Clinical Presentation, Long-Term Follow-Up, and Outcomes of 1001 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients and Family Members

• Published in: Circulation. Cardiovascular genetics Vol. 8; no. 3; pp. 437 - 446
• Main Authors: Groeneweg, Judith A., Bhonsale, Aditya, James, Cynthia A., te Riele, Anneline S., Dooijes, Dennis, Tichnell, Crystal, Murray, Brittney, Wiesfeld, Ans C.P., Sawant, Abhishek C., Kassamali, Bina, Atsma, Douwe E., Volders, Paul G., de Groot, Natasja M., de Boer, Karin, Zimmerman, Stefan L., Kamel, Ihab R., van der Heijden, Jeroen F., Russell, Stuart D., Jan Cramer, Maarten, Tedford, Ryan J., Doevendans, Pieter A., van Veen, Toon A., Tandri, Harikrishna, Wilde, Arthur A., Judge, Daniel P., van Tintelen, J. Peter, Hauer, Richard N., Calkins, Hugh
• Format: Journal Article
• Language: English
• Published: United States 01.06.2015
• Subjects: Adult; Arrhythmogenic Right Ventricular Dysplasia - diagnosis; Arrhythmogenic Right Ventricular Dysplasia - genetics; Arrhythmogenic Right Ventricular Dysplasia - mortality; Death, Sudden, Cardiac; Defibrillators, Implantable; Desmocollins - genetics; Desmoglein 2 - genetics; Desmoplakins - genetics; Female; Follow-Up Studies; gamma Catenin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Plakophilins - genetics; Polymorphism, Genetic; arrhythmias, cardiac; arrhythmogenic right ventricular dysplasia; genetics; cardiomyopathies; arrhythmogenic right ventricular dysplasia-cardiomyopathy
• ISSN: 1942-325X; 1942-3268; 1942-3268
• DOI: 10.1161/CIRCGENETICS.114.001003

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. 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. 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.