QI-452785-2 INDIVIDUALIZED FAMILY SCREENING FOR ARRHYTHMOGENIC RIGHT VENTRICULAR CARDIOMYOPATHY

Abstract

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a clinically heterogeneous disease for which guidelines recommend a one-size-fits-all screening approach to monitor at-risk relatives. Prioritizing relatives on their predicted probability of definite ARVC development could ensure that low-risk people are not unnecessarily followed-up, while resources can be allocated to more frequently monitor high-risk relatives. Determine the probability of definite ARVC diagnosis, identify predictors of new TFC development, and describe the incidence of ventricular arrhythmias (VA) among at-risk relatives of ARVC probands. We included all relatives without definite ARVC diagnosis by 2010 Task Force Criteria (TFC) referred to our center for family screening. Demographics, symptoms and multi-generation pedigrees were ascertained. Relatives underwent electrocardiogram, Holter monitor, and cardiac imaging at baseline and follow-up. Subjects were divided by baseline clinical phenotype: “possible ARVC” (only genetic/familial predisposition) or “borderline ARVC” (one minor TFC criterion plus genetic/familial predisposition). A multi-state model was used to determine probability of definite ARVC development. VA (defined as sustained ventricular tachycardia, ICD therapy or aborted sudden cardiac death) was ascertained by record review. Overall, 78 relatives (50% male, age 22.2 (interquartile range (IQR) 14.8-40.9)) without definite ARVC diagnosis were included. At baseline, 54 (69%) had possible ARVC and 24 (31%) borderline ARVC. During 7.9 (IQR 4.2-10.8) years of follow-up, 42 (54%) relatives developed a new TFC criterion and 27 (35%) progressed towards definite ARVC. Siblings of the proband were at higher hazard of new TFC criterion development (hazard ratio 2.37, p=0.042), while having symptoms was associated with definite ARVC diagnosis (hazard ratio 2.87, p=0.009)(Table 1). Those with borderline ARVC had >10-fold higher probability of progressing to definite ARVC compared to those with possible ARVC (p<0.01)(Figure 1). Two relatives had a VA >9 years after definite ARVC diagnosis; no VA occurred in relatives without definite ARVC diagnosis. Symptomatic patients, siblings, and those with borderline ARVC have higher probability of developing definite ARVC. These patients will benefit from more frequent follow-up, while others may be monitored less often. VAs are rare among relatives without definite ARVC diagnosis.