title: Yield of serial evaluation in at-risk family members of patients with ARVD/C.
abstract: BACKGROUND
  Incomplete penetrance and variable expressivity of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) complicate family screening.
  
  
  OBJECTIVE
  The objective of the present study was to determine the optimal approach to longitudinal follow-up regarding: 1) screening interval; and 2) testing strategy in at-risk relatives of ARVD/C patients.
  
  
  METHODS
  We included 117 relatives (45% male, age 33.3 ± 16.3 years) from 64 families who were at risk of developing ARVD/C by virtue of their familial predisposition (72% mutation carriers [92% plakophilin-2]; 28% first-degree relatives of a mutation-negative proband). Subjects were evaluated by electrocardiography (ECG), Holter monitoring, signal-averaged ECG, and cardiac magnetic resonance (CMR). Disease progression was defined as the development of a new criterion by the 2010 Task Force Criteria (not the "Hamid criteria") at last follow-up that was absent at enrollment.
  
  
  RESULTS
  At first evaluation, 43 subjects (37%) fulfilled an ARVD/C diagnosis according to the 2010 Task Force Criteria. Among the remaining 74 subjects (63%), 11 of 37 (30%) with complete re-evaluation experienced disease progression during 4.1 ± 2.3 years of follow-up. Electrical progression (n = 10 [27%], including by ECG [14%], Holter monitoring [11%], or signal-averaged ECG [14%]) was more frequently observed than structural progression (n = 1 [3%] on CMR). All 5 patients (14%) with clinical ARVD/C diagnosis at last follow-up had an abnormal ECG or Holter monitor recording, and the only patient with an abnormal CMR already had an abnormal ECG at enrollment.
  
  
  CONCLUSIONS
  Over a mean follow-up of 4 years, our study showed that: 1) almost one-third of at-risk relatives have electrical progression; 2) structural progression is rare; and 3) electrical abnormalities precede detectable structural changes. This information could be valuable in determining family screening protocols.
authors.affiliation: Department of Medicine, Division of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Anneline S J M
authors.initials: AS
authors.lastname: te Riele
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: James
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Neda
authors.initials: N
authors.lastname: Rastegar
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Aditya
authors.initials: A
authors.lastname: Bhonsale
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Brittney
authors.initials: B
authors.lastname: Murray
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Crystal
authors.initials: C
authors.lastname: Tichnell
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Judge
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland; Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland.
authors.forename: David A
authors.initials: DA
authors.lastname: Bluemke
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Stefan L
authors.initials: SL
authors.lastname: Zimmerman
authors.affiliation: Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Ihab R
authors.initials: IR
authors.lastname: Kamel
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
authors.forename: Hugh
authors.initials: H
authors.lastname: Calkins
authors.affiliation: Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: htandri1@jhmi.edu.
authors.forename: Harikrishna
authors.initials: H
authors.lastname: Tandri
mesh_terms: D000293:Adolescent; D000328:Adult; D019571:Arrhythmogenic Right Ventricular Dysplasia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D055815:Young Adult
keywords: cardiomyopathy; electrocardiography; magnetic resonance imaging; progression; screening