Epigenetic signatures of treatment with intravenous furosemide plus hypertonic saline solution in decompensated heart failure patients: A Randomized Controlled Trial ( RCT)

In a randomised controlled trial (RCT) , we compared the effects of treatment with furosemide + small volumes of hypertonic saline solution (HSS) to furosemide alone in patients with decompensated heart failure (HF) and evaluated the effects after administration of an acute saline bolus on inflammatory and remodelling markers and epigenetic signatures.Methods: All consecutive patients with acute decompensated heart failure (ADHF) due to heart failure with reduced ejection fraction (HFrEF) were enrolled. Patients were randomly assigned to treatment with i.v. furosemide plus HSS or i.v. furosemide alone. Patients were evaluated at T0 (admission), T1 (after treatment), and T2 (after a saline bolus) to determinate serum concentrations of NT-proBNP, hsTnT, s-ST2, galectin-3, IL-6, and CRP and to evaluate some selected miRNA concentrations.Results: We enrolled 200 subjects, 107 randomized to the furosemide plus HSS, and 93 to furosemide alone. At T1, patients treated with high-dose furosemide + HSS had higher absolute delta values of IL-6, hsTnT, NT-proBNP and galectin-3. At T2, after acute administration of a saline bolus, patients treated with i.v. furosemide + HSS showed significantly lower increases in the serum concentrations of IL-6, hsTNT, sST2, galectin-3 and NT-proBNP. In terms of differentially expressed miRNAs, we observed a decrease in the expression of miR181b in subjects treated with i.v. furosemide plus HSS in comparison to patients treated with i.v. furosemide alone and a more significant reduction of miRNA181b expression in subjects treated with furosemide plus HSS. Intragroup analysis revealed significant differences in the expression of miR214, miR1505p, and miR125a5p at T0 vs. T1 and of miR214, miR365, miR181b, miR1505p, and miR125a5p at T1 vs. T2.Conclusions: Our findings revealed that in subjects with ADHF , treatment with i.v. furosemide plus HSS significantly decreased the serum levels of IL-6, sST2, hsTnT, galectin-3, and NT-proBNP and modulated some miRNA expression.