Abstract
INTRODUCTION: Current family screening approaches in dilated cardiomyopathy (DCM) depend on the presence or absence of a familial genetic variant, in which variant pathogenicity (i.e. benign or pathogenic) classification drives screening recommendations. However, this approach has never been systematically evaluated. METHODS: To describe the yield of DCM family screening stratified by variant classification in the Netherlands, we included 358 relatives (mean age ± standard deviation: 44.4 ± 15.9 years at baseline; 52% female; 41% (likely) pathogenic (LP/P) variant carriers from 210 families). Demographics, symptoms and genetic/cardiac test results were obtained. Endpoints were the development of DCM (left ventricular ejection fraction < 50% of non-ischaemic aetiology) or occurrence of major adverse cardiovascular events (MACE) (i.e. heart failure hospitalisation, ventricular arrhythmia or death). Probability of DCM or MACE was assessed with the Kaplan-Meier method. RESULTS: DCM was present in 32 relatives (9%) (25/32 (78%) with LP/P variant) at baseline and in an additional 10/97 relatives (10%) (9/10 (90%) with LP/P variant) who were re-evaluated during a median follow-up time of 5.0 years (interquartile range: 3.2-7.4). Of the 128 relatives without the familial LP/P variant, none developed DCM. MACE was experienced by 5 relatives (1%) (4/5 (80%) with LP/P variant), all of whom had DCM at the time of the event. CONCLUSION: The yield of DCM family screening was ~10% at baseline and another ~10% during 5‑year follow-up. Relatives without the familial LP/P variant could be safely discharged. These results reinforce the use of a genetics-first screening approach in relatives from families with an LP/P variant. This will lower the burden on resources in Dutch hospitals and help allocate resources to those who are most likely to benefit.