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Inflammatory Biomarkers and Their Associations with Arrhythmic Burden Following SGLT2-I Treatment in Chronic Heart

Martin Benedikt1, Markus Herrmann2, Faisal Aziz3,4

  • 1Department of Internal Medicine, Division of Cardiology, Medical University of Graz, 8010 Graz, Austria.

Journal of Clinical Medicine
|June 26, 2026
PubMed

Insights

Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) like Ertugliflozin may increase ventricular arrhythmia (VA) burden in chronic heart failure (CHF) patients with high inflammation. This suggests caution when using SGLT2-Is in patients with elevated high-sensitivity C-reactive protein (hsCRP).

Area of Science:

  • Cardiology
  • Pharmacology
  • Biomarkers

Background:

  • Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) demonstrate benefits in chronic heart failure (CHF) irrespective of left ventricular ejection fraction (LVEF).
  • Inflammation is a critical factor in cardiac pathology, yet its role in ventricular arrhythmia (VA) burden among SGLT2-I treated patients remains understudied.
  • This study addresses the gap in understanding the association between inflammatory biomarkers and VA in CHF patients receiving SGLT2-Is.

Purpose of the Study:

  • To investigate the impact of Ertugliflozin on inflammatory biomarkers over 52 weeks in CHF patients.
  • To explore the relationship between changes in these biomarkers and the incidence of ventricular arrhythmia (VA) burden.
  • To determine if Ertugliflozin treatment modifies the association between inflammation and VA in CHF.

Main Methods:

  • A pre-defined subanalysis of a clinical trial involving 36 CHF patients (18 Ertugliflozin, 18 placebo) with available biobank samples.
  • Measurement of inflammatory biomarkers including leukocyte and neutrophil counts, high-sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) at baseline and week 52.
  • Analysis of the association between biomarker changes and the incidence of VA burden.

Main Results:

  • Ertugliflozin treatment led to numerically higher leukocyte, neutrophil counts, hsCRP, and IL-6 levels at week 52.
  • Lymphocyte counts were significantly higher in the Ertugliflozin group (mean difference 19.0 ± 10.78%, p=0.028).
  • A significantly higher incidence of VA burden was observed in Ertugliflozin-treated patients with elevated hsCRP levels (IRR 3.58; 95% CI, 1.12-11.40, p=0.031).

Conclusions:

  • Ertugliflozin treatment in CHF patients was associated with an increased VA burden in those with elevated hsCRP.
  • This suggests a potential heightened risk for VA in SGLT2-I treated patients experiencing heightened inflammatory activity.
  • Findings are exploratory due to small sample size and single interaction analysis, requiring cautious interpretation and further research.

Keywords:
Ertugliflozinarrhythmiachronic heart failurehigh-sensitive C-reactive proteininflammation

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