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

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.

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.

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.

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.