Update: Cardiac Myosin Inhibitors in Obstructive and Non-obstructive Hypertrophic Cardiomyopathy

We aim to review rapidly evolving data regarding clinical benefits of cardiac myosin inhibition in obstructive and non-obstructive hypertrophic cardiomyopathy (HCM). Both EXPLORER-HCM and VALOR-HCM have demonstrated a long-term clinical benefit from mavacamten in decreasing New York Heart Association (NYHA) class and degree of left ventricular outflow tract (LVOT) obstruction with a good safety profile, and potential for favorable long term myocardial remodeling. Similarly SEQUOIA-HCM and MAPLE-HCM demonstrated aficamten significantly decreased LVOT obstruction and symptoms and was more effective than standard medical therapy in improving exercise capacity and decreasing symptoms. Mavacamten (ODYSSEY‑HCM)) did not lead to significant clinical improvement in nonobstructive HCM. For aficamten, randomized evidence in non-obstructive HCM is still accruing. While there is strong evidence in favor of cardiac myosin inhibition in obstructive HCM, our understanding of the potential impact on long-term remodeling, and in heterogenous non-obstructive HCM is still developing. Better understanding of the impact of long-term remodeling and factors that modulate drug efficacy will further guide our use of these medications.