Authors: Abdulrazzaq Qattea , Samhar Samer Alouch , Abdul Rahman Sukar , Sami Qattea , Saud Khalaf , Aghiad Alkhachem , Amjad Ajam , Abdul Razzak Chalab Cham , Kenan Badran , Khaled S. M. Elshaer , Mohamed Naim Khalil , Sanad Syam ,

Abstract

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.

Keywords: Myosin inhibitors, Hypertrophic cardiomyopathy, mavacamten, aficamten