Evolving Strategies for the Management of Obstructive Hypertrophic Cardiomyopathy

Highlights•Current treatment of obstructive hypertrophic cardiomyopathy is targeted at symptom relief by means of beta-blockers, calcium channel blockers and disopyramide, with invasive septal-reduction therapy considered as the only definitive therapy for those with refractory symptoms. Mavacamten, a cardiac myosin modulator, reduces the pathologic actin-myosin interactions that are characteristic of hypertrophic cardiomyopathy, leading to improved cardiac energetics and reduction in hypercontractility.•EXPLORER-HCM and VALOR-HCM were groundbreaking trials in hypertrophic cardiomyopathy that demonstrated that mavacamten improves exercise capacity, left ventricular outflow tract obstruction and symptoms in patients with obstructive hypertrophic cardiomyopathy; however, long-term safety and efficacy data are needed.•Hypertrophic cardiomyopathy is a complex and heterogeneous disease, and not all patients will respond to mavacamten, nor is it accessible to all patients, given its cost, frequency of required monitoring and pharmacological properties.ABSTRACTFor many years, treatment of hypertrophic cardiomyopathy (HCM) has focused on non-disease-specific therapies. Cardiac myosin modulators (ie, mavacamten and aficamten) reduce the pathologic actin-myosin interactions that are characteristic of HCM, leading to improved cardiac energetics and reduction in hypercontractility. Several recently published randomized clinical trials have demonstrated that mavacamten improves exercise capacity, left ventricular outflow tract obstruction and symptoms in patients with obstructive HCM and may delay the need for septal-reduction therapy. Long-term data in real-world populations will be needed to fully assess the safety and efficacy of mavacamten. Importantly, HCM is a complex and heterogeneous disease, and not all patients will respond to mavacamten; therefore, careful patient selection and shared decision making will be necessary in guiding the use of mavacamten in obstructive HCM.