Left Atrial Remodeling, Hemodynamic Burden, and Time-Varying Risk of Newly Documented Atrial Fibrillation in Heart Failure With Preserved Ejection Fraction
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Background
Left atrial volume index (LAVI) reflects chronic left atrial remodelling in heart failure with preserved ejection fraction (HFpEF), but its nonlinear, haemodynamic, and time-varying associations with newly documented atrial fibrillation (AF) remain uncertain.
Methods
We studied 764 patients with HFpEF without documented AF at baseline from a deidentified electronic health record registry in Hong Kong. Baseline LAVI was evaluated continuously, by tertiles, and using restricted cubic splines. Documented incident AF was defined as the first qualifying AF diagnosis or electrocardiographic record after the index echocardiogram. Cause-specific Cox and Fine–Gray models were used, with death before AF treated as a competing event. A haemodynamic overlap-adjusted model additionally included E/e′ ratio and pulmonary artery systolic pressure (PASP).
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 higher risk of documented 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 adjustment for E/e′ ratio and PASP, the continuous association was attenuated. However, the highest LAVI tertile remained associated with documented incident AF in both cause-specific Cox regression (HR, 1.78; 95% CI, 1.28–2.49) and Fine–Gray regression (sHR, 1.47; 95% CI, 1.05–2.04). Restricted cubic splines demonstrated a nonlinear association, with excess risk concentrated in the upper LAVI range. Period-specific analyses showed that the LAVI–AF association was strongest during the first year after echocardiography and attenuated thereafter.
Conclusions
In HFpEF patients without documented AF at baseline, marked left atrial enlargement identified a high-risk structural–haemodynamic phenotype for clinically documented incident AF. Routine echocardiographic measures may support risk-enriched rhythm surveillance, particularly early after echocardiographic assessment.
