Metabolic remodeling and cardiac functional adaptation mediated by dapagliflozin in patients with acute heart failure: a retrospective cohort study

Aims Grounded in the “myocardial metabolic starvation” hypothesis, this study evaluated the pharmacological effects of dapagliflozin on serum metabolic profiles, ventricular remodeling, and cardiac function in patients hospitalized with acute heart failure (AHF), and explored the associations between circulating metabolic alterations, ventricular remodeling, and cardiac functional parameters. Methods This single-center retrospective cohort study included 50 AHF patients (25 pairs) after 1:1 propensity score matching. The dapagliflozin group received standard care plus dapagliflozin 10 mg once daily for 6 months, while the control group received standard care alone. Changes in circulating metabolic parameters, including fasting blood glucose, lactic acid, free fatty acids, and ketone-related metabolites (β-hydroxybutyrate and acetoacetic acid), as well as glycolytic enzyme activity (pyruvate kinase), were compared between groups. Echocardiographic parameters, 6-min walk test (6 MWT) distance, B-type natriuretic peptide (BNP), and major adverse cardiovascular events (MACE) were also assessed. Results The dapagliflozin group showed greater reductions in circulating metabolic parameters, particularly fasting plasma glucose, free fatty acids, β-hydroxybutyrate, and acetoacetic acid, compared with controls (all P < 0.05). Left ventricular end-systolic diameter (37.29 ± 4.07 vs. 43.16 ± 4.41 mm) and end-diastolic diameter (45.17 ± 5.02 vs. 52.63 ± 6.20 mm) improved more markedly in the dapagliflozin group (both P < 0.001). left ventricular ejection fraction (48.36% ± 4.88% vs. 43.85% ± 4.90%, P = 0.002), BNP (116.45 ± 12.15 vs. 214.50 ± 20.36 pg mL -1 , P < 0.001), and 6 MWT distance (385.56 ± 51.42 vs. 314.78 ± 42.17 m, P < 0.001) were also significantly superior in the dapagliflozin group. FFA reduction correlated positively with LVEDD reduction (r = 0.638, P < 0.001). Multiple regression analysis identified ΔFFA (β = −0.412, P = 0.008) and Δβ-HB (β = −0.385, P = 0.012) as independent predictors of ΔLVEF improvement. MACE incidence was numerically lower in the dapagliflozin group (8.0% vs. 32.0%, P = 0.076). Conclusion In this small retrospective cohort, early in-hospital initiation of dapagliflozin was associated with favorable changes in circulating metabolic profiles, ventricular remodeling, and cardiac function in patients with acute heart failure. These findings suggest potential therapeutic benefits for ventricular remodeling, but require confirmation in larger prospective studies.