Mavacamten improves left ventricular systolic synchrony in obstructive hypertrophic cardiomyopathy: real-world data from China
W Liang, M Sun, Y Sun, X Wei, Y Liu, N Zhou, Y Chen, S Zhang, X Shu, J GeAbstract
Background
Mavacamten, a first-in-class cardiac myosin inhibitor, effectively reduces left ventricular outflow tract gradients (LVOTG) in obstructive hypertrophic cardiomyopathy (HCM). However, real-world data on its impact on advanced myocardial mechanics, specifically peak systolic dispersion (PSD) and non-invasive myocardial work, remain limited.
Purpose
To evaluate the 24-week longitudinal effects of mavacamten on haemodynamics, mechanical dispersion, and myocardial work indices in a real-world cohort of patients with symptomatic obstructive HCM.
Methods
In this single-centre observational cohort, 32 symptomatic patients (12 women, 38%; age 56±11 years) with obstructive HCM initiating mavacamten underwent comprehensive transthoracic echocardiography at baseline and 4, 8, 12, 24, and 48 weeks. We assessed resting and Valsalva LVOTG, left ventricular ejection fraction (LVEF), global longitudinal strain (LVGLS), PSD, and myocardial work indices including global work efficiency (GWE) and global wasted work (GWW). Data were analysed using a Mixed Model for Repeated Measures (MMRM) with a first-order autoregressive [AR(1)] covariance structure. We report the least squares mean (LS mean) changes from baseline to 24 weeks with 95% confidence intervals (CI).
Results
At 24 weeks, mavacamten treatment was associated with marked haemodynamic relief. Resting LVOTG decreased by an LS mean of 25.68 mmHg (95% CI -41.80 to -9.55; p<0.001) and Valsalva LVOTG by 32.37 mmHg (95% CI -52.73 to -12.02; p<0.001) versus baseline. Left ventricular mechanical dyssynchrony improved, with a reduction in PSD of 34.68 ms (95% CI -56.72 to -12.64; p<0.001). LVEF showed a modest, non-significant decline (-3.72%, 95% CI -8.12 to 0.69; p=0.13) but remained within the normal range, and LVGLS tended to became more negative (-1.4%; p=0.06). Myocardial work indices suggested enhanced efficiency, with a reduction in GWW (-56.17 mmHg%; p=0.09) and an increase in GWE (+3.01%; p=0.08).
Conclusions
In a real-world Chinese cohort with obstructive HCM, mavacamten provided sustained relief of resting and provokable LVOT obstruction over 24 weeks without compromising global systolic function. Treatment significantly improves left ventricular mechanical dispersion and was associated with signals of improved myocardial work efficiency, supporting early reverse remodelling and restoration of systolic synchrony beyond gradient reduction alone.LVOTG and PSD over 48 weeks of mavacamten