

            GW33-e0626
            Aerobic exercise ameliorates dysfunctional high-density lipoprotein sub-fractions via protein composition alteration in youth with obesity

            Qian Chen, Zhijian He, Wenhao Liu, Hongwei Li, Qi Guo, Runlu Sun, Xiaoying Wu, Xiangkun Xie, Jingjing Huang, Jingfeng Wang, Yuling Zhang

            Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University

            OBJECTIVES Obesity becomes an emerging cardio-metabolic problem globally. High-density lipoprotein (HDL) might be compromised in obesity. The mechanisms for beneficial effects of aerobic exercise on HDL has not been investigated comprehensively. This study was designed to investigate whether aerobic exercise without restricted diet ameliorates dysfunctional HDL by altering protein composition in youth with obesity.

            METHODS This was a single centre and self-control study. All youth participants with body mass index > 28 kg/m2 received a personalized 12-week moderately aerobic exercise program according to the result of cardiorespiratory fitness test. Fasting plasma samples of each participant were collected before and after exercise intervention. HDL from each sample was isolated by fast protein liquid chromatography and further evenly divided into three sub-fractions: large-HDL fraction, medium-HDL fraction, and small-HDL fraction. The protein composition of three HDL sub-fractions were analyzed by mass spectrometry using label-free protein quantification. We detected HDL-cholesterol, HDL2- cholesterol and HDL3-cholesterol concentrations from samples before and after exercise intervention, and further measured the following functional characteristics in each HDL sub-fraction: cholesterol efflux capacity, anti-oxidative capacity (by HDL inflammatory index), and HDL-related endothelial protection capacity.

            RESULTS Though the levels of plasma HDL-cholesterol levels were similar before and after the 12-week exercise training, HDL2-cholesterol level was significantly increased. One hundred sixteen HDL-bound proteins were detected in HDL-subfractions and further grouped into 4 functional categories (lipid metabolism, immune response, coagulation, and others). The composition of HDL-bound proteins was significantly altered after 12-week exercise intervention. In medium-HDL fraction, the levels of apoA1 and apoE were increased. Meanwhile, the aerobic exercise induced a significant improvement in cholesterol efflux capacity of medium-HDL. We also found that the function, inhibiting the tumor necrosis factor-α-induced monocyte adhesion to endothelial cells, were improved in large-HDL fraction along with the significant elevation of apoM level. However, HDL inflammatory index in all three sub-fractions were not changed after exercise intervention.

            CONCLUSIONS A 12-week aerobic exercise program might lead to an efficient cardio-protective improvement on HDL via protein composition alterations.

            GW33-e0634
            Association of trajectories of lipid profile and carotid atherosclerosis progression

            Haixu Yu1,2, Wei Zhao1, Wei Gao1

            1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing 100191, China

            2Department of Cardiology, Beijing Jishuitan Hospital, Beijing 100035, China

            OBJECTIVES Early assessment of carotid atherosclerotic plaque characteristics is essential for atherosclerotic cardiovascular disease (ASCVD) risk stratification and prediction. We aimed to identify different trajectories of lipid profiles and to investigate the association of lipid trajectories with Carotid atherosclerosis (CAS) progression in a large, longitudinal cohort of the Chinese population.

            METHODS Ten thousand four hundred and twelve participants aged ≥18 years with ≥2 times general health checks were included in this longitudinally prospective cohort study at Peking University Third Hospital. We used latent class trajectory models to identify trajectories of four lipid profiles (TG, TC, LDL-C, HDL-C) over follow-up time (757 days, IQR: 388–844 days).

            RESULTS Participants categorized by the presence of carotid plaque were more likely to be older, male, have higher BMI, have a higher prevalence of hypertension, diabetes, dyslipidemia, have a higher level of blood pressure, HbA1c, TG, TC, LDL-C, compared with carotid intima-media thickness (cIMT) and normal group.

            CONCLUSIONS Borderline elevated lipid (TC, TG, and LDL-C) with stable and elevated-increasing trajectories were associated with CAS progression. Long-term strategies for low-level lipid are beneficial for ASCVD management.

            STRUCTURAL HEART DISEASE
            GW33-e0007
            Current treatment and future prospect of LVHT

            Yifeng Xu, Hongli Li

            Shanghai General Hospital

            OBJECTIVES Left ventricular hypertrabeculation (LVHT) is a rare myocardiopathy associated with indistinct aetiology and significant mortality. Although LVHT is increasingly recognized among cardiologists nowadays, few advances have been achieved to conquer this disease up to now, particularly its treatment. Therefore, in this investigation we aimed to analyze and summarize current clinical treatment of LVHT and come up with novel therapeutic strategies for lower mortality, combined to updating therapeutic technologies in cardiology.

            METHODS Five patients were selected (two females, three males) from Shanghai General Hospital on the basis of suspicious CMRI (cardiac magnetic resonance imaging) manifestations and typical clinical presentations for diagnosing LVHT. The average age of those five patients were 56.60±6.31 years, ranging from 46 to 62 years.

            RESULTS Through analyzing five patients’ therapeutic protocols, we discover that clinical treatment of LVHT is mainly focus on the symptoms or the complications of LVHT, such as heart failure, arrhythmia and thromboembolism. For patients who suffered from heart failure, tablets like βBlockers, angiotensinconvertingenzyme inhibitors (ACEI), angio tensin II receptor blockers (ARB), mineralocorticoid receptor antagonists, and diuretics were used to manage cardiac dysfunction. For patients who were undergoing arrhythmia such as atrial fibrillation (AF), radiofrequency catheter ablation (RFCA) and oral anticoagulation were applied. Implantable cardioverter defibrillator (ICD) implantation were executed when ventricular tachycardias were recorded for the prevention of sudden cardiac death (SCD). βBlockers were also used for heart rate stabilization and long-term cardiac benefit. For patients who had the history of thromboembolism, antiplatelet therapy was utilized.

            CONCLUSIONS Currently, clinical therapy of LVHT is symptomatic treatment. Complications such as heart failure, arrhythmia and thromboembolism in LVHT patients are treated in the same way as those diseases caused by other aetiologies. Lack of specific therapeutic strategies for treating LVHT is an intractable obstacle for reducing the mortality of this disorder.

            GW33-e0436
            A nomogram for predicting patent foramen ovale-related stroke recurrence

            Zhuonan Wu1, Jufang Chi2

            1Shaoxing University School of Medicine

            2The First Affiliated Hospital of Shaoxing University

            OBJECTIVES The high prevalence of patent foramen ovale (PFO) in cryptogenic stroke suggested a stroke-causing role for PFO. As risk factors for recurrence of such stroke are not recognized, clinicians cannot sufficiently identify, treat, and follow-up high-risk patients. Therefore, this study aimed to establish a prediction model for PFO-related stroke recurrence.

            METHODS This study included 392 patients with PFO-related stroke in a training set and 164 patients with PFO-related stroke in an independent validation set. In the training set, independent risk factors for recurrence identified using forward stepwise Cox regression were included in nomogram1, and those identified using least absolute shrinkage and selection operator (LASSO) regression were included in nomogram2. Nomogram performance and discrimination were assessed using the concordance index (C-index), area under the curve (AUC), calibration curve, and decision curve analyses (DCA). The results were also validated in the validation set.

            RESULTS Nomogram1 was based on homocysteine (Hcy), high-sensitivity C-reactive protein (hsCRP) and albumin (ALB), and nomogram2 was based on Age, Diabetes, Hypertension, right-to-left shunt, ALB, prealbumin, hsCRP and Hcy. The C-index of nomogram1 was 0.861, which was not significantly different from that of nomogram2 (0.893). The 2- and 5-year AUCs of nomogram1 were 0.863 and 0.777, respectively. In the validation set, nomogram1 still had good discrimination (C-index, 0.862; 2-year AUC, 0.839; 5-year AUC, 0.990). The calibration curve showed good homogeneity between the prediction by nomogram1 and the actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were successfully divided into two distinct risk groups (low and high risk) for recurrence rate by nomogram1.

            CONCLUSIONS Nomogram1 based on Hcy, hsCRP, and ALB levels provided a more clinically realistic prognostic prediction for patients with PFO-related stroke. This model could help patients with PFO-related stroke to facilitate personalized prognostic evaluations.

            GW33-e0545
            Association between proportionality of tricuspid regurgitation with outcome after tricuspid annuloplasty

            Yi-Kei Tse, Hang-Long Li, Ka-Lam Leung, Qing-Wen Ren, Kai-Hang Yiu

            Division of Cardiology, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, China

            OBJECTIVES Patients with secondary tricuspid regurgitation (TR) benefit differentially from tricuspid annuloplasty. We hypothesized that TR severity may be proportional or disproportional to right ventricular (RV) remodeling and investigated the prognostic implication of this novel framework.

            METHODS The ratios of pre-procedural effective regurgitant orifice area (EROA) with right ventricular end-diastolic area (RVDA) and tricuspid annular plane systolic excursion (TAPSE) were retrospectively assessed in 307 patients undergoing tricuspid annuloplasty. Based on optimal thresholds derived from cubic splines and maximally selected rank statistics, patients were stratified into 3 groups: proportionate TR (Group 1: EROA/RVDA≤1.70 and EROA/TAPSE≤3.42), disproportionate TR to RV size (Group 2: EROA/RVDA>1.70 and EROA/TAPSE≤3.42), and disproportionate TR to RV size and function (Group 3: EROA/RVDA>1.70 and EROA/TAPSE;3.42).

            RESULTS Overall, 77 (25%), 126 (41%), and 104 (34%) patients were classified into Group 1, 2, and 3, respectively. Compared with those with proportionate TR (Group 1), patients with disproportionate TR (Group 2 and 3) had a higher prevalence of atrial fibrillation and smaller left ventricular end-diastolic and end-systolic volumes. During a median (interquartile range) follow-up of 4.1 (2.5–6.2) years, 81 adverse events (49 HF hospitalizations and 32 deaths) occurred. Patients with disproportionate TR (Group 2 and 3) had higher rates of adverse events than those with proportionate TR (22 and 44 versus 9%; P=0.018 and P<0.001, respectively) and were independently associated with poor outcomes on multivariate analysis. TR proportionality outperformed guideline-based prediction algorithm comprising EROA and RV assessment in outcome prediction (C-statistic 0.70 versus 0.62, P=0.015; likelihood ratio test<0.001).

            CONCLUSIONS Disproportionate TR is independently associated with poor prognosis in patients undergoing tricuspid annuloplasty. Characterization of TR severity to RV size and function may aid patient selection and risk stratification for tricuspid annuloplasty.

            GW33-e0555
            Characteristics and outcomes of patients with mixed mitral valve disease

            Yi-Kei Tse, Hang-Long Li, Ka-Lam Leung, Qing-Wen Ren, Kai-Hang Yiu

            Division of Cardiology, Department of Medicine, The University of Hong Kong Shenzhen Hospital, Shenzhen, China

            OBJECTIVES Concurrent presence of mitral stenosis (MS) and mitral regurgitation (MR) is termed mixed mitral valve disease. Although several studies have examined patients with isolated MS or MR, few have explored the characteristics and outcomes of patients with mixed mitral valve disease. The present study aimed to investigate the fate and predictors of clinical outcomes in patients with mixed mitral valve disease compared to isolated MS.

            METHODS This observational cohort study evaluated 117 adult patients (age 67±9 years; 27% male) with at least moderate MS with or without concomitant MR, excluding those with significant aortic stenosis or regurgitation. Clinical, laboratory, and echocardiographic characteristics were correlated with adverse events, defined as the composite of heart failure (HF) hospitalization, stroke, and all-cause mortality.

            RESULTS Isolated MS was present in 39 (33%) patients, while concomitant MS and MR was present in 78 (67%). Compared to patients with isolated MS, those with mixed mitral valve disease more frequently had HF and more prevalent use of diuretics. Left ventricular end-diastolic and end-systolic volumes, left atrial volume, and right ventricular systolic pressure were higher in patients with mixed mitral valve disease than their counterparts. Over a median follow-up of 5.7 years (interquartile range: 4.4 to 9.0 years), 50 adverse events (35 HF hospitalizations, 10 strokes, and 5 deaths) occurred. In multivariable Cox regression analysis, left ventricular end-diastolic volume was the only independent echocardiographic predictor for adverse events (adjusted hazard ratio 1.05, 95% confidential interval 1.01–1.09, P=0.043), after adjusting for baseline HF, use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, and estimated glomerular filtration rate. There was no difference in event rates between patients with mixed mitral valve disease and isolated MS (38 vs. 51%, P=0.790).

            CONCLUSIONS Mixed mitral valve disease confers a high risk of adverse events. Left ventricular end-diastolic volume appears to be the most important echocardiographic predictor of clinical outcomes in patients with mixed mitral valve disease.

            GW33-e0629
            CT anatomy characteristics based on transcatheter aortic valve replacement in aortic regurgitation

            Yang Chen1, Jie Zhao1, Qingrong Liu1, Hongliang Zhang1, Moyang Wang1, Guannan Niu1, Zhenyan Zhao1, Qian Zhang1, Zheng Zhou1, Yunqing Ye1, Zhe Li1, Dejing Feng1, Erli Zhang1, Bin Zhang1, Bin Lv2, Haiyan Xu1, Guangyuan Song3, Yongjian Wu1

            1Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

            2Department of Radiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

            3Interventional Center of Valvular Heart Disease, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

            OBJECTIVES The current functional classification of aortic regurgitation (AR) cannot guide transcatheter aortic valve replacement (TAVR). The aim of this study was to analyze CT measurement characteristics and morphological types based on TAVR in patients with AR.

            METHODS This retrospective cohort study included 144 consecutive patients diagnosed with moderate to severe AR from July 2017 to April 2022. Patients were classified into four morphological types based on dual-anchoring multiplanar measurement, type-1 transcatheter heart valve (THV) anchoring at the annulus, left ventricular outflow tract (LVOT), and ascending aorta (AA); type-2 anchoring at the annulus and AA; type-3 anchoring at the annulus and LVOT; and type-4 anchoring at only one level or not anchoring at all. Among them, types 1–3 were considered as candidates for TAVR, while type 4 was not.

            RESULTS Patients (n=136) with AR (mean age, 68.7 years ± 10.7; 98 men) were included, with 117 (86.0%) tricuspid, 14 bicuspid, and 5 quadricuspid valves. Dual-anchoring multiplanar measurements showed the annulus shorter than LVOT, 2, 4, 6, 8, and 10 mm on annulus (27.2±3.3 vs. 27.5±3.6, 27.6±3.0, 28.7±2.8, 29.9±2.7, 30.9±3.0, and 31.7±3.5 mm, respectively); AA 40 mm was wider than AA 30 and 35 mm, but narrower than AA 45 and 50 mm (39.9±6.3 vs. 38.3±6.9, 39.1±6.6, 40.7±6.3, and 41.4±6.4 mm, respectively). For 10% oversize of THV, the proportions of the annulus, LVOT, and AA unable to meet the diameter were 22.8, 37.5, and 50%, and proportions of anatomical classification types 1–4 were 32.4, 5.9, 30.1, and 31.6%, respectively. Moreover, for 20% oversize, the proportion of type 4 was 59.5%. However, the newly designed THV could significantly improve the type 1 proportion (88.2%).

            CONCLUSIONS The existing THV could not meet the anatomical characteristics of the patients with AR, whereas the newly designed THV based on the anatomical characteristics could theoretically facilitate TAVR.

            GW33-e0683
            Evolution of cardiac damage and clinical outcome after transcatheter aortic valve replacement

            Yaoyao Zhou1,2, Qifeng Zhu1

            1Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

            2Department of Cardiology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua, China

            OBJECTIVES The impact of transcatheter aortic valve replacement (TAVR) on extra-valvular cardiac damage stage of aortic stenosis (AS) patients in the short term and its association with subsequent long-term prognosis is unknown. This study aims to shed light on the evolution of extra-valvular cardiac damage after TAVR and its association with clinical outcomes in TAVR recipients.

            METHODS AS patients undergoing TAVR were consecutively enrolled following additional exclusion criteria. Based on the echocardiographic parameters at baseline, within 30 days and 1-year post-TAVR, patients were classified into five cardiac damage stages (0–4), respectively. Data collection included baseline characteristics, procedural data, and predischarge outcomes. Baseline characteristics consisted of clinical, laboratory, and echocardiographic data. Predischarge outcomes were obtained from the local hospital database and were rigorously assessed for quality. The primary clinical outcome was all-cause mortality, defined according to the Valve Academic Research Consortium-3 criteria.

            RESULTS Among 644 included patients, 18 (2.8%) were Stage 0, 74 (11.5%) Stage 1, 427 (66.3%) Stage 2, 72 (11.2%) Stage 3, and 53 (8.2%) Stage 4 at baseline. In general, the baseline cardiac damage stage changed in 22.2% of TAVR recipients (mostly regressed), accompanied by improvement of dyspnea degree and left ventricular ejection fraction (LVEF) within 30 days post-TAVR. Afterward, no further significant changes in the proportion of respective stage groups were observed in the whole cohort during one-year post-TAVR. During a median follow-up period of 2 years after TAVR, a total of 43 (6.7%) deaths occurred. Two-year mortality was associated with both baseline stage (HR 1.59, 95% CI 1.10–2.30; P=0.014, for linear trend) and residual cardiac damage within 30 days post-TAVR (HR 2.97, 95% CI 2.07–4.25; P<0.001, for linear trend). In a multivariate-adjusted Cox proportional hazards regression model, both baseline stage and 30 days post-TAVR residual cardiac damage were independent risk factors for 2-year mortality (P<0.001).

            CONCLUSIONS This investigation provided insight into the evolution of the cardiac damage stage in AS subpopulation after TAVR and confirmed the superior predictive value of post-TAVR cardiac damage over its baseline counterpart. These findings suggest the significance of echocardiographic reassessment following TAVR in the light of development prospects for the extent of cardiac damage. Thirty days post-TAVR cardiac damage could act as a straw in the wind to hint at long-term outcomes for TAVR recipients.

            GW33-e0691
            Development and validation of a risk score to predict mortality for elder patients with mitral regurgitation

            Dejing Feng, Yungqing Ye, Haiyan Xu, Yongjian Wu

            Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College

            OBJECTIVES Risk stratification for elder patients with mitral regurgitation (MR) is crucial in the context of an increasing number of patients accepting transcatheter treatments. We aim to develop and validate a simple risk score to predict mortality for elder MR patients (≥60 years).

            METHODS Two thousand seven hundred thirty-eight patients with moderate or severe MR from the China Elderly Valve Disease study (China-DVD) were used to develop the Elder-MR score. Two thousand three hundred seventy-one patients with moderate or severe MR from the China Valvular Heart Disease Study (China-VHD) were used to externally validate the Elder-MR score. The primary outcome was 1-year mortality. Cox’s proportional hazards model and the stepwise selection with Akaike’s information criterion (AIC) were used to select potential predictors. The discrimination was assessed using Harrell’s c-statistic and the calibration was evaluated with the calibration plot. The overall performance of the Elder-MR score was measured by the Brier score.

            RESULTS Eight predictors were selected to build the Elder-MR score: age ≥75 years, BMI<20 kg/m2, NYHA class III/IV, functional MR, anemia, eGFR<60 mL/ (min×1.73 m2), albumin<35 g/L, and LVEF<60%. The Elder-MR score ranges from 0 to 15 points according to the sum of the weights of these factors. The score exhibited good performance both in the development cohort (c-statistic 0.73, 95% CI: 0.69–0.77; Brier Score 0.06) and the validation cohort (c-statistic 0.73, 95% CI: 0.68–0.78; Brier Score 0.06). One-year mortality of patients under medical management with low risk (0–4 points), moderate risk (5–9 points), or high risk (10–15 points) was 2.7, 9, and 20% in the development cohort (P<0.01), and 2.9%, 6.8%, and 17.7% in the validation cohort (P<0.01). Each point increase in the Elder-MR score was associated with a 1.27-fold risk of death (HR 1.27, 95% CI: 1.21–1.34) in the development cohort and a 1.24-fold risk of death (HR 1.24, 95% CI: 1.17–1.30) in the validation cohort. When compared to the EuroScore II, the Elder-MR score exhibited better predictive accuracy in predicting 1-year mortality (Net reclassification improvement, NRI 0.266, P<0.01; Integrated discrimination improvement, IDI 0.026, P<0.01) in the validation cohort.

            CONCLUSIONS The Elder-MR score showed good performance in predicting 1-year mortality both in the development cohort and the validation cohort. it may serve as a useful risk stratification tool to help clinical decision-making in elder MR patients.

            GW33-e0695
            Measurement consistency and short-term prognosis of preoperative analysis software anythink in transcatheter aortic valve replacement

            Zeyu Sun1,2, Dongkai Shan1, Jing Wang1, Changfu Liu1, Minhan Wang3, Ran Xin1,2, Yipu Ding1,2, Xi Wang1, Yang Mu1, Tao Chen1, Bo Jiang1, Lin Wang1, Ming Zhang1, Yundai Chen1

            1The Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing 100048, China

            2School of Medicine, NanKai University, Tianjin 300071, China

            3Beijing Crealife Technology Co., Ltd, Beijing 100853, China

            OBJECTIVES

            Transcatheter aortic valve replacement (TAVR) is an effective treatment for aortic valve disease, and the correct selection of prosthetic valve size plays a crucial role in the operation, what directly affects the success rate of operation and the incidence of major complications, such as perivalvular leakage and permanent pacemaker implantation. The objective of this study is to evaluate the consistency and reproducibility of Anythink for aortic root measurements by comparing the measurement data of Anythink, domestic semi-automatic preoperative CT analysis software, with those of 3mensio.

            METHODS Sixty-seven patients who underwent TAVR in the First Medical Center of the Chinese PLA General Hospital from December 2016 to February 2022 were retrospectively included. The new semi-automated software Anythink and the 3mensio “gold standard” measurement software were used to analyze the aortic annulus and surrounding structures. The correlation and consistency of the measurement results of two softwares were analyzed. Two independent doctors applied Anythink software to repeat the measurements to assess the reproducibility of Anythink measurements for the same subjects. The valve models were selected based on the measurements of Anythink and 3mensio software and the similarities and differences between the two software were assessed for practical use in guiding clinical valve selection.

            RESULTS There was no statistical difference in the t-test for the measured parameters of the aortic root between Anythink and 3mensio. Annulus average diameter: 24.0±2.2 vs. 23.9±2.3 mm (P=0.321); annulus area: 450.6±88.3 vs. 447.5±90.0 mm2 (P=0.069); annulus perimeter: 76.5±7.2 vs. 76.1±7.6 mm (P=0.075); Distance from annulus plane to left coronary ostium (LCO): 13.37±3.35 vs. 13.19±3.19 mm (P=0.268); distance from annulus plane to right coronary ostium (RCO): 15.45±2.89 vs. 15.75±2.93 mm (P=0.075); Angle between annulus and horizontal plane: 53.5±10.0 vs. 51.1±9.7° (P=0.647). The Pearson correlation analysis between software showed a positive correlation (r=0.884–0.981 and all P values less than 0.01). The kappa-test values of valve models selected by Anythink and 3mensio based on average diameter, area diameter and perimeter diameter were 0.886, 0.796 and 0.775. In patients with postoperative paravalvular leakage, the recommendations from area diameter measured by Anythink had a larger trend compared with 3mensio, while in patients with postoperative new-onset conduction block, the recommendations from Anythink had a smaller trend.

            CONCLUSIONS Anythink, the domestic semi-automatic TAVR preoperative CT analysis software, has excellent measurement consistency and high reproducibility for aortic root measurements.

            GW33-e0718
            Pressure related parameters derived from patient-specific computer simulation technology for prediction of new-onset conduction disturbances in transcatheter aortic valve replacement

            Zeyu Sun1,2, Dongkai Shan1, Jing Wang1, Changfu Liu1, Yundai Chen1

            1The Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing 100853, China

            2School of Medicine, NanKai University, Tianjin 300071, China

            OBJECTIVES The pressure generated by valve frame on aortic wall plays an important role in new-onset conduction disturbances (CDs) after TAVR. Some preoperative pressure related parameters have been proposed to predict the occurrence of postoperative CDs, but still remain further clinical validation. To validate contact pressure index (CPI) and maximum contact pressure (MCP) derived from patient-specific computer simulation technology (FEops HEARTguide, Ghent, Belgium) based on the anatomical and biomechanical properties of the aortic root for predicting the risk of new-onset CDs in TAVR.

            METHODS Finite-element computer simulations have been performed in 43 patients undergoing TAVR with the self-expanding Venus-A valve. Quantitative measurements of aortic annulus and left ventricular outflow tract (LVOT) by FEops reconstruction model have been compared with those by standard preoperative multidetector computed tomography (MDCT) analysis software 3mensio. The new CDs related plane has been determined in 30 patients, whose CPI and MCP has been quantified using FEops. The postoperative new-onset CDs has been assessed and diagnosed by postoperative electrocardiogram data.

            RESULTS There was no significant difference between FEops and 3mensio for the measured parameters of aortic annulus (perimeter: 74.00±8.05 vs. 74.64±7.39 mm, P=0.087; area: 423.62±86.84 vs. 429.60±85.24 mm2, P=0.054) and LVOT (perimeter: 77.74±11.06 vs. 77.92±10.14 mm, P=0.830; area: 4338.11±130.98 vs. 438.00±125.67 mm2, P=0.540). The Pearson correlation analysis between FEops and 3mensio measurements showed a positive correlation (r=0.878–0.974 and all P values less than 0.01). Of the 30 patients completed the finite element simulation, 8 (27%) patients developed new complete left bundle branch block or a high-degree atrioventricular block after TAVR, which could be consider as postoperative new-onset CDs. The CPI and MCP in new-onset CDs were significantly higher [30 (24–57) vs. 9 (2–12)%; 0.60 (0.38–0.77) vs. 0.28 (0.05–0.47) MPa] compared with that of patients without new-onset CDs. Other parameters between the two groups show no statistical difference. The AUC of receiver of operating characteristic curve for CPI and MCP for discrimination of postprocedural new-onset CDs was 0.937 (95% CI [0.785–0.993], P<0.01) and 0.750 (95% CI [0.559–0.889], P=0.039), respectively. The CPI represented better prediction power for adverse prognosis than MCP (P=0.044).

            CONCLUSIONS The patient-specific computer simulation technology FEops can reconstruct a model with high consistency with standard 3mensio. Pressure related parameters derived from FEops, especially CPI, can precisely predict the risk of postprocedural new-onset CDs, which means they reflect a clinical predictive value for identifying patients with adverse prognosis.

            GW33-e0743
            The 100 most-cited articles on total anomalous pulmonary venous connection

            Chen Wen

            Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University

            OBJECTIVES The number of times an article is cited reflects its impact on the research community. The aim of this study was to explore the characteristics of the most frequently cited articles published on total anomalous pulmonary venous connection (TAPVC).

            METHODS The database of the Clarivate Analytics’ Web of Science Core Collection Expanded Science Citation Index (1900 to present) was searched using the topic words ‘total anomalous pulmonary venous connection’, ‘total anomalous pulmonary venous drainage’ or ‘total anomalous pulmonary venous return’ on 21 May 2022. This database indexed more than 53 million records from over 9500 high impact journals across 178 scientific disciplines. The ‘document type’ was activated to limit the document type to ‘Article’ or ‘Review’. Two authors read the abstract or full text if need to identify the 100 most-cited articles dedicated to TAPVC. The following information was recorded: title, corresponding author, number of citations, publication year, country origin, institution, journal, funding source, and article type. The institution and country origin were defined by the address of the corresponding author. Data analysis was performed using statistical software SPSS version 19.0 (SPSS Inc., Chicago, IL, USA).

            RESULTS A total of 1352 papers were retrieved after the initial search, with 984 as ‘Article’ and 32 as ‘Review’. The top 100 cited articles were published between 1952 and 2018 with a mean number of citations of 52 (range 26 to 148). The 1990s was the most productive decade. The 100 top-cited articles were published in 24 journals, led by Journal of Thoracic and Cardiovascular Surgery (21 articles), followed by Annals of Thoracic Surgery (20 articles), and Circulation (16 articles). Hospital for Sick Children, Toronto led the list of classics with six papers. All articles except one were written in English. The United States of America contributed most of the top 100 cited articles (60 articles). Christopher A. Caldarone, John W. Kirklin, and P. E. F. Daubeney were the most productive authors with 3 articles each. The majority of the top 100 list were clinical articles, among which cohort study (n=51) was the most common type, and only 1 reported a clinical trial. Among these articles, 31 were funded by public foundations, none received support from commercial companies, for the remaining 69 the funding source was not specified. Specifically, 15 studies received grants from the National Institutes of Health.

            CONCLUSIONS The bibliometric analysis gives a historical perspective on the scientific progress in the field of TAPVC and informs people of important advances in the study of this disease.

            GW33-e0744
            Review of surgical experience in 61 patients with mixed total anomalous pulmonary venous connection

            Chen Wen

            Department of Cardiothoracic Surgery, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University

            OBJECTIVES Prior studies have reported a high mortality and incidence of post-repair pulmonary venous obstruction (PVO) in mixed total anomalous pulmonary venous connection (TAPVC). This study sought to review the surgical outcomes in this entity.

            METHODS A review of 61 patients undergoing surgical repair of mixed TAPVC was conducted. Patients with a single ventricle were excluded. Patients were subdivided into 3 groups according to Chowdhury’s classification. Predictors for death and postoperative PVO were explored by Cox regression model.

            RESULTS This study trended towards an older cohort with a median age of 88 days (interquartile range, 56.5–177). Twelve patients belonged to ‘2+2’ type, 40 belonged to ‘3+1’ type and the remaining 9 belonged to bizarre type. There were no early death and 7 late deaths. Follow-up was available in 96.7% of the patients after discharge with a median duration of 53 months (range, 1–177). Nineteen patients developed post-repair PVO among whom 2 required reintervention. Patients with preoperative PVO had a 4-fold higher risk (95% confidence interval, 1.36–12.38) of postoperative PVO than those without and were more likely to die (P=0.009). No statistical difference was observed among the 3 subgroups in terms of mortality (P=0.058) and postoperative PVO (P=0.186).

            CONCLUSIONS Preoperative PVO was significantly associated with postoperative PVO. There was no statistical difference in terms of death and postoperative PVO among the 3 subtypes of mixed TAPVC. Mid-term results favoured a complete rechanneling of pulmonary veins in ‘3+1’ type.

            CARDIOMYOPATHY
            GW33-e0169
            Genomic analysis of patients with hypertrophic cardiomyopathy and risk prediction

            Wenli Gu

            Sun Yat-sen Memorial Hospital of Sun Yat-sen University

            OBJECTIVES Gene mutation is associated with high risk of cardiovascular events in patients with hypertrophic cardiomyopathy, especially for sudden cardiac death. However, traditional predictive model for risk stratification did not take gene mutation into account, and currently whether gene mutation can predict cardiovascular risk in hypertrophic cardiomyopathy is not well known.

            METHODS This study selected patients who were first diagnosed with hypertrophic cardiomyopathy at Sun Yat-sen Memorial Hospital from 2014 to 2021, with whole-exome genomic testing performed, clinical data and endpoints recorded subsequently. The endpoint events were defined as sustained ventricular tachycardia, ventricular fibrillation, sudden cardiac death, ICD with electrotherapeutic events, all-cause death and heart failure requiring hospitalization or heart transplantation, which were further statistically analyzed as composite endpoints. Lasso regression was used to construct a predictive model of such composite endpoints, Cox proportional risk regression was used to predict these composite endpoints and finally the model was compared and combined with traditional model. Besides, predictive performance of the combined model was evaluated by C-index, ROC curve, net reclassification index (NRI) and integrated discrimination improvement (IDI).

            RESULTS A total of 60 patients with hypertrophic cardiomyopathy were eligible and enrolled in this study, including 36 males (60%). The median follow-up time was 20 months. Whole-exome genetic tests revealed that 25 patients (41.7%) carried pathogenic or likely pathogenic mutations, of which MYH7 and MYBPC3 were the most common (32 and 28%, respectively). Of all patients, 18 (30%) had cardiovascular composite endpoints, and presented with higher rate of gene mutation than those without cardiovascular composite endpoints (72.2 vs 28.6%, P=0.004). Logistic regression showed that gene mutation and reduced left ventricular ejection fraction contributed mostly to predict these composite endpoints (AUC were both 0.72), while Lasso regression only selected the variable of gene mutation for model construction. Kaplan-Meier analysis indicated that the endpoints-free survival time in patients with gene mutation was significantly shortened (Log-rank P=0.014). In Cox regression analysis, it was predicted that the rate of cardiovascular risk was 3.13 times in patients with gene mutation as those without gene mutation (HR=3.13, 95% CI=1.89–2.54, P<0.001). Compared with traditional model, using gene mutation to predict 5-year cardiovascular risk showed high sensitivity (0.71 vs 0.35), low specificity (0.74 vs 0.84) and high accuracy (C-index: 0.69 vs 0.54); when combined with traditional model, gene mutation could not improve its predictive ability of cardiovascular risk at 5 year (C-index: 0.65 vs 0.54; AUC:0.71 vs 0.68; NRI=17.7%, P=0.498; IDI=1.5%, P=0.617), but it could significantly increase model performance at 1 year and 7.8 years (1 year: C-index: 0.73 vs 0.55; NRI=43.6%, P=0.020; IDI=8.0%, P=0.010; 7.8 years: C-index: 0.88 vs 0.54; NRI=81.9%, P=0.049; IDI=24.9%, P=0.049).

            CONCLUSIONS Gene mutation is an independent risk factor for cardiovascular events in patients with hypertrophic cardiomyopathy, and when combined with traditional model, it can increase model’s ability of risk prediction in early and late stage. The cumulative burden of gene mutation on patients with hypertrophic cardiomyopathy may be enormous, and the application of whole-exon genomic testing has certain significance for guiding risk stratification and prognosis assessment in clinics.

            GW33-e0370
            Modulation of activated microglias in the hypothalamic paraventricular nucleus to prevent ventricular arrhythmia in stress-induced cardiomyopathy rat model

            Pengqi Lin1, Quanwei Pei1, Jiemei Yang2, Bin Li1, Mbabazi Nadine3, Lina Zou1, Junpei Zhang1, Hongpeng Yin1, Jiaxin Wang1, Weifa Wang1, Dechun Yin1

            1Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China

            2Department of Echocardiography, The First Affiliated Hospital of Harbin Medical University, Harbin, China

            3Department of Cardiology, King Faisal Hospital, Kigali, Rwanda

            OBJECTIVES Life-threatening ventricular arrhythmias have been reported in patients with stress-induced cardiomyopathy (SICMP). Growing evidence suggests a major role of the brain, particularly during stress. Paraventricular nucleus (PVN) of the hypothalamus may play an important role on this context, however, the mechanisms remain unknown. In this study, we investigated whether inhibition of activated microglias in the PVN could reduce ventricular arrhythmia (VA) in rats with SICMP.

            METHODS Male SD rats were selected to immobilization stress for 6 h lasting 7 days to establish SICMP model. The anesthetized rats were randomly divided into three groups of normal control, SICMP, and SICMP+minocycline. Electrocardiogram was continuously recorded. RNA sequencing, sympathetic nerve activity (heart rate variability and norepinephrine levels) and ventricular electrical instability (ventricular effective refractory period and ventricular fibrillation inducibility) were measured. Furthermore, brain tissues were extracted to detect expression of inflammatory cytokines, microglias and neuro activation.

            RESULTS RNA sequencing analysis showed that functions of differentially expressed genes in the PVN of SICMP rats were significantly enriched in neuro-inflammatory-related pathways. Microglias were activated and sympathetic activity increased in PVN in SICMP rats. The induction of ventricular fibrillation rate was significantly increased in rats with SICMP. Inhibiting microglia activation could significantly reduce the induction of ventricular fibrillation rate and maintain cardiac electrical stability.

            CONCLUSIONS Activated in the hypothalamic paraventricular nucleus in stress-induced cardiomyopathy, to prevent ventricular arrhythmia complicating Inhibition of activated Microglias in the PVN could reduce VA occurrence and improve ventricular electrical instability in SICMP rats by central neuro-inflammatory-related pathways. These findings suggest that Microglias are a potential target for prevention and treatment of VA complicating SICMP.

            GW33-e0402
            The prognostic value of serum calcium levels in elderly patients with non-ischemic dilated cardiomyopathy

            Xinyi Li1,2,3, Xiaonan Zhang1,2, Ning Tan1,2,3, Lei Jiang1,2,3

            1Guangdong Provincial People’s Hospital

            2Guangdong Provincial Geriatrics Institute

            3School of Medicine, South China University of Technology

            OBJECTIVES Dilated cardiomyopathy (DCM) is the most commonly diagnosed type of systolic heart failure, at present, there are no clear clinical risk factors for elderly patients with non-ischemic dilated cardiomyopathy (NIDCM). Thus, we conducted a retrospective study with a relatively large sample size to investigate the prognostic value of baseline serum calcium in elderly patients with NIDCM.

            METHODS A total of 1089 elderly patients (age ≥60 years) diagnosed with NIDCM were retrospectively enrolled from January 2010 to December 2019. Univariate and multivariate analyses were performed to investigate the association of serum calcium with their clinical outcomes.

            RESULTS Univariate and multivariate logistic regression analyses showed that serum calcium was independently associated with in-hospital mortality and long-term MACEs. Receiver operating characteristic (ROC) curve analysis showed that a serum calcium ≤8.62 mg/dL had a great sensitivity and specificity for predicting in-hospital death, with an AUC of 0.732. Kaplan–Meier survival analysis showed that patients with a serum calcium ;8.62 mg/dL had a better prognosis than those with a serum calcium ≤8.62 mg/dL (log-rank χ2 40.84, P<0.001). Multivariate Cox proportional hazard analysis showed that a serum calcium ≤8.62 mg/dL was related to a higher risk of long-term mortality in elderly patients with NIDCM (HR: 1.449; 95% CI: 1.115∼1.882; P=0.005).

            CONCLUSIONS Serum calcium level produced more prognostic value in elderly patients with NIDCM, which may be considered as a new prognostic indicator to reduce the future risk of death. Hypocalcemia in patients should be noted.

            GW33-e0514
            Analysis of changing trends in the clinical features and treatment of dilated cardiomyopathy

            Xiao-Lei Li, Dilare Adi, Abibanmu Aizezi, Yan-Peng Li, Yi-Tong Ma

            Department of Cardiology, The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

            OBJECTIVES To explore the trends of the disease clinical features and treatment of DCM (Dilated Cardiomyopathy) patients in the First Affiliated Hospital of Xinjiang Medical University from 2011 to 2020.

            METHODS DCM patients (n=3950) from the hospitalized patient were divided into five calendar periods of inclusion, 2011–2012 (Period 1, n=690), 2013–2014 (Period 2, n=765), 2015–2016 (Period 3, n=786) T, 2017–2018 (Period 4, n=838), 2019–2020 (Period 5, n=871).The demographic information and clinical data including medical past history, diagnosis, investigations, current treatment and comorbidities were collected.

            RESULTS The total number of inpatient with DCM showed an increasing trend over the five calendar periods, The Han, Uyghur, Kazakh, Hui and others nationalities accounted for 54.3%(2143), 29.9%(1142), 6.6%(260), 6.2%(244), 4.1%(161), respectively. Over the periods, patients were older (P<0.05), the symptoms by New York Heart association were more severe (P<0.05), and left ventricular ejection fraction was higher (P<0.05). Patients had a higher proportion of comorbid conditions, including atrial fibrillation, cerebral infarction, gallstone, comparing with the former period. With the passage of time, the proportion of DCM patients with complete left bundle branch block, unsustainable ventricular tachycardiaand grade II and above atrioventricular blockwere increased (P<0.05). The drug treatment regimen was optimized, such as the proportion of ACEI/ARB, beta-blocker and aldosterone antagonists usage rate gradually increased (P<0.05), and the proportion of digoxin useage decreased by 24.3% (mean 46.1%, 49.2%, 40.1%, 26.3%, 21.8%, P<0.05). Device (implantable cardioverter defbrillator and/or cardiac resynchronization) therapy increased by 12.31% over the time (mean 0.43%, 3.27%, 5.22%, 8.59%, 12.74%, P<0.05). The overall treatment outcome was valid, and the average length of stay was gradually shortened (P<0.05).

            CONCLUSIONS From 2011 to 2020, the number of DCM visits has been gradually on the rise, paralleled by a continuous change in both clinical characteristics and phenotypes in the DCM population in Xinjiang, towards a more complex phenotype. Although the treatment plan has been optimized and proved to be effective, the diagnosis and treatment of DCM still has a long way to go.

            GW33-e0521
            The clinical value of MHR in chronic heart failure with dilated cardiomyopathy

            Yu Jia-Qing, Ma Yi-Tong

            Department of Cardiology The First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang, China

            OBJECTIVES To explore the clinical value of monocyte count and high-density lipoprotein cholesterol ratio (MHR) in the diagnosis and treatment of chronic heart failure (CHF) in patients with dilated cardiomyopathy (DCM).

            METHODS A total of DCM 300 patients with chronic heart failure treated in the the first affiliated Hospital of Xinjiang Medical University in the past four years were selected and divided into NYHA II, NYHA III and NYHA IV group (100 patients), according to the cardiac function classification of New York Heart Association. In the same period, 100 patients with organic heart disease and chronic heart failure were selected as the control group. The level of MHR, the relationship between MHR and N-terminal precursor B-type natriuretic peptide (NT-pro BNP), and the relationship between MHR and echocardiographic indexes related to cardiac remodeling and cardiac function were observed and analyzed in DCM patients with chronic heart failure.

            RESULTS The MHR of DCM patients with chronic heart failure was significantly higher than that of the control group (P<0.001), and there were differences among different grades of heart failure in the case group (P<0.05). After controlling the influence of gender, it was found that MHR was positively correlated with left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and NT-proBNP. It was negatively correlated with LVEF. Correlation analysis showed that MHR was positively correlated with left atrial diameter (LAD), left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and NT-pro BNP (P<0.05), and negatively correlated with LVEF (P<0.05). The diagnostic value of MHR combined with NT-pro BNP (AUC=0.983) was higher than that of NT-pro BNP alone (AUC=0.974) (P<0.05). These results suggest that MHR may be associated with cardiac remodeling and cardiac function in DCM. The higher the MHR, the more pronounced the cardiac remodeling of DCM, and the more severe the heart failure. The combination of MHR and NT-proBNP may further improve the diagnostic efficacy of NT-pro BNP in chronic heart failure in DCM.

            CONCLUSIONS Clinically, doctors can try to use MHR as an indicator of the presence of chronic heart failure and the severity of heart failure in DCM patients. In particular, the combined determination of MHR and NT-proBNP may be more helpful to improve the sensitivity and specificity of clinical diagnosis of chronic heart failure in DCM. As a result, doctors can have more early identification and accurate implementation of the standardized treatment of chronic heart failure in DCM patients.

            GW33-e0659
            A novel cardiac MRI based nomogram for risk stratification in dilated cardiomyopathy with reduced ejection fraction

            Xiaorui Xiang, Xiuyu Chen, Shihua Zhao

            Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Dilated cardiomyopathy (DCM) patients with reduced ejection fraction (EF) are at high risk of adverse consequences, but effective and specific risk evaluation remain challenging. This study aimed to develop and validate a new nomogram score to predict outcomes in DCM patients with reduced EF.

            METHODS A total of 335 consecutive DCM patients with reduced EF who underwent cardiac magnetic resonance imaging (MRI) were retrospectively enrolled. The major adverse cardiac events (MACEs) included all-cause mortality and heart transplantation. These patients were randomly divided into training and validation cohort (7:3). In the training cohort, LASSO regression analysis and two-step multivariate Cox regression analysis were utilized to identify prognostic factors. A nomogram based on the selected predictive variables was built to predict MACEs. AUC, Harrell’s C-index, and calibration curves were used to evaluate the efficiency of the nomogram in both training and validation cohorts. The decision curve analysis was applied to assess its clinical utility.

            RESULTS MACEs occurred in 93 (39.7%) out of 234 patients in the training cohort, and in 41 (40.6%) out of 101 patients in the validation cohort. Six variables including hypertension, NT-proBNP, LA diameter, LVESVI, LGE presence, and LVGLS were found to be significantly associated with MACEs and were used for constructing the nomogram. The nomogram achieved good discrimination with C-indexes of 0.80 (95% CI 0.72 to 0.93, P<0.001) and 0.82 (95% CI, 0.77 to 0.96, P<0.001) in the training and validation cohorts respectively. The calibration curve for 1-, 3-, and 5-year survival also showed high coherence between the predicted and actual probability of MACEs. Decision curve analysis identified our model was clinically useful in predicting MACEs.

            CONCLUSIONS This study presents a predictive model and constructs a nomogram that incorporates the cardiac MRI parameters and clinical risk factors, which can be conveniently used to facilitate the risk stratification in DCM patients with reduced EF.

            GW33-e0660
            Incremental prognostic value of left atrial and biventricular feature-tracking in dilated cardiomyopathy

            Xiaorui Xiang, Xiuyu Chen, Yanyan Song, Kankan Zhao, Shiqin Yu, Shujuan Yang, Shihua Zhao

            Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Although cardiac magnetic resonance feature-tracking (CMR-FT) has been used to detect myocardial deformation, the association between atrial and ventricular strain with outcomes is unclear in dilated cardiomyopathy (DCM). This study therefore aimed to investigate whether CMR-FT derived left atrial (LA), left ventricular (LV) and right ventricular (RV) strain provide long-term incremental prognostic information in patients with DCM.

            METHODS Consecutive DCM patients were included retrospectively. Comprehensive clinical evaluation and imaging investigation were obtained, including measurements of CMR-FT derived LA total, passive, active strain (εs, εe, εa), LV global longitudinal, radial, circumferential strain (GLS, GRS, GCS), as well as RV GLS. Patients were followed up for major adverse cardiac events (MACEs) including all-cause mortality, heart transplantation and ICD discharge.

            RESULTS Of 412 patients (45±14 years) followed for a median of 5.03 years, 149 (36.1%) patients experienced MACEs. On multivariable analysis, LAεe, LVGLS and RVGLS were independently associated with the outcomes ([HR] 0.76, 95% CI 0.705–0.819, P<0.001; [HR] 1.137, 95% CI 1.077–1.200, P<0.001; [HR] 1.052, 95% CI 1.021–1.085, P=0.001, respectively). After adjusting for the clinical data, conventional imaging factors, and LGE presence, the addition of LAεe provided the best discrimination of the model (χ2 254.6, P<0.001; C-index 0.842), followed by LVGLS and RVGLS (χ2 213.7, 197.6, all P<0.001; C-index 0.808, 0.775, respectively). Moreover, LAεe with a cutoff of 5.29% could further discriminate the risk of MACEs in patients with LGE+ or LVEF<35% (all log-rank P<0.001).

            CONCLUSIONS In patients with DCM, CMR-FT derived LAεe, LVGLS and RVGLS were independently associated with long-term MACEs. Moreover, LAεe provides the best incremental prognostic value beyond conventional predictors.

            GW33-e0696
            Construction and analysis of nomogram prediction model for unplanned admission to ICU of dilated cardiomyopathy patients

            Xiaolei Li, Dilare Adi, Aibibanmu Aizezi, Yanpeng Li, Yitong Ma

            Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES To construct a nomogram prediction model for DCM patients who require intensive care unit (ICU) transfer after general ward admission, and to identify patients early in order to improve the clinical treatment and reasonably allocate medical resources.

            METHODS We enrolled a total of 2022 DCM patients from January 2011 to December 2020, and randomly split into modeling group and verification group according to the ratio of 7:3. The demographic information, clinical data and inspection results were collected. The optimal lasso model was refifined to the whole data set, and multivariate logistic regression was used to assign relative weights. A nomogram incorporating these predictors was constructed to visualize these predictors and their corresponding points of the risk for un-planned intensive care unit admission. Finally, the prediction performance of nomogram is evaluated by C-index, bootstrapped-concordance index, and calibration plots.

            RESULTS (1) A total of 2022 patients were fifinally included in this study, and 190 (9.39%) patients unplanned intensive care unit admissions. One thousand four hundred sixteen patients were included in the derivation cohort (mean age 53.74 years, 27.33% female) and 606 were included in the validation cohort (mean age 53.42 years, 25.58% female). (2) According to the LASSO regression and multivariate logistic regression analyses, four variables were selected for the fifinal prediction model:emergency admission mode [odds ratio (OR): 2.55; 95% confifidence interval (CI): 1.73–3.78; P<0.001], NYHA classification (OR: 2.66; 95% CI: 1.79–3.95; P<0.001), neutrophil (OR: 1.13; 95% CI: 1.05–1.21; P=0.001), and serum sodium (OR: 0.39; 95% CI: 0.26–0.57; P<0.001). (3) We used these independent risk factors to construct a nomogram prediction model to predict unscheduled intensive care unit admission in DCM. ROC cure analysis result showed that in modeling group and validation group, the area under curve (AUC) of the model were 0.77 (95% CI: 0.73–0.82) and 0.76 (95% CI: 0.68–0.83), with good discrimination. The Hosmer-Lemesshow test showed that the nomogram prediction model had good correction ability (χ2=3.48, P=0.529), with good consistency. The clinical decision curve indicates that the model has better diagnostic value.

            CONCLUSIONS Our nomogram can accurately predict un-planned intensive care unit admission in DCM patients and can be used for early identifification of high-risk DCM patients.

            GW33-e0697
            Value of new inflammatory markers in predictiong unplanned admission to ICU of dilated cardiomyopathy

            Xiaolei Li, Dilare Adi, Aibibanmu Aizezi, Yanpeng Li, Yitong Ma

            Department of Cardiology Heart disease, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES To investigate the value of five new inflammatory markers (platelet-lymphocyte ratio [PLR], neutrophil-lymphocyte ratio [NLR], monocyte-lymphocyte ratio [MLR], systemic immune inflflammation index [SII], and system inflflammation response index [SIRI]) in predictiong unplanned admission to intensive care unit (ICU) of dilated cardiomyopathy patients.

            METHODS A total of 1441 DCM patients in The First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2020 were included in this study. Patients were divided into two groups according to whether unplanned ICU admission. The association between each of the five indices and endpoint was assessed by the Logistic regression analysis.

            RESULTS (1) A total of 1441 patients were fifinally included in this study, and 136 (9.44%) patients unplanned intensive care unit admissions. (2) Compared with non-unplanned ICU admissions group, PLR, NLR, MLR, SII and SIRI were significantly higher in the unplanned ICU admissions group. In multivariate analysis, PLR (odds ratio [OR]: 1.003; 95% confidence interval [CI]: 1.002–1.005; P<0.001), NLR (OR: 1.144; 95% CI: 1.093–1.198; P<0.001), SII (OR: 1.000; 95% CI: 1.000–1.001; P<0.001) and SIRI (OR: 1.164; 95% CI: 1.099–1.233; P<0.001) were independent predictors of unplanned ICU admissions. (3) The addition of PLR, NLR, SII, or SIRI to the MAGGIC risk score, especially SIRI (AUC: 0.702[0.652–0.752], P<0.001; net reclassifification improvement [NRI]: 0.287[0.071,0.467], P=0.005; integrated discrimination improvement [IDI]: 0.079[0.045–0.112], P<0.001), outperformed the MAGGIC risk score alone in the risk predictive unplanned ICU admissions.

            CONCLUSIONS This study identifified the PLR, NLR, SII and SIRI all associated with unplanned ICU admission and the combination of SIRI with the MAGGIC risk score could predict unplanned ICU admission more accurately.

            CARDIOVASCULAR SURGERY
            GW33-e0012
            Impact of repeat revascularization within 5 years on 10-year mortality after percutaneous or surgical revascularization

            Rutao Wang1,2,3, Mattia Lunardi2,4, Hironori Hara2,5, Chao Gao1,2,3, Masafumi Ono2,5, Piroze M. Davierwala6, David R. Holmes7, Friedrich W. Mohr8, Nick Curzen9, Francesco Burzotta10, Robert-Jan Van Geuns3, Arie Pieter Kappetein11, Stuart J. Head11, Daniel J.F.M. Thuijs11, Scot Garg12, Yoshinobu Onuma2, William Wijns2,13, Patrick W. Serruys2,14

            1Department of Cardiology, Xijing Hospital, Xi’an, China

            2Department of Cardiology, National University of Ireland, Galway (NUIG), Galway, Ireland and CORRIB Research Center for Advanced Imaging and Core laboratory

            3Department of Cardiology, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, the Netherlands

            4Department of Cardiology, University Hospital of Verona, Verona, Italy

            5Amsterdam UMC, University of Amsterdam, Heart Center, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands

            6Division of Cardiovascular Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, University Health Network, Toronto, Canada

            7Mayo Clinic, Rochester, MN, United States

            8Department of Cardiac Surgery, Heart Centre Leipzig, Leipzig, Germany

            9Faculty of Medicine, University of Southampton & Cardiology Department, University Hospital Southampton, Southampton, United Kingdom

            10Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy

            11Department of Cardiothoracic Surgery, Erasmus University Medical Centre, Rotterdam, the Netherlands

            12East Lancashire Hospitals NHS Trust, Blackburn, Lancashire, United Kingdom

            13The Lambe Institute for Translational Medicine, The Smart Sensors Laboratory and Curam, National University of Ireland, Galway (NUIG), Galway, Ireland

            14NHLI, Imperial College London, London, United Kingdom

            OBJECTIVES The SYNTAX trial demonstrated negative impact of repeat revascularization on 5-year outcomes following percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with three-vessel (3VD) and/or left main coronary artery disease (LMCAD). We aimed to investigate the impact of repeat revascularization within 5 years, on 10-year all-cause death in patients with 3VD and/or LMCAD after PCI or CABG.

            METHODS The SYNTAXES study evaluated the vital status out to 10 years of patients with 3VD and/or LMCAD. Patients were stratified by repeat revascularization within 5 years and randomized treatment. The association between repeat revascularization within 5 years and 10-year mortality was assessed.

            RESULTS A total of 330 (220 repeat revascularization after initial PCI and 110 repeat revascularization after initial CABG) out of 1800 patients (18.3%) underwent repeat revascularization within 5 years from initial revascularization. Repeat revascularization occurred more frequently after initial PCI than after initial CABG (25.9 vs 13.7%, P<0.001). Overall, 10-year mortality was comparable between patients undergoing repeat revascularization and those not (28.2 vs 26.1%, adjusted HR: 1.17, 95% CI: 0.93–1.48, P=0.187). Among patients requiring repeat revascularization, those who underwent PCI as initial revascularization had a higher risk of 10-year mortality compared to initial CABG (33.5 vs 17.6%, adjusted HR: 2.09, 95% CI: 1.21–3.61, P=0.008).

            CONCLUSIONS In the SYNTAXES study, repeat revascularization within 5 years had no impact on 10-year all-cause death in the population overall. Among patients requiring any repeat procedures, mortality was higher after initial treatment with PCI than after CABG. These exploratory findings should be investigated with larger populations in future studies.

            GW33-e0070
            Is vertebral V1 revascularization combined with ipsilateral carotid endarterectomy safe?

            Yuanrui Gu

            Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES The recommendation of the European Society for Vascular Surgery (ESVS) is vertebral revascularization combined with Ipsilateral CEA should not be performed in the same operation. ESVS believes that vertebral revascularization combined with Ipsilateral CEA increases Perioperative death/stroke rates. In our opinion, compared with vertebral V1 revascularization, vertebral V1 revascularization combined with Ipsilateral CEA is safe. The purpose of this study is to prove vertebral V1 revascularization combined with Ipsilateral CEA is safe.

            METHODS We describe our experience with vertebral V1 revascularization combined with Ipsilateral CEA and vertebral V1 revascularization in 48 consecutive patients during a 5-year period. OY incisions were used in all operations.

            RESULTS There was no significant difference between group A and group B in terms of red blood cell reduction, postoperative ventilator using time, postoperative drainage volume, postoperative drainage days, Postoperative hospital days and postoperative complications.

            CONCLUSIONS Vertebral revascularization combined with Ipsilateral CEA should divide into vertebral V1 revascularization combined with Ipsilateral CEA and vertebral V3 revascularization combined with Ipsilateral CEA. Vertebral V3 revascularization combined with Ipsilateral CEA should not be performed in the same operation. Vertebral V1 revascularization combined with Ipsilateral CEA is safe, it can be performed for suitable patients. OY incisions can fully expose the target blood vessels and simplify the operations without transecting the sternocleidomastoid muscles in vertebral V1 revascularizations combined with Ipsilateral CEAs and vertebral V1 revascularizations.

            GW33-e0120
            Circulating exosomal miRNAs as novel biomarkers for acute aortic dissection

            Dan Zhang, Xaing Ma

            The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES Objective: Acute aortic dissection (AAD) is a serious and life-threatening cardiovascular emergency. The aim of this study was to investigate whether miRNAs in circulating exosomes could serve as novel diagnostic biomarkers for AAD.

            METHODS Using miRNA microarray sequencing, the differentially expressed exosomal miRNAs between AAD group and healthy control (HC) were found. In this study, we investigated 8 miRNAs (miR-499a-5p/miR-543/miR-143-3p)/(miR-4433b-3p/miR-744-5p/miR-4488/miR-202-3p/miR-206), 4 genes (MMP-9/MMP-12/TGF-β/D-Dimer) in AAD (n=30) and HC (n=30) expression levels between the two groups. The combined diagnosis of exosomal miRNA and gene was performed (AUC>0.8, r;0.4 and P<0.05). The ROC curve was drawn to evaluate the diagnostic efficacy. Predict the gene targets of differentially expressed miRNAs and analyze the functions and signaling pathways of these targets using online databases.

            RESULTS The exosomes isolated from the two groups of serum were bilayer membranes with a diameter of about 100 nm. Stably expressed in CD9, CD63 and TSG101. Compared with the healthy control group, 8 exosomal miRNAs (miR-499a-5p, miR-543, miR-206, miR-143-3p, miR-4433b-3p, miR-744-5p, miR- 4488 and miR-202-3p) were regulated to varying degrees (P<0.05). miR-499a-5p, miR-143-3p and miR-202-3p had higher diagnostic efficacy (AUC>0.80). Among them, miR-499a-5p had the highest diagnostic accuracy, reaching 93.35%, AUC=0.939. Positively correlated miRNAs The combined diagnostic efficiency of -499a-5p and miR-143-3p was improved, with a diagnostic accuracy of 95%, AUC=0.990. The combined diagnostic accuracy of miR-499a-5p and MMP-9 was 98.35%, AUC was 0.983, and the sensitivity was 98.35%. was 96.7%, and the specificity was 100%. GO enrichment analysis and KEGG signaling pathway analysis, some predicted targets of these miRNAs are involved in the pathophysiological process of AAD.

            CONCLUSIONS Serum exosomal miR-499a-5p, miR-143-3p and miR-202-3p can be used as potential diagnostic biomarkers for AAD, and the combination of various markers can coordinate and complement each other, and can significantly improve the diagnosis of aortic dissection sensitivity and specificity.

            GW33-e0167
            Implication of pulmonary artery systolic pressure for prolonged cardiopulmonary bypass duration in patients undergoing re-repair for degenerative mitral regurgitation

            Hang Xu, Shanshan Zheng, Zhaoji Zhong, Sheng Liu

            Department of Cardiac Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

            OBJECTIVES Emerging evidence revealed that the longer duration of cardiopulmonary bypass (CPB) during cardiac surgery renders patients at higher risk of adverse outcomes. However, little is known regarding the risk factor of prolonged CPB in patients undergoing re-repair of degenerative mitral regurgitation (DMR). We aimed to explore the prognostic significance of pulmonary artery systolic pressure (PASP) on CPB duration in patients undergoing re-repair of DMR.

            METHODS Patients with DMR undergoing re-repair in our center were consecutively enrolled from Jan 2009 to Dec 2021. Patients were stratified into the prolonged CPB group (CPB time≥132 min, n=61) and the shorter CPB (CPB time<132, n=59). Preoperative Univariable and multivariable logistic regression analyses were used to evaluate the impact of PASP on the risk of prolonged CPB duration.

            RESULTS Of the 120 patients enrolled, 61 had prolonged CPB time (50.8%). The mean preoperative PASP was higher in the prolonged CPB group compared with the shorter CPB group (45.2±21.9 vs. 37.7±15.1, P<.05). CPB time increased with higher preoperative PASP (P<.05). For per 10 units of pre-PASP value increase in patients undergoing re-repair for DMR, there were 1.25 times more likely to be associated with a prolonged CPB time (adjusted odds ratio [OR] 1.25, 95% confidence interval [CI] 1.01–1.56, P<.05). Patients with preoperative PASP≥50 mmHg had an adjusted OR of 3.66 (95% CI 1.36–9.84, P<.05) for a prolonged CPB period compared with those with preoperative PASP<50 mmHg.

            CONCLUSIONS Preoperative PASP in patients requiring re-repair for DMR was associated with a higher likelihood of an extended time of CPB. Regular screening of pulmonary hypertension may aid in perioperative risk-stratification in patients prior to re-repair for DMR.

            GW33-e0556
            Long-term prognostic implications of concomitant inflammation and malnutrition in valvular heart surgery

            Denise Hung1,2, Yi-Kei Tse2, Qing-Wen Ren2, Jia-Yi Huang2, Kai-Hang Yiu1,2

            1Cardiology Division, Department of Medicine, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

            2Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China

            OBJECTIVES Novel strategies to improve the long-term risk stratification of valvular surgery are urgently needed as a result of the increasing prevalence of valvular heart diseases globally. This study aimed to evaluate the long-term prognostic implications of inflammatory and nutritional status in predicting survival and adverse outcomes in patients undergoing valvular heart surgery.

            METHODS One thousand forty-six patients who underwent valvular heart surgery were stratified into three groups according to their inflammatory and nutritional status: without inflammation and malnutrition (normal), inflammation or malnutrition alone (mild), and concomitant inflammation and malnutrition (severe). Inflammatory and nutritional status were defined using neutrophil-to-lymphocyte ratio (NLR) and prognostic nutritional index (PNI) respectively. Optimal NLR and PNI thresholds for predicting all-cause mortality were determined using receiver-operating characteristic analysis. Any discrimination improvement of NLR and PNI to EuroSCORE II and STS score was assessed by C-statistics, continuous net reclassification (cNRI) and integrated discrimination improvement (IDI) indices. The endpoints of interest included all-cause mortality, cardiovascular death and adverse events (composite of death and heart failure [HF] hospitalization).

            RESULTS Over a median follow-up of 4.3 years (IQR: 2.6 to 6.4 years), 139 (13.3%) deaths and 148 (14.1%) HF hospitalizations occurred. Based on the optimal cut-offs of NLR>4.06 (inflammation) and PNI<45.8 (malnutrition), 714 (68.3%), 214 (20.5%) and 118 (11.3%) patients were categorized into normal, mild and severe groups respectively. Compared with patients without inflammation and malnutrition, those with concomitant inflammation and malnutrition before surgery had the highest risk of all-cause mortality (hazard ratio [HR] 5.60, 95% confidence interval [CI] 3.66–8.57), cardiovascular death (subdistribution HR [SHR] 5.19, 95% CI 2.33–11.60) and adverse events (HR 3.14, 95% CI 2.25–4.38) (P<0.001 for all), adjusted for demographics, cardiovascular risk factors and diseases, medications, valvular surgeries and conventional risk scores. Discriminatory improvement for predicting all-cause mortality was observed when baseline NLR and PNI were added to EuroSCORE II (C-statistic 0.77 vs 0.73, P=0.04; cNRI 0.24, 95% CI 0.12–0.36, P=0.004; IDI 0.04, 95% CI 0.01–0.08, P=0.004) and STS score (C-statistic 0.78 vs 0.73, P=0.03; cNRI 0.16, 95% CI 0.06–0.32, P=0.002; IDI 0.02, 95% CI 0.000–0.049, P=0.048) respectively. One year following surgery (n=740), those with persistent concomitant inflammation and malnutrition experienced the highest risk of all-cause mortality (HR 8.82, 95% CI 4.21–18.49), cardiovascular death (SHR 12.63, 95% CI 3.85–41.39) and adverse events (HR 5.83, 95% CI 3.16–10.76) than those without (P<0.001 for all).

            CONCLUSIONS Concomitant inflammation and malnutrition is common and is strongly associated with mortality and HF in patients undergoing valvular surgery. Beyond conventional risk scores, assessments of inflammatory and nutritional status of patients before and after surgery using NLR and PNI may provide additional prognostic and discriminatory value for long-term outcomes following valvular surgery.

            GW33-e0559
            Low serum albumin level is associated with higher long-term mortality in patients with acute aortic syndrome

            Zhanyi Qiu1,2, Muli Wu1, Zhongbo Xiao1, Shiwan Wu1, Rongbing Chen1,2, Zhaotao Huang1,2, Jiaxuan She1, Yequn Chen1,2,3, Xuerui Tan1,2,3

            1The First Affiliated Hospital of Shantou University Medical College, Shantou, China

            2Shantou University Medical College, Shantou, China

            3Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College (SUMC)

            OBJECTIVES Previous studies found that low serum albumin (SA) is independently associated with increased in-hospital mortality in both type A and B acute aortic dissections (AD). However, few studies have reported the long-term outcomes of patients admitted with hypoalbuminemia. This study aimed to evaluate the association between admission SA levels and long-term all-cause mortality in patients with acute aortic syndrome (AAS).

            METHODS Demographic and clinical data were collected from 1072 patients diagnosed with AAS (intramural haematoma or aortic dissection) from 2015 to 2020 in the First Affiliated Hospital of Shantou University Medical College. Patients were divided into low-albumin group and high-albumin group. The association between long-term all-cause mortality of AAS patients and SA levels on admission was analyzed using Cox proportional hazards regression models.

            RESULTS A total of 1072 patients with AAS were enrolled, of whom 304 patients (28.4%) died during the follow-up period. The long-term mortality rate of AAS patients in the low albumin group is higher than that in the high albumin group, regardless of AAS type (type A: 50.2 vs 30.6%, P<0.001; type B: 24.8 vs 12.6%, P<0.001). The survival curve showed that the mortality rate of the high albumin group was significantly lower in the low albumin group (P<.001). Multivariate Cox regression analysis further showed that SA is an independent predictor of long-term mortality in AAS patients (HR, 0.498; 95% CI, 0.394–0.628; P=.000).

            CONCLUSIONS SA is independently associated with increased long-term all-cause mortality in both type A and B AAS. We should pay enough attention to AAS patients whose serum albumin level is reduced at the time of admission, and give appropriate treatment when necessary.

            GW33-e0676
            Risk factors for radial expansion rate of stent after carotid artery stent: a high-resolution magnetic resonance vessel wall imaging research

            Yumeng Sun, Wei Yu

            Department of Medical Imaging, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases

            OBJECTIVES No studies have investigated risk factors affecting radial expansion rate of stent after carotid artery stenting (CAS). This study aimed to investigate risk factors influencing radial expansion rate of stent after CAS.

            METHODS Eighty-nine patients with CAS for carotid atherosclerotic stenosis who had high-resolution magnetic resonance vessel wall imaging (HR-VWI) prior to stenting were included in this analysis. Carotid plaque burden and component were evaluated by HR-VWI. The plaque calcification circumference and site were evaluated on the 5-point and 4-point grading scale respectively. The radial expansion rate of stent (%)=(preoperative stenosis rate)–(the post-stenting stenosis rate). The low radial expansion rate of stent was defined as radial expansion rate of stent (%)≤50%. The baseline and clinical characteristics, plaque burden and component were compared between the patients with low radial expansion rate of stent and high radial expansion rate of stent. Univariable and multivariable logistic analysis were used to explore risk factors influencing radial expansion rate of stent.

            RESULTS Among the 89 patients, 46 patients (51.7%) developed low radial expansion rate of stent after CAS. The logistic regression analysis showed that coronary artery disease (OR, 0.12; 95% CI, 0.02 to 0.63, P=0.01), higher Max wall thickness (OR, 0.58; 95% CI, 0.38–0.88, P=0.01), higher circumference total scores of calcification (OR, 1.19; 95% CI, 1.04–1.36, P=0.01), higher Maximum circumference score of calcification in single slice (OR, 0.16; 95% CI, 0.05–0.50, P=0.00) and higher Maximum area percentage of calcification (OR, 0.84; 95% CI, 0.71–0.99, P=0.04) were independently associated with low radial expansion rate of stent.

            CONCLUSIONS Coronary artery disease, Max wall thickness, circumference degree of calcification and Maximum area percentage of calcification influenced radial expansion rate of stent after CAS.

            GW33-e0701
            Candida tropicalis bioprosthetic valve endocarditis inducing mitral valve stenosis: case report and pathological analysis

            Jinglun Shen1, Haibo Zhang2

            1Capital Medical University

            2Department of Cardiac Surgery, Beijing Anzhen Hospital

            OBJECTIVES Candida tropicalis (C. tropicalis) is a general non-albicans Candida species often causes superficial and localized mucosal Infections, vaginal infections, urinary tract infections, invasive infections and disseminated infections. C. tropicalis seldom cause endocarditis in the bioprosthetic valve. In the reports of infective endocarditis in prosthetic valves, most occurred in aortic valves. As a less frequent clinical case, we report a case of mitral bioprosthetic valve stenosis due to Candida tropicalis infection.

            METHODS A 72-year-old woman suffered from diabetes and obesity. She developed fever six months after a bioprosthetic mitral valve replacement, and blood cultures showed C. tropicalis infection. The damaged valve was removed and redo valve replacement was performed. Vegetations were found on both sides of the damaged valve. Pathological examination was also consistent with C. tropicalis infection.

            RESULTS The patient recovered well and continued to receive antifungal treatment with caspofungin until blood culture was negative. At six months follow-up, the patient was afebrile and the valve function was acceptable.

            CONCLUSIONS Bioprosthetic valve endocarditis should be comprehensive treated to avoid serious infections and complication. Active control of underlying diseases could reduce the risk of infectious endocarditis. Active control of risk factors will contribute to the prevention of fungal infections. Comprehensive treatment is required including drug therapy and active surgical treatment.

            CLINICAL DRUG RESEARCH AND DEVICE DEVELOPMENT
            GW33-e0062
            Characteristics of new and old anticoagulants in the ventricular mural thrombus

            Qing Yang1, Xinyue Lang2, Xin Quan3, Yan Liang4

            1National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            2Medical Research & Biometrics Center, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences

            3Echocardiographic Imaging Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            4Emergency Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES To describe the characteristics, treatment practices, and thrombus outcomes of patients with ventricular mural thrombus (VMT), with emphasis on the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs).

            METHODS We performed a retrospective cohort study in National Center of Cardiovascular Diseases of China between 2010 and 2019. Patients with VMT newly treated with either NOACs or VKAs were included. The primary outcome was the rate of thrombus resolution within 3 months.

            RESULTS We included a total of 196 patients-68.9% (n=135) were treated with VKAs while 31.1% (n=61) on NOACs. Patients with a medical history of heart failure (OR 2.10, 95% CI 1.17 to 3.77, P=0.013) or low LVEF (OR 0.36, 95% CI 0.20 to 0.65, P=0.001) at baseline might have a higher thrombus resolution. At 3 months follow-up, a significant difference was observed in the thrombus resolution between the NOACs and VKAs group with or without adjustment (OR 2.61, 95% CI 1.39 to 4.89, P=0.003; adjusted OR 3.21, 95% CI 1.58 to 6.52, P=0.001) with a similar time to resolution. Further analysis showed when patients were male, more than 50 years old, LVEF≥30%, or had a medical history with heart failure, thrombus resolution were greater in NOACs group.

            CONCLUSIONS Patients with a medical history of heart failure or low LVEF had a greater thrombus resolution. And with or without adjusting for baseline covariates, the resolution of VMT after NOACs treatment was significantly higher than the result obtained with VKAs therapy at 3 months.

            GW33-e0197
            A comparative study of structural parameters for spiral groove bearing in centrifugal rotary blood pump

            Cong Xue1, Yu Chen2, Bin Zhu3, Xiuying Wang2

            1Department of Cardiology, The Third Affiliated Hospital of Soochow University

            2School of Mechanical Engineering, Jiangsu University of Technology

            3Department of Critical Care Medicine, The Third Affiliated Hospital of Soochow University

            OBJECTIVES At present, centrifugal pumps are widely used in extracorporeal membrane oxygenation (ECMO), left heart assist and conventional CPB heart surgery. It is well known that the spiral groove bearing plays an important role in the centrifugal pumps. However, the two difficult technology problems should be solved. The first question is the description of physical characteristics for blood film, which includes the pressure distribution and velocity distribution. The other one is that the mapping relationship between structural parameters and hydrodynamic performance of spiral groove bearing. Therefore, it is valuable to establish an available model for illustrating the hydrodynamic behavior of spiral groove bearing and the effects of spiral groove parameters on the hydrodynamic performance should be represented. In this work, the hydrodynamic characteristics of spiral groove bearing in centrifugal rotary blood pump is investigated for the cases with different structural parameters.

            METHODS The simulation model is proposed based on the CFD technology, which is satisfied with Navier-Stokers equations and momentum conservation equations. And, the effectiveness of simulation model is demonstrated by the published data. Then, the orthogonal design method is employed in the optimization analysis of spiral groove bearing.

            RESULTS The pressure, load carrying capacity and friction torque are calculated and the characteristics of pressure distribution are analyzed. It is found that the structural parameters of spiral groove would lead to the complex pressure distribution of blood film and the load carrying capacity also changes at the same time. Moreover, the deep analysis of structural characteristics for spiral groove bearing is conducted based on the orthogonal design method, which could illustrate the mapping relationship between structural parameter and hydrodynamic performance of bearing preferably.

            CONCLUSIONS The modeling and simulation approach of spiral groove bearing with different structural parameters are proposed based on the CFD technology. The structural characteristics of spiral groove is considered and the viscosity of blood molecules is treated. Furthermore, the optimization design of spiral groove bearing is carried out based on orthogonal design method and the optimization design object is proposed. More structural parameters of spiral groove are analyzed by the presented method and the case number could be decreased obviously, which improves the computational efficiency of spiral groove bearing.

            CARDIOVASCULAR DISEASES IN SPECIAL POPULATIONS (CHILDREN, WOMEN, ETC.)
            GW33-e0161
            Acute high-risk chest pain diseases during pregnancy and puerperium

            Suxuan Liu1, Shengyong Wu2, Cheng Wu2

            1Department of Cardiology, Changhai Hospital, Navy Medical University, Shanghai, China

            2Department of Military Health Statistics, Navy Medical University, Shanghai, China

            OBJECTIVES Acute high-risk chest pain diseases, including acute myocardial infarction (AMI), aortic dissection (AD), and pulmonary embolism (PE) during pregnancy and puerperium are devastating, yet data regarding contemporary incidence and outcomes are limited. We aimed to investigate the incidence and outcomes of these diseases during pregnancy and puerperium.

            METHODS The National Inpatient Sample was queried to identify women aged ≥18 years with pregnancy-related hospitalizations from 2008 to 2017. Temporal trends in the incidence and outcomes of these diseases were extracted.

            RESULTS Among 41,174,101 hospitalizations, acute high-risk chest pain diseases were diagnosed in 40,285 (0.098%). The incidence increased from 79.92/100,000 in 2008 to 114.79/100,000 in 2017 (Ptrend<0.0001). The most frequent disease was PE (86.5%), followed by AMI (9.6%) and AD (3.3%). In pregnancy, the incidence of PE decreased significantly after 2014 and was lower than that of AMI and AD in 2016 and 2017. In puerperium, the incidence of PE was markedly higher than that of AMI and AD from 2008 to 2017. Subgroup analysis showed the incidence of these diseases was higher in black women, lowest-income households, and elderly parturients (Ptrend<0.0001). The mortality slightly decreased from 2.24% in 2008 to 2.21% in 2017 (Ptrend=0.0240), exhibiting 200-fold higher than patients without these diseases. The mortality of AMI decreased from 5.51% in 2008 to 2.56% in 2017 (Ptrend=0.0240). No such trend was found in AD and PE patients. The following factors were significantly associated with these diseases: over 45 years old (OR, 4.25; 95% CI, 3.80–4.75), valvular disease (OR, 10.20; 95% CI, 9.73–10.70), and metastatic cancer (OR, 9.75; 95% CI, 7.78–12.22).

            CONCLUSIONS The incidence of acute high-risk chest pain diseases, especially PE in puerperium, increased consistently. Although mortality has shown a downward trend, it is still at a high level. Monitoring and management of these diseases in pregnancy and puerperium, especially for those over 45 years old, with valvular disease or metastatic cancer, should be strengthened in the future.

            GW33-e0450
            Suspected facioscapulohumeral muscular myodystrophy with cardiac symptom

            Kun Li, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES Facioscapulohumeral muscular myodystrophy (FSHD) is a hereditary myodystrophy typically affecting skeletal muscles of the facial muscles, shoulder girdles, and upper arms. The clinical course of FSHD is highly variable and the heart is rarely involved. We aim to describe the detailed clinical characteristics of an unusual FSHD case.

            METHODS We collected data on ten family members from a Chinese FSHD family with their ages, gender, physical examination, investigations, and clinical manifestation details. Radiology, electromyography (EMG), 24-hour Holter monitor, echocardiography, cardiopulmonary exercise test (CPET), audiometry and muscle biopsy were only performed for the proband.

            RESULTS We report the case of a 32-year-old man with recurrent chest pain, elevated myocardial injury markers, and incomplete right bundle branch block (iRBBB). Coronary angiography, echocardiography, and cardiac magnetic resonance (CMR) did not identify any structural or functional abnormality. Medical and family history of muscle weakness suggested the diagnosis of dystrophy with cardiac involvement. Electromyography (EMG), muscle MRI, and muscle biopsy did not provide any indicative evidence for definitive diagnosis. Whole exon sequencing (WES) did not find pathogenic variant. Clinical diagnosis was made according to clinical criteria depending on the presence of typical clinical findings and the absence of other explanations. Cardio-pulmonary exercise test (CPET) revealed reduced excise capacity with maximal exercise 138watt under RAMP protocol with peak oxygen uptake (Peak VO2) was 53%pred and anaerobic threshold (AT) 43%pred.

            CONCLUSIONS Our study provided detailed information of an unusual FSHD case with cardiac presentation mimicking coronary artery disease. Persistent elevated cardiac enzymes, family history of myopathy could be the prelude of FSHD.

            GW33-e0631
            Comorbid diseases in patients after COVID-19

            Umida Kamilova1, Akbal Ermekbaeva2, Abror Khamraev2, Gulnoza Zakirova1, Nuriddin Nuritdinov1

            1Republican Specialized Scientific-Practical Medical Center Therapy and Medical Rehabilitation

            2Tashkent Medical Academy

            OBJECTIVES Objective the study was to study the features of comorbid conditions in patients who underwent COVID-19 and the features of the course of the postcovid period.

            METHODS We analyzed the dynamics in 220 patients who underwent COVID-19. The mean age of the patients was 54.6±11.4 years. Of these, men accounted for 107 (48.6%) and women - 113 (51.4%).

            RESULTS Analysis of the obtained data showed that 121 (55%) patients had arterial hypertension (AH), 1/3 of patients had 74 (33.6%) obesity, 39 (17.7%) patients had coronary heart disease (CHD) and 26 (11.8%) patients had chronic heart failure (CHF). Slightly less common diseases such as chronic kidney disease (CKD), atrial fibrillation (AF), chronic obstructive pulmonary disease (COPD). In the post-hospital period, many patients continued to present various complaints. After 3 months observation, at least 1 symptom persisted in 36.6% of patients, and after 6 months. observations - in 25.7%. The most common symptoms that persisted in patients up to the 3rd and 6th months were weakness - 70 (31.8%) and 51 (24.1%), as well as shortness of breath - 63 (28.6%) and 38 (17.9%). These symptoms were observed in every third patient after 3 months and every fifth in 6 months. Attention was drawn to the fact that in the first 3 months many patients −40 (18.1%) complained of rises in blood pressure against the background of previously effective antihypertensive therapy, as well as palpitations 26 (11.6%). According to the survey, after 3 months. after COVID-19 convalescence: 14.5% of patients had shortness of breath with significant exercise, 8.2% of patients with normal exercise, 5% of patients with minor exercise, 1.4% of patients at rest. Persistence of dyspnea after 6 months most often observed in patients with cardiovascular pathology. According to data analysis after 6 months. Shortness of breath with significant physical exertion, shortness of breath persisted in 4.7% of patients, with normal physical exertion in 3.8% of patients, with slight physical exertion in 2.3% of patients, at rest in 0.5% of patients.

            CONCLUSIONS In patients after COVID-19, cardiovascular diseases were most common.

            GW33-e0658
            Assessment of cardiovascular risk factors in patients with COVID-19 convalescents

            Umida Kamilova1, Dilaphruz Masharipova1, Abdurahmon Rakhimov1, Nuriddin Nuritdinov1, Gulnoza Zakirova1, Kholmurod Akhmedov2

            1Republican Specialized Scientific-Practical Medical Center Therapy and Medical Rehabilitation

            2Tashkent Medical Academy

            OBJECTIVES Assessment of cardiovascular risk factors in convalescent COVID-19 with chronic heart failure.

            METHODS One hundred thirty patients the average age of 60, 82±0.42 years (women 57 (43,84%), men 73 (56,16%) were divided into 3 functional classes (FC) using a six-minute walk test in convalescent COVID-19 with chronic heart failure. This included FC I-36, II FC-60, III FC-34 patients. The presence of adiposity in established groups, heredity, hypodynamia, cigarette smoking, cholesterol, hypertension, heart ischemic disease were studied.

            RESULTS Among the total number of patients, hypertension was 122 (93.8%), hypodynamics 117 (90,0%), hereditary 110 (84,6%), coronary heart disease 109 (83,8%), and adiposity 105 (80,8%), cigarette smoking 73 (56,0%), cholesterol 72 (55,4%) observed in the patient. When gender risk factors were observed, the incidence of risk factors was higher among men than women in particular, the presence of coronary heart disease was 95 to 70%, cholesterol 60 to 40%, especially cigarette smoking 96% 5%. Distribution of risk factors in functional classes as the functional class of patients increased, the type of risk factors encountered in them and the frequency of their occurrence increased. When analyzed according to the meeting of risk factors in one patient, patients with 1 risk factor in the group account for 8.4%, patients with 2 risk factors account for 14.6%, patients with 3 risk factors account for 76.6%.

            CONCLUSIONS Studies have shown that risk factors for patients with chronic heart failure in the period after coronavirus infection COVID-19 are directly correlated with the degree of disease, and there are correlations between age, gender, and functional classes.

            GW33-e0714
            Influence of long-term controlled therapeutic exercises on blood pressure profile parameters, elastic properties of arterial wall, metabolic and mineral indices in females with arterial hypertension

            Tatiana Petelina, Natalia Musikhina, Svetlana Bykova, Ksenia Avdeeva, Lyidmila Gapon

            Tyumen Cardiology Research Center - Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES To study the role of therapeutic exercises (TE) in the correction of blood pressure, stiffness of the vascular wall metabolic indices of body structure (volume, mass, area of visceral fat) and bone mineral metabolism in postmenopausal hypertensive patients.

            METHODS The study included 158 patients (mean age was 58.32±7.61 years). All patients are divided into 3 groups. The first control group is 20 women without arterial hypertension and menopause. The second group consisted of 58 patients with arterial hypertension (AH) and postmenopause who were not undergone complex of TE and the 3rd group - 60 women with AH and postmenopause who was undergone TE complex. Patients of all groups were examined in dynamics: at the starting point of the study and in 12 months after, ambulatory monitoring of blood pressure; sphygmography; densitometry and test for serum biochemistry parameters of blood samples, including sex hormones, vitamin D.

            RESULTS In the course of the study, blood pressure, vascular wall stiffness parameters, metabolic indices of body structure and disorder parameters of bone mineral metabolism were comparable in group 2 and 3 against the background of significantly reduced levels of sex hormones. Multidirectional correlation relationships between the studied parameters are revealed. The therapy in combination with therapeutic exercises led to a significant decrease in blood pressure and metabolic indices of body structure (P<.001) and to a persistent tendency of decrease the pulse wave velocity and increase of bone mineral metabolism in gr.3.

            CONCLUSIONS The result of the study indicates that the exercise therapy complex used in the form of regular classes can be recommended for implementation in clinical practice with the aim of comprehensively affecting the patient’s body and developing personalized treatment tactics for postmenopausal women with hypertension.

            GW33-e0736
            Association of brachial-ankle pulse wave velocity and left ventricular longitudinal strain three months after COVID-19 pneumonia

            Elena Yaroslavskaya, Anastasia Migacheva, Dmitriy Krinochkin, Nikita Shirokov, Elena Gorbatenko, Alexandra Mamarina, Nadezhda Osokina

            Tyumen Cardiology Research Center - Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES Data regarding the influence of arterial stiffness on longitudinal myocardial strain has been scarce. This is especially important for those who have undergone a complicated course of COVID-19. The objective was to investigate the associations between brachial-ankle pulse wave velocity (baPWV) and left ventricular (LV) longitudinal strain 3 months after COVID-19 pneumonia.

            METHODS Three hundred sixty-nine participants (52±11 (from 19 to 84) years; 50.9% women) 3 months ± 3 weeks after discharge after COVID-19 pneumonia were prospectively enrolled into the study. All participants underwent conventional echocardiography, including 2D speckle-tracking echocardiography. baPWV measurements were made at the same day as the echocardiography in 322 patients. The parameters of LV global and segmental longitudinal strain were studied in 296 patients with optimal visualization quality in echocardiography. Both baPWV and LV longitudinal strain were measured in 243 patients.

            RESULTS Three months after discharge, obesity was noted in 46.5% of patients, cardiovascular diseases were diagnosed in 73.4%. Arterial hypertension occurred in 71.5% of patients, coronary artery disease - in 22.5%. The median baPWV were 13.3 [11.8; 15.1] cm/s and 13.4 [11.9; 15.1] cm/s for the left and right sides, respectively. Mean LV ejection fraction was 67.8±5.0%, mean LV global longitudinal strain was −19.6±2.5%. The baPWV showed a weak correlation with longitudinal strain of LV basal level (r=0.289 for the right side and r=0.272 for the left side, both P<0.001) and of LV mid level (r=0.229, P<0.001 for the right side and r=0.218 for the left side, P=0.001). The baPWV showed a correlation of medium strength only with the longitudinal strain of the LV basal anterior segment (r=0.303 for the right side and r=0.309 for the left side, both P<0.001). There were no correlations between baPWV and longitudinal strain of LV apical level segments.

            CONCLUSIONS In patients 3 months after COVID-19 pneumonia baPWV increase associated with deterioration of LV longitudinal strain at basal and mid levels, more pronounced in LV basal anterior segment.

            GW33-e0769
            Pregnancy outcomes of women with eisenmenger syndrome: a single-center study

            Yang Liu, Yanna Li, Xiangming Fan, Jiangang Wang

            Beijing Anzhen Hospital, Capital Medical University

            OBJECTIVES Eisenmenger syndrome (ES), first described by Victor Eisenmenger in 1897, is a congenital heart defect characterized by right-to-left or bidirectional shunting with severe pulmonary hypertension (PH). Women with ES have poor tolerance of pregnancy-related physiological changes and develop high-risk complications, including rapidly progressive cardiopulmonary decompensation, thrombotic complications, and sudden death.

            METHODS Pregnant women with ES admitted to the Beijing Anzhen Hospital between 2010 and 2019 were retrospectively analyzed and followed-up.

            RESULTS Forty-two parturient women with ES were recruited. Their average age was 26.7 years (standard deviation [SD], ±4.0 years). The average gestational age was 33.7 weeks (SD, ±2.5 weeks). The average percutaneous oxygen saturation was 84.1 (±9.2). Thirty-eight (90.5%) patients had finger clubbing. Seventeen (40.5%) women had congenital heart disease (CHD) diagnosed before age 10 years, 28 (66.7%) had ventricular septal defects, and 40 (95.2%) had experienced cesarean delivery. The average pulmonary artery systolic pressure was 107.5 mmHg (SD, ±20.3 mmHg). Twelve (28.6%) women experienced pulmonary hypertensive crisis; 11 (26.2%) of these women died. Regarding the offspring, the average fetal weight was 1778.1 g (SD, ±555.3 g) and six (14.3%) offspring died. CHD was diagnosed in three (7.1%) offspring. There were significant differences in age, gestational age, percutaneous oxygen saturation, Apgar score, and heart failure between the maternal death and non-death groups (P<0.05). Death was mainly related to pulmonary hypertensive crisis and heart failure.

            CONCLUSIONS We recommend pregnancy termination if ES occurs during early pregnancy; however, if it occurs during late pregnancy, then patients should be informed of the risks. Multidisciplinary cooperation should be strengthened to improve the prognosis of the mothers and their offspring.

            CARDIOVASCULAR DISCIPLINARY RESEARCH

            PULMONARY VASCULAR DISEASE
            GW33-e0200
            Larger nocturnal hypoxemic burden due to obstructive sleep apnea predicts a higher risk of long-term adverse outcomes in patients with pulmonary hypertension

            Zhihua Huang, Zhihong Liu, Qin Luo, Anqi Duan, Meixi Hu, Zhihui Zhao, Qing Zhao, Yi Zhang, Xin Li, Lu Yan

            Center for Respiratory and Pulmonary Vascular Disease Diagnosis and Treatment, Fuwai Hospital, National Clinical Research Center for Cardiovascular Diseases, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Despite the improvement in the prognosis of pulmonary hypertension (PH), substantial morbidity and mortality remain. We aimed to investigate the prognostic value of obstructive sleep apnea (OSA) on the incidence rate of major adverse cardiovascular events (MACEs) in a large cohort of patients with PH, with a focus on the role of nocturnal hypoxemic burden.

            METHODS Consecutive patients diagnosed with PH by right heart catheterization who underwent overnight cardiorespiratory polygraphy for OSA assessment at our center were enrolled. Pulse oximetry was used to determine hypoxemic burden (time percentage spent with oxygen saturation <90% [T90]) during the night. The primary endpoint was the incidence of MACEs defined as the composite events of all-cause mortality and clinical worsening and was recorded via medical hospital records or phone calls to patients. Univariable and multivariable Cox regression analyses were used to calculate the hazard ratios (HR), and Kaplan-Meier curves were used to compare the survival probabilities between groups.

            RESULTS Of 469 eligible Chinese patients with PH, 160 (34.1%) had OSA at baseline. Over a median follow-up of 12.1 months, 79 (16.8%) patients experienced MACEs. Apnea-hypopnea index (AHI) derived from polygraphy did not predict a higher risk of incident MACEs (HR: 0.966, 95% confidence interval [CI]: 0.932–1.001, P=0.055), whereas T90 was associated with an increased risk of MACEs (HR: 1.009, 95% CI 1.002–1.014, P=0.009). After adjustment for potential confounders, T90 was still an independent predictor of MACEs with an adjusted HR of 1.006 (95% CI: 1.001–1.012, P=0.033). The likelihood of MACEs increased by 8% (95% CI 1.020–1.144) per 10-unit increase in T90. One-year event-free survival probability for patients in groups of T90 longer and shorter than 25% were 22.0 and 11.4%, respectively (Log-rank P=0.003).

            CONCLUSIONS Among patients with PH, OSA-related T90 but not AHI was a robust risk predictor of long-term MACEs. Investigation of nocturnal hypoxemic burden in PH may aid in the early risk-stratification in patients with PH.

            GW33-e0327
            The effects of choline in patients with pulmonary hypertension and monocrotaline induced pulmonary hypertension rats

            Yicheng Yang

            Center of Pulmonary Vascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Plasma choline might be a potential biomarker in cardiovascular diseases while its value on PH was still unknown. We aimed to examine the hypothesis that circulating choline levels serve as a biomarker in PH, and to determine the effects of elevated levels of plasma choline in monocrotaline (MCT)-induced PAH rats.

            METHODS Inpatients diagnosed with PH in Fuwai Hospital were included in this study. Fasting blood samples were obtained to assess choline levels and other laboratory values. An animal study was conducted to further explore the specific effects of choline in PH. Rats were randomly divided into 4 groups after a 1-week adaptation period including normal control group, choline group, monocrotaline group, and MCT+choline group. Finally, the choline levels, hemodynamic examinations, changes in organ-tissue and molecular levels were all evaluated.

            RESULTS In total, 272 inpatients with PH were included in this study. After adjusting for confounders, the high circulating choline level was still associated with poor severity. Moreover, high choline levels were associated with poor prognosis in total PH cohort. The choline levels in the rats increased in MCT + choline group, accompanied by improved hemodynamic parameters, decreased right ventricular hypertrophy, and amelioration of pulmonary vascular remodelling. The decrease in abnormal apoptosis, excessive cell proliferation, and restoration of endothelial nitric oxide synthase after choline treatment further explained the amelioration of PH.

            CONCLUSIONS Elevated choline level might be a consequence caused by disease and promisingly serve as a potential biomarker in PH.

            GW33-e0633
            Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL): a novel biomarker for prognostic assessment and risk stratification of acute pulmonary embolism

            Haixu Yu1,2, Wei Rong1, Jie Yang1, Jie Du1

            1Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China

            2Department of Cardiology, Beijing Jishuitan Hospital, Beijing 100035, China

            OBJECTIVES Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is associated with poor prognosis in cardiovascular diseases. However, the predictive value of TRAIL in acute pulmonary embolism (PE) for the short-term outcome and risk stratification remains unknown.

            METHODS This study prospectively included 151 normotensive patients with acute PE. The study outcome was a composite of 30-day adverse events, defined as PE-related death, shock, mechanical ventilation, cardiopulmonary resuscitation, and major bleeding.

            RESULTS Overall, nine of 151 (6.0%) patients experienced 30-day adverse composite events. Multivariable logistic regression showed that TRAIL was an independent predictor of study outcome (OR 0.19 per SD; 95% CI 0.04–0.90). ROC curve revealed that TRAIL’s area under the curve (AUC) was 0.83 (95% CI 0.76–0.88). The optimal cut-off value for TRAIL was 18 pg/mL, with sensitivity, specificity, negative predictive value, positive predictive value, positive likelihood ratio and negative likelihood ratio of 89%, 69%, 99%, 15%, 2.87 and 0.16, respectively. Compared with the risk stratification algorithm outlined in the 2019 ESC guidelines, our biomarker-based risk stratification strategy (combining TRAIL, hs-cTnI) has a similar risk classification effect.

            CONCLUSIONS Reduced plasma TRAIL levels predict short-term adverse events in normotensive patients with acute PE. The combination of the 2019 ESC algorithm and TRAIL is helpful for risk stratification in normotensive patients with acute PE.

            DIABETES, CEREBROVASCULAR DISEASES, KIDNEY - DISEASES, CARDIO-ONCOLOGY
            GW33-e0034
            Predictive value of plasma big endothelin-1 in adverse events of patients with coronary artery restenosis and diabetes mellitus: a prospective cohort study in China

            Ma Yue, Tian Tao, Wang Tianjie, Wang Juan, Guan Hao, Yuan Jiansong, Song Lei, Yang Weixian, Qiao Shubin

            Research Center for Coronary Heart Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, CAMS & PUMC

            BACKGROUND Diabetes patients are a high-risk group for coronary in-stent restenosis (ISR), and it is of great significance to identify biomarkers with predictive value. The plasma big endothelin-1 (Big ET-1) level is closely related to cardiovascular adverse events and is used as a predictor of risk for various cardiovascular diseases. However, for patients with ISR and diabetes who undergo percutaneous coronary intervention (PCI), whether big ET-1 is correlated with prognosis is still uncertain.

            METHODS Patients with ISR after drug-eluting stent (DES) implantation were enrolled at the Chinese Academy of Medical Sciences Fuwai Hospital from January 2017 to December 2018. The plasma big ET-1 level of each patient was examined at baseline, and the patients were divided into 3 groups according to the tertiles of big ET-1. All patients were followed up for 3 years to ascertain the prognosis. The primary endpoints were major adverse cardiovascular events (MACEs): cardiac death, nonfatal myocardial infarction (MI), target lesion revascularization (TLR), and stroke. A Cox multivariate proportional hazard model was constructed to evaluate the association between big ET-1 and the prognosis of patients with ISR and diabetes. The C statistic was used to evaluate the predictive value of big ET-1 for traditional cardiovascular risk factors.

            RESULTS A total of 1574 patients with ISR (60.79±9.77 years, 80.76% male) were included in this study, of which 795 patients were diabetic patients (61.39±9.03 years, 79.37% male). The diagnosis of diabetes significantly modified the relationship between big ET-1 and MACEs (P for interaction=0.022). In patients with ISR and diabetes, with an average follow-up of 2.96±0.56 years, a one-standard-deviation increase in big ET-1 was associated with an 86% (HR: 1.86, 95% CI: 1.30 to 2.67, P=0.001) increase in the risk of MACEs after adjustment for traditional cardiovascular risk factors. Using the 1st tertile of Big ET-1 as a reference, the HRs (95% CI) of the 2nd and 3rd tertile groups were 1.40 (0.61–3.24) and 2.53 (1.17–5.46), respectively. Furthermore, Big ET-1 added moderate but statistically significant predictive value for MACEs upon traditional cardiovascular risk factors (C statistic: 0.64 vs. 0.60, P=0.03). However, among ISR patients without diabetes, big ET-1 was not associated with the risk of MACEs.

            CONCLUSION Elevated plasma Big ET-1 was associated with a higher risk of adverse cardiovascular prognosis and therefore might be used as a predictive biomarker in ISR patients with diabetes. Further research is needed to confirm our findings.

            GW33-e0061
            Risk of arrhythmia with exposure to anthracyclines: a systematic review and meta-analysis

            Hongzheng Li1,2, Wenwen Yang1, Hua Qu1, Zikai Yu1, Linzi Long1, Changgeng Fu1

            1Xiyuan hospital, China Academy of Chinese Medical Sciences

            2Beijing University of Chinese Medicine

            OBJECTIVES Several anthracyclines have been associated with cardiac side effects, such as supraventricular arrhythmia, QT prolongation and atrial fibrillation. In order to evaluate the arrhythmic risk of anthracyclines as a class, and the comparative risk for each individual drug, we conducted a systematic review, meta-analysis, and network meta-analysis.

            METHODS Pubmed, Web of Science, EMBASE and the Cochrane Library were searched, up to March 2022, for randomized controlled trials, cohort studies, and case control studies that investigated the association between anthracyclines treatment and the risk of arrhythmia. We followed the PRISMA 2020 guidelines for data selection and extraction. Outcomes were pooled using fixed effects models in cohort studies and randomized controlled studies, and random models in single-arm studies. Direct and indirect comparisons in network meta-analysis were performed using frequentist methods.

            RESULTS Three cohort studies, 9 RCTs, and 18 single-arm studies were included in our analysis. Anthracyclines use was associated with a statistically significant 90% increase in the risk for arrhythmia (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.62–2.24) and 114% increase in the risk for supraventricular arrhythmia (OR 2.14; 95% CI 1.18–3.89). And the single-arm studies also indicated that incidence of arrhythmia rate is 20%, 95% CI is 15/100–25/100. Epirubicin ranked most likely to have the highest risk for arrhythmia compared with non-anthracycline antineoplastic drugs in the analysis (OR 43.07 [95% CI 2.80–2105.83]) by network meta-analysis.

            CONCLUSIONS Our findings show a significant association between anthracyclines use and an increased risk for arrhythmia, especially supraventricular arrhythmia. Epirubicin application ranked with the highest probability for arrhythmia. Further study is required to determine how to reduce the risk for anthracyclines-associated arrhythmia and add the evaluation of patients’ ECG in studies with the use of anthracyclines.

            GW33-e0064
            Treatment and prognosis of primary cardiac angiosarcoma: 18-year single-institution experience

            Honghong Zhang, Yuqi Liu

            Department of Cardiology, Chinese PLA General Hospital

            OBJECTIVES To investigate the clinical, pathological and imaging features, treatment and prognosis of patients with primary cardiac angiosarcoma.

            METHODS The patients with primary cardiac angiosarcoma diagnosed by pathology in Chinese PLA general hospital from January 2004 to December 2021 were retrospectively reviewed. The clinical data of the patients were collected through the electronic medical record system, including demographics, clinical symptoms, initial diagnosis, treatment strategies, pathology, survival, and imaging characteristics.

            RESULTS A total of 15 (60% male) patients with primary cardiac angiosarcoma were reviewed, median age 50 (18–60) years at diagnosis, and 1 (0.35–7.0) months from symptom onset to diagnosis. The main symptoms were dyspnea (13/15), fever (3/15), cough (3/15), edema (3/15), chest pain (3/15), abdominal pain (2/15), hemoptysis (2/15) and sudden disturbance of consciousness (2/15). Imaging examinations revealed that the tumors originated from the right heart in 10 patients (9 from the right atrium and 1 from the right ventricular outflow), 4 from the pericardium, and 1 from the pulmonary valve. Eight patients had distant metastases from lung, bone, adrenal gland, and brain. The tumor marker CA-125 was elevated in most patients (8/11). Treatment strategies included surgical resection (6 underwent complete resection, 3 underwent partial resection), 4 received chemotherapy, targeted therapy, or immunotherapy, and 2 received radiotherapy. The median overall survival (OS) was 7.9 months. Among them, patients who received multimodal therapy (surgery combined with radiotherapy, chemotherapy, targeted therapy, or immunotherapy) had a higher median OS than those who received surgery alone or not (12 vs. 5 months, P=0.016).

            CONCLUSIONS Primary cardiac angiosarcoma is rare disease with poor prognosis and lack of specificity in early clinical manifestations. Imaging examination has a certain hinting effect. Multimodal treatment will improve its prognosis.

            GW33-e0380
            Unveiling the underlying mechanism of ibrutinib-induced ventricular arrhythmias --AMPK mediated calcium handling dysfunction

            Beibei Du1,2, Praloy Chakraborty2, Mohammed Ali Azam2, Stéphane Massé2, Patrick FH Lai2, Ahmed Niri2, Xingtong Wang3, Daoyuan Si1,2, Ou Bai3, Paaladinesh Thavendiranathan2, Kumaraswamy Nanthakumar2, Ping Yang1

            1Department of Cardiology, China-Japan Union Hospital of Jilin University, Jilin Provincial Cardiovascular Research Institute, Changchun 130031, China

            2The Hull Family Cardiac Fibrillation Management Laboratory, Peter Munk Cardiac Center, Toronto General Hospital, Toronto, Cananda

            3National Key Discipline in Hematology, Department of Hematology, The First Hospital of Jilin University, Changchun, China

            OBJECTIVES Our previous study (JACC: CardioOncology (2020) 2(4):614–29) showed the acute administration of ibrutinib in spontaneous hypertension rats (SHRs) can lead to increased ventricular arrhythmias (VA) vulnerability. AMPK mediated calcium handling was assumed to be the underlying mechanism. The in-vivo study was designed to unveil and verify the molecular mechanisms.

            METHODS Old Sprague-Dawley (SD) rats were selected, and ibrutinib 10 mg/kg/d was chosen as the treatment dose. After 2 weeks and 4 weeks of oral gavage (control group (DMSO) and Ibrutinib group), the hearts of the SD rats were harvested, Langendorff-perfused and subjected to incremental stimulation for 30s. Then calcium mapping of the Langendorff-perfused hearts was done. Frequency and threshold of post incremental pacing VA, time duration of VF after pacing, the composition of VF after pacing were compared in two groups to validate the ibrutinib-induced VA animal model. Besides, the calcium dynamics was analyzed. Proteins related with calcium handling, PI3K-Akt pathway, AMPK level were analyzed with Western blot method.

            RESULTS 10 mg/kg/d ibrutinib oral gavage for 4 weeks can establish an ibrutinib-induced VA rat model. In this model, ibrutinib can significantly increase the rate of VA after incremental pacing (15.38 vs 5.77%, P=0.04) and lower the threshold of post pacing VA (10.7±0.9 hz vs 13.7±0.5 hz, P=0.02). After burst pacing, ibrutinib significantly prolonged the total duration of VF (190.3±18.4s vs 82.5±3.9s, P=0.0017) and increased sustained VF induction rate (40 vs 10%, P=0.004). Besides, the post-pacing VF composition analysis showed that, ibrutinib significantly increased the proportion VF needs defibrillation (40 vs 10%) and lowered the proportion of self-terminating (40 vs 75%). Calcium dynamics analysis showed ibrutinib prolonged CaTD80 (P=0.01), reduced calcium transient amplitude alternans ratio (P=0.008), and shortened time to peak (P=0.046). WB showed in ibrutinib group, PI3K110α expression (P=0.01), AMPK phosphorylation level (P=0.04), and Akt phosphorylation level (P=0.05) were reduced.

            CONCLUSIONS In-vivo study established an animal model of ibrutinib-induced VA. Besides, ibrutinib related calcium handling dysfunction include both the calcium release function by RyR2 and the calcium uptake capacity by SERCA2a in the sarcoplasmic reticulum. AMPK mediated calcium dysfunction is the underlying mechanism of Ibrutinib-related VA.

            GW33-e0444
            Prevalence of albuminuria and its association with cardiovascular diseases in Chinese residents aged over 35 years

            Runqing Gu1,2, Congyi Zheng2, Linfeng Zhang2, Zuo Chen2, Xin Wang2, Xue Cao2, Yixin Tian2, Lu Chen2, Haoqi Zhou2, Chen Chen2, Zhen Hu2, Yuxin Song2, Lan Shao2, Ye Tian2, Zengwu Wang2

            1School of Population Medicine and Public Health, Chinese Academy of Medical Sciences and Peking Union Medical College

            2Division of Prevention and Community Health, National Center for Cardiovascular Diseases and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES To investigate the prevalence of albuminuria in Chinese residents aged over 35 years and its potential association with cardiovascular diseases.

            METHODS Based on the database of “Twelfth Five-Year” National Science and Technology Support Project-China’s Important Cardiovascular Diseases Prevalence Survey and Key Technology Research Projects, 46,600 participants aged ≥35 years old were selected by stratified multi-stage random sampling in different regions of the east, middle and west part of China during 2012 to 2015. Data were collected through questionnaires, physical examinations and laboratory tests. Finally, data on 34,647 subjects were pooled into this study and further analyzed. Albuminuria grade were determined according to urinary albumin to creatinine ratio: <30 mg/g was identified as normal, whereas ≥30 mg/g as abnormal albuminuria, 30–300 mg/g as microalbuminuria (MAU), and ≥300 mg/g as macroalbuminuria.

            RESULTS The prevalence of abnormal albuminuria was 19.09%; it was 17.24% for MAU, lower in male (13.83%) than in female (20.08%, P<0.001). Compared with those with normal albuminuria, the risk of CVD increased among subjects with MAU (OR=1.225, 95% CI 1.115–1.346) and macroalbuminuria (OR=1.864 95% CI 1.5–2.316). When MAU complicated by hypertension and diabetes mellitus, the risk of CVD increased by 1.758 times.

            CONCLUSIONS The prevalence of abnormal albuminuria was high among Chinese aged 35 years and over. Those with abnormal albuminuria have higher CVD risk, especially with hypertension and diabetes mellitus.

            GW33-e0489
            Prognostic value of 1, 5-anhydroglucitol level in patients with acute myocardial infarction

            Yijia Wang, Ruiyue Yang, Yanan Zhang, Zhe Wang, Xinyue Wang, Siming Wang, Wenduo Zhang, Xue Yu, Jun Dong, Wenxiang Chen, Fusui Ji

            Beijing Hospital, The Affiliated Hospital of Qingdao University, China-Japan Friendship Hospital

            OBJECTIVES Diabetes mellitus is an essential risk element for cardiovascular disease. Whether 1,5-anhydroglucitol (1,5-AG), a new marker for glucose monitoring, can predict poor outcomes in acute myocardial infarction (AMI) patients is unclear.

            METHODS A prospective cohort study was employed in the present study. We enrolled 270 AMI patients who underwent coronary angiography at Beijing Hospital from March 2017 to 2020. Serum 1,5-AG concentration and biochemical indicators were tested before CAG. Cox regression analysis was conducted to investigate the relationship between 1,5-AG levels and major adverse cardiovascular and cerebrovascular events (MACCEs) and all-cause mortality.

            RESULTS During a median follow-up of 44 months, 49 MACCEs occurred, and 33 patients died. The levels of 1,5-AG were significantly lower in the MACCEs group than that in the Non-MACCEs group (P=0.001). Kaplan-Meier analysis revealed that low 1,5-AG levels were related to MACCEs (P=0.005) and all-cause mortality (P=0.024). Multivariate analysis indicated that 1,5-AG≤8.8 μg/mL was an independent predictor of MACCEs (HR 2.000, 95% CI 1.047–3.821, P=0.036). However, no predictive value of 1,5-AG was found for all-cause mortality in AMI patients (P;0.05).

            CONCLUSIONS Low 1,5-AG levels can forecast MACCEs in AMI patients but not all-cause mortality.

            GW33-e0668
            A mouse model for metabolic-associated steatohepatitis with advanced liver fibrosis and cardiac dysfunction

            Jinyao Liu1, Yumiko Oba1, Seiko Yamano2

            1Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan

            2Science Research Center, Institute of Life Science and Medicine, Yamaguchi University, Ube, Japan

            OBJECTIVES Metabolic-associated fatty liver disease (MAFLD) is frequently complicated with cardiovascular events leading to a higher mortality rate. Animal models mimicking this condition are scarce. We aim to create a mouse model for metabolic-associated steatohepatitis with advanced liver fibrosis and cardiac dysfunction.

            METHODS We maintained 12-week-old male apolipoprotein E/low-density lipoprotein receptor double-knockout (AL) mice on a low-carbohydrate–high-protein-high-fat atherogenic diet (AD) and a standard chow diet (SCD) with or without ethanol treatment for 16 weeks. Age-matched male C57BL/6J mice on SCD without ethanol treatment served as controls, and a total of 5 groups of hepatic and myocardial tissues were analyzed using Sirius-Red-, HE-, Oil-Red-O-staining, fluorescent immunostaining observed with a confocal microscope, and PCR. We conducted echocardiography and blood chemistry tests to evaluate cardiac function, hyperlipidemia, and hepatic damage.

            RESULTS AL mice showed significant hyperlipidemia. AD induced increased body weight, hepatic steatosis, and hepatic damage; however, ethanol and the AD co-diet resulted in hepatic sympathetic activation accompanied by hepatic steatosis, lobular inflammation, bridging fibrosis, and hepatic damage, which complicated with cardiac dysfunction, dilation, and sympathetic activation.

            CONCLUSIONS This study defines a mice model for metabolic-associated steatohepatitis with advanced liver fibrosis and cardiac dysfunction. By adaptation of the co-diet of ethanol and AD, either hepatic inflammation with advanced fibrosis or cardiac dysfunction can be aggravated with sympathetic activation in mice with hyperlipidemia.

            GW33-e0712
            The analysis of laboratory and instrumental parameters in prediction of long-term events in patients with cardiovascular pathology in combination with type 2 diabetes mellitus who underwent COVID-19 associated pneumonia

            Tatiana Petelina, Natalia Musikhina, Valerya Garanina, Yulia Sharoyan, Anastasia Shcherbinina, Anastasia Kapustina, Lyidmila Gapon

            Tyumen Cardiology Research Center - Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES By given pandemic status, the viral infection has shown how SARS-CoV-2 can affect patients involved in other noninfectious epidemics that have been gaining momentum for years. The objective was to perform a prospective analysis of blood biomarkers in patients with cardiovascular diseases (CVD) who underwent COVID-19 associated pneumonia in groups with and without type 2 diabetes mellitus (DM2); to assess the nature of their relationship with instrumental parameters and to identify indicators of long-term adverse cardiovascular events.

            METHODS The study was prospective, the protocol was approved by the local ethics committee - No 159 dated July 23, 2020 and registered in the international registry of clinical trials of the US National Institute of Health (ClinicalTrials.gov Identifier: NCT04501822).

            Out of 380 patients with SARS-CoV-2 associated pneumonia participating in the study, we used data from 65 patients in the present work. Patients were divided into 2 groups: group 1 included patients with CVD: arterial hypertension (AH) in combination with coronary artery disease (CAD) without DM2 (n=45), mean age 60.91±6.61 years; group 2 included patients with CVD and DM2 (n=20), mean age 62.51±4.81 years. Patients were examined at baseline in the infectious disease hospital and 3 months after discharge. During laboratory examination of blood biosamples we evaluated parameters of general blood test; biochemical parameters; concentration of highly sensitive C-reactive protein (hs-CRP), levels of interleukins (IL-1,6,8), homocysteine; from instrumental parameters - ABPM, pulse wave velocity in right and left elastic arteries, echocardiography with the study of left ventricular (LV) apical myocardial strain, computer tomography of lungs.

            RESULTS The analyzed parameters of general blood test showed that leukocyte parameters and their index coefficients - increase in NLR ratio (neutrophils/lymphocytes) and decrease in LYM/CRP ratio (lymphocytes/CRP) were more significantly changed in DM2 group. Patients in both groups had a significant excess of baseline max CRP concentrations with decrease in parameters after 3 months, but with persistent excess values in group 2 (P<0.0011). Three months after discharge patients with DM2 had levels of hs-CRP, IL-1b and TNFa (P<0.05) that exceeded both the reference values and those in group 1, which reflected the presence of more pronounced vascular inflammatory potential for possible adverse events in this group of patients in post-COVID period. In addition, the exceeding values of NT-proBNP, SBP and DBP 24, PWV-L and apical LV myocardial strain in group 2 patients compared to group 1 may be indicators of the occurrence and progression of adverse cardiovascular events in patients with DM2.

            CONCLUSIONS Thus, in groups of patients with AH and CAD, which differ only by the presence of DM2, it is clearly seen that comorbid condition can significantly affect the development of adverse cardiovascular complications due to increased inflammatory potential of blood parameters, increased stiffness of the vascular wall, and the presence of myocardial longitudinal strain of LV apical segments.

            GW33-e0760
            Resveratrol ameliorates doxorubicin-induced myocardial injury by improving mitochondrial function

            Qingling Zhang1,2, Yunpeng Zhang1,2, Yueying Wang1,2, Bingxin Xie1,2, Daiqi Liu1,2, Tong Liu1,2

            1Department of Cardiology, The Second Hospital of Tianjin Medical University

            2Tianjin Institute of Cardiology

            OBJECTIVES Doxorubicin (DOX), an anthracycline antitumor agent, is the most effective and widely used cytotoxic chemotherapy agent in clinical practice for the treatment of various tumors. However, doxorubicin has severe dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patients’ quality of life and survival time. Resveratrol (RES), a polyphenol compound and naturally occurring phytoalexin, found in many plants and red wine. Studies have shown that RES can exert antioxidant effects by scavenging the generation of oxygen radical, inhibiting lipid peroxidation and regulating the activities of antioxidation-related enzymes. Preclinical studies have shown that RES has a protective effect on several disease models, including cardiovascular disease. In this study, we established the animal model of doxorubicin-induced cardiomyopathy (DIC) to preliminarily explore the pathogenesis of DOX-induced myocardial injury, and investigated the possible treatment strategy for alleviating myocardial injury through RES intervention in vitro.

            METHODS Adult male C57BL/6J mice (10 weeks old) were randomly divided into Control group (Con, n=10) and doxorubicin group (DOX, n=10). DOX group was injected with DOX (7.5 mg/kg, twice every other day, intraperitoneal) to establish DIC model, which was assessed by observing the changes of behavior, appearance and body weight, echocardiographic, surface electrocardiogram, myocardial histomorphology. To further verify the possible mechanism of DIC, H9c2 cell lines were used and the experiment were divided into three groups: control group (Con), doxorubicin group (DOX) and resveratrol group (DOX+RES).

            RESULTS Compared with Con group, the body weight of DOX group was significantly decreased (21.68±0.87 g vs 19.74±1.35 g, P=0.043) and systolic arterial pressure in DOX group was significantly increased (112.67±5.60 mmHg vs 125.93±12.33 mmHg, P=0.007). Echocardiogram showed that the left ventricular ejection fraction (53.10±5.28% vs 41.63±6.44%, P=0.019), short axis shortening rate (26.97±3.53% vs 20.21±3.74%, P=0.021), left ventricular posterior wall thickness during diastolic period (1.28±0.07 mm vs 0.99±0.18 mm, P<0.01) were significantly decreased in DOX group. Compared with Con group, surface electrocardiograph showed that the PR interval (42.75±2.99 ms vs 62.23±12.59 ms, P=0.006), QT interval (19.75±2.50 ms vs 29.93±5.13 ms, P=0.004) and QTc interval (50.82±9.90 ms vs 80.24±16.38 ms, P=0.009) in DOX group were significantly prolonged. High power transmission electron microscopy (TEM) observed that cardiac cells in DOX group were extensively vacuolated and disordered, with smaller mitochondria, higher membrane density, less cristae and incomplete membrane structure. Western Blot showed that the protein expressions of α-SMA, Mfn2 and Caspase3 were significantly increased in DOX group, while the protein expressions of Sirt1 and Sirt3 were significantly reduced. Compared with DOX group, the protein expressions of Mn-SOD and Mfn2 in DOX+RES group decreased, and mitochondrial morphology tended to be stable. Caspase3 protein expression and cell apoptosis was significantly reduced in DOX+RES group.

            CONCLUSIONS DOX induced myocardial injury might lead to abnormal mitochondrial morphology and function, induce apoptosis and promote fibrosis formation by interfering with mitochondrial fusion and division. Resveratrol, the Sirt1 agonist, ameliorates Doxorubicin-induced myocardial injury by regulating mitochondrial function.

            GW33-e0762
            The impact of acute myeloid leukemia subtypes on cardiovascular mortality among patients receiving chemotherapy

            Xiaodong Peng, Cuicui Feng, Yukun Li, Xuesi Wang, Xinmeng Liu, Yanfei Ruan, Nian Liu, Changsheng Ma

            Beijing Anzhen Hospital, Capital Medical University

            OBJECTIVES The anthracycline regimen is the cornerstone of acute myeloid leukemia (AML) chemotherapy. The anthracycline-induced cardiotoxicity is a common problem in clinical settings, but there are limited data concerning its cardiac-specific mortality in patients with AML, especially among different histological subtypes.

            METHODS The present study was based on the Surveillance, Epidemiology, and End Results (SEER) database. Participants with established AML from 2000 to 2019 were included in our analysis. The demographic data (age, gender, race, marital status, and economic condition), histological types of AML, and prognosis information was collected. The patients were divided into histological groups according to the 2016 World Health Organization (WHO) classification. The subdistribution hazard ratios (SHRs) were estimated to evaluate the association of AML subtypes with cardiac-specific death using Fine and Gray competing risk-adjusted models.

            RESULTS A total of 20,177 patients diagnosed with AML and receiving chemotherapy were enrolled in this study. Among them, 54.7% of patients (11,040) were male. The most common histological subtype was AML not otherwise specified (NOS) (50.9%), followed by AML with recurrent genetic abnormality (RGA) (24.6%), AML with myelodysplastic syndromes (MDS) (18.1%) and therapy-related AML (6.5%), respectively. After adjusting the competing risk, the cardiac-specific mortality was 3.6, 2.4, 2.1, and 1.2% for AML with RGA, AML with NOS, AML with MDS, and therapy-related AML, respectively. The multivariate Fine-Gray analysis indicated the therapy-related AML (SHR=0.33, 95% CI: 0.18–0.62, P=0.001), AML with MDS (SHR=0.51, 95% CI: 0.36–0.72, P<0.001), AML NOS (SHR=0.66, 95% CI: 0.50–0.86, P=0.002), female sex (SHR=0.78, 95% CI: 0.62–0.98, P=0.032) and higher-income (≥85,000$) (SHR=0.68, 95% CI: 0.51–0.91, P=0.009) were protective factors concerning cardiovascular mortality. On the contrary, older age was an independent risk factor. No significant difference was found between race/marital status and cardiac death.

            CONCLUSIONS The incidence of cardiovascular mortality was highest in AML patients with recurrent genetic abnormality compared to other histological subtypes. Besides, patients who were male, old age and poor economic condition were associated with a high risk of cardiac-specific death. The incidence of cardiovascular mortality was highest in AML patients with recurrent genetic abnormality compared to other histological subtypes. Besides, patients who were male, old age and poor economic condition were associated with a high risk of cardiac-specific death.

            PERIPHERAL VASCULAR DISEASE
            GW33-e0387
            Relationship between physical performance and peripheral arterial diseases in different age groups of Chinese community- dwelling older adults

            Xiya Fu1, Qi Guo2

            1Department of Sport Rehabilitation, Shanghai University of Sport

            2Department of Rehabilitation Medicine, Shanghai University of Medicine and Health Sciences

            BACKGROUND AND AIMS This study aimed to examine the relationship between physical performance and peripheral artery disease (PAD) in different age groups of Chinese older adults.

            METHODS We enrolled 1416 relatively healthy ≥65 years old participants of Chinese ethnicity. We classified the participants into two age categories, the pre-old group (65–74 years, n=1, 015) and the old group (≥75 years, n=401). We assessed the cross-sectional association of the ankle-brachial index (ABI), which is used for the classification of patients with PAD (ABI≤0.9). Physical performance mainly focused on muscle strength, mobility and balance, which were measured via hand grip, 4-m walking speed, and the Timed Up and Go Test (TUGT).

            RESULTS A total of 125 (8.8%) patients met the diagnostic criteria and were defined as having PAD. After multivariate adjustment, we found that grip strength and 4-metre walking speed were correlated negatively with PAD [odds ratio (OR)=0.952, 95% CI=0.918–0.998; OR=0.265, 95% confidence interval (CI)=0.083–0.843] in pre-old participants, while TUGT (OR=1.058, 95% CI=1.007–1.112) was correlated positively with PAD only in older participants.

            CONCLUSIONS Our study further confirmed the association between physical performance and PAD in community-dwelling older Chinese adults. Muscle strength and mobility correlated negatively with PAD in pre-old participants, and balance was positively associated with PAD in older participants. These findings might help with better early screening and management of PAD.

            GW33-e0576
            Identification of pivotal chromatin regulators in the progression from asymptomatic to symptomatic carotid plaque: a new perspective for the early diagnosis

            Yufei Zhou1, Shengjue Xiao2, Xiaotong Wang3, Kai Wang4

            1Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China

            2Department of Cardiology, Zhongda hospital, School of Medicine, Southeast University, Nanjing 210009, China

            3Department of Cardiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221004, China

            4Department of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

            OBJECTIVES Patients with symptomatic carotid plaque (SCP) are at risk of developing severe complications. Previous studies have mainly focused on plaque pathology classification, which is inconsistent with clinical manifestations. Chromatin regulators (CRs) play a critical part in epigenetic regulation. Our study aimed to identify differentially expressed CRs (DECRs) for early SCP diagnosis.

            METHODS GSE111782 was downloaded from GEO database. CRs were extracted using Perl. A series bioinformatics and machine learning approaches were used to screen the DECRs in the progression from asymptomatic carotid plaque (ASCP) to SCP, including DECRs identification using Limma, functional enrichment analysis, protein-protein interaction (PPI) network construction, support vector machine recursive feature elimination (SVM-RFE) and random forest algorithms application. Finally, the receiver operating characteristic curve (ROC) was used to determine the diagnostic value, and the nomogram was created for clinical usage.

            RESULTS Seven hundred and forty CRs were extracted and 39 DECRs were identified from the dataset, of which seven and 32 were up- and down-regulated, respectively. DECRs were mainly enriched in chromatin organization and histone modification. After removing non-connection DECRs from the PPI network, a total of 30 DECRs were visualized and 19 DECRs with nodes over three were chosen for machine learning. Seven DECRs with the highest accuracy and lowest error in SCP diagnosis were filtrated using SVM-RFE. Ten DECRs were selected by random forest based on the importance score. From the intersection of SVM-RFE and random forest, three DECRs (JAK2, RBBP7, EHMT1) were selected. Finally, the area under curve (AUC) of JAK2, RBBP7, EHMT1, and nomogram calculated from the ROC curve were 0.765, 0.815, 0.790 and 0.852, respectively, indicating the optimal diagnostic value.

            CONCLUSIONS We identified three DECRs (JAK2, RBBP7, EHMT1) for the early diagnosis of the progression from ASCP and SCP. The DECRs were primarily involved in regulating chromatin structure and histone modification. Meanwhile, we provided the nomogram for further clinical practice.

            GW33-e0582
            Clinical relevance of uric tobacco-specific nitrosamines and severe abdominal aortic calcification in a national survey

            Fang Wang, Jingang Zheng

            Department of Cardiology, China-Japan Friendship Hospital, Beijing, China

            OBJECTIVES Smoking is recognized as the independent risk factor of cardiovascular diseases (CVDs), although the prevalence of CVDs varies drastically among smokers. Actually, it is difficult to measure the extent of tobacco use and exposure to environmental tobacco smoke. Tobacco-specific nitrosamines (TSNAs) are becoming an important class of biomarkers for tobacco carcinogen uptake. No previous study discussed the association between TSNAs and CVDs. The aim of this cross-sectional study is to investigate the relationship between uric TSNAs and abdominal aortic calcification (AAC), an independent predictor of CVDs, in the United States (US) adults.

            METHODS The data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2013–2014, including 2713 individuals aged 40–79 years. The measurement of uric N’-nitrosonornicotine (NNN), one of the major TSNAs, was performed by an isotope-dilution high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (ID HPLC-ESI MS/MS). AAC was quantified by the Kauppila score system based on dual-energy X-ray absorptiometry. The association between uric NNN and severe AAC was determined by multivariable logistic regression models. Finally, stratified and interactive analyses were performed to determine whether the results were stable in different subgroups.

            RESULTS The median (interquartile range, IQR) age of all participants was 59.0 (49.0, 68.0) years. The median (IQR) uric NNN level was 0.2 (0.2, 0.2) ng/dL. The uric NNN level was categorized as normal or high by means of the median concentration (0.2 ng/dL). After adjustment for multiple covariates, compared with normal, high uric NNN level was associated with greater risk of severe AAC (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.65 to 3.82; P<0.001). In multivariable analyses, every 1-unit (ng/dL) increase in uric NNN was associated with a greater risk of severe AAC (OR: 1.15; 95% CI: 1.01 to 1.31; P=0.03). The association between uric NNN and severe AAC was not modified by sex, age, race, body mass index (BMI), alcohol consumption, hypertension, or diabetes mellitus (Interaction P;0.05 for all). The association between other TSNAs such as the 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), N’-nitrosoanatabine (NAT), N’-nitrosoanabasine (NAB), and severe AAC did not reach statistical significance.

            CONCLUSIONS We are the first to reveal the positive relationship between uric TSNAs level and severe AAC in a sample of US adults. Our findings indicated that uric TSNAs may become a promising tool to reflect the exposure to tobacco, and to predict the incidence and prognosis of CVD.

            CARDIOVASCULAR IMAGING
            GW33-e0079
            DeepCAG: coronary angiography deep learning model for diagnosis of neoatheroslcerosis

            Yingqian Zhang1, Peng Zhang2, Xiangjun Wu3, Zechen Wei4, Jing Jing1, Feng Tian1, Hui Hui4, Jie Tian3, Yundai Chen1

            1Chinese PLA General Hospital

            2Department of Biomedical Engineering, School of Computer and Information Technology, Beijing Jiaotong University

            3Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, School of Medicine and Engineering, Beihang University

            4CAS and Beijing Key Laboratory of Molecular Imaging, Institute of Automation

            OBJECTIVES We aimed to develop a deep learning-based nomogram model (DeepCAG) to diagnose neoatherosclerosis from coronary angiography in patients with in-stent restenosis.

            METHODS We included 123 consecutive in-stent restenosis patients with OCT during angiography follow-up after percutaneous coronary intervention. The enrolled patients were randomly divided into the training cohort (85 lesions) and testing cohort (41 lesions). We adopted Inception V3 as the main network, and added two convolutional layers, a pooling layer and a fully connected layer. To further promote the diagnosis performance, we fused the deep learning signature with related clinical features to construct nomogram.

            RESULTS The AUC of the nomogram is 0.751. The accuracy of neoatherosclerosis diagnosis is more balanced (sensitivity: 0.733, specificity: 0.692) compared with deep learning signature (sensitivity: 0.867, specificity: 0.462). To compare the performance of the nomogram with cardiologists, an independent dataset of 41 lesions were employed. The accuracy of the nomogram is 0.707, which is comparable to those of the two senior cardiologists (0.659, 0.634, P=0.416, P=0.316) and the three junior cardiologists (0.610, 0.561, 0.463, P=0.181, P=0.337, P=0.056). The sensitivity of nomogram is 0.733, which is comparable with both senior and junior cardiologists. The specificity of the nomogram is 0.692, which is similar to the senior cardiologists (0.692, 0.692, P=1.00, P=1.00). However, it is relatively higher than those of the junior cardiologists (0.500, 0.423, 0.269, P=0.020, P=0.059, P=0.005).

            CONCLUSIONS The deep learning model using coronary angiography showed the potential to differentiate in-stent restenosis lesions with and without neoatherosclerosis.

            GW33-e0115
            Dual left anterior descending artery with anomaly origin of the long left coronary artery from the right coronary sinus or right coronary artery

            Xiaolong Liu, Zhanguo Sun, Xiaoqiang Wang

            Department of Radiology, Affiliated Hospital of Jining Medical University

            OBJECTIVES Dual left anterior descending (LAD) is a rare type of coronary variant, in which the short LAD travels and terminates in the upper anterior interventricular groove (AIVG) and the long LAD travels in the middle and lower AIVG. It is rare that long LAD originates from right coronary sinus (RCS) or right coronary artery (RCA), but the special origin and course of the long LAD branch may lead to hemodynamic changes, causing myocardial ischemia. Moreover, accurate knowledge of the origin and course of the two LADs is crucial to the success of coronary artery bypass grafting.

            METHODS Twenty-five patients with dual LAD anomaly with long LAD originating from RCS or RCA who underwent coronary CT angiography (CCTA) in our hospital from were retrospectively collected. According to the course of the long LAD, it was divided into pre-pulmonic (pre-LAD, 12 cases) and sub-pulmonic (sub-LAD, 13 cases), and the CCTA examination of 30 patients without coronary artery variation was collected as control group. The length and diameter of each segment were measured. And the origin, course, branching, and atherosclerotic plaques of short LAD and long LAD were evaluated.

            RESULTS The LAD long branch of 16 patients originated from the RCS, and 9 originated from the proximal RCA. The total length of the long LAD and short LAD were (137.52±23.38) mm and (47.59±12.33) mm, and the difference was statistically significant (P<0.001); the diameters of the initial section were [2.10 (2.00, 2.65)] mm and [2.30 (1.90, 2.80)] mm, the difference was not statistically significant (P>0.05). There was no significant difference in the origin of pre-LAD and sub-LAD, and the presence of diagonal branches (P;0.05). Septal branches were seen in 3 pre-LAD and 11 sub-LAD, and the difference was statistically significant (P<0.05). In the pre-LAD group, the right conical branches all originated from the long LAD; in the sub-LAD group, the right conical branches all originated from the RCA or RCS. Plaques were seen in 2 pre-LADs, but no plaques were found in sub-LADs; plaques were seen in 12 short LADs. The length of the LAD in the control group was longer than that of the sub-LAD, the segment before the anterior interventricular groove of the pre-LAD was longer than these of the sub-LAD and the control group, and the distal diameter of the sub-LAD and control group LAD were larger than those of the pre-LAD, and these differences were all statistically significant (P<0.05). In addition, the diameter of the distal segment of the sub-LAD was larger than that of the middle segment, and the difference was statistically significant (P<0.05).

            CONCLUSIONS The anatomical differences between the dual LAD anomaly with long LAD originating from the right RCS or RCA and the normal LAD are large. CCTA can comprehensively evaluate the origin, course, branches, anatomical relationships, and lumen condition of the two LADs in the dual LAD variant.

            GW33-e0123
            Reverse remodeling of left atrium assessed by cardiac MR feature rracking in hypertrophic obstructive cardiomyopathy after septal myectomy

            Yang Shu Juan, Zhao Shi Hua

            Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Assessing the structure and function of left atrial (LA) is crucial in hypertrophic obstructive cardiomyopathy (HOCM) because LA remodeling correlates to atrial fibrillation. However, there is little evidence showing the effect of myectomy on LA phasic remodeling in patients with hypertrophic obstructive cardiomyopathy using cardiac MR (CMR) feature tracking (FT). This study aimed to evaluate the effect of septal myectomy on left atrial structural and functional remodeling in patients with hypertrophic obstructive cardiomyopathy (HOCM) by using CMR-FT and to further investigate the determinants of postoperative LA strains.

            METHODS We retrospectively studied 88 patients with HOCM who received pre- and postmyectomy CMR between January 2011 and June 2021 in this single-center study. Pre- and postmyectomy left atrial (LA) parameters derived from CMR-FT were compared, including LA reservoir function (total ejection fraction [EF], total strain [εs], peak positive strain rate [SRs]), conduit function (passive EF, passive strain [εe], peak early negative strain rate [SRe]) and booster function (booster EF, active strain [εa], late peak negative strain rate [SRa]). Eighty-six healthy participants were collected for comparison. Univariate and multivariate linear regression determined the variables associated with postoperative LA strains.

            RESULTS Compared with preoperative parameters, LA reservoir function (total EF, εs, SRs), booster function (booster EF, εa, SRa), and SRe were significantly improved (all P<0.05) after myectomy, while no significant difference was observed in passive EF and εe. However, postoperative patients with HOCM still had larger LA and worse LA phasic function than healthy controls (all P<0.05). On multivariable regression analysis, LV maximal wall thickness ≥30 mm and minimum LA volume index were significantly associated with postoperative εs and εa.

            CONCLUSIONS In patients with HOCM, septal myectomy leads to the LA reverse remodeling with a reduction in LA size and improvement in LA reservoir and booster function, but unchanged LA conduit function. Besides, patients with massive LV hypertrophy and larger minimum LA volume index before myectomy may have poor LA deformation function postoperatively.

            GW33-e0153
            Molecular imaging of fibroblast activation protein in patients with acute myocardial infarction complicating gastrointestinal bleeding using 68Ga-FAPI

            Suxuan Liu1, Guokun Wang2, Qinqin Yang3, Chao Cheng3

            1Department of Cardiology, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

            2Department of Cardiovascular Surgery, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

            3Department of Nuclear Medicine, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

            OBJECTIVES Acute myocardial infarction (AMI) complicating gastrointestinal bleeding (GIB) poses significant management challenges and may be associated with poor outcomes. Endoscopic examination in these patients is risky because of hemorrhagic and cardiovascular events. Radiolabeled fibroblast activation protein inhibitor (FAPI) is a novel target for molecular imaging in multiple cancers. We sought to demonstrate the feasibility of FAPI PET imaging to detect the potential tumor and identify the injured myocardium simultaneously in AMI patients complicating GIB.

            METHODS From January 2021 to March 2022, 10 AMI patients complicating GIB were enrolled in the study. All patients underwent coronary angiography (CAG) and PET-CT/MR examination using 68Ga-FAPI-04.

            RESULTS The median age of the 10 AMI patients (six male and four female) was 55 years old (45–76 years). Four patients presented with ST-segment elevation MI (STEMI), and the other six presented with non-ST-segment elevation MI (NSTEMI). Nine patients underwent emergent percutaneous coronary intervention (PCI) and showed melena or hematochezia after PCI. The other patient presented with melena first was diagnosed with gastric cancer and developed NSTEMI later. All of them were found high focal uptake of 68Ga-FAPI-04 in the injured myocardium correlated with the area and the position of the culprit artery. The activity of FAPI imaging was associated with the increased levels of circulating cTnI. Three patients found a significant high 68Ga-FAPI-04 uptake in the gastrointestinal tract or prostate. They were diagnosed with gastric cancer, rectal cancer, and prostate cancer following a biopsy, respectively. Other patients with negative FAPI imaging were diagnosed with gastric ulcers and did not detect gastroenteric tumors by the gastroenterological endoscope.

            CONCLUSIONS FAPI PET-CT/MR imaging is an invasive tool to identify the area of activated cardiac fibroblasts and detect the potential gastroenteric tumor simultaneously in AMI patients complicating GIB.

            GW33-e0155
            Molecular imaging of fibroblast activity in pressure overload heart failure

            Suxuan Liu1, Guokun Wang2, Qinqin Yang3, Chao Cheng3

            1Department of Cardiology, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

            2Department of Cardiovascular Surgery, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

            3Department of Nuclear Medicine, the First Affiliated Hospital (Changhai Hospital) of Naval Medical University, Shanghai, China

            OBJECTIVES Cardiac fibrosis, mediated by the activation of cardiac fibroblasts, is critical in pressure overload-induced heart failure. Fibroblast activation protein (FAP), specifically expressed by activated fibroblasts, can be visualized by radiolabeled FAP inhibitors (FAPI) PET/CT. We aimed to evaluate whether 68Ga-FAPI-04 can characterize the early stages of cardiac fibrosis in pressure overload heart failure.

            METHODS Sprague-Dawley rats underwent abdominal aortic constriction (AAC) (n=12) and sham surgery (n=10). All rats were scanned with 68Ga-FAPI-04 PET/CT at 2, 4, and 8 weeks after surgery. Cardiac function was measured by echocardiography. The expression of FAP in the myocardium was detected by immunohistochemistry.

            RESULTS Compared with the sham group, we observed decreased ejection fraction (EF) and fractional shortening (FS) and increased left ventricular internal dimensions in systole (LVIDs) and diastole (LVIDd) in the AAC group at 4 and 8 weeks (all P<0.05). The AAC group showed higher 68Ga-FAPI-04 accumulation in the heart than the sham group at 2, 4, and 8 weeks (P<0.05), and FAPI increased significantly from 2 to 8 weeks. Immunohistochemistry confirmed the higher density of the FAP+ area in the AAC group. The intensity of the 68Ga-FAPI-04 PET signal correlated with the density of the FAP+ area on histology (P<0.05). The expression of the 68Ga-FAPI-04 signal at 4 weeks correlated with the deteriorated cardiac function at 8 weeks (EF: r=-0.78; FS: r=−0.67; LVIDd=0.8; LVIDs=0.65; all P<0.05). The AAC group also showed an increased 68Ga-FAPI-04 signal in the liver, peaking at 4 weeks and then declining after that. Cardiac and liver PET signals directly correlated at 4 weeks in the AAC group (r=0.69, P=0.001). A combination of the FAPI intensity in the heart and liver at 4 weeks better predicted the deterioration of cardiac function at 8 weeks.

            CONCLUSIONS The activated fibroblasts in the heart and liver after pressure overload can be monitored by 68Ga-FAPI-04 PET/CT. This imaging technique reveals an early fibrotic link in cardio-liver interactions and could predict nonischemic heart failure prognosis.

            GW33-e0196
            Ischemia-like late gadolinium enhancement related to adverse outcomes in hypertrophic cardiomyopathy patients with non-extensive fibrosis

            Shu Juan Yang, Shi Hua Zhao

            MR Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases of China, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Late gadolinium enhancement (LGE) has been established as an independent predictor for adverse outcomes in hypertrophic cardiomyopathy (HCM). However, the prevalence and clinical significance of some LGE subtypes have not been well demonstrated. The current study aims to investigate the prognostic value of ischemia-like LGE pattern and right ventricle insertion points (RVIP) LGE location in HCM patients.

            METHODS In this single-center retrospective study, 497 consecutive HCM patients with LGE confirmed by cardiac MR (CMR) were included. Ischemia-like LGE pattern was defined as LGE involving subendocardium; RVIP LGE was defined as LGE involving the junctions of the interventricular septum and right ventricular free walls. Cases with ischemic heart disease were excluded from the study. Endpoint included a composite of heart failure events, arrhythmic events, and stroke.

            RESULTS Of the 497 patients, ischemia-like LGE and RVIP LGE were observed in 184 (37.0) and 414 (83.3%), respectively. All patients were divided into two groups based on the LGE amount of 15%. During follow-up of 57.8 months, 66 of 497 patients (13%) experienced composite endpoint. Spline analysis showed a non-linear association between LGE extent with hazard ratios for adverse outcomes: the incidence of composite endpoint was not closely related to LGE extent in patients with non-extensive LGE (<15%), whereas the risk of composite endpoint increased with per percentage increase in LGE extent in patients with extensive LGE (≥15%). In Cox proportional hazard regression analysis, after adjusting for left ventricular (LV) ejection fraction, age, sex, LV outflow tract obstruction, and maximum LV wall thickness, ischemia-like LGE was associated with composite endpoint instead of LGE extent in group with non-extensive LGE (HR, 2.87; P=0.003), while LGE extent significantly related to composite endpoint instead of ischemia-like LGE in patients with extensive LGE (HR, 1.05; P=0.03). RVIP LGE was not significantly associated with poor outcomes in both groups.

            CONCLUSIONS In HCM patients with non-extensive LGE, ischemia-like LGE rather than LGE extent is associated with unfavorable outcomes, which is an underrecognized phenotype showing the potentiality to improve risk stratification. However, the presence of RVIP LGE did not merit a prognostic value.

            GW33-e0201
            Personalizing CMR-based risk stratification for outcomes in dilated cardiomyopathy with LVEF≥35%: cohort study with a long-term follow-up

            Shuang Li1, Wenjing Yang1, Xiaohan Fan2, Sharma Piyush3, Sirajuddin Arlene4, E. Arai Andrew4, Shihua Zhao1, Minjie Lu1

            1Department of Magnetic Resonance Imaging, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

            2Department of Cardiac Arrhythmia Center, Fuwai Hospital, State Key Laboratory of Cardiovascular Disease, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

            3Saint James School of Medicine, Park Ridge, Illinois, USA

            4Department of Health and Human Services, National Heart, Lung and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, USA

            OBJECTIVES Recent studies have demonstrated that a considerable number of patients who succumbed to SCD had a LVEF≥35%. The risk of adverse events have not yet been systematically studied in these DCM patients. This study aims to identify the risk factors for adverse events in DCM patients with a LVEF≥35% and establish a scoring model to predict the adverse event risk.

            METHODS A cohort of 466 consecutive DCM patients (358 men, 44±14 years) with a LVEF≥35% who had undergone gadolinium-enhanced cardiac magnetic resonance (CMR) imaging were enrolled in this study. The primary endpoint was a composite of SCD or aborted SCD. The secondary endpoints were all-cause mortality, heart transplantation, and hospitalization for heart failure. The risk factors for primary and secondary endpoints were identified by multivariate cox analysis and used to create a nomogram.

            RESULTS During a mean follow-up period of 79.4±29.5 months, a total of 40 and 61 patients reached the primary and secondary endpoints, respectively. Multivariate stepwise analyses showed that age (hazard ratio, HR=1.027; 95% CI, 1.001–1.053), family history of SCD (HR=3.551; 95% CI, 1.378–9.150), NYHA (HR=2.054; 95% CI, 1.100–3.837), and late gadolinium enhancement (LGE)≥7.7% (HR=6.519; 95% CI, 2.751–15.443) had a significant prognostic association with the primary endpoints (all P<0.05). Multivariate stepwise analyses showed that NYHA (HR=1.944; 95% CI, 1.161–3.255), left atrium volume index (LAVi);47.3 mL/m2 (HR=2.142; 95% CI, 1.274–3.601), LGE>6.9% (HR=2.296; 95% CI, 1.370–3.846), and global longitudinal strain (GLS);-8.5% (HR=2.454; 95% CI, 1.467–4.105) had significant prognostic associations with the secondary endpoints (all P<0.05). Nomograms for the adverse events were created by using these factors.

            CONCLUSIONS LGE and GLS are new parameters derived from CMR that identify the risk of adverse events in DCM patients with a LVEF≥35%. The nomogram we created using these parameters provides a novel way to clinically assess and risk stratify this patient population.

            GW33-e0456
            Electrophysiological-related CT imaging of cardiac anatomy

            Xue Xia

            China-Japan Union Hospital of Jilin University

            OBJECTIVES By analyzing the relationship between electrophysiological cardiac anatomy, we hope to help electrophysiologists adjust the length and curvature of ablation catheter during radiofrequency ablation.

            METHODS Patients who underwent the coronary CTA and the atrium CTA between October 2020 and June 2021 were screened. After evaluation, 105 patients were included in our study. A heart rate of <65 beats/min was used as the target heart rate to ensure accurate image capture and proper visualization. The distance of cardiac anatomy (fossa ovalis, coronary sinus, pulmonary vein, inferior vena cava) were measured and compared. Data were analyzed using SPSS 26.0 statistical software.

            RESULTS We measured the distance between the midpoint of inferior vena cava opening to the midpoint of the fossa ovalis at different heights, then we find that the fossa ovalis is not a regular membranous plane. Because there is no regularity in the distance between them. The distance between the inferior vena cava opening and the front of the midpoint of 1/2 height of the fossa ovalis (16.29 mm) is longer than the midpoint (10.02 mm) and posterior (5.85 mm). By measuring above distance, it is aimed to assist the operator in adjusting the length and curvature of the needle, preventing damaging the atrium and leading to cardiac pressure plug. The distance from the midpoint of the inferior vena cava opening to the midpoint of 1/2 height of the fossa ovalis and distance from the middle point of 1/2 height of to the coronary sinus fit the equation of y=0.385x+0.548 (The former represents y, and the latter represents x). Indicating that if we have determined the position of the coronary sinus, it is easy for us to determine the position of the fossa ovalis and adjust the length and curvature of the needle and catheter. The distance from the inferior vena cava to the anatomical structure of right atrium (fossa ovalis, coronary sinus, tricuspid orifice of the central fiber) increased with the right atrium diameter, and the distance from the pulmonary vein to the fossa ovalis increased with the left atrium diameter.

            CONCLUSIONS In conclusion, fossa ovalis and coronary sinus exhibit significant individual anatomical variability, which could influence the process of radiofrequency ablation. With the cardiac computed tomography, we can infer the position of the fossa ovalis from the position of the coronary sinus. Furthermore, the length and curvature of the ablation catheter can be adjusted timely for patients with large atrium.

            GW33-e0531
            Endogenous assessment of late gadolinium enhancement gray zone in patients with non-ischemic cardiomyopathy with T1ρ and native T1 mapping

            Zhixiang Dong, Shihua Zhao

            Department of Magnetic Resonance Imaging, Fuwai Hospital, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

            OBJECTIVES Both T1ρ and native T1 mapping are promising tools to endogenously assess myocardial tissue characterization. However, the comparison of their abilities in characterizing LGE gray zone has not been reported yet. This study aims to validate and compare the feasibility of T1ρ and native T1 mapping in detection of myocardial fibrosis in patients with non-ischemic cardiomyopathy, focusing on the performance of both methods in identifying LGE gray zone.

            METHODS Twenty-seven hypertrophic cardiomyopathy (HCM) patients, 16 idiopathic dilated cardiomyopathy (DCM) patients and 18 healthy volunteers were prospectively enrolled. All the CMR protocols were conducted in 3.0T MR system (Ingenia 3.0T, Philips Healthcare, the Netherlands). T1ρ mapping, pre-contrast T1 (native T1) mapping, post-contrast T1 mapping and LGE imaging were performed in all the patients. T1ρ mapping and native T1 mapping were performed in healthy controls. Patients were divided into LGE positive group and LGE negative group for the comparison of global T1ρ and native T1 values. Besides, the LGE areas were divided into LGE core (6 SDs above remote myocardium) and gray zone (2–6 SDs above remote myocardium) according to the signal intensity of LGE. Native T1 value, T1ρ value and ECV were calculated at each region of interest (ROI, with a radius of ≥2 mm) according to the classification of LGE for comparison.

            RESULTS LGE was detected in 17 HCM patients and 10 DCM patients respectively. Patients showed significant higher native T1 values than controls (HCM: 1301.2±10.2 ms and DCM: 1285.0±12.3 ms versus Control: 1252.1±5.1 ms, P<0.01). Meanwhile, patients also showed higher T1ρ values than controls and HCM patients had the highest T1ρ value than other two groups (HCM: 48.6±0.6 ms versus DCM: 46.2±1.0 ms and Control: 41.7±0.8 ms, P<0.001). No matter the presence of LGE, patients had significantly higher native T1 and T1ρ values than controls (native T1: 1301.53±50.97 ms for LGE+ group and 1285.47±52.38 ms for LGE- group versus 1252.1±5.1 ms for Control; T1ρ: 48.48±3.47 ms for LGE+ group and 46.52±3.39 ms for LGE- group versus 41.7±0.8 ms for control, all P<0.001). There were significant differences in native T1 and T1ρ values among 4 different types of myocardia (LGE core, gray zone, remote area and control, P<0.0001). However, the T1ρ values of gray zone were significantly higher than control (P<0.01) while the native T1 values were not (P=0.089). T1ρ values were significantly associated with both native T1 values (r=0.54, P<0.001) and ECV values (r=0.54, P<0.001).

            CONCLUSIONS T1ρ mapping is a feasible method to detect myocardial fibrosis in patients with non-ischemic cardiomyopathy no matter the presence of LGE. Compared with native T1, T1ρ may serve as a better discriminator in the identification of LGE gray zone.

            GW33-e0560
            Coronary microvascular dysfunction in nonobstructive hypertrophic cardiomyopathy: assessment with first-pass perfusion imaging using 3.0 T cardiac magnetic resonance

            Wei Gao1,2, Wei Zhao1, Zhi-Ming Li1, Jie Deng1, Wei Chen1

            1The First Affiliated Hospital of Kunming Medical University

            2Honghe Affiliated Hospital of Kunming Medical University

            OBJECTIVES To assess coronary microvascular dysfunction in nonobstructive hypertrophic cardiomyopathy (NOHCM) patients using CMR resting first-pass perfusion (FFP) imaging to create a more robust understanding of this largely ignored HCM subgroup.

            METHODS Forty-seven NOHCM patients and 28 healthy controls (HCs) were retrospectively analyzed. All subjects underwent a 3T CMR scanning. Imaging protocols included short axis cine, FPP, and late gadolinium enhancement (LGE). TTM, SImax, and upslope in multiple groups were assessed and compared by ANOVA test. The Pearson’s correlation test was used to determine the relationships between LV EDTH, LGE, left ventricular outflow tract/aortic valve diameter ratio (LVOT/AO), and FPP parameters (TTM, upslope).

            RESULTS Compared with HCs, NOHCM patients had a longer TTM and lower upslope in the basal, mid-ventricular and apical myocardial segments (all P<0.01), but there were no significant differences in SImax. Compared with myocardial segments in HCs (n=448), hypertrophic- LGE- segments (n=357) had prolonged TTM and decreased upslope in NOHCM (TTM: 25.47±4.30 vs. 29.71±5.09; upslope: 10.23±2.72 vs. 8.77±2.30, P<.001). In NOHCM patients, TTM was positively correlated with LV EDTH and LGE, and was negatively correlated with LVOT/AO diameter ratio; upslope was negatively correlated with LV EDTH and LGE, and was positively correlated with LVOT/AO diameter ratio.

            CONCLUSIONS Patients with nonobstructive HCM have coronary microvascular dysfunction, which has a consistent relationship with myocardial structure and myocardial fibrosis.

            GW33-e0570
            Functional evaluation of constructed pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble

            Lina Guan, Ailifeire Ainiwan, Yuming Mu

            Department of Echocardiography, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, People’s Republic of China

            OBJECTIVES This study aimed to construct pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble pAd-AAV-9/miRNA-1 NBs and evaluate its characteristics, targeting, and function.

            METHODS The pAd-AAV-9/miRNA-1 gene complex was linked to nanobubble NBs by the “avidin-biotin bridging” method to prepare cardiomyocyte-targeted nanobubble pAd-AAV-9/miRNA-1 NB. The shape, particle size, dispersion, and stability of nanobubbles and the connection of pAd-AAV-9/miRNA-1 gene complex to nanobubble NB were observed. The virus loading efficiency was determined and the myocardium-targeting ability was evaluated using contrast-enhanced ultrasound imaging in vivo and in vitro. Also, the cytotoxic effects were assessed.

            RESULTS The particle size of NBs was 504.02±36.94 nm and that of pAd-AAV-9/miRNA-1 NBs was 568.00±37.39 nm. The particle size and concentration of pAd-AAV-9/miRNA-1 NBs did not change significantly within 1 h at room temperature (P;0.05). pAd-AAV-9/miRNA-1 NBs had the highest viral load rate of 86.3±2.2% (P<0.05), and the optimum viral load was 5 μL (P<0.05). Both NBs and pAd-AAV-9/miRNA-1 NBs had good contrast-enhanced ultrasound imaging in vivo and in vitro. In vivo, pAd-AAV-9/miRNA-1 NBs targeted the myocardial tissue. pAd-AAV-9/miRNA-1 NBs had no cytotoxic effect on cardiomyocytes (P>0.05).

            CONCLUSIONS The targeted lipid ultrasound nanobubble pAd-AAV-9/miRNA-1 NBs constructed in this study could carry miRNA-1 for targeted transport into myocardial tissue successfully and had good contrast-enhanced imaging effects in vivo and in vitro.

            GW33-e0681
            Validation of hemodynamic stress calculation in coronary CTA versus intravascular ultrasound

            Yipu Ding1,2, Zinuan Liu1,3, Xi Wang1, Ran Xin1,2, Dongkai Shan1, Bai He1, Jing Jing1, Qi Gao4, Yundai Chen1, Junjie Yang1

            1Senior Department of Cardiology, the Sixth Medical Centre, Chinese PLA General Hospital, Beijing, China

            2School of Medicine, Nankai University, Tianjin, China

            3Medical School of Chinese PLA General Hospital, Beijing, China

            4Institute of Fluid Engineering, School of Aeronautics and Astronautics, Zhejiang University, Hangzhou, China

            OBJECTIVES Development in computational fluid dynamics and 3D construction could facilitate the calculation of hemodynamic stresses in coronary computed tomography angiography (CCTA). However, the agreement between CCTA derived stresses and intravascular ultrasound/intravascular coronary angiography (IVUS/ICA)-derived stresses remains undetermined. Thus, the purpose of this study is to investigate if CCTA can serve as alternative to IVUS/ICA for hemodynamic evaluation.

            MATERIALS AND METHODS In this retrospective study, 13 patients (14 arteries) with unstable angina who underwent CCTA and IVUA/ICA were included in this study. Slice-level minimal lumen area (MLA), percent area stenosis (AS%), velocity, pressure, Reynolds number, wall shear stress (WSS) and axial plaque stress (APS) were determined by both modalities. The agreement between CCTA and IVUS/ICA was assessed using the intraclass correlation coefficient, Pearson’s correlation coefficient and Bland–Altman analysis.

            RESULTS Excellent intraobserver agreement and interobserver agreement were found for WSS with ICCs of 0.926 and 0.928 (P<0.001 for both) and for APS with ICCs of 0.884 and 0.910, respectively. CCTA overestimated the degree of area stenosis (50.22±16.15% vs. 36.41±19.37%, P=0.004) with a smaller MLA (5.81±2.24 mm2 vs. 6.72±2.04 mm2, P=0.126). No statistical difference was observed in WSS (6.57±6.26 Pa vs. 5.98±5.55 Pa, P=0.420) and APS (16.03±1159.45 Pa vs. −1.27±890.39 Pa, P=0.691) between CCTA and IVUS. Good correlation was found in velocity (0.796), Reynolds number (0.810) and WSS (0.770), while the ICC of APS was 0.329, indicating a relatively poor correlation. In the mildly calcified vessels, good or moderate agreement was found between CCTA and IVUS/ICA in WSS and APS, with an ICC of 0.800 and 0.415, while a significantly lower agreement was found in severely calcified vessels, with an ICC of 0.479 (WSS) and 0.230 (APS).

            CONCLUSION CCTA can serve as a satisfactory alternative to the reference standard, IVUS/ICA in morphology simulation and hemodynamic stress calculation, especially in the calculation of wall shear stress.

            GW33-e0684
            Incremental diagnostic value of perivascular fat attenuation index for identifying hemodynamically significant ischemia with severe calcification

            Dongkai Shan1, Yipu Ding1,2, Xi Wang1, Zinuan Liu1,3, Guanhua Dou4, Kai Wang1,2, Wei Zhang3, Jing Jing3, Bai He3, Yang Li1, Junjie Yang1, Yundai Chen1

            1Senior Department of Cardiology, the Sixth Medical Center of PLA General Hospital, Beijing, China

            2School of Medicine, Nankai University, Tianjin, China

            3Department of Cardiology, the First Medical Center of PLA General Hospital, Beijing, China

            4Department of Cardiology, the Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China

            OBJECTIVES To explore the incremental value of perivascular fat attenuation index (FAI) to identify hemodynamically significant ischemia in severe calcified vessels.

            METHODS Patients who underwent coronary computed tomographic angiography (CCTA) examination at Chinese PLA General Hospital from 2017 to 2020 and subsequently underwent fractional flow reserve (FFR) examination within 1 month were consecutively included. Several CCTA-derived indices were measured, including the coronary artery calcification score (CACS), lesion length, ≥CAD-RADS 4 proportion, perivascular FAI and CT-FFR. The included vessels were divided into a nonsevere calcification group and a severe calcification group according to the quartile of CACS. FFR≤0.80 represents the presence of hemodynamically significant ischemia.

            RESULTS A total of 124 patients with 152 vessels were included (age: 61.1±9.2 years; male 64.5%). Significant differences in lesion length (28.4±14.2 vs. 23.1±12.3 mm, P=0.021), perivascular FAI (−73.0±7.5 vs. −79.0±7.4 HU, P<0.001) and CT-FFR (0.78±0.06 vs. 0.86±0.04, P<0.001) were noted between the FFR≤0.80 group (47 vessels) and the FFR>0.80 group (105 vessels). Furthermore, the perivascular FAI in the FFR≤0.80 group was significantly greater than that in the FFR;0.80 group (nonsevere calcification: −73.2±7.5 vs. −78.2±7.4 HU, P=0.002; severe calcification: −72.8±7.7 vs. −82.7±6.3 HU, P<0.001). In discriminating hemodynamically significant ischemia, the specificity and accuracy of CT-FFR were significantly affected by severe calcification, which demonstrated a significantly declining trend (P=0.033 and P=0.010, respectively). The diagnostic performance of CT-FFR in the severe calcification group was lower than that in the nonsevere calcified group. However, perivascular FAI showed good discriminative performance in the severe calcification group. In combination with perivascular FAI, the predictive value of CT-FFR in identifying hemodynamically significant ischemia with severe calcification increased from an AUC of 0.740 to 0.919.

            CONCLUSIONS For coronary artery with severe calcification, the diagnostic performance of CT-FFR in discriminating flow-limiting lesions could be greatly impaired. Perivascular FAI represents a potential reliable imaging marker to provide incremental diagnostic value over CT-FFR for identifying hemodynamically significant ischemia with severe calcification.

            GW33-e0692
            Perivascular fat attenuation index provides incremental prognostic value for 5-year major adverse cardiovascular events in patients with type 2 diabetes mellitus

            Yipu Ding1,2, Dongkai Shan1,3, Zinuan Liu1,3, Xi Wang1,3, Ran Xin1,2, Junjie Yang1,3, Yundai Chen1,3

            1Senior Department of Cardiology, the Sixth Medical Center of PLA General Hospital, Beijing, China

            2School of Medicine, Nankai University, Tianjin, China

            3Department of Cardiology, the First Medical Center of PLA General Hospital, Beijing, China

            OBJECTIVES Perivascular fat attenuation index (FAI) has been introduced as a marker to quantify the coronary artery inflammation and showed independent prognostic importance of all-cause and cardiac mortality over traditional risk factors. We aimed to investigate if FAI provides an incremental prognostic value of MACEs in Type 2 diabetes mellitus (T2DM) patients over the current coronary computed tomography angiography (CCTA) parameters.

            METHODS We prospectively included 1030 DM patients who underwent CCTA because of suspected CAD between January 2015 and December 2017 and examined their CCTA findings, including coronary artery calcium score (CACS), obstructive lesion (≥50% diameter stenosis), presence of high-risk plaque (HRP), lesion-specific ischemia determined by CT-derived fractional flow reserve (CT-FFR), and FAI of all three coronary arteries. The composite endpoint, major adverse cardiovascular events (MACEs), were defined as cardiovascular death, nonfatal myocardial infarction, stroke, and unstable angina requiring hospitalization. The incremental predictive abilities for MACEs were compared among 3 models (model 1: clinical characteristics, model 2: model+adverse CCTA findings, and model 3: model 2+FAI).

            RESULTS During a median follow-up of 56.5 months (interquartile range, 50.9–70.1 months), 5 cardiovascular death, 24 non-fatal myocardial infarctions, 89 unstable angina requiring hospitalization and 34 strokes were observed. Perivascular FAI around 3 coronary arteries had a moderate correlation with each other (RCA vs LAD, ρ=0.585; RCA vs LCX, ρ=0.582; LAD vs LCX, ρ=0.645). Obstructive lesion (HR: 2.98, 95% CI: 2.09–4.24, P<.001), CACS≥300 (HR: 2.34, 95% CI: 1.61–3.42, P<.001), presence of HRP (HR: 4.26, 95% CI: 3.07–5.90, P<.001), CT-FFR≤0.8 (HR: 4.23, 95% CI: 3.07–6.83, P<.001), RCA FAI (HR: 2.75, 95% CI: 1.86–4.07, P<.001) and LCX FAI (HR: 1.54, 95% CI: 1.12–2.12, P=.008) were associated with the outcomes. After adjusting for age, sex, hyperlipidemia, obstructive lesion, presence of HRP, CACS≥300, and CT-FFR≤0.8, RCA FAI (HR: 1.62, 95% CI: 1.15–2.19, P=.008) remained independent predictors of 5-year MACEs in T2DM patients. Model 2 had a significantly higher predictive ability in comparison to Mode1, whereas adding RCA FAI brought further improvement with an AUC increase from 0.763 to 0.779 (P=.030).

            CONCLUSIONS Adverse CCTA findings including RCA FAI were strongly associated with MACEs. Nonetheless, RCA FAI was of incremental prognostic value in T2DM patients beyond clinical characteristics, CACS, obstructive lesion, presence of HRP, and lesion-specific ischemia.

            GW33-e0739
            Clinical and echocardiographic parameters of patients three months after COVID-19 pneumonia: correlations of left ventricular global longitudinal strain

            Elena Yaroslavskaya, Dmitriy Krinochkin, Nikita Shirokov, Elena Gorbatenko, Valeria Garanina, Nadezhda Osokina, Anasyasia Migacheva

            Tyumen Cardiology Research Center - Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES To study the prevalence of cardiovascular diseases and the relationships of left ventricle global longitudinal strain (LV GLS) in patients 3 months after proven COVID-19 pneumonia.

            METHODS Three hundred and sixty-nine patients underwent a comprehensive clinical examination 3 months±3 weeks after COVID-19 pneumonia. The mean age was 52±11 (from 19 to 84) years, 50.9% women. The LV GLS was studied in 296 (80%) examined patients with optimal visualization quality during echocardiography. LV GLS;-18% was considered reduced.

            RESULTS Three months after discharge, obesity was noted in 46.5% of patients, cardiovascular diseases were diagnosed in 73.4%. Arterial hypertension occurred in 71.5% of patients, coronary artery disease - in 22.5%. The average left ventricular (LV) ejection fraction was 67.8±5.0%, the average LV GLS was −19.5±2.3%. LV GLS was reduced in 24.4% of the patients. LV GLS showed no relationship with the patient age, NYHA functional class and LV ejection fraction. Reduced LV GLS was independently associated with male sex (OR 1.399; 95% CI 1.239–1.580; P<0.001), obesity (OR 1.268; 95% CI 1.132–1.421; P<0.0001), diabetes mellitus (OR 1.204; 95% CI 1.017–1.425; P=0.031) and hypertension (OR 1.120; 95% CI 1.002–1.252; P=0.046). LV GLS showed moderate positive correlations with echocardiographic parameters of right ventricle (RV): the length (r=0.346), diastolic (r=0.333) and systolic area (r=0.326), width at the basal (r=0.358) and mid level (r=0.321), as well as with the dimension of the proximal RV outflow tract (r=0.302, all P<0.001). LV GLS showed a weak correlation with the severity of lung lesions during hospitalization (r=0.184; P=0.002).

            CONCLUSIONS Three months after COVID-19 pneumonia, cardiovascular diseases were diagnosed in 73.4%. Reduced LV GLS was observed in 24.4% of survivors and was associated with male sex, obesity, diabetes mellitus and arterial hypertension. LV GLS showed positive moderate correlations with linear and planimetric parameters of right ventricle.

            GW33-e0748
            Serum free thyroxine to free triiodothyronine (FT4/FT3) ratio: a novel biomarker predicts coronary microvascular dysfunction (CMD) in euthyroid patients with ischemia and no obstructive coronary artery disease (INOCA)

            Han Zhang1,2, Fei Yu1,2

            1Department of Nuclear Medicine, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China

            2Institute of Nuclear Medicine, Tongji University School of Medicine, Shanghai 200072, People’s Republic of China

            OBJECTIVES Ischemia and no obstructive coronary artery disease (INOCA) patients who presented coronary microvascular dysfunction (CMD) demonstrate a poor prognosis, yet the risk factors for CMD remain unclear. Subtle changes in thyroid hormone levels within the normal range, especially the free thyroxine (FT4)/ free triiodothyronine (FT3) ratio, have been shown to regulate the cardiovascular system. This prospective study investigated the correlation between FT4/FT3 ratio and CMD in euthyroid patients with INOCA.

            METHODS This prospective study (www.chictr.org.cn/, ChiCTR2000037112) recruited patients with myocardial ischemia symptoms who underwent both coronary angiography (CAG) and myocardial perfusion imaging (MPI) with dynamic single-photon emission computed tomography (D-SPECT). INOCA was defined as coronary stenosis<50% and CMD was defined as coronary flow reserve (CFR)<2.5. All patients were excluded from abnormal thyroid function and thyroid disease history.

            RESULTS Among 71 INOCA patients (15 [21.1%] CMD), FT4 and FT4/FT3 ratio in CMD group were significantly higher and both showed significantly moderate correlation with CFR (r=-0.25, P=0.03; r=-0.34, P=0.003, respectively). The ROC curve revealed that FT4/FT3 ratio had the highest efficacy for predicting CMD with an optimized cutoff value;3.39 (AUC 0.78, P<0.001, sensitivity, 80.0%; specificity, 71.4%). Multivariate logistic regression showed that FT4/FT3 ratio was an independent predictor of CMD (OR 7.62, 95% CI 1.12–51.89, Pfor trend=0.006).

            CONCLUSION In euthyroid INOCA patients, increased FT4/FT3 ratio levels are associated with the occurrence of CMD, presenting a novel biomarker for improving the risk stratification.

            GW33-e0749
            Effect of myocardial function as measured by the strain technique and molecular changes in the myocardiumin obese mice

            Xin Ma1, Qin Wang1, Lu Pan1, Jing Xu2, Na Gao1, Fu-Xin Wan1

            1Department of Cardiac Function Examination, Heart Center, General Hospital of Ningxia Medical University, YinChuan, Ningxia 750003, China

            2Ultrasoud Department Shandong Provincial Third Hospital, Jinan, Shandong 25003l, China

            BACKGROUND Obesity is a major independent risk factor for cardiovascular diseases, such as coronary heart disease. Patients with obesity havealtered cardiac structure and function before the development of coronary atherosclerosis. Obesity-induced myocardial remodeling refers to alterations in myocardial structure, function, and phenotype, including changes in ventricular mass, volume or morphology, increased fibrotic content, cellular hypertrophy, and cell death. Patients with obesity often have a normal left ventricular ejection fraction in routine echocardiography. However, myocardial strain technology can identify subclinical changes in myocardial function. Therefore, this study assessed myocardial function in obese mice by strain technique and differential expression of myocardial molecular mechanism between obese and normal mice was analyzed by pathology, immunofluorescence detection and exosome miRNA sequencing reveal changes of molecular of obese myocardium.

            METHODS Eight-week-old C57BL/6J mice (n=32) were equally divided into the control (control diet for 12 weeks) and obese (high-fat diet for 12 weeks) groups. The characteristics of mice were evaluated using metabolic tests, two-dimensional strain analysis, and histopathology. Pathology, immunofluorescence detection, and miRNA sequencing of exosomes were used to determine molecular changes in the obese myocardium.

            RESULTS The ventricular septum of obese mice was significantly thickened, and the cardiomyocytes inobese mice were increased. Nucleotide oligomerization domain-like receptor protein 3 expression was increased in obese mice as shown by immunofluorescence (P<0.001). Left ventricular remodeling was more marked in the obese group than in the control group (P<0.001). Longitudinal and radial peak strain was significantly lower in the obese group compared with the control group (P<0.001). The components of circulating exosomes in obese mice are highly express a set of specific miRNAs, such as mir-215, mir-369, miR-21, mir-29 and the function and pathway enrichment of these target genes were analyzed using go and KEGG databases. Among them, the pathway related to obese myocarditis response is nf-kb-nlrp3.

            CONCLUSION The strain technique can detect changes inmyocardial systolic function earlier than the left ventricular ejection fraction in obese mice. Left ventricular remodeling and a nucleotide oligomerization domain–like receptor protein 3-mediated inflammatory response occurs in obese mice. The components of circulating exosomes in obese mice highly express a set of specific miRNAs, such as miR-215, miR-369, miR-21, and miR-29.

            GW33-e0750
            Using late Iodine enhancement via dual-energy computed tomography to quantify myocardial extracellular volume fraction can in assist risk stratification in patients with non-ischemic heart failure

            Jie Deng, Dan Han, Zhiming Li, Wei Gao, Tianfu Qi, Hongen Zheng, Jiguo Zhou, Xihan Fan, Wei Chen

            The First Affiliated Hospital of Kunming Medical University

            OBJECTIVES Myocardial extracellular volume fraction (ECV) derived from late iodine enhancement (LIE) via using dual-energy computed tomography (DECT) for disease risk stratification in patients with non-ischemic heart failure (NIHF) is not well studied.

            METHODS Forty-five NIHF patients (52±13 years, 21 female), who were patients with heart failure unrelated to significant coronary artery disease (CAD) (defined as ≥50% diameter stenosis) by X-ray coronary angiography or computed tomography angiography, underwent DECT and were divided into four subgroups according to New York functional class I-IV. 41 healthy subjects (43±10 years, 17 female) were serve as control groups. LIE was acquired 7 minutes after iodine administration of 0.9 mL/kg of iopamidol. LIE images were reconstructed at 8 mm slice thickness, 6 mm slice gap to the short-axis plane of the left ventricular (LV) myocardium and then the basal, mid and apical slices were extracted. ROIs were manually drawn on LIE images using the AHA’s 16-segmentation to calculate ECV. Differences of ECV between subgroups were compared and correlation between ECV and NYHA Classification were analyzed.

            RESULTS The CT-ECV in NIHF patients was significantly higher than that in Cs (34.63%±3.68 vs 28.03%±2.85, P<0.05). In NIHF patients, there was a significant correlation between CT-ECV and NYHA Classification could be observed (r=0.761, P<0.05). Furthermore, there was a significant difference between NIHF patients with varied NYHA classes (NYHA I: 27.62%±1.86, NYHA II: 31.53%±2.17, NYHA III: 34.40%±3.33, NYHA IV: 38.47%±3.12; all P<0.05).

            CONCLUSIONS CT-ECV derived from Late Iodine enhancement can assist in risk stratification in patients with non-ischemic heart failure.

            GW33-e0761
            Declined hematopoiesis-inflammation response in patients with recurrent myocardial infarction

            Yao Lu, Xiao-li Zhang

            Beijing Anzhen Hospital affiliated Capital Medical University

            OBJECTIVES Recurrent myocardial infarction (MI) after an acute coronary syndrome portends an unfavorable outcome, which might be induced by a diminished hematopoiesis-inflammatory activation after recurrent MI.18F-FDG PET in hematopoietic tissues provides a non-invasive measurement of proliferative activity. We analyzed the FDG activity of bone marrow (BM), as a surrogate biomarker for prolonged hematopoiesis-inflammation activation in categorized patients after the primary (PMI) and secondary myocardial infarction (SMI). Further, in comparison with chronic stable angina (CSA) patients.

            METHODS We retrospectively recruited 97 patients who experienced acute MI [PMI=43 (38 males) vs. SMI=24 (20 males)] and 30 CSA patients (24 males). All patients underwent 18F-FDG cardiac PET and gated myocardial perfusion imaging. PMI and SMI were determined by clinical criteria. BM and splenic 18F-FDG activity were quantified as standardized uptake activity (SUVmax). The aorta target-to-background ratio (TBR) was derived. Total perfusion defect (TPD, %LV), hibernating myocardium (HM, %LV), and scar (%LV) were analyzed. LV ejection fraction (LVEF, %), end-diastolic volume (EDV, mL), and end-systolic volume (ESV, mL) were calculated. One-way ANOVA, and Kruskal–Wallis H test were used to compare variables. Spearman correlation analysis was performed to identify the relationship. Statistical significance was defined as P<0.05.

            RESULTS The prevalence of CVD risk factors did not differ significantly among the 3 groups (P>0.05). There were significant increases in troponin-I and C-reactive protein from the CSA group to the PMI group (P<0.05). Nevertheless, white blood cell, neutrophils counts and BNP did not differ significantly among groups.

            Scar was larger in the SMI group than the CSA group [25.0 (16.0) vs. 7.5% (21.0%), P<0.001]. In contrast, there was no significant difference in TPD and HM among groups (P>0.05). The SMI group exhibited significantly deteriorated cardiac function compared to the PMI and CSA groups, respectively (P<0.001). Besides, the SMI and PMI groups had adverse cardiac remodeling compared with CSA group (SMI vs. CSA group, P=0.005; PMI vs. CSA group, P=0.032). While the cardiac function and LV remodeling didn’t differ between the PMI and SMI groups (P;0.05).

            The TBR of BM activity was highest in the PMI group, intermediate in the SMI group, and lowest in the CSA group [2.28±0.34 vs. 1.97±0.27 vs. 1.41±0.21, P<0.001). The spleen TBR did not differ significantly among the three groups (P;0.05). Aortic arch TBR in both PMI [1.46±0.29 vs. 1.04±0.19, P<0.001] and SMI groups [1.31±0.30 vs. 1.04±0.19, P=0.002] were higher than the CSA group. BM and spleen metabolic activity were significantly correlated with the aorta TBR (P<0.001).

            CONCLUSIONS In summary, prolonged hematopoiesis is upregulated after acute phase of MI in comparison to chronic stable angina. Patients with SMI presented subsequent enlarged scar and worsened cardiac dysfunction than PMI. Further studies of this diminished hematopoiesis, including the hemopoietic-cardiovascular immune axis in recurrent MI patients, are warranted.

            CARDIOVASCULAR LAB MED
            GW33-e0713
            Prospective analysis of hematological parameters as a basis for prevention of post-COVID complications in patients with cardiovascular diseases

            Tatiana Petelina, Natalia Musikhina, Valerya Garanina, Ksenia Avdeeva, Liana Valeeva, Anastasia Shcherbinina, Lyidmila Gapon

            Tyumen Cardiology Research Center - Branch of Tomsk National Research Medical Center, Russian Academy of Sciences

            OBJECTIVES The study of the characteristics and dynamics of laboratory biomarkers in patients with cardiovascular diseases (CVD) undergoing COVID-19-associated pneumonia may be of great importance for the development of patient monitoring algorithms for the prevention of long-term complications. The objective was to study prospectively the dynamics of hematological parameters in patients with CVD to identify predictors of disease severity and potential indicators of post-COVID vascular complications 3 months after discharge from a COVID isolation hospital.

            METHODS The study was prospective, the protocol was approved by the local ethics committee - No 159 dated July 23, 2020 and registered in the international registry of clinical trials of the US National Institute of Health (ClinicalTrials.gov Identifier: NCT04501822). The study included 116 patients who underwent COVID-19-associated pneumonia. The patients were divided into 2 groups. The first group −49 patients without CVD, the second group - 67 patients with CVD. A blood sample was performed in all patients at the time of hospitalization and 3 months after discharge from the hospital. The parameters of general blood count, biochemistry, hemostasis, and biomarkers of inflammation were assessed - concentration of C-reactive protein (CRP), highly sensitive CRP (hs-CRP), homocysteine and IL-6. All patients initially underwent computed tomography of the chest organs.

            RESULTS We found that erythrocyte sedimentation rate (ESR), WBC (leukocytes), neutrophils/lymphocytes ratio, fibrinogen, lactate dehydrogenase (LDH), lymphocytes/CRP ratio were parameters that significantly distinguished patients in the 1st and 2nd groups. Three months after discharge from the hospital in patients of both groups the increased indicators approached the reference values, however, some parameters such as CRP, ESR, WBC, fibrinogen remained at a higher level in group 2. Correlation analysis revealed the relationship between parameters of inflammation and hemostasis in the 2nd group of patients, which confirms the presence of latent vascular inflammatory potential in this group. It was revealed that such indicators as lymphocytes, neutrophils and LDH were associated with the initial volume of lung lesion more than 50%. Increase of these parameters by 1 unit contributes to increase in the volume of lung tissue damage by 6.5, 6.4, 11 and 0.6% respectively.

            CONCLUSIONS Thus, dynamic control of laboratory parameters has prognostic value in assessing the nature of the course of COVID-19 associated pneumonia in patients with CVD and developing an algorithm for personalized monitoring of patients in the post-COVID period with the aim of timely correction of therapy to prevent unwanted vascular complications.

            TRADITIONAL CHINESE MEDICINE
            GW33-e0187
            Salvianolic acid B protects cardiomyocyte injury through Nrf2/ HO-1-ANT signaling pathway

            Xu Chen, Dongqing Guo, Yong Wang

            Beijing University of Chinese Medicine

            OBJECTIVES In recent years, lipid accumulation has been proved to play an important role in the pathological process after myocardial infarction and is considered to be one of the important causes of ferroptosis. However, whether salvianolic acid B (SAB) plays a protective role in myocardium by inhibiting ferroptosis of myocardium by inhibiting lipid accumulation after myocardial infarction remains unclear. Therefore, we decided to determine whether SAB plays an important role in myocardial protection by inhibiting lipid accumulation.

            METHODS The protective effect of SAB on myocardium was studied in vivo and in vitro. Male C57BL/6 mice were treated with SAB (50 mg/kg/d, gavage) for 14 days after permanent myocardial infarction caused by coronary artery ligation, and echocardiography was performed to assess cardiac function. H9c2 was divided into control group, model group (PA induction), SAB treatment group (20 μM) and SAB +NAC (5 μmol/L, ROS inhibitor) group. CCK8 staining was used to detect cell viability, LipidTOX™ was used to detect lipid accumulation in H9c2, electron microscopy was used to observe cell morphology, and Iron Assay Kit was used to detect intracellular Iron levels. The expressions of Nrf2, HO-1, ANT1, GPX4, SLC7A11, Ferritin and Ferritin Light Chain were detected by Western blot.

            RESULTS Compared with model group, the area of myocardial infarction was significantly reduced and cardiac function was significantly improved in SAB treatment group. In addition, we found that ferroptosis caused by myocardial infarction mainly manifested as mitochondrial outer membrane rupture, increased density of bilayer membrane rupture, release of inflammatory mediators such as arachidonic acid, and decreased expression of ferroptosis related proteins GPX4, SLC7A11, Ferritin and Ferritin Light Chain. All of these changes can be prevented by SAB intervention, which is as effective as the ROS inhibitor NAC. In vitro, SAB was found to reduce elevated intracellular ferroptosis levels.

            CONCLUSIONS We believe that SAB can prevent cardiac injury and dysfunction caused by myocardial infarction to a certain extent by reducing lipid accumulation, and provide a new approach for clinical treatment of heart failure.

            GW33-e0463
            A randomized, placebo-controlled, double-blind trial to evaluate efficacy and safety of Shen-Yuan-Dan capsules, a traditional Chinese medicine, for treatment of peri-procedure myocardial injury following percutaneous coronary intervention

            Xiang Li1, Ying Zhang2, HongXu Liu1, Juju Shang1, Qi Zhou1, Aiyong Li1, Xiaolei Lai1, Wenlong Xing1, Sihan Jia1

            1Beijing Hospital of Traditional Chinese Medicine, Capital Medical University

            2Beijing University of Traditional Chinese Medicine

            OBJECTIVES Peri-procedural myocardial injury (PMI) is a common complication of percutaneous coronary intervention (PCI), which cannot be entirely avoided using available treatments. The findings of earlier research have shown that Shen-Yuan-Dan (SYD) capsules, a traditional Chinese medicine, can potentially alleviating PMI. This study aimed to confirm further this hypothesis in a rigorous, well-designed randomized controlled study.

            METHODS Our clinical trial was randomized, double-blinded, and placebo-controlled. A total of 181 patients with unstable angina (UA) undergoing elective PCI were randomized to pretreatment with SYD or a placebo under the basis of conventional treatment; 87 patients were pretreated with SYD (four capsules, 3 times a day, with a further four capsules 2 hours before PCI) 3 days before the procedure, and 94 patients were given a placebo. No patients received reloading statins before PCI, and SYD or placebo was maintained for 1 month after PCI. The primary endpoint was the incidence of PMI. The secondary endpoint was calculating the incidence rate of all 30-day major adverse cardiovascular events (all-cause mortality, non-fatal myocardial infarction, unplanned revascularization). The safety outcomes, including abnormalities in electrocardiogram and serum biochemical examinations caused by drug use, were also tested.

            RESULTS The levels of creatine kinase-myocardial band (CK-MB) in both the SYD and placebo groups were increased at 4 hours and 24 hours after PCI compared with before the procedure (P<0.05). The incidence rate of PMI in the SYD group (10.3%) was lower than that in the placebo group (34%) (absolute difference, 23.7% [95% CI, 11.7–34.8%], P<0.01). After taking SYD, the relative risk reduction (RRR) and absolute risk reduction (ARR) were 69.7 and 24.3%, respectively; further, number needed to treat (NNT) was 4.2. The 30-day major adverse cardiovascular event (MACE) rate was not statistically different between the SYD and placebo groups (6.9 vs. 9.6%, P=0.352). There were no abnormal situations during the trial.

            CONCLUSIONS These findings showed that pretreatment with SYD could safely reduce the incidence rate of PMI in patients with UA undergoing elective PCI. Further study on the effects of SYD and how it can improve adverse cardiovascular events outcomes is needed.

            GW33-e0604
            The effects of acupuncture for atrial fibrillation: a critical overview of systematic reviews and meta-analyses

            Yiyi Cai, Boyan Tang, Wensheng Chen

            The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Academy of Chinese Medical Sciences, Guangzhou, China

            OBJECTIVES Atrial fibrillation (Af) poses substantial burden to patients, physicians and healthcare systems globally. According to experts’ consensus, acupuncture was recommended as an adjunctive therapy to regulate heartbeat rhythm for patients with arrhythmia. Although the number of randomized controlled trials (RCTs) on acupuncture for Af increased in recent years, the results were inconsistence. Therefore, we conducted this review to identify and evaluate the existing evidence of acupuncture in the treatment Af.

            METHODS Two English-language databases (PubMed and EMBASE) and two Chinese-language databases (SinoMed and CNKI) were searched from their inception to 28 May 2022 for systematic reviews (SRs) and/or meta-analysis (MAs) of acupuncture for atrial fibrillation. The Methodological Quality of Systematic Reviews 2 (AMSTAR-2) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist 2020 were used to assess the methodological and reporting quality of SRs and/or MAs respectively. The confidence of evidence was evaluated using the Grades of Recommendations, Assessment, Development and Evaluation (GRADE) approach. SRs and/or MAs were included if their included RCTs: 1) recruited patients ≥18 and diagnosed with Af; 2) compared the effects of acupuncture to sham or placebo acupuncture, or guidelines-recommended therapies; or evaluated the add-on effects of acupuncture to standard treatment for patients diagnosed with Af; 3) reported survival (primary outcome measures) or any one of the following secondary outcomes as suggested by existing Af core outcome sets (COS), including clinical response (such as Af recurrence, Af progression), cardiovascular events, patient reported outcomes (such as AFEQT, SF-36), resource utilization outcomes (such as emergency room visits and drug costs) and safety outcome (adverse events). SRs and/or MAs were excluded if their studies: 1) adopted complex treatment that could not specify the effects of acupuncture; 2) compared different types of acupuncture therapies.

            RESULTS Twenty-three citations were identified through database search and eventually five SRs and/or MAs were included in this review. One SR assessed as high quality in both methodology and reporting involving four RCTs, suggested that compared with amiodarone, acupuncture had no better effect for reconverting to sinus rhythm (RR 1.09, 95% CI [0.79, 1.49], I2 =61%). However, one sham-controlled RCT included in this SR suggested the add-on benefits of acupuncture in reducing the recurrence of Af in patients that had undergone an electrical conversion (RR 1.39; 95% CI [1.08, 1.79]). The other four SRs were evaluated as insufficiently conducted and reported according to AMSTAR-2 and PRISMA Checklist 2020. The overall confidence in current evidence of acupuncture for reducing recurrence of Af was downgraded due to small sample size and high heterogeneity. Critical problems were also observed in lacking reports of long term outcomes such as survival and cardiac events as suggested by established Af COS and variations in both acupuncture treatment protocols and timeframes for outcome assessment.

            CONCLUSIONS Moderate level of evidence suggested the potential benefits of acupuncture in reducing recurrence of Af. To provide robust evidence for confirmed conclusions and to advice clinical practice with optimal acupuncture treatment protocol, rigorously designed sham-controlled RCTs in accordance with existing Af COS are warranted.

            CARDIOVASCULAR PREVENTION AND REHABILITION

            EPIDEMIOLOGY AND EVIDENCE-BASED MEDICINE
            GW33-e0008
            Prevalence trend of obesity and abdominal obesity in US adults: evidence from the National Health and Nutrition Examination Survey (2001–2018)

            Jin-Yu Sun, Hua Yang, Qiang Qu, Xiang-Qing Kong, Wei Sun

            Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

            OBJECTIVES This study investigates the prevalence trends of obesity and abdominal obesity in US adults from 2001 to 2018.

            METHODS We included 44,184 adults from the nine cycles of the continuous NHANES (2001–2002, 2003–2004, 2005–2006, 2007–2008, 2009–2010, 2011–2012, 2013–2014, 2015–2016, 2017–2018). The weighted mean body mass index and waist circumference were canulated, and the sex-specific annual change was illustrated by the survey cycle. We used the weighted sex-specific logistic regression models to analyze the prevalence of obesity and abdominal obesity from 2001 to 2018. The weighted adjusted odds ratio (OR) with 95% confidence interval (CI) was calculated.

            RESULTS In the obese population, the prevalence of class I obesity ranked first (20.17%), followed by class II obesity (8.98%) and class III obesity (6.32%). Abdominal obesity was observed in 53.13% of all populations, with a significantly higher prevalence in females (62.92 vs. 43.15%; P<0.001). Females showed significantly lower waist circumference (95.45 vs. 100.66 cm; mean difference, −5.20 cm; P<0.001), whereas BMI (28.78 vs. 28.54 kg/m2; mean difference, 0.24 kg/m2; P=0.005) was slightly higher in females than males. Consistently, the sex-specific smoothed density distribution curve showed a lower and right-shifted curve of BMI and waist circumference stratified by sex. A rightward shift change was observed in BMI and waist circumference distribution over the past three intervals. The weighted mean BMI (β-coefficient, 0.10; P<0.001) and waist circumference (β-coefficient, 0.28; P<0.001) significantly increased over the 18-year survey. The mean BMI has increased from 27.83 to 29.55 kg/m2, whereas the mean waist circumference increased from 95.28 to 100.18 cm. We observed the significant association of survey year with obesity (adjusted OR, 1.007; 95% CI 1.005–1.009, P<0.001) and abdominal obesity (adjusted OR, 1.006; 95% CI, 1.004–1.008; P<0.001). In contrast, males showed a decreasing overweight trend, while the increased prevalence was observed in all three different classes of obese (class I, from 17.87 to 25.17%; class II, from 5.14 to 10.74%; class III, from 3.42 to 6.50%). From 2001–2002 to 2017–2018, the prevalence of abdominal obesity has increased from 46.19 to 58.55%. The prevalence of abdominal obesity in males has increased close to that of normal weight. Importantly, we have observed a reversed trend of abdominal obesity in females since 2015. The percentage of the BMI<30 kg/m2 without abdominal obesity decreased, while the group of BMI≥30 kg/m2 with abdominal obesity showed a consistently increasing trend. In the subgroup of BMI≥30 kg/m2, the percentage of those without abdominal obesity remained low, while those with abdominal obesity showed an increasing trend. BMI and waist circumference were generally in a good match, and waist circumference maintained sustainable growth with the increase of BMI.

            CONCLUSIONS Obesity and abdominal obesity were a heavy health burden among US adults, and the increasing trend remained in both males and females from 2001 to 2018.

            GW33-e0019
            Association of cardiovascular health at old age with all-cause mortality: a prospective cohort study in China

            Shimin Chen

            Institute of Geriatrics, Beijing Key Laboratory of Aging and Geriatrics, National Clinical Research Center for Geriatric Disease, Second Medical Center of Chinese PLA General Hospital & Chinese PLA Medical School, Beijing, China

            OBJECTIVES In the context of population increasing and aging, cardiovascular disease (CVD) remains the biggest cause of global death and rising health care costs. Older adults have an excess burden of CVD while there is a paucity of data specifically in China. We aim to evaluate the relationship between cardiovascular health (CVH) and all-cause mortality among Chinese older adults.

            METHODS Data was derived from Beijing Elderly Comprehensive Health Cohort Study, a community-based longitudinal study initiated in 2009 and followed up by 2021. According to AHA guideline and modified to the subjects, CVH was assessed by 6 metrics: smoking status, physical activity, BMI, blood pressure, total cholesterol, fasting plasma glucose. CVH score ranged from 0–12 as each metric was operationalized for poor (0 point), intermediate (1 point) and ideal (2 points). The time of death was record confirmed by authorized institute. Mosaic plot and bar plots were used to present the distribution of each CVH metric by age, gender and residence group. Restricted cubic spline and survival curve were generated to identify the relationship between CVH score and all-cause mortality primarily. Cox proportion regression was conducted to estimate HRs and 95% CIs for the association with gradual adjustment. Subgroup and sensitivity analysis was applied to test the robustness of results.

            RESULTS A total of 4499 subjects were included in this study, the average age of whom was 70.49(SD 6.77) years old, with 40.3% male and 98.1% Han nationality. Only 8% study participants had 11–12 points and 1.6% of participants obtained all the 6 metrics of ideal CVH. CVH score was generally more favorable among participants with urban male aged under 75 years. During a mean follow-up time of 8.13 years (36595.72 person years), 667 deaths were occurred in the study population. Compared with the participants whose CVH score at 0–4, whose score at 11–12 had lower risk of all-cause mortality in all the models with gradual adjustments (HR=0.584, 95% CI: 0.373–0.913). For each one-unit greater CVH score, participants had a 7.5% decreased risk of all-cause mortality (HR=0.925, 95% CI: 0.885–0.967) with linearly decreasing trend (P nonlinear = 0.575). In age-stratified analysis, each one-unit higher CVH score was similarly associated with a smaller likelihood of all-cause mortality among the participants aged under 75 years (P<0.001). In both male and female groups, the higher CVH score, the lower risk of all-cause mortality (P male=0.008, P female=0.042). After omitting the participants who had CHD or stroke previously (1356), who had BMI under 18kg/m2 (100), who had died within 2 years after follow-up (95), individually, the results remain consistent.

            CONCLUSIONS This study provides evidence for the benefits of CVH metrics in reducing risk of all-cause mortality among Chinese older population. Obtaining ideal CVH would definitely be a long-term goal, the immediate action or short-term goal is to encourage the attainment of per point of CVH score at a time progressively. Public health policies and strategies should be implemented especially focusing on behavior interventions among Chinese older adults.

            GW33-e0040
            Impact of muscle on glucose and lipid metabolism depends on body fat accumulation in children

            Liwang Gao1, Hong Cheng2, Yinkun Yan1, Junting Liu2, Xinying Shan2, Xi Wang1, Jie Mi1,2

            1Department of Non-Communicable Disease Management, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health

            2Department of Epidemiology, Capital Institute of Pediatrics

            OBJECTIVES The limitations associated with the use of body mass index in assessing obesity make it impossible to study the influence of muscle-fat composition on cardiometabolic risk. The aim of the present study was to investigate the associations of muscle-fat composition, especially the muscle mass, with glucose and lipids metabolism in children and adolescents.

            METHODS This nationwide cross-sectional study included 8905 children and adolescents (50.1% boys) aged 6 to 18 years. All participants underwent dual-energy x-ray absorptiometry for body composition, and their glucose and lipids were measured. Multivariable-adjusted linear regression coefficients and odds ratios were calculated to assess the associations between muscle mass and glucose and lipids metabolism. Hierarchical analysis and piecewise regression model were used to study the effect of muscle-fat composition on glucose and lipids metabolism.

            RESULTS The greatest proportion of high total cholesterol (TC, 6.9 and 6.9%) and high triglyceride (TG, 22.3 and 6.6%) was found in both female and male participants with high muscle and high fat, while girls with high muscle and high fat also had the highest proportion of hyperglycemia (7.1%). After fat stratification, higher muscle mass was associated with lower odds of hyperglycemia (OR=0.62, 95% CI: 0.46–0.84, P=0.002) and muscle mass was inversely associated with TC (β=−0.07; 95% CI: −0.12, −0.03; P<0.001) in boys with normal fat. Muscle mass was not associated with hyperglycemia (OR=0.83, 95% CI: 0.55–1.25, P=0.368) and TC (β=0.04, 95% CI: −0.05, 0.14, P=0.374) in high fat boys. Children with high-muscle and high-fat had higher risks of having insulin resistance, high TC, high TG, high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and high non-HDL-C than those with different body fat compositions.

            CONCLUSIONS Fat modifies the effect of muscle on glucose and lipid metabolism. Higher muscle mass was only associated with a lower risk of hyperglycemia and TC levels in individuals with normal weight. Children with high-muscle and high-fat mass were at greater risk of abnormal glucose and lipids metabolism.

            GW33-e0118
            A bibliometric study and visualization analysis of chronotherapy

            Yajun Xue, Boda Zhou, Lange Li, Ping Zhang

            Beijing Tsinghua Changgung Hospital

            OBJECTIVES This study aimed to review the research status and to demonstrate the hotspots and frontiers of chronotherapy.

            METHODS Literatures regarding chronotherapy from inception to 2021 were retrieved from the Web of Science Core Collection database. CiteSpace 5.8. R1 was used to generate network maps about the collaborations between authors, countries, and institutions and reveal hot spots and frontiers of chronotherapy.

            RESULTS A total of 829 studies related to chronotherapy were included. The number of literatures regarding chronotherapy was generally increased with some fluctuations. Hermida RC was the most prolific author (79 articles, 9.53%). The USA and Universidad de Vigo were the leading country and institution in this field with 221 and 85 publications, respectively. Chronobiol Int was the most commonly cited journal (514 articles). The first co-cited reference reported the MAPEC trial which analyzed the effect of circadian rhythm time of hypertension treatment on cardiovascular risk. Hot topics focused on the circadian rhythm, hypertension, melatonin, sleep deprivation, cancer and rheumatoid arthritis.

            CONCLUSIONS This study suggested the prosperous research trends and close cooperation. Major ongoing research trends include the timing of antihypertensive medication dosing, melatonin, sleep deprivation, cancer and rheumatoid arthritis.

            GW33-e0135
            Causal association between vitamins and atrial fibrillation risk: a Mendelian randomization study

            Xintao Li, Shi Peng, Xiaoyu Wu, Songwen Chen, Genqing Zhou, Yong Wei, Juan Xu, Xiaofeng Lu, Shaowen Liu

            Shanghai General Hosptial

            OBJECTIVES Dietary intake and high blood concentration of vitamins have been associated with low atrial fibrillation (AF) risk. However, the causal relationship between vitamins and AF have not been fully elucidated. Here, we investigated causality between genetically determined vitamin levels and AF by conducting a Mendelian randomization (MR) study.

            METHODS Single-nucleotide polymorphisms for circulating vitamin levels, including vitamin A, B, C, D, E, determined either as absolute levels or metabolites were obtained from public genome-wide association studies (GWAS) and were used as genetic instrumental variables. Summary statistics for gene-AF associations were retrieved from the largest GWAS of AF mainly based on European population, which included 65,446 AF cases and 522,744 controls. Two-sample Mendelian randomization analysis was implemented to investigate the causality between vitamin levels and AF.

            RESULTS Our MR study found that genetically predicted circulating vitamin levels were not causally associated with AF risk. For absolute vitamins, the odds ratio for AF ranged from 0.97 (95% confidence interval [CI]: 0.82–1.16, P=0.76) for vitamin B9 to 1.43 (95% CI 0.95–2.15, P=0.09) for vitamin E. For vitamin metabolites, the odds ratio ranged between 0.97 (95% CI: 0.64–1.47, P=0.21) for α-tocopherol and 1.11 (95% CI: 0.90–1.36, P=0.34) for vitamin B6.

            CONCLUSIONS Our study did not find convincing evidence to support genetically determined circulating vitamin levels were associated with AF. Therefore, there may be no direct beneficial effects of vitamin intake on prevention of primary AF.

            GW33-e0226
            Transitions in metabolic healthy and association with progression of carotid atherosclerosis across body mass index categories

            Jiangtao Li, Jing Liu, Dong Zhao, Miao Wang, Jiayi Sun, Jun Liu, Tianxiao Liu, Youling Duan, Piaopiao Hu, Zhaoqing Sun, Qiuju Deng, Yue Qi

            Center for Clinical and Epidemiological Research, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China

            OBJECTIVES Debate over the cardiovascular disease risk associated with metabolically healthy obesity continues. Several studies have investigated the relationship between metabolically healthy obesity and clinical cardiovascular events, while evidence for the effect of metabolically healthy obesity on progression of atherosclerosis is limited. This study was aimed to investigate the association between transitions in metabolic healthy and progression of carotid atherosclerosis and to examine the impact of obesity on this link.

            METHODS This study enrolled 918 participants aged 45 to 74 years who were free of cardiovascular disease at baseline and completed carotid ultrasound measurements twice in 2002 and 2007 over a 5-year interval from the Chinese Multi-Provincial Cohort Study-Beijing Project. Metabolic health was defined as having 0–1 metabolic abnormality from the following criteria: elevated blood pressure (≥130/85 mmHg); elevated fasting blood glucose (≥5.6 mmol/L); decreased level of high-density lipoprotein cholesterol (<1.04 mmol/L for male and <1.29 mmol/L for female), and elevated level of triglyceride (≥1.7 mmol/L). Participants were cross-classified by change in metabolic health status from 1992 to 2002 and body mass index (BMI) categories (normal weight: BMI<24 kg/m2; overweight: BMI≥24 kg/m2) in 1992. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariate logistic regression adjusting for age, sex, current smoking status, low density lipoprotein cholesterol, and high-sensitivity C-reactive protein.

            RESULTS The mean age of the participants was 59.6±7.9 years at baseline and 45.2% were men. There were 445 (48.5%) participants maintaining metabolic health from 1992 to 2002. During 5-year follow-up period, a total of 422 (62.7%) participants had carotid plaque progression. Transitions from metabolically health to unhealth or initial metabolically unhealth was associated with a higher risk of plaque progression (OR=1.51; 95% CI: 1.14, 2.00; P=0.004). Compared with sustaining metabolically healthy participants with normal weight, stable metabolically healthy overweight participants had 72% increased risk of plaque progression (OR=1.72; 95% CI: 1.09, 2.70; P=0.020).

            CONCLUSIONS Metabolic unhealth, either initially unhealth or transition from health to unhealth, is a risk factor of carotid atherosclerosis progression. Even when metabolic health is maintained during long periods of time, overweight individuals have a higher risk of carotid atherosclerosis progression.

            GW33-e0228
            Cardiovascular outcomes of SGLT2 inhibitors in patients with CHF, with or without diabetes mellitus: a network meta-analysis of randomized controlled trials

            Qianru Yuan, Yitong Ma, Baozhu Wang, Aibibanmu Aizeze, Nazila Yaliqin

            Heart Center, The First Affiliated Hospital of Xinjiang Medical University

            OBJECTIVES A network meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the cardiovascular protective effect of prophylactic use of SGLT2 inhibitors in patients with CHF, without diabetes mellitus.

            METHODS We will search, with no time restrictions, the following databases for relevant English language literature: PubMed, Cochrane Library, Embase and Web of Science. All the English publications until 6 March 2022 will be searched without any restriction of countries or article type. Reference list of all selected articles will independently screened to identify additional studies left out in the initial search. We included RCTs comparing any SGLT2 inhibitor with placebo or other standard treatmeant without SGLT2 inhabitor in patients with CHF, reporting desired cardiovascular outcomes and with a follow-up duration of at least 6 months. Cardiovascular outcomes was defined as major adverse cardiovascular event, cardiovascular death, cardiovascular readmission, patient readmission, acute myocardial infarction and all-cause mortality.

            RESULTS Our network meta-analysis included 11 articles, comprising a combined cohort of 20,392 patients with CHF. Frequentist network meta-analysis demonstrated that application of SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin, atogliflozin) in patients with CHF reduced the risk of MACE (HR 0.52; 95% CI 0.36–0.68), cardiovascular death (HR 0.66, 95% CI 0.58–0.75), cardiovascular readmission (HR 0.62, 95% CI 0.55–0.71), cardiovascular death (HR 0.81, 95% CI 0.70–0.95), acute myocardial infarction (HR 0.73, 95% CI 0.53–0.90), and all-cause death (HR 0.86, 95% CI 0.72–0.90), with no significant heterogeneity detected.

            CONCLUSIONS In patients with CHF, SGLT2 inhibitors were associated with reduced risks of MACE, cardiovascular death, cardiovascular readmission, acute myocardial infarction, all-cause mortality. Therapy with SGLT2 inhibitors in patients with CHF, without diabetes mellitus results in a sustained reduction of the cardiovascular outcomes.

            GW33-e0258
            Association between extreme temperature and myocardial infarction hospitalizations in Beijing, China from 2007 to 2019: a time series study

            Piaopiao Hu, Qiuju Deng, Jie Chang, Jiayi Sun, Jing Liu

            The Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University; Beijing Institute of Heart, Lung and Blood Vessel Diseases

            OBJECTIVES The increasingly frequent and intense extreme temperatures have raised concerns regarding their deleterious impacts on public health. We aimed to assess the association between extreme temperature and daily myocardial infarction (MI) hospitalizations in Beijing, China from 2007 to 2019.

            METHODS From 2007 to 2019, all MI hospitalizations among permanent Beijing residents aged ≥35 years old were collected from the Beijing Cardiovascular Disease Surveillance System. The associations between ambient temperature and MI hospitalizations were estimated by a combination of Poisson generalized additive models and distributed lag nonlinear models controlling for relative humidity, PM2.5, long-term trends, and day of the week. For the single-lag association, we depicted the overall lag structure figure for the extreme cold (at 29.6°C, the 97.5th centile) and heat (at −5.2°C, the 2.5th centile) temperatures. For the cumulative association over 0–21 lag days, we depicted the cumulative exposure-response curve and defined the heat and cold effect as cumulative-lag risks at the extreme heat and cold temperatures relative to the minimum estimated, respectively. The Z test was used to compare the difference in the two effect estimates among subgroups in gender and age groups.

            RESULTS Between 2007 and 2019, 216,883 events of MI hospitalizations were recorded. On average, there were 46 cases per day. The daily mean temperature ranged from −14.3°C to 34.5°C, with an average of 13.6°C. For the single-lag association, the effects in extreme cold occurred on lag day 1, increased up to lag day 3, and decreased with mild effects on subsequent days. By contrast, the effects of extreme heat were the most pronounced on the present day and followed by mild effects on the subsequent days. For the cumulative association over 0–21 lag days, the exposure-response curve between daily mean temperatures and MI hospitalizations was inverse J-shaped and the impact of low temperature was greater. The cold and heat effects were 1.68 (95% CI: 1.39 to 2.02) and 1.03 (95% CI: 0.97 to 1.09), respectively. Subgroup analysis showed that older individuals (aged ≥65 years) had a greater risk of cold effect than younger individuals (aged 35–64 years) (RR, 1.97 [95% CI, 1.55 to 2.50] vs 1.34 [95% CI, 1.02 to 1.75]; P=0.036). There were no significant gender differences for both cold and heat effects.

            CONCLUSIONS Extreme temperatures were associated with increased MI hospitalizations. The single-lag effects lasted longer for extreme cold than heat and the analysis of the cumulative-lag effects showed a significant cold effect, but not the heat effect. The elderly was more sensitive to cold. The evidence has important implications for public health practices to minimize the adverse health effects of temperatures, especially low temperatures.

            GW33-e0367
            Joint effect of homocysteine and uric acid on arterial stiffness in the general population

            Zhiyuan Wu1,2, Jinqi Wang1, Lixin Tao1, Xiuhua Guo1,2

            1Beijing Municipal Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing, China

            2Centre for Precision Health, Edith Cowan University, Perth, Australia

            OBJECTIVES Homocysteine (Hcy), serum uric acid (UA) and arterial stiffness are closely associated with cardiovascular diseases. Both serum Hcy and UA could affect the arterial stiffness level. In this study, we evaluated the joint effect of Hcy and UA on arterial stiffness in the general population.

            METHODS The study consisted of 17,697 participants from Beijing Health Management Cohort, who underwent health examination between January 2012 and December 2019. Brachial-ankle pulse wave velocity (baPWV) was used as an index of arterial stiffness. Unadjusted and adjusted linear regression models were used to estimate the sex-specific association of Hcy and UA concentrations with baPWV level.

            RESULTS On multivariable linear regression analysis, one-standard deviation (SD) rise of Hcy (7.6 μmol/L) and UA (78.7 μmol/L) were associated with an 7.38 and 7.65 increased baPWV (cm/s) in male. Similarly, one-SD rise of Hcy (4.0 μmol/L) and UA (49.2 μmol/L) were associated with an 11.00 and 16.60 increased baPWV in female. Individuals with both high Hcy and UA had the highest baPWV, compared with those with low Hcy and low UA (β: 30.76, 95% CI: 18.36–43.16 in male; β: 53.53, 95% CI: 38.46–68.60 in female).

            CONCLUSIONS This study indicated the joint effect of elevated Hcy and UA on arterial stiffness. People with simultaneously high Hcy and UA should be aware of the risk of arteriosclerosis and cardiovascular events.

            GW33-e0404
            Cardiovascular disease and all-cause mortality attributable to individual and combined cardiometabolic risk factors among Chinese

            Xue Cao1, Linfeng Zhang1, Xin Wang1, Zuo Chen1, Congyi Zheng1, Lu Chen1, Haoqi Zhou1, Jiayin Cai1, Zhen Hu1, Yixin Tian1, Runqing Gu2, Yilin Huang1, Zengwu Wang1

            1Division of Prevention and Community Health, National Center for Cardiovascular Disease, National Clinical Research center of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences

            2School of Population Medicine and Public Health, Peking Union Medical College & Chinese Academy of Medical Sciences

            OBJECTIVES Few have systematically clarified cardiovascular disease (CVD) and all-cause mortality attributable to individual and combined cardiometabolic risk factors, especially for Chinese people. The present study was to investigate and quantify the individual and combined associations and population attributable fraction (PAF) of cardiometabolic risk factors, including hypertension, diabetes and dyslipidemia, on CVD and all-cause mortality, and calculate the reductions in CVD-free years and life expectancy in relation to cardiometabolic risk factors among Chinese population.

            METHODS Twenty-two thousand six hundred sixty participants aged ≥35 without self-reported medical history of CVD at baseline were included between October 2012 and December 2015 based on a nationally representative population-based study. CVD events and mortality were followed up in 2018 and 2019. Cox regression was applied to evaluate the association of individual and combined cardiometabolic risk factors (including hypertension, diabetes and dyslipidemia) with CVD risk and all-cause mortality. We also described the PAF for CVD and mortality, and reductions in CVD-free years and life expectancy associated with different combination of cardiometabolic conditions.

            RESULTS Mean age of the participants was 56.14±13.10 years. During the 4.92 years of follow-up, we detected 438 fatal or nonfatal CVD (including 279 stroke, 126 coronary heart disease and 33 other cardiovascular events) and 1128 deaths. Hazard ratio were 1.57 (95% confidential interval (CI) 1.32–1.86), 1.71 (95% CI 1.42–2.08) and 2.34 (95% CI 1.74–3.09) for CVD and 1.54 (95% CI 1.32–1.79), 1.45 (95% CI 1.21–1.75) and 2.36 (95% CI 1.80–3.09) for all-cause mortality, respectively, in participants with one, two or three cardiometabolic risk factors compared with participants without diabetes, hypertension, and dyslipidemia. Subjects with the combination of diabetes, hypertension, and dyslipidemia had greater than 2-fold increased CVD and all-cause mortality. The cardiometabolic multi-morbidities showed a multiplicative increased CVD and all-cause mortality risk and similar results were found for CVD subtypes. The PAFs for total CVD, stroke, coronary heart disease and all-cause mortality attributable to all cardiometabolic risk factors were 24.52 (95% CI 24.11–24.94), 24.21 (95% CI 23.79–24.64), 23.58 (95% CI 23.06–24.06) and 22.11 (95% CI 21.75–22.49), respectively. For participants with only one risk factor, we found that the PAFs of CVD and mortality were mainly caused by hypertension. We estimated that participants aged between 40 and 60 years old, with three cardiometabolic disorders, had approximately 2.4 years of reduced CVD-free years and 3.3 years of reduced life expectancy compared with participants without any abnormalities of cardiometabolic disorders.

            CONCLUSIONS Cardiometabolic risk factors were additively associated with a higher risk of CVD incidence and all-cause mortality. A large proportion of CVD and all-cause mortality and reduction in CVD-free years and life expectancy were significantly associated with cardiometabolic risk factors, highlighting the importance of cardiometabolic multi-morbidities in the primary prevention of CVD and comprehensive management for hypertension, diabetes and dyslipidemia.

            GW33-e0405
            The burden of cardiovascular disease attributable to high systolic blood pressure across China and its provinces, 2005–2018

            Xue Cao1, Zhenping Zhao2, Yuting Kang3, Yixin Tian1, Yuxin Song1, Limin Wang2, Linfeng Zhang1, Xin Wang1, Zuo Chen1, Congyi Zheng1, Lu Tian4, Lu Chen1, Jiayin Cai1, Zhen Hu1, Haoqi Zhou1, Runqing Gu1, Yilin Huang1, Peng Yin2, Yuehui Fang5, Mei Zhang2, Yuna He5, Zugui Zhang6, William S. Weintraub7, Maigeng Zhou2, Zengwu Wang1

            1Division of Prevention and Community Health, National Center for Cardiovascular Disease, National Clinical Research Center of Cardiovascular Disease, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China

            2National Center for Chronic Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China

            3Office of National Clinical Research for Geriatrics, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

            4Department of Biomedical Data Science, Stanford University, Stanford, California

            5National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing, China

            6Christiana Care Health System, Newark, DE

            7MedStar Health Research Institute, Washington, DC

            OBJECTIVES Temporal trends and geographical variations in cardiovascular disease (CVD) burden attributable to high systolic blood pressure (SBP) in China have not been fully elucidated in the past. The current study was performed to quantify the CVD burden attributable to high SBP at both the national and provincial level in China, assisting public policy making in promoting blood pressure control measures.

            METHODS We evaluated SBP levels and estimated the number of deaths, age-standardised mortality rates, years of life lost (YLLs) for death related to CVD and its subcategories (including ischaemic heart disease, ischaemic stroke, haemorrhagic stroke and other cardiovascular diseases) attributable to high SBP at both national and provincial levels in China from 2005 to 2018. We pooled blood pressure data of 1·30 million adults from the China Chronic Disease and Risk Factor Surveillance project, the China Health and Nutrition Survey and China Hypertension Survey. We applied a temporal-spatial Bayesian hierarchical model to estimate all year-specific local SBP levels, and a comparative risk assessment method to compute the health burden attributable to high SBP by age, sex, year and province.

            RESULTS Nationally, age-standardised mean SBP was 132·4 mmHg (95% uncertainty interval [UI] 124·6 to 140·1) for (95%UI 2·61 to 2·73) CVD deaths in China were attributable to elevated SBP, consisting of 1·12 million (95%UI 1·08 to 1·16) deaths from ischaemic heart disease, 0·63 million (95%UI 0·60 to 0·65) deaths from ischaemic stroke, 0·58 million (95%UI 0·57 to 0·60) deaths from haemorrhagic stroke and 0·34 million (95%UI 0·32 to 0·36) death from other CVD. The age-standardised CVD mortality rates associated with high SBP decreased by 17·89% between 2005 and 2018 with an estimated annual percentage change was −1·50 (95%UI −1·55 to −1·45). Despite the decline in corresponding age-standardised mortality rates, the number of deaths from ischaemic heart disease and ischaemic stroke attributable to high SBP, however, increased in most provinces from 2005 to 2018, consistent with the national trend, because of the change in demographic structure in the population. YLLs for total CVD deaths attributable to high SBP increased from 40·13 million (95%UI, 39·70 to 40·52) in 2005 to 48·16 million (95%UI, 47·44 to 48·90) in 2018 nationally. YLL rates also varied substantially across provinces, ranging from 3217·15 (95%UI 2947·43 to 3441·83) per 100,000 people in Fujian to 7196·20 (95%UI 6864·28 to 7498·94) per 100,000 people in Heilongjiang in 2018. Age-standardised YLL rates for ischaemic heart disease and ischaemic stroke attributable to high SBP were particularly high in northeastern provinces, including Heilongjiang, Liaoning and Jilin.

            CONCLUSIONS The deaths and YLLs for CVD attributable to high SBP increased substantially in recent years, especially among the elderly, although age-standardised CVD mortality rates decreased in China between 2005 and 2018. Effective and locally adapted preventive interventions should be implemented to lower the prevalence of high SBP to reduce the health burden of SBP-related CVD in the population.

            GW33-e0408
            Intermediate-density lipoproteins particle numbers are independently associated with progression of carotid atherosclerosis

            Tianxiao Liu, Dong Zhao, Jing Liu, Miao Wang, Jiayi Sun, Jun Liu, Jiangtao Li, Youling Duan, Piaopiao Hu, Zhaoqing Sun, Yue Qi

            Center for Clinical and Epidemiological Research, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China

            OBJECTIVES Despite lipid-lowering therapy, residual risk still exists for atherosclerotic cardiovascular disease (ASCVD). As the precursor of low-density lipoprotein, intermediate-density lipoprotein (IDL) has been reported to be prone to promote atherosclerotic plaque formation in experimental studies and related with occurrence of ASCVD in prospective cohort studies. However, it remains unclear whether IDL was associated with development of atherosclerosis. This study aims to examine the association between IDL particles numbers and 5-year progression of carotid atherosclerosis in a community-based study.

            METHODS Baseline IDL particle number (IDL-P) was measured using nuclear magnetic resonance spectroscopy in 927 participants aged 45 to 74 years with no history of cardiovascular disease (CVD) at baseline. They were recruited from the Chinese Multi-Provincial Cohort Study-Beijing Project. Progression of carotid atherosclerosis was indicated by progression of carotid plaque and changes in total plaque area (TPA) in participants without baseline plaque. Modified Poisson regression was used to estimate multivariate adjusted risk ratio (RR) for the associations between IDL-P and 5-year progression of carotid plaque. Ordinal logistic regression model was used to examine the associations between IDL-P levels and changes in TPA.

            RESULTS During 5-year follow-up period, the progression of carotid plaque was observed in 45.8% of participants. The median level of baseline IDL-P was 199 nmol/L. Baseline IDL-P was independently associated with plaque progression and changes in TPA. Compared with the lowest quartile of IDL-P, RR in the highest quartile of IDL-P was 1.36 (95% confidence interval: 1.09 to 1.69) for progression of carotid plaque. Among participants without baseline plaque, adjusted OR in the highest quartile of IDL-P was 1.68 (95% CI: 1.05 to 2.70). Similar results were found in participants without lipid-lowering therapy or diabetes at baseline. This relation still preserved even among participants with low-density lipoprotein cholesterol less than 130 mg/dL.

            CONCLUSIONS Increased IDL-P levels are associated with an increased risk of carotid atherosclerosis progression in participants free of cardiovascular disease from a community-based population study, suggesting IDL-P exerting an important role in the pathogenesis of atherosclerosis and be a potential target for the early prevention of cardiovascular disease.

            GW33-e0505
            Exploring optimal exercise-based rehabilitation program for pulmonary hypertension: a systematic review and meta-analysis of randomized controlled trials

            Zeying Zhang1, Yingxu Ma1, Yunbin Xiao2, Qiming Liu1

            1Department of Cardiovascular Medicine, The Second Xiangya Hospital of Central South University, Changsha 410007, China

            2Department of Cardiology, Hunan Children’s Hospital, Changsha 410007, China

            OBJECTIVES The optimal individualized exercise training program for patients with pulmonary hypertension (PH) is unclear. In this study, we aimed to perform a meta-analysis of randomized controlled trials (RCTs) to estimate the efficacy of exercise training and determine the optimal exercise training program characteristics.

            METHODS We searched studies up to May 2022 from PubMed, MEDLINE, Embase and Cochrane. We included all RCTs analyzing the effectiveness of exercise training in PH patients. The primary outcomes of this meta-analysis were changes in six-minute walk distance (6MWD) and changes in peak oxygen uptake (peak VO2). Other outcomes included changes in N-terminal pro brain natriuretic peptide (NT-pro BNP), physical summation score of short-form health survey 36 (SF-36 PCS), and mental summation score of short-form health survey 36 (SF-36 MCS). We performed subgroup analyses based on 2 factors: exercise training duration and exercise training modality. We accessed risk of publication bias and study quality of included studies.

            RESULTS In total, 13 studies with 552 PH patients were included. Intervention duration ranged from 3 weeks to 6 months. Exercise modality included aerobic exercise only, inspiratory muscle training (IMT) only, combined exercise, and mixed exercise. Exercise training was associated with significant improvement of 6MWD [MD: 47.89 meters (95% CI: 34.77 to 61.01)], peak VO2 [MD: 1.77 mL/kg/min (95% CI: 0.75 to 2.79)], SF- 36 PCS [MD: 4.13 (95% CI: 1.93 to 6.33)] and SF-36 MCS [MD: 3.70 (95% CI: 1.71 to 5.69)]. Exercise training did not reduce NT-pro BNP levels. Long duration exercise training subgroup [MD: 56.03 meters (95% CI: 37.17 to 74.89) in 6MWD, MD: 2.04 mL/kg/min (95% CI: 0.63 to 3.45) in peak VO2] had better improvement compared with the other subgroups. In a subgroup analysis using exercise training modality as a grouping factor, the aerobic exercise only subgroup did not improve 6MWD [MD: 48.42 meters (95% CI: −13.03 to 109.87)] and only the mixed exercise subgroup was associated with a significant improvement in peak VO2 [MD: 2.25 mL/kg/min (95% CI: 0.58 to 3.92)].

            CONCLUSIONS Long duration exercise training with mixed exercise form of modality is probably an effective supplementary treatment for stable and well-compensated PH patients.

            GW33-e0525
            Effect of a web-based platform on hypertension control in community: a randomized clinical trial

            Haoqi Zhou, Zengwu Wang

            Fuwai Hospital, Peking Union Medical College & Chinese Academy of Medical Sciences

            OBJECTIVES We aimed to assess the effect of a web-based platform on improving the blood pressure (BP) control.

            METHODS A cluster randomized clinical trial of a hypertension management program was conducted in 66 communities, which were randomized to either the intervention group (n=44) or control group (n=22). The intervention included health education, lifestyle modification, self-monitoring and treatment. A web based-platform was established to support the implementation of intervention. The primary outcome was the change in BP control rate from baseline to 12 months among hypertension patients in the intervention and control group. The analysis was by intention to treat. The trial has registered in the Chinese Clinical Trial Registry, number ChiCTR1800017791.

            RESULTS BP control rate at baseline was 23.5% in the intervention group and 22.7% in the control group. After 12 months of the intervention, the BP control rate for the intervention group compared with the control group was significantly higher (48.2 vs 31.1%; odds ratio, 1.18; 95% CI: 1.13 to 1.23; P<0.001). At 12 months, the mean systolic BP fell by 11.8 mmHg in the intervention group and by 2.0 mmHg in the control group; the mean reduction was 9.8 mmHg (95% CI: −11.4 to −8.2; P<0.001) greater with the intervention. The mean reduction in diastolic BP was 1.7 mmHg (95% CI: −2.8 to −0.7, P<0.001) greater in the intervention group than the control group.

            CONCLUSIONS Intervention program supported by a web-based platform appeared to be more effective than usual care, resulting in improved hypertension control, and lower BP level. A suitable designed web-based platform may provide a new way to improve the unsatisfactory status of BP control faced in many countries.

            GW33-e0553
            Association of access to urban parks with incident cardiovascular disease: findings from the Chinese multi-provincial cohort study

            Yulin Huang1,2,3,4, Qiuju Deng1,2,3,4, Dong Zhao1,2,3,4, Miao Wang1,2,3,4, Yue Qi1,2,3,4, Jiayi Sun1,2,3,4, Jun Liu1,2,3,4, Yan Li1,2,3,4, Jing Liu1,2,3,4

            1Department of Epidemiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China

            2Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China

            3The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China

            4Beijing Municipal Key Laboratory of Clinical Epidemiology, Beijing, China

            OBJECTIVES Living in neighborhoods with better accessibility of parks may be related to lower risk for cardiovascular disease (CVD), but limited findings are available among older adults from Asian countries. We aimed to estimate the association between neighborhood accessibility of parks and incident CVD in China.

            METHODS A total of 4505 participants aged 51 to 80 years from the Chinese Multi-provincial Cohort Study without CVD at baseline were included. Outcomes were defined as incident CVD, coronary heart disease (CHD), and stroke using 12 years follow-up data. Neighborhood accessibility of parks was defined as the presence of parks (yes or no) and the count of parks within 1000 m buffer around residential addresses with points of interest data based on Geographic Information Systems. Shared frailty models were used to estimate the associations of neighborhood accessibility of parks with the risk for incident CVD, CHD, and stroke, adjusting for potential confounders. Hazard ratios (HRs) between subgroups were compared using Z-test.

            RESULTS The mean age of the participants was 62.4 (±7.5) years at baseline and 2298 (51.0%) participants were women. A total of 1985 individuals (44.1%) reported the presence of parks within 1000 m buffer around residences. Over a median follow-up of 11.3 years, there were 468 CVD events, 207 CHD events and 282 stroke events, respectively. Using the presence indicator, we found a significantly decreased risk of stroke (HR=0.70, 95% CI 0.51–0.95) for participants with the presence of parks compared with those without any parks in 1000 m buffer, but not CVD (HR=0.89, 95% CI 0.71–1.11) and CHD (HR=1.10, 95% CI 0.81–1.51) in fully adjusted models. Further analysis with count indicator indicated living within 1000 m of one park was associated with a decreased risk of stroke (HR=0.64, 95% CI 0.44–0.93), but no significant association was found for two or more parks (HR=0.79, 95% CI 0.52–1.19) compared with those without. The relationships were not significant for CVD and CHD incidence. Subgroup analyses showed a significant interaction between the presence of parks and history of hypertension on incident CVD (P for interaction=0.021).

            CONCLUSIONS Residing in neighborhoods with better accessibility of parks is associated with a lower risk of incident CVD. Urban planning intervention policies that increase the accessibility of urban parks could contribute to CVD prevention.

            GW33-e0589
            Preserved ratio impaired spirometry in relation to cardiovascular outcomes

            Jiazhen Zheng1,2, Qingwen Ren1,2, Meizhen Wu1,2, Jiayi Huang1,2, Kaihang Yiu1,2

            1Cardiology Division, Department of Medicine, The University of Hong Kong Shen Zhen Hospital, No. 1 Haiyuan 1st Rd, Futian District, Shenzhen City, Guangdong Province 518009, China

            2Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Pok Fu Lam Rd 102. Hong Kong Island, Hong Kong 999077, China

            OBJECTIVES Preserved ratio impaired spirometry (PRISm) is a heterogeneous condition characterized by a normal forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio despite underlying impairment of pulmonary function. Data relating to the association of baseline and trajectory of PRISm with diverse cardiovascular outcomes is sparse.

            METHODS Based on the UK Biobank study, this population-based prospective cohort included cardiovascular disease (CVD) free participants with spirometry (best measure FEV1 and FVC values) at baseline (2006–2010). Those with baseline spirometry and had a follow-up spirometry at 2014+ were included in the lung function trajectory analysis. Normal spirometry was defined as a FEV1≥80% predicted and a FEV1/FVC ratio ≥0·70. Airflow obstruction was defined as a FEV1/FVC ratio <0·70. PRISm was defined as a FEV1 <80% predicted and a FEV1/FVC ratio ≥0·70. Cox proportional hazards multivariable regression was performed to evaluate the outcomes of major adverse cardiovascular events (MACE), incident myocardial infarction (MI), stroke, heart failure (HF), and CVD mortality in association with lung function. Linear associations of relative FEV1 and FVC predicted percentage change with diverse cardiovascular outcomes were also evaluated by cubic spline model.

            RESULTS Among 329,954 adults with spirometry data available at baseline, 242,553 (73.5%) had normal spirometry, 37,897 (11.5%) had PRISm and 49,504 (15.0%) had airflow obstruction. For baseline analysis, the median follow-up time was 9.0 years (interquartile range: 8.4–9.8 years). The multivariable adjusted hazard ratios for participants had PRISm (vs. normal spirometry) were 1.26 (95% confidence interval 1.17 to 1.35) for MACE, 1.12 (1.01 to 1.25) for MI, 1.88 (1.72 to 2.05) for HF, 1.26 (1.13–1.40) for stroke, and 1.55 (1.37–1.76) for CVD mortality, respectively. A total of 22,781 participants had a follow-up spirometry after 6.4 years. Longitudinal analysis showed that persistent PRISm and airflow obstruction was associated with a higher incidence of MACE (1.96 (1.24 to 3.09) and 1.43 (1.00 to 2.04)) versus consistently normal lung function, respectively. Compared with persistent PRISm, changing from PRISm to normal spirometry was associated with a lower incidence of MACE (0.41 (0.17 to 0.96)). Each five unit increase in relative FEV1 or FVC predicted percentage change was associated with a lower risk of MACE (FEV1: 0.91 (0.88–0.95); FVC: 0.94 (0.90–0.97)) and MI (FEV1: 0.92 (0.86–0.97); FVC: 0.94 (0.90–0.99)).

            CONCLUSIONS Individuals with baseline or persistent PRISm were at a higher risk of diverse cardiovascular outcomes even after adjusting for a wide range of confounding factors. Early detection and interventions for lung pathology may reduce subsequent MACE inflicted by lung diseases.

            GW33-e0652
            Trends in incidence, long-term all-cause and cardiovascular and cerebrovascular mortality of metabolic syndrome in U.S. adults from 1999–2014: an observational study

            Weiya Li1, Han Yin1, Haochen Wang1, Bingqing Bai2, Huan Ma1, Qingshan Geng1,2

            1Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

            2School of Medicine, South China University of Technology, Guangzhou, China

            OBJECTIVES Metabolic syndrome (MetS) is very prevalent and related to severe diseases and death. This study aimed to investigate the incidence and mortality trends of MetS in recent decades. The gender and age differences of MetS are also been explored.

            METHODS Patients with MetS were screened in National Health and Nutrition Examination Survey (NHANES) adults from 1999 to 2014. The prognosis data of them was also acquired. Then we assessed the trends of incidence and mortality of MetS in the US.

            RESULTS Fourteen thousand one hundred seventy-one participates were included in our study, in which the mean age was 46.8±19.3 years and 7354 (51.9%) were female. Four thousand seven hundred eighty-nine participates finally were diagnosed with MetS. The overall trend of incidence of MetS from 1999 to 2014 was upward (from 27.6 to 32.3%; adjusted odds ratios [aOR], 1.71; 95% confidence interval [CI], 1.42–2.05; P-value<0.001, P for trend<0.001). In more detail, the incidence of MetS rose first but subsequently stalled and declined. Obvious downward trends were observed from 29.6 to 2.7% for all-cause mortality (aOR, 0.12; 95% CI, 0.07–0.21; P-value<0.001, P for trend<0.001) and 4.8 to 0.8% for cardio-cerebrovascular mortality (aOR, 0.17; 95% CI, 0.05–0.61; P-value=0.007, P for trend<0.001). The all-cause mortality had a yearly decline trend, while the cardio-cerebrovascular death experienced a short period of rise then declined and stabilized. Similarly, the temporal mortality trends in MetS patients of different ages and gender had the same results. Specifically, the incidence of MetS in female was higher than that in male (Adjusted P=0.003; OR, 1.14; 95% CI, 1.05–1.24), but the mortality was much lower after an average of 7.7 years’ follow-up (All-cause mortality, Adjusted P<0.001; HR, 0.68; 95% CI, 0.57–0.81; Cardio-cerebrovascular mortality, Adjusted P=0.004; HR, 0.55; 95% CI, 0.37–0.83).

            CONCLUSIONS From 1999–2014, the incidence of MetS in U.S. adults was significantly increased overall, while the mortality rate of MetS had a significant downward trend. Both trends showed marked gender differences, being more prevalent and at lower risk in female compared with male. It is important to identify the factors to curb the incidence of MetS and decrease the mortality especially in male.

            GW33-e0657
            Associations of high triglyceride-glucose index onset age with cardiovascular disease and mortality: the Kailuan Study

            Xianxuan Wang1,2, Zegui Huang1,2, Xinran Yu3, Hui Zhou3, Xiong Ding3, Zefeng Cai2, Zekai Chen4, Guanhzi Chen5, Zhiwei Cai1,2, Shouling Wu6, Youren Chen2

            1Shantou University Medical College, Shantou, Guangdong, China

            2Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China

            3North China University of Science and Technology, Tangshan, China

            4Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands

            5China Medical University, Shenyang, China

            6Department of Cardiology, Kailuan General Hospital, Tangshan, China

            OBJECTIVES A high triglyceride-glucose index (TyG index) is associated with cardiovascular diseases (CVDs) and all-cause mortality, but the associations of a high TyG index new-onset age with CVD and all-cause mortality remain unclear.

            METHODS This study included a total of 130,197 participants free of a high TyG index and CVD at baseline from the Kailuan Study, a prospective cohort study in Tangshan, China. All participants were monitored biennially until 31 December 2019. A total of 28,749 new-onset high TyG index cases were identified during the follow-up period. We randomly selected one control participant for each new-set high TyG index participant, matching for age (±1 year) and sex. The final analysis included 25,708 case–control pairs. The multivariable Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) across the age groups.

            RESULTS During a median follow-up of 8.31 years, 1964 incident CVD cases and 1704 deaths occurred. After adjusting for potential confounders, participants with a new-onset high TyG index identified that were aged <45 years had the highest relative risks of CVD and all-cause mortality compared with the matched control subjects (HR: 1.89; 95% CI: 1.33–2.67 and HR: 2.24, 95% CI: 1.50–3.36, respectively). The HR and 95% CI of CVD were 1.22 (1.07–1.40) and 1.18 (1.02–1.39) for the high TyG index onset age 45–60 years old group and ≥60 years old group, respectively, and the HR and 95% CI of all-cause mortality were 1.86 (1.55–2.22) and 1.77 (1.54–2.03) for the high TyG index onset age 45–60 years old group and ≥60 years old group, respectively. The hazards of CVD and all-cause mortality gradually attenuated with increasing new-onset age.

            CONCLUSIONS A high TyG index was associated with a higher risk for CVD and all-cause mortality. The relative risks differed across high TyG index onset age groups, and the associations were more intense with a younger age of onset.

            GW33-e0725
            Associations between mental health problems and elevated blood pressure: findings from the CHCN-BTH cohort study and two-sample Mendelian randomization analysis

            Han Qi1,2, Ling Zhang1

            1Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, and Beijing Municipal Key Laboratory of Clinical Epidemiology

            2The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & the Advanced Innovation Center for Human Brain Protection, Beijing Anding Hospital, School of Mental Health, Capital Medical University

            OBJECTIVES The associations of mental health problem and blood pressure (BP) are controversial, and the causality remain unclear. We aimed to explore whether mental health problem is associated with risk of elevated blood pressure by longitudinal and Mendelian randomization (MR) analyses.

            METHODS This prospective cohort study used the data of the Cohort Study on Chronic Disease of Community Natural Population in the Beijing-Tianjin-Hebei region (CHGN-BTH) from 2017 to 2021 with a two years’ follow-up among the participants who aged 18 to 80 years old living in Northern China. The Depression-Anxiety-Stress Scale (DASS-21) were used to evaluate the symptoms of depression, anxiety, and stress (mental health problems) in population. The longitudinal associations between mental health problems and elevated blood pressure were estimated the Cox proportional regression models. The two-sample MR analysis was also performed to explore the causal relationships and the summary data of the SNPs were obtained from publicly available dataset of MRC-IEU Consortium and Neale lab.

            RESULTS Totally, 5624 participants were included with the mean age of 39.68 ±12.76 years old. In the follow-up, the risk of SBP≥140 mmHg or DBP≥90 mmHg was significantly higher in participants with baseline anxiety symptoms (HR=1.48, 95% CI: 1.03 to 2.12, P=0.033; HR=1.56, 95% CI: 1.05 to 2.32, P=0.028), especially in men and higher educational level population, independent of baseline depression and anxiety in two years’ follow-up. The two-sample MR analysis that regarded 38 SNPs as instrumental variables showed the positive associations between mental health problems and elevated blood pressure (OR=1.17, 95% CI: 1.06 to 1.28, P<0.001).

            CONCLUSIONS Anxiety was positively associated with higher BPs in longitudinal designs independent of the depression, stress, and other confounders. The results were verified in MR analysis with the evidence for a causal risk effects of mental health problem on elevated blood pressure.

            PREVENTION RESEARCH
            GW33-e0021
            The improvement effect of resistance training on cardiovascular health of middle-aged and elderly women

            Jin Li, Peizhen Zhang

            Beijing Sport University

            OBJECTIVES “Report on Cardiovascular Health and Diseases in China 2020” shows that the incidence of cardiovascular disease in China continues to rise. Some studies have demonstrated that elderly women have a higher mortality rate from cardiovascular disease than men. Therefore, it is more important for middle-aged and elderly women (MEW) to prevent cardiovascular disease. The American College of Sports Medicine recommends resistance training (RT) to prevent the functional decline of the body brought by aging and to improve muscle strength and physical function. Therefore, this study will focus on the effects of RT on cardiovascular health in MEW so as to prevent cardiovascular disease.

            METHODS In this study, the latest research results of “RT”, “MEW”, “cardiovascular health” and other related research fields were searched in databases such as CNKI, Wanfang Data, VIP, PubMed, Web of Science. Finally, the articles with low relevance to the topic were excluded, 59 targeted articles were selected for further analysis to explore the effects of RT on cardiovascular health of MEW.

            RESULTS (1) RT promotes cardiovascular protection by inducing post-exercise hypotension; improves endothelial cell function, regulates blood pressure (BP); causes hemodynamic and neurohumoral factors such as plasma catecholamines and vascular tone to interact to induce BP changes, promote cardiovascular health in MEW. (2) RT can raise the activity of lipolytic enzymes in muscles, significantly improve local muscle metabolism, enhance cholesterol catabolism in peripheral tissues, reduce LDL-C deposition in the vascular endothelium, lessen visceral and subcutaneous fat, improve lipid metabolism. (3) RT can increase nitric oxide bioavailability, increase the expression and activity of nitric oxide synthase; improve vagal regulation and promote sympathetic-vagal balance, reduce heart rate variability, decrease the risk of cardiovascular disease. (4) RT improves arterial stiffness by activating muscles, increasing glycolysis, causing a hypermetabolic reflex, and decreasing baroreflex sensitivity. However, some studies have shown that high intensity RT may increase arterial stiffness, it is important to choose the right intensity for MEW. (5) RT can improve the total antioxidant capacity, upregulate the activity of endogenous antioxidant defense system and balance the redox state; increase the activity of antioxidant enzymes, improve the antioxidant capacity and reduce the oxidative stress response, decrease the inflammatory response associated with increasing age. (6) It is suggested that MEW should perform RT at least twice a week. Further studies may focus on appropriate frequency and intensity of RT for MEW.

            CONCLUSIONS RT can improve dyslipidemia, heart rate variability, arterial stiffness; lower blood pressure and reduce oxidative stress. In MEW, RT can counteract the effects of menopause and changes in hormone levels on the cardiovascular system to a certain extent and reduce the risk of cardiovascular disease. Therefore, it is recommended that MEW perform appropriate RT in daily life to delay the adverse effects of aging.

            GW33-e0067
            The prevention and control effect of exercise on abnormal lipid metabolism induced by changes in postmenopausal hormone secretion

            Qian Duan, Peizhen Zhang

            Beijing Sport University

            OBJECTIVES Due to the insidious form of the disease, abnormal lipid metabolism in postmenopausal women tends to develop further due to delayed intervention, which can lead to obesity, cardiovascular disease and non-alcoholic fatty liver, etc. Studies show that this is related to the change of hormone secretion in the body after menopause. Regular exercise can effectively improve blood lipid indexes in postmenopausal women by promoting hormone secretion and activating estrogen receptor. This study summarized the changes of hormone secretion related to lipid metabolism after menopause and its effects on lipid metabolism, and explored the intervention effects and regulatory mechanisms of different exercise modes on abnormal lipid metabolism in postmenopausal women, so as to provide theoretical support and practical guidance for the prevention and treatment of postmenopausal abnormal lipid metabolism.

            METHODS Using the method of literature review, the related articles were searched in CNKI and PubMed databases by computer, and the key words were “menopause”, “hormones”, “lipid metabolism”, “exercise” and “training”. The research included postmenopausal hormone secretion change patterns, effects and mechanisms on lipid metabolism, and results and mechanisms of exercise interventions. The articles with low relevance to the topic were excluded, and 64 targeted articles were selected for further analysis.

            RESULTS (1) The abnormalities of lipid metabolism in postmenopausal women are due to hormonal changes. Previous studies have suggested that this is mainly related to estrogen deficiency, but more and more studies in recent years have found that follicle stimulating hormone is also related. (2) Changes in E2 and FSH levels in women during the menopausal transition and postmenopause do not follow a single pattern, but are related to multiple factors such as race/ethnicity, weight, age and health status. (3) Abnormalities in postmenopausal lipid metabolism are formed by E2 through increased energy intake, involved in lipid metabolism in multiple tissues, and reduced energy expenditure, suggesting that the mechanism of the problem is not unique and unilateral, but may be the result of multiple mechanisms acting together. (4) Compared with E2, the mechanism of the effect of FSH on lipid metabolism in postmenopausal women is less. It may be involved in the proliferation of bile duct cells and lipid synthesis in adipose tissue, or the regulation of fat accumulation and distribution during aging. (5) Different types of exercise such as aerobic exercise, resistance training, combined aerobic and resistance training, high-intensity interval training, handball exercise and water exercise all have positive effects on lipid metabolism of postmenopausal women. (6) Exercise promotes improved lipid metabolism by improving the secretion of E2 and FSH in plasma, skeletal muscle and other tissues, activating estrogen receptors and ERE and other mechanisms.

            CONCLUSIONS Abnormal lipid metabolism caused by changes in hormone levels leads to a series of problems such as obesity and cardiovascular diseases, which plague many postmenopausal women, endangering their life and health, and seriously affecting the quality of life. Exercise can improve abnormal lipid indicators in postmenopausal women and should be promoted as soon as possible to reduce the medical burden on families and the country.

            GW33-e0098
            Effect of HIIE and MICE on vascular function of recessive obese women with family history of hypertension

            Peizhen Zhang

            Beijing Sport University

            OBJECTIVES To reveal features of changes in vascular function among recessive obese women with family history of hypertension after different types of exercise with same energy expenditure, instruct them to do exercise scientifically and prevent hypertension and atherosclerotic cardiovascular disease (ASCVD).

            METHODS Forty-five recessive obese women (20.5±1.7 yrs) with family history of hypertension participated in the study. They were evenly randomized to moderate intensity continuous exercise (MICE) group, high intensity interval exercise (HIIE) group and control (CONT) group. The exercise began after 2 hours of the meal. The HIIE group performed an interval running session consisting of 4×4 min bouts (running at the intensity of 85–95% HRmax 4 min, interspersed by 3-min rest). The MICE group did exercise 40 min at the intensity of 65–75% HRmax. The energy expenditure was similar between those two groups. The pulse wave velocity (PWV) and ankle brachial index were determined at the time points of pre-exercise, immediately after exercise, then every 5 minutes till 40 minutes.

            RESULTS (1) Immediately after exercise, participants in the MICE group had a significant reduction in the PWV level (12.3%, P<0.01). Forty min after exercise, PWV level in MICE group returned to the baseline. (2) The HIIE group demonstrated significantly decreased level of PWV (867.00±84.33 vs 972.50±93.05 cm/s, P<0.01) immediately after exercise. Forty min after exercise, participants in HIIE group still had a significant lower PWV level compared with the baseline (4.4%, P<0.01). (3) During recovery period, compared with CONT group, participants in HIIE and MICE groups had significant lower PWV level from 5 min to 25 min (P<0.05). There were no significant differences in PWV level between HIIE group and MICE group at all time.

            CONCLUSIONS Both HIIE and MICE could reduce arterial stiffness and ameliorate vascular elasticity of recessive obese women with family history of hypertension, which were beneficial to prevent hypertension and ASCVD in early life. It was suggested that HIIE may result in a greater stimulus for vascular adaptations when compared to MICE.

            GW33-e0103
            Canagliflozin and atrial fibrillation in type 2 diabetes mellitus: a secondary analysis from the CANVAS program and CREDENCE trials and meta-analysis

            Chao Li1,2, Jie Yu2,3,4, Carinna Hockham5, Vlado Perkovic2,3,6, Brendon L Neuen2, Sunil V Badve2,3,7, Lauren Houston2,3, Vivian YJ Lee2,3, Jennifer Y Barraclough2, Robert A Fletcher2, Kenneth W Mahaffey8, Hiddo J L Heerspink2,9, Christopher P Cannon10, Bruce Neal2,3,11, Clare Arnott2,3,12,13

            1Cardiovascular Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China

            2The George Institute for Global Health, UNSW Sydney, Sydney, Australia

            3Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia

            4Department of Cardiology, Peking University Third Hospital, Beijing, China

            5The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom

            6The Royal North Shore Hospital, Sydney, Australia

            7Department of Nephrology, St George Hospital, Sydney, Australia

            8Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California

            9Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

            10Cardiovascular Division, Brigham & Women’s Hospital and Baim Institute for Clinical Research, Boston, MA

            11Imperial College London, London, United Kingdom

            12Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia

            13Sydney Medical School, University of Sydney, Australia

            OBJECTIVES The effect of sodium-glucose co-transporter 2 inhibitors on atrial fibrillation/flutter (AF/AFL) is unclear. We assessed the effects of canagliflozin on the incidence of AF/AFL and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials.

            METHODS Participants with T2D and high risk of cardiovascular disease or chronic kidney disease were included and randomly assigned to canagliflozin or placebo. We explored the effects of canagliflozin on the incidence of first AF/AFL events and AF/AFL related complications (ischemic stroke/transient ischemic attack/hospitalisation for heart failure). Major adverse cardiovascular events (MACE), and a renal-specific outcome by baseline AF/AFL status were analysed using Cox regression models.

            RESULTS Overall 354 participants experienced a first AF/AFL event. Canagliflozin had no detectable effect on AF/AFL (HR 0.82; 95% CI, 0.67, 1.02) compared with placebo. Subgroup analysis, however, suggested a possible reduction in AF/AFL in those with no AF/AFL history (HR 0.78; 95% CI, 0.62, 0.99). Canagliflozin was also associated with a reduction in AF/AFL related complications (HR 0.74; 95% CI, 0.65, 0.86). There was no evidence of treatment heterogeneity by baseline AF/AFL history for other key cardiorenal outcomes (all Pinteraction>0.14). Meta-analysis of five SGLT2 inhibitor trials demonstrated a 19% reduction in AF/AFL events with active treatment (HR 0.81; 95% CI 0.72, 0.92).

            CONCLUSIONS Overall, a significant effect of canagliflozin on the incidence of AF/AFL events could not be shown, however, a possible reduction in AF/AFL events in those with no prior history requires further investigation. Meta-analysis suggests SGLT2 inhibition reduces AF/AFL incidence.

            GW33-e0141
            Effects of interval training on cardiopulmonary endurance and cardiovascular disease risk factors in young adults

            Xue Song, Peizhen Zhang

            Beijing Sport University

            OBJECTIVES The number of people suffering from cardiovascular disease (CVD) in China is estimated to have reached 330 million, which has become an important public health problem. Low cardiorespiratory fitness (CRF) in early adulthood is associated with increased long-term risk of CVD, subclinical CVD and mortality. Evaluation and improvement of CRF in early adulthood play an important role in promoting cardiovascular health and preventing CVD. Exercise can improve CRF, but lack of time has become the main reason for insufficient exercise in young people. Therefore, interval training has become a research hotspot in the field of public fitness, but there is still no consensus on the effect of exercise in young people. The study analyzed the effects of sprint interval training (SIT) and high intensity interval training (HIIT) on CRF and cardiovascular risk factors in young people, and provided theoretical support for improving CRF and preventing and delaying the occurrence and development of CVD in early adulthood.

            METHODS PubMed, Web of science, Zhiwang, and Wanfang databases were searched for “high intensity interval training”, “high intensity intermittent exercise”, “sprint interval training”, “sprint interval exercise”, “HIIT”, “HIT”, “SIT”, “cardiorespiratory fitness”, “VO2max”, and “VO2peak” in English and Chinese. Subjects aged 18 to 30 years with changes in CRF and any cardiovascular risk factors (blood pressure, lipids, blood glucose) after HIIT or SIT were included. The final 28 articles that were more targeted were selected for further analysis.

            RESULTS (1) Both SIT and HIIT for 2 weeks or more significantly improved CRF in healthy young men and women independent of changes in body weight. (2) For blood pressure, the intervention period may be an important factor. Acute SIT and HIIT lowered blood pressure, and generally occurred within 2 h after exercise; neither SIT nor HIIT for 2 to 4 weeks had a positive effect on resting blood pressure in young people; positive changes in blood pressure were seen after HIIT lasting 6 weeks and more, while studies on the effect of SIT on blood pressure are scarce and controversial. (3) In terms of blood glucose, gender difference is a non-negligible factor. Acute SIT and HIIT improved glycemic-related indicators in young men; positive changes in glycemia were observed in both men and women after 6 weeks or more. Glycemic-related indicators in young people improved after SIT for 2 to 4 weeks, but no changes were found after HIIT. (4) For lipid profile, both acute SIT and HIIT reduced lipid levels at 24 h after exercise, but the effects of SIT and HIIT beyond 2 weeks or more on blood lipids are controversial and need further study.

            CONCLUSIONS SIT and HIIT are time-efficient and effective exercise modalities for improving CRF and cardiovascular risk factors (blood pressure, blood glucose, lipid profile) in young people who “lack the time” to exercise, while SIT is a more efficient alternative to HIIT for those who can tolerate the intensity of SIT.

            GW33-e0237
            Effect of exercise and CRF improvement on CVD risk in postmenopausal women

            Xingrui Zhang, Peizhen Zhang

            Beijing Sport University

            OBJECTIVES Cardiovascular disease (CVD) is one of the major threats to the health of postmenopausal women. The decrease in cardiorespiratory fitness (CRF) may be related to the increased CVD risk caused by the reduction of estrogen levels. Exercise and physical activity (PA) can improve CRF and reduce the risk of CVD. Most of postmenopausal women have low CRF, lack of sufficient exercise time, and high-intensity exercise may expose them to adverse cardiovascular events. Therefore, it is very important to explore suitable exercise prescription for them. This study started from the level of PA, exercise intensity and type of exercise, trying to summarize and provide a reference for improving CRF and quality of life for them.

            METHODS The literature method was used to retrieve relevant articles in databases such as PubMed and CNKI by computer. The search terms were: “postmenopausal women”, “cardiorespiratory fitness”, “cardiovascular risk”, “exercise” and “physical activities”. Articles related to CVD risk factors, exercise, PA level, and improvement of CRF were included; repeated studies and low correlation studies were excluded, and finally 38 articles with strong pertinence were selected for further analysis.

            RESULTS (1) Obesity, hypertension, hyperlipidemia, type 2 diabetes, sedentary lifestyle and insufficient PA are the main cardiovascular risk factors in postmenopausal women. Among them, changing sedentary lifestyle and increasing PA levels are easier to intervene. Substituting low-intensity or moderate-intensity PA for sedentary time was associated with a significantly lower risk of death from CVD through the “isochronous substitution model”. (2) Compared with aerobic exercise alone, aerobic combined with resistance exercise can significantly reduce SBP, DBP, baPWV and HR, especially in overweight postmenopausal women over 60 years. In addition, SBP and DBP can be more effectively reduced when combined aerobic and resistance exercise frequency <3 times per week, total weekly exercise time ≥150 min, and exercise duration is 12 weeks. (3) Nordic walking (NW) at lipid metabolism intensity for 6 weeks significantly reduced body mass, body fat mass, resting BP, and HR, significantly increased VO2max in sedentary postmenopausal women, showing its effectiveness in improving CRF, body composition, and etc.

            CONCLUSIONS Substituting PA for sedentary time, performing aerobic combined with resistance exercise and NW with lipid metabolism intensity can effectively improve CRF and cardiovascular function of postmenopausal women, and reduce the risk of CVD.

            GW33-e0442
            Chinese doctors’ awareness and practice on the medication adherence in hypertensive patients: a questionnairebased study

            Tao Liu, Xiexiong Zhao, Xiaogang Li, Weihong Jiang

            Department of Cardiovascular Medicine, The Third Xiangya Hospital, Central South University, Changsha, China (mainland)

            OBJECTIVES Medication adherence refers to the patient’s medication behavior is consistent with the doctor’s requirements. Poor medication compliance is one of the main influencing factors to achieve the goal of blood pressure. There are few studies about medication adherence in hypertensive patients in China, and most of the researchers focused on exploring the status and influencing factors of patients’ medication adherence such as gender, age, type of medications, number of medications, and so on, but seldom on doctors’ awareness and practice in this regard. We aimed to investigate the current situation and influencing factors of Chinese doctors’ awareness and practice on medication adherence in hypertensive patients.

            METHODS We formulated a questionnaire and used an online platform to conduct a questionnaire survey on Chinese doctors. Through the analysis, we obtained an overall cognitive or practical score from 0 to 50 and explored the influencing factors of Chinese doctors’ awareness and practice of medication adherence through univariate analysis and multivariate analysis. Spearman correlation coefficient method was used to analyze the correlation between cognitive scores and practical scores.

            RESULTS A total of 236 valid questionnaires were collected. The average cognitive scores of the total study population, 186 physicians and 122 cardiologists were 29.79±8.78, 31.04±8.43, and 34.25±7.29, respectively. The average practical scores of the total study population, 186 physicians and 122 cardiologists were 39.42±7.13, 40.46±6.16, and 41.55±6.01, respectively. Doctors with more professionalism, higher professional titles, and higher education tended to have better awareness and practice (P<0.05). And there was a significant correlation between doctors’ awareness and practice of medication adherence (R=0.682, P=0.000). Chinese doctors have many misunderstandings and deficiencies on awareness and practice of medication adherence.

            CONCLUSIONS Chinese doctors have insufficient awareness and practice of medication compliance in hypertensive patients, related to doctor’s education, professional title, and major.

            CARDIAC REHABILITATION
            GW33-e0055
            Effects of continuous management on anxiety and depression after pacemaker implantation: thoughts in the post-epidemic era

            Jing Zheng1, Yi Zhuge2, Dongjian Chai1, Yu Jin1, Wenjun He1, Yumei Wang1, Deling Zu1, Keyun Cheng1

            1Department of Cardiology, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People`s Hospital

            2Faculty of Medicine, Quzhou Technology College

            OBJECTIVES Pacemaker implantation is the main treatment for bradyarrhythmia, but perioperative anxiety and depression might affect the prognosis, especially in the post-pandemic era. There are few reports on the clinical application of continuous management mode. We investigated the effect of continuous management on postoperative mental improvement in patients with pacemaker implantation.

            METHODS In this prospective, single-center, single-blind randomized clinical trial, a total of 140 patients with dual chamber permanent pacemaker implantation were included, and randomly divided into conventional management group (control group) and continuous management group (study group). The mental status were evaluated by self-rating depression scale (SDS) and self-rating anxiety scale (SAS) before the operation, 4 weeks and 12 weeks after the operation respectively.

            RESULTS A total of 137 patients finished the whole follow-up, including 67 in the control group and 70 in the study group. Of these, 72 (52.6%) were female, and the mean age was 66.0 (IQR: 62.0–72.0) years. In terms of preoperative mental status, there were 87 (63.5%) cases with mild to moderate depression, while 63 (46.0%) with mild to moderate anxiety. Compared with the control group, among those in the study group, SDS standard scores of 55 (IQR: 47.2–59.0) before operation decreased to 45 (IQR: 38.0–50.0) at 4 weeks and 36.5 (IQR: 32.0–43.5) at 12 weeks after operation. Meanwhile, SAS standard score of 48 (IQR: 38.0–58.0) before operation decreased to 42 (IQR: 36.0–52.0) at 4 weeks and 36 (IQR: 31.0–40.0) at 12 weeks after operation. Additionally, at 4 weeks after operative, the SDS standard scores scored 8 (IQR: 4.2–13.0) points lower than baseline and the SAS standard scores scored 6 (IQR: 3.0–9.0) points lower in the study group. At 12 weeks after operative, the SDS standard scores scored 15 (IQR: 11.0–18.0) points lower than baseline and the SAS standard scores scored 13 (IQR: 9.0–26.0) points lower in the study group. Compared with the control group, the postoperative SAS and SDS standard scores decreased more significantly from baseline in the study group (all P<0.005).

            CONCLUSIONS Anxiety and depression are common in patients with pacemaker implantation, which needs more attention especially in the post-epidemic era. The continuous management is a feasible and promising management mode, which is worth recommending in improving patients’ mental status after operation.

            GW33-e0411
            Study on current status and influencing factors of exercise adherence in home-based cardiac rehabilitation in patients with coronary artery disease

            Wen Guo1, Ting Zhou2, Liyuan Tao3, Hongling Chu3, Wei Zhao1,4

            1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research

            2Department of Medical Psychology, The School of Health Humanities, Peking University

            3Clinical Epidemiology Research Center, Peking University Third Hospital

            4Medical Examination Center, Peking University Third Hospital

            OBJECTIVES Applying the theory of planned behavior to investigate the exercise adherence behavior and factors influencing home-based cardiac rehabilitation in patients with coronary artery disease.

            METHODS From April 2021 to October 2021, 303 patients with coronary artery disease who visited and followed up at the Peking University Third Hospital were recruited by convenience sampling. The Physical Activity Rating Scale (PARS-3) was used to measure the physical activity level of patients. Patients’ adherence was evaluated by comparing it with the recommended physical activity level of guidelines. A questionnaire based on the theory of planned behavior with exercise planning and self-regulation added was used to investigate the factors influencing exercise adherence. Logistic regression was used to analyze the influence of each factor on exercise adherence.

            RESULTS 36% (109/303) of patients had poor exercise adherence. Logistic regression analysis found that attitude (OR=6.271, 95% CI 2.855–13.773, P<0.05), subjective norm (OR=4.492, 95% CI 2.277–8.865, P<0.05), self-regulation (OR=3.678, 95% CI 1.778–7.606, P<0.05), and exercise planning (OR=1.980, 95% CI 1.026–3.821, P<0.05) had a statistically significant effect on promoting home exercise adherence.

            CONCLUSIONS The overall exercise adherence of home-based cardiac rehabilitation needs to be improved in patients with coronary artery disease. Enhancing the attitude, subjective norm, exercise planning, and self-regulation of patients can promote home exercise adherence.

            GW33-e0513
            Effect of enhanced external counterpulsation therapy on left ventricular strains: a prospective cohort study

            Ling Xu1, Shaomin Chen1, Yang Yu1, Wei Zhao1,2, Ming Cui1

            1Department of Cardiology, Peking University Third Hospital; NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing 100191, China

            2Physical Examination Center, Peking University Third Hospital, Beijing 100191, China

            OBJECTIVES Enhanced external counterpulsation (EECP) is currently a safe, effective treatment for coronary heart disease (CHD). However, its effect on cardiac systolic function has not been elucidated yet. Three-dimensional speckle tracking echocardiography (3D-STE) is more sensitive and comprehensive to evaluate cardiac function. However, there is currently no study to evaluate the effect of EECP on systolic function through 3D-STE. Here, we aimed to evaluate the effect of EECP on the cardiac systolic function through 3D-STE.

            METHODS Totally, forty patients with CHD after incomplete revascularization (IR) participated in the study. Twenty subjects chose the treatment protocol of standard course of EECP combined with drug therapy (EECP group) and the other twenty chose drug therapy (control group). All subjects underwent 3D-STE, transthoracic echocardiography (TTE) examinations at baseline, after 18 hours of treatment (at 3–4 weeks of follow-up for control group) and 35 hours of treatment (at 7 weeks of follow-up for control group).

            RESULTS After 35 hours of EECP treatment, the myocardial strain parameters, including twist (6.2 (3.9, 11.9) vs. 3.0 (1.4, 5.9), P=0.013) and torsion (1.2 (1.0, 1.9)°/cm vs. 0.7 (0.6, 1.0)°/cm, P=0.002) improved significantly, and were significantly better than those in the control group. There were no significant differences in any of the indicators from baseline at the 18-hour follow-up point.

            CONCLUSIONS For patients with CHD after IR, the EECP can significantly increase twist and torsion values, suggesting that EECP can effectively improve cardiac systolic function in such patients, which might be helpful for clinical application of EECP.

            GW33-e0551
            Cardiac rehabilitation for heart failure with preserved ejection fraction exercise capability, ventilation efficiency, quality of life, systolic and diastolic function: a systematic review and meta-analysis

            Qian Luo, Qiuheng Wang, Yuqin Shen

            Department of Cardiac Rehabilitation, Tongji Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China

            OBJECTIVES Cardiac rehabilitation can significantly improve physical function and prognosis in heart failure with reduced ejection fraction (HFrEF), but there is little evidence of its effect on heart failure with preserved ejection fraction (HFpEF). Therefore, this study conducted a meta-analysis on randomized controlled trial (RCT) to evaluate the effects of cardiac rehabilitation on the exercise capacity, ventilation efficiency, and quality of life, cardiac systolic and diastolic function of HFpEF.

            METHODS Cochrane library, PubMed, Embase and Web of Science were searched for published RCT researchs on cardiac rehabilitation on HFpEF, forming a database dating till May 2022. Based on inclusion and exclusion criterias, 586 patients were included in the meta-analysis.

            RESULTS Compared with the control group, meta-analysis showed improvement in exercise capability after treatment in the cardiac rehabilitation group [6-minute walk distance (6MWD): weight mean difference (WMD): 35.42, 95CI% 12.34 to 58.50, P=0.003, I2=0%; peak oxygen uptake (peakVO2): WMD: 2.80, 95CI% 2.09 to 3.51, P<0.00001, I2=0%; anaerobic threshold oxygen uptake (VO2AT): WMD: 1.93, 95CI% 0.66 to 3.20, P=0.003, I2=72%; exercise test duration: standard weight mean difference (SWMD): 0.62, 95CI% 0.34 to 0.91, P<0.0001, I2=0%], improvement in quality of life [minnesota living heart failure questionnaire (MLHFQ): WMD: – 11.76, 95CI% −16.64 to −6.88, P<0.00001, I2=0%], improvement in systolic function (left ventricular ejection fraction (LVEF): WMD: 1.79, 95CI% 0.63 to 2.94, P=0.002, I2=47%], partial improvement in diastolic function [E/E′ ratio: WMD: −2.33, 95CI% −2.96 to −1.70, P<0.00001, I2=62%, while E/A ratio: WMD: −0.04, 95CI% −0.11 to 0.03, P=0.25, I2=19%], and no improvement in ventilation efficiency [minute ventilation to carbon dioxide production slope (VE/VCO2): WMD: −1.12, 95CI% −2.74 to 0.50, P=0.18, I2=70%].

            CONCLUSIONS Cardiac rehabilitation had a positive effect on HFpEF, improving exercise capability, quality of life and cardiac systolic function, but had no effect on ventilation efficiency. As for the diastolic function, improvement was obvious in E/E′ ratio, while not in E/A ratio, thus entailing more relevant researchs to assess the effect of cardiac rehabilitation on the diastolic function.

            GW33-e0554
            Ratio of minute ventilation to carbon dioxide production slope to peak oxygen uptake in the prognostic assessment of chronic heart failure patients with diabetes

            Qian Luo, Bo Zhuang, Ting Shen, Yuqin Shen

            Department of Cardiac Rehabilitation, Tongji Hospital Affiliated to Tongji University, Tongji University School of Medicine, Shanghai, China

            OBJECTIVES To analyze the value of the ratio of carbon dioxide ventilation equivalent slope to peak oxygen uptake (VE/VCO2 slope/peakVO2 ratio) in predicting prognosis for chronic heart failure (CHF) patients with diabetes.

            METHODS A total of 158 CHF patients with diabetes who visited the Cardiac Rehabilitation Center of Tongji Hospital Affiliated to Tongji University and completed cardiopulmonary exercise test from March 2007 to December 2018 were enrolled in the study. The clinical data, cardiopulmonary exercise test results and followup information of patients were collected to explore the predictors of allcause mortality in CHF patients with diabetes.

            RESULTS The median follow-up time was 394 (153∼950) days. All-cause death occurred in 28 patients. Compared with the surviving patients, the peakVO2 of all-cause death patients were lower [12.95 (11.05∼14.66) mL min−1 kg−1 VS 14.66 (12.90∼16.40) mL min−1 kg−1, P=0.003], the VE/VCO2 slope [36.48 (34.65∼44.80) VS 34.70 (30.72∼37.50), P=0.001] and VE/VCO2 slope/peakVO2 ratio [3.01 (2.44∼4.10) VS 2.44 (1.89∼3.01), P<0.001] were higher, and the proportion of digoxin [12 (42.9%) VS 23 (17.7%), P=0.004], diuretic [19 (67.9%) VS 49 (37.7%), P=0.003] and spironolactone [17 (60.7%) VS 45 (34.6%), P=0.01] were higher. The areas under the receiver operating characteristic curve (AUC) of VE/VCO2 slope, peakVO2 and VE/VCO2 slope/peakVO2 ratio in predicting all-cause mortality in CHF patients with diabetes were 0.697(P=0.001), 0.682(P=0.003) and 0.711 (P<0.001) respectively; the optimal thresholds were >34.10 (HR=3.50, 95% CI 1.21 to 10.16, P=0.021), ;13.55 mL min−1 kg−1 (HR=0.39, 95% CI 0.18 to 0.87, P=0.021) and ;2.79 min kg mL−1 (HR=2.37, 95% CI 1.10 to 5.08, P=0.027) respectively; the sensitivities were 0.857, 0.679 and 0.607, and the specificity were 0.485,0.631 and 0.715, respectively. Multivariate Cox regression analysis showed that after adjusting related risk factors, VE/VCO2 slope/peakVO2 ratio was independent risk factor for allcause mortality in CHF patients with diabetes (HR=3.21, 95% CI 1.38 to 7.45, P=0.007).

            CONCLUSIONS VE/VCO2 slope/peakVO2 ratio could provide a predictive value for allcause mortality of CHF patients with diabetes.

            OTHERS

            OTHERS
            GW33-e0063
            A meta-analysis comparing different oral anticoagulation for the treatment of ventricular thrombus

            Qing Yang1, Liyun He2, Xin Quan3, Yan Liang4

            1National Clinical Research Center of Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            2Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

            3Echocardiographic Imaging Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            4Emergency Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College

            OBJECTIVES Patients with ventricular thrombus (VT) often require anticoagulation therapy and it remains unknown that whether non-vitamin K antagonist oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) is more effective. We aimed to compare the effectiveness and safety of NOACs and VKAs on the rate of thrombus resolution and clinical outcomes.

            METHODS MEDLINE, PUBMED, EMBASE, Cochrane Library, Web of Science, China National Knowledge Infrastructure Database and Wanfang Database, were searched up to November 22, 2021. Observational studies comparing the two agents in patients with VT were included. The primary outcome was the rate of thrombus resolution, and the secondary outcomes were bleeding, systemic embolism, stroke and all-cause death. Odds ratio (OR) and 95% confidential intervals (CI) were used for the pooled results.

            RESULTS Eighteen studies with 1755 participants (NOACs, n=607; VKAs, n=1148) were included. NOACs compared to VKAs had no insignificant difference in thrombus resolution (OR 0.92, 95% CI 0.68–1.23, P=0.558, I2=0%), bleeding (OR 0.85, 95% CI 0.54–1.35, P=0.496), systemic embolism (OR 0.77, 95% CI 0.41–1.43, P=0.401), stroke (OR 0.65, 95% CI 0.29–1.49, P=0.312) and all-cause death (OR 1.02, 95% CI 0.63–1.67, P=0.925). Subgroup analyses showed an insignificance in thrombus resolution between NOACs and VKAs according to baseline characteristics.

            CONCLUSIONS Our findings showed that NOACs were comparable to VKAs in thrombus resolution, as well as systemic embolism, stroke, bleeding events and all-cause death. And in different proportion of baseline LVEF, history of ischemic cardiomyopathy and combination with antiplatelet agents, the thrombus resolution among the two groups remained similar.

            GW33-e0109
            Discovery of novel desmoplakin mutations in carvajal syndrome: two case reports and literature review

            Xuanxuan Li

            Shijiazhuang Great Wall Hospital of Integrated Traditional Chinese and Western Medicine, Shijiazhuang

            OBJECTIVES Carvajal syndrome (CS) is an autosomal dominant (AD) or autosomal recessive (AR) genetic cardiocutaneous syndrome that associates with mutations in desmoplakin (DSP) gene and characterized by woolly hair, palmoplantar keratoderma (PPK) as well as left ventricular dilated cardiomyopathy (DCM).

            METHODS In this report, whole exome sequencing (WES) was conducted to examine the mutations of patients and the Sanger sequencing was applied to identify suspicious variants in their parents.

            RESULTS A 7 years old female patient was admitted to our center due to heart failure. She had curly hair at birth, developed palmoplantar keratosis at the age of 4 years, and heart failure at the age of 6 years. WES result suggested she carried a novel homozygous variant c.4597C>T(p.Q1533X) in DSP gene, whereas her parents carried the same variant in heterozygous state. Patient 2 presented with similar symptoms and carried a de novo heterozygous variants c.1853A>C(p.H618P) in DSP gene.

            CONCLUSIONS This report extended the spectrum of CS associated DSP gene mutations and provided important clinical references.

            GW33-e0351
            Predictive value of visceral fat-related and lipid-related indicators for metabolic syndrome in a Chinese population over 60 years of age: a cross-sectional study

            Jianqiang Xue1, Guohua Ni2, Yuping Liu1

            1Sichuan Academy of Medical Sciences and Sichuan People’s Hospital

            2Chengdu Jinjiang Sohome Comprehensive Outpatient Clinic

            OBJECTIVES To explore the predictive power of metabolic syndrome (Mes) for lipid-related parameters, including visceral adiposity index (VAI), lipid accumulation product (LAP), ambulatory arterial stiffness index (AI), plasma arteriosclerosis (AI), plasma arteriosclerotic index (AIP), and lipid composite index (LCI) in identifying Mes in the Chinese population over 60 years old.

            METHODS A total of 10,588 elderly Chinese subjects (aged ≥60 years) were enrolled in the community-based cross-sectional study from January 2018 to December 2020. Gender, age, height, body mass index and waist circumference were measured, serum samples were retained, and relevant metabolic indicators such as blood glucose and lipid levels were measured.

            RESULTS All seven parameters had a predictive value in identifying Mes based on the subject receiver operating characteristic curve (ROC) analysis. The statistical significance of the differences in the area under the curved (AUC) indicated that the AUC for LAP was the largest in both sexes (0.881 in men and 0.887 in women). The optimal critical value of LAP was 38.44 in men and 43.00 in women.

            CONCLUSIONS Visceral fat-related and lipid-related indicators in people over 60 years old have a predictive value for metabolic syndrome, and the predictive value of LAP is higher than that of VAI, TC/HDL-C, non-HDL-C, AI, AIP, and LCI by sex.

            GW33-e0378
            Impairment of left ventricular function in the depressed Chinese miniature swine model by cardiovascular magnetic resonance feature-tracking

            Huihui Kong1, Cao Jiaxin1, An Jing2, Zhang Lijun3, He Yi1

            1Department of Radiology, Beijing Friendship Hospital, Capital Medical University

            2Siemens Shenzhen Magnetic Resonance, MR Collaboration NE Asia

            3Department of Radiology, Beijing Anzhen Hospital, Capital Medical University

            OBJECTIVES Depression increases the risk of cardiovascular disease and an independent predictor of worse cardiovascular outcomes. Few studies have examined the relationship between depression and left ventricular (LV) alterations using cardiovascular magnetic resonance feature-tracking (CMR-FT). So, the aim of this study was to investigate the effect of depression on LV systolic function by CMR-FT.

            METHODS Seven anaesthetized, healthy Chinese Miniature swine were completed basic data and CMR scan baseline and after 14 days of depression modeling. The behavioral tests, including open-Field Test (OFT), sucrose Preference Test (SPT), the time to intake a certain amount of food and suger were carried out to test the depression models. CMR cine images were acquired and CVI software was utilized to analyze global longitudinal strain (GLS), global circumferential strain (GCS) and global radial strain (GRS). Besides, late gadolinium enhancement (LGE) imaging detected myocardial infarction and/or scar.

            RESULTS The decrease of Open-Field Test, sucrose Preference Test, extension of time to intake a certain amount of food and suger compared with baseline indicated a successful modeling of depressed swine. There was no significant difference in LV end diastolic volume (LVEDV), LV end systolic volume (LVESV), LV ejection fraction (LVEF), LV end diastolic myocardial mass (LVMASSED) and cardiac output (CO) before and after modeling. For LV global strain parameters, after the modeling, it showed a downward trend in GRS (25.35±6.9% vs 22.86±6.4%, P=0.021), GCS (−16.71±4.2% vs −14.78±2.3%, P=0.043), GLS (−17.66±2.9% vs −14.53±2.5%, P=0.056) and GRS, GCS were significantly reduced after modeling compared with baseline.

            CONCLUSIONS Depression has a tendency to lead to LV early systolic dysfunction in especial LV global circumferential strain and global radial strain.

            GW33-e0620
            Characterization of an aging-based diagnostic gene signature and molecular subtypes with diverse immune infiltrations in HF

            Shengnan Li1, Yandan Wu2

            1Department of Cardiology, Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, China

            2Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, Jiangsu 210009, China

            OBJECTIVES Aging is a major risk factor for heart failure (HF). At present, the relationship between aging and heart failure is not completely clear. There is an urgent need to explore new diagnostic biomarkers, as well as molecular subtypes and therapeutic targets.

            METHODS Gene expression data of HF and normal samples were collected from GEO database. Differential expression analysis was used to screen for HF-specific aging-related genes. Logistic regression analysis was proposed to construct a diagnostic model and ROC curves were used to assess the discriminatory ability. Consensus cluster analysis was used to classify the molecular subtypes based on aging. Immunity levels were estimated based on immune cell infiltration, immune checkpoints, and immune reaction gene-set. Aging molecular phenotype-relevant genes were then identified by Weighted gene co-expression network (WGCNA). The Connectivity Map (CMAP) database were used to predict small-molecule drugs.

            RESULTS We obtained six HF-specific aging-related genes based on differentially expressed genes between HF and normal samples. In addition, we identified 2 distinct subtypes of HF characterized by markedly different immune infiltration. A yellow-green module containing 321 genes that were highly correlated with the subtypes in WGCNA was subsequently identified. On the basis of the differentially expressed genes between HF and normal samples, we used the CMAP database to explore small molecule drugs that could be used as therapeutic agents.

            CONCLUSIONS Our study evaluated different immune cell infiltrations in HF and normal samples and identified different aging-related subtypes, which provide more individualized treatment options and prognostic predictions for HF patients. Small molecule drugs were discovered that may be potentially useful in treating patients with HF.

            GW33-e0635
            Relationship of altmetric metrics to science communication for high-impact clinical and cardiovascular publications: the era of social media

            Haixu Yu1, Weijia Li2, Wei Liu1

            1Department of Cardiology, Beijing Jishuitan Hospital, Beijing 100035, China

            2School of Journalism and communication, Nankai University, Tianjin 300350, China

            OBJECTIVES The relationship between science communication on social media and impact on citation is controversial. The Altmetric attention score (AAS) is a qualitative metric that is complementary to traditional metrics, such as impact factors or citation counts. We would explore the association between AAS and traditional bibliometric metrics among high-impact clinical and cardiovascular publications in 2018.

            METHODS The most-cited articles published in the top 10 highest Web of Science (WOS) Impact Factor journals (according to Journal Citation Reports 2020: category “Medicine, General & Internal” and “Cardiac & Cardiovascular systems”) in 2018 were included. The 3-year citations, AAS, and associated social media impact for each article were collected using WOS and AAS calculator. Descriptive statistics and Spearman rank correlation analyses were determined using the SPSS software. Bibliometric data from total articles were analyzed using the VOS viewer.

            RESULTS A total of 100 articles were published in this study period, including 34 (34%) original research, 31 (31%) reviews, and 23 (23%) guidelines or scientific statements. AAS (r=0.353, P<0.01) and Tweets (r=0.305, P<0.01) were significantly positively correlated with citation number. News outlets, Twitter, and blogs were the most weighted variables correlated with AAS. Research hot keywords focused on myocardial infarction, guidelines/scientific statements, sudden cardiac death, hypertension, and open-label/randomized controlled trials.

            CONCLUSIONS Results of this cross-sectional study showed moderate correlation between AAS and citation rates. Further science dissemination strategy on social media and online platform may beneficial for impact and citations.

            GW33-e0770
            Analysis of differentially expressed genes between paroxysmal and persistent atrial fibrillation

            Wenhui Wang1, Zhongping Ning2, Xinming Li3

            1Tongji University School of Medicine, Shanghai 200082, China

            2Department of Cardiology, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China

            3Shanghai Pudong New Area Center for Disease Control and Prevention, Shanghai 200136, China

            OBJECTIVES Comparative studies of differentially expressed genes (DEGs) between paroxysmal and persistent atrial fibrillation (PAF and PsAF) patients are scarce. This study aimed to analyze the differentially expressed long noncoding RNAs and messenger RNAs (DELncRNAs and DEmRNAs) in PAF and PsAF patients and explored the novel AF-related molecular mechanisms.

            METHODS Two target datasets about paroxysmal and persistent atrial fibrillation patients (GSE75092 and GSE113013) were downloaded and further analyzed from the Gene Expression Omnibus database by R software. Upregulated and downregulated differentially expressed genes (DEGs) and the co-expressed differentially expressed genes (co-DEGs) of the two datasets were identified, of which enrichment analyses and protein-protein interaction network construction were performed.

            RESULTS A total of 127 DELncRNAs and 321 DEmRNAs were screened in GSE75092; while 46 DELncRNAs and 64 DEmRNAs were screened in GSE113013. We further identified 8 co-DEGs in the overlap between the two datasets on Venn Diagram, which comprised 3 LncRNAs and 5 mRNAs. The GO analyses of GSE75092-DEGs showed that the top 5 biological processes were mainly enriched in response to virus (P<0.001), positive regulation of cytokine production (P<0.001), defense response to virus (P<0.001), nuclear transport (P=0.004) and nucleocytoplasmic transport (P=0.009). The cellular component category was mainly enriched in focal adhesion (P=0.042) and cell-substrate junction (P=0.042). The GO analysis of GSE113013-DEGs showed that no significant functions were enriched in any category. And two identical pathways, influenza A and adrenergic signaling in cardiomyocytes, were found in the KEGG analysis of the DEGs between the two datasets. In addition, the protein-protein interaction network of DEGs was constructed while no common hub genes were found between the PPI modules of the two datasets.

            CONCLUSIONS Multiple DEGs were found in patients with either paroxysmal or persistent AF, and their functions were mainly enriched in metabolism and inflammation-related signaling pathways. The antiviral defense mechanism of PAF was an exciting difference we found.

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            Journal
            CVIA
            Cardiovascular Innovations and Applications
            CVIA
            Compuscript (Ireland )
            2009-8782
            2009-8618
            October 2022
            October 2022
            : 7
            : s1
            : C1-C104
            Article
            cvia.2022.0015
            10.15212/CVIA.2022.0015
            9321612b-e513-499b-9912-456148336f52
            Copyright © 2022 Cardiovascular Innovations and Applications

            This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 Unported License (CC BY-NC 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See https://creativecommons.org/licenses/by-nc/4.0/.

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            General medicine,Medicine,Geriatric medicine,Transplantation,Cardiovascular Medicine,Anesthesiology & Pain management

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