Abstract
BACKGROUND: Left atrial (LA) dysfunction is common in heart failure with preserved ejection fraction (HFpEF). The LA volumetric/mechanical coupling index (LACI), calculated as the LA volume index divided by the late diastolic mitral annular velocity (a'), is a recently advocated parameter reflecting LA contractile function based on the atrial Frank-Starling mechanism. An elevated LACI signifies impaired mechanical performance despite greater atrial volume, indicating volumetric/mechanical uncoupling. Its associations with echocardiographic indices and prognostic significance in HFpEF remain unclear. METHODS: This study included 562 patients from the PURSUIT-HFpEF (Prospective Multicenter Observational Study of Patients With Heart Failure With Preserved Ejection Fraction) registry, a prospective multicenter registry for HFpEF. LACI was calculated and categorized into quartiles. Associations with echocardiographic indices and clinical outcomes were examined. RESULTS: LA volume index and late diastolic mitral annular velocity were negatively correlated (r=-0.26; P<0.001), reflecting impaired atrial Frank-Starling mechanism in this cohort. The median LACI was 6.44 (interquartile range, 4.16-9.69). Patients with elevated LACI had unfavorable backgrounds with increased filling pressure and diastolic dysfunction. During a median follow-up of 40 months, 171 patients experienced cardiovascular death or rehospitalization for heart failure, with event incidence increasing across LACI quartiles (quartile 1, 26.4%; quartile 2, 39.0%; quartile 3, 46.1%; quartile 4, 46.4%; log-rank, P=0.001). After multivariable adjustment, LACI remained a significant predictor of cardiovascular outcomes (hazard ratio, 1.18 per quartile increase [95% CI, 1.00-1.38]; P=0.045). CONCLUSIONS: In patients with HFpEF, LA mechanical activity decreased with LA enlargement, suggesting volumetric/mechanical uncoupling inherent in this cohort. LACI may serve as a clinically relevant index for risk stratification of cardiovascular death or rehospitalization for heart failure in patients with HFpEF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000021831.