biostudies-literatureUnknown14(15)Okada M<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>LA volume index and late diastolic mitral annular velocity were negatively correlated (<i>r</i>=-0.26; <i>P</i><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, <i>P</i>=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]; <i>P</i>=0.045).<h4>Conclusions</h4>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.<h4>Registration</h4>URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000021831.Journal of the American Heart Associatione040646https://www.ebi.ac.uk/biostudies/studies/S-EPMC12449986biostudies-literatureLeft Atrial Volumetric/Mechanical Coupling Index in Heart Failure With Preserved Ejection Fraction.PMC12449986Onishi TOkada KYasumura YYamada TOkada MHayashi TSeo MSakata YOCVC‐Heart Failure InvestigatorsSakamoto DNakatani DNakagawa ATanaka NTamaki SSotomi YNakagawa YIwakura KYano MHikoso SfalseLeft Atrial Volumetric/Mechanical Coupling Index in Heart Failure With Preserved Ejection Fraction.<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>LA volume index and late diastolic mitral annular velocity were negatively correlated (<i>r</i>=-0.26; <i>P</i><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, <i>P</i>=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]; <i>P</i>=0.045).<h4>Conclusions</h4>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.<h4>Registration</h4>URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000021831.2025-01-01T00:00:00Z2025 Aug2026-06-03T14:37:06.519Z2026-05-29T03:05:10.483ZS-EPMC124499864073608210.1161/JAHA.124.040646