Left Atrial Volumetric Enlargement in Heart Failure With Reduced Ejection Fraction: Obligatory Consequence or...

Left atrial (LA) remodeling, characterized by progressive enlargement, is commonly observed in heart failure with reduced ejection fraction and reflects left ventricular (LV) dysfunction and functional mitral regurgitation (FMR). However, its independent prognostic significance remains uncertain.

This study aims to investigate the independent association between LA volume index (LAVI) and long-term mortality in patients with heart failure, considering its interaction with FMR severity.

A cohort of 13,954 patients who received a diagnosis of heart failure stage B or C and a first diagnosis of reduced LV ejection fraction (<50%) at Mayo Clinic was analyzed. Comprehensive echocardiographic quantification of LAVI, LV function, FMR, and hemodynamics was performed. Survival analysis included Kaplan-Meier curves, Cox proportional hazards models, and spline modeling, adjusted for demographic, clinical, and echocardiographic variables.

Mean LAVI increased with worsening FMR (35 ± 14 mL/m² in no FMR to 61 ± 23 mL/m² in severe FMR). Higher LAVI was associated with increased mortality (HR: 1.13 per 10 mL/m²; P < 0.0001), independent of LV function, FMR, and comorbidities. A mortality risk threshold emerged at LAVI >40 mL/m², with excess mortality increasing steeply beyond this point. Stratification showed significant interactions between LAVI, LV ejection fraction, atrial fibrillation, and pulmonary hypertension. Although LAVI threshold of excess mortality shifted from about 40 mL/m² in no-mild FMR to about 60 mL/m² in severe FMR, the slope of the relationship persisted unaltered, confirming the graded relationship between LAVI and outcome at each FMR grade (P for interaction = 0.35).

LAVI is an independent predictor of mortality in heart failure stage B or C, with excess risk starting at 40 mL/m². The prognostic impact of LAVI persisted with a graded relationship in all FMR severity grades, emphasizing its role in risk stratification. These findings support the integration of LA remodeling assessment into heart failure management to refine prognostic evaluation and therapeutic strategies.