Current and emerging medical and surgical therapy in hypertrophic cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is a disease characterized by unexplained left ventricular hypertrophy and is caused by mutations in cardiac sarcomeric proteins. Despite advances in diagnostic modalities and risk stratification, therapeutic strategies have until recently mostly focused on the management of symptoms and the prevention of sudden cardiac death, rather than modifying the underlying sarcomeric dysfunction itself. Conventional pharmacological therapies such as β-blockers and nondihydropyridine calcium channel blockers are effective first-line treatments for obstructive HCM, and established invasive septal reduction therapies, such as surgical myectomy and alcohol septal ablation, provide effective relief of obstruction in refractory patients. However, these therapies address anatomical and hemodynamical consequences rather than the molecular etiology of the disease. In recent years, novel therapeutic approaches have emerged that target the pathophysiological mechanisms of HCM more directly. Sodium-glucose cotransporter 2 inhibitors have demonstrated clinical benefits in HCM through improvements in myocardial energetics. Cardiac myosin inhibitors directly attenuate sarcomeric hypercontractility and have shown improvements in symptoms, functional status, and hemodynamic parameters in obstructive HCM. Furthermore, preliminary gene-targeted therapies are under active investigation and offer the prospect of definitive cure. This review provides a comprehensive overview of current and emerging treatment modalities for HCM. Overall, the management of HCM is evolving toward a more mechanism-targeted approach spanning from gene to myocardium. Ongoing research will be essential to integrate the emerging molecularly targeted therapies with established management strategies into a personalized, multidisciplinary management of HCM.