The Evolving Landscape of Hypertrophic Cardiomyopathy: Clinical Assessment, Precision Therapies, and Emerging Strategies

Hypertrophic cardiomyopathy (HCM) is a genetically and phenotypically heterogeneous disease in which management requires integration of clinical assessment, cardiovascular physiology, multimodality imaging, functional evaluation, and arrhythmic risk. This review examines contemporary evaluation, risk stratification, and treatment of sarcomeric HCM across obstructive and non-obstructive phenotypes. In obstructive HCM, conventional negative inotropic therapy and septal reduction therapy remain established treatments, while cardiac myosin inhibitors have introduced a mechanism-based approach that improves left ventricular outflow tract obstruction, symptoms, and exercise capacity. Their role relative to septal reduction therapy should be individualized according to anatomy, hemodynamics, treatment burden, durability, and patient preference. In non-obstructive HCM, treatment remains largely symptom-directed, although recent trials of myosin inhibition have yielded divergent results, emphasizing the importance of appropriate patient selection. Emerging strategies targeting myocardial energetics and earlier disease stages may further expand treatment options. Gene-based therapies, including first-in-human MYBPC3 replacement, offer the possibility of targeting the underlying molecular defect but require careful evaluation of safety, durability, and timing. Overall, HCM remains a paradigmatic disease for physiology-driven, phenotype- and stage-specific care, increasingly complemented by molecularly targeted therapies.