Left atrioventricular coupling index predicts prognosis and pulmonary vascular dysfunction in heart failure with preserved ejection fraction

Background In heart failure with preserved ejection fraction (HFpEF), left atrial (LA) enlargement is associated with adverse outcomes and pulmonary vascular disease.1 Although LA remodeling has traditionally been attributed to hypertension and chronic pressure overload secondary to left ventricular (LV) diastolic dysfunction, indexing LA volume to LV volume suggests atrial dysfunction may occur earlier. Because LA enlargement often exceeds LV remodeling, LA parameters alone may not fully reflect atrial vulnerability. Purpose To clarify HFpEF pathophysiology by evaluating the prognostic value of the left atrioventricular ratio (LA:LV), defined as LA end-systolic volume divided by LV end-diastolic volume (left atrioventricular coupling index [LACI]),2 and to identify its determinants. Methods We prospectively analyzed 788 patients (median age 83 years; 57% women) from the PURSUIT-HFpEF registry. LACI was calculated from echocardiography at discharge. The primary endpoint was all-cause mortality or heart failure rehospitalization. Patients were stratified into tertiles: <0.76 (n=264), 0.76–1.20 (n=267), and ≥1.21 (n=257). Results During a median follow-up of 760 days, the highest LACI tertile had a higher incidence of the primary endpoint. LACI was independently associated with outcomes (unadjusted HR 1.17, P=0.0038; adjusted HR 1.19, P=0.0096). Among echocardiographic and hemodynamic variables, pulmonary artery capacitance (PAC) showed a stronger association with LACI than E/e’. In multivariable analysis, PAC was the strongest determinant of LACI (standardized β −0.47, P<0.001), independent of atrial fibrillation. Higher LACI was also associated with reduced pulmonary vascular resistance–compliance (RC) time (P=0.0014). Conclusion LACI strongly predicts adverse outcomes in HFpEF and is closely linked to pulmonary artery capacitance and disruption of the pulmonary vascular RC relationship. These findings support mechanisms beyond pressure overload-mediated LA remodeling. Consistent with REDUCE LAP-HF II,3 greater benefit in patients without advanced pulmonary vascular disease may reflect earlier–stage HFpEF with preserved LA–pulmonary coupling. LACI may serve as a clinically relevant imaging biomarker to phenotype patients for targeted interventions along the LA–pulmonary vascular axis.Abstract picture