Left Atrioventricular Coupling Index in Health and Disease: A Longitudinal Multicohort Analysis

BACKGROUND: The Left Atrioventricular Coupling Index (LACI), calculated as the ratio of left atrial (LA) to left ventricular (LV) end-diastolic volume (EDV) has emerged as a novel imaging biomarker of LA-LV coupling. However, reference thresholds are undefined and its predictive value beyond established clinical and imaging markers remains uncertain, limiting broader clinical implementation. METHODS: Two large datasets were leveraged to 1) investigate demographic variations of LACI in health, 2) establish population-specific reference thresholds, 3) characterise the relationship between LACI and cardiac structure/function, and 4) investigate its incremental predictive value for cardiovascular outcomes. Cardiovascular magnetic resonance (CMR) scans were performed and analysed using standardised protocols. In the Healthy Hearts Consortium (HHC), a large image bank of verified healthy individuals, demographic variations of LACI were examined, and population-specific reference thresholds were calculated using the 95% prediction interval method. Associations between LACI and markers of LA/LV structure and function were assessed using linear regression models. In UK Biobank, associations of LACI with incident outcomes atrial fibrillation (AF), heart failure (HF), myocardial infarction, cardiovascular death, all-cause death were examined over a median 5.5 years prospective follow-up, using Cox regression models adjusted for demographic, clinical, and established CMR variables. RESULTS: In the HHC (n=7,111, 54% female, median 61.5 years), a higher LACI was observed in older age, ethnicities other than White, and women (who also had a greater age-related increase in LACI). After adjustment for demographic factors, higher LACI was associated with poorer LA function and higher LV filling pressures. In UK Biobank (n=25,849, 52% female, median 63.0 years), higher LACI was independently predictive of incident AF HR per 1 standard deviation increase 1.31 (1.19, 1.44) and HF HR 1.15 (1.07, 1.24), in Cox models adjusted for demographic, clinical, and established CMR variables. Applying the newly derived reference thresholds in a population-specific manner to the UKB cohort revealed a significantly higher probability of AF and HF amongst those with a raised LACI. CONCLUSION: LACI is a robust predictor of AF and HF with incremental value over established clinical and imaging markers. The provided population-specific reference thresholds permit its broader clinical application.