Research Paper|Volume 18|pp 190—212

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)

Mario Daidone^1,^2,³, Alessandra Casuccio², John Sebastian Soldano^1,², Valerio Vassallo^1,², Gaetano Pacinella^1,², Maria Grazia Puleo^1,², Roberta Oliveri^1,², Giuseppe Clemente^1,², Daniela Colomba¹, Giuseppe Miceli^1,², Vittoriano Della Corte^1,², Rosaria Pecoraro^1,², Tiziana Di Chiara^1,², Domenico Di Raimondo^1,², Carlo Domenico Maida^1,^2,³, Sergio Ferrantelli^1,², Antonino Tuttolomondo^1,²

¹Internal Medicine and Stroke Care Ward, University Hospital, Policlinico, Paolo Giaccone, 90127 Palermo, Italy
²Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy
³Molecular and Clinical Medicine PhD Program, University of Palermo, 90127 Palermo, Italy

Received: April 19, 2025Accepted: November 24, 2025Published: March 26, 2026

https://doi.org/10.18632/aging.206364

Copyright: © 2026 Daidone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.