Impact of mavacamten on left atrial remodeling in obstructive hypertrophic cardiomyopathy: data from 3 portuguese centers

Background Left atrial (LA) remodeling is a key marker of diastolic burden and atrial arrhythmic risk in hypertrophic cardiomyopathy (HCM). Mavacamten improves left ventricular outflow tract (LVOT) obstruction and filling pressures, but real-world data on its impact on LA structure and function remain limited. Objective To evaluate LA structural and functional remodeling in patients with obstructive HCM treated with mavacamten across three Portuguese centers. Methods We conducted a multicenter observational study including consecutive patients with symptomatic obstructive hypertrophic cardiomyopathy treated with mavacamten. Clinical data, laboratory parameters, ECG, cardiopulmonary exercise testing, and comprehensive echocardiography were collected at baseline, 4, 8 and 12 weeks, and at individually defined optimal dosing. Cardiac magnetic resonance was incorporated when available. Echocardiographic analysis focused on left atrial remodeling and diastolic burden, including LA diameter (LAd), indexed LA volume, E/e′, transmitral inflow patterns. Paired comparisons across timepoints were performed with appropriate parametric tests, and effect sizes (Cohen’s d) and 95% confidence intervals (CI) were calculated. LA enlargement was defined as LAD ≥ 40 mm; changes in its prevalence were tested with McNemar’s test. Results Eighty-three patients were included (mean age 65 ± 12 years; 68.7% female). LAd showed no significant change at 12 weeks (44.2 ± 6.6 vs 43.2 ± 6.2 mm; mean change -1.0 mm, 95% CI 2.1 to 0.2; p = 0.11). At optimal dosing, however, LA structural reverse remodeling became evident: LAd decreased from 44.8 ± 6.0 to 41.2 ± 6.0 mm (mean change -3.7 mm, 95% CI -5.3 to -2.0; p < 0.001; Cohen’s d = 0.66). The prevalence of LA enlargement fell from 79.1% to 55.8% (p = 0.013, McNemar). Similarly, E/e′ decreased from 16.6 ± 6.3 to 13.7 ± 5.4 at 12 weeks (mean change -2.9; 95% CI -4.3 to -1.6; p < 0.001; d = 0.66) and further to 10.6 ± 3.6 at optimal dose (mean change -4.3; 95% CI -5.7 to -2.8; p < 0.001; d ≈ 1.0). Conclusion Mavacamten produced clear left atrial reverse remodeling, reflected by reductions in LA size and filling pressures, indicating effective and sustained atrial unloading. Given the central role of LA burden in arrhythmic risk, these real-world findings suggest a potential atrial disease-modifying effect of mavacamten, supporting further evaluation of its impact on AF susceptibility.