Cardiac myosin inhibitors in hypertrophic cardiomyopathy: gaps in knowledge and future opportunities

Abstract: Hypertrophic cardiomyopathy (HCM) is an inherited cardiovascular disease affecting 1:200 to 1:500 individuals. It is characterized by a complex interplay of factors including increased septal wall thickness, small ventricular size, left ventricular outflow tract (LVOT) obstruction, mitral valve abnormalities, myocardial hypercontractility, and diastolic dysfunction. Despite therapeutic advancements, critical knowledge gaps persist particularly concerning the use of cardiac myosin inhibitors. This review aimed to consolidate existing knowledge, identify these gaps, and delineate the directions for future research in HCM management. Our comprehensive literature search, spanning PubMed/MEDLINE and Google Scholar, explored HCM, cardiac surgery, and myosin inhibitors. Studies unveiled the potential of β-cardiac myosin ATPase inhibitors to improve symptoms, LVOT gradients, and overall health in HCM patients. Drops in left ventricular ejection fraction associated with these medications may be addressed by proper dose adjustments or discontinuation. While long-term data are further needed, initial studies point to their cost-effectiveness. Notably, minority ethnic groups and women continue to be underrepresented in clinical trials and experience disproportionately higher cardiovascular mortality. Global collaboration, comprehensive registries, and data-sharing initiatives are key to advancing HCM research and improving patient outcomes. Future research must prioritize the inclusivity and diversity of ethnic minority groups to improve the applicability of conclusions and comprehensively advance HCM management.