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      Smoking aggravates ventricular arrhythmic events in non-ischemic dilated cardiomyopathy associated with a late gadolinium enhancement in cardiac MRI

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          Abstract

          Smoking is known to increase cardiovascular events, but the association and mechanisms between smoking and ventricular arrhythmic events in dilated cardiomyopathy (DCMP) are unknown. The purpose of this study is to investigate the hypothesis that smoking is associated with sudden cardiac death (SCD) and ventricular arrhythmia in DCMP patients. We enrolled 378 patients who underwent cardiovascular magnetic resonance imaging (cMRI) and were diagnosed with DCMP at two general hospitals in Korea. The clinical data and left ventricular late-gadolinium enhancement (LV-LGE) of all patients were analyzed according to being never-smokers or smokers. Smokers were more likely to be male than never-smokers, but there was no other clinical difference between them. Smokers had a greater LV-LGE ratio, and multi-segment involvement of LV-LGEs. Smoking and a low left ventricular (LV) ejection fraction were significant predictors of the presence of LV-LGEs even after adjusting for optimal medical therapy. In addition, smokers had a higher fatal ventricular arrhythmic (FVA; sustained ventricular tachycardia, and ventricular fibrillation) and FVA + SCD, and ex-smokers had a similar FVA to never-smokers during 44.3 ± 36.4 months of follow-up. Finally, smoking independently increased the FVA + SCD even after adjusting for the clinical variables and LV-LGE. Smoking is associated with a multi-segmental involvement of LV-LGE and increased FVA + SCD in DCMP patients when compared to never-smokers.

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          Fibrosis--a common pathway to organ injury and failure.

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            Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy.

            Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively). Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.
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              Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy.

              We studied the prognostic implications of midwall fibrosis in dilated cardiomyopathy (DCM) in a prospective longitudinal study. Risk stratification of patients with nonischemic DCM in the era of device implantation is problematic. Approximately 30% of patients with DCM have midwall fibrosis as detected by late gadolinium-enhancement (LGE) cardiovascular magnetic resonance (CMR), which may increase susceptibility to arrhythmia and progression of heart failure. Consecutive DCM patients (n = 101) with the presence or absence of midwall fibrosis were followed up prospectively for 658 +/- 355 days for events. Midwall fibrosis was present in 35% of patients and was associated with a higher rate of the predefined primary combined end point of all-cause death and hospitalization for a cardiovascular event (hazard ratio 3.4, p = 0.01). Multivariate analysis showed midwall fibrosis as the sole significant predictor of death or hospitalization. However, there was no significant difference in all-cause mortality between the 2 groups. Midwall fibrosis also predicted secondary outcome measures of sudden cardiac death (SCD) or ventricular tachycardia (VT) (hazard ratio 5.2, p = 0.03). Midwall fibrosis remained predictive of SCD/VT after correction for baseline differences in left ventricular ejection fraction between the 2 groups. In DCM, midwall fibrosis determined by CMR is a predictor of the combined end point of all-cause mortality and cardiovascular hospitalization, which is independent of ventricular remodeling. In addition, midwall fibrosis by CMR predicts SCD/VT. This suggests a potential role for CMR in the risk stratification of patients with DCM, which may have value in determining the need for device therapy.
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                Author and article information

                Contributors
                cby6908@yuhs.ac
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                23 October 2018
                23 October 2018
                2018
                : 8
                : 15609
                Affiliations
                [1 ]ISNI 0000 0001 2171 7754, GRID grid.255649.9, Department of Cardiology, College of Medicine, , Ewha Womans University, ; Seoul, Korea
                [2 ]ISNI 0000 0004 0470 5454, GRID grid.15444.30, Department of Radiology, Research Institute of Radiological Science, , Yonsei University College of Medicine, ; Seoul, Korea
                [3 ]ISNI 0000 0001 0840 2678, GRID grid.222754.4, Department of Biomedical Engineering, Medical College, , Korea University, ; Seoul, Korea
                [4 ]ISNI 0000 0004 0647 3052, GRID grid.415292.9, Division of Cardiology, Department of Internal Medicine, , Gangneung Asan Hospital, ; Gangneung, Republic of Korea
                [5 ]ISNI 0000 0001 2171 7818, GRID grid.289247.2, Department of Medicine, Graduate School, , Kyung Hee University, ; Seoul, Korea
                [6 ]ISNI 0000 0001 2171 7754, GRID grid.255649.9, Department of Radiology, College of Medicine, , Ewha Womans University, ; Seoul, Korea
                [7 ]ISNI 0000 0004 0439 4086, GRID grid.413046.4, Department of Cardiology, Internal medicine, , Yonsei University Health System, ; Seoul, Korea
                Author information
                http://orcid.org/0000-0001-9036-7225
                Article
                34145
                10.1038/s41598-018-34145-9
                6199322
                30353108
                75425093-3fba-4984-a14e-082a4e3011bd
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 16 May 2018
                : 10 October 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100003725, National Research Foundation of Korea (NRF);
                Award ID: NRF-2015R1C1A1A02037085
                Award ID: NRF-2014R1A1A1003699
                Award ID: NRF-2017R1A2B3003303
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100003625, Ministry of Health and Welfare (Ministry of Health, Welfare and Family Affairs);
                Award ID: HI16C0058
                Award ID: HI15C1200
                Award Recipient :
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