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

doi:10.1016/j.jacc.2021.09.1381

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

Medicine, Cardiology Division

Research output: Contribution to journal › Article › peer-review

77 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2518-2532
Number of pages	15
Journal	Journal of the American College of Cardiology
Volume	78
Issue number	25
DOIs	https://doi.org/10.1016/j.jacc.2021.09.1381
State	Published - Dec 21 2021

Funding

The authors thank the patients who participated in the EXPLORER-HCM study and their families, as well as the study coinvestigators, research nurses, and coordinators at each of the clinical sites. The authors also thank the cardiac sonographers at each site and the entire Brigham and Women’s Hospital Cardiovascular Imaging Core Laboratory team. Editorial support was provided by Kim Fuller, PhD, of Cello Health Communications/SciFluent Communications, and was supported by MyoKardia, Inc, a wholly owned subsidiary of Bristol Myers Squibb.

Keywords

N-terminal pro–B-type natriuretic peptide
diastolic function
hypertrophic cardiomyopathy
mavacamten

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2021.09.1381

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Hegde, S. M., Lester, S. J., Solomon, S. D., Michels, M., Elliott, P. M., Nagueh, S. F., Choudhury, L., Zemanek, D., Zwas, D. R., Jacoby, D., Wang, A., Ho, C. Y., Li, W., Sehnert, A. J., Olivotto, I., & Abraham, T. P. (2021). Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy. Journal of the American College of Cardiology, 78(25), 2518-2532. https://doi.org/10.1016/j.jacc.2021.09.1381

@article{aced73211cfd4ac18980f06aa49a1108,

title = "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{\textquoteright} (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{\textquoteright} 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{\textquoteright} 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.",

keywords = "N-terminal pro–B-type natriuretic peptide, diastolic function, hypertrophic cardiomyopathy, mavacamten",

author = "Hegde, {Sheila M.} and Lester, {Steven J.} and Solomon, {Scott D.} and Michelle Michels and Elliott, {Perry M.} and Nagueh, {Sherif F.} and Lubna Choudhury and David Zemanek and Zwas, {Donna R.} and Daniel Jacoby and Andrew Wang and Ho, {Carolyn Y.} and Wanying Li and Sehnert, {Amy J.} and Iacopo Olivotto and Abraham, {Theodore P.}",

note = "Publisher Copyright: {\textcopyright} 2021 American College of Cardiology Foundation",

year = "2021",

month = dec,

day = "21",

doi = "10.1016/j.jacc.2021.09.1381",

language = "English (US)",

volume = "78",

pages = "2518--2532",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "25",

}

Hegde, SM, Lester, SJ, Solomon, SD, Michels, M, Elliott, PM, Nagueh, SF, Choudhury, L, Zemanek, D, Zwas, DR, Jacoby, D, Wang, A, Ho, CY, Li, W, Sehnert, AJ, Olivotto, I & Abraham, TP 2021, 'Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy', Journal of the American College of Cardiology, vol. 78, no. 25, pp. 2518-2532. https://doi.org/10.1016/j.jacc.2021.09.1381

TY - JOUR

T1 - Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy

AU - Hegde, Sheila M.

AU - Lester, Steven J.

AU - Solomon, Scott D.

AU - Michels, Michelle

AU - Elliott, Perry M.

AU - Nagueh, Sherif F.

AU - Choudhury, Lubna

AU - Zemanek, David

AU - Zwas, Donna R.

AU - Jacoby, Daniel

AU - Wang, Andrew

AU - Ho, Carolyn Y.

AU - Li, Wanying

AU - Sehnert, Amy J.

AU - Olivotto, Iacopo

AU - Abraham, Theodore P.

PY - 2021/12/21

Y1 - 2021/12/21

N2 - 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.

AB - 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.

KW - N-terminal pro–B-type natriuretic peptide

KW - diastolic function

KW - hypertrophic cardiomyopathy

KW - mavacamten

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SN - 0735-1097

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

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