A Discussion on oHCM: Part 1—How Cardiac Myosin Inhibitors Are Changing Treatment

In an interview with Pharmacy Times, Craig Beavers, PharmD, FACC, FAHA, FCCP, BCCP, BCPS-AQ Cardiology, CACP, a cardiovascular clinical pharmacist with Baptist Health System and the University of Kentucky College of Pharmacy, discussed the clinical and pharmacological landscape of hypertrophic cardiomyopathy (HCM), with a focus on obstructive HCM (oHCM) and the emerging role of cardiac myosin inhibitors (CMIs) in transforming patient outcomes.

Beavers opened by drawing a clear distinction between obstructive and nonobstructive HCM—2 subtypes that fall under the same diagnostic umbrella but differ meaningfully in pathophysiology, prognosis, and treatment approach. Obstructive HCM is defined by a left ventricular outflow tract gradient greater than 30 mm Hg at rest or with provocation, driven by a combination of hypertrophic tissue and systolic anterior motion of the mitral valve apparatus. Nonobstructive HCM, by contrast, lacks these hemodynamic features and may present with significant anatomical heterogeneity, including apical hypertrophy or midventricular obstruction.

On the mechanism of CMIs, Beavers explained that in untreated oHCM, a destabilization of myosin’s auto-inhibited conformation shifts the equilibrium toward an overactive “on” state, increasing cross-bridge formation, adenosine triphosphate expenditure, and sarcomere contractility. CMIs correct this imbalance by restoring the on/off equilibrium, which Beavers likens to slowing down an overworked rowing machine to help patients visualize the concept.

Regarding mavacamten (Camzyos; Bristol Myers Squibb), Beavers noted that publicly available Risk Evaluation and Mitigation Strategy (REMS) data from over 11,000 patients spanning more than 3 years show that 85% of treated patients had no obstruction at the 32-month data cut, findings he said are consistent with his own clinical experience. Beavers described the REMS program not as a burden, but as a valuable source of long-term safety data that supports shared decision-making conversations with patients.

Beavers also addressed the paradigm shift away from β-blockers, arguing that CMIs offer a more targeted, cleaner tolerability profile for managing oHCM symptoms compared with traditional nonspecific therapies.