Myosin inhibitors for the treatment of obstructive hypertrophic cardiomyopathy: a Canadian perspective on a first-in-class therapy

Hypertrophic cardiomyopathy (HCM) is a relatively common heritable cardiac condition (∼1 in 500), which poses significant morbidity and mortality. Severe symptoms are often from dynamic left ventricular outflow tract (LVOT) obstruction which may result in dyspnea, chest pain, fatigue, and (pre)syncope. This obstructive phenotype is present in more than half of cases. Traditional pharmacological therapies used to treat symptomatic LVOT obstruction are ineffective in many patients thereby necessitating septal reduction therapy in the form of alcohol septal ablation or surgical myectomy. In recent years, the demand for improved HCM treatment without surgical intervention has led to the development of a new class of drugs called cardiac myosin inhibitors. Mavacamten represents the first-in-class cardiac myosin inhibitor, which is now approved in Canada, available for special authorization cost coverage in most provinces, and is increasingly being prescribed in both specialized HCM programs and general cardiology clinics. As such, many general cardiologists, internists, and family physicians will need to be familiar with these agents. This review on the myosin inhibitors, particularly mavacamten, provides a perspective for more general cardiovascular providers by summarizing the key mechanisms, clinical trials, expected outcomes, and potential impacts on the Canadian healthcare system.