Exercise Increases Age-Related Penetrance and Arrhythmic Risk in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy–Associated Desmosomal Mutation Carriers

• Published in: Journal of the American College of Cardiology Vol. 62; no. 14; pp. 1290 - 1297
• Main Authors: James, Cynthia A., Bhonsale, Aditya, Tichnell, Crystal, Murray, Brittney, Russell, Stuart D., Tandri, Harikrishna, Tedford, Ryan J., Judge, Daniel P., Calkins, Hugh
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2013; Elsevier; Elsevier Limited
• Subjects: Adult; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - physiopathology; arrhythmogenic right ventricular dysplasia; Arrhythmogenic Right Ventricular Dysplasia - complications; Arrhythmogenic Right Ventricular Dysplasia - genetics; Arrhythmogenic Right Ventricular Dysplasia - physiopathology; Biological and medical sciences; Cardiac arrhythmia; Cardiac dysrhythmias; Cardiology; Cardiology. Vascular system; cardiomyopathy; Cardiovascular; Defibrillators; Desmosomes - genetics; Electrocardiography; exercise; Exercise - physiology; Female; Follow-Up Studies; General aspects. Genetic counseling; Heart; Heart attacks; heart failure; Humans; Male; Medical genetics; Medical sciences; Mutation; Penetrance; Prospective Studies; Risk Factors; ventricular arrhythmias; heart failure; OR; VT/VF; RV; ARVD/C; CI; penetrance; ECG; exercise; ICD; IQR; TFC; ventricular arrhythmias; arrhythmogenic right ventricular dysplasia; cardiomyopathy; HF; 2010 Revised Task Force Criteria; (stage C) heart failure; interquartile range; odds ratio; ventricular tachycardia/ventricular fibrillation; electrocardiogram; implantable cardioverter-defibrillator; right ventricular; arrhythmogenic right ventricular dysplasia/cardiomyopathy; confidence interval; Physical exercise; Arrhythmia; Cardiovascular disease; Risk; Increase; Genetic disease; Genetic counseling; Arrhythmogenic right ventricular dysplasia; Heart disease; Gene penetrance; Risk factor; Exercise tolerance test; Circulatory system; Mutation; Carrier; Cardiology; Age
• ISSN: 0735-1097; 1558-3597; 1558-3597
• DOI: 10.1016/j.jacc.2013.06.033

This study sought to determine how exercise influences penetrance of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) among patients with desmosomal mutations. Although animal models and anecdotal evidence suggest that exercise is a risk factor for ARVD/C, there have been no systematic human studies. 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. 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). 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.