The Role of Levosimendan in Patients with Decreased Left Ventricular Function Undergoing Cardiac Surgery
DOI:
https://doi.org/10.3889/oamjms.2016.071Keywords:
Cardiac surgery, Levosimendan, Ventricular function, Heart failure, Myocardial dysfunctionAbstract
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.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
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. http://dx.doi.org/10.1016/j.ijcard.2015.02.022 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. http://dx.doi.org/10.1038/sj.bjp.0707526 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. http://dx.doi.org/10.1016/j.athoracsur.2005.08.073 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. http://dx.doi.org/10.1002/14651858.cd002230.pub2
Overgaard CB, DzavÃk V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation. 2008;118(10):1047-56. http://dx.doi.org/10.1161/CIRCULATIONAHA.107.728840 PMid:18765387
Packer M. The search for the ideal positive inotropic agent. N Engl J Med. 1993;329:201–2. http://dx.doi.org/10.1056/NEJM199307153290310 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. http://dx.doi.org/10.1016/0002-9149(90)90699-2
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. http://dx.doi.org/10.1016/j.pharmthera.2007.01.008 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. http://dx.doi.org/10.1097/FJC.0b013e318220e491 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. http://dx.doi.org/10.1111/jcpt.12067 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. http://dx.doi.org/10.2147/vhrm.2006.2.4.389
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. http://dx.doi.org/10.1097/01.fjc.0000246151.39758.2a PMid:17086092
Ng TM. Levosimendan, a new calcium-sensitizing inotrope for heart failure. Pharmacotherapy. 2004;24:1366–84. http://dx.doi.org/10.1592/phco.24.14.1366.43145
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. http://dx.doi.org/10.1046/j.1365-2125.2003.01778.x 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. http://dx.doi.org/10.1016/j.repc.2014.05.009 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. http://dx.doi.org/10.1016/j.athoracsur.2008.10.029 PMid:19161758
Kivikko M, Lehtonen L, Colucci WS. Sustained hemodynamic effects of intravenous levosimendan. Circulation. 2003;107:81–6.
http://dx.doi.org/10.1161/01.CIR.0000043245.00859.11 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. http://dx.doi.org/10.1016/j.ijcard.2016.05.009 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. http://dx.doi.org/10.1016/j.hlc.2015.03.007 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. http://dx.doi.org/10.1093/eurheartj/ehi875 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. http://dx.doi.org/10.1016/j.ijcard.2008.08.020 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. http://dx.doi.org/10.1093/eurjhf/hfn045 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. http://dx.doi.org/10.1016/j.jacc.2009.02.058 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. http://dx.doi.org/10.1053/j.jvca.2013.03.027 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. http://dx.doi.org/10.1053/j.jvca.2009.05.031 PMid:19700350
Maharaj R, Metaxa V. Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomised controlled trials. Crit Care. 2011;15:R140. http://dx.doi.org/10.1186/cc10263 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. http://dx.doi.org/10.1111/jocs.12562 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. http://dx.doi.org/10.1093/bja/aeq402 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. http://dx.doi.org/10.1053/j.jvca.2008.01.024 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. http://dx.doi.org/10.1053/j.jvca.2011.09.006 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. http://dx.doi.org/10.1093/bja/aen367 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. http://dx.doi.org/10.1016/j.jcrc.2015.03.008 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. http://dx.doi.org/10.1053/j.jvca.2011.01.001 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. http://dx.doi.org/10.1097/CCM.0b013e3182227b97 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. http://dx.doi.org/10.1016/S1885-5857(06)60770-6
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. http://dx.doi.org/10.1053/j.jvca.2006.02.012 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. http://dx.doi.org/10.1097/CCM.0b013e3181b0314a 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. http://dx.doi.org/10.1007/s00380-008-1077-2 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. http://dx.doi.org/10.1097/FJC.0000000000000028 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. http://dx.doi.org/10.1590/S0066-782X2012005000048 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. http://dx.doi.org/10.1053/j.ajkd.2015.09.015 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. http://dx.doi.org/10.1053/j.jvca.2013.09.004 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. http://dx.doi.org/10.1186/s13019-014-0167-8 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. http://dx.doi.org/10.1111/ctr.12424 PMid:25053182
Fedele F, et al. Cost-effectiveness of levosimendan in patients with acute heart failure. J Cardiovasc Pharmacol. 2011; 58(4):363-6. http://dx.doi.org/10.1097/FJC.0b013e318224e0a2 PMid:21697728
Downloads
Published
How to Cite
Issue
Section
License
http://creativecommons.org/licenses/by-nc/4.0