Key result
Mavacamten achieves NYHA class I in ~56% of oHCM patients with low rates of systolic dysfunction.
Why the study?
The efficacy and safety of mavacamten needed evaluation in a nationwide real-world Italian obstructive hypertrophic cardiomyopathy population that was older and had more advanced disease than registrational trial cohorts.
Does mavacamten improve symptoms, echocardiographic parameters, and health status while maintaining safety over 12 months in a real-world cohort of patients with symptomatic obstructive hypertrophic cardiomyopathy?
Cohort (n=369)
Yes
Does mavacamten improve symptoms, echocardiographic parameters, and health status while maintaining safety over 12 months in a real-world cohort of patients with symptomatic obstructive hypertrophic cardiomyopathy?
In a nationwide real-world cohort of older patients with more advanced obstructive hypertrophic cardiomyopathy than in registrational trials, mavacamten demonstrated sustained 12-month improvements in functional status, LVOT gradients, and cardiac remodeling with a 5% rate of transient LVEF <50% primarily predicted by older age.
May support real-world use in older oHCM patients; extends RCT findings but leaves open need for randomized confirmation.
Introduction Mavacamten has radically changed the treatment strategy for obstructive hypertrophic cardiomyopathy (oHCM) for patients who remain symptomatic despite optimal conventional medical therapy.1 Baseline characterization of the Italian cohort has been previously reported, showing a more advanced disease and an older population compared with registrational clinical trials.2 Purpose To evaluate efficacy and safety of mavacamten in the nationwide Italian oHCM population treated with mavacamten within the Early Access Program (EAP). Methods We analyzed baseline and follow-up data at 3, 6, 9 and 12 months between October 2023 and November 2025. Clinical, echocardiographic and biomarker data were collected prospectively in the context of EAP by 54 cardiology centers in Italy. Given the multicenter design and repeated measurements, we used linear mixed-effects models for repeated measures, including random effects for patient and center. Results Longitudinal data from 369 patients treated with mavacamten showed a statistically significant improvement in functional status over the first nine months. At baseline, 73.2% of patients were in NYHA class II and 26.8% in class III; at 12 months, 56.3% were in class I, 41.0% in class II and 2.8% in class III. Mixed-effects models showed a marked shift toward lower NYHA class over follow-up versus baseline, with progressively stronger effects across timepoints (OR -3.35 to -5.25). A marked and sustained reductions in left ventricular outflow tract gradients were observed both at rest (−32.2 mmHg at week 12 to −43.8 mmHg at week 48) and with Valsalva (−41.4 to −66.6 mmHg). Echocardiographic reverse remodeling paralleled hemodynamic improvement, with progressive reductions in maximum left ventricular thickness (−1.00 mm at week 12 to −2.44 mm at week 48) and left atrial volume indexed (−3.3 to −7.7 mL/m²). Patient-reported health status improved throughout follow-up (EQ-5D-5L +9.9 to +12.4). Overall, LVEF <50% occurred in 5% of the cohort, with 76% of events within the first 3 months of treatment. In multivariable analysis, age (per decade) was associated with LVEF <50% (OR 1.67, 95% CI 1.08–2.58, p=0.020), whereas sex, baseline LVEF, baseline NYHA class (II vs III), and treatment in high-volume centers were not significantly associated. Conclusions In a nationwide real-world cohort of older patients with more advanced disease than those enrolled in registrational trials, mavacamten was associated with sustained longitudinal improvement in symptoms, echocardiographic parameters, and biomarkers through 12 months.2 Transient systolic dysfunction occurred in 5% of patients, mainly within the first 3 months, and was comparable to that observed in registrational trials.3 Increasing age emerged as the main predictor of LVEF <50%, supporting closer early surveillance in older patients, while a lower left ventricular ejection fraction prior to therapy was not predictive.
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Bonacchi et al. (2026) conducted a cohort in Obstructive hypertrophic cardiomyopathy (oHCM) (n=369). Mavacamten vs. Baseline (pre-treatment) was evaluated on Functional status (NYHA class I at 12 months) and safety (LVEF <50%) (OR -3.35 to -5.25). Mavacamten improved NYHA class to I in 56.3% of oHCM patients and reduced resting LVOT gradients by 43.8 mmHg at 48 weeks, with LVEF <50% occurring in 5%.
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