Yield of family screening for dilated cardiomyopathy: 10-year experience at a multidisciplinary cardiogenetic outpatient clinic.

introductionCurrent 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.

methodsTo 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.

resultsDCM 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.

conclusionThe 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.