Heart Failure Etiology and 6-Month Cardiorenal Recovery Patterns After Early In-Hospital SGLT2 Inhibitor Initiation in HFrEF: A Prospective Real-World Cohort

Background: SGLT2 inhibitors improve outcomes in heart failure with reduced ejection fraction (HFrEF), but whether early recovery patterns after initiation differ according to HF etiology in real-world practice remains uncertain. Objective: To evaluate whether ischemic versus non-ischemic etiology is associated with different 6-month cardiac, renal, biomarker, and exploratory metabolic trajectories after early in-hospital SGLT2 inhibitor initiation in HFrEF. Materials and Methods: In this prospective single-center observational cohort (2022–2025), consecutive adults hospitalized with first-presentation acute HFrEF who initiated empagliflozin or dapagliflozin within 48 h of admission were enrolled. Patients were classified as having ischemic cardiomyopathy (ICM) or non-ischemic cardiomyopathy (NICM). The primary analytic cohort included patients with paired baseline and 6-month echocardiography. The primary outcome was change in left ventricular ejection fraction (LVEF); eGFR and NT-proBNP were secondary outcomes. Exploratory metabolic/laboratory variables were summarized descriptively using paired available-case follow-up. The study was approved by the institutional ethics committee and registered in ClinicalTrials.gov under the CaRD registry framework (NCT06090591). Results: The paired 6-month echocardiographic analytic cohort comprised 241 patients who survived to reassessment (ICM n = 90; NICM n = 151). NICM showed greater improvement in LVEF than ICM (ΔLVEF +10% [IQR 0–18] vs. +5% [IQR 0–12]; p = 0.049) and a more favorable eGFR trajectory (ΔeGFR 0.30 [IQR −5.90 to 6.60] vs. −2.70 [IQR −12.60 to 3.40] mL/min/1.73 m2; p = 0.038). NT-proBNP declined substantially in both groups, with no between-group difference in change magnitude (p = 0.845), although 6-month values remained higher in ICM (p = 0.034). However, after multivariable adjustment, ischemic etiology was no longer independently associated with 6-month LVEF or eGFR outcomes. Exploratory metabolic findings varied descriptively by etiology but should be interpreted cautiously because follow-up completeness and background treatment intensity varied across variables. Conclusions: In this real-world cohort of patients with HFrEF who initiated SGLT2 inhibitors during hospitalization, HF etiology was associated with different short-term cardiorenal recovery patterns, whereas NT-proBNP reduction was similar across groups. These findings characterize etiology-related recovery within a treated cohort rather than differential SGLT2 inhibitor efficacy and should therefore be considered as hypothesis-generating.