Increasingly identified as a result of higher visibility as a diagnosis, improved imaging techniques, and development and approval for the first time of specific pathology-targeted medical treatment, hypertrophic cardiomyopathy (HCM) is a genetic heart disease inherited in an autosomal dominant pattern and is the leading cause of sudden cardiac death in young athletes. Early epidemiological studies reported a prevalence of 0.2% in the general population but it is now recognized that this is underestimated and that up to 0.6% of the population may carry HCM-causing sarcomere mutations.  HCM is characterized by LVHin the absence of other cardiac, systemic, or metabolic diseases capable of explaining the degree of LVH. Clinical manifestations of HCM vary considerably, with symptoms ranging from none or mild exercise intolerance, to severe lifestyle-limiting symptoms such as chest pain attributable to microvascular ischemia; syncope or dyspnea on exertion secondary to LVOT obstruction; atrial and/or ventricular arrhythmias; diastolic dysfunction; advanced heart failure; and SCD.

Conventional management options for HCM include lifestyle modification, familial screening with genetic counseling, pharmacotherapy for symptom control, sudden cardiac death risk stratification with or without defibrillator implantation, septal reduction therapy (SRT) and, in some cases, heart transplantation. Until recently, pharmacotherapy in HCM was limited to beta-blockers, calcium channel blockers, and disopyramide and (in refractory cases) diuretics, which may provide symptom relief for a time, but do not impact the underlying structural pathology. Cardiac myosin inhibitors (CMIs) are rapidly becoming the preferred medical therapy in HCM, with mavacamten being the first-in-class approved agent to specifically target symptomatic oHCM. Even as other CMIs are being developed, this targeted therapy has already been included in recent cardiomyopathy management guidelines updates (ESC, 2023; AHA/ACC/AMSSM/HRS/PACES/SCMR, 2024), and recent data updates continue to lend support to its use. As CMI treatment becomes more and more widely available and practical experience with it grows, it is an opportune time to educate clinicians who manage patients with HCM about it, as well to provide updates on diagnostic and risk stratification approaches.

Drs Olivotto, Michels, and Desai lead the learner through a review of the pathophysiology, epidemiology, and diagnostic evaluation of HCM, and then review clinical trial and observational data on the use of CMIs as targeted medical therapy.  This program provides an essential update on oHCM management that aligns with the 2023 ESC Cardiomyopathy Guidelines.