Cardiac Myosin Inhibitors in Hypertrophic Cardiomyopathy: Clinical Advances and Therapeutic Prospects

Hypertrophic cardiomyopathy (HCM) is a common inherited disease with substantial residual morbidity despite established pharmacological and surgical therapies. We conducted a narrative review of the current evidence on cardiac myosin inhibitors, drawing on published studies up to July 2025, including pivotal clinical trials, real-world cohorts, and pharmacokinetic analyses. Mavacamten and Aficamten consistently reduced left ventricular outflow tract (LVOT) gradients, improved New York Heart Association class, and were generally well tolerated under echocardiography-guided titration. Long-term extensions and real-world registries confirmed sustained efficacy, while pharmacogenetic factors and monitoring strategies continue to shape individualized use. Comparative analyses suggest Aficamten offers more rapid pharmacokinetics and simplified dosing, though both require careful safety surveillance. Remaining challenges include limited data in non-obstructive HCM, uncertain antifibrotic and rhythm outcomes, high cost, and the burden of frequent imaging and genetic testing. Beyond HCM, early studies are exploring broader indications and next-generation modulators. Cardiac myosin inhibition is reshaping the therapeutic landscape of HCM, but cost-effective, precision-based implementation and long-term outcome studies remain critical priorities.