The Early Pharmacological Strategy with Inodilator, bEta-blockers, Mineralocorticoid Receptor Antagonists, Sodium-glucose coTransporter-2 Inhibitors and Angiotensin Receptor-neprylisin Inhibitors in Acute Heart Failure (PENTA-HF)

Abstract Purpose: The management of acute heart failure (AHF) is crucial and challenging. Regarding the use of inotropes, correct patient selection and time of administration are of the essence. We hypothesize that the early use of Levosimendan favouring hemodynamic stabilization and enables rapid optimization of guideline-directed medical treatment (GDMT) in patients with HF, eventually impacting the patient's prognosis during the vulnerable phase. Methods: This prospective, observational study enrolled consecutive patients admitted due to AHF. Propensity score matching (PSM) analysis has been used to homogenize differences between groups. In group 1 (G1), patients were treated with early 24-h Levosimendan infusion followed by in-hospital introduction/up-titration of GDMT. In group 2 (G2), patients were treated with alternative inotropes/ vasopressors followed by in-hospital introduction/up-titration of GDMT. The comparison between the two groups has been performed at the 6-month follow-up in terms of cardiovascular (CV) mortality and HF hospitalizations (HFH). Results: 233 patients were included in the present study, and after propensity match adjustments, 176 patients were analysed, 88 patients for each group. No differences in the baseline characteristics have been reported between the groups. At 6 months follow-up, no statistically significant differences were shown in terms of the composite endpoint of CV death and HFH (p= 0.445) and CV death (p=0.62). Statistically significant differences between the two groups were reported in terms of HFH (p= 0.02). The Kaplan-Meier survival analysis showed that patients in G1 were significantly less hospitalized compared to G2 during the 6 months after the index hospitalization (log-rank p= 0.03). Conclusions: Early 24-hour infusion of Levosimendan followed by rapid optimization of HF diseasemodifying therapies results in a significant reduction of HFH in the vulnerable post-discharge phase. Keywords: Acute heart failure; PENTA-HF; heart failure hospitalization.; pharmacological treatment; vulnerable phase.