Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy.

Abstract

BACKGROUND:

EXPLORER-HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy) demonstrated that mavacamten, a cardiac myosin inhibitor, improves symptoms, exercise capacity, and left ventricular outflow tract (LVOT) obstruction in patients with obstructive hypertrophic cardiomyopathy (oHCM).

OBJECTIVES:

The purpose of this study was to evaluate mavacamten's effect on measures of cardiac structure and function and its association with changes in other clinical measures.

METHODS:

Key echocardiographic parameters from serial echocardiograms over 30 weeks from 251 symptomatic oHCM patients (mavacamten [n = 123], placebo [n = 128]) were assessed in a core laboratory.

RESULTS:

More patients on mavacamten (80.9%; n = 76 of 94) vs placebo (34.0%; n = 33 of 97) showed complete resolution of mitral valve systolic anterior motion after 30 weeks (difference, 46.8%; P < 0.0001). Mavacamten also improved measures of diastolic function vs placebo, including left atrial volume index (LAVI) (mean ± SD baseline: 40 ± 12 mL/m2 vs 41 ± 14 mL/m2; mean change from baseline of -7.5 mL/m2 [95% CI: -9.0 to -6.1 mL/m2] vs -0.09 mL/m2 [95% CI: -1.6 to 1.5 mL/m2]; P < 0.0001) and lateral E/e' (baseline, 15 ± 6 vs 15 ± 8; change of -3.8 [95% CI: -4.7 to -2.8] vs 0.04 [95% CI: -0.9 to 1.0]; P < 0.0001). Among mavacamten-treated patients, improvement in resting, Valsalva, and post-exercise LVOT gradients, LAVI, and lateral E/e' was associated with reduction in N-terminal pro-B-type natriuretic peptide (P ≤ 0.03 for all). Reduction in LAVI was associated with improved peak exercise oxygen consumption (P = 0.04).

CONCLUSIONS:

Mavacamten significantly improved measures of left ventricular diastolic function and systolic anterior motion. Improvement in LVOT obstruction, LAVI, and E/e' was associated with reduction in a biomarker of myocardial wall stress (N-terminal pro-B-type natriuretic peptide). These findings demonstrate improvement in important markers of the pathophysiology of oHCM with mavacamten. (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy; NCT03470545).

• Authors: Sheila M Hegde, Steven J Lester, Scott D Solomon, Michelle Michels, Perry M Elliott, Sherif F Nagueh, Lubna Choudhury, David Zemanek, Donna R Zwas, Daniel Jacoby, Andrew Wang, Carolyn Y Ho, Wanying Li, Amy J Sehnert, Iacopo Olivotto, Theodore P Abraham
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 78 Issue 25 Pg. 2518-2532 (12 21 2021) ISSN: 1558-3597 [Electronic] United States
• PMID: 34915982 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Benzylamines
• Biomarkers
• MYK-461
• Uracil
• Cardiac Myosins

Topics

• Aged
• Benzylamines (pharmacology, therapeutic use)
• Biomarkers (blood)
• Cardiac Myosins (antagonists & inhibitors)
• Cardiomyopathy, Hypertrophic (blood, diagnostic imaging, drug therapy)
• Double-Blind Method
• Echocardiography
• Exercise Tolerance (drug effects)
• Female
• Heart (drug effects)
• Humans
• Male
• Middle Aged
• Uracil (analogs & derivatives, pharmacology, therapeutic use)