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      Current Outcomes after Revascularization for Coronary Very Late Stent Thrombosis



            Objective: Limited data are available regarding current outcomes after revascularization for angiographically confirmed very late stent thrombosis (VLST). Therefore, this study investigated the current outcomes of patients with VLST and the risk factors for major adverse cardiovascular events (MACE).

            Methods: Consecutive patients who underwent revascularization for angiographically confirmed VLST between January 2014 and January 2016 were enrolled in this study. The patients were divided into two groups according to the occurrence of MACE during follow-up. The clinical and interventional parameters between groups were compared.

            Results: A total of 564 patients with an average age of 61.61 ± 10.71 years were enrolled. Eight patients died during hospitalization. MACE occurred in 100 patients after a mean follow-up of 620 days. The total MACE rate was 35.46%, and Kaplan-Meier survival analysis indicated an estimated MACE-free survival rate of 22%. Multivariable Cox regression analysis revealed that left ventricular ejection fraction and peak troponin I at VLST onset were independent predictors of MACE.

            Conclusions: Long-term outcomes after revascularization for VLST remained unfavorable. Left ventricular ejection fraction and peak troponin I at the onset of VLST were independent risk factors for poor prognosis.

            Main article text


            Percutaneous coronary intervention (PCI) is currently the primary treatment for acute coronary syndrome (ACS), one of the most serious threats to human health worldwide [1]. Very late stent thrombosis (VLST), defined as thrombosis occurring more than 1 year after stent implantation, is a rare but catastrophic complication of PCI that presents primarily as acute myocardial infarction (MI) or even sudden cardiac death [2]. The mechanism underlying VLST is complicated. VLST risk factors include patient- and lesion-related factors, procedural and stent-related factors, and pharmacotherapy-related factors [3]. Recent studies have suggested that: hypersensitivity and inflammation reactions, changes in shear stress, plaque rupture, and neointimal erosion may be involved in the development of VLST [3].

            Emergent revascularization combined with optimized drug therapies have become the standard strategy for patients with VLST [4]. However, studies have provided limited information regarding the outcomes of patients with angiographically confirmed VLST as therapies have improved [5]. Therefore, we conducted a two-center registry study enrolling consecutive patients presenting with definite VLST, to identify the current incidence of major adverse cardiac events (MACE) after revascularization for VLST and the determinants of these events.


            Patient Population

            All consecutive patients with angiographically confirmed very late stent thrombosis (according to the Academic Research Consortium (ARC) stent thrombosis definitions [6]) at the First Hospital of Jilin University and First affiliated Hospital of Shantou University between January 1, 2014, and January 1, 2016, were enrolled (ClinicalTrials.gov: NCT03491891). This study was approved by the Institutional Review Board of the First Hospital of Jilin University (No. 2013256). All participants provided informed consent.

            VLST was defined according to the ARC definition [6]. Coronary angiograms of both procedures (index PCI and PCI for VLST) were reviewed by two experienced interventional cardiologists independently. A consensus was established between reviewers or, in the event of divergent results, by a third reviewer.

            Data Collection

            Clinical follow-up information was obtained from hospital records or telephone interviews with the patients and their relatives every 3 months until 3 years after discharge. MACE were defined as nonfatal MI, recurrent of stent thrombosis, target vessel revascularization (TVR), heart failure requiring hospitalization, and all-cause death. Recurrent stent thrombosis was defined according to the ARC stent thrombosis definitions [6]. The diagnosis of myocardial infarction (MI) conformed to the 2012 ESC global definition of acute MI. TVR was defined as ischemia-driven PCI or coronary artery bypass grafting (CABG) performed in the same vessel as the index PCI.

            Statistical Analysis

            Data are summarized as numbers (and percentages) for categorical variables. Continuous variables are expressed as mean ± SD. Qualitative data were compared with chi-square or Fisher’s exact tests, whereas quantitative data were compared with the Mann-Whitney U test. All tests were two-sided and had a significance level of 0.05. Predictors of MACE were assessed with Cox regression, with univariate and multivariate analyses. Kaplan-Meier survival analyses were used to demonstrate the cumulative incidence of MACE and estimate MACE-free survival. Various correction methods were applied according to specific situations. Statistical analysis was performed in Statistical Package for Social Sciences version 23 (SPSS, Chicago, IL, USA).


            Patient Characteristics

            In this follow-up study, 564 patients with an angiographically confirmed VLST were enrolled. The clinical characteristics of the patients are shown in Table 1. Angiographic and interventional parameters for both procedures are shown in Table 2. A total of 428 men (75.89%) were included in this study, and the average age was 61.61 ± 10.71 (29–91) years. The mean time from the index PCI to the occurrence of VLST was 1678.91 ± 1167.22 (365–5247) days. The clinical diagnosis for the index PCI was acute MI in 394 (69.86%) patients. Most patients (n = 546, 96.81%) had acute MI and underwent emergent PCI. Of these, 12 (2.12%) patients presented with cardiac arrest, and 18 (3.19%) patients had complications of cardiogenic shock. VLST occurred most frequently in the left anterior descending artery (LAD) (LAD, 51.06%; right coronary artery, 32.62%; circumflex, 16.31%). VLST was associated with a first-generation drug-eluting stent (DES) in 442 patients (78.37%) and a second-generation DES in 122 (21.63%) patients. Additionally, 222 (39.36%) patients were taking clopidogrel at the time of VLST, 302 (53.55%) patients were taking aspirin, and 218 (38.65%) patients were undergoing dual antiplatelet therapy (DAPT).

            Table 1

            Patient Characteristics.

            VariablesOverall (n = 564)Event free (n = 364)With event (n = 200)P value
            Baseline characteristics
             Age (years)61.61 ± 10.7160.18 ± 10.4264.23 ± 10.00.001
             Male, n (%)428 (75.89%)282 (77.47%)146 (73%).401
             BMI (kg/m2)24.74 ± 2.7324.96 ± 2.8124.33 ± 2.54.070
             History of HT, n (%)308 (54.61%)192 (34.04%)116 (58%).072
             History of DM, n (%)210 (37.23%)122 (33.52%)88 (44%).397
             History of HL, n (%)74 (13.12%)44 (12.09%)30 (15%).081
             Current drinking, n (%)82 (14.54%)48 (13.19%)34 (17%).488
             Current smoking, n (%)336 (59.57%)206 (56.596%)130 (65%).379
             History of MI, n (%)384 (68.09%)250 (68.68%)134 (67%).379
             History of HF, n (%)62 (10.99%)14 (3.85%)48 (24%).772
             AMI as initial diagnosis, n (%)394 (69.86%)256 (70.33%)138 (69%).401
             STEMI as initial diagnosis, n (%)268 (47.52%)158 (43.41%)110 (55%).062
             Duration to occurrence of VLST (days)1678.91 ± 1165.141515.21 ± 1105.501976.84 ± 1222.16.001
             Cardiac arrest, n (%)12 (2.13%)6 (1.65%)6 (3%).484
             Cardiac shock, n (%)18 (3.19%)6 (1.65%)12 (6%).669
             Systolic pressure (mmHg)132.74 ± 20.85133.46 ± 19.57131.43 ± 23.04.623
             Diastolic pressure (mmHg)78.35 ± 11.3678.86 ± 11.4477.41 ± 11.22.572
             Heart rate (bpm)76.27 ± 14.2275.13 ± 14.4478.35 ± 13.63.019
             Killip ≥2, n (%)80 (14.18%)22 (6.04%)58 (29%)<0.001
            Laboratory tests
             Peak troponin I (ng/mL)42.57 ± 83.9833.04 ± 71.0959.91 ± 101.54.023
             WBC (×109/L)9.54 ± 3.459.14 ± 3.0210.28 ± 4.03.026
             RBC (×1012/L)4.62 ± 0.584.65 ± 0.594.57 ± 0.55.143
             HGB (g/L)140.48 ± 17.49141.63 ± 17.58138.39 ± 17.23.090
             Platelets (×109/L)213.73 ± 64.56213.32 ± 64.86214.47 ± 64.34.685
             TC (mmol/L)4.38 ± 1.334.38 ± 1.264.37 ± 1.45.716
             LDL (mmol/L)2.71 ± 1.052.71 ± 1.072.73 ± 1.01.787
             HDL (mmol/L)1.12 ± 0.261.12 ± 0.271.12 ± 0.25.843
             TG (mmol/L)2.04 ± 1.292.08 ± 1.381.96 ± 1.11.977
             Fasting blood glucose (mmol/L)7.17 ± 3.127.00 ± 3.187.49 ± 2.99.051
             HbA1c (%)6.54 ± 1.836.50 ± 1.926.61 ± 1.64.269
             Fibrinogen (g/L)3.37 ± 0.963.33 ± 0.933.45 ± 1.00.193
             eGFR (mL/min/1.73 m2)94.22 ± 21.4397.34 ± 18.3088.54 ± 25.32.001
             LVEF (%)51.21 ± 8.9553.44 ± 7.2547.14 ± 10.27<0.001
            Medications before VLST
             Aspirin, n (%)302 (53.55%)200 (54.95%)102 (51%).834
             Clopidogrel, n (%)222 (39.36%)154 (42.31%)68 (34%).525
             Statins, n (%)258 (45.74%)178 (48.9%)80 (40%).214
            Discharge medications (n = 548, 364, 184 per group)
             Aspirin, n (%)498 (90.88%)340 (93.41%)158 (85.87%).001
             Clopidogrel, n (%)268 (47.52%)182 (50%)86 (46.74%).041
             Ticagrelor, n (%)126 (22.34%)80 (21.98%)46 (25%).610
             DAPT, n (%)374 (66.31%)248 (68.13%)126 (68.48%).954
             Statins, n (%)460 (81.56%)306 (84.07%)154 (83.70%).937
             ACEI/ARB, n (%)292 (51.77%)202 (55.49%)90 (48.91%).366
             β blockers, n (%)336 (59.57%)242 (66.48%)94 (51.09%).302

            ACEI, angiotensin converting enzyme inhibitor; AMI, acute myocardial infarction; ARB, angiotensin receptor inhibitor; CABG, coronary artery bypass graft; DAPT, dual antiplatelet therapy; EES, everolimus eluting stent; eGFR, estimated glomerular filtration rate; HDL, high density lipoprotein; HGB, hemoglobin; LAD, left anterior descending artery; LCX, left circumflex artery; LDL, low density lipoprotein; LM, left main; LVEF, left ventricular eject fraction; MI, myocardial infarction; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; RCA, right coronary artery; SES, sirolimus eluting stent; TCL, total cholesterol; TG, triglyceride; TIA, transient ischemic attack; TIMI, thrombolysis in myocardial infarction; WBC, white blood cell; VLST, very late stent thrombosis; ZES, zotarolimus eluting stent.

            Table 2

            Angiographic and Interventional Characteristics of both Procedures.

            VariablesOverall (n = 564)Event free (n = 364)With event (n = 200)P value
            Parameters during index PCI
             No. of diseased vessels, n (%)2.20 ± 0.802.12 ± 0.812.34 ± 0.78.025
            PCI related vessel
             LAD, n (%)288 (51.06%)186 (51.10%)102 (51%).987
             LCX, n (%)92 (16.31%)62 (17.03%)30 (15%).658
             RCA, n (%)184 (32.62%)116 (31.87%)68 (34%).631
             Chronic total occlusion, n (%)32 (5.67%)22 (6.04%)10 (5%).005
             Severe calcification, n (%)14 (2.48%)8 (2.20%)6 (3%).989
             Severe tortuosity, n (%)12 (2.13%)6 (1.65%)6 (3%).666
             Ostial lesion, n (%)30 (5.32%)24 (6.59%)6 (3%).761
             Proximal lesion, n (%)406 (71.99%)260 (71.43%)146 (73%).198
             Bifurcation lesion, n (%)128 (22.70%)84 (23.08%)44 (22%).836
             Visual thrombosis, n (%)30 (5.32%)22 (6.04%)8 (4%).464
             Vessel dilation, n (%)8 (1.42%)4 (1.10%)4 (2%).349
             Two stent technique during index PCI, n (%)12 (2.13%)8 (2.20%)4 (2%).912
             Aspiration during procedure, n (%)36 (6.38%)28 (4.96%)8 (4%).912
            Stent type during index PCI
             SES, n (%)442 (78.37%)274 (75.27%)168 (84%).134
             ZES, n (%)62 (11.00%)46 (12.64%)16 (8%).234
             EVS, n (%)62 (11.00%)44 (12.09%)18 (9%).428
             Stent overlap, n (%)178 (31.56%)108 (29.67%)70 (35%).357
             Post-dilation, n (%)126 (22.34%)86 (23.63%)40 (20%).357
             Minimum stent diameter (mm)2.89 ± 0.372.91 ± 0.382.84 ± 0.33.130
             Maximum stent diameter (mm)2.99 ± 0.373.03 ± 0.382.93 ± 0.33.042
             Total stent length (mm)39.63 ± 19.4738.62 ± 20.0441.47 ± 18.34.026
             Release pressure (atm)13.46 ± 2.7313.62 ± 2.8813.16 ± 2.42.171
             No. of stents per artery1.42 ± 0.641.40 ± 0.641.44 ± 0.66.579
            Parameters during PCI for VLST
             Spontaneous recanalization after AMI, n (%)228 (40.43%)146 (40.11%)82 (41%)<0.001
             Aspiration during procedure, n (%)102 (18.09%)60 (16.48%)42 (21%).884
            Revascularization therapy
             Angioplasty only, n (%)212 (37.59%)126 (34.62%)86 (43%).346
             Re-stenting, n (%)336 (59.57%)224 (61.54%)118 (54%).218
             CABG, n (%)20 (3.55%)14 (3.85%)6 (3%).975
            Stent type during re-stenting
             SES (n = 334, 226, 108 in each group)208 (62.28%)134 (59.29%)74 (68.52%).713
             ZES (n = 334, 226, 108 in each group)80 (23.95%)60 (26.55%)20 (18.52%).250
             EVS (n = 334, 226, 108 in each group)46 (13.77%)32 (14.16%)14 (12.96%).255

            AMI, acute myocardial infarction; CABG, coronary artery bypass graft; CABG, coronary artery bypass graft; EES, everolimus eluting stent; LAD, left anterior descending artery; LCX, left circumflex artery; PCI, percutaneous coronary intervention; RCA, right coronary artery; PCI, percutaneous coronary intervention; SES, sirolimus eluting stent; ZES, zotarolimus eluting stent.

            Parameters of Emergent PCI for VLST

            The parameters for emergent PCI for VLST are listed in Table 2. Spontaneous reperfusion occurred in 228 patients (40.43%), and thrombus aspiration was performed in 102 (18.09%) patients. Of these, 184 patients (32.62%) were treated with balloon angioplasty only, 24 patients (4.26%) were treated with drug coated balloons after balloon angioplasty, 332 patients (58.87%) underwent balloon angioplasty followed by implantation of an additional stent, and 20 patients (3.55%) underwent CABG after urgent coronary angiography.

            Outcomes of Patients with VLST

            After a median follow-up of 620 (249–1281) days, MACE occurred in 200 (35.46%) patients. Sixteen patients (2.8%) died of a cardiac cause during hospitalization. At the longest available follow-up, 24 of 40 deaths (60%) were cardiac in nature. The cumulative incidence of all-cause mortality and cardiac mortality was 3.7% and 2.1%, respectively, at 1 year; 7.2% and 5.1%, respectively, at 2 years; and 12.1% and 8.4%, respectively at 3 years. During the follow-up, heart failure requiring hospitalization occurred in 122 (21.63%) patients, 86 of whom (70.5%) had MI twice, and 70 (57.4%) of whom had LAD lesions. The cumulative incidence of heart failure requiring hospitalization at 1, 2, and 3 years was 15.6%, 20.7%, and 27.1%, respectively. A total of 44 (7.8%) cases of angiographically confirmed recurrent stent thrombosis were observed. The timing of definite recurrent stent thrombosis was subacute in two patients, late in 18 patients, and very late in 24 patients. The cumulative incidence of definite recurrent stent thrombosis at 30 days, and 1, 2, and 3 years was 0.4%, 3.8%, 6.8%, and 11.3%, respectively. Of note, recurrent stent thrombosis was the most common cause of MI (84%) during follow up. At the longest follow-up, TVR (including emergent PCI for recurrent stent thrombosis) was performed in 64 (11.35%) patients: 62 (96.88%) with repeated PCI and 2 (3.12%) with CABG. Twenty-four (37.5%) TVRs were associated with angioplasty only, 6 (9.38%) were associated with balloon angioplasty followed by drug coated balloons, and 32 (50%) were associated with additional DES implantation.

            At the longest available follow-up, continuous DAPT had been administered to 374 (68.25%) patients. In the remaining patients, aspirin or clopidogrel was taken at least 1 year after the occurrence of VLST, but no significant difference was observed between patients with versus without MACE. Moreover, no significant difference was found among revascularization strategies (angioplasty alone, 37.59%, P = 0.346; re-stent, 58.87%, P = 0.218; CABG, 3.55%, P = 0.975). Kaplan-Meier survival analysis indicated that the estimated MACE free survival during follow-up was only 22% (Figure 1). After adjustment in the Cox proportional hazard model, peak troponin I and left ventricular ejection fraction (LVEF) were found to be independent predictors of MACE (Table 3 and Supplementary Table S1).

            Next follows the figure caption
            Figure 1

            Kaplan–Meier Cumulative Major Adverse Cardiac Event (MACE)-Free Survival During Follow-Up.

            Table 3

            Multivariable Cox Regression Analysis of the Predictors of MACE.

            VariablesHR95%CIP value
            Killip ≥21.6750.999–2.801.051
            Peak troponin I1.0031.001–1.005.015

            eGFR, estimated glomerular filtration rate; LVEF, left ventricular eject fraction; WBC, white blood cell.


            This observational study in a large cohort of patients with definite VLST demonstrated that the clinical outcomes after revascularization remained unfavorable despite improvements in various revascularization strategies. Peak troponin I and LVEF were independent predictors of MACE in this group of patients.

            The rates of in-hospital mortality and long-term mortality observed in patients with VLST were similar to those previously reported (3% and 10%, respectively) [710]; hence, our findings suggested that no improvement was achieved in mortality during the past decade. The high incidence of heart failure was remarkable. More than one-fifth of patients had heart failure requiring hospitalization during the follow-up. Prior studies on the prognosis of patients with VLST have rarely paid substantial attention to readmission for heart failure [7, 8], although this complication is not rare among patients with VLST. Possible explanations for the high incidence of heart failure may include the following: first, patients who receive PCI for MI might be likely to develop stent thrombosis [11]; second, most patients with VLST have acute MI [12]; third, stented LADs are likely to develop VLST [13]. Currently, recurrent stent thrombosis and TVR have not been completely eradicated. In this study, the incidence of both events was lower than previously reported [7, 8], possibly because of progress in PCI technology and the application of more effective antiplatelet agents in recent years.

            Given the observational nature of the present study, the best available treatment for VLST could not be determined. Previous observational studies have reported varying results regarding the effects of angioplasty alone and re-stenting in patients with stent thrombosis [7, 10, 13, 14]. In this study, no significant difference in long-term outcomes was observed among revascularization strategies. Of note, intravascular ultrasound or optical coherence tomography may provide new insights into the treatment of patients with VLST [9], and randomized controlled trials are urgently needed to determine the optimal revascularization strategy for this group of patients. Moreover, controversy regarding the duration of DAPT after DES implantation persists. Previous studies have shown that prolonged DAPT may decrease ischemic events but increase bleeding events, without changing the overall prognosis [15]. Studies in patients with VLST have indicated that extending the duration of DAPT might improve overall prognosis [7]. However, in this study, all patients received standard antiplatelet therapy for more than 1 year after PCI. More than half the patients received aspirin at the onset of VLST, and nearly one-third of the patients received DAPT, yet VLST nonetheless occurred. Moreover, long-term antiplatelet therapy was not found to decrease the incidence of MACE in this study. The DAPT guidelines released in 2017 recommended shortening the duration of DAPT according to the DAPT risk score [16]. Hence, individualized anti-platelet therapy based on patient characteristics and the results of intravascular imaging might be favorable. Additionally, although univariable Cox regression analysis indicated that age, Killip ≥2, peak troponin I, WBC count, LVEF, and eGFR were possible predictors of MACE after VLST in this study, multivariable Cox regression analysis confirmed that the independent risk factors affecting the prognosis were LVEF and peak troponin I, thus potentially indicating diminished heart function after recurrence of myocardial infarction. Therefore, VLST prevention might be more important than treatment. Identifying potential high-risk patients with VLST and providing active intervention as early as possible might be a valuable strategy to avoid VLST. However, determining the pathogenesis underlying VLST is much more important. We have obtained serum samples from patients before and after the initial PCI, and hope to find additional clues regarding VLST pathogenesis.

            This study had several limitations. First, this study was an observational study, and the sample size was insufficient to allow for more specific subgroup analysis; second, because few patients underwent intravascular imaging, the effects of such imaging on prognosis were not determined; third, the observational nature of the present study did not enable the effects of different revascularization strategies on prognosis to be assessed.


            Long-term outcomes after revascularization for VLST remained unfavorable. LVEF and peak troponin I at VLST onset were independent risk factors for poor prognosis.

            Data Availability Statement

            Data will be made available if required.

            Ethics Statement

            The study was approved by our institute’s ethics committee (No. 2013-256). Written consent for submission and publication of this research was obtained from the patients.

            Author Contributions

            Yang Zheng, Xinxin Chen, and Xiang Wang conceived and designed the paper. Yunqing Hou, Yan Gu, and Muli Wu coordinated the data acquisition. Xiang Wang and Yang Zheng contributed to critical revision of the manuscript for important intellectual content and approved the final version of the manuscript. Xiang Wang and Xinxin Chen were responsible for the overall content of the article and data analysis.

            Conflicts of Interest

            The authors of this work have no conflict of interest to declare.

            Supplementary Material

            Supplementary material for this paper is available at https://cvia-journal.org/wp-content/uploads/2024/03/supplementary_table.pdf

            Citation Information


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            Author and article information

            Cardiovascular Innovations and Applications
            Compuscript (Ireland )
            03 May 2024
            : 9
            : 1
            : e951
            [1] 1Department of Cardiovascular Disease Center, First Hospital of Jilin University, Jilin University, Changchun, China
            [2] 2Department of Cardiovascular Disease Center, First Affiliated Hospital of Shantou University, Shantou University, Shantou, China
            [3] 3Department of Burns, First Hospital of Jilin University, Jilin University, Changchun, China
            [4] 4Pediatric Research Institute, Department of Pediatrics, University of Louisville, Louisville, KY, 40202, USA
            Author notes
            Correspondence: Xinxin Chen and Xiang Wang, No.1 Xinmin Ave, Changchun, Jilin 130021, China, Tel: +86-0431-8878-2417, E-mail: sskcxx@ 123456126.com ; jdwxiang123@ 123456jlu.edu.cn

            aYunqing Hou and Yan Gu contributed equally to this work.

            Copyright © 2024 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/.

            : 06 September 2023
            : 15 February 2024
            : 11 March 2024
            Page count
            Figures: 1, Tables: 3, References: 16, Pages: 9
            Funded by: Health Talent Project of Jilin Province
            Award ID: JLSWSRCZX2021
            Funded by: General Project of Natural Science Foundation of Jilin Province
            Award ID: YDZJ202201ZYTS013
            Funded by: National Natural Science Foundation Youth Program
            Award ID: 82200397
            The authors thank Ming Gao for assistance with statistical analysis. This work was supported partly by the Health Talent Project of Jilin Province (JLSWSRCZX2021 to Xiang Wang, China), the General Project of Natural Science Foundation of Jilin Province (YDZJ202201ZYTS013 to Xiang Wang, China), and the National Natural Science Foundation Youth Program (82200397 to Xiang Wang, China).
            Research Article

            General medicine,Medicine,Geriatric medicine,Transplantation,Cardiovascular Medicine,Anesthesiology & Pain management
            risk factors,very late stent thrombosis,prognosis


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