Impaired 3D left atrial volumetric/ mechanical coupling index is related to unfavorable mitral remodeling and adverse clinical events in primary mitral regurgitation

Background Left atrial (LA) remodeling in mitral regurgitation (MR) involves progressive LA dilatation and declining LA function. A LA volumetric/ mechanical uncoupling, detected in 2D echocardiography by the ratio of LA maximum volume index to mitral late diastolic annular velocity (LACI), signals advanced LA disease and has been retrospectively linked to worse survival in mitral valve prolapse. However, prospective conformation using 3D echocardiography is lacking. Purpose To assess the association of increased 3DLACI with 3D mitral valve remodeling and adverse clinical outcomes in moderate or greater primary MR. Methods We measured 3DLACI in 122 patients (34% women) in sinus rhythm included in the prospective 3D Echocardiography and Cardiovascular Prognosis in Mitral Regurgitation (3D-PRIME) study. We compared 3D mitral geometry (annular and leaflet areas), LA function (3DLACI, reservoir strain: LASr) and LV remodeling (3D volumes, ejection fraction (EF), global longitudinal strain (GLS)) across tertiles of 3DLACI. MR severity was quantified by regurgitant fraction. The primary outcome was a composite of mitral intervention, heart failure hospitalization, or death over 2 years. Results 3DLACI did not differ by sex but increased with age, comorbidity (notably diabetes and antihypertensive treatment), and MR severity (p<0.05, Figure 1). Higher 3DLACI was associated with larger mitral annulus and leaflet areas- most pronounced in the anterior leaflet (Figure 1), reduced LASr and larger LV volumes (all p<0.001). LV EF and GLS were comparable across tertiles. Systolic pulmonary vein flow declined sharply in the highest tertile (p<0.001). In multivariable Cox analysis, the highest 3D LACI tertile had an 8.3-fold higher hazard (95% CI 3.0-22.9) and the middle tertile a 3.0-fold higher hazard (95% CI 1.3-7.1) for the composite outcome after adjusting for age, LASr, LV end-systolic volume, and MR severity (p<0.001, Figure 2). Conclusion 3D LA volumetric-mechanical uncoupling is easy to assess echocardiographically, correlates with adverse mitral and atrio-pulmonary remodeling, and strongly predicts unfavorable clinical events in primary MR.Figure 1Figure 2