Key result
Mavacamten improves symptoms and helps ~90% of obstructive HCM patients avoid septal reduction therapy.
Why the study?
To evaluate the clinical efficacy and safety of mavacamten, a first-in-class selective cardiac myosin inhibitor, in symptomatic obstructive hypertrophic cardiomyopathy using data from randomized trials and real-world studies.
Does mavacamten improve hemodynamics, functional capacity, and quality of life in patients with symptomatic obstructive hypertrophic cardiomyopathy?
Systematic Review
Does mavacamten improve hemodynamics, functional capacity, and quality of life in patients with symptomatic obstructive hypertrophic cardiomyopathy?
Mavacamten is a transformative, mechanism-targeted therapy that significantly improves hemodynamics, functional capacity, and quality of life in patients with symptomatic obstructive hypertrophic cardiomyopathy, though it requires rigorous echocardiographic monitoring for LVEF reductions.
Mavacamten may benefit symptomatic oHCM; hypothesis-generating Level 3 data leave efficacy and safety open for confirmation in RCTs.
Introduction: Hypertrophic cardiomyopathy (HCM) is an inherited condition characterized by sarcomeric hypercontractility, leading to dynamic left ventricular outflow tract (LVOT) obstruction in approximately 70% of patients. Mavacamten, a first-in-class selective cardiac myosin inhibitor, addresses the underlying molecular cause by reducing excessive actin-myosin cross-bridge formation. Aim: To evaluate the clinical efficacy and safety of mavacamten in symptomatic obstructive HCM (oHCM) using data from randomized trials and real-world studies. Methods: A systematic search of PubMed, Embase, and Cochrane Library identified 110 publications. Following predefined criteria, 44 studies were included in the final analysis, including pivotal phase III trials (EXPLORER-HCM, VALOR-HCM) and long-term extensions. Results: Mavacamten demonstrated a significant reduction in LVOT gradients (mean reduction of ~47 mmHg in EXPLORER-HCM) and improved quality of life, with KCCQ-CSS scores increasing by an average of 14.2 points. Between 60% and 80% of patients achieved ≥1 NYHA functional class improvement. In the VALOR-HCM trial, approximately 90% of patients avoided invasive septal reduction therapy (SRT) through 128 weeks. The primary safety concern was a transient reduction in LVEF (<50%) occurring in 5–14% of patients, which was typically reversible with dose titration. Conclusion: Mavacamten is a transformative non-invasive therapy that shifts oHCM management from palliative care to mechanism-targeted treatment. While highly effective in improving hemodynamics and functional capacity, rigorous echocardiographic monitoring remains mandatory to ensure safety regarding systolic function.
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Szkatuła et al. (2026) conducted a systematic review in Symptomatic obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten vs. Placebo or standard of care was evaluated on Reduction in left ventricular outflow tract (LVOT) gradients, NYHA functional class improvement, and avoidance of septal reduction therapy. Mavacamten significantly reduced left ventricular outflow tract gradients, improved NYHA functional class in 60-80% of patients, and enabled ~90% of patients to avoid septal reduction therapy.
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