title: Exercise increases age-related penetrance and arrhythmic risk in arrhythmogenic right ventricular dysplasia/cardiomyopathy-associated desmosomal mutation carriers.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland. Electronic address: cjames7@jhmi.edu.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bhonsale
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Tedford
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.affiliation: Department of Medicine, Division of Cardiology, The Johns Hopkins University, Baltimore, Maryland.
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
mesh_terms: D000328:Adult; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D003896:Desmosomes / Q000235:genetics*; D004562:Electrocardiography; D015444:Exercise / Q000502:physiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009154:Mutation; D019683:Penetrance; D011446:Prospective Studies; D012307:Risk Factors
keywords: (stage C) heart failure; 2010 Revised Task Force Criteria; ARVD/C; CI; ECG; HF; ICD; IQR; OR; RV; TFC; VT/VF; arrhythmogenic right ventricular dysplasia; arrhythmogenic right ventricular dysplasia/cardiomyopathy; cardiomyopathy; confidence interval; electrocardiogram; exercise; heart failure; implantable cardioverter-defibrillator; interquartile range; odds ratio; penetrance; right ventricular; ventricular arrhythmias; ventricular tachycardia/ventricular fibrillation