Mavacamten Improves Cardiac Function in Patients With Obstructive HCM

Mavacamten, a cardiac myosin inhibitor, improved left ventricular (LV) diastolic function and systolic anterior motion among adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM), according to a study published in the Journal of the American College of Cardiology.

The Clinical Study to Evaluate Mavacamten (MYK-461) in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy (EXPLORER-HCM) (ClinicalTrials.gov Identifier: NCT03470545) was a multicenter, double-blind, placebo-controlled, randomized phase 3 trial. Patients with obstructive HCM who had unexplained LV hypertrophy were randomly assigned to receive mavacamten or placebo for 30 weeks. Patients were evaluated via resting echocardiogram at baseline and weeks 4, 6, 12, 18, 22, 26, 30, and 38, and via a postexercise echocardiogram at baseline and week 30.

The treatment and control cohorts had a mean age of 58.5±12.2 and 58.5±11.8 years; 46% and 35% were women; body mass index (BMI) was 29.7±4.9 and 29.2±5.6; systolic blood pressure (BP) was 128±16.2 and 128±14.6 mm Hg; diastolic BP was 75±10.8 and 76±9.9 mm Hg; 46% and 41% had hypertension; and 10% and 18% had atrial fibrillation, respectively.

Baseline echocardiogram demonstrated typical obstructive HCM features of increased maximum LV wall thickness, mild left atrial (LA) enlargement, elevated E/e’, and reduced tissue Doppler indexes of mitral annular e’ velocities.

Mavacamten therapy compared with placebo significantly improved LV diastolic function (mean decrease from baseline, -7.5 vs -0.1 mL/m²; P <.0001). Mavacamten was also associated with improved septal e’ (mean increase, 0.7 vs -0.02 cm/s; P <.0001), septal E/e’ (mean decrease, -3.5 vs -0.3; P <.0001), and lateral E/e’ (mean decrease, -3.8 vs 0.04; P <.0001). These improvements were observed as early as week 18.

For structural changes, mavacamten was associated with increased LV end-systolic dimension (mean change, 1.0 vs -0.3 mm; P =.02) and decreased inferolateral wall thickness (mean change, -0.6 vs 0.3 mm; P <.0001).

Outcomes had a significant interaction with baseline LV outflow tract, in which patients with higher baseline LV outflow tract Valsalva gradient had greater placebo-corrected reduction in LA volume index (P =.03).

Among patients with mitral valve systolic anterior motion, mavacamten induced a complete resolution at 30 weeks among 80.9% compared with 34.0% of patients receiving placebo (P <.0001). A small, but significant proportion of patients with baseline mitral regurgitation had complete resolution with mavacamten (9.0% vs 0%; P <.001).

The exercise capacity evaluation indicated that the reduced LV outflow tract gradient was associated with the decrease in N-terminal pro-B-type natriuretic peptide (b, 0.02; 95% CI, 0.01-0.03; P <.0001) and LA volume index reduction with serum cardiac troponin I (b, 0.02; 95% CI, 0.00-0.05; P =.048) and peak oxygen consumption (b, -0.08; 95% CI, -0.15 to 0.00; P =.041).

These findings may not be generalizable to the entire obstructive HCM population, as patients with mild symptoms were excluded.

This study found that mavacamten facilitated favorable changes to cardiac structure and function through week 30 among patients with symptomatic obstructive HCM. The study authors noted, “The ongoing long-term extension study (MAVA-LTE) will reveal whether these early benefits with mavacamten treatment persist beyond 30 weeks.”

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.

Reference

Hegde SM, Lester SJ, Solomon SD, et al. Effect of mavacamten on echocardiographic features in symptomatic patients with obstructive hypertrophic cardiomyopathy. J Am Coll Cardiol. Published online December 13, 2021. doi:10.1016/j.jacc.2021.09.1381