Atrial reverse remodelling and restored atrioventricular coupling define diastolic recovery during mavacamten therapy in obstructive hypertrophic cardiomyopathy
S Gonzalez De Alaiza, A Al Wazzan, P C Craciun, M Lacout, G L'Official, A Guichard, M Bezard, J Broustaille, E DonalAbstract
Background
In obstructive hypertrophic cardiomyopathy (oHCM), diastolic dysfunction is a major determinant of symptoms, yet its echocardiographic assessment relies on ASE algorithms centered on ventricular relaxation parameters that are not validated in this disease. The mechanisms underlying diastolic improvement during mavacamten therapy remain uncertain.
Purpose
To characterise the temporal sequence and mechanistic determinants of diastolic recovery during the first 6 months of mavacamten therapy, with specific focus on atrial remodelling and atrioventricular (AV) coupling.
Methods
In this prospective single-centre study, 99 consecutive patients with symptomatic oHCM initiating mavacamten underwent standardised echocardiography at baseline and at 1, 2, 3, and 6 months. Conventional diastolic indices (e′, E/e′, E/A) were analysed alongside atrial volumetric, functional, and coupling metrics (LAVImin, LASI, LACI, LAVCI, LAEF). Longitudinal trajectories and mixed-effects models assessed relationships among filling pressure, atrial remodelling, and mitral regurgitation (MR).
Results
Ventricular relaxation (e′) improved early (at 1 month), followed by coordinated reductions in E/e′, MR, LAVI, LASI, and LAVCI at 2 months. Minimal left atrial volume index (LAVImin) decreased later but markedly, reaching −5.6 ± 1.1 mL/m² at 6 months (p<0.001). In contrast, atrial strain and LAEF remained unchanged. Longitudinal modelling showed that E/e′ independently tracked LAVImin (β 0.64, 95% CI 0.38–0.90, p<0.001) and LAVCI (β 0.02, 95% CI 0.01–0.02, p<0.001), while MR severity was associated only with LAVImin (β 0.19 per +1 SD, 95% CI 0.08–0.30, p=0.001). Among atrial metrics, LAVImin demonstrated the strongest independent association with diastolic grade and uniformly predicted filling-pressure normalisation. ASE diastolic grading was frequently non-applicable and only modestly correlated with atrial indices.
Conclusions
Diastolic recovery during mavacamten therapy in oHCM follows a reproducible sequence of early ventricular relaxation, rapid pressure unloading, and subsequent atrial reverse remodelling with restoration of AV coupling. Minimal LA volume emerges as the dominant structural marker of this process, whereas conventional ASE grading incompletely reflects its magnitude and mechanism. Atrial volumetric-coupling metrics may provide a more physiologically grounded framework for monitoring diastolic improvement in oHCM.Staged diastolic recovery with Mavacamten.Reach of variables to signification over time