Background— Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a progressive cardiomyopathy. We aimed to define long-term outcome in a transatlantic cohort of 1001 individuals. Methods and Results— Clinical and genetic characteristics and follow-up data of ARVD/C index-patients (n=439, fulfilling of 2010 criteria in all) and family members (n=562) were assessed. Mutations were identified in 276 index-patients (63%). Index-patients presented predominantly with sustained ventricular arrhythmias (268; 61%). During a median follow-up of 7 years, 301 of the 416 index-patients presenting alive (72%) experienced sustained ventricular arrhythmias. Sudden cardiac death during follow-up occurred more frequently among index-patients without an implantable cardioverter-defibrillator (10/63, 16% versus 2/335, 0.6%). Overall, cardiac mortality and the need for cardiac transplantation were low (6% and 4%, respectively). Clinical characteristics and outcomes were similar in index-patients with and without mutations, as well as in those with familial and nonfamilial ARVD/C. ARVD/C was diagnosed in 207 family members (37%). Symptoms at first evaluation correlated with disease expression. Family members with mutations were more likely to meet Task Force Criteria for ARVD/C (40% versus 18%), experience sustained ventricular arrhythmias (11% versus 1%), and die from a cardiac cause (2% versus 0%) than family members without mutations. Conclusions— Long-term outcome was favorable in diagnosed and treated ARVD/C index-patients and family members. Outcome in index-patients was modulated by implantable cardioverter-defibrillator implantation, but not by mutation status and familial background of disease. One third of family members developed ARVD/C. Outcome in family members was determined by symptoms at first evaluation and mutations.

BackgroundExercise is associated with age‐related penetrance and arrhythmic risk in carriers of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C)‐associated desmosomal mutations; however, its role in patients without desmosomal mutations (gene‐elusive) is uncertain. This study investigates whether exercise is (1) associated with onset of gene‐elusive ARVD/C and (2) has a differential impact in desmosomal and gene‐elusive patients.Methods and ResultsEighty‐two ARVD/C patients (39 desmosomal, all probands) were interviewed about regular physical activity from age 10. Participation in endurance athletics, duration (hours/year), and intensity (MET‐Hours/year) of exercise prior to clinical presentation were compared between patients with desmosomal and gene‐elusive ARVD/C. All gene‐elusive patients were endurance athletes. Gene‐elusive patients were more likely to be endurance athletes (P<0.001) and had done significantly more intense (MET‐Hrs/year) exercise prior to presentation (P<0.001), particularly among cases presenting < age 25 (P=0.027). Family history was less prevalent among gene‐elusive patients (9% versus 40% desmosomal, P<0.001), suggesting a greater environmental influence. Gene‐elusive patients without family history did considerably more intense exercise than other ARVD/C patients (P=0.004). Gene‐elusive patients who had done the most intense (top quartile MET‐Hrs/year) exercise prior to presentation had a younger age of presentation (P=0.025), greater likelihood of meeting ARVD/C structural Task Force Criteria (100% versus 43%, P=0.02), and shorter survival free from a ventricular arrhythmia in follow‐up (P=0.002).ConclusionsGene‐elusive, non‐familial ARVD/C is associated with very high intensity exercise suggesting exercise has a disproportionate role in the pathogenesis of these cases. As exercise negatively modifies cardiac structure and promotes arrhythmias, exercise restriction is warranted.

61Background: The Tpeak -Tend interval, an electrocardiographic marker reflecting transmural

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Pediatric patients with ARVD/C are typically male mutation carriers presenting in adolescence. Pediatric patients disproportionately present with sudden cardiac death. However, once diagnosed, clinical characteristics and outcomes are similar between pediatric and adult patients.