Key result
Cardiac myosin inhibitors reduce resting LVOT gradients by ~38 mmHg vs placebo in oHCM.
Why the study?
The effects of cardiac myosin inhibitors on echocardiographic parameters and cardiopulmonary performance across randomized controlled trials have not yet been systematically synthesized.
Do Cardiac Myosin Inhibitors improve echocardiographic parameters and cardiopulmonary performance in patients with obstructive Hypertrophic Cardiomyopathy?
Meta-Analysis (n=767)
Do Cardiac Myosin Inhibitors improve echocardiographic parameters and cardiopulmonary performance in patients with obstructive Hypertrophic Cardiomyopathy?
Mean Difference: -37.59 (95% CI -47.35–-27.83)
p-value: p=<0.01
Cardiac myosin inhibitors significantly improve hemodynamics, promote reverse cardiac remodeling, and enhance exercise tolerance in patients with obstructive hypertrophic cardiomyopathy.
Supports myosin inhibitor adoption to defer septal reduction in obstructive HCM; extends RCT data via meta-analytic confirmation.
Background: Cardiac Myosin Inhibitors (CMIs), including mavacamten and aficamten, represent a novel class of targeted therapies for obstructive Hypertrophic Cardiomyopathy (oHCM).Their effects on echocardiographic parameters and cardiopulmonary performance across Randomized Controlled Trials (RCTs) have not yet been systematically synthesized.Objectives: To conduct a systematic review and meta-analysis of RCTs in accordance with the PRISMA guidelines.Methods: Primary echocardiographic outcomes included Left Ventricular Ejection Fraction (LVEF), Left Ventricular Mass Index (LVMI), Interventricular Septal Thickness (IVST), E/e' septal ratio, and resting, Valsalva, and post-exercise Left Ventricular Outflow Tract gradients (LVOT-G).Cardiopulmonary Exercise Testing (CPET) outcomes were also assessed.Data were pooled using random-effects models and reported as Mean Differences (MDs) or Standardized Mean Differences (SMDs), with 95% Confidence Intervals (CIs).Results: Five RCTs comprising 767 participants were included.CMIs significantly reduced resting LVOT-G (MD: -37.59 mmHg), Valsalva gradients (MD: -46.45 mmHg), and post-exercise gradients (MD: -49.45 mmHg; all p < 0.01).Reverse cardiac remodeling was reflected by reductions in LVMI (MD: -11.96 g/m²), IVST (SMD: -0.98), and E/e' septal ratio (MD: -3.53), along with an expected modest reduction in LVEF (MD: -4.33%).CPET outcomes also improved significantly, including ventilatory efficiency (MD: -2.25), peak metabolic equivalents (METs) (MD: +0.45), peak circulatory power (MD: +482.78 mL/kg/min × mmHg), and exercise duration (MD: +0.88 min; all p < 0.01).Subgroup analyses revealed no significant differences between the agents.Conclusion: CMIs promote reverse cardiac remodeling, improve hemodynamics, and enhance exercise tolerance in patients with oHCM, supporting their role as disease-modifying targeted therapies.
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Ramos et al. (2026) conducted a meta-analysis in Obstructive Hypertrophic Cardiomyopathy (oHCM) (n=767). Cardiac Myosin Inhibitors (mavacamten and aficamten) vs. Placebo was evaluated on Resting Left Ventricular Outflow Tract Gradient (LVOT-G) (MD -37.59, 95% CI -47.35 to -27.83, p=<0.01). Cardiac myosin inhibitors significantly reduced resting left ventricular outflow tract gradients (MD -37.59 mmHg) and improved cardiopulmonary performance compared to placebo in patients with obstructive hypertrophic cardiomyopathy.
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