Predictors of functional status and quality-of-life improvement with mavacamten in obstructive hypertrophic cardiomyopathy: one-year results from a real-world nationwide cohort

Introduction A substantial proportion of patients with obstructive hypertrophic cardiomyopathy (oHCM) treated with mavacamten do not achieve symptomatic improvement despite significant reductions in, or resolution of, left ventricular outflow tract gradients. In parallel, myectomy remains a highly effective option in experienced, high-volume centers. Identifying predictors of clinical and quality-of-life response to myosin inhibitors is needed to optimize treatment selection and patient management. Purpose To identify predictors of clinical status improvement 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 from oHCM patients treated with mavacamten in Italy between October 2023 and November 2025, within the EAP across 54 cardiology centers. We assessed longitudinal changes in New York Heart Association (NYHA) class and EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) and explored baseline and treatment-related predictors of response over follow-up. Changes from baseline were tested at each timepoint. Results NYHA class improved significantly through 9 months (p<0.001 at 3 months, p=0.002 at 6 months, p=0.001 at 9 months), with a marked reduction in NYHA III (26.8% to 7.4%, 4.9%, and 2.1%, respectively). Quality of life improved early: EQ-5D-5L increased from 70 (55–80) to 80 (65–90) at 3 months (p<0.001) and remained stable thereafter. Improvements were observed in all parameters collected during follow-up, including the severity of mitral regurgitation (MR), which improved early (p<0.001 at 3 months). In univariable analyses, NYHA improvement at nine months was associated with patient age (p=0.027), baseline NYHA class (p<0.001), baseline left ventricular ejection fraction (LVEF) (p=0.01), baseline MR grade (p=0.02), and discontinuation of non-dihydropyridine calcium channel blockers during follow-up (p=0.03), but not with discontinuation of beta-blocker therapy (p=0.10). In multivariable analysis, age (per decade) remained an independent predictor (p=0.01), together with baseline NYHA class (p<0.001) and baseline LVEF (per 5% increase) (p=0.007). Functional class improvement did not differ between patients treated at high-volume centers, defined as centers in the upper quartile of treated patient volume, and those treated at low-volume centers (p=0.56). Conclusion In the Italian nationwide real-world cohort treated with mavacamten, patients experienced improvement in functional class up to nine months of therapy. Lower age, higher baseline NYHA class and higher LVEF predicted improvement in NYHA class. Quality of life showed a marked improvement in the first three months of therapy and became comparable to that of the Italian general population during follow-up. No difference was observed in functional class improvement or adverse event rates between high-volume and low-volume centers.