The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery


  • Marija Bozhinovska Clinical Department of Anesthesiology and Perioperative Intensive Therapy, Division of Cardiac Anesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Zaloska 7, 1000 Ljubljana
  • Gordana Taleska Clinical Department of Anesthesiology and Perioperative Intensive Therapy, Division of Cardiac Anesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Zaloska 7, 1000 Ljubljana
  • Andrej Fabian Institute of Physiology, Medical Faculty, University of Ljubljana; Department of Vascular Neurology and Neurological Intensive Therapy, University Clinical Centre Ljubljana
  • Maja Å oÅ¡tarič Clinical Department of Anesthesiology and Perioperative Intensive Therapy, Division of Cardiac Anesthesiology and Intensive Therapy, University Clinical Center Ljubljana, Zaloska 7, 1000 Ljubljana



Cardiac surgery, Levosimendan, Ventricular function, Heart failure, Myocardial dysfunction


The postoperative low cardiac output is one of the most important complications following cardiac surgery and is associated with increased morbidity and mortality. The condition requires inotropic support to achieve adequate hemodynamic status and tissue perfusion. While catecholamines are utilised as a standard therapy in cardiac surgery, their use is limited due to increased oxygen consumption. Levosimendan is calcium sensitising inodilatator expressing positive inotropic effect by binding with cardiac troponin C without increasing oxygen demand. Furthermore, the drug opens potassium ATP (KATP) channels in cardiac mitochondria and in the vascular muscle cells, showing cardioprotective and vasodilator properties, respectively. In the past decade, levosimendan demonstrated promising results in treating patients with reduced left ventricular function when administered in peri- or post- operative settings. In addition, pre-operative use of levosimendan in patients with severely reduced left ventricular ejection fraction may reduce the requirements for postoperative inotropic support, mechanical support, duration of intensive care unit stay as well as hospital stay and a decrease in post-operative mortality. However, larger studies are needed to clarify clinical advantages of levosimendan versus conventional inotropes.


Download data is not yet available.


Metrics Loading ...

Plum Analytics Artifact Widget Block


Toller W, Heringlake M, Guarracino F , Algotsson L, Alvarez, J, Argyriadou H, et al. Preoperative and perioperative use of levosimendan in cardiac surgery: European expert opinion. Int J Cardiol. 2015;184:323-36. PMid:25734940

Suleiman MS, Zacharowski K, Angelini G D.Inflammatory response and cardioprotection during open-heart surgery: the importance of anaesthetics. Br J Pharmacol. 2008;153(1)21-33. PMid:17952108 PMCid:PMC2199383

Malliotakis P, Xenikakis T, Linardakis M, Hassoulas J. Hemodynamic effects of Levosimednan for low cardiac output after cardiac surgery: A case series. Hellenic J Cardiol. 2007;48: 80-88. PMid:17489345

Raja SG, Rayen BS. Levosimendan in cardiac surgery: current best available evidence. Ann Thorac Surg. 2006;81(4):1536-46. PMid:16564321

Amsallem E, Kasparian C, Haddour G, Boissel J P, Nony P. Phosphodiesterase III inhibitors for heart failure. Cochrane Database of Syst. Rev. 2005; (1): CD002230.

Overgaard CB, Dzavík V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047-56. PMid:18765387

Packer M. The search for the ideal positive inotropic agent. N Engl J Med. 1993;329:201–2. PMid:8515793

Lee JC, Downing SE. Cyclic AMP and the pathogenesis of myocardial injury. Res Commun Chem Pathol Pharmacol. 1980;27:305–18. PMid:6245436

Ferrick KJ, Fein SA, Ferrick AM, et al. Effect of milrinone on ventricular arrhythmias in congestive heart failure. Am J Cardiol. 1990;66:431–4.

Nieminen MS, Fruhwald S, Heunks LM, Suominen PK, Gordon AC, Kivikko M, et al. Levosimendan: current data, clinical use and future development. Heart Lung Vessel. 2013;5:227–245. PMid:24364017 PMCid:PMC3868185

Antoniades C, Tousoulis D, Koumallos N, Marinou K, Stefanadis C. Levosimendan: beyond its simple inotropic effect in heart failure. Pharmacol Ther. 2007;114(2):184-97. PMid:17363065

Caimmi PP, Kapetanakis EI, Beggino C, Molinari C, Giustini G, Crosio E, et al. Management of acute cardiac failure by intracoronary administration of levosimendan. J Cardiovasc Pharmacol. 2011;58:246–53. PMid:21654504

Kamath SR, Jaykumar I, Matha S. Levosimendan. Indian Pediatr. 2009;46:593–596. PMid:19638658

Pathak A, Lebrin M, Vaccaro A, Senard JM, Despas F. Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. J Clin Pharm Ther. 2013;38(5):341-9. PMid:23594161

Kasikcioglu HA, Cam N. A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400.

Lepran I, Pollesello P, Vajda S, Varró A, Papp G J. Preconditioning effects of levosimendan in a rabbit cardiac ischemia–reperfusion model. J. Cardiovasc. Pharmacol. 2006;48:148–152. PMid:17086092

Ng TM. Levosimendan, a new calcium-sensitizing inotrope for heart failure. Pharmacotherapy. 2004;24:1366–84.

Jonsson N E, Antila S, McFadyen L, Lehtonen L, Karlsson M. Population pharmacokinetics of levosimendan in patients with congestive heart failure. Br J Clin Pharmacy. 2003;55(6):544-551. PMCid:PMC1884248

Moreno N, Tavares-Silva M, Lourenço AP, Pinto J O, Henriques-Coelho T, Leite-Moreira AF. Levosimendan: The current situation and new prospects. Rev Port Cardiol. 2014;33(12):795-800. PMid:25459636

Eriksson HI, Jalonen JR, Heikkinen LO, Kivikko M, Laine M, Leino KA, et al. Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. Ann Thorac Sure. 2009;87:448–454. PMid:19161758

Kivikko M, Lehtonen L, Colucci WS. Sustained hemodynamic effects of intravenous levosimendan. Circulation. 2003;107:81–6. PMid:12515747

Nieminen MS, Buerke M, Cohen-Solál A, Costa S, Édes I, Erlikh A, Franco F, et al. The role of levosimendan in acute heart failure complicating acute coronary syndrome: A review and expert consensus opinion. Int J Cardiol. 2016;218:150-157. PMid:27232927

Shi WY, Li S, Collins N, Cotten DB, Bastian BC, James AN, Mejia R. Peri- operative Levosimendan in Patients Undergoing Cardiac Surgery: An Overview of the Evidence. Heart Lung Circ. 2015;24(7):667-72. PMid:25862519

De Luca L, Colucci WS, Nieminen MS, Massie BM, Gheorghiade M. Evidence-based use of levosimendan in different clinical settings. Eur Heart J. 2006;27:1908-20. PMid:16682381

Delaney A, Bradford, C, McCaffrey J, Bagshaw S M, Lee R. Levosimendan for the treatment of acute severe heart failure: A meta-analysis of randomised controlled trials. Int J Cardiol. 2010;138(3):281-9. PMid:18817994

Mebazaa A, Nieminen MS, Filippatos G S, Cleland JG, Salon JE, Thakkar R, Padley RJ, Huang B, Cohen-Solal A. Levosimendan vs. dobutamine: outcomes for acute heart failure patients on beta-blockers in SURVIVE. Eur J Heart Fail. 2009;11:304–311. PMid:19158152 PMCid:PMC2645051

Cohen-Solal A, Logeart D, Huang B, et al.Lowered B type natriuretic peptide in response to levosi mendan or dobutamine treatment is associated with improved survival in patients with severe acutely decompensated heart failure. J Am Coll Cardiol. 2009;53:23432348. PMid:19539144

Harrison R W, Hasselblad V, Mehta R H, Levin R, Harrington RA, Alexander JH. Effect of levosimendan on survival and adverse events after cardiac surgery: a meta-analysis. J Cardiothorac Vasc Anesth. 2013;27:1224–32. PMid:24050857

Landoni G, Mizzi A, Biondi-Zoccai G, et al., Reducing mortality in cardiac surgery with levosimendan: a meta-analysis of randomized controlled trials. J Cardiothorac Vasc Anesth. 2010;24:51–57. PMid:19700350

Maharaj R, Metaxa V. Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomised controlled trials. Crit Care. 2011;15:R140. PMid:21651806 PMCid:PMC3219012

Lim JY , Deo SV, Rababa'h A, Altarabsheh SE, Cho YH, Hang D, et al. Levosimendan reduces mortality in adults with left ventricular dysfunction undergoing cardiac surgery: a systematic review and meta-analysis. J Card Surg. 2015;30:547–554. PMid:25989324

Levin R, Degrange M, Del Mazo C, Tanus E, Porcile R. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol. 2012;17:125–30. PMid:23620700 PMCid:PMC3628425

Leppikangas H, Järvelä K, Sisto T, Maaranen P, Virtanen M, Lehto P, et al. Preoperative levosimendan infusion in combined aortic valve and coro- nary bypass surgery. Br J Anaesth. 2011;106:298–304. PMid:21258075

Järvelä K, Maaranen P, Sisto T, Ruokonen E. Levosimendan in aortic valve surgery: car- diac performance and recovery. J Cardiothorac Vasc Anesth. 2008;22:693–698. PMid:18922425

Lomivorotov VV, Boboshko VA, Efremov SM, et al. Levosimendan versus an intra-aortic balloon pump in high-risk cardiac patients. J Cardiothorac Vasc Anesth. 2012;26:596–603. PMid:22051419

Tritapepe L, De Santis V, Vitale D, Guarracino F, Pellegrini F, Pietropaoli P, et al. Levosimendan pre-treatment improves outcomes in patients undergoing coronary artery bypass graft surgery. Br J Anaesth. 2009;102: 198–204. PMid:19151048

Treskatsch S, Balzer F, Geyer T, Spies CD, Kastrup M, Grubitzsch H, et al. Early levosimendan administration is associated with decreased mortality after cardiac surgery. J Crit Care. 2015;30(4):859.e1-6. PMid:25837801

Elahi MM, Lam J, Asopa S, Matata BM. Levosimendan versus an intra-aortic balloon pump in adult cardiac surgery patients with low cardiac output. J Cardiothorac Vasc Anesth. 2011; 25(6):1154–62. PMid:21376634

Lahtinen P, Pitkänen O, Pölönen P, et al. Levosimendan reduces heart failure after cardiac surgery – a prospective, randomized, placebocontrolled trial. Crit Care Med. 2011;39:2263-2270. PMid:21666445

Levin R, Porcile R, Salvagio F, Del Mazo C, Botbol A, Tanus E, et al. Levosimendan reduces mortality in post-operative low cardiac output syndrome after coronary surgery. Circulation. 2009;120:S987–8.

Alvarez J, Bouzada M, Fernández AL, et al. Hemodynamic effects of levosimendan compared with dobutamine in patients with low cardiac output after cardiac surgery. Rev Esp Cardiol. (Engl. Ed.). 2006;59:338–345.

Al-Shawaf E, Ayed A, Vislocky I, Radomir B, Dehrab N, Tarazi R. Levosimendan or milrinone in the type 2 diabetic patient with low ejection fraction undergoing elective coronary artery surgery. J Cardiothorac Vasc Anesth. 2006;20:353–357. PMid:16750735

Russ MA, Prondzinsky R, Carter JM, Schlitt A, Ebelt H, Schmidt H, Lemm H. et al. Right ventricular function in myocardial infarction complicated by cardiogenic shock: Improvement with levosimendan. Crit Care Med. 2009;37(12):3017–3023. PMid:19661807

Yilmaz M B, Yontar C, Erdem A, Karadas F, Yalta K, Turgut O, et al. Comparative effects of levosimendan and dobutamine on right ventricular function in patients with biventricular heart failure. Heart Vessels. 2009;24(1):16–21. PMid:19165563

Niu ZZ, Wu SM, Sun WY, Hou WM, & Chi YF. Perioperative levosimendan therapy is associated with a lower incidence of acute kidney injury after cardiac surgery: a meta- analysis. J Cardiovasc Pharmacol. 2014;63(2):107-12. PMid:24126568

Zorlu A, Yucel H, Yontar OC, Karahan O, Tandogan I, Katrancioglu N, et al. Effect of levosimendan in patients with severe systolic heart failure and worsening renal function. Arq Bras Cardiol. 2012;98:537–43. PMid:22641390

Zhou C, Gong J, Chen D, Wang W, Liu M, Liu B. Levosimendan for prevention of acute kidney injury after cardiac surgery: A Meta-analysis of controlled trials. Am J Kidney Dis. 2016;67(3):408-16. PMid:26518388

Baysal A, Yanartas M, Dogukan M , Gundogus N , Kocak T, Koksal C. Levosimendan improves renal outcome in cardiac surgery: a randomised trial. J Cardiothorac Vasc Anesth. 2014;28:586–594. PMid:24447501

Balzer F, Treskatsch S, Spies C, Sander M, Kastrup M, Grubitzsch H, et al. Early administration of levosimendan is associated with improved kidney function after cardiac surgery, a retrospective analysis. J Cardiothorac Surg. 2014;9:167. PMid:25399779 PMCid:PMC4240807

Knezevic I, Poglajen G, Hrovat E, Oman A, Pintar T, et al. The effects of levosimendan on renal function early after heart transplantation: results from a pilot randomized trial. Clin Transplant. 2014;28(10):1105-11. PMid:25053182

Fedele F, et al. Cost-effectiveness of levosimendan in patients with acute heart failure. J Cardiovasc Pharmacol. 2011; 58(4):363-6. PMid:21697728



How to Cite

Bozhinovska M, Taleska G, Fabian A, Šoštarič M. The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery. Open Access Maced J Med Sci [Internet]. 2016 Jun. 28 [cited 2022 Oct. 6];4(3):510-6. Available from:



F - Review Articles