Effects of intravenous furosemide plus small-volume hypertonic saline solutions on markers of heart failure

Aims We sought to compare the effects of furosemide + hypertonic saline solution (HSS) treatment in patients with acute decompensated heart failure in comparison with furosemide alone and the response in a compensated state after an acute saline load with regard to serum levels of heart failure biomarkers. Methods and results We enrolled 141 patients with acute decompensated heart failure with reduced ejection fraction admitted to our Internal Medicine ward from March 2017 to November 2019. A total of 73 patients were randomized to treatment with i.v. high-dose furosemide plus HSS, whereas 68 patients were randomized to i.v. high-dose furosemide alone. Patients treated with furosemide plus HSS compared with controls treated with furosemide alone showed a comparable degree of reduction in the serum levels of interleukin (IL)-6, soluble suppression of tumorigenicity 2 (sST2), and N-terminal pro-brain natriuretic peptide (NT-proBNP) in the 'between-group' analysis. Nevertheless, patients treated with high-dose furosemide + HSS showed significantly higher absolute delta values of IL-6 (2.3 +/- 1.2 vs. 1.7 +/- 0.9, P < 0.0005, and 2.0 +/- 0.8 vs. 1.85 +/- 1.1, P = 0.034), sST2 (41.2 +/- 8.6 vs. 27.9 +/- 7.6, P < 0.0005, and 37.1 +/- 6.6 vs. 28.4 +/- 6.7, P < 0.0005), high-sensitivity troponin T (0.03 +/- 0.02 vs. 0.02 +/- 0.01, P = 0.001, and 0.03 +/- 0.02 vs. 0.02 +/- 0.01, P = 0.009), NT-proBNP (7237 +/- 7931 vs. 3244 +/- 4159, P < 0.005, and 5381 +/- 4829 vs. 4466 +/- 4332, P = 0.004), and galectin-3 (15.7 +/- 3.2 ng/mL vs. 11.68 +/- 1.9 ng/mL, P < 0.0005, and 16.7 +/- 3.9 ng/mL vs. 11.8 +/- 2.4 ng/mL, P < 0.0005) than patients treated with furosemide alone. After acute saline load, patients treated with i.v. furosemide + HSS in comparison with subjects treated with furosemide alone showed a significantly lower increase in the serum concentrations of IL-6 (-0.26 +/- 0.42 pg/mL vs. -1.43 +/- 0.86 pg/mL, P < 0.0005), high-sensitivity troponin T (0 vs. -0.02 +/- 0.02 ng/mL, P < 0.0005), sST2 (-8.5 +/- 5.9 ng/mL vs.-14.6 +/- 6.2 ng/mL, P < 0.0005), galectin-3 (-2.1 +/- 1.5 ng/mL vs. -7.1 +/- 3.6 ng/mL, P < 0.0005), and NT-proBNP (77 +/- 1373 vs. -1706 +/- 2259 pg/mL, P < 0.0005). Conclusions Our findings concerning a comparable degree of reduction in the serum levels of three cardinal biomarkers indicate that a reduction in serum heart failure markers is not linked to the higher degree of congestion relief with a more rapid achievement of a clinical compensation state. This issue may have possible benefits on clinical practice concerning its therapeutic effects over and beyond the simple amelioration of clinical congestion signs and symptoms. Nevertheless, our findings of higher delta values after treatment with i.v. furosemide plus HSS indicate a possible higher efficacy by means of modulation of the stretching and fibrosis mechanisms.

Automated summary

Comparing the effects of furosemide + hypertonic saline solution treatment and furosemide alone in patients with acute decompensated heart failure, along with the response after an acute saline load, showed similar reductions in serum heart failure biomarkers. However, treatment with furosemide + HSS may have a higher efficacy in modulating stretching and fibrosis mechanisms.