Mavacamten in Hypertrophic Cardiomyopathy: An Updated Review of Clinical Evidence, Patient Selection, and Outcomes.

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy, with obstructive forms often requiring septal reduction therapy. Conventional pharmacologic treatments focus on symptom relief but do not address the underlying sarcomeric hypercontractility. Mavacamten, a selective cardiac myosin inhibitor, represents a novel therapeutic approach by stabilizing the super-relaxed state of β-cardiac myosin to reduce contractile excess. We conducted a structured review of 30 peer-reviewed sources, including data from the EXPLORER-HCM, VALOR-HCM, MAVERICK-HCM, and ODYSSEY-HCM trials, as well as cardiac MRI substudies and long-term extension data. Key clinical outcomes included reductions in LVOT gradient (−36 mmHg, p<0.0001), improvements in NYHA class (65% vs 31% placebo), and increases in peak VO₂. Cardiac MRI showed decreased LV mass index (−17.4 g/m², p<0.0001) and left atrial volume. NT-proBNP and hs-Troponin I levels declined across studies. Sustained benefit was observed through 84 weeks, with transient LVEF reductions (<50%) in <6% of patients, reversible with dose adjustment. Mavacamten provides meaningful symptomatic and structural benefits and offers a noninvasive alternative to septal reduction, particularly relevant in regions with limited access to invasive therapies, such as Latin America. Ongoing studies will help define its role in nonobstructive and genotype-positive HCM.