Targeted Therapies in Hypertrophic Cardiomyopathy: A Practical Review of Evidence, Implementation, and Innovation

Hypertrophic cardiomyopathy (HCM) is a common inherited disorder characterized by sarcomere dysfunction leading to myocardial hypertrophy, diastolic impairment, and, in many patients can result in dynamic left ventricular outflow tract obstruction (LVOTO). Traditional pharmacologic management of HCM has relied on β-blockers and nondihydropyridine calcium channel blockers, which provide symptomatic relief but do not directly target underlying molecular pathology of the disease. Advances in mechanistic understanding of HCM, particularly the role of hyperactive actin-myosin cross-bridge cycling, have led to the development of cardiac myosin inhibitors (CMIs), a novel class of targeted therapeutics. This review systematically summarizes the pharmacology, clinical trial evidence, dosing strategies, and safety considerations surrounding CMIs. While CMIs have transformed the management of obstructive HCM, their role in non-obstructive HCM disease remains uncertain, highlighting ongoing unmet needs. Emerging therapies, including next-generation myosin modulators, metabolic agents, sodium-glucose cotransporter inhibitors, and RNA-targeted approaches, offer promise for broader disease modification across all HCM phenotypes. As therapeutic options expand, combining pharmacology and clinical assessment endpoints in the treatment of HCM patients will be essential to define long-term benefit.