Background: Patients with acute decompensated heart failure (ADHF) and acute liver failure or deterioration of pre-existing chronic liver failure are at high risk for outpatient and in-hospital complications. Furthermore, elevated total bilirubin (TB) in acute heart failure prognosticates rehospitalisation and exacerbation. SGLT2 inhibitors are an established part of the heart failure therapy. Few reports have highlighted the occurrence of drug induced liver injury (DILI) after treatment initiation with empagliflozin. The prospective, double-blind, placebo-controlledtrial Effects of EMPAGliflozin on diuresis and renal function in patients with acute decompensated Heart Failure(EMPAG-HF) assessed the impact of early empagliflozin initiation on renal function and urine output in patients with ADHF. 

Aim / Purpose: The aim of this pre-defined secondary analysis was to evaluate markers of hepatic function, blood gas analysis parameters and the 30-day outcomes of patients with acute decompensated heart failure treated with empagliflozin 25 mg vs. placebo.

Methods:Patients with ADHF were screened and randomized within 12 hours following hospital admission to receive either empagliflozin 25 mg or placebo in addition to standard medical treatment over five days. Sixtypatients (age 74.7±9.9 yrs, 38% female) were enrolled and randomized 1:1 irrespective of left ventricular ejection fraction or presence of diabetes. Total Bilirubin (TB),aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), Gamma-GT, Lactate-Dehydrogenase (LDH), Blood gas analysis parameters and MELD XI-Score were evaluated every day from day 1 to 5 and 30 after treatment cessation.Mann-U-Whitney and Wilcoxon rank-sum test were used for statistical analyses.

Results: 30 patients were randomized to receive empagliflozin and 29 patients received placebo. There were no statistically significant differences in baseline patient characteristics including total bilirubin (TB), aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), Gamma-Glutamyl Transferase(Gamma-GT), Lactate-Dehydrogenase (LDH), Blood gas analysis (BGA) and MELD XI-Score. Interestingly, we documented a statistically significant reduction in total bilirubin in the verum group 5 days after treatment initiation. Total bilirubin increased in the placebo group during the trial. No significant differences were observed between groups for each value investigated at 30-day outcome. 

Conclusion:Our data suggest that the additive treatment with empagliflozin in patients with ADHF is safe and does not contribute to additional acute or exacerbation of hepatic injury due to heart failure. These findings add to the beneficial effects of SGLT2 inhibition in patients with HF and show the safety of early initiation of SGLT2 inhibition in patients with ADHF. It remains to be clarified whether the reduction in total bilirubin represents an acute effect of empagliflozin regarding congestive hepatopathy. This aspect may further contribute to its prognostic benefits in heart failure.