Effects of intravenous furosemide plus small-volume hypertonic saline solutions on inflammatory, remodelling markers and epigenetics signatures of patients with congestive acute decompensated heart failure (ADHF)

Aims: In a randomised controlled trial (RCT), we compared the effects of treatment with furosemide + small volumes of hypertonic saline solution (HSS) with those of furosemide alone in patients with decompensated heart failure (HF), and their effects 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 determine 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. 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 after saline load. We observed a decrease in miR181b expression 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. 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.