Left Atrial Remodeling, Hemodynamic Burden, and Time-Varying Risk of Newly Documented Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction

Abstract

Background: Left atrial volume index (LAVI) reflects atrial remodeling in heart failure with preserved ejection fraction (HFpEF), but its nonlinear, hemodynamic, and time-varying associations with atrial fibrillation (AF) remain uncertain. Objectives: To assess the association of baseline LAVI with documented incident AF in HFpEF. Methods: We studied 764 patients with HFpEF without documented AF in a Hong Kong registry. LAVI was analyzed continuously, by tertiles, and with restricted cubic splines. Incident AF was the first qualifying AF diagnosis or electrocardiographic record after echocardiography. Cause-specific Cox and Fine-Gray models were used, with death before AF as a competing event. A hemodynamic overlap-adjusted model additionally included E/e' ratio and pulmonary artery systolic pressure. Results: During a median follow-up of 5.81 years, 360 patients developed documented incident AF and 272 died before AF was documented. In the primary clinical model, each 10-mL/m2 increase in LAVI was associated with incident AF in cause-specific Cox regression (HR, 1.08; 95% CI, 1.06-1.11) and Fine-Gray regression (sHR, 1.06; 95% CI, 1.04-1.09). After hemodynamic overlap adjustment, the continuous association was attenuated. However, the highest LAVI tertile remained associated with incident AF (HR, 1.78; 95% CI, 1.28-2.49; sHR, 1.47; 95% CI, 1.05-2.04). Splines showed nonlinear excess risk at higher LAVI, and period-specific analyses showed the strongest association during the first year. Conclusions: Marked left atrial enlargement identified a structural-hemodynamic phenotype associated with early documented incident AF and may support risk-enriched rhythm surveillance.