Impact of SGLT2 ınhibitors on nutritional and ımmunologic status in chronic heart failure.

BACKGROUND

The prognostic nutritional index (PNI), combining serum albumin and lymphocyte count, is a validated marker of nutritional-inflammatory status and an independent predictor of outcomes in heart failure (HF). Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) improve cardiovascular and renal prognosis; however, their effect on dynamic changes in PNI remains insufficiently defined.

METHODS

This study included 365 patients with chronic HF receiving stable guideline-directed medical therapy. Patients treated with SGLT2 inhibitors in addition to triple therapy constituted the treatment group (n = 209), while those without SGLT2 inhibitor therapy formed the control group (n = 156). PNI was calculated at baseline and at 12-month follow-up. The primary endpoint was the change in PNI (ΔPNI). Linear regression analyses were performed to determine independent predictors of ΔPNI.

RESULTS

Baseline PNI did not differ significantly between the treatment and control groups (50.15 ± 8.52 vs. 50.12 ± 8.05, p = 0.196 At 12 months, PNI increased significantly in the SGLT2 inhibitor group and declined in the control group, yielding higher follow-up PNI with SGLT2 inhibitor therapy (52.48 ± 8.50 vs. 46.07 ± 9.35, p < 0.001). HF-related rehospitalizations were more frequent in the control group (p < 0.001). In multivariate regression, SGLT2 inhibitor use was independently associated with higher ΔPNI (B = 5.468, p < 0.001), whereas the other parameters were not independently associated with higher or lower ΔPNI. Furthermore, in ejection fraction (EF)-stratified longitudinal analysis, the increase in PNI was most pronounced in patients with heart failure with mildly reduced EF (HFmrEF) and heart failure with preserved EF (HFpEF) (ΔPNI + 4.63 and + 3.16, respectively; both Bonferroni-adjusted p < 0.0167), whereas the change in heart failure with reduced EF (HFrEF) (+ 1.33) did not remain significant after adjustment.

CONCLUSIONS

SGLT2 inhibitor therapy was associated with significant longitudinal improvement in PNI, particularly in patients with HFmrEF and HFpEF, whereas the change in HFrEF did not reach the Bonferroni-adjusted level of significance. These findings suggest that SGLT2 inhibitors may favorably modify the nutritional-inflammatory profile, with more pronounced effects observed in patients with preserved or mildly reduced ejection fraction.