Author + information
- Received January 29, 2014
- Revision received April 17, 2014
- Accepted April 21, 2014
- Published online July 22, 2014.
- Anneline S.J.M. te Riele, MD∗,†,
- Cynthia A. James, PhD†,
- Neda Rastegar, MD‡,
- Aditya Bhonsale, MD†,
- Brittney Murray, MS†,
- Crystal Tichnell, MGC†,
- Daniel P. Judge, MD†,
- David A. Bluemke, MD, PhD‡,§,
- Stefan L. Zimmerman, MD‡,
- Ihab R. Kamel, MD, PhD‡,
- Hugh Calkins, MD† and
- Harikrishna Tandri, MD†∗ ()
- ∗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
- ‡Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, Maryland
- §Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland
- ↵∗Reprint requests and correspondence:
Dr. Harikrishna Tandri, Division of Cardiology, Department of Medicine, The Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 538, Baltimore, Maryland 21287.
Background Incomplete penetrance and variable expressivity of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) complicate family screening.
Objectives 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.
The authors wish to acknowledge funding from the Alexandre Suerman Stipend (to Dr. te Riele); the National Heart, Lung, and Blood Institute (K23HL093350 to Dr. Tandri); the Dr. Francis P. Chiaramonte Private Foundation; the St. Jude Medical Foundation; and Medtronic Inc. The Johns Hopkins ARVD/C Program is supported by the Bogle Foundation, the Healing Hearts Foundation, the Campanella family, the Patrick J. Harrison Family, the Peter French Memorial Foundation, the Wilmerding Endowments and the Dr. Satish, Rupal, and Robin Shah ARVD Fund at Johns Hopkins. Dr. Calkins has received ARVD/C research support from Medtronic Inc. and St. Jude Medical. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 29, 2014.
- Revision received April 17, 2014.
- Accepted April 21, 2014.
- American College of Cardiology Foundation