Inflammatory Biomarkers and Their Associations with Arrhythmic Burden Following SGLT2-I Treatment in Chronic Heart Failure—A Subanalysis of the ERASe Trial

Background: Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) are well known to exert beneficial effects in chronic heart failure (CHF) independent of left ventricular ejection fraction (LVEF). As inflammation plays a key role in cardiac diseases, data on the association of inflammatory biomarkers and ventricular arrhythmic (VA) burden in SGLT2-I-treated patients is lacking. Methods: This pre-defined subanalysis investigated changes in pre-specified inflammatory biomarkers from baseline to week 52 in response to 5 mg Ertugliflozin compared to placebo and their associations to the incidence of VA burden. Results: A total of 36 patients (18 versus 18) with available biobank samples were included in the analysis. At week 52, leukocyte and neutrophil counts, as well as high-sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6), were numerically higher in the Ertugliflozin group. In contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were lower in the Ertugliflozin group, although these differences did not reach statistical significance. Notably, lymphocyte counts were significantly higher in Ertugliflozin showing a mean difference of 19.0 ± 10.78% (p = 0.028). Further, a significantly higher incidence of VA burden was observed among Ertugliflozin-treated patients with elevated hsCRP levels (incidence rate ratio [IRR] 3.58; 95% Confidence interval [CI], 1.12–11.40, p = 0.031). Conclusions: In patients with CHF, Ertugliflozin treatment was associated with a higher incidence of VA burden in those with elevated hsCRP levels. This may suggest a potential higher risk for VA in SGLT2-I-treated patients in the setting of heightened inflammatory activity. However, this finding is based on a single interaction analysis in a small sample size, and the results should therefore be considered exploratory and hypothesis-generating, and must be interpreted cautiously.