Improving risk prediction in hypertrophic cardiomyopathy: the key role of Dutch founder variants

Abstract

Hypertrophic cardiomyopathy (HCM) is an important cardiac condition that can lead to sudden cardiac death (SCD) or heart failure in a subset of patients. Although HCM has been the subject of intense investigation for several decades now, our ability to predict disease onset and progression-in particular, to identify those patients at highest risk of severe clinical events-remains limited and represents one of the key challenges facing clinicians and researchers in this field. Genetic testing is a useful but blunt tool for risk prediction in HCM patients and their families. Causative rare variants in the index patient (identified in 30-50% of cases) enable cascade screening and the discharge from ongoing clinical surveillance of relatives without the variant.However, the factors that influence disease penetrance (which pathogenic variant carriers will develop the phenotype?) remain poorly understood, and asymptomatic genotype-positive individuals require regular and costly cardiac screening to monitor disease onset. While some risk prediction models are recommended for HCM patients, e.g. the HCM Risk-SCD calculator for prioritising patients who may benefit from prophylactic implantable cardioverter defibrillators [1], more comprehensive and accurate predictors of clinical severity are required.The BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort described in this issue of the Netherlands