Cardiac myosin inhibitors are a novel class of drugs developed to target the underlying molecular defect of hyperactivation of the cardiac sarcomere in patients with hypertrophic cardiomyopathy (HCM).1 The first in class, mavacamten, received US Food and Drug Administration (FDA) approval in 2022 following results of the EXPLORER-HCM trial,2 which reported significant reductions in left ventricular outflow tract gradients, improvement in New York Heart Association (NYHA) classification, and improvement in exercise capacity with mavacamten compared with placebo in symptomatic patients with obstructive HCM. Similarly, in the VALOR-HCM trial,3 patients randomized to receive mavacamten had significant reductions in left ventricular outflow tract gradients and symptomatic improvement compared with patients randomized to receive placebo. VALOR-HCM enrolled more symptomatic patients (all NYHA class III or class II with syncope) whereas approximately 25% of patients in EXPLORER-HCM were NYHA class III. All patients in VALOR-HCM were eligible for invasive septal reduction therapy at trial entry; at 16 weeks, 70% of patients in the placebo group remained eligible for septal reduction therapy compared with 14% in the mavacamten group.