Supra-Normal Ejection Fraction at Hospital Admission Stratifies Mortality Risk in HFpEF Patients Aged ≥ 70 Years

Background: During the last few years, significant pathophysiological differences between heart failure (HF) patients with "normal" ejection fraction (EF) (50% to 64%) and those with supra-normal EF (>= 65%) have been highlighted. However, these distinct EF phenotypes have been poorly investigated in elderly patients aged >= 70 y. Accordingly, the present study aimed at assessing the clinical and echocardiographic characteristics of a retrospective cohort of elderly HFpEF patients (aged >= 70 y), categorized on the basis of "normal" EF (50 to 64%) or "supra-normal" EF (>= 65%). Methods: All patients aged >= 70 y that were discharged from our Institution with a first diagnosis of HF with preserved EF (HFpEF) between January 2020 and March 2021 entered the study. All patients underwent clinical evaluation, blood tests, and transthoracic echocardiography. The primary endpoint was "all-cause mortality", while the secondary one was the composite "all-cause mortality or rehospitalization for all causes" over a mid-term follow-up. Results: A total of 200 HFpEF patients (86.4 +/- 6.6 y, 70% females) were retrospectively evaluated. The "normal" EF group (n = 99) and the "supra-normal" EF one (n = 101) were separately analyzed. Compared to patients with "normal" EF, those with "supra-normal" EF were older, with greater comorbidity burden, and moderate-to-severe frailty status. The mean follow-up duration was 3.6 +/- 0.3 y. During follow-up, 79 patients died, and 73 were rehospitalized. In the multivariate Cox regression analysis, age (HR 1.09, 95% CI 1.03-1.16, p = 0.002), EF (HR 1.08, 95% CI 1.03-1.14, p = 0.004), tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio (HR 0.14, 95% CI 0.03-0.61, p = 0.009), and infectious disease occurring during the baseline stay (HR 7.23, 95% CI 2.41-21.6, p < 0.001) were independently associated with the primary endpoint in the whole study population. EF (HR 1.04, 95% CI 1.01-1.07, p = 0.02) also predicted the secondary endpoint. EF >= 65% was the best cut-off to predict both endpoints. Conclusions: "Supra-normal" EF (>= 65%) at hospital admission is independently associated with all-cause mortality and rehospitalization for all causes in elderly HFpEF patients over a mid-term follow-up.