Key result
Cardiac myosin inhibitors reduce resting LVOT gradient by ~59 mmHg vs placebo in HCM.
Why the study?
Cardiac myosin inhibitors alter cardiomyocyte contractility in HCM, but their hemodynamic and cardiac functional effects needed systematic evaluation.
Do cardiac myosin inhibitors improve hemodynamic and functional outcomes in adult patients with hypertrophic cardiomyopathy compared to placebo?
Meta-Analysis (n=883)
Yes
Do cardiac myosin inhibitors improve hemodynamic and functional outcomes in adult patients with hypertrophic cardiomyopathy compared to placebo?
Effect estimate: MD -59.38 (95% CI -63.24 to -55.52)
p-value: p=0.00001
Cardiac myosin inhibitors significantly improve LVOT gradients, NYHA functional class, and NT-proBNP levels in patients with hypertrophic cardiomyopathy, though they are associated with a modest reduction in LVEF.
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“The patients on CMIs (mavacamten or aficamten) unequivocally demonstrated a significant reduction in both resting and post-Valsalva LVOT gradients, as compared with a placebo. There were notable improvements in NYHA functional class, NT-proBNP and cTnI levels, and quality of life over a follow-up of 10–30 weeks. However, it is critical to acknowledge that all six RCTs reported significant reduction (mean difference of 4.7%; 95% CI −7.22% to −2.26%) in LVEF.”
Warrants LVEF monitoring with myosin inhibitor therapy in HCM; reinforces RCT evidence for hemodynamic benefit.
Background: Cardiac myosin inhibitors are new medications found to change the course of hypertrophic cardiomyopathy (HCM) by altering cardiomyocyte contractility. This systematic review and meta-analysis aimed to investigate the effects on hemodynamic and cardiac function changes with mavacamten and aficamten in obstructive and non-obstructive hypertrophic cardiomyopathy. Methods: A meta-analysis of randomized controlled trials was conducted following PRISMA standards. We searched PubMed, Scopus, and Cochrane CENTRAL from December 2025 to February 2026 and assessed studies comparing cardiac myosin inhibitors with placebo groups and analyzed results based on hemodynamic and cardiac functional changes, including left ventricular ejection fraction (LVEF), resting left ventricular outflow tract (LVOT), and post-Valsalva LVOT. Other outcomes such as New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ) score, serious adverse events, pVO₂, and NT-proBNP were evaluated. RevMan was used to perform statistical analyses. Result: Seven RCTs, including 883 patients, were analyzed. Treatment with myosin inhibitors demonstrated significant improvement in resting LVOT (MD -59.38, 95% CI: -63.24 to -55.52) and post-Valsalva LVOT gradients (MD -58.05, 95% CI: -67.28 to -48.81) compared with placebo. LVEF decreased significantly in the myosin inhibitor group (MD −4.38, 95% CI −6.71 to −2.06). Myosin inhibitors significantly improved NYHA class (RR 2.15, 95% CI 1.80 to 2.57) and KCCQ scores (MD 7.36, 95% CI 4.71 to 10.01) versus placebo. NT-proBNP was significantly decreased in the myosin inhibitor group (MD -16.61%, 95%CI: -26.85 to -6.38). PVO₂ and serious adverse events were similar between groups. Conclusion: Our systematic review meta-analysis found that myosin inhibitors significantly improved resting and post-Valsalva LVOT gradients, reduced LVEF, improved NYHA class and NT-proBNP, and had similar pVO₂ and serious adverse events compared to placebo. Key words: Myosin inhibitors, hypertrophic cardiomyopathy, mavacamten, aficamten
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Qattea et al. (2026) conducted a meta-analysis in Hypertrophic cardiomyopathy (n=883). Cardiac myosin inhibitors (mavacamten and aficamten) vs. Placebo was evaluated on Mean change from baseline in resting LVOT gradient (MD -59.38, 95% CI -63.24 to -55.52, p=0.00001). Cardiac myosin inhibitors significantly reduced resting left ventricular outflow tract gradient (MD -59.38) compared to placebo in patients with hypertrophic cardiomyopathy.
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