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.
N1 - Funding Information:
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.
Publisher Copyright:
© 2021 American College of Cardiology Foundation
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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U2 - 10.1016/j.jacc.2021.09.1381
DO - 10.1016/j.jacc.2021.09.1381
M3 - Article
C2 - 34915982
AN - SCOPUS:85120373019
SN - 0735-1097
VL - 78
SP - 2518
EP - 2532
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 25
ER -