Use of Levosimendan in Patients with Advanced Heart Failure: An Update
Abstract
:1. Introduction
2. Pharmacology of Levosimendan
2.1. Pharmacokinetic of Levosimendan
2.2. Pharmacodynamics of Levosimendan
2.3. Side Effects and Contraindications of Levosimendan
3. Intermittent Levosimendan Infusion in Patients with advHFrEF
4. Levosimendan in Patients with advHFrEF Undergoing LVAD Implantation
5. Levosimendan in Patients with advHFrEF on the Waiting List for a Heart Transplant
6. Levosimendan in Patients with advHFpEF as a Future Perspective
7. Tips and Tricks for the Use of Levosimendan in Clinical Practice
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study | N° of Patients | Levosimendan Dose | Time of Infusion | Interval of Infusion | Results |
---|---|---|---|---|---|
Nanas 2005 [35] | 36 | Bolus dose (6 mg/kg) plus Infusion rate (0.2 mcg/Kg/min). Levosimendan was added to dobutamine infusion | 24 h | 2 weeks for 45 days | Improvement in survival (6% vs. 61% p = 0.0002) |
Parissis 2006 [36] | 25 | Bolus dose (6 mg/kg) plus Infusion rate (0.1–0.4 mcg/Kg/min) | 24 h | 3 weeks for 114 days | Reduction of LVEDVi (120 vs. 156 mL/m2; p < 0.01), LVESVi (80 vs. 106 mL/m2; p < 0.01) and NT-proBNP plasma levels (966 vs. 1529 pg/mL; p < 0.01) increase of LVEF (26 vs. 22%, p < 0.01) |
Mavrogeni 2007 [37] | 50 | Bolus dose (6 mg/kg) plus Infusion rate (0.1–0.2 mcg/Kg/min) | 24 h | 30 days for 6 months | Increase of LVEF (28 + 7 vs. 21 + 4%, p = 0.003) and LVFS (15 + vs. 11 + 3%, p = 0.006). |
Papadopoulou [38] | 20 | No bolus dose Infusion rate (0.1 mcg/kg/min) | 24 h | 30 days for 6 months | Increase of LVEF (30.3 ± 6.9 vs. 32.1 ± 7.4%; p = 0.01) and quality of life (LIhFE score i 35.4 ± 18.6 vs. 22.2 ± 13.0; p < 0.0001). |
Malfatto 2012 [39] | 33 | No bolus dose Infusion rate (0.1–0.4 mcg/kg/min) | 24 h | 30 days for 12 months | Increase of LVEF (25.9 + 5.1 vs. 28.7 ± 5.4%; p < 0.05) and CI (2.34 + 0.58 vs. 2.77 + 0.65 L/min/m2; p < 0.05). Reduction of PASP (51.8 ± 15.4 vs. 42.6 ± 13.0 mmHg; p < 0.05), E/e’ ratio (18.3 ± 8.9 vs. 13.8 ± 4.1; p < 0.05) |
Oliva (RELEVANT-HF) 2018 [33] | 185 | No bolus dose Infusion rate (0.2 mcg/Kg/min) | 24 h | 3–4 weeks for 6 months | Reduction of days in hospital (9.4 vs. 2.8 days; p < 0.0001) and length of HF admissions (17.4 vs. 21.6 days; p = 0.0001) |
Masarone 2020 [29] | 15 | No bolus dose Infusion rate (0.2 mcg/Kg/min | 6 h | 2 weeks for 12 months | Reduction of HF-related hospitalizations (2 vs. 10; p < 0.05) and increase of distance walked at six-minute walking test (282 ± 52 vs. 248 ± 30 meters; p < 0.05) |
Altenberger (LevoRep) 2014 [40] | 120 | No bolus dose Infusion rate (0.2 mcg/Kg/min) | 6 h | 2 weeks for 42 days | No increase in the distance walked on the 6-minute walking test and no increase in score on the Kansas City Cardiomyopathy Questionnaire (19% vs. 15%; OR.25; 95% CI 0.44–3.59; p = 0.810). |
Comín-Colet (LION HEART) 2018 [41] | 69 | No bolus dose Infusion rate (0.2 mcg/Kg/min) | 6 h | 2 weeks for 6 months | Reduction of NT-proBNP plasma levels (mean change in NT-proBNP–1446 vs. –1320 pg/mL; p < 0.001) and of the rate of HF-related hospitalization (hazard ratio 0.25; 95% CI 0.11–0.56; p = 0.001) |
García-González (LAICA) 2021 [42] | 97 | No bolus dose Infusion rate (0.1 mcg/Kg/min) | 24 h | 4 weeks for 12 months | No reduction in HF-related hospitalizations (HR 0.66; 95% CI, 0.32–1.32; p = 0.24). Reduction of cumulative incidence of HF-related hospitalizations and death at 1 month (5.7% vs. 25.9%; p = 0.004) and 3 months (17.1% vs. 48.1%; p = 0.001). Improvement in survival (log-rank: 4.06; p = 0.044). |
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Masarone, D.; Kittleson, M.M.; Pollesello, P.; Marini, M.; Iacoviello, M.; Oliva, F.; Caiazzo, A.; Petraio, A.; Pacileo, G. Use of Levosimendan in Patients with Advanced Heart Failure: An Update. J. Clin. Med. 2022, 11, 6408. https://doi.org/10.3390/jcm11216408
Masarone D, Kittleson MM, Pollesello P, Marini M, Iacoviello M, Oliva F, Caiazzo A, Petraio A, Pacileo G. Use of Levosimendan in Patients with Advanced Heart Failure: An Update. Journal of Clinical Medicine. 2022; 11(21):6408. https://doi.org/10.3390/jcm11216408
Chicago/Turabian StyleMasarone, Daniele, Michelle M. Kittleson, Piero Pollesello, Marco Marini, Massimo Iacoviello, Fabrizio Oliva, Angelo Caiazzo, Andrea Petraio, and Giuseppe Pacileo. 2022. "Use of Levosimendan in Patients with Advanced Heart Failure: An Update" Journal of Clinical Medicine 11, no. 21: 6408. https://doi.org/10.3390/jcm11216408
APA StyleMasarone, D., Kittleson, M. M., Pollesello, P., Marini, M., Iacoviello, M., Oliva, F., Caiazzo, A., Petraio, A., & Pacileo, G. (2022). Use of Levosimendan in Patients with Advanced Heart Failure: An Update. Journal of Clinical Medicine, 11(21), 6408. https://doi.org/10.3390/jcm11216408