Mavacamten Improves Pathophysiological Markers in Obstructive HCM

Treatment with mavacamten may improve left ventricular (LV) diastolic function, systolic anterior motion, and other important markers in the pathophysiology of obstructive hypertrophic cardiomyopathy (HCM), according to a secondary analysis of the EXPLORER-HCM trial published Dec. 13 in the Journal of the American College of Cardiology.

EXPLORER-HCM was a multicenter, double-blind, placebo-controlled, randomized, phase 3 study which demonstrated significant reduction in LV outflow tract gradients, improved exercise capacity, improved health status and decreased symptom burden without clinically significant changes in LV ejection fraction after 30 weeks of mavacamten treatment.

In the analysis, Sheila M. Hegde, MD, FACC, and colleagues evaluated the effect of mavacamten on measures of cardiac structure and function using serial echocardiograms over 30 weeks from 251 symptomatic patients treated with either mavacamten or placebo. Resting echocardiograms were performed at screening; day 1; and weeks 4, 6, 12, 18, 22, 26, 30 (end of treatment) and 38 (end of study). Post-exercise echocardiograms were performed at screening and week 30. All studies were assessed by a core laboratory. The mean age was 58.5 years, 41% of patients were women, and most (92%) were taking background beta-blocker or calcium-channel blocker therapies at baseline.

Results showed that patients on mavacamten were more likely than those on placebo to show complete resolution of mitral valve systolic anterior motion after 30 weeks (80.9% vs. 34.0%; difference, 46.8%; p<0.0001). They also demonstrated improved echocardiographic measures of diastolic function, including left atrial volume index (LAVI) (mean change from baseline of –7.5 mL/m2 vs. –0.09 mL/m2; p<0.0001) and early diastolic mitral annular velocity (e’), with an associated reduction in NT-proBNP and improvements in LV hypertrophy. Reduction in LAVI was also associated with improved peak exercise oxygen consumption (p=0.04). Improvements in markers of diastolic function were seen after as little as 18 weeks of treatment.

“The improvements in LV diastolic function, cardiac morphology, and biomarkers observed with mavacamten have not been reported in relation to contemporary pharmacologic therapies for symptomatic obstructive HCM, such as beta-blockers, nondihydropyridine calcium-channel blockers, and disopyramide,” note the authors, stressing that these demonstrate improvement in important markers of the pathophysiology of obstructive HCM.

In an accompanying editorial comment, Ahmed Masri, MD, MS, FACC, writes that although more study is needed, “Overall, the current evidence supports an indication for mavacamten use in patients who continue to be symptomatic despite treatment with [beta-blockers] or calcium-channel blockers.”

Clinical Topics: Heart Failure and Cardiomyopathies, Noninvasive Imaging, Statins, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Hypertrophy, Heart Atria, Oxygen Consumption, Health Status, Biomarkers, Cardiology, Echocardiography, Diastole, Cardiomyopathy, Hypertrophic, Uracil, Benzylamines, Double-Blind Method, Laboratories, Exercise Tolerance, Stroke Volume, Mitral Valve, Disopyramide, Calcium Channel Blockers

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