## Summary Mavacamten (Camzyos) is a first-in-class cardiac myosin inhibitor that reduces excessive myocardial contractility by allosterically modulating cardiac myosin. This action decreases myocardial force generation and alleviates left ventricular outflow tract obstruction in obstructive hypertrophic cardiomyopathy. ## Detailed Answer Mavacamten, marketed as Camzyos, is a first-in-class cardiac myosin inhibitor specifically designed for the treatment of obstructive hypertrophic cardiomyopathy (oHCM)^[0,3,4,12]. Its mechanism of action involves directly targeting the underlying pathophysiology of the disease by reducing excessive myocardial contractility^[1,8,14]. Mavacamten functions as an allosteric modulator of cardiac myosin, binding to the myosin motor protein^[7,11,12]. By doing so, it stabilizes the myosin head in a conformation that reduces the number of myosin heads bound to actin^[1,8,18]. This ultimately decreases myocardial force generation and reduces excessive contractility, which is a hallmark of HCM^[1,8,18]. Specifically, it lowers the sensitivity of cardiac myosin to calcium and reduces myosin-actin cross-bridging^[18]. By dampening this hypercontractility, mavacamten effectively alleviates the pressure gradient and obstruction in the left ventricular outflow tract (LVOT) commonly seen in patients with oHCM^[2,15]. ## Clinical Pearls • Mavacamten targets the fundamental molecular abnormality in hypertrophic cardiomyopathy: excessive contractility due to abnormal cardiac myosin function. • By reducing the number of myosin-actin cross-bridges, mavacamten lessens the force generated by the heart muscle, thereby decreasing left ventricular outflow tract obstruction.