Pharmacologic therapies for hypertrophic cardiomyopathy: The past,the present,and the future

Abstract

Hypertrophic cardiomyopathy (HCM) stands as the most common monogenic cardiac disease, with an estimated prevalence historically reported as 1:500, but likely closer to 1:200 based on contemporary population studies in the general population. The past decade has marked a fundamental shift in therapeutic strategy: from symptomatic relief toward interventions directly targeting pathological sarcomeric hypercontractility. Conventional therapy relies on beta-blockers and non-dihydropyridine calcium channel antagonists, which provide symptomatic benefits through negative inotropic effects. For refractory left ventricular outflow tract obstruction, disopyramide constitutes an effective third-line option, although its anticholinergic profile requires cautious administration. Cardiac myosin inhibitors, mavacamten and aficamten, have introduced a novel therapeutic paradigm through direct modulation of actin-myosin cross-bridge formation. Pivotal clinical trials have demonstrated significant improvements in exercise capacity, reduction in obstruction severity, and enhancement of functional status, validating for the first time a therapeutic strategy that directly targets the underlying sarcomeric mechanism of hypercontractility. The therapeutic horizon includes next-generation myosin modulators, metabolic pathway interventions, and gene-based strategies. Current challenges involve accessibility to these therapies, substantial costs, and the requirement for mandatory regular echocardiographic monitoring. Future perspectives are oriented toward precision personalized medicine, integrating molecular therapeutics with genetic profiling to enable increasingly individualized risk stratification and therapeutic decision making.