Mavacamten reduced LVOT gradient by ~80%, improved diastolic function (LA ESV ↓19%, E/E' ratio ↓27%), NYHA class, and NT-proBNP in obstructive HCM over ~5 months.
Does Mavacamten improve diastolic function and left atrial remodeling in patients with symptomatic obstructive hypertrophic cardiomyopathy?
Mavacamten improves diastolic function and reduces left atrial volume in obstructive hypertrophic cardiomyopathy, though left atrial stiffness may persist.
Absolute Event Rate: 0% vs 0%
Abstract Background Obstructive hypertrophic cardiomyopathy (HCM) is characterized by dynamic left ventricular outflow tract (LVOT) obstruction, leading to disabling symptoms. Mavacamten, a selective cardiac myosin inhibitor, has demonstrated efficacy in reducing obstruction and improving clinical outcomes. However, its impact on diastolic function and left atrial remodeling remains poorly characterized. Objectives Primary objective to evaluate the effect of Mavacamten on diastolic function and left atrial (LA) remodeling in patients with obstructive HCM. Secondary objectives to assess its impact on echocardiographic parameters, clinical outcomes (NYHA class, symptoms), and biomarkers (NT-proBNP). Methods This single-center prospective study included 55 symptomatic HCM patients (mean 67.5 11.99 years, 22 men 40%). Mavacamten was titrated to achieve a maximum LVOT gradient 30 mmHg at rest or after Valsalva while maintaining a left ventricular ejection fraction (LVEF) 55%. Parameters assessed before and after titration included diastolic function markers: left atrial end-systolic volume (LA ESV), E/E' ratio, E/A ratio, PALS, PACS, and obstruction gradients (rest, Valsalva), LVEF, LV 2D strain, myocardial wall thickness, and clinical and biological parameters (NYHA class, and NT-proBNP). Results The mean titration duration was 5.11 months. After titration, a significant clinical improvement was observed with a reduction in NYHA class from 2.53 to 1.44 (p0.001) and a decrease in NT-proBNP levels from 2276.8 pg/mL to 395.3 pg/mL (p0.001). LVOT gradient decreased at rest from 65.7 mmHg to 11.9 mmHg, p0.001) and after Valsalva (102.2 mmHg → 19.3 mmHg, p0.001). Mavacamten significantly improved several diastolic function parameters. LA ESV decreased from 53.1 mL/m² to 43.3 mL/m² (p0.001). E/E' ratio improved from 14.5 to 10.6 (p0.001). However, the E/A ratio remained unchanged (1.07 → 1.08, p=NS). LA strain parameters worsened under therapy, with PALS decreasing from 20.6% to 17.5% (p0.01) and PACS from 10.8% to 8.0% (p0.01). LVEF decreased (69% → 66%, p0.001) while remaining above 55%. Left ventricular 2D strain remained unchanged after treatment (-14.56% to -14.89%, p=NS). Conclusions Mavacamten significantly improves diastolic function in patients with obstructive HCM, as evidenced by the decrease in left atrial volume and improvement in the E/E' ratio. This reduction in left ventricular filling pressures is associated with a decrease in outflow gradient and a significant clinical improvement, without negative impact on ejection fraction and with stable global longitudinal ventricular function. However, the observed reduction in PALS and PACS suggests persistent left atrial stiffness despite reduced volume overload. These findings support the role of Mavacamten in the management of obstructive HCM, but further studies are needed to better understand its long-term impact on diastolic function and left atrial remodeling.Graphical abstract
Cohen et al. (Sat,) reported a other. Mavacamten reduced LVOT gradient by ~80%, improved diastolic function (LA ESV ↓19%, E/E' ratio ↓27%), NYHA class, and NT-proBNP in obstructive HCM over ~5 months.