Effect of mavacamten on left atrial remodeling and function in obstructive hypertrophic cardiomyopathy. A real-world multicentric prospective study

Abstract

Mavacamten, a selective cardiac myosin inhibitor, improves left ventricular outflow tract (LVOT) obstruction and symptoms in patients with obstructive hypertrophic cardiomyopathy (OHCM). Its beneficial effects on LV diastolic indices have been documented, whereas its impact on left atrial strain has only recently been explored.

Aims

To assess the effect of Mavacamten on left atrial remodeling and function in patients with OHCM.

Methods

In this prospective multicenter French study, 273 symptomatic OHCM patients (mean age 67.5 ± 12.0 years, 40% male) were evaluated. NYHA functional class, NT-proBNP values, and echocardiographic data were collected before initiation and at the end of Mavacamten titration. Echocardiographic parameters included left atrial end-systolic volume (LA-ESV), PALS (Peak Atrial Longitudinal Strain), PACS (Peak Atrial Contraction Strain), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), and maximal LVOT gradients.

Results

Primary objective: assessing left atrial remodeling and function

After a mean titration of 5.1 months (final median maintenance dose 5 mg/day), LA-ESV decreased from 87 [69-107] to 70 [56-93] ml (p < 0.001), and indexed LA-ESV from 45[37-56] to 37 [30-46] mL/m² (p < 0.001). PALS remained stable at 19% and PACS decreased from 10 [6-13] % to 9 [5-12] % (p=0.08).

Secondary objectives: clinical, biological and LV systolic effects

NYHA class decreased from 2 [2-3]to 1[1-1] (p<0.001) and NT-proBNP from 876 [316-2130] to 186 [80-445] pg/mL (p=0.001). LVEF decreased from 65 [60-70] to 63 [57-68] % (p<0.001) and GLS was unchanged. Maximum septal thickness decreased from 19 to 17 mm (p<0.001). Resting LVOT gradients decreased from 50.5 to 9.5 mmHg, and Valsalva gradients decreased from 82 to 16 mmHg (both p<0.001).

Conclusion

Mavacamten significantly improves LA remodeling with marked clinical and hemodynamic benefit in OHCM. However, persisting LA dysfunction assessed by strain parameters suggests a dissociation between structural reverse remodeling and functional recovery, possibly related to residual myocardial stiffness or fibrosis. Further studies with longer follow-up are warranted to clarify the temporal relationship between structural and functional remodeling under myosin inhibition.tablecentral illustration