Value of genetic testing in the diagnosis and risk stratification of arrhythmogenic right ventricular cardiomyopathy

Abstract

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by risk of malignant ventricular arrhythmia (VA). ARVC is diagnosed using an array of clinical tests in the consensus-based Task Force Criteria (TFC), one of which is genetic testing.

Objective: The purpose of this study was to investigate the value of genetic testing in diagnosing ARVC and its relation to the occurrence of first malignant VA.

Methods: A multicenter cohort of patients with ARVC was scored using the revised 2010 TFC with and without genetic criterion, analyzing any resulting loss or delay of diagnosis. Malignant VA was defined as sustained VA (≥30-second duration at ≥100 beats/min or requiring intervention).

Results: We included 402 subjects (221 [55%] male; 216 [54%] proband; 40 [27-51] years old at presentation) who were diagnosed with definite ARVC. A total of 232 subjects (58%) fulfilled genetic testing criteria. Removing the genetic criterion caused loss of diagnosis in 18 patients (4%) (11 of 216 probands [5%] and 7 of 186 relatives [4%]) and delay of diagnosis by ≥30 days in 22 patients (5%) (21 of 216 probands [10%] and 1 of 186 relative [0.5%]). A first malignant VA occurred in no patients who lost diagnosis and in 3 patients (3 of 216 probands [1%] and no relatives) during their diagnosis delay, none fatal. Time-to-event analysis showed no significant difference in time from diagnosis to malignant VA between pathogenic variant carriers and noncarriers.

Conclusion: Disregarding the genetic criterion of the TFC caused loss or delay of diagnosis in 10% of patients with ARVC (40 of 402). Malignant VA occurred in 1% of cases with lost or delayed diagnosis (3 of 402), none fatal.

Keywords: ACM; ARVC; Arrhythmogenic right ventricular dysplasia/cardiomyopathy; Diagnosis; Genetic screening; Malignant ventricular arrhythmia; Screening; Task Force Criteria.