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. Objective: Determine predictors and probability of ARVC development over time among at-risk relatives. Methods: We included 136 relatives (46% male, 25.5 (interquartile range (IQR):15.8-44.4) years) from the Netherlands ACM Registry without definite ARVC by 2010 Task Force Criteria (TFC). Phenotype was ascertained using electrocardiograms, Holter monitoring, and cardiac imaging. Subjects were divided into "possible ARVC" (only genetic/familial predisposition) and "borderline ARVC" (one minor TFC criterion plus genetic/familial predisposition). We performed Cox regression to determine predictors, and multi-state modeling to assess probability of ARVC development. Results were replicated in an unrelated Italian cohort (57% male, 37.0 (IQR:25.4-50.4) years). Results: At baseline, 93 (68%) had possible and 43 (32%) borderline ARVC. Follow-up was available for 123 (90%) relatives. After 8.1 (IQR:4.2-11.4) years, 41 (33%) developed definite ARVC. Independent of baseline phenotype, symptomatic subjects (p=0.014) and those 20-30 years old (p=0.002) had higher hazard of developing definite ARVC. Furthermore, borderline ARVC patients had higher probability of developing definite ARVC compared to possible patients (1-year probability: 13% vs. 0.6%; 3-year probability: 35% vs. 5%, p<0.01). External replication showed comparable results (p>0.05). Conclusion: Symptomatic relatives, those in 20-30 age range and with borderline ARVC have higher probability of developing definite ARVC. These patients may benefit from more frequent follow-up, while others may be monitored less often.