Two Phenotypes, One Prognosis: Period-Specific Mortality and Prediction of Post-Discharge Events in Acute Heart Failure

Background: The prognostic relevance of left ventricular ejection fraction (LVEF) categories in acute heart failure (AHF) remains debated. We compared the clinical phenotype of patients hospitalized for AHF with preserved (LVEF ≥ 50%) versus reduced (LVEF < 50%) ejection fraction (EF), and compared the prognostic influence of the two phenotypes on in-hospital and post-discharge mortality. Methods: We analyzed 530 consecutive patients enrolled in a prospective single-center AHF registry (February 2023–June 2025), followed through June 2026, grouped as preserved (LVEF ≥ 50%, n = 264) or reduced (LVEF < 50%, n = 266). Baseline characteristics, in-hospital course, and post-discharge events (death, renal replacement therapy [RRT], acute HF rehospitalization, and a triple composite) were compared. Given the distinct prognostic mechanisms operating during hospitalization and after discharge, the two periods were analyzed separately. In-hospital mortality was reported descriptively, whereas predictors of post-discharge mortality were evaluated using multivariable Cox regression with follow-up beginning at discharge. Results: Patients with preserved LVEF were older, predominantly women, and more often frail and in atrial fibrillation, whereas LVEF < 50% was associated with an ischemic etiology, right heart failure, and higher values of natriuretic peptides (all p < 0.05). In-hospital mortality was higher with LVEF < 50% (7.1% vs. 3.0%, p = 0.046) and was almost entirely cardiovascular (6.4% vs. 1.1%, p = 0.002). Among the 503 patients discharged alive, post-discharge mortality did not differ between phenotypes (27.7% vs. 22.7%, p = 0.23), nor did terminal RRT (2.7% vs. 3.2%) or the triple composite (49.6% vs. 42.1%, p = 0.11); emergency-department visits were more frequent with preserved LVEF (69.1% vs. 58.6%, p = 0.048). In the multivariable model of post-discharge mortality (n = 494, 124 deaths), frailty (HR 1.96, 95% CI 1.09–3.51) and log NT-proBNP (HR 1.86, 95% CI 1.45–2.38) were independent predictors, whereas worsening renal function was not. LVEF < 50% was associated with lower post-discharge mortality in the full model (HR 0.58, 95% CI 0.38–0.89), but this association was not robust across specifications, as follows: it disappeared when NT-proBNP was omitted (HR 0.88, 95% CI 0.60–1.27), and no alternative LVEF cut-point was associated with mortality. Conclusions: The two phenotypes are dissimilar in in-hospital mortality and similar in post-discharge mortality, with no consistent independent contribution to prognosis of this specific cut-off of LVEF of 50%.