Hegde, SM;
Lester, SJ;
Solomon, SD;
Michels, M;
Elliott, PM;
Nagueh, SF;
Choudhury, L;
... Abraham, TP; + view all
(2021)
Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy.
Journal of the American College of Cardiology
, 78
(25)
pp. 2518-2532.
10.1016/j.jacc.2021.09.1381.
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Hegde-JACC060421-2341NR - merged PDF (small).pdf - Accepted Version Download (3MB) | Preview |
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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)
Type: | Article |
---|---|
Title: | Effect of Mavacamten on Echocardiographic Features in Symptomatic Patients With Obstructive Hypertrophic Cardiomyopathy |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.jacc.2021.09.1381 |
Publisher version: | http://dx.doi.org/10.1016/j.jacc.2021.09.1381 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | diastolic function, hypertrophic cardiomyopathy, mavacamten, N-terminal pro–B-type natriuretic peptide |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science |
URI: | https://discovery.ucl.ac.uk/id/eprint/10139960 |
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