Intermittent Levosimendan infusion according to the lion-heart protocol in advanced heart failure: first pilot experience in fragile patient

Abstract Background Intermittent intravenous Levosimendan has been shown to improve symptoms and reduce heart failure hospitalizations in patients with advanced HF (AdvHF). However, evidence in frail, elderly outpatients remains limited. Objective To evaluate the feasibility, efficacy and safety of repeated Levosimendan infusions according to the LION-HEART protocol through our preliminary pilot experience in frail patients with advanced heart failure. Methods We retrospectively included consecutive outpatients with advanced heart failure (AdvHF) fulfilling the ESC Heart Failure Association criteria and presenting a Clinical Frailty Scale ≥4 who were referred to our day-hospital between 06/2024 and 06/2025 for intermittent Levosimendan infusions. Levosimendan was administered as a 6–8-hour intravenous infusion at 0.2 µg/kg/min (total dose 6.25 mg) every 2 weeks, without loading bolus, according to the LION-HEART protocol. Clinical status, NYHA class, laboratory parameters, echocardiography and 6-minute walk test (6MWT) were assessed at baseline and after 3 months. Heart-failure–related hospitalizations and implantable cardioverter-defibrillator (ICD) therapies were recorded for the 3 months of the treatment. Results We enrolled 11 frail outpatients (mean age 73 ± 6 years; 2 18% female; ischemic etiology 7 64%; median Clinical Frailty Scale 5 IQR 4–6). All were in NYHA class III–IV with severe systolic dysfunction. Levosimendan was used as bridge-to-decision in 2 patients (18 %) and as palliative therapy in 9 (82 %). At 3 months, NT-proBNP decreased from 6 975 ± 1 825 to 6 215 ± 1 740 pg/ml (p=0.18), LVEF showed a non-significant trend from 24 ± 5% to 27 ± 6% (p = 0.2). The 6-minute walk test distance improved modestly from 185 ± 35 to 200 ± 40 m (p = 0.08) (Figure 1). During the 3 months of therapy, HF-related hospitalizations recorded were 2, with no deaths and no sustained ventricular arrhythmias or appropriate ICD therapies. No patient discontinued infusions for adverse effects; only transient mild hypotension (n = 2) and headache (n = 1) were reported. Conclusions In this exploratory pilot cohort, repeated levosimendan infusions according to the LION-HEART protocol were feasible and well tolerated in frail patients with advanced heart failure. Our findings suggest that frailty alone should not preclude consideration of intermittent levosimendan therapy, a hypothesis that warrants confirmation in larger prospective studies.Figure 1