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

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

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

68 Citations (Scopus)

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)

Original languageEnglish
Pages (from-to)2518-2532
Number of pages15
JournalJournal of the American College of Cardiology
Volume78
Issue number25
Early online date13 Dec 2021
DOIs
Publication statusPublished - 21 Dec 2021

Bibliographical note

Funding Information:
Study funding was provided by MyoKardia, Inc, Brisbane, CA, a wholly owned subsidiary of Bristol Myers Squibb. Dr Hegde serves on the faculty of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital; and her institution has received payments for her consulting work from MyoKardia. Dr Lester’s institution has received payments for his consulting work for MyoKardia. Dr Solomon is Director of the Cardiovascular Imaging Core Laboratory at Brigham and Women’s Hospital; has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, NeuroTronik, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, and Theracos; and has consulted for Abbott, Action Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Lilly, Merck, MyoKardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, AOBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, DiNAQOR, Tremeau, CellProthera, Moderna, and American Regent. Dr Michels has received personal fees and payments as a consultant from MyoKardia. Dr Elliott has received payments as a consultant from MyoKardia, Pfizer, AstraZeneca, and Sanofi Genzyme; and has received speaker fees from Sanofi Genzyme. Dr Zemanek has received speaking honoraria from Abbott and Bayer. Dr Zwas has received personal fees from MyoKardia. Dr Jacoby has received personal fees from MyoKardia. Dr Wang has received grants and payments as a consultant from MyoKardia; and has received personal fees from Cytokinetics. Dr Ho has received payments as a consultant from MyoKardia, Tenaya, Novartis, and Ambry Genetics. Drs Li and Sehnert are employees of and have stocks or stock options in MyoKardia. Dr Olivotto has received grants from MyoKardia, Sanofi Genzyme, Shire, and Bayer; has received personal fees from Sanofi Genzyme, Shire, Amicus, and Bayer; and has received payments as a consultant from MyoKardia and Cytokinetics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Publisher Copyright:
© 2021 American College of Cardiology Foundation

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