Development and evaluation of a transesophageal echocardiography–derived left atrial appendage structure–function coupling index across the atrial fibrillation disease continuum

Background Atrial fibrillation (AF) is a progressive disorder associated with atrial remodeling and thromboembolic risk. We developed a transesophageal echocardiography (TEE)-derived left atrial appendage (LAA) structure-function coupling index (LAA-SFCI), defined as LAA volumetric load relative to longitudinal deformation, and assessed its distribution along the AF disease continuum and its potential for risk re-stratification of patients without documented AF. Methods This single-center, prospective, cross-sectional study included 267 patients undergoing clinically indicated TEE, classified by the 2023 American College of Cardiology/American Heart Association/American College of Clinical Pharmacy/Heart Rhythm Society (ACC/AHA/ACCP/HRS) framework as Stage 1 ( n = 68), Stage 2 ( n = 65), Stage 3a ( n = 66), or Stage 3b ( n = 68). Seven candidate LAA-SFCIs were calculated as the LAA volume index (LAA-VI) divided by a functional measure, and the principal index was selected by ordinal logistic regression using the Akaike information criterion. Discrimination was compared using the DeLong test and internally validated by bootstrapping, and patients without documented AF (Stages 1–2) were stratified by the exploratory cutoff. Results LAA-VI/LAA-GLS (LAA global longitudinal strain) provided the best model fit and rose across AF stages from 0.33 ± 0.11 to 0.86 ± 0.36 (mL/m 2 )/% ( P < 0.001). In ordinal regression with the log-transformed index, each 1-SD increase remained associated with higher AF stage after adjustment for age, sex, body mass index, left ventricular ejection fraction, and left atrial volume index (odds ratio 11.04, 95% confidence interval 7.17–16.98). For Stage 1–2 versus Stage 3a–3b, its area under the curve (0.904; optimism-corrected 0.900) was significantly higher than those of LAA-VI (0.661) and LAA-GLS (0.824) (both DeLong P < 0.001). Among 133 patients without documented AF, 18 (13.5%) exceeded the cutoff of 0.460 (mL/m 2 )/%; these patients did not differ from the others in left atrial volume index or age. Conclusion In this cross-sectional study, LAA-VI/LAA-GLS characterized LAA structure–function uncoupling along the AF disease continuum. In patients without documented AF undergoing clinically indicated TEE, it identified a subgroup with an AF-like LAA phenotype not captured by conventional atrial size measures. These findings are hypothesis-generating and require external validation and longitudinal follow-up to determine their prognostic value.