The experience of more than three hundred levosimendan administrations: what we have learned

Abstract Introduction Levosimendan is a positive inotrope used in advanced heart failure (adHF) as a bridge to transplant, to decision, to recovery or as a palliative therapy. As the experience with this calcium sensitizer increases, real world data is becoming more robust about the effect on adHF. Objectives To describe the experience of intermittent intravenous (IV) administration of Levosimendan (24-hour infusion period) in a heart failure (HF) unit. Methods We conducted a single center study of consecutive adHF patients with reduced ejection fraction, integrated in the ambulatory intermittent levosimendan infusion program of our Institution. Patients were included if: 1) they were in New York HF Association (NYHA) class III-IV; 2) they had recurrent hospital admissions; 3) intolerant to up-titration of guideline medical therapy. Exclusion criteria were acute infections, systolic arterial pressure less than 80 mmHg, severe hepatic or kidney dysfunction. They received levosimendan by continuous infusion (0,05-0,1 mcg/Kg/min) for 24 hours once a month or fortnightly, with no bolus dose. Vital signs, hemogram and biochemistry were evaluated before and up to 2 hours after the end of infusion. Results From January 2021 to August 2024, 44 patients underwent 330 levosimendan infusions. Median age was 67 years (IQR 56-75), and 84% (n=34) were male. Ischemic HF was observed in 64% (n=28), median ejection fraction was 23% (IQR 19-30), and 95% (n=42) were in NYHA class III. Most patients were chronically medicated with guideline directed medical therapy beta-blockers (89%), ACE inhibitors/ARNI (100%), MRAs (89%), and SGLT2 inhibitors (86%). Palliation was the primary treatment goal in 41% (n=20). Initial infusion frequency was fortnightly in 16% (n=7), with 18% (n=8) requiring increased frequency due to clinical worsening. The mean treatment duration was 7 ± 5 months. Notably, 60% of patients discontinued levosimendan due to improved functional status and HF stabilization. Four patients underwent heart transplantation, and one received a left ventricular assist device (LVAD). By December 2024, there were 7 deaths (16%): 4 from advanced HF, 2 of unknown causes, and 1 from meningitis. NT-proBNP decreased by 30% (7660 ng/dL to 5436 ng/dL) over 6 months, while creatinine showed a slight increase (1.58 to 1.72 g/dL; 9%). Conclusion Intermittent levosimendan infusions offer a valuable therapeutic option for patients with adHF, improving functional status, stabilizing HF progression, and supporting palliation in select cases.