Abstract
Hypertrophic cardiomyopathy is the most common monogenic cardiovascular disease that is caused by sarcomeric protein gene mutations. A hallmark of the most common form of the disease is outflow obstruction secondary to systolic narrowing of the left ventricular outflow tract from septal hypertrophy, mitral valve abnormalities and, most importantly, hyperdynamic contractility. Recent mechanistic studies have identified excessive myosin adenosine triphosphatase activation and actin-myosin cross-bridging as major underlying causes. These studies have led to the development of mavacamten, a first-in-class myosin adenosine triphosphatase inhibitor and the first specific therapy for hypertrophic obstructive cardiomyopathy. Preclinical and subsequent pivotal clinical studies have demonstrated the efficacy and safety of mavacamten. A remarkable improvement among treated patients in peak oxygen consumption, functional capacity, symptom relief and post-exercise left ventricular outflow tract gradient, along with dramatic reductions in heart failure biomarkers, suggests that this new medication will be transformative for the symptom management of hypertrophic obstructive cardiomyopathy. There is also hope and early evidence that mavacamten may delay or obviate the need for invasive septal reduction therapies. In this article, we review the current evidence for the efficacy and safety of mavacamten and highlight important considerations for its clinical use.