title: Clinical Presentation, Long-Term Follow-Up, and Outcomes of 1001 Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Patients and Family Members.
abstract: 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.
  
  
  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.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Groeneweg
authors.forename: Aditya
authors.initials: A
authors.lastname: Bhonsale
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.forename: Anneline S
authors.initials: AS
authors.lastname: te Riele
authors.forename: Dennis
authors.initials: D
authors.lastname: Dooijes
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.forename: Ans C P
authors.initials: AC
authors.lastname: Wiesfeld
authors.forename: Abhishek C
authors.initials: AC
authors.lastname: Sawant
authors.forename: Bina
authors.initials: B
authors.lastname: Kassamali
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
authors.forename: Paul G
authors.initials: PG
authors.lastname: Volders
authors.forename: Natasja M
authors.initials: NM
authors.lastname: de Groot
authors.forename: Karin
authors.initials: K
authors.lastname: de Boer
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Zimmerman
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
authors.forename: Jeroen F
authors.initials: JF
authors.lastname: van der Heijden
authors.forename: Stuart D
authors.initials: SD
authors.lastname: Russell
authors.forename: Maarten
authors.initials: M
authors.lastname: Jan Cramer
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Tedford
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Toon A
authors.initials: TA
authors.lastname: van Veen
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
authors.forename: Arthur A
authors.initials: AA
authors.lastname: Wilde
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Richard N
authors.initials: RN
authors.lastname: Hauer
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
mesh_terms: D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality; D016757:Death, Sudden, Cardiac; D017147:Defibrillators, Implantable; D051187:Desmocollins / Q000235:genetics; D051301:Desmoglein 2 / Q000235:genetics; D051180:Desmoplakins / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D051191:Plakophilins / Q000235:genetics; D011110:Polymorphism, Genetic; D051185:gamma Catenin
chemical_list: C081561:DSC2 protein, human; C495314:DSG2 protein, human; C495294:DSP protein, human; D051187:Desmocollins; D051301:Desmoglein 2; D051180:Desmoplakins; C495292:JUP protein, human; C495337:PKP2 protein, human; D051191:Plakophilins; D051185:gamma Catenin
keywords: arrhythmias, cardiac; arrhythmogenic right ventricular dysplasia; arrhythmogenic right ventricular dysplasia-cardiomyopathy; cardiomyopathies; genetics