Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers

Cynthia A. James, Aditya Bhonsale, Crystal Tichnell, Brittney Murray, Stuart D. Russell, Harikrishna Tandri, Ryan J. Tedford, Daniel P. Judge, Hugh Calkins

Research output: Contribution to journalArticle

Abstract

Objectives This study sought to determine how exercise influences penetrance of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) among patients with desmosomal mutations. Background Although animal models and anecdotal evidence suggest that exercise is a risk factor for ARVD/C, there have been no systematic human studies. Methods Eighty-seven carriers (46 male; mean age, 44 ± 18 years) were interviewed about regular physical activity from 10 years of age. The relationship of exercise with sustained ventricular arrhythmia (ventricular tachycardia/ventricular fibrillation [VT/VF]), stage C heart failure (HF), and meeting diagnostic criteria for ARVD/C (2010 Revised Task Force Criteria [TFC]) was studied. Results Symptoms developed in endurance athletes (N = 56) at a younger age (30.1 ± 13.0 years vs. 40.6 ± 21.1 years, p = 0.05); they were more likely to meet TFC at last follow-up (82% vs. 35%, p < 0.001) and have a lower lifetime survival free of VT/VF (p = 0.013) and HF (p = 0.004). Compared with those who did the least exercise per year (lowest quartile) before presentation, those in the second (odds ratio [OR]: 6.64, p = 0.013), third (OR: 16.7, p = 0.001), and top (OR: 25.3, p < 0.0001) quartiles were increasingly likely to meet TFC. Among 61 individuals who did not present with VT/VF, the 13 subjects experiencing a first VT/VF event over a mean follow-up of 8.4 ± 6.7 years were all endurance athletes (p = 0.002). Survival from a first VT/VF event was lowest among those who exercised most (top quartile) both before (p = 0.036) and after (p = 0.005) clinical presentation. Among individuals in the top quartile, a reduction in exercise decreased VT/VF risk (p = 0.04). Conclusions Endurance exercise and frequent exercise increase the risk of VT/VF, HF, and ARVD/C in desmosomal mutation carriers. These findings support exercise restriction for these patients.

Original languageEnglish (US)
Pages (from-to)1290-1297
Number of pages8
JournalJournal of the American College of Cardiology
Volume62
Issue number14
DOIs
StatePublished - Oct 1 2013

Keywords

  • arrhythmogenic right ventricular dysplasia
  • cardiomyopathy
  • exercise
  • heart failure
  • penetrance
  • ventricular arrhythmias

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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