Impact of Functional Frailty Measured by Short Physical Performance Battery Test on the Effectiveness of SGLT2 Inhibitors in Elderly Patients with Acute Heart Failure:PROFUND-IC Registry

Background/Objectives: Acute heart failure (AHF) is the leading cause of hospitalization among patients over 65 years and is frequently associated with frailty. Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) currently represent the only drug class recommended across the entire ejection fraction spectrum, although evidence regarding their effectiveness according to frailty status remains limited. Aims: To determine whether functional frailty, measured by the Short Physical Performance Battery (SPPB) test, influences the effectiveness of SGLT2i in reducing hospital readmission and mortality in elderly patients with AHF. Methods: Observational study of 794 polypathological patients admitted to Internal Medicine with AHF. An interaction analysis assessed whether SPPB, as a continuous variable, modified the association between SGLT2i and the composite outcome (hospital readmission or death), using a Cox model. The sample was further divided by SPPB test score (below 4 (N = 477) or ≥4 (N = 317)) for exploratory analyses. Descriptive and comparative analyses were performed according to SGLT2i administration, using the chi-squared test for qualitative variables and Student’s t-test for quantitative ones (Fisher’s and Mann–Whitney U test as appropriate). Survival analysis was done using Kaplan–Meier curves and Cox regression, with multivariable adjustment for confounders. Results: No significant interaction was found between SPPB score and SGLT2i (p = 0.506). When SPPB was dichotomised, SGLT2i treatment was associated with significantly lower all-cause mortality (3.7% vs. 12.0%; p = 0.018) and readmission (30.3% vs. 45.2%; p = 0.021) in SPPB ≥ 4, with mortality and readmission also numerically lower, without reaching statistical significance, in SPPB < 4 (mortality 12.9% vs. 16.9%, p = 0.410; readmission 34.5% vs. 42.0%, p = 0.220). After adjustment, SGLT2i treatment in the SPPB ≥ 4 group remained associated with a numerically lower hazard for the composite outcome (HR 0.652; 95% CI 0.418–1.018; p = 0.060). Conclusions: No evidence was found that functional frailty modifies the effectiveness of SGLT2i in elderly polypathological patients with AHF. An exploratory analysis suggested a possible gradient of greater association with SPPB ≥ 4, although this should be interpreted as hypothesis-generating.