Individualized Family Screening for Arrhythmogenic Right Ventricular Cardiomyopathy.

Background: Clinical guidelines recommend regular screening for arrhythmogenic right ventricular cardiomyopathy (ARVC) to monitor at-risk relatives, resulting in a significant burden on clinical resources. Prioritizing relatives on their probability of developing definite ARVC may provide more efficient patient care.
Objectives: The aim of this study was to determine the predictors and probability of ARVC development over time among at-risk relatives.
Methods: A total of 136 relatives (46% men, median age 25.5 years [IQR: 15.8-44.4 years]) from the Netherlands Arrhythmogenic Cardiomyopathy Registry without definite ARVC by 2010 task force criteria were included. Phenotype was ascertained using electrocardiography, Holter monitoring, and cardiac imaging. Subjects were divided into groups with "possible ARVC" (only genetic or familial predisposition) and "borderline ARVC" (1 minor task force criterion plus genetic or familial predisposition). Cox regression was performed to determine predictors and multistate modeling to assess the probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% men, median age 37.0 years [IQR: 25.4-50.4 years]).
Results: At baseline, 93 subjects (68%) had possible ARVC, and 43 (32%) had borderline ARVC. Follow-up was available for 123 relatives (90%). After 8.1 years (IQR: 4.2-11.4 years), 41 (33%) had developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (P = 0.014) and those 20 to 30 years of age (P = 0.002) had a higher hazard of developing definite ARVC. Furthermore, patients with borderline ARVC had a higher probability of developing definite ARVC compared with those with possible ARVC (1-year probability 13% vs 0.6%, 3-year probability 35% vs 5%; P < 0.01). External replication showed comparable results (P > 0.05).
Conclusions: Symptomatic relatives, those 20 to 30 years of age, and those with borderline ARVC have a higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.
Competing Interests: Funding Support and Author Disclosures This study was supported by the Netherlands Cardiovascular Research Initiative, an initiative with support of the Netherlands Heart Foundation (grants CVON 2015-12 eDETECT, CVON 2020B005 Double Dose, and CVON 2018-30 Predict 2). The Netherlands Arrhythmogenic Cardiomyopathy Registry is supported by the Netherlands Heart Institute (project 06901). Dr te Riele is supported by the ZonMW Off Road Grant 2021. Dr Asselbergs is supported by the University College London Hospitals National Institute for Health and Care Research Biomedical Research Centre. Dr Schmidt is supported by British Heart Foundation grants PG/18/5033837 and PG/22/10989 and the University College London British Heart Foundation Research Accelerator (AA/18/6/34223). Dr Gasperetti has served on the advisory board of LEXEO Therapeutics for unrelated work. Dr Schmidt has received funding from NewAmsterdam for unrelated work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)