simendan profile

Simendan: A hydrazone and pyridazine derivative; the levo-form is a phosphodiesterase III inhibitor, calcium-sensitizing agent, and inotropic agent that is used in the treatment of HEART FAILURE. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	60867
CHEMBL ID	313136
SCHEMBL ID	80460
MeSH ID	M0206272

Synonym
CHEMBL313136
131741-08-7
simendan
mesoxalonitrile (+-)-(p-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazone
propanedinitrile, ((4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)-
simendan [inn]
2-[[4-(4-methyl-6-oxo-4,5-dihydro-1h-pyridazin-3-yl)phenyl]hydrazinylidene]propanedinitrile
FT-0657758
349552krhk ,
unii-349552krhk
FT-0631139
AKOS015907719
SCHEMBL80460
propanedinitrile, 2-(2-(4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazinylidene)-
157968-98-4
2-(2-(4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazinylidene)propanedinitrile
mesoxalonitrile (+/-)-(p-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazone
HMS3656A21
DB12286
{[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazono} propanedinitrile
simsndan;or-1259
BCP09589
DTXSID20861357
AMY18162
SB17415
HMS3744M15
propanedinitrile, 2-[2-[4-(1,4,5,6-tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl]hydrazinylidene]-
Q27256351
bdbm50469701

Research Excerpts

Overview

Levosimendan is a calcium sensitizer used for managing heart failure (HF) because of its inotropic and vasodilatory effects. It increases calcium sensitivity to cardiac myocytes, which results in improved cardiac contractility that last for approximately 7 days.

Excerpt	Reference	Relevance
"Levosimendan is a calcium sensitizer used for managing heart failure (HF) because of its inotropic and vasodilatory effects. "	( Effect of levosimendan combined with recombinant human brain natriuretic peptide on diuretic resistance. Jun, M; Lan, L; Libiya, Z; Shubin, J; Xiangli, S, 2021)	1.54
"Levosimendan (LEVO) is a positive inotropic drug which could increase myocardial contractility and reduce the mortality rate in cardiac surgical patients. "	( Levosimendan administration is not associated with increased risk of bleeding and blood transfusion requirement in patients undergoing off-pump coronary artery bypass grafting: a retrospective study from single center. Fu, RQ; He, LX; Lin, Y; Tan, JC; Wang, LH; Wang, XH; Yao, YT, 2023)	2.03
"Levosimendan (LEV) is a calcium sensitizer with a pleiotropic effect on multiple organs."	( The Effect of Levosimendan on Phosphine-Induced Nephrotoxicity: Biochemical and Histopathological Assessment. Abdollahi, M; Armandeh, M; Baeeri, M; Bameri, B; Farhadi, R; Haghi-Aminjan, H; Khalid, M; Rahimifard, M, 2022)	1.54
"Levosimendan is a safe and effective short-term therapy in AHF and offers comparable long-term survival to COSI in patients who require BTD or BTT therapy."	( Levosimendan and Continuous Outpatient Support With Inotropes in Patients With Advanced Heart Failure: A Single-Centre Descriptive Study. Bergin, P; Cieslik, L; Dagan, M; Hare, JL; Kaye, DM; Lankaputhra, M; Leet, A; Patel, HC; Taylor, AJ; Warner, V; Yeung, T, 2022)	1.76
"Levosimendan is a potent inotropic drug that increases calcium sensitivity to cardiac myocytes, which results in improved cardiac contractility that last for approximately 7 days."	( Effect of perioperative levosimendan administration on postoperative N-terminal pro-B-type natriuretic peptide concentration in patients with increased cardiovascular risk factors undergoing non-cardiac surgery: protocol for the double-blind, randomised, Adamowitsch, N; Berger, C; Clement, T; Fleischmann, E; Fraunschiel, M; Graf, A; Horvath, K; Kabon, B; Kuhrn, M; Reiterer, C; Taschner, A; Treskatsch, S, 2022)	1.5
"Levosimendan is a novel drug often used to treat heart failure. "	( Effects of Levosimendan Preconditioning on Left Ventricular Remodeling after Myocardial Reperfusion in Acute Myocardial Infarction Patients Receiving Percutaneous Coronary Intervention. Yu, S; Zhang, J, 2022)	1.63
"Levosimendan is an inotropic and vasodilator drug used to treat heart failure."	( A New Approach in the Treatment of Traumatic Brain Injury: The Effects of Levosimendan on Necrosis, Apoptosis, and Oxidative Stress. Akyol, ME; Aycan, A; Ergur, B; Gonullu, E; Kume, T; Kuyumcu, F; Oksuz, E; Tas, A, 2022)	1.43
"Levosimendan (LVSMD) is a calcium-sensitizer inotropic and vasodilator agent whose use might have a beneficial effect on the weaning of venoarterial extracorporeal membrane oxygenation (VA-ECMO). "	( Population Pharmacokinetics of Levosimendan and its Metabolites in Critically Ill Neonates and Children Supported or Not by Extracorporeal Membrane Oxygenation. Berthomieu, L; Bourgoin, P; Chenouard, A; Davril, E; Duflot, T; Joram, N; Lamoureux, F; Lecomte, J; Oualha, M; Pereira, T, 2023)	1.75
"Levosimendan is an effective inotropic agent used to maintain cardiac output similar to classic cardiotonic like dobutamine/dopamine."	( Preoperative Levosimendan Administration in Heart Transplant Patients with Severe Hepatic and Renal Impairment: A Retrospective Study. Dong, N; Guo, Q; Lan, H; Li, C; Shi, J; Wang, G; Xiong, T; Zhang, J; Zheng, Q, 2023)	1.73
"Levosimendan is a calcium sensitizer and inodilator, and it is known to improve ventricular function, but its use in newborns is limited."	( Use of levosimendan in hemodynamic management of heart failure in two neonates with intracranial arteriovenous shunts: a case series. Capolupo, I; Columbo, C; De Rose, DU; Di Chiara, L; Dotta, A; Gandolfo, C; Giliberti, P; Landolfo, F; Martini, L; Pugnaloni, F; Ronchetti, MP; Santisi, A; Toscano, A, 2023)	1.78
"Levosimendan is a vasodilating and inotropic agent used in patients with acute heart failure and has resulted in decreased morbidity and mortality in these patients."	( Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy. Guan, Q; Huang, D; Li, A; Li, B; Qin, J; Zhang, C; Zhang, X, 2023)	1.66
"Levosimendan is a calcium sensitizer associated with an influx of calcium ions and activation of ATP-dependent potassium channels that increases myocardial contractility contractions, enhances vasodilation and improves oxygen supply to the cells and tissues."	( Meta-Analysis of the Efficacy of Levosimendan in the Treatment of Severe Sepsis Complicated with Septic Cardiomyopathy. Guan, Q; Huang, D; Li, A; Li, B; Qin, J; Zhang, C; Zhang, X, 2023)	1.74
"Levosimendan is a calcium sensitizer and ATP-dependent potassium channel opener that was developed as an inodilating drug for the treatment of acute heart failure and cardiogenic shock."	( Rationale, experimental data, and emerging clinical evidence on early and preventive use of levosimendan in patients with ventricular dysfunction. Agostoni, P; Cosentino, N; Fracassi, F; Marenzi, G; Niccoli, G; Rebuzzi, A, 2020)	1.26
"Levosimendan is a calcium sensitizer that promotes myocyte contractility through its calcium-dependent interaction with cardiac troponin C. "	( Potential of the Cardiovascular Drug Levosimendan in the Management of Amyotrophic Lateral Sclerosis: An Overview of a Working Hypothesis. Al-Chalabi, A; Heunks, LMA; Papp, Z; Pollesello, P, 2019)	1.34
"Levosimendan is an inotropic agent for the treatment of low cardiac output syndrome that seems to have a protective effect on renal function."	( Preservation of renal function in cardiac surgery patients with low cardiac output syndrome: levosimendan vs beta agonists. Barrera Serrano, R; Bellido Estevez, I; Cruz Mañas, J; Escalona Belmonte, JJ; Gomez Luque, A; Guerrero Orriach, JL; Hernandez Rodriguez, P; Malo Manso, A; Navarro Arce, I; Raigón Ponferrada, A; Ramirez Aliaga, M; Ramirez Fernandez, A; Rubio Navarro, M; Toledo Medina, CS, 2019)	1.21
"Levosimendan is a potent non-adrenergic inodilator agent. "	( Levosimendan and systemic vascular resistance in cardiac surgery patients: a systematic review and meta-analysis. Carrel, T; Eberle, B; Erdoes, G; Friess, JO; Guensch, D; Heinisch, PP; Lenz, A; Terbeck, S, 2019)	1.63
"Levosimendan is a calcium sensitizer and phosphodiesterase inhibitor that has potent antioxidant and anti-inflammatory activities."	( Levosimendan Prevents Memory Impairment Induced by Diabetes in Rats: Role of Oxidative Stress. Alzoubi, KH; Baydoun, S; Khabour, OF; Rababa'h, AM, 2019)	1.63
"Levosimendan is a positive inotropic agent characterized by vasodilatory properties, which is used for the treatment of acute decompensated heart failure or in patients needing inotropic treatment, including cardiogenic shock, septic shock, pulmonary hypertension and right ventricular dysfunction, needed for hemodynamic support in patients with diuretic resistance, and weaning either from ventilator or from extracorporeal membrane oxygenation."	( Levosimendan to facilitate weaning from cardiorespiratory support in critically ill patients: current evidence and future directions. Affronti, A; Bellani, G; Feri, M; Guarracino, F; Marini, M; Quacquarelli, A; Sangalli, F; Vitale, D; Volpi, F, 2020)	1.6
"Levosimendan is a new inodilator which involves 3 main mechanisms: increases the calcium sensitivity of cardiomyocytes, acts as a vasodilator due to the opening of potassium channels, and has a cardioprotective effect. "	( Levosimendan in the treatment of patients with acute cardiac conditions: an expert opinion of the Association of Intensive Cardiac Care of the Polish Cardiac Society. Bugajski, J; Deja, M; Depukat, R; Gierlotka, M; Gruchała, M; Grześk, G; Kasprzak, JD; Kubica, J; Kucewicz-Czech, E; Leszek, P; Płonka, J; Sobkowicz, B; Stępińska, J; Straburzyńska-Migaj, E; Tycińska, A; Wilk, K; Zawiślak, B; Zymliński, R, 2020)	1.67
"Levosimendan (LEVO), is an inotropic agent which has been shown to be associated with better myocardial performance, and higher survival rate in cardiac surgical patients. "	( The effect of levosimendan on postoperative bleeding and blood transfusion in cardiac surgical patients: a PRISMA-compliant systematic review and meta-analysis. He, LX; Yao, YT; Zhao, YY, 2021)	1.51
"Levosimendan is an effective calcium sensitizer with complementary mechanisms of action: calcium sensitization and opening of adenosine triphosphate-dependent potassium channels, both on the sarcolemma of the smooth muscle cells in the vasculature and on the mitochondria of cardiomyocytes. "	( Pre-bypass levosimendan in ventricular dysfunction-effect on right ventricle. Ahlawat, V; Kumar, D; Kundu, A; Prakash, A; Yadav, A; Yadava, OP, 2021)	1.53
"Levosimendan is a novel long acting effect inodilator used in cardiogenic shock and terminal heart failure decompensation."	( Levosimendan in venoarterial ECMO weaning. Rational and design of a randomized double blind multicentre trial. Abou-Arab, O; Besnier, E; Bouhemad, B; Cransac, A; Ellouze, O; Fischer, MO; Guinot, PG; Ksiazek, E; Mertes, PM; Moussa, M; Radhouani, M; Soudry Faure, A, 2021)	1.66
"Levosimendan is a calcium sensitizer and opens adenosine triphosphate-dependent potassium channels. "	( [Levosimendan - a 20-Year Experience]. Häberle, HA, 2021)	1.69
"Levosimendan is a distinctive inodilator combing calcium sensitization, phosphodiesterase inhibition and vasodilating properties through the opening of adenosine triphosphate-dependent potassium channels. "	( Evidence and Current Use of Levosimendan in the Treatment of Heart Failure: Filling the Gap. Conti, N; Diemberger, I; Gatti, M; Potena, L; Raschi, E, 2021)	1.46
"Levosimendan is an inotropic agent that has been shown in small studies to prevent or treat the low cardiac output syndrome after cardiac surgery."	( Levosimendan in Patients with Left Ventricular Dysfunction Undergoing Cardiac Surgery. Alexander, JH; Anstrom, KJ; Argenziano, M; Bozinovski, J; Duncan, A; Fremes, S; Goodman, SG; Harrington, RA; Harrison, RW; Hay, D; Heringlake, M; Jankowich, R; Kalavrouziotis, D; Leimberger, JD; Levy, JH; Luber, J; Marcel, R; Mehta, RH; Meza, J; Murphy, E; Nagpal, D; Park, S; Soltesz, EG; Toller, W; van Diepen, S; Wang, A, 2017)	1.57
"Levosimendan appears to be a promising drug to reduce mortality and worsening HF in patients with HF/CS-ACS. "	( Effects of Levosimendan on Patients with Heart Failure Complicating Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials. Shang, G; Shang, Y; Song, D; Tang, M; Ti, Y; Wang, Z; Yang, X; Zhang, W; Zhang, Y; Zhong, M, 2017)	1.37
"Levosimendan is a cardiac inotropic drug and vasodilator."	( Efficacy and safety of levosimendan in patients with acute right heart failure: A meta-analysis. Hao, Y; Huang, S; Jia, L; Li, X; Ma, Y; Mao, Y; Qiu, J; Wang, M, 2017)	1.23
"Levosimendan is a calcium sensitizer and adenosine triphosphate-dependent potassium channel opener, which exerts sustained hemodynamic, symptomatic, and organ-protective effects. "	( Use of Levosimendan in Cardiac Surgery: An Update After the LEVO-CTS, CHEETAH, and LICORN Trials in the Light of Clinical Practice. Bettex, D; Bouchez, S; Cholley, B; Guarracino, F; Heringlake, M; Kivikko, M; Lomivorotov, VV; Pollesello, P; Rajek, A, 2018)	1.43
"Levosimendan is a cardiac inotropic and vasodilator agent that has pleotropic effects including antioxidant, anti-inflammatory, and smooth muscle vasodilatory actions."	( Levosimendan enhances memory through antioxidant effect in rat model: behavioral and molecular study. Alzoubi, KH; Atmeh, A; Rababa'h, AM, 2018)	1.52
"Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. "	( Levosimendan for Perioperative Cardioprotection: Myth or Reality? Incalzi, RA; Massini, C; Migale, M; Santillo, E, 2018)	1.6
"Levosimendan is a novel calcium sensitizer commonly administered after cardiac surgery."	( Perioperative Use of Levosimendan Improves Clinical Outcomes in Patients After Cardiac Surgery: A Systematic Review and Meta-Analysis. Huo, JH; Luo, X; Qiang, H; Wang, ZQ, 2018)	1.27
"Levosimendan is a calcium sensitiser and adenosine triphosphate (ATP)-sensitive potassium channel (I"	( [Perioperative use of levosimendan in cardiac surgery. Hungarian recommendation]. Babik, B; Bertalan, A; Bogáts, G; Csomós, Á; Gombocz, K; Hartyánszky, I; Hejjel, L; Koszta, G; Molnár, A; Németh, E; Nyolczas, N; Paulovich, E; Prodán, Z; Sápi, E; Sax, B; Székely, L; Szerafin, T; Szolnoky, J; Szudi, L; Zima, E, 2018)	1.26
"Levosimendan is a new inotropic drug that causes calcium sensitization of troponin C, thus increasing contraction force of myofilaments."	( Use of levosimendan in the treatment of cerebral vascular vasospasm: a case study. Goraj, R; Jalali, R; Nosek, K; Onichimowski, D; Pawlos, A; Tuyakov, B; Wińska, A, 2018)	1.35
"Levosimendan is a calcium sensitizer that is used as positive inotropic drug in acute decompensated heart failure. "	( Ranolazine Prevents Levosimendan-Induced Atrial Fibrillation. Dechering, DG; Eckardt, L; Ellermann, C; Fehr, M; Frommeyer, G; Kochhäuser, S; Kohnke, A; Reinke, F, 2018)	1.35
"Levosimendan is an inotropic agent that has been shown in small studies to treat low cardiac output syndrome in cardiac surgery. "	( Levosimendan in patients with low cardiac output syndrome undergoing cardiac surgery: A systematic review and meta-analysis. Chen, L; He, Y; Qing, X; Zhang, Y; Zhu, J, 2019)	1.63
"Levosimendan is a first-in-class calcium sensitizer and potassium channel opener indicated for the management of acute HF."	( Repetitive levosimendan infusions for patients with advanced chronic heart failure in the vulnerable post-discharge period. Allipour Birgani, S; Altenberger, J; Comín-Colet, J; Delgado, JF; Fedele, F; García-Gonzáles, MJ; Gustafsson, F; Masip, J; Papp, Z; Pölzl, G; Störk, S; Ulmer, H; Vrtovec, B; Wikström, G, 2019)	1.35
"Levosimendan is a cardiac inotropic and vasodilator agent that has been reported to have anti-oxidative, anti-inflammatory, and smooth muscle vasodilatory properties. "	( Cardioprotective effect of levosimendan against homocysteine-induced mitochondrial stress and apoptotic cell death in H9C2. Aminzadeh, A; Mehrzadi, S, 2018)	1.33
"Levosimendan is an inodilator that promotes cardiac contractility primarily through calcium sensitization of cardiac troponin C and vasodilatation via opening of adenosine triphosphate-sensitive potassium (KATP) channels in vascular smooth muscle cells; the drug also exerts organ-protective effects through a similar effect on mitochondrial KATP channels. "	( Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper. Bouchez, S; Girardis, M; Guarracino, F; Herpain, A; Knotzer, J; Levy, B; Liebregts, T; Pollesello, P; Ricksten, SE; Riha, H; Rudiger, A; Sangalli, F, 2019)	1.46
"Levosimendan is a positive inotropic and a vasodilator agent with pleotropic characteristics that include antioxidation, anti-inflammation and smooth muscle vasodilation."	( Assessment of Genotoxicity of Levosimendan in Human Cultured Lymphocytes. Ababneh, M; Al-Momani, D; Alzoubi, KH; Khabour, OF; Rababa'h, AM, 2019)	1.35
"Levosimendan is a novel drug for treatment of sepsis-induced myocardial dysfunction."	( Levosimendan as a new force in the treatment of sepsis-induced cardiomyopathy: mechanism and clinical application. Chen, Z; Sun, Y; Yang, F; Zhao, LN, 2019)	1.55
"Simendan is a calcium sensitizer that enhances myocardial contractility but does not affect ventricular diastole. "	( The efficacy of simendan in the treatment of acute heart failure and its impact on NT-proBNP. Li, J; Li, Y; Wang, XY; Yang, F; Yang, J; Yang, ZY; Yuan, P, 2019)	2.3
"Levosimendan is a new molecule with inotropic and vasodilator effect and is widely used for acute decompensated heart failure."	( Rapid recovery from acute myocarditis under levosimendan treatment: report of two cases. Alici, H; Cakici, M; Davutoglu, V; Ercan, S; Kus, E; Sari, I, 2013)	1.13
"Levosimendan is a novel calcium sensitizer that is an established treatment for congestive heart failure. "	( Functional effects of levosimendan in rat basilar arteries in vitro. Guresir, E; Konczalla, J; Mrosek, J; Platz, J; Schuss, P; Seifert, V; Vatter, H; Wanderer, S, 2013)	1.25
"Levosimendan (LS) is a novel inodilator for the treatment of severe congestive heart failure (CHF). "	( Intermittent levosimendan treatment in patients with severe congestive heart failure. Kivikko, M; Kurttila, M; Laitinen, T; Magga, J; Miettinen, K; Parviainen, I; Peuhkurinen, K; Punnonen, K; Timonen, K; Timonen, P; Tuomainen, PO; Uusaro, A; Vanninen, E; Vuolteenaho, O, 2013)	1.29
"Levosimendan is an inotropic agent with an original mechanism of action."	( Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects. Despas, F; Lebrin, M; Pathak, A; Senard, JM; Vaccaro, A, 2013)	1.19
"Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure."	( Renal effects of levosimendan: a consensus report. Édes, I; Fedele, F; Grossini, E; Harjola, VP; Hasslacher, J; Kivikko, M; le Noble, J; Mebazaa, A; Morelli, A; Oldner, A; Oulego Erroz, I; Parissis, JT; Parkhomenko, A; Poelzl, G; Pollesello, P; Rehberg, S; Ricksten, SE; Rodríguez Fernández, LM; Salmenperä, M; Silva Cardoso, JC; Singer, M; Treskatsch, S; Vrtovec, B; Wikström, G; Yilmaz, MB, 2013)	1.19
"Levosimendan is a new positive inotropic drug, which induces preconditioning-like adaptive mechanisms due to opening of mitochondrial KATP channels."	( Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury? Balla, Z; Fulop, A; Garbaisz, D; Harsanyi, L; Hegedus, V; Lotz, G; Onody, P; Rakonczay, Z; Rosero, O; Stangl, R; Szijarto, A; Turoczi, Z, 2013)	1.43
"Levosimendan is a noncatecholamine inotrope that does not increase oxygen consumption, utilized for the treatment for acute heart failure with left ventricular (LV) systolic dysfunction. "	( Safety and feasibility of levosimendan administration in takotsubo cardiomyopathy: a case series. Brunetti, ND; Carpagnano, G; Di Biase, L; Di Biase, M; Ferraretti, A; Ienco, V; Ieva, R; Lodispoto, M; Santoro, F, 2013)	1.24
"Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use. "	( Perioperative levosimendan therapy is associated with a lower incidence of acute kidney injury after cardiac surgery: a meta-analysis. Chi, YF; Hou, WM; Niu, ZZ; Sun, WY; Wu, SM, 2014)	1.29
"Levosimendan is a calcium sensitizer with inotropic and vasodilatory effects used in the treatment of severe heart failure."	( Levosimendan may improve weaning outcomes in venoarterial ECMO patients. Affronti, A; Carino, D; di Bella, I; Ragni, T, )	1.17
"Levosimendan is a positive inotropic agent improving cardiac contractility without increasing myocardial oxygen consumption in HF."	( Impact of levosimendan on right ventricular functions by using novel tissue Doppler derived indices in patients with ischaemic left ventricular failure. Alibaz-Oner, F; Erguney, M; Gurbuz, OZ; Oner, E; Yurdakul, S, 2013)	1.23
"Levosimendan (LS) is a novel inodilator that improves cardiac performance, central hemodynamics, and symptoms of patients with decompensated chronic heart failure. "	( Comparison of single-dose and repeated levosimendan infusion in patients with acute exacerbation of advanced heart failure. Acarturk, E; Bacaksiz, A; Bozkurt, A; Demir, M; Eker, RA; Kanadasi, M; Sahin, DY; Tasal, A; Vatankulu, MA, 2014)	1.22
"Levosimendan is a calcium sensitizer drug which has been used in cardiac surgery for the prevention of postoperative low cardiac output syndrome (LCOS) and in difficult weaning from cardiopulmonary bypass (CPB). "	( Study of levosimendan during off-pump coronary artery bypass grafting in patients with LV dysfunction: a double-blind randomized study. Brahmbhatt, A; Malhotra, A; Patel, J; Rathod, B; Shah, B; Shah, R; Sharma, P; Shastri, N, )	1.06
"Levosimendan is an inotropic drug with organ-protective properties due to its activation of mitochondrial K(ATP) channels. "	( Influence of levosimendan on organ dysfunction in patients with severely reduced left ventricular function undergoing cardiac surgery. Beutlhauser, T; Erb, J; Feldheiser, A; Grubitzsch, H; Schuster, B; Spies, C; Treskatsch, S, 2014)	1.3
"Levosimendan is a calcium-sensitizing agent shown to prevent myocardical contractile depression in various heart diseases. "	( Improved myocardial function with supplement of levosimendan to Celsior solution. Chen, YY; Shen, YL; Wang, LL; Zhang, LN; Zheng, MZ; Zhou, HY, 2014)	1.21
"Levosimendan is a new calcium sensitizing drug with vasodilatory and inotropic properties, which is used for the treatment of postoperative low cardiac output syndrome and difficult weaning from cardiopulmonary bypass."	( Preoperative levosimendan in ischemic mitral valve repair. Bishnoi, A; Gandhi, H; Gandhi, S; Garg, P; Malhotra, A; Sharma, P, 2014)	1.3
"Levosimendan is an inodilator with cardioprotective and neuroprotective effects."	( The role of Levosimendan in cardiopulmonary resuscitation. Aroni, F; Stefaniotou, A; Varvarousi, G; Varvaroussis, D; Xanthos, T, 2014)	1.23
"Levosimendan is a promising therapy for prevention of IRI."	( Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury. Abdel-Gaber, SA; Abdelrahman, AM; Amin, EF; Ibrahim, MA; Ibrahim, SA; Mohammed, RK, 2014)	1.12
"Levosimendan is a positive inotropic drug for the treatment of acute decompensated heart failure (HF). "	( Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. Aliabadi, A; Buchberger, E; de Martin, R; Demyanets, S; Gröger, M; Hofer-Warbinek, R; Huber, K; Kastl, SP; Kaun, C; Krychtiuk, KA; Maurer, G; Pisoni, J; Rauscher, S; Speidl, WS; Watzke, L; Wojta, J; Zuckermann, A, 2015)	1.53
"Levosimendan is a calcium-sensitizing agent that improves cardiac function, hemodynamic performance, and survival in critically ill adult patient. "	( A systematic review on levosimendan in paediatric patients. Azzolini, ML; Dossi, R; Landoni, G; Silvani, P; Silvetti, S; Zangrillo, A, 2015)	1.27
"Levosimendan is a pyridazinone-dinitrile derivative with positive inotropic and vasodilatory effects that has beneficial effects on myocardial performance. "	( Levosimendan: The current situation and new prospects. Henriques-Coelho, T; Leite-Moreira, AF; Lourenço, AP; Moreno, N; Oliveira-Pinto, J; Tavares-Silva, M, 2014)	1.52
"Levosimendan proved to be a safe, effective strategy in our paediatric population."	( Experience with levosimendan in 32 paediatric patients. Martín Herranz, MI; Martínez Roca, C; Vilaboa Pedrosa, C; Yáñez Gómez, P, 2015)	1.22
"Levosimendan is a calcium sensitizer and K(+)-ATP channel opener with inotropic and vasodilatatory effects irrespective of myocardial oxygen consumption, used for treatment of heart failure (HF). "	( Effects of levosimendan on heart failure in normotensive patients: does loading dose matter? Favilli, R; Lunghetti, S; Mondillo, S; Palmerini, E; Söderberg, S, 2015)	1.33
"Levosimendan is a calcium-sensitising ionodilator."	( Peri-operative Levosimendan in Patients Undergoing Cardiac Surgery: An Overview of the Evidence. Bastian, BC; Collins, N; Cottee, DB; James, AN; Li, S; Mejia, R; Shi, WY, 2015)	1.23
"Levosimendan is a non-adrenergic inotropic Ca(+2) sensitizer with not only beneficial hemodynamic properties but also pleiotropic effects, contributing to its cardioprotective and neuroprotective role."	( Role of levosimendan in the management of subarachnoid hemorrhage. Eforakopoulou, M; Georgiadou, M; Katsioula, E; Pavlou, H; Sarafidou, P; Varvarousi, G; Xanthos, T, 2016)	1.29
"Levosimendan is an inotropic agent with cardioprotective and vasodilating properties used for the management of acutely decompensated heart failure. "	( Effect of levosimendan therapy on myocardial infarct size and left ventricular function after acute coronary occlusion. Duvall, E; Haavisto, M; Kentala, R; Knuuti, J; Levijoki, J; Nyman, L; Pietilä, M; Roivainen, A; Saraste, A; Saukko, P; Saunavaara, V; Savunen, T; Stark, C; Strandberg, M; Tarkia, M; Teräs, M; Tolvanen, T; Vähäsilta, T, 2016)	1.35
"Levosimendan is an inodilator developed for treatment of acute heart failure and other cardiac conditions where the use of an inodilator is considered appropriate. "	( Levosimendan meta-analyses: Is there a pattern in the effect on mortality? Harjola, VP; Kivikko, M; Parissis, J; Pollesello, P, 2016)	1.55
"Levosimendan is a new positive inotropic agent having ATP-dependent potassium-channel opening, and calcium-sensitizing effects, which increases cardiac contractility and performance along with vasodilatatory action without increasing myocardial oxygen demand."	( Levosimendan. A promising future drug for refractory cardiac failure in children? Kumar, A; Kushwah, S; Sahana, KS, 2016)	1.47
"Levosimendan is a calcium-sensitizing drug with positive inotropic properties. "	( [Use of levosimendan in children]. Mauriat, P; Séguéla, PE; Tafer, N; Thambo, JB, 2016)	1.37
"Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. "	( Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper. Alvarez, J; Brito, D; Farmakis, D; Fedele, F; Fonseca, C; Gal, TB; Gordon, AC; Gotsman, I; Grossini, E; Guarracino, F; Harjola, VP; Hellman, Y; Heunks, L; Ivancan, V; Karavidas, A; Kivikko, M; Lomivorotov, V; Longrois, D; Masip, J; Metra, M; Morelli, A; Nikolaou, M; Papp, Z; Parissis, J; Parkhomenko, A; Poelzl, G; Pollesello, P; Ravn, HB; Rex, S; Ricksten, SE; Riha, H; Schwinger, RHG; Vrtovec, B; Yilmaz, MB; Zielinska, M, 2016)	1.55
"Levosimendan is a pyridazinone-dinitrile derivative, emerged as a potent cardiotonic agent with dual inotropic and vasodilator activities in higher animals. "	( A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites. Asif, M, 2018)	1.28
"Levosimendan is an inodilator for the treatment of acute decompensated heart failure (HF). "	( Anti-thrombotic and pro-fibrinolytic effects of levosimendan in human endothelial cells in vitro. de Martin, R; Eppel, W; Hohensinner, PJ; Huber, K; Kastl, SP; Kaun, C; Krychtiuk, KA; Maurer, G; Rauscher, S; Seigner, J; Speidl, WS; Stojkovic, S; Wojta, J; Zuckermann, A, 2017)	1.26
"Levosimendan is a positive inotropic drug with vasodilatory properties that is indicated for acute heart failure."	( The use of Levosimendan for myocardiopathy due to acute Chagas' disease. de Albernaz Muniz, RZ; de March Ronsoni, R; Feijó, RV; Filho, WJ; Melo, LH; Moro, A; Schwingel, FL; Weber, S, 2009)	1.19
"Levosimendan is a new calcium sensitizer that enhances the contractile force of the myocardium and exhibits additional vasodilating properties. "	( Safety and effectiveness of levosimendan in patients with predominant right heart failure. Frick, M; Grander, W; Jonetzko, P; Metzler, B; Pachinger, O; Poelzl, G; Roithinger, FX; Ulmer, H; Zwick, RH, 2008)	1.19
"Levosimendan is a calcium-sensitizing drug for the treatment of heart failure. "	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	1.13
"Levosimendan is a calcium-sensitizing agent with effective inotropic properties. "	( First experiences with intraoperative Levosimendan in pediatric cardiac surgery. Boethig, D; Goerler, H; Huber, D; Osthaus, WA; Sasse, M; Sümpelmann, R; Winterhalter, M, 2009)	1.18
"Levosimendan is a novel agent in the treatment of decompensated heart failure, representing a newer class of medications aimed at increasing calcium sensitivity."	( Levosimendan and calcium sensitization of the contractile proteins in cardiac muscle: impact on heart failure. Economides, C; Kota, B; Prasad, AS; Singh, BN, 2008)	1.38
"Levosimendan is a new cardiac enhancer that exerts positive inotropic effects on the failing heart mediated by calcium sensitization of contractile proteins as well as peripheral vasodilatory effects mediated by opening of ATP-sensitive potassium channels in vascular smooth-muscle cells. "	( Levosimendan: from basic science to clinical practice. Mebazaa, A; Paraskevaidis, I; Parissis, JT; Rafouli-Stergiou, P, 2009)	1.47
"Levosimendan acts as a vasodilator through the opening of ATP-sensitive K(+) channels (K(ATP)) channels. "	( Levosimendan induces NO production through p38 MAPK, ERK and Akt in porcine coronary endothelial cells: role for mitochondrial K(ATP) channel. Caimmi, PP; Grossini, E; Molinari, C; Uberti, F; Vacca, G, 2009)	1.47
"Levosimendan is a compound with vasodilatory and inotropic properties. "	( Levosimendan facilitates weaning from cardiopulmonary bypass in patients undergoing coronary artery bypass grafting with impaired left ventricular function. Eriksson, HI; Heikkinen, LO; Jalonen, JR; Kivikko, M; Kuitunen, AH; Kuttila, KT; Laine, M; Leino, KA; Peräkylä, TK; Salmenperä, MT; Sarapohja, T; Suojaranta-Ylinen, RT; Valtonen, M, 2009)	1.47
"Levosimendan is a novel inodilator agent, which enhances myocardial performance without substantial changes in oxygen consumption. "	( Effects of levosimendan on the energy balance: preclinical and clinical evidence. Nieminen, MS; Papp, Z; Pollesello, P; Vajda, G, 2009)	1.26
"Levosimendan is a promising adjunct in our therapeutic repertoire for the treatment of CF; however, it has not been evaluated in CF patients undergoing non-cardiac surgery."	( Prophylactic preoperative levosimendan administration in heart failure patients undergoing elective non-cardiac surgery: a preliminary report. Drimousis, P; Filis, K; Kapralou, A; Katsaragakis, S; Kofinas, G; Larentzakis, A; Markogiannakis, H; Misthos, P; Theodorou, D, )	0.9
"Levosimendan (LS) is a new inodilator agent that improves cardiac contractility by increasing the sensitivity of troponin C to calcium, which usage in cardiac surgery has been growing in the recent years. "	( Timing of levosimendan in cardiac surgery. Adanir, T; Aksun, M; Aran, G; Gürbüz, A; Karahan, N; Ozgürbüz, U; Oztürk, T; Sencan, A; Yetkin, U, 2009)	1.27
"Levosimendan is a calcium-sensitising inotropic agent and a vasodilator used in the treatment of heart failure. "	( Prophylactic treatment with levosimendan: a retrospective matched-control study of patients with reduced left ventricular function. Kirkeby-Garstad, I; Kolseth, SM; Nordhaug, DO; Sellevold, O; Stenseth, R; Wahba, A, 2009)	1.19
"Levosimendan is a novel calcium sensitizing inotropic agent with anti-apoptotic properties."	( Effects of levosimendan in experimental acute coxsackievirus myocarditis. Kytö, V; Latva-Hirvelä, J; Levijoki, J; Saraste, A; Saukko, P; Vuorinen, T, 2009)	1.19
"Levosimendan is a new inodilatory agent with calcium sensitizing activity. "	( Levosimedan improves hemodynamics functions without sympathetic activation in severe heart failure patients: direct evidence from sympathetic neural recording. Despas, F; Franchitto, N; Galinier, M; Labrunee, M; Pathak, A; Senard, JM; Trouillet, C, 2010)	0.92
"Levosimendan is a calcium sensitizer that is able to enhance myocardial contractility without increasing myocardial oxygen use."	( Levosimendan reduces mortality in critically ill patients. A meta-analysis of randomized controlled studies. Ajello, V; Bignami, E; Biondi-Zoccai, G; Guarracino, F; Landoni, G; Marino, G; Mizzi, A; Prati, P; Zangrillo, A, 2010)	1.4
"Levosimendan is a new calcium sensitizer and K-ATP channel opener, has emerged as an alternative option of pharmacologic inotropic support in patients with decompensated heart failure."	( A promising new inotrope: levosimendan. Duman, D; Fotbolcu, H, 2010)	1.13
"Levosimendan is a calcium sensitizer developed for the treatment of heart failure. "	( Absence of mitochondrial activation during levosimendan inotropic action in perfused paced guinea pig hearts as demonstrated by modular control analysis. Calmettes, G; Deschodt-Arsac, V; Diolez, P; Franconi, JM; Massot, P; Pollesello, P; Raffard, G, 2010)	1.18
"Levosimendan is a 'Ca(2+)sensitiser', which exerts its inotropic effect by increasing the affinity of troponin C for Ca(2+), directly stabilising the Ca(2+)-induced conformation of troponin C. "	( Levosimendan - a calcium sensitising agent with potential anti-arrhythmic properties. Banach, M; Kowalczyk, M; Kozłowski, D; Lip, GY; Mikhailidis, DP; Rysz, J, 2010)	1.48
"Levosimendan is a relatively new inotropic agent. "	( Efficacy of levosimendan in patients with chronic heart failure: Does rhythm matter? Tandoğan, I; Yalta, K; Yilmaz, MB; Yontar, OC, 2010)	1.26
"Levosimendan is a unique therapeutic agent that decreases mortality in acute episodes of decompensated heart failure by increasing myocardial contractility without increasing oxygen consumption or ATP demands, decreasing preload, or decreasing afterload. "	( Levosimendan: calcium sensitizer and inodilator. Fields, AM; Milligan, DJ, 2010)	1.48
"Levosimendan is a novel inotropic agent that enhances cardiac contractility without increasing cellular calcium intake, so that it is not supposed to cause intracellular calcium overload and related arrhythmias. "	( Acute effects of levosimendan and dobutamine on QRS duration in patients with heart failure. Erdem, A; Tandogan, I; Yalta, K; Yilmaz, MB; Yontar, OC, 2010)	1.24
"Levosimendan is a promising new inodilator agent but its effectiveness in peripartum cardiomyopathy (PPCM) has not been tested in a clinical trial. "	( Effect of levosimendan and predictors of recovery in patients with peripartum cardiomyopathy, a randomized clinical trial. Akgün, T; Biteker, M; Duran, NE; Gökdeniz, T; Gündüz, S; Kahveci, G; Kaya, H; Õzkan, M; Tanboğa, HÎ; Yildiz, M, 2011)	1.29
"Levosimendan is a calcium sensitizer with positive inotropic and vasodilating properties. "	( The protective effects of levosimendan on ischemia/reperfusion injury and apoptosis. Beiras-Fernandez, A; Mutlak, H; Scheiermann, P; Weis, F, 2011)	1.22
"Levosimendan is an inotropic agent with clinical indications for open-heart surgery."	( Levosimendan decreases intracranial pressure after hypothermic circulatory arrest in a porcine model. Eija, R; Fredrik, Y; Hannu, T; Jensen, H; Jussi, M; Kai, K; Kirsi, A; Matti, P; Tatu, J; Tuomas, M; Vesa, A, 2011)	1.41
"Levosimendan is a new drug used in heart failure though it is limited by the systemic hypotension, which develops with intravenous administration."	( Management of acute cardiac failure by intracoronary administration of levosimendan. Beggino, C; Caimmi, PP; Crosio, E; Giustini, G; Grossini, E; Kapetanakis, EI; Micalizzi, E; Molinari, C; Reposo, G; Vacca, G, 2011)	1.08
"Levosimendan is a cardiovascular drug for the treatment of acute and decompensated heart failure. "	( Multiple signalling pathways underlie the protective effect of levosimendan in cardiac myocytes. Galatou, E; Lazou, A; Makridou, Z; Markou, T, 2011)	1.16
"Levosimendan is an extensively investigated inodilator showing also cardioprotective and antiinflammatory effects. "	( Levosimendan inhibits release of reactive oxygen species in polymorphonuclear leukocytes in vitro and in patients with acute heart failure and septic shock: a prospective observational study. Bellmann, R; Bertocchi, C; Bijuklic, K; Dunzendorfer, S; Hasslacher, J; Joannidis, M; Kountchev, J, 2011)	1.49
"Levosimendan is a calcium sensitizer that enhances myocardial contractility without increasing myocardial oxygen use."	( Effects of levosimendan on mortality and hospitalization. A meta-analysis of randomized controlled studies. Bignami, E; Biondi-Zoccai, G; Greco, M; Greco, T; Guarracino, F; Landoni, G; Morelli, A; Zangrillo, A, 2012)	1.21
"Levosimendan is a calcium-sensitizing inotrope that may support cardiac output, but little is known regarding its differential hemodynamic effects in asphyxiated neonates."	( Differential hemodynamic effects of levosimendan in a porcine model of neonatal hypoxia-reoxygenation. Bigam, D; Cheung, PY; Esch, J; Joynt, C; Lee, TF; Li, YQ; Manouchehri, N; Vento, M, 2012)	1.13
"Levosimendan is a novel positive inotropic agent which, improves myocardial contractility through its calcium-sensitizing action, without causing an increase in myocardial oxygen demand. "	( [Levosimendan treatment of severe acute congestive heart failure refractory to dobutamine/milrinone in children]. Jovicić, B; Kosutić, J; Nikolić, L; Prijić, S; Rakić, S; Stajević, M; Vukomanović, V, 2011)	1.44
"Levosimendan is a novel inotropic agent claimed to improve myocardial contractility by a calcium-sensitizing effect. "	( A dose-response study of levosimendan in a porcine model of acute ischaemic heart failure. Aro, S; Høydal, M; Kirkeby-Garstad, I; Kolseth, SM; Nordgaard, H; Nordhaug, D; Rognmo, Ø; Wahba, A, 2012)	1.23
"Levosimendan (Levo) is an inodilator improving cardiac output (CO) and reducing afterload in heart failure. "	( Levosimendan infusion improves cardiac output but not blood pressure in a rodent model of severe metoprolol toxicity. Graudins, A; Kalam, Y, 2012)	1.5
"Levosimendan is an inodilator indicated for acute heart failure (AHF). "	( The clinical effects of levosimendan are not attenuated by sulfonylureas. Colucci, WS; Kivikko, M; Mebazaa, A; Nieminen, MS; Pohjanjousi, P; Pollesello, P; Teerlink, JR, 2012)	1.23
"Levosimendan (LEVO) is a new calcium sensitizer with positive inotropic and vasodilating properties that represents a new pharmacological class of inotropic drugs that stimulate elevated cardiac output. "	( Beneficial pharmacological effects of levosimendan on antioxidant status of acute inflammation induced in paw of rat: involvement in inflammatory mediators. Albayrak, A; Aydin, A; Bayir, Y; Cadirci, E; Ferah, I; Halici, Z; Karakus, E; Odaci, E; Unal, D, 2013)	1.21
"Levosimendan is a relatively recent inodilatory agent, presenting superior outcomes in comparison with traditional inotropes."	( Economic evaluation of levosimendan versus dobutamine for the treatment of acute heart failure in Italy. Apajasalo, M; D'Ambrosi, A; Fedele, F; Lucioni, C; Mazzi, S; Pollesello, P, 2012)	1.16
"Levosimendan is a new calcium sensitizer with additional vasodilatory properties developed for the short-term intravenous treatment of congestive heart failure. "	( Pharmacokinetics of levosimendan and its metabolites during and after a 24-hour continuous infusion in patients with severe heart failure. Antila, S; Eha, J; Kivikko, M; Lehtonen, L; Pentikäinen, PJ, 2002)	1.18
"Levosimendan is a potent calcium sensitiser with vasodilating properties that has been shown to provide symptomatic and haemodynamic improvement with no increase in oxygen consumption."	( Pharmacotherapeutic approaches for decompensated heart failure: a role for the calcium sensitiser, levosimendan? Borghi, C; Greenberg, B; Perrone, S, 2003)	1.01
"Levosimendan is a new and relevant calcium sensitizer developed for the short-term intravenous treatment of congestive heart failure."	( [Levosimendan: a new option in the pharmacologic management of cardiac insufficiency]. Campos Lara, MG; Carballal-Sanjurjo, JC; Del-Razo, OE; Palma-Aguirre, JA, )	1.13
"Levosimendan is a new agent for the treatment of acute heart failure. "	( Levosimendan: a new dual-action drug in the treatment of acute heart failure. Erhardt, L; Mebazaa, A, 2003)	1.44
"Levosimendan, is a new calcium sensitiser with 2 major effects. "	( [Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?]. Blome, M; Boldt, J; Isgro, F; Lang, J; Lehmann, A, 2003)	1.31
"Levosimendan is a promising calcium sensitizer that potentially could be useful in settings of pulmonary vasoconstriction and right ventricular dysfunction. "	( Effects of levosimendan on right ventricular function and ventriculovascular coupling in open chest pigs. Herijgers, P; Leather, HA; Segers, P; Vandermeersch, E; Ver Eycken, K; Wouters, PF, 2003)	1.23
"Levosimendan is a calcium sensitizer with no major inhibition of PDE at clinically relevant doses."	( The role of Ca++-sensitizers for the treatment of heart failure. Boldt, J; Kirchner, J; Lehmann, A, 2003)	0.8
"Levosimendan is a novel calcium sensitizing agent in development for the treatment of acute and chronic heart failure. "	( Levosimendan: implications for clinicians. McBride, BF; White, CM, 2003)	1.44
"Levosimendan is a representative of this new class recently launched in the Portuguese market."	( Levosimendan: a new approach for the treatment of patients with severe heart failure. A brief summary based on a clinical case. Dias, B; Morais, J; Pontes, N, )	1.17
"Levosimendan is a new vasodilator agent with properties which improve cardiac contractility by calcium sensitization. "	( Considerations on the efficacy and safety of levosimendan in ischemic heart failure. Nieminen, MS; Sandell, EP, 2003)	1.13
"Levosimendan (Simdax) is a calcium-sensitising drug that stabilises the troponin molecule in cardiac muscle, thus prolonging its effects on contractile proteins, with concomitant vasodilating properties. "	( Levosimendan: a review of its use in the management of acute decompensated heart failure. Innes, CA; Wagstaff, AJ, 2003)	1.44
"Levosimendan is a recently developed drug which is not yet approved for clinical routine use in Germany. "	( [Levosimendan. Clinical indications of a new vasoactive substance]. Borges, A; Braun, JP; Dohmen, P; Döpfmer, U; Kastrup, M; Kox, W; Roots, I; Schneider, M; Spies, C, 2004)	1.4
"Levosimendan (LS) is a new calcium sensitizer that exerts positive inotropic effects without increasing intracellular cAMP or Ca2+ at therapeutic doses and therefore may avoid major limitations of beta-adrenergic agents. "	( [Levosimendan in cardiology and intensive care medicine]. Delle Karth, G; Heinz, G, 2004)	1.4
"Levosimendan (Simdax) is a novel intravenous agent that exerts inotropic effects through sensitization of myofilaments to calcium and vasodilator effects by opening ATP-dependent potassium channels on vascular smooth muscle."	( Levosimendan: first in a new class of inodilator for acute and chronic severe heart failure. Cleland, JG; McGowan, J; Nikitin, N, 2004)	1.36
"Levosimendan is a novel calcium sensitizer that increases contraction force without change in intracellular calcium ([Ca2+]i); milrinone is a phosphodiesterase inhibitor that exerts a positive inotropic effect by increasing [Ca2+]i. "	( Effects of levosimendan and milrinone on oxygen consumption in isolated guinea-pig heart. Haikala, H; Kaheinen, P; Levijoki, J; Pollesello, P, 2004)	1.23
"Levosimendan is a calcium sensitizer that increases the contractility of the myofilaments and is considered not to affect cardiac electrophysiology. "	( The calcium sensitizer levosimendan and cardiac arrhythmias: an analysis of the safety database of heart failure treatment studies. Lehtonen, L; Lilleberg, J; Toivonen, L; Ylönen, V, 2004)	1.18
"Levosimendan is a new calcium sensitizer, which enhances myocardial contractility while simultaneously having vasodilatory and cardioprotective effects. "	( Levosimendan in patients with cardiogenic shock undergoing surgical revascularization: a case series. Boldt, J; Isgro, F; Kiessling, AH; Lang, J; Lehmann, A, 2004)	1.44
"Levosimendan is a novel drug developed for treatment of decompensated heart failure. "	( Effect of levosimendan on balance between ATP production and consumption in isolated perfused guinea-pig heart before ischemia or after reperfusion. Eriksson, O; Haikala, H; Pollesello, P, 2004)	1.24
"Levosimendan is a distinct calcium sensitizer, as it stabilizes the interaction between calcium and troponin C by binding to troponin C in a calcium-dependent manner, improving inotropy without adversely affecting lusitropy."	( Levosimendan, a new calcium-sensitizing inotrope for heart failure. Ng, TM, 2004)	1.36
"Levosimendan is a novel calcium sensitiser which has been discovered by using cardiac troponin C (cTnC) as target protein."	( The contractile apparatus as a target for drugs against heart failure: interaction of levosimendan, a calcium sensitiser, with cardiac troponin c. Pollesello, P; Solaro, RJ; Sorsa, T, 2004)	1.03
"Levosimendan is a new calcium sensitizer developed for the treatment of congestive heart failure. "	( Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Kivikko, M; Lehtonen, L, 2005)	1.44
"Levosimendan is a calcium-sensitizing agent and an inodilator under current investigation in the treatment of decompensated heart failure. "	( Effects of intravenous levosimendan on human coronary vasomotor regulation, left ventricular wall stress, and myocardial oxygen uptake. Chatterjee, K; Foster, E; Gerber, IL; Jordan, MV; Kostal, M; McKeown, B; Michaels, AD; Vakharia, KT, 2005)	1.18
"Levosimendan is a new Ca2+-sensitizer for the treatment of acutely decompensated heart failure that has proved to be effective during the decompensation of chronic heart failure and acute myocardial infarction."	( Pharmacological mechanisms contributing to the clinical efficacy of levosimendan. Csapó, K; Edes, I; Haikala, H; Papp, Z; Pollesello, P, 2005)	1.04
"Levosimendan is a new inodilator. "	( Levosimendan: a calcium-sensitizing agent for the treatment of patients with decompensated heart failure. Lehtonen, L, 2004)	1.44
"Levosimendan is a novel inotropic vasodilator agent."	( [The novelty in the treatment of heart failure]. Reingardiene, D, 2005)	0.81
"Levosimendan is a calcium sensitizer that demonstrates enhanced myocardial contractility. "	( Effects of levosimendan on left ventricular functional remodelling and exercise intolerance: a tissue Doppler study. Cam, N; Kasikcioglu, E; Kasikcioglu, HA; Okmen, E; Tartan, Z; Unal, S; Uyarel, H, )	1.04
"Levosimendan proved to be a 1300-fold more potent and a 90-fold more selective PDE III inhibitor (IC50 for PDE III 1.4 nM, and IC50 for PDE IV 11 microM, selectivity factor approximately 8000) than enoximone (IC50 for PDE III 1.8 microM, and IC50 for PDE IV 160 microM, selectivity factor approximately 90)."	( Two inotropes with different mechanisms of action: contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone. Bak, I; Borbély, A; Edes, I; Haikala, H; Levijoki, J; Papp, Z; Pollesello, P; Szilágyi, S; Tósaki, A, 2005)	1.02
"Levosimendan is a new calcium sensitizer with inodilatory properties. "	( Levosimendan in cardiac surgery. Harjola, VP; Siirilä-Waris, K; Suojaranta-Ylinen, R, 2005)	1.44
"Levosimendan is a novel inotropic agent that has several mechanisms of action including calcium sensitization, and is undergoing clinical trials at present."	( The myofilament force-calcium relationship as a target for positive inotropic therapy in congestive heart failure. MacGowan, GA, 2005)	0.81
"Levosimendan is a novel calcium-sensitising agent that has been shown to have beneficial inotropic, metabolic and vasodilatory effects in the treatment of acute and advanced chronic heart failure. "	( Levosimendan for the treatment of acute heart failure syndromes. Adamopoulos, S; Farmakis, D; Filippatos, G; Kremastinos, D; Paraskevaidis, I; Parissis, JT, 2005)	1.44
"Levosimendan is a novel compound recently approved for the management of acute heart failure in Sweden and several European countries. "	( Levosimendan: dual mechanisms for acute heart failure...and beyond? Akhter, MW; Ng, TM, 2005)	1.44
"Levosimendan is a calcium sensitizer that, besides increasing contractility, has a vasodilating effect due to the activation of K(ATP) channels, being both mechanisms responsible for an advantageous therapeutic option."	( [Levosimendan: a new strategy in the treatment of heart failure]. Arias Sánchez, EA; Chacón Mercado, MA; García López, SM; González-Chon, O; Vega Zapata, RE, )	1.13
"Levosimendan is a new inodilator that improves cardiac contractility by sensitizing troponin C to calcium. "	( [Successful use of levosimendan in a patient with cardiogenic shock complicating acute myocardial infarction]. Anis, L; Habib, H; Iheb, L; Moufida, H; Mustapha, F; Nedia, B, 2005)	1.2
"Levosimendan is a new Ca-sensitizing drug with combined positive inotropic and vasodilatory effects that offers new therapeutic possibilities in patients with severe heart failure. "	( Effects of levosimendan on left ventricular diastolic function after primary angioplasty for acute anterior myocardial infarction: a Doppler echocardiographic study. Battagliese, A; Benedetti, G; De Luca, L; Di Roma, A; Fedele, F; Proietti, P; Sardella, G, 2006)	1.24
"Levosimendan is an inotropic and vasodilator drug that has proved to be useful in cardiogenic shock. "	( Effects of levosimendan in normodynamic endotoxaemia: a controlled experimental study. Barán, M; Canales, HS; Dubin, A; Edul, VS; Estenssoro, E; Maskin, B; Murias, G; Pozo, MO; Sottile, JP, 2006)	1.24
"Levosimendan is a calcium sensitizer with positive inotropic and vasodilatory effects and has been developed for treatment of decompensated heart failure."	( Successful administration of levosimendan in a patient with low-gradient low-output aortic stenosis. Hoefer, D; Hoermann, C; Jonetzko, P; Laufer, G; Poelzl, G, 2006)	1.1
"Levosimendan is a new calcium sensitizer with positive inotropic properties. "	( Cardiogenic shock after primary percutaneous coronary intervention: Effects of levosimendan compared with dobutamine on haemodynamics. Abreu-González, P; Domínguez-Rodríguez, A; Ferrer-Hita, JJ; García-González, MJ; Muñoz, MB, 2006)	1.12
"Levosimendan is a potent inotropic and vasodilator drug used in the treatment of decompensated heart failure. "	( Potassium channel-related relaxation by levosimendan in the human internal mammary artery. Demirkilic, U; Nacitarhan, C; Seyrek, M; Yildirim, V; Yildiz, O, 2006)	1.15
"Levosimendan is a new calcium sensitizer and K-ATP channel opener. "	( Evidence-based use of levosimendan in different clinical settings. Colucci, WS; De Luca, L; Gheorghiade, M; Massie, BM; Nieminen, MS, 2006)	1.19
"Levosimendan is a calcium-sensitizing agent and inodilator working via potassium channels, which is under current investigation in the treatment of heart failure. "	( Potassium channels in the vasodilating action of levosimendan on the human umbilical artery. Nacitarhan, C; Seyrek, M; Yildiz, O, 2006)	1.14
"Levosimendan is an inotropic agent that is effective in the treatment of heart failure. "	( [Hemodynamic effects of levosimendan compared with dobutamine in patients with low cardiac output after cardiac surgery]. Alvarez, J; Bouzada, M; Caruezo, V; Fernández, AL; García-Bengoechea, JB; Ginesta, V; González-Juanatey, JR; Rodríguez, J; Rubio, J; Taboada, M, 2006)	1.19
"Levosimendan is a novel inodilator drug developed for the treatment of heart failure. "	( Vasorelaxing effect of levosimendan against 5-hydroxytryptamine-induced contractions in isolated human conduit bypass grafts. Hegedus, Z; Krassói, I; Kun, A; Papp, JG; Pataricza, J; Szolnoky, J; Varró, A, 2006)	1.19
"Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. "	( Effects of serial levosimendan infusions on left ventricular performance and plasma biomarkers of myocardial injury and neurohormonal and immune activation in patients with advanced heart failure. Adamopoulos, S; Farmakis, D; Filippatos, G; Iliodromitis, E; Kremastinos, DT; Panou, F; Paraskevaidis, I; Parissis, JT, 2006)	1.21
"Levosimendan is a positive inotropic drug with vasodilator action and proposed myocardioprotective properties. "	( Effects of levosimendan on myocardial infarct size and hemodynamics in a closed-chest porcine ischemia-reperfusion model. Berg, JS; Busk, M; Kristensen, J; Maeng, M; Mortensen, UM; Nielsen, TT; Nielsen-Kudsk, JE, 2006)	1.24
"Levosimendan is a novel inodilator that beneficially affects hemodynamics and left ventricular systolic and diastolic function in patients with advanced heart failure."	( Effects of levosimendan on right ventricular function in patients with advanced heart failure. Bistola, V; Farmakis, D; Filippatos, G; Kourea, K; Kremastinos, D; Nikolaou, M; Panou, F; Paraskevaidis, I; Parissis, JT, 2006)	1.17
"Levosimendan is a calcium sensitizer that is currently in the focus of intensive care medicine because it may be superior to standard inotropic agents in the treatment of acute myocardial insufficiency. "	( [Role of Levosimendan in intensive care treatment of myocardial insufficiency]. Bröking, K; Ertmer, C; Lange, M; Morelli, A; Rehberg, S; Van Aken, H; Westphal, M, 2007)	1.27
"Levosimendan is a novel calcium sensitizer with vasodilating properties and a complex mechanism of action."	( Effect of levosimendan on ventricular arrhythmias and prognostic autonomic indexes in patients with decompensated advanced heart failure secondary to ischemic or dilated cardiomyopathy. Flevari, P; Kourea, K; Kremastinos, DT; Leftheriotis, D; Panou, F; Parissis, JT, 2006)	1.18
"Levosimendan is a novel positive inotropic calcium sensitizer agent used in acute heart failure. "	( Effect of levosimendan on E/E' ratio in patients with ischemic heart failure. Akilli, A; Akin, M; Duygu, H; Ergene, O; Nalbantgil, S; Nazli, C; Ozerkan, F; Zoghi, M, 2008)	1.26
"Levosimendan is a new positive inotropic agent having ATP-dependent potassium-channel-opening and calcium-sensitizing effects."	( A review of levosimendan in the treatment of heart failure. Cam, N; Kasikcioglu, HA, 2006)	1.16
"Levosimendan is a calcium sensitiser developed for the treatment of congestive heart failure. "	( Effect of severe renal failure and haemodialysis on the pharmacokinetics of levosimendan and its metabolites. Häkkinen, S; Harjola, VP; Kantele, S; Kivikko, M; Koskinen, P; Pentikäinen, PJ; Puttonen, J, 2007)	1.12
"Levosimendan (LS) is a novel calcium sensitizer drug that enhances cardiac contractility without increasing myocardial oxygen consumption, and induces vasodilatation. "	( Successful use of levosimendan in a patient during cardiopulmonary bypass. Erer, D; Iriz, E; Ozdogan, ME; Ozkose, Z; Unal, Y; Zor, H, )	1
"Levosimendan is a relatively new Ca(2+) sensitizer which offers haemodynamic and symptomatic improvement by combining a positive inotropic action via Ca(2+) sensitization and a vasodilatory effect via adenosine triphosphate(ATP)-sensitive K(+) (K(ATP)), Ca(2+)-activated K(+) (K(Ca)(2+)) and voltage-dependent K(+) (K(V)) channels activation."	( Levosimendan: beyond its simple inotropic effect in heart failure. Antoniades, C; Koumallos, N; Marinou, K; Stefanadis, C; Tousoulis, D, 2007)	1.38
"Levosimendan is a new calcium sensitizer with inotropic and vasodilatory actions mediated by the sensitization of contractile proteins to calcium, opening of potassium channels and inhibition of phosphodiesterase-3. "	( The use of levosimendan in comparison and in combination with dobutamine in the treatment of decompensated heart failure. Cavusoglu, Y, 2007)	1.25
"Levosimendan is a calcium sensitizer with a positive inotropic effect without increasing oxygen consumption. "	( Experiences of levosimendan as an inotropic agent in conjunction with passive containment surgery. Bredin, F; Franco-Cereceda, A, 2007)	1.23
"Levosimendan is a new inotropic vasodilator for the treatment of decompensated heart failure. "	( Haemodynamic effects of levosimendan for low cardiac output after cardiac surgery: a case series. Hassoulas, J; Linardakis, M; Malliotakis, P; Xenikakis, T, )	0.98
"Levosimendan is a myocardial calcium sensitiser and potassium-ATP channel opener Levosimendan has been used in critically ill patients in various conditions to support myocardial function as an inotrope, lusitrope and vasodilator. "	( Myocardial depression associated with pneumococcal septic shock reversed by levosimendan. Bihari, D; Ramaswamykanive, H; Solano, TR, 2007)	1.12
"Levosimendan (Simdax) is an approved drug in approximately 40 countries and currently in phase III clinical studies in the USA and Europe. "	( A strategy for high-throughput analysis of levosimendan and its metabolites in human plasma samples using sequential negative and positive ionization liquid chromatography/tandem mass spectrometric detection. El-Shourbagy, TA; Gage, EM; Ji, QC; Zhang, J, 2007)	1.15
"Levosimendan is a new calcium sensitizer with positive inotropic properties. "	( Effects of levosimendan versus dobutamine on left ventricular diastolic function in patients with cardiogenic shock after primary angioplasty. Abreu-Gonzalez, P; Dominguez-Rodriguez, A; Garcia-Gonzalez, MJ; Samimi-Fard, S, 2008)	1.26
"Levosimendan is a promising new inotrope. "	( Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Antoniou, T; Degiannis, D; Geroulanos, S; Kriaras, I; Papadopoulos, K; Stavridis, G; Tasouli, A, 2007)	1.15
"Levosimendan is a safe and efficient choice in the management of low-output syndrome during and after open-heart surgery. "	( Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Antoniou, T; Degiannis, D; Geroulanos, S; Kriaras, I; Papadopoulos, K; Stavridis, G; Tasouli, A, 2007)	1.15
"Levosimendan is a novel drug used for inotropic support in heart failure, but its efficacy in local anesthetic-induced myocardial depression is not known. "	( The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated guinea pig heart preparations. Christ, T; Deussen, A; Hübler, M; Koch, T; Rasche, B; Rasche, S; Ravens, U; Stehr, SN; Wettwer, E, 2007)	1.23
"Levosimendan is an effective inotropic drug in ropivacaine-induced myocardial depression and levosimendan myocardial sensitivity, and efficacy was not affected by the local anesthetic. "	( The effects of levosimendan on myocardial function in ropivacaine toxicity in isolated guinea pig heart preparations. Christ, T; Deussen, A; Hübler, M; Koch, T; Rasche, B; Rasche, S; Ravens, U; Stehr, SN; Wettwer, E, 2007)	1.23
"Levosimendan (LEV) is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-dependent potassium channels."	( Pharmacological preconditioning by levosimendan is mediated by inducible nitric oxide synthase and mitochondrial KATP channel activation in the in vivo anesthetized rabbit heart model. Das, B; Sarkar, C, 2007)	1.09
"Levosimendan is a novel calcium-sensitising agent that has been proposed as a potentially valuable inotrope for the treatment of acute or decompensated severe heart failure. "	( Is there a place for levosimendan in the intensive care unit? Bagshaw, SM; Bradford, C; Delaney, A; Lee, R; McCaffrey, J, 2007)	1.2
"Levosimendan is a calcium-sensitizing drug that enhances myocardial contractility without increasing intracellular calcium. "	( Levosimendan in patients with acute myocardial ischaemia undergoing emergency surgical revascularization. Boldt, J; Isgro, F; Kiessling, AH; Lehmann, A; Thaler, E; Zeitler, C, 2008)	1.46
"Levosimendan is an inotropic agent used in the treatment of heart failure. "	( Treatment of experimental verapamil poisoning with levosimendan utilizing a rodent model of drug toxicity. Graudins, A; Najafi, J; Rur-SC, MP, 2008)	1.15
"Levosimendan is an inodilatory drug with hemodynamic effects in patients with decompensated chronic heart failure."	( Evaluation of the clinical, hemodynamic and neurohormonal response to levosimendan administration in decompensated heart failure patients. One-month follow-up. Brito, D; Madeira, H; Matias, JS; Sargento, L, )	0.92
"Levosimendan is a novel positive inotropic calcium sensitiser agent used in acute left heart failure. "	( Effect of levosimendan on right ventricular systolic and diastolic functions in patients with ischaemic heart failure. Akilli, A; Akin, M; Duygu, H; Ergene, O; Nalbantgil, S; Nazli, C; Ozerkan, F; Yildiz, A; Zoghi, M, 2008)	1.26
"Levosimendan is a relatively new cardiac inotropic agent with calcium sensitizing activity. "	( Levosimendan improves renal function in patients with acute decompensated heart failure: comparison with dobutamine. Erdem, A; Karadas, F; Tandogan, I; Turgut, OO; Yalta, K; Yilmaz, A; Yilmaz, MB; Yontar, C, 2007)	1.46
"Levosimendan is an established substance in the treatment of acute heart failure in several countries despite disappointing findings concerning a possible survival benefit in two recent clinical trials. "	( Levosimendan: current status and future prospects. Archan, S; Toller, W, 2008)	1.46
"Levosimendan is a novel agent used in the treatment of patients with decompensated heart failure to enhance cardiac contractility. "	( Repeated infusions of levosimendan: well tolerated and improves functional capacity in decompensated heart failure - a single-centre experience. Best, M; Dembo, L; Driscoll, GO; Parle, NM; Thomas, MD, 2008)	1.2
"Levosimendan is a vasodilator used in the treatment of acute heart failure. "	( Pharmacokinetics of intravenous levosimendan and its metabolites in subjects with hepatic impairment. Häkkinen, S; Kantele, S; Kivikko, M; Pentikäinen, PJ; Puttonen, J; Ramela, M; Ruck, A, 2008)	1.18
"Levosimendan is a new inodilatory agent that enhances cardiac contractility via Ca(2+) sensitization and induces vasodilation through the activation of KATP/BKCa."	( Levosimendan in decompensated heart failure patients: efficacy in a Brazilian cohort. Results of the BELIEF study. Albuquerque, D; Baima, J; Barretto, AC; Bocchi, EA; Lage, S; Moreira, Mda C; Rassi, S; Ribeiro, JP; Vilas-Boas, F, 2008)	1.46
"Levosimendan is a novel positive inotropic drug targeted to increase contraction force of the heart through its calcium-dependent binding to troponin C (cTnC). "	( Troponin C-mediated calcium sensitization induced by levosimendan does not impair relaxation. Etemadzadeh, E; Haikala, H; Levijoki, J; Lindén, IB; Nissinen, E, 1995)	1.09
"Levosimendan proved to be a potent cardioto"	( Cardiovascular effects of the calcium sensitizer, levosimendan, in heart failure induced by rapid pacing in the presence of aortic constriction. Papp, JG; Udvary, E; Végh, A, 1995)	1.02
"Levosimendan is a novel inodilator that increases the calcium sensitivity of troponin C in a calcium-dependent way. "	( Hemodynamic and neurohumoral effects of levosimendan, a new calcium sensitizer, at rest and during exercise in healthy men. Lehtonen, L; Lilleberg, J; Nieminen, MS; Sundberg, S, 1995)	1.11
"Levosimendan is a new calcium-sensitiser intended for the treatment of congestive heart failure. "	( Haemodynamic dose-efficacy of levosimendan in healthy volunteers. Akkila, J; Häyhä, M; Lilleberg, J; Nieminen, MS; Sundberg, S, 1994)	1.13
"Simendan is a novel cardiotonic drug with mixed properties, including calcium sensitization. "	( Hemodynamic effects of the novel cardiotonic drug simendan: echocardiographic assessment in healthy volunteers. Leikola-Pelho, T; Lilleberg, JM; Nieminen, MS; Sundberg, S, 1994)	1.98
"Levosimendan is a new phosphodiesterase inhibitor with calcium-sensitizing properties."	( Functional and antiischaemic effects of the phosphodiesterase inhibitor levosimendan in isolated rabbit hearts. Acar, D; Klaus, W; Rösen, R; Rump, AF, )	0.84
"Levosimendan is an inotrope with coronary dilator activity, showing antiischaemic effects in isolated rabbit hearts. "	( Functional and antiischaemic effects of the phosphodiesterase inhibitor levosimendan in isolated rabbit hearts. Acar, D; Klaus, W; Rösen, R; Rump, AF, )	0.92
"Levosimendan is a new inodilatory agent that sensitizes troponin-C in heart muscle cells to calcium, thus improving contractility. "	( Pharmacokinetics of levosimendan in healthy volunteers and patients with congestive heart failure. Antila, S; Hayha, M; Heikkinen, P; Lehtonen, LA; Ottoila, P; Pentikainen, PJ; Sandell, EP, 1995)	1.16
"Levosimendan is a new calcium-sensitizing drug intended for congestive heart failure."	( The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan. Antila, S; Honkanen, T; Lehtonen, L; Neuvonen, PJ, 1998)	0.99
"Levosimendan is a pyridazinone-dinitrile derivative belonging to a new class of cardiac inotropic drugs, Ca++ sensitizers. "	( Levosimendan, a calcium sensitizer in cardiac muscle, induces relaxation in coronary smooth muscle through calcium desensitization. Bowman, P; Haikala, H; Paul, RJ, 1999)	1.42
"Levosimendan is a new calcium sensitizer, acting calcium-dependently on cardiac troponin C. "	( Integrated pharmacokinetics and pharmacodynamics of the novel calcium sensitizer levosimendan as assessed by systolic time intervals. Antila, S; Häyhä, M; Lehtonen, L; Scheinin, H; Sundberg, S; Virtanen, M, 1998)	1.08
"Levosimendan is a new myofilament calcium (Ca2+) sensitizer that increases myocardial contractility by stabilizing the Ca2+-bound conformation of troponin C. "	( Levosimendan enhances cardiac performance after cardiopulmonary bypass: a prospective, randomized placebo-controlled trial. Aggarwal, A; Montgomery, MW; Nicolosi, AC; Nijhawan, N; Pagel, PS; Warltier, DC, 1999)	1.42
"Levosimendan is a new inodilator, whose mechanism of action includes calcium sensitization of contractile proteins and the opening of ATP-dependent potassium channels. "	( Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure. Lehtonen, L, 2000)	1.42
"Levosimendan is a calcium sensitizer for treatment of acute decompensated heart failure."	( Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. Akkila, J; Hasenfuss, G; Kleber, FX; Lehtonen, LA; Mitrovic, V; Nieminen, MS; Nyquist, O; Remme, WJ, 2000)	1.1
"Levosimendan is an inodilatory drug that mediates its cardiac effect by the calcium sensitization of contractile proteins. "	( Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. Abbott, MB; Abusamhadneh, E; Annila, A; Drakenberg, T; Heikkinen, S; Kilpelainen, I; Laakso, T; Pollesello, P; Rosevear, PR; Serimaa, R; Sorsa, T; Tilgmann, C, 2001)	1.22
"Levosimendan (Simdax) is a new inodilator developed specifically for the treatment of decompensated heart failure. "	( Levosimendan: a parenteral calcium-sensitising drug with additional vasodilatory properties. Lehtonen, LA, 2001)	1.43
"Levosimendan is a novel inodilator that improves cardiac contractility by sensitizing troponin C to calcium. "	( Effects of levosimendan, a novel inotropic calcium-sensitizing drug, in experimental septic shock. Konrad, D; Oldner, A; Rossi, P; Rudehill, A; Wanecek, M; Weitzberg, E, 2001)	1.22
"Levosimendan is a new calcium sensitizer developed for the short-term intravenous treatment of congestive heart failure. "	( Pharmacodynamics and safety of a new calcium sensitizer, levosimendan, and its metabolites during an extended infusion in patients with severe heart failure. Antila, S; Eha, J; Kivikko, M; Lehtonen, L; Pentikäinen, PJ, 2002)	1.11
"Levosimendan is a new inotropic and vasodilator agent. "	( Levosimendan: a new era for inodilator therapy for heart failure? Cleland, JG; McGowan, J, 2002)	1.43

Effects

Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels. Simendan also has a vasodilatation effect, which causes coronary artery resistance and venous volume blood vessel relax, thereby improving coronary blood supply.

Levosimendan has anti-ischaemic effects, improves myocardial contractility and increases systemic, pulmonary and coronary vasodilatation. Simendan causes coronary artery resistance and venous volume blood vessel relax, thereby improving coronary blood supply.

Excerpt	Reference	Relevance
"Levosimendan has a long-acting metabolite with a half-life of approximately 80 h."	( Pre-bypass levosimendan in ventricular dysfunction-effect on right ventricle. Ahlawat, V; Kumar, D; Kundu, A; Prakash, A; Yadav, A; Yadava, OP, 2021)	1.46
"Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (K"	( Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits. Babik, B; Balogh, AL; Fodor, GH; Ivankovitsne-Kiss, O; Petak, F; Sudy, R, 2017)	1.57
"Simendan also has a vasodilatation effect, which causes coronary artery resistance and venous volume blood vessel relax, thereby improving coronary blood supply."	( The efficacy of simendan in the treatment of acute heart failure and its impact on NT-proBNP. Li, J; Li, Y; Wang, XY; Yang, F; Yang, J; Yang, ZY; Yuan, P, 2019)	1.58
"Levosimendan has a unique dual mechanism of action by enhancing cardiac contractility and causing peripheral vasodilatation. "	( Novel biologic mechanisms of levosimendan and its effect on the failing heart. Andreadou, I; Bistola, V; Filippatos, G; Kremastinos, DT; Paraskevaidis, I; Parissis, JT, 2008)	1.19
"Levosimendan has a cardioprotective effect when administered before ischemia in ischemia-reperfusion injury. "	( Levosimendan attenuates reperfusion injury in an isolated perfused rat heart model. Gok, S; Nese, N; Ozturk, T, 2010)	1.48
"Levosimendan has a better profile of security than its predecessors (amrinone and milrinone), improves the haemodynamics parameters of special significant form in the cardiac output, the systolic pressure of the pulmonary artery and the telediastolic pressure of the left ventricle, without significantly increasing the consumption of oxygen by the myocardium."	( [Levosimendan: a new option in the pharmacologic management of cardiac insufficiency]. Campos Lara, MG; Carballal-Sanjurjo, JC; Del-Razo, OE; Palma-Aguirre, JA, )	1.13
"Levosimendan has an active metabolite, OR-1896."	( Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Kivikko, M; Lehtonen, L, 2005)	1.37
"Levosimendan has a more beneficial profile than milrinone regarding the development of ventricular arrhythmias during and after regional myocardial ischemia."	( Effect of levosimendan and milrinone on regional myocardial ischemia/reperfusion-induced arrhythmias in dogs. Papp, JG; Pollesello, P; Varró, AF; Végh, AS, 2006)	1.18
"Levosimendan has a cardioprotective action by inducing coronary vasodilatation and preconditioning by opening KATP channels. "	( Effects of levosimendan on myocardial ischaemia-reperfusion injury. Altunkan, Z; Apa, D; Balli, E; Bilgin, E; Birbicer, H; Doruk, N; Oral, U; Ozeren, M; Tamer, L; Yapici, D, 2008)	1.26
"Levosimendan has a dual mechanism of action: it improves myocardial contractility and causes vasodilatation without increasing myocardial oxygen demand. "	( Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal-arterial pCO2 gradient in abdominal aortic aneurysm surgery. Leppikangas, H; Lindgren, L; Ruokonen, E; Salenius, JP; Tenhunen, JJ, 2008)	1.26
"Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. "	( Myocardial efficiency during levosimendan infusion in congestive heart failure. Akkila, J; Iida, H; Karanko, M; Knuuti, J; Lehikoinen, P; Lehtonen, L; Någren, K; Saraste, M; Ukkonen, H; Voipio-Pulkki, LM, 2000)	1.15
"Levosimendan increasingly has been used to treat heart failure and cardiac dysfunction in pediatric patients. "	( Effect of Levosimendan Treatment in Pediatric Patients With Cardiac Dysfunction: An Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials. Belletti, A; Bianzina, S; Momeni, M; Silvetti, S, 2022)	1.64
"Levosimendan has been demonstrated to reduce the incidence of cardiogenic shock and facilitate weaning from cardiopulmonary bypass. "	( Short-term effects of levosimendan use for venoarterial extracorporeal membrane oxygenation: A systematic review and meta-analysis. Guo, B; Li, Y; Yang, B; Zhao, T, 2023)	1.77
"Levosimendan has proven beneficial in improving RV function."	( The effect of levosimendan on the right ventricular function in patients with right ventricular dysfunction undergoing mitral valve surgery. Bharathi, KS; Dhananjaya, M; Pruthi, G; Simha, PP, )	0.95
"Levosimendan has proven to be effective in patients with cardiogenic shock and in those with end-stage heart failure."	( Efficacy of levosimendan infusion in patients undergoing a left ventricular assist device implant in a propensity score matched analysis of the EUROMACS registry-the Euro LEVO-LVAD study. Abdelshafy, M; Berchtold-Herz, M; Caliskan, K; de By, TMMH; Elkoumy, A; Elsherbini, H; Elzomor, H; Gollmann-Tepeköylü, C; Gummert, J; Kimman, JR; Loforte, A; Meyns, B; Mohacsi, P; Paluszkiewicz, L; Reineke, D; Schoenrath, F; Simpkin, AJ; Soliman, O, 2023)	1.74
"Levosimendan has been suggested to reduce mortality of patients with perioperative myocardial dysfunction."	( Long-term outcome of perioperative low cardiac output syndrome in cardiac surgery: 1-year results of a multicenter randomized trial. Abubakirov, MN; Belletti, A; Bianchi, A; Brazzi, L; Calabrò, MG; Crivellari, M; Di Tomasso, N; Fominskiy, EV; Garofalo, E; Grigoryev, EV; Guarracino, F; Landoni, G; Lembo, R; Likhvantsev, VV; Lomivorotov, VV; Monaco, F; Oriani, A; Pasyuga, VV; Paternoster, G; Pisano, A; Scandroglio, AM; Yavorovskiy, A; Zangrillo, A, 2020)	1.04
"Levosimendan has a long-acting metabolite with a half-life of approximately 80 h."	( Pre-bypass levosimendan in ventricular dysfunction-effect on right ventricle. Ahlawat, V; Kumar, D; Kundu, A; Prakash, A; Yadav, A; Yadava, OP, 2021)	1.46
"Levosimendan has salutary effects on right ventricular function in patients with severe left ventricular dysfunction undergoing coronary artery bypass, in terms of improved hemodynamic parameters."	( Pre-bypass levosimendan in ventricular dysfunction-effect on right ventricle. Ahlawat, V; Kumar, D; Kundu, A; Prakash, A; Yadav, A; Yadava, OP, 2021)	1.53
"Levosimendan has shown potential benefits in CA patients."	( Levosimendan Ameliorates Post-resuscitation Acute Intestinal Microcirculation Dysfunction Partly Independent of its Effects on Systemic Circulation: A Pilot Study on Cardiac Arrest in a Rat Model. Jia, T; Liu, G; Lu, X; Luo, C; Shang, Z; Wang, S; Wang, Z; Yang, Q; Zhu, C, 2021)	1.66
"Levosimendan has no benefit in terms of mortality at longest follow up in comparison to dobutamine (Odds ratio 0.77, 95% CI 0.45, 132; p=0.34) and length of ICU stay (MD -4.7days, 95% CI -10.3, 0.9days, p=0.10)."	( Levosimendan does not provide mortality benefit over dobutamine in adult patients with septic shock: A meta-analysis of randomized controlled trials. Baidya, DK; Bhattacharjee, S; Maitra, S; Soni, KD, 2017)	1.49
"Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life."	( Repetitive use of levosimendan in advanced heart failure: need for stronger evidence in a field in dire need of a useful therapy. Altenberger, J; Baholli, L; Beltrán, P; Borbély, A; Bover, R; Comin-Colet, J; Delgado, JF; Fedele, F; Fontana, A; Fruhwald, F; Garcia-González, MJ; Giamouzis, G; Giannakoulas, G; Gustafsson, F; Kaikkonen, K; Kivikko, M; Kubica, J; Löfman, I; Malfatto, G; Manito, N; Martínez-Sellés, M; Masip, J; Merkely, B; Morandi, F; Mølgaard, H; Oliva, F; Pantev, E; Papp, Z; Perna, GP; Pfister, R; Piazza, V; Pollesello, P; Pölzl, G; Rangel-Sousa, D; Recio-Mayoral, A; Reinecke, A; Rieth, A; Sarapohja, T; Schmidt, G; Seidel, M; Störk, S; von Lewinski, D; Vrtovec, B; Wikström, G; Yerly, P, 2017)	1.25
"Levosimendan has a calcium-sensitizing effect in the myocardium and opens ATP-sensitive potassium channels (K"	( Levosimendan prevents bronchoconstriction and adverse respiratory tissue mechanical changes in rabbits. Babik, B; Balogh, AL; Fodor, GH; Ivankovitsne-Kiss, O; Petak, F; Sudy, R, 2017)	1.57
"Levosimendan has been developed for treatment of severe heart failure. "	( Impact of levosimendan on platelet function. Fabiszak, T; Grześk, G; Kubica, J; Marszałł, MP; Pstrągowski, K; Sikora, A; Sikora, J; Skibińska, N; Sobczak, P, 2017)	1.37
"Levosimendan has vasorelaxant and anti-aggregatory properties."	( Cardioprotective and Anti-Aggregatory Effects of Levosimendan on Isoproterenol-Induced Myocardial Injury in High-Fat-Fed Rats Involves Modulation of PI3K/Akt/mTOR Signaling Pathway and Inhibition of Apoptosis: Comparison to Cilostazol. El-Kherbetawy, MK; Makary, S; Tawfik, MK, 2018)	1.21
"Simendan also has a vasodilatation effect, which causes coronary artery resistance and venous volume blood vessel relax, thereby improving coronary blood supply."	( The efficacy of simendan in the treatment of acute heart failure and its impact on NT-proBNP. Li, J; Li, Y; Wang, XY; Yang, F; Yang, J; Yang, ZY; Yuan, P, 2019)	1.58
"Levosimendan has anti-ischaemic effects, improves myocardial contractility and increases systemic, pulmonary and coronary vasodilatation. "	( Effectiveness of prophylactic levosimendan in high-risk valve surgery patients. Boysan, E; Cicekcioglu, F; Ersoy, O; Katircioglu, F; Unal, EU; Yay, K; Yener, U, 2013)	1.23
"Levosimendan has been extensively used to treat heart failure (HF) for nearly 10 years, but data on levosimendan used in elderly patients with refractory HF remains limited. "	( Levosimendan Improves Clinical Outcomes of Refractory Heart Failure in Elderly Chinese Patients. Huang, J; Qian, J; Yao, Y; Zhang, D, 2015)	1.53
"Levosimendan has been shown to confer direct renoprotection in renal endotoxemic and ischemia-reperfusion injury and could increase renal blood flow in patients with low-cardiac-output heart failure. "	( Levosimendan for Prevention of Acute Kidney Injury After Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials. Chen, D; Gong, J; Liu, B; Liu, M; Wang, W; Zhou, C, 2016)	1.55
"Levosimendan has been studied in different therapeutic settings including acutely decompensated chronic heart failure, advanced heart failure, right ventricular failure, cardiogenic shock, septic shock, and cardiac and non-cardiac surgery."	( Levosimendan meta-analyses: Is there a pattern in the effect on mortality? Harjola, VP; Kivikko, M; Parissis, J; Pollesello, P, 2016)	1.47
"Levosimendan has been seemingly confirmed to reduce mortality in patients undergoing cardiac surgery. "	( Levosimendan: new indications and evidence for reduction in perioperative mortality? Landoni, G; Monti, G; Pisano, A, 2016)	1.55
"Levosimendan has not only improved the cardiac systolic function but also the diastolic relaxation in CHF."	( A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites. Asif, M, 2018)	1.2
"Levosimendan has a unique dual mechanism of action by enhancing cardiac contractility and causing peripheral vasodilatation. "	( Novel biologic mechanisms of levosimendan and its effect on the failing heart. Andreadou, I; Bistola, V; Filippatos, G; Kremastinos, DT; Paraskevaidis, I; Parissis, JT, 2008)	1.19
"Levosimendan has cardioprotective effects, resulting in reduced postoperative cardiac troponin release."	( Levosimendan reduces cardiac troponin release after cardiac surgery: a meta-analysis of randomized controlled studies. Bignami, E; Biondi-Zoccai, G; Bruno, G; De Santis, V; Gerli, C; Landoni, G; Mizzi, A; Tritapepe, L; Zangrillo, A, 2009)	1.47
"Levosimendan has total clearance 175-250 mL/h/kg and most importantly a short half-life (about 1.5 hours)."	( Relationship between the pharmacokinetics of levosimendan and its effects on cardiovascular system. Antoniades, C; Antonopoulos, AS; Bakogiannis, C; Stefanadi, E; Stefanadis, C; Tousoulis, D, 2009)	1.09
"Levosimendan has cardioprotective effects that could result in a reduced postoperative mortality. "	( Reducing mortality in cardiac surgery with levosimendan: a meta-analysis of randomized controlled trials. Bignami, E; Biondi-Zoccai, G; Bruno, G; Corno, L; Gerli, C; Landoni, G; Mizzi, A; Zambon, M; Zangrillo, A, 2010)	1.18
"Levosimendan has a cardioprotective effect when administered before ischemia in ischemia-reperfusion injury. "	( Levosimendan attenuates reperfusion injury in an isolated perfused rat heart model. Gok, S; Nese, N; Ozturk, T, 2010)	1.48
"Levosimendan has been shown to exert beneficial hemodynamic effects in presence of global myocardial ischemia and heart failure through vasodilatation and increase of cardiac contractility."	( Modulation of programmed forms of cell death by intracoronary levosimendan during regional myocardial ischemia in anesthetized pigs. Caimmi, PP; Cattaneo, M; Grossini, E; Mary, DA; Molinari, C; Platini, F; Tessitore, L; Uberti, F; Vacca, G; Valente, G, 2010)	1.08
"Levosimendan has cardioprotective effects that could result in a reduced mortality in critically ill patients. "	( Levosimendan reduces mortality in critically ill patients. A meta-analysis of randomized controlled studies. Ajello, V; Bignami, E; Biondi-Zoccai, G; Guarracino, F; Landoni, G; Marino, G; Mizzi, A; Prati, P; Zangrillo, A, 2010)	1.48
"Levosimendan has been proposed, in the recent past, to be non-inferior and may have some advantages to standard inotropes; further possible indications for levosimendan have been described, in some observational studies, such as a perioperative use, cardioprotection, cardiogenic shock, sepsis and right ventricular dysfunction."	( Levosimendan: from basic science to clinical trials. Bongo, AS; Lazzero, M; Lupi, A; Rognoni, A; Rognoni, G, 2011)	1.41
"Levosimendan has been reported to exert cardioprotection. "	( Intracoronary levosimendan prevents myocardial ischemic damages and activates survival signaling through ATP-sensitive potassium channel and nitric oxide. Caimmi, PP; Grossini, E; Mary, DA; Micalizzi, E; Molinari, C; Uberti, F; Vacca, G; Valente, G, 2011)	1.26
"Levosimendan has been proposed as an attractive alternative to adrenergic agents for the treatment of sepsis-induced heart failure and haemodynamic derangements. "	( No beneficial effects of levosimendan in acute porcine endotoxaemia. Bendall, J; Chew, MS; Hawthorne, WJ; Huang, S; McLean, A; Simond, D; Ting, I; Whereat, S, 2011)	1.22
"Levosimendan treatment has inotropic, anti-stunning, and cardioprotective effects in the setting of acute decompensated heart failure (HF). "	( Value of IGF-I levels in the evaluation of response to treatment with levosimendan in patients with severe heart failure. Bakır, F; Berker, D; Cetin, M; Çetin, ZG; Ciçekçioğlu, H; Güler, S; Işık, S; Ozuğuz, U; Uçar, O, 2011)	1.16
"Levosimendan has better inotropic and lusitropic effects than epinephrine during rewarming from deep hypothermic circulatory arrest with cardiopulmonary bypass."	( Levosimendan is superior to epinephrine in improving myocardial function after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats. Faggian, G; Linardi, D; Luciani, GB; Mazzucco, A; Menon, T; Rungatscher, A; Tessari, M, 2012)	1.5
"Levosimendan has no significant effect as a phosphodiesterase III inhibitor on in-vitro platelet aggregation in clinically relevant doses."	( The inhibitory in-vitro effect of high-dose levosimendan on platelet function may be mediated through its action as a phosphodiesterase inhibitor. Bent, F; Hofer, S; Kopitz, J; Plaschke, K; Rosenhagen, C; Wagner, S, 2012)	1.19
"Levosimendan has been proposed as a promising drug candidate because of its cardioprotective properties, improved haemodynamic effects in vivo and reduced traumatic brain injury in vitro."	( The effects of levosimendan on brain metabolism during initial recovery from global transient ischaemia/hypoxia. Bleilevens, C; Goetzenich, A; Hein, M; Kipp, M; Kuehn-Velten, N; Roehl, AB; Rossaint, R; Schiefer, J; Tolba, R; Zoremba, N, 2012)	1.19
"Levosimendan also has not been shown to impair ventricular relaxation, which was an initial concern with this class of drugs."	( Levosimendan: a unique approach to the treatment of heart failure. Anderson, JR; Nawarskas, JJ, )	1.17
"Levosimendan has a better profile of security than its predecessors (amrinone and milrinone), improves the haemodynamics parameters of special significant form in the cardiac output, the systolic pressure of the pulmonary artery and the telediastolic pressure of the left ventricle, without significantly increasing the consumption of oxygen by the myocardium."	( [Levosimendan: a new option in the pharmacologic management of cardiac insufficiency]. Campos Lara, MG; Carballal-Sanjurjo, JC; Del-Razo, OE; Palma-Aguirre, JA, )	1.13
"Levosimendan has been shown to have beneficial survival effects in several populations; its use improves patient outcomes relative to the standard of care and has the potential to reduce hospital costs associated with heart failure."	( Levosimendan: implications for clinicians. McBride, BF; White, CM, 2003)	1.36
"Levosimendan has an active metabolite, OR-1896."	( Levosimendan: a new inodilatory drug for the treatment of decompensated heart failure. Kivikko, M; Lehtonen, L, 2005)	1.37
"Levosimendan has the potential of improving postresuscitation myocardial function. "	( Comparison between dobutamine and levosimendan for management of postresuscitation myocardial dysfunction. Huang, L; Sun, S; Tang, W; Wang, J; Weil, MH, 2005)	1.16
"Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function."	( Levosimendan: a calcium-sensitizing agent for the treatment of patients with decompensated heart failure. Lehtonen, L, 2004)	1.36
"Levosimendan has shown lower mortality compared to dobutamine in patients with acute congestive heart failure."	( [Medical and ventilatory treatment of acute heart failure]. Atar, D; Hodt, A; Steine, K, 2006)	0.81
"Levosimendan has a more beneficial profile than milrinone regarding the development of ventricular arrhythmias during and after regional myocardial ischemia."	( Effect of levosimendan and milrinone on regional myocardial ischemia/reperfusion-induced arrhythmias in dogs. Papp, JG; Pollesello, P; Varró, AF; Végh, AS, 2006)	1.18
"Levosimendan has been developed for the treatment of decompensated heart failure and is used intravenously when patients with heart failure require immediate initiation of drug therapy. "	( Clinical pharmacology of levosimendan. Antila, S; Lehtonen, LA; Sundberg, S, 2007)	1.19
"Levosimendan has a cardioprotective action by inducing coronary vasodilatation and preconditioning by opening KATP channels. "	( Effects of levosimendan on myocardial ischaemia-reperfusion injury. Altunkan, Z; Apa, D; Balli, E; Bilgin, E; Birbicer, H; Doruk, N; Oral, U; Ozeren, M; Tamer, L; Yapici, D, 2008)	1.26
"Levosimendan has been used successfully in the treatment of ischaemic cardiac failure and myocardial stunning. "	( Levosimendan in acute pulmonary embolism. Powell, BP; Simes, D, 2007)	1.46
"Levosimendan has inotropic and vasodilatory effects. "	( Effects of levosimendan on coronary artery flow and cardiac performance in patients with advanced heart failure. Bistola, V; Filippatos, G; Ikonomidis, I; Kourea, K; Kremastinos, DT; Lekakis, J; Paraskevaidis, I; Parissis, JT, 2007)	1.25
"Levosimendan has a dual mechanism of action: it improves myocardial contractility and causes vasodilatation without increasing myocardial oxygen demand. "	( Effects of levosimendan on indocyanine green plasma disappearance rate and the gastric mucosal-arterial pCO2 gradient in abdominal aortic aneurysm surgery. Leppikangas, H; Lindgren, L; Ruokonen, E; Salenius, JP; Tenhunen, JJ, 2008)	1.26
"Simendan has favorable and predictable hemodynamic actions. "	( Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers. Antila, S; Karlsson, M; Lilleberg, J; Nieminen, MS; Pentkäinen, PJ, 1994)	2
"Levosimendan has inotropic and lusitropic actions in failing human myocardium. "	( Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium. Castell, M; Hasenfuss, G; Just, H; Kretschmann, B; Maier, LS; Pieske, B, 1998)	1.12
"Levosimendan has been extensively studied in various animal models of heart failure, in which the drug has increased contractility without adverse effects on diastolic function."	( Levosimendan: A promising agent for the treatment of hospitalized patients with decompensated heart failure. Lehtonen, L, 2000)	1.35
"Levosimendan has an energetically favorable short-term profile in the treatment of congestive heart failure. "	( Myocardial efficiency during levosimendan infusion in congestive heart failure. Akkila, J; Iida, H; Karanko, M; Knuuti, J; Lehikoinen, P; Lehtonen, L; Någren, K; Saraste, M; Ukkonen, H; Voipio-Pulkki, LM, 2000)	1.15
"Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole."	( Levosimendan. Figgitt, DP; Gillies, PS; Goa, KL, 2001)	1.35
"Levosimendan has been reported to increase cardiac Ca(2+) sensitivity, thereby not enhancing intracellular Ca(2+) or diastolic tension. "	( Beneficial effects of the Ca(2+) sensitizer levosimendan in human myocardium. Brixius, K; Reicke, S; Schwinger, RH, 2002)	1.13

Actions

Levosimendan can increase cardiac ejection function, reduce the heart blood and vascular preload, intrathoracic lung water, improve heart function and systemic hemodynamic indexes of patients with septic shock. The drug has shown lower mortality compared to dobutamine in patients with acute congestive heart failure.

Excerpt	Reference	Relevance
"Levosimendan group had lower incidence of atrial fibrillation, shorter length of ICU, and hospital stay."	( Comparison of Levosimendan versus Dobutamine in Patients with Moderate to Severe Left Ventricular Dysfunction Undergoing Off-pump Coronary Artery Bypass Grafting: A Randomized Prospective Study. Ali, MM; Annadurai, M; Kandasamy, A; Murthy, P; Ramanathan, G; Simon, HA, )	0.95
"Levosimendan can increase cardiac ejection function, reduce the heart blood and vascular preload, intrathoracic lung water, improve heart function and systemic hemodynamic indexes of patients with septic shock."	( [Effects of levosimendan on hemodynamics and cardiac function in patients with septic shock]. Dong, S; Fang, M, 2014)	1.31
"Levosimendan-induced increase in heart rate possibly facilitated the recovery from bupivacaine intoxication."	( The effect of levosimendan on bupivacaine-induced severe myocardial depression in anesthetized pigs. Aittomäki, J; Heavner, JE; Liuhanen, S; Rosenberg, PH; Sallisalmi, M; Salmenperä, MT, )	0.95
"Levosimendan produced an increase in cΔHbD (p < 0.05) and pΔHbD (NS) and a decrease in heart rate (p < 0.001) and lactate (p < 0.05)."	( Acute effects of levosimendan on cerebral and systemic perfusion and oxygenation in newborns: an observational study. Bravo, MC; Bravo, Mdel C; Cabañas, F; López, P; Pellicer, A; Pérez-Fernández, E; Pérez-Rodríguez, J; Quero, J, 2011)	1.17
"Levosimendan does not increase myocardial oxygen demand and also reduces significantly systemic vascular resistance, pulmonary artery pressure, and pulmonary vascular resistance."	( [The novelty in the treatment of heart failure]. Reingardiene, D, 2005)	0.81
"Levosimendan has shown lower mortality compared to dobutamine in patients with acute congestive heart failure."	( [Medical and ventilatory treatment of acute heart failure]. Atar, D; Hodt, A; Steine, K, 2006)	0.81
"Levosimendan does not increase markers of oxidative and nitrosative stress in contrast to the placebo treatment, thus, exerting cardioprotective effects in advanced CHF patients. "	( Effects of Levosimendan on circulating markers of oxidative and nitrosative stress in patients with advanced heart failure. Andreadou, I; Bistola, V; Filippatos, G; Iliodromitis, EK; Kremastinos, DT; Louka, A; Markantonis, SL; Paraskevaidis, I; Parissis, JT; Pyriochou, A, 2007)	1.25
"Levosimendan was shown to increase calcium sensitivity by a novel mechanism and to inhibit phosphodiesterase III activity in animal myocardium."	( Influence of the novel inotropic agent levosimendan on isometric tension and calcium cycling in failing human myocardium. Castell, M; Hasenfuss, G; Just, H; Kretschmann, B; Maier, LS; Pieske, B, 1998)	1.12

Treatment

Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels. The drug can be hepatoprotective and it could be useful before extensive liver resection.

Excerpt	Reference	Relevance
"Levosimendan treatment in preterm infants is associated with a rapid improvement of CD and PH, an increase of the mean arterial pressure, and a significant decrease in arterial lactate levels, as"	( Evaluation of levosimendan as treatment option in a large case-series of preterm infants with cardiac dysfunction and pulmonary hypertension. Dresbach, T; Geipel, A; Holcher, S; Kipfmueller, F; Leyens, J; Mueller, A; Schroeder, L; Strizek, B, 2023)	1.72
"Levosimendan treatment resulted in a 29.3 m (95% CI: 2.5 to 56.1; p = 0.033) improvement in 6MWD compared with placebo."	( Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial. Borlaug, BA; Burkhoff, D; Chung, ES; Lewis, GD; Majure, DT; Mazurek, JA; Preston, IR; Raza, F; Rich, JD; Rich, S; Shah, SJ; Simon, MA; Tedford, RJ; Thenappan, T; Zamanian, RT; Zolty, R, 2021)	1.66
"Levosimendan-treated animals showed significantly higher brain PbtO"	( Levosimendan increases brain tissue oxygen levels after cardiopulmonary resuscitation independent of cardiac function and cerebral perfusion. Dünges, B; García-Bardon, A; Hartmann, EK; Heimann, A; Kamuf, J; Kelm, RF; Krebs, N; Liu, T; Mohr, K; Morsbach, S; Thal, SC; Ziebart, A, 2021)	1.66
"Levosimendan treatment improved cardiac output (VEH vs."	( Levosimendan Prevents and Reverts Right Ventricular Failure in Experimental Pulmonary Arterial Hypertension. Andersen, A; Bogaard, HJ; Hansen, MS; Happé, C; Holmboe, S; Nielsen-Kudsk, JE; Ringgaard, S; Schultz, JG; Simonsen, U, 2017)	1.49
"Levosimendan pretreatment resulted in significant improvement of liver redox homeostasis."	( Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury? Balla, Z; Fulop, A; Garbaisz, D; Harsanyi, L; Hegedus, V; Lotz, G; Onody, P; Rakonczay, Z; Rosero, O; Stangl, R; Szijarto, A; Turoczi, Z, 2013)	1.43
"Levosimendan pretreatment can be hepatoprotective and it could be useful before extensive liver resection."	( Levosimendan: a cardiovascular drug to prevent liver ischemia-reperfusion injury? Balla, Z; Fulop, A; Garbaisz, D; Harsanyi, L; Hegedus, V; Lotz, G; Onody, P; Rakonczay, Z; Rosero, O; Stangl, R; Szijarto, A; Turoczi, Z, 2013)	1.51
"Levosimendan treatment significantly improved all three systolic parameters."	( Long-term levosimendan treatment improves systolic function and myocardial relaxation in mice with cardiomyocyte-specific disruption of the Serca2 gene. Andersson, KB; Christensen, G; Golz, S; Hillestad, V; Knorr, A; Kramer, F, 2013)	1.23
"Levosimendan treatment was associated with significant changes in hematological variables in patients with ADHF. "	( Utility of the neutrophil to lymphocyte ratio for predicting in-hospital mortality after levosimendan infusion in patients with acute decompensated heart failure. Bacaksiz, A; Erdogan, E; Ergelen, M; Erturk, M; Karakurt, H; Sonmez, O; Tasal, A; Turfan, M; Uyarel, H; Vatankulu, MA, 2014)	1.18
"Levosimendan pretreatment (24 h infusion) in patient for OPCABG with poor LVEF shows better outcomes and hemodynamics in terms of inotropes, CPB and IABP requirements. "	( Study of levosimendan during off-pump coronary artery bypass grafting in patients with LV dysfunction: a double-blind randomized study. Brahmbhatt, A; Malhotra, A; Patel, J; Rathod, B; Shah, B; Shah, R; Sharma, P; Shastri, N, )	1.06
"Levosimendan treatment significantly reduced cerebral infarct size in the cortex, but not in the striatal and insular regions."	( Insular infarct size but not levosimendan influenced myocardial injury triggered by cerebral ischemia in rats. Bleilevens, C; Hein, M; Roehl, AB; Rossaint, R; Tolba, R; Zoremba, N, 2015)	1.18
"Levosimendan treatment further reduced adhesion of PMN to activated endothelial cells under both static and flow conditions by approximately 50 %."	( Levosimendan exerts anti-inflammatory effects on cardiac myocytes and endothelial cells in vitro. Aliabadi, A; Buchberger, E; de Martin, R; Demyanets, S; Gröger, M; Hofer-Warbinek, R; Huber, K; Kastl, SP; Kaun, C; Krychtiuk, KA; Maurer, G; Pisoni, J; Rauscher, S; Speidl, WS; Watzke, L; Wojta, J; Zuckermann, A, 2015)	1.46
"Levosimendan-treated patients stayed 1.01 (1.61-0.42) days shorter when compared to control (p = 0.001)."	( Levosimendan Reduces Mortality in Adults with Left Ventricular Dysfunction Undergoing Cardiac Surgery: A Systematic Review and Meta-analysis. Altarabsheh, SE; Avery, EG; Cho, YH; Deo, SV; Hang, D; Lim, JY; Markowitz, AH; McGraw, M; Park, SJ; Rababa'h, A, 2015)	1.46
"Levosimendan alone-treatment concentration-dependently increased phosphorylation of Akt (Ser473)."	( Levosimendan inhibits interleukin-1β-induced apoptosis through activation of Akt and inhibition of inducible nitric oxide synthase in rat cardiac fibroblasts. Okada, M; Yamawaki, H, 2015)	1.46
"Levosimendan treatment prevented deterioration of right ventricular function measured by CI and right ventricular ejection fraction (RVEF) (CI: VEH vs."	( Levosimendan Prevents Pressure-Overload-induced Right Ventricular Failure. Andersen, A; Andersen, S; Hillgaard, TK; Nielsen, JM; Nielsen-Kudsk, JE; Ringgaard, S; Vildbrad, MD, 2016)	1.47
"Levosimendan treatment in patients undergoing surgical revascularization resulted in improved CI, decreased SVR and lower heart rate. "	( Comparison of levosimendan and nitroglycerine in patients undergoing coronary artery bypass graft surgery. Das, A; Hote, M; Malik, V; Sahu, MK; Singh, SP; Subramanian, A, )	1.02
"Levosimendan treated patients had a lower 180-day mortality compared to dobutamine treated (17% vs."	( Effect of baseline characteristics on mortality in the SURVIVE trial on the effect of levosimendan vs dobutamine in acute heart failure: Sub-analysis of the Finnish patients. Harjola, VP; Kivikko, M; Nieminen, MS; Pollesello, P; Sarapohja, T; Tarvasmäki, T, 2016)	1.14
"Levosimendan-treated patients had higher stroke volume index (SVI), cardiac index (CI), LVEF, and left ventricular stroke work index (LVSWI), and lower extravascular lung water index (EVLWI) compared to dobutamine-treated patients (p<0.05)."	( Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial. Hu, MH; Ji, CL; Lai, ZZ; Meng, JB; Tian, S; Xu, XJ; Zhang, G, 2016)	1.47
"Levosimendan treatment improved both objective echocardiographic measurements and the subjective QOL questionnaires. "	( Assessment of quality of life using three activity questionnaires in heart failure patients after monthly, intermittent administration of levosimendan during a six-month period. Cokkinos, DV; Dritsas, A; Mavrogeni, SI; Papadopoulou, EF, )	0.89
"Levosimendan treatment significantly improved ventricular function (fractional shortening 0.32 +/- 0.04 vs."	( Effects of levosimendan in experimental acute coxsackievirus myocarditis. Kytö, V; Latva-Hirvelä, J; Levijoki, J; Saraste, A; Saukko, P; Vuorinen, T, 2009)	1.19
"Levosimendan treatment has inotropic, anti-stunning, and cardioprotective effects in the setting of acute decompensated heart failure (HF). "	( Value of IGF-I levels in the evaluation of response to treatment with levosimendan in patients with severe heart failure. Bakır, F; Berker, D; Cetin, M; Çetin, ZG; Ciçekçioğlu, H; Güler, S; Işık, S; Ozuğuz, U; Uçar, O, 2011)	1.16
"Levosimendan treatment improves preimplant hemodynamic performance and permits the identification of patients who will develop right ventricular failure."	( Preoperative treatment with levosimendan in candidates for mechanical circulatory support. Hetzer, R; Ivanitskaia, E; Krabatsch, T; Lehmkuhl, H; Potapov, E; Sponga, S, )	0.9
"Levosimendan treatment resulted in both clinical and echocardiography improvement with the improved EF (42%, 34%, 44%), FS (21%, 16%, 22%) and SV (59, 82, 93 mL/m2)."	( [Levosimendan treatment of severe acute congestive heart failure refractory to dobutamine/milrinone in children]. Jovicić, B; Kosutić, J; Nikolić, L; Prijić, S; Rakić, S; Stajević, M; Vukomanović, V, 2011)	1.36
"Levosimendan treatment shows similar effects in heart failure patients with anemia to that of patients without anemia. "	( Effects of levosimendan on TNF-alpha, BNP and MMP-1 in patients with heart failure with anemia. Büyüklü, M; Kürüm, AT; Set, T; Tatlý, E, 2012)	1.29
"Levosimendan treatment was not followed by clinically relevant adverse reactions requiring infusion termination and therapy discontinuation."	( [Possibilities of using levosimendan in patients with idiopathic pulmonary hypertension]. Arkhipova, OA; Chazova, IE; Danilov, NM; Kobal', EA; Martyniuk, TV, 2012)	1.15
"Levosimendan treatment improved contractility in post-ischaemic myocardium in patients with PCI-treated STEMI complicated by HF. "	( Levosimendan in acute heart failure following primary percutaneous coronary intervention-treated acute ST-elevation myocardial infarction. Results from the LEAF trial: a randomized, placebo-controlled study. Andersen, GØ; Arnesen, H; Bjørnerheim, R; Eritsland, J; Husebye, T; Mangschau, A; Müller, C; Sandvik, L; Seljeflot, I, 2013)	1.51
"Levosimendan treatment appears to be well-tolerated, with the primary adverse events being headache and hypotension."	( Levosimendan: a unique approach to the treatment of heart failure. Anderson, JR; Nawarskas, JJ, )	1.17
"Levosimendan-treated patients experienced lower risk of death and worsening heart failure than patients receiving placebo, during both the 6h infusion (2.0% vs 5.9%; P=0.033) and over 24h (4.0% vs 8.8%; P=0.044)."	( Safety and efficacy of a novel calcium sensitizer, levosimendan, in patients with left ventricular failure due to an acute myocardial infarction. A randomized, placebo-controlled, double-blind study (RUSSLAN). Andrejevs, N; Golikov, AP; Kobalava, ZD; Laine, T; Lazebnik, LB; Lehtonen, LA; Lie, KI; Moiseyev, VS; Nieminen, MS; Põder, P; Ruda, MY, 2002)	1.04
"Levosimendan treatment is also associated with significantly improved clinical symptoms."	( Randomized clinical trials with levosimendan. Barraud, D; Mebazaa, A; Welschbillig, S, 2005)	1.08
"Levosimendan pretreatment resulted in a significantly smaller elevation from the preischemic level in left ventricular end-diastolic pressure during reperfusion (37 +/- 17 mm Hg) compared with controls (56 +/- 14 mm Hg) and ischemia-preconditioned hearts (53 +/- 34 mm Hg)."	( Preconditioning effects of levosimendan in a rabbit cardiac ischemia-reperfusion model. Leprán, I; Papp, JG; Pollesello, P; Vajda, S; Varró, A, 2006)	1.1
"Levosimendan treatment offers short-term survival benefit in acute heart failure but its effect on long-term outcome remains unclear."	( Effects of levosimendan versus dobutamine on long-term survival of patients with cardiogenic shock after primary coronary angioplasty. Abreu-González, P; Domínguez-Rodríguez, A; García-González, MJ; Samimi-Fard, S, 2008)	1.18

Toxicity

The most frequent adverse events were increased heart rate, fall, headache and dyspnoea. There were less adverse effects including hypokalemia, hypotension and ventricular premature beats in the levosimendan group than in the dobutamine group. In patients with an acute myocardial infarction the rate of ischemia or hypotension were similar in both groups.

Excerpt	Reference	Relevance
" Because these compounds are not yet available for clinical use, the adverse drug events (ADEs) during levosimendan treatment cannot be predicted in detail."	( Safety of levosimendan and other calcium sensitizers. Akkila, J; Lehtonen, L; Mills-Owens, P, 1995)	0.87
" However in patients with an acute myocardial infarction the rate of ischemia or hypotension were similar in levosimendan- and placebo-treated patients and in the dobutamine controlled trials no major adverse effects were seen or they were more frequent in dobutamine patients."	( Considerations on the efficacy and safety of levosimendan in ischemic heart failure. Nieminen, MS; Sandell, EP, 2003)	0.78
"Levosimendan is a safe and efficient choice in the management of low-output syndrome during and after open-heart surgery."	( Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Antoniou, T; Degiannis, D; Geroulanos, S; Kriaras, I; Papadopoulos, K; Stavridis, G; Tasouli, A, 2007)	1.15
" The primary combined endpoint of clinical effectiveness (as defined by a eight-variable clinical score) and safety (defined by the absence of serious adverse events) was assessed at 24 hours after the beginning of treatment; a second similar primary combined endpoint was assessed at 5 days."	( Effectiveness and safety of levosimendan in clinical practice. Abreu-Lima, C; Amorim, S; Damasceno, A; Ferreira, J; Ferreira, R; Fonseca, C; Ilídio-Moreira, J; Lousada, N; Martins-de-Campos, J; Oliveira-Soares, A; Rabaçal, C; Seabra-Gomes, R; Silva-Cardoso, J, 2009)	0.64
"In daily practice, levosimendan was clinically effective and safe in 80."	( Effectiveness and safety of levosimendan in clinical practice. Abreu-Lima, C; Amorim, S; Damasceno, A; Ferreira, J; Ferreira, R; Fonseca, C; Ilídio-Moreira, J; Lousada, N; Martins-de-Campos, J; Oliveira-Soares, A; Rabaçal, C; Seabra-Gomes, R; Silva-Cardoso, J, 2009)	0.95
" An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects."	( Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events? Campia, U; Gheorghiade, M; Nodari, S, 2010)	0.36
" The incidences of adverse reactions and events were similar between two groups."	( [Comparison on efficacy and safety between domestic levosimendan versus dobutamine for patients with acute decompensated heart failure]. Bai, XJ; Huang, Y; Jiang, YN; Li, H; Liu, WX; Qing, EM; Qu, P; Sun, YX; Wei, BQ; Zhang, J; Zhang, L; Zhang, YH; Zhou, Q, 2012)	0.63
" Clinical course of patients, electrocardiogram presentation, LV function, and adverse events at follow-up were recorded."	( Safety and feasibility of levosimendan administration in takotsubo cardiomyopathy: a case series. Brunetti, ND; Carpagnano, G; Di Biase, L; Di Biase, M; Ferraretti, A; Ienco, V; Ieva, R; Lodispoto, M; Santoro, F, 2013)	0.68
" Only 15% of subjects had adverse events during hospital stay; two patients incurred noncardiovascular death at follow-up."	( Safety and feasibility of levosimendan administration in takotsubo cardiomyopathy: a case series. Brunetti, ND; Carpagnano, G; Di Biase, L; Di Biase, M; Ferraretti, A; Ienco, V; Ieva, R; Lodispoto, M; Santoro, F, 2013)	0.68
"The use of levosimendan may be safe and feasible in patients with TTC."	( Safety and feasibility of levosimendan administration in takotsubo cardiomyopathy: a case series. Brunetti, ND; Carpagnano, G; Di Biase, L; Di Biase, M; Ferraretti, A; Ienco, V; Ieva, R; Lodispoto, M; Santoro, F, 2013)	1.03
"Repetitive levosimendan infusions in children with DCM appeared to be hemodynamically well tolerated without severe adverse events."	( The Hemodynamic Effects and Safety of Repetitive Levosimendan Infusions on Children With Dilated Cardiomyopathy. Mattila, N; Nyblom, O; Rahkonen, O; Rautiainen, P; Suominen, P; Turanlahti, M, 2017)	1.06
" Adverse events did not significantly differ between the two groups."	( Efficacy and safety of levosimendan in patients with acute right heart failure: A meta-analysis. Hao, Y; Huang, S; Jia, L; Li, X; Ma, Y; Mao, Y; Qiu, J; Wang, M, 2017)	0.75
" Secondary endpoints included changes in 6-min walk distance (6-MWD), biochemical markers and right heart structure and function together with adverse events on day 7 and incidence of major cardiovascular events (death or readmission due to RHF) on day 30."	( Efficacy and safety of a calcium sensitizer, levosimendan, in patients with right heart failure due to pulmonary hypertension. Gong, SG; He, J; Jiang, R; Liu, JM; Luo, CJ; Qiu, HL; Wang, L; Wu, WH; Yuan, P; Zhang, R; Zhao, QH, 2018)	0.74
" In conclusion, prolonged AI and/or LS infusions in HF are safe and beneficial even in small infants, allowing stabilization and reasonable social and family life out of the hospital."	( Ambulatory Intravenous Inotropic Support and or Levosimendan in Pediatric and Congenital Heart Failure: Safety, Survival, Improvement, or Transplantation. Apostolopoulou, SC; Kakava, F; Rammos, S; Tsoutsinos, A; Vagenakis, GA, 2018)	0.73
" However, side-effects including nephrotoxicity, ototoxicity, gastrointestinal effects and neuropathy restrict the use of the drug due to their adverse impacts on quality of life."	( Levosimendan ameliorates cisplatin-induced ototoxicity: Rat model. Askin, S; Ekinci Akdemir, FN; Eser, G; Gozeler, MS; Sahin, A; Yildirim, S, 2019)	1.07
" Levosimendan is therefore effective and safe in the short-term treatment of chronic systolic heart failure."	( Short-term efficacy and safety of levosimendan in patients with chronic systolic heart failure. Bai, L; Cui, XR; Jia, M; Li, RB; Wang, D; Yang, XH; Zhang, JD, )	0.92
" We select literature according to prespecified inclusion and exclusion criteria and record data such as drug type, mortality, and adverse reactions."	( Network Meta-Analysis of the Safety of Drug Therapy for Cardiogenic Shock. Chen, X; Lei, J; Liao, X; Qian, L; Zhang, S, 2020)	0.56
" Milrinone was most effective at reducing mortality and had the lowest incidence of adverse reactions."	( Network Meta-Analysis of the Safety of Drug Therapy for Cardiogenic Shock. Chen, X; Lei, J; Liao, X; Qian, L; Zhang, S, 2020)	0.56
"This network meta-analysis demonstrated that milrinone was the most effective medication at reducing mortality and adverse events in patients suffering from cardiogenic shock."	( Network Meta-Analysis of the Safety of Drug Therapy for Cardiogenic Shock. Chen, X; Lei, J; Liao, X; Qian, L; Zhang, S, 2020)	0.56
"The use of levosimendan was safe and associated with clinical improvement and reduction in BNP level in AdvHF patients hospitalized due to HF decompensation, although the mortality and re-hospitalization rate during the one-year follow-up remains high."	( Multicenter experiences with levosimendan therapy and its safety in patients with decompensated advanced heart failure. Gruchała, M; Korościk, E; Lelonek, M; Stopczyńska, I; Straburzyńska-Migaj, E, 2020)	1.19
" The most frequent adverse events were increased heart rate (106 [33%] of 326 receiving levosimendan vs 12 [7%] of 166 receiving placebo), fall (85 [26%] vs 48 [29%]), headache (93 [29%] vs 36 [22%]), and dyspnoea (59 [18%] vs 32 [19%])."	( Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial. Aho, VV; Al-Chalabi, A; Cudkowicz, M; Garratt, C; Genge, A; Kuoppamäki, M; Maragakis, N; Petri, S; Sarapohja, T; van den Berg, L, 2021)	1.13

Pharmacokinetics

The pharmacokinetic profile of levosimendan in children with congenital heart disease is similar to that in adult patients with congestive heart failure. The aim of this exploratory study was to assess the hemodynamic and Pharmacokinetic interactions between digoxin and oral levosIMendan as well as the proarrhythmic potential.

Excerpt	Reference	Relevance
" There were only minor differences between the pharmacokinetic profiles of the enantiomers of simendan."	( Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers. Antila, S; Karlsson, M; Lilleberg, J; Nieminen, MS; Pentkäinen, PJ, 1994)	0.77
" The pharmacokinetic profile facilitates rapid dose adjustments during intravenous administration."	( Pharmacokinetics and pharmacodynamics of simendan, a novel calcium sensitizer, in healthy volunteers. Antila, S; Karlsson, M; Lilleberg, J; Nieminen, MS; Pentkäinen, PJ, 1994)	0.55
" To observe possible pharmacodynamic interactions psychomotoric tests were made before drug administration and 1h, 2h, 3h and 6h thereafter."	( Studies on psychomotoric effects and pharmacokinetic interactions of the new calcium sensitizing drug levosimendan and ethanol. Akkila, J; Antila, S; Honkanen, T; Järvinen, A; Karlsson, M; Lehtonen, L, 1997)	0.51
" Itraconazole had no significant effects on the pharmacokinetic parameters of levosimendan."	( The CYP3A4 inhibitor intraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan. Antila, S; Honkanen, T; Lehtonen, L; Neuvonen, PJ, 1998)	0.74
" Pharmacokinetic parameters of levosimendan from the third and fourth treatment days were compared with each other."	( Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin. Antila, S; Honkanen, T; Jarvinen, A; Lehtonen, L, 2000)	0.81
" The distribution volume of warfarin was higher and elimination half-life shorter after concomitant levosimendan administration than after warfarin alone."	( Pharmacokinetic and pharmacodynamic interactions between the novel calcium sensitiser levosimendan and warfarin. Antila, S; Honkanen, T; Jarvinen, A; Lehtonen, L, 2000)	0.74
" The elimination half-life of levosimendan was approximately 1 hour and of the metabolites 70 to 80 hours."	( Pharmacodynamics and safety of a new calcium sensitizer, levosimendan, and its metabolites during an extended infusion in patients with severe heart failure. Antila, S; Eha, J; Kivikko, M; Lehtonen, L; Pentikäinen, PJ, 2002)	0.84
" a one-, two- or three-compartment pharmacokinetic model)."	( Population pharmacokinetics of levosimendan in patients with congestive heart failure. Antila, S; Jonsson, EN; Karlsson, MO; Lehtonen, L; McFadyen, L, 2003)	0.6
"The aim was to study the pharmacodynamic interactions and safety of the co-administration of the calcium sensitizer levosimendan and the calcium antagonist felodipine in patients with coronary heart disease (CHD) and with normal ejection fraction (EF)."	( Pharmacodynamic interactions of levosimendan and felodipine in patients with coronary heart disease. Akkila, J; Antila, S; Eha, J; Heinpalu, M; Lehtonen, L; Loogna, I; Mesikepp, A; Planken, U; Põder, P, )	0.61
"No clinically significant pharmacodynamic interactions between levosimendan and felodipine were seen."	( Pharmacodynamic interactions of levosimendan and felodipine in patients with coronary heart disease. Akkila, J; Antila, S; Eha, J; Heinpalu, M; Lehtonen, L; Loogna, I; Mesikepp, A; Planken, U; Põder, P, )	0.64
"The pharmacokinetic profile of levosimendan in children with congenital heart disease is similar to that in adult patients with congestive heart failure."	( Pharmacokinetics of levosimendan in pediatric patients evaluated for cardiac surgery. Antila, S; Boldt, T; Lehtonen, L; Palkama, T; Pesonen, E; Turanlahti, M, 2004)	0.91
" Pharmacodynamic variables consisted of heart rate-corrected electromechanical systole, heart rate, and systolic and diastolic blood pressure."	( Pharmacodynamics and pharmacokinetics of oral levosimendan and its metabolites in patients with severe congestive heart failure: a dosing interval study. Antila, S; Eha, J; Heinpalu, M; Lehtonen, L; Loogna, I; Planken, U; Põder, P; Rantanen, S; Sundberg, S, 2004)	0.58
"The purpose of this study was to investigate the pharmacokinetics of levosimendan and to determine the primary pharmacokinetic parameters of the pharmacologically active metabolite OR-1896 in rapid and slow acetylators."	( Pharmacokinetics of levosimendan and its active metabolite OR-1896 in rapid and slow acetylators. Antila, S; Lehtonen, L; Nikkanen, H; Pesonen, U; Scheinin, H; Tapanainen, P; Vaahtera, K, 2004)	0.86
"This study was an open-label, nonrandomised, phase I pharmacokinetic study."	( Effect of severe renal failure and haemodialysis on the pharmacokinetics of levosimendan and its metabolites. Häkkinen, S; Harjola, VP; Kantele, S; Kivikko, M; Koskinen, P; Pentikäinen, PJ; Puttonen, J, 2007)	0.57
" In addition, pharmacokinetic parameters of total radiocarbon and the deacetylated congener, OR-1855, were determined."	( Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men. Häkkinen, S; Koskinen, M; Laine, T; Pentikäinen, P; Pradhan, R; Puttonen, J; Ramela, M; Zhang, W, 2007)	0.56
" The pharmacokinetic parameters were calculated by three-compartmental methods."	( Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men. Häkkinen, S; Koskinen, M; Laine, T; Pentikäinen, P; Pradhan, R; Puttonen, J; Ramela, M; Zhang, W, 2007)	0.56
" Mean terminal elimination half-life of OR-1896 (t(1/2)) was 70."	( Pharmacokinetics and excretion balance of OR-1896, a pharmacologically active metabolite of levosimendan, in healthy men. Häkkinen, S; Koskinen, M; Laine, T; Pentikäinen, P; Pradhan, R; Puttonen, J; Ramela, M; Zhang, W, 2007)	0.56
" The aim of this exploratory study was to assess the hemodynamic and pharmacokinetic interactions between digoxin and oral levosimendan as well as the proarrhythmic potential of this combination in patients with chronic heart failure."	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	0.78
" Pharmacokinetic variables of levosimendan and digoxin were calculated in both treatment periods."	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	0.85
" In contrast to the earlier data with intravenous levosimendan, the results indicate a pharmacokinetic interaction between levosimendan and digoxin."	( The hemodynamic and pharmacokinetic interactions between chronic use of oral levosimendan and digoxin in patients with NYHA Classes II-III heart failure. Harjola, VP; Jurkko, R; Nieminen, MS; Oikarinen, L; Puttonen, J; Sarapohja, T; Sundberg, S; Toivonen, L, 2008)	0.82
" A two compartment pharmacokinetic model with zero-order input and first-order elimination has been found to describe best the pharmacokinetics of levosimendan."	( Relationship between the pharmacokinetics of levosimendan and its effects on cardiovascular system. Antoniades, C; Antonopoulos, AS; Bakogiannis, C; Stefanadi, E; Stefanadis, C; Tousoulis, D, 2009)	0.81
" After a 24-hour infusion of levosimendan, the pharmacodynamic effect of the drug is observed for at least one week."	( The importance of pharmacokinetics, pharmacodynamic and repetitive use of levosimendan. Banach, J; Dobosiewicz, M; Gilewski, W; Grześk, G; Hertmanowski, W; Kowalkowska, M; Rogowicz, D; Wołowiec, Ł, 2022)	1.23
" In light of LVSMD pharmacological characteristics, we hypothesized that ECMO may induce major pharmacokinetic (PK) modifications for LVSMD and its metabolites."	( Population Pharmacokinetics of Levosimendan and its Metabolites in Critically Ill Neonates and Children Supported or Not by Extracorporeal Membrane Oxygenation. Berthomieu, L; Bourgoin, P; Chenouard, A; Davril, E; Duflot, T; Joram, N; Lamoureux, F; Lecomte, J; Oualha, M; Pereira, T, 2023)	1.19

Compound-Compound Interactions

Levosimendan, a calcium sensitizer, was used in combination with beta-adrenergic antagonists in a man aged 56 yr with cardiogenic shock, complicating acute myocardial infarction. The patient developed severe tachycardia after dobutamine administration. Increasing evidence suggests the use of levosim endan in combination to treat decompensated heart failure that is refractory to dobutamines alone.

Excerpt	Reference	Relevance
"Levosimendan, a calcium sensitizer, was used in combination with beta-adrenergic antagonists in a man aged 56 yr with cardiogenic shock, complicating acute myocardial infarction, who developed severe tachycardia after dobutamine administration."	( Treatment of cardiogenic shock with levosimendan in combination with beta-adrenergic antagonists. Alhashemi, JA, 2005)	1.15
" Increasing evidence suggests the use of levosimendan in combination with dobutamine in patients with decompensated heart failure that is refractory to dobutamine alone."	( The use of levosimendan in comparison and in combination with dobutamine in the treatment of decompensated heart failure. Cavusoglu, Y, 2007)	0.95
" We examined whether intermittent inotropic agents combined with oral amiodarone to prevent the proarrhythmic effect of inotropic agents results in better outcomes."	( Intermittent inotropic infusions combined with prophylactic oral amiodarone for patients with decompensated end-stage heart failure. Bonios, M; Drakos, SG; Kaldara, E; Kanakakis, JV; Katsaros, F; Nanas, JN; Nanas, S; Pantsios, C, 2009)	0.35
"Intermittent intravenous inotropic agents combined with prophylactic oral amiodarone seem to improve the outcomes of patients with end-stage chronic heart failure."	( Intermittent inotropic infusions combined with prophylactic oral amiodarone for patients with decompensated end-stage heart failure. Bonios, M; Drakos, SG; Kaldara, E; Kanakakis, JV; Katsaros, F; Nanas, JN; Nanas, S; Pantsios, C, 2009)	0.35
"Levosimendan combined with epinephrine may be superior to either drug alone for lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest."	( Levosimendan combined with epinephrine improves rescue outcomes in a rat model of lipid-based resuscitation from bupivacaine-induced cardiac arrest. Cai, X; Chen, L; Li, M; Li, Z; Nan, F; Xu, X; Ye, Y, 2017)	1.57
"To investigate the clinical effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures."	( Effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures. Fu, M; Liu, Y; Wang, Z, 2020)	1.07
" Clinical manifestations; left ventricular ejection fraction (LVEF); left ventricular end-diastolic dimension (LVEDD); left ventricular end-systolic dimension (LVESD); B-type natriuretic peptide (BNP), superoxide dismutase (SOD), malondialdehyde (MDA), nitric oxide (NO), and endothelin-1 (ET-1) levels; and self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were compared between before and after treatment to evaluate the curative effects of Xinkeshu combined with levosimendan."	( Effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures. Fu, M; Liu, Y; Wang, Z, 2020)	0.99
"Levosimendan combined with Xinkeshu can improve cardiac function, alleviate oxidative stress, and relieve anxiety and depression in oldest-old patients with perioperative heart failure and hip fracture."	( Effects of Xinkeshu combined with levosimendan on perioperative heart failure in oldest-old patients with hip fractures. Fu, M; Liu, Y; Wang, Z, 2020)	1.39
" The aim of this study was to investigate efficacy of levosimendan when combined with rhBNP in patients with diuretic resistance and low ejection fraction (EF) rate."	( Effect of levosimendan combined with recombinant human brain natriuretic peptide on diuretic resistance. Jun, M; Lan, L; Libiya, Z; Shubin, J; Xiangli, S, 2021)	1.23

Bioavailability

Oral levosimendan has high bioavailability (approximately equal to 85%). In clinical practice it has been hitherto administered intravenously. Site specific bioavailability and metabolism of levosicendan was studied in ten dogs by placing intestinal access port catheters.

Excerpt	Reference	Relevance
" The bioavailability of oral levosimendan was 85 +/- 6% in healthy volunteers and 84 +/- 4% in patients."	( Pharmacokinetics of levosimendan in healthy volunteers and patients with congestive heart failure. Antila, S; Hayha, M; Heikkinen, P; Lehtonen, LA; Ottoila, P; Pentikainen, PJ; Sandell, EP, 1995)	0.88
" The bioavailability of CT and CC was 83 and 87%, while that of SR was only 31%."	( Integrated pharmacokinetics and pharmacodynamics of the novel calcium sensitizer levosimendan as assessed by systolic time intervals. Antila, S; Häyhä, M; Lehtonen, L; Scheinin, H; Sundberg, S; Virtanen, M, 1998)	0.52
"Site specific bioavailability and metabolism of levosimendan was studied in ten dogs by placing intestinal access port catheters in different parts of the gastrointestinal tract."	( Site dependent bioavailability and metabolism of levosimendan in dogs. Antila, S; Huuskonen, H; Kanerva, H; Lehtonen, L; Nevalainen, T; Vanninen, P, 1999)	0.8
"The aim of this study was to investigate the possibility of developing different levels of correlation between in vitro release and in vivo absorption rate for four modified-release levosimendan capsule formulations."	( Development of level A, B and C in vitro-in vivo correlations for modified-release levosimendan capsules. Antila, S; Bäckman, M; Kortejärvi, H; Marvola, M; Mikkola, J, 2002)	0.73
" Three bioavailability studies of levosimendan were used to develop IVIVC model."	( Level A in vitro-in vivo correlation (IVIVC) model with Bayesian approach to formulation series. Kortejärvi, H; Malkki, J; Marvola, M; Pajunen, P; Urtti, A; Yliperttula, M, 2006)	0.6
" Although oral levosimendan has high bioavailability (approximately equal to 85%), in clinical practice it has been hitherto administered intravenously."	( Relationship between the pharmacokinetics of levosimendan and its effects on cardiovascular system. Antoniades, C; Antonopoulos, AS; Bakogiannis, C; Stefanadi, E; Stefanadis, C; Tousoulis, D, 2009)	0.94

Dosage Studied

Levosimendan was associated with an increased risk of adverse cardiovascular events. A suitably powered randomised controlled trial is required to confirm these findings and to address the unresolved questions about the timing and dosing of levosim endan.

Excerpt	Relevance	Reference
"0 mg to define its safety and dose-response effects."	( Hemodynamic effects of the novel cardiotonic drug simendan: echocardiographic assessment in healthy volunteers. Leikola-Pelho, T; Lilleberg, JM; Nieminen, MS; Sundberg, S, 1994)	0.54
" A dose-response relationship was demonstrated for levosimendan on increases in CO and SV, and reductions in PCWP during the infusion (for all, p< or =0."	( Hemodynamic and neurohumoral effects of continuous infusion of levosimendan in patients with congestive heart failure. Akkila, J; Hasenfuss, G; Kleber, FX; Lehtonen, LA; Mitrovic, V; Nieminen, MS; Nyquist, O; Remme, WJ, 2000)	0.79
" A sensitivity analysis on dosage of drug and duration of survival was performed."	( Intravenous levosimendan treatment is cost-effective compared with dobutamine in severe low-output heart failure: an analysis based on the international LIDO trial. Apajasalo, M; Cleland, JG; Kobelt, G; Takala, A; Zethraeus, N, 2003)	0.66
" Dobutamine was continuously infused at a dosage of 3 microg kg(-1) min(-1)."	( Levosimendan improves postresuscitation outcomes in a rat model of CPR. Cammarata, G; Cao, L; Huang, L; Sun, S; Tang, W; Weil, MH, 2005)	0.89
" More data are needed regarding patient selection and the optimum regimen and dosing of levosimendan before this treatment modality become the first line therapy of acutely decompensated chronic heart failure patients."	( Classical inotropes and new cardiac enhancers. Farmakis, D; Nieminen, M; Parissis, JT, 2007)	0.56
" We investigate the proper time for its infusion during or after open-heart surgery to avoid complications related with low-output syndrome and high dosage of inotropes."	( Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use. Antoniou, T; Degiannis, D; Geroulanos, S; Kriaras, I; Papadopoulos, K; Stavridis, G; Tasouli, A, 2007)	0.59
" We assessed the dose-response relationship of oral LS in nine normal and seven pacing-induced heart failure (HF), conscious, chronically instrumented mongrel dogs."	( Orally available levosimendan dose-related positive inotropic and lusitropic effect in conscious chronically instrumented normal and heart failure dogs. Cheng, CP; Cheng, HJ; Heikkilä, A; Hyttilä-Hopponen, M; Levijoki, J; Little, WC; Masutani, S; Vuorela, A, 2008)	0.66
" The mean dosing interval was 66."	( Repeated infusions of levosimendan: well tolerated and improves functional capacity in decompensated heart failure - a single-centre experience. Best, M; Dembo, L; Driscoll, GO; Parle, NM; Thomas, MD, 2008)	0.65
" However, because the maximum duration of levosimendan infusion is 24 hours, dosing adjustments of levosimendan may not be required in subjects with impaired hepatic function."	( Pharmacokinetics of intravenous levosimendan and its metabolites in subjects with hepatic impairment. Häkkinen, S; Kantele, S; Kivikko, M; Pentikäinen, PJ; Puttonen, J; Ramela, M; Ruck, A, 2008)	0.88
" Five patients presenting with reduced ejection fraction (EF<30%) and high dosed catecholamines after heart transplantation were treated with levosimendan (Simdax, Abbot GesmbH, Vienna, Austria) in a 24-hour continuous infusion (0."	( Primary graft failure and Ca2+ sensitizers after heart transplantation. Beiras-Fernandez, A; Kaczmarek, I; Kur, F; Reichart, B; Schmoeckel, M; Weis, FC; Weis, M, 2008)	0.55
" The frequency and dosing of inotropic infusions in patients admitted with acute heart failure was assessed in detail."	( The use of more than one inotrope in acute heart failure is associated with increased mortality: a multi-centre observational study. Harjola, VP; Lassus, J; Melin, J; Nieminen, MS; Peuhkurinen, K; Rossinen, J; Siirila-Waris, K, 2008)	0.35
" A suitably powered randomised controlled trial is required to confirm these findings and to address the unresolved questions about the timing and dosing of levosimendan."	( Levosimendan and mortality after coronary revascularisation: a meta-analysis of randomised controlled trials. Maharaj, R; Metaxa, V, 2011)	1.12
"To assess the effect of various levosimendan dosing regimens on hemodynamics in a rodent model of propranolol poisoning."	( Levosimendan does not improve cardiac output or blood pressure in a rodent model of propranolol toxicity when administered using various dosing regimens. Graudins, A; Kalam, Y, 2012)	1.21
" Levosimendan did not improve CO or BP with any dosing regimen."	( Levosimendan does not improve cardiac output or blood pressure in a rodent model of propranolol toxicity when administered using various dosing regimens. Graudins, A; Kalam, Y, 2012)	1.45
" Anemia is a deteriorating situation that causes increase of drug dosing in patients with heart failure."	( Effects of levosimendan on TNF-alpha, BNP and MMP-1 in patients with heart failure with anemia. Büyüklü, M; Kürüm, AT; Set, T; Tatlý, E, 2012)	0.73
" LEVO may have advantages over MR in terms of the dosing regimen."	( Phase 1 study of two inodilators in neonates undergoing cardiovascular surgery. Bravo, MC; Buño, A; Cabañas, F; Castro, L; Labrandero, C; Lopez-Ortego, P; Lubomirov, R; Madero, R; Pellicer, A; Perez-Rodriguez, J; Quero, J; Riera, J, 2013)	0.39
" As dosed in this trial, levosimendan was associated with an increased risk of adverse cardiovascular events."	( Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. Colucci, W; Delgado-Herrera, L; Fisher, L; Garratt, C; Huang, B; Massie, BM; Packer, M; Padley, RJ; Salon, J; Sarapohja, T; Teerlink, JR; Thakkar, R; Young, J, 2013)	1.04
" The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience."	( Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus. Altenberger, J; Ben-Gal, T; Böhmer, A; Comin-Colet, J; Dickstein, K; Edes, I; Fedele, F; Fonseca, C; García-González, MJ; Giannakoulas, G; Iakobishvili, Z; Jääskeläinen, P; Karavidas, A; Kettner, J; Kivikko, M; Lund, LH; Matskeplishvili, ST; Metra, M; Morandi, F; Nieminen, MS; Oliva, F; Parissis, J; Parkhomenko, A; Pollesello, P; Pölzl, G; Schwinger, RH; Segovia, J; Seidel, M; Vrtovec, B; Wikström, G, 2014)	0.72
" Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring."	( Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus. Altenberger, J; Ben-Gal, T; Böhmer, A; Comin-Colet, J; Dickstein, K; Edes, I; Fedele, F; Fonseca, C; García-González, MJ; Giannakoulas, G; Iakobishvili, Z; Jääskeläinen, P; Karavidas, A; Kettner, J; Kivikko, M; Lund, LH; Matskeplishvili, ST; Metra, M; Morandi, F; Nieminen, MS; Oliva, F; Parissis, J; Parkhomenko, A; Pollesello, P; Pölzl, G; Schwinger, RH; Segovia, J; Seidel, M; Vrtovec, B; Wikström, G, 2014)	0.72
" Our aim was to compare acute dose-response hemodynamic effects of inodilators dobutamine (DOB), milrinone (MIL), and levosimendan (LEV) in chronic experimental PH."	( Dose-Response Head-to-Head Comparison of Inodilators Dobutamine, Milrinone, and Levosimendan in Chronic Experimental Pulmonary Hypertension. Alaa, M; Leite, S; Leite-Moreira, AF; Lopes, L; Lourenço, AP; Oliveira-Pinto, J; Tavares-Silva, M, 2017)	0.89
"Based on these data it can be assumed that the use of prolonged infusion of levosimendan in a dosage of 12."	( [A COMPARISON OF TWO APPROACHES FOR INTRAOPERATIVE LEVOSIMENDAN ADMINISTRATION IN CARDIAC SURGICAL PATIENTS WITH SEVERE LEFT VENTRICLE DYSFUNCTION.] Adzhigaliev, RR; Belov, SI; Berezhnoy, SA; Panov, OS; Pasyuga, VV; Tarasov, DG; Yavorovsky, AG; Yusupova, ES, 2016)	0.91
" The cumulative dosage of levosimendan was recorded to assess the required dosage in the context of individualized treatment."	( [Individualized use of levosimendan in cardiac surgery]. Dashkevich, A; Juchem, G; Kilger, E; Mehringer, L; Schünemann, M; Weis, M; Woehrle, T, 2021)	1.21
"2% of patients, a cumulative dosage of 5 mg levosimendan or less was considered sufficient."	( [Individualized use of levosimendan in cardiac surgery]. Dashkevich, A; Juchem, G; Kilger, E; Mehringer, L; Schünemann, M; Weis, M; Woehrle, T, 2021)	1.17
"25 mg levosimendan followed by individualized additional dosing in cardiac surgery patients with preoperative LVEF ≤40% suggests that this concept is safe, with possible advantages regarding the need of inotropic agents, renal replacement therapy, and 30-day mortality, compared to the current literature."	( [Individualized use of levosimendan in cardiac surgery]. Dashkevich, A; Juchem, G; Kilger, E; Mehringer, L; Schünemann, M; Weis, M; Woehrle, T, 2021)	1.32
" The dosage and administration time of dopamine and epinephrine, mechanical ventilation time, ICU length of stay, and postoperative adverse events were recorded."	( Prospective Study on the Postoperative Use of Levosimendan After Conventional Heart Valve Replacement. Li, H; Lv, X; Niu, Z; Qiao, H; Sheng, W; Wang, T; Wu, J; Zhang, W, 2021)	0.87
" The purpose of this review is to discuss clinical controversies in the management of septic patients, including the use of novel medications and dosing strategies, to assist providers in appropriately determining what treatment strategy is best suited for patients."	( Beyond the bundle: Clinical controversies in the management of sepsis in emergency medicine patients. Bonderski, V; Krishnan, K; Rech, MA; Tednes, P; Wassermann, TB, 2022)	0.72
" Levosimendan dosing varied considerably with only three studies using a loading dose."	( Levosimendan in paediatric cardiac anaesthesiology: A systematic review and meta-analysis. Lapere, M; Rega, F; Rex, S, 2022)	1.79
" Simulated data revealed that standard dosing may not be appropriate for patients under ECMO, with a decrease in the steady-state concentration of LVSMD and lower exposure to the active metabolite OR-1896."	( Population Pharmacokinetics of Levosimendan and its Metabolites in Critically Ill Neonates and Children Supported or Not by Extracorporeal Membrane Oxygenation. Berthomieu, L; Bourgoin, P; Chenouard, A; Davril, E; Duflot, T; Joram, N; Lamoureux, F; Lecomte, J; Oualha, M; Pereira, T, 2023)	1.19

[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	53 (4.27)	18.2507
2000's	472 (38.06)	29.6817
2010's	534 (43.06)	24.3611
2020's	181 (14.60)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	255 (19.54%)	5.53%
Reviews	263 (20.15%)	6.00%
Case Studies	114 (8.74%)	4.05%
Observational	13 (1.00%)	0.25%
Other	660 (50.57%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (91)

Trial Overview

Trial	Phase	Enrollment	Study Type	Start Date	Status
The Effects of Levosimendan on Haemodynamics in Patients Undergoing Elective Aortic Valve Replacement (AVR)Together With Coronary Artery Bypass Grafting [NCT01210976]	Phase 4	24 participants (Actual)	Interventional	2009-01-31	Completed
Perioperative Levosimendan Administration in Neonates With Transposition of the Great Arteries: Randomized Controlled Trial [NCT01120106]	Phase 2	63 participants (Actual)	Interventional	2009-01-31	Completed
Preoperative Optimization of the High-Risk Patient Undergoing Hip Fracture Surgery [NCT01219712]		200 participants (Anticipated)	Interventional	2011-01-31	Not yet recruiting
Inotropic Treatment With Levosimendan (SimdaxR)in Heart Surgery [NCT01221116]		23 participants (Actual)	Interventional	2003-01-31	Terminated(stopped due to The study was stopped due to difficulties in including patients)
Early Use of Levosimendan Compared to Usual Care in Advanced Chronic Heart Failure (ACHF) [NCT01290146]	Phase 3	13 participants (Actual)	Interventional	2011-02-28	Terminated(stopped due to Due to lack of enrollment)
Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS: Open-Label Extension for Patients Completing Study 3119002 [NCT03948178]	Phase 3	227 participants (Actual)	Interventional	2019-06-26	Terminated(stopped due to This was an open label extension for patients completing the REFALS study (3119002; NCT03505021). Study 3119002 showed lack of efficacy of ODM109 so the sponsor decided to terminate this study)
Open-Label Rollover Study of Levosimendan in Patients With Pulmonary Hypertension With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF) [NCT03624010]	Phase 2	36 participants (Anticipated)	Interventional	2018-11-14	Active, not recruiting
Levosimendan Versus Milrinone to Support Hemodynamics During Off Pump Coronary Artery Bypass Grafting Surgery in Patients With Poor Ejection Fraction [NCT03855579]	Phase 4	60 participants (Anticipated)	Interventional	2019-03-06	Recruiting
Phase II Study to Evaluate the Efficacy and Safety of Levosimendan in Severe Acute Heart Failure in Critical Children [NCT01301313]	Phase 2	116 participants (Actual)	Interventional	2011-02-28	Terminated
Effects of Levosimendan in Acute Kidney Injury After Cardiac Surgery [NCT02531724]	Phase 4	30 participants (Actual)	Interventional	2015-09-30	Completed
Effectiveness of a Repetitive Use of 24-hour Levosimendan Infusions in Patients With Severe Systolic Heart Failure in Order to Prevent Rehospitalizations [NCT03764722]	Phase 4	100 participants (Anticipated)	Interventional	2018-08-01	Recruiting
Pilot Study on the Effects of Levosimendan on in Vivo Respiratory Muscle Function in Healthy Subjects [NCT01101620]		30 participants (Actual)	Interventional	2010-04-30	Completed
Effects of Levosimendan Pretreatment in Patients With Low Ejection Fraction (40 % or Less) Undergoing CABG: a Randomised, Double Blind, Multicenter Trial [NCT02184819]	Phase 3	335 participants (Actual)	Interventional	2013-06-30	Completed
The Prophylactic Effect of Levosimendan in Reducting Acute Kidney Injury Postoperatively in Pediatric Patients Undergoing Corrective Heart Surgery [NCT02232399]	Phase 2	72 participants (Actual)	Interventional	2014-10-31	Completed
Ensayo clínico, Fase III, Aleatorizado, Prospectivo, unicéntrico, Doble Ciego y Controlado Con Placebo, Para Estimar la Eficacia y Seguridad Del Levosimendan Intravenoso, en Las Primeras 24 Horas Tras la Angioplastia Primaria, en Pacientes Con síndrome Co [NCT03699215]	Phase 3	184 participants (Anticipated)	Interventional	2018-11-17	Recruiting
Pretreatment With Levosimendan In Patients Undergoing Left Ventricular Assist Device Implantation [NCT03659851]		50 participants (Anticipated)	Observational [Patient Registry]	2009-06-01	Recruiting
A Randomized Controlled Clinical Study of Early Application of Levosimendan to Improve Cardiac Dysfunction and Neurological Prognosis in Patients With Cardiac Arrest [NCT05956431]	Phase 4	60 participants (Anticipated)	Interventional	2023-08-01	Not yet recruiting
Efficacy of Intravenous Levosimendan Compared With Dobutamine on Renal Hemodynamics and Function in Chronic Heart Failure [NCT02133105]	Phase 3	33 participants (Actual)	Interventional	2014-04-30	Completed
Prophylactic Administration of Levosimendan in Patients With Impaired Left Ventricular Function Undergoing Coronary Surgery [NCT01318460]	Phase 4	32 participants (Actual)	Interventional	2011-03-31	Completed
Effects of Oral Levosimendan on Ambulatory Electrocardiographic Variables and Cerebrovascular Reactivity in Patients With Recent Stroke or TIA. [NCT00698763]	Phase 2	32 participants (Actual)	Interventional	2008-08-31	Completed
Effect of Levosimendan or Placebo on Exercise Capacity and Hemodynamics in Patients With Advanced Chronic Heart Failure (LOCO-CHF Trial) [NCT03576677]	Phase 4	42 participants (Anticipated)	Interventional	2019-08-01	Recruiting
The Role of Preoperative Use of Levosimendan in Ischemic Cardiac Patients Undergoing Major Abdominal Cancer Surgeries: A Prospective Randomized Study [NCT03557255]	Phase 2	60 participants (Actual)	Interventional	2017-08-01	Completed
A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Pulmonary Hypertension Patients With Heart Failure and Preserved Left Ventricular Ejection Fraction (PH-HFpEF) [NCT03541603]	Phase 2	38 participants (Actual)	Interventional	2018-11-14	Completed
Effects of Oral Levosimendan (ODM-109) on Respiratory Function in Patients With ALS [NCT03505021]	Phase 3	496 participants (Actual)	Interventional	2018-06-21	Completed
Double-blind Randomized Placebo-controlled Study to Evaluate the Efficacy and Safety of Intermittent, Long-term Administration of Levosimendan in Patients With Advanced Heart Failure [NCT00988806]	Phase 4	213 participants (Anticipated)	Interventional	2009-11-30	Enrolling by invitation
Platform Adaptive Embedded Trial for Acute Respiratory Distress Syndrome [NCT05658692]	Phase 4	1,000 participants (Anticipated)	Interventional	2022-10-01	Recruiting
Potential Differences Between Levosimendan and Milrinone on Myocardial and Hemodynamic Variables in Patients With Septic Cardiomyopathy. Effects of Norepinephrine on Right Ventricular Function in Patient With Septic Shock. [NCT02640846]	Phase 4	30 participants (Actual)	Interventional	2015-12-31	Active, not recruiting
Use of Levosimendan as Treatment of Aneurysmal SubArachnoid Hemorrhage [NCT05664191]	Phase 2	30 participants (Anticipated)	Interventional	2023-03-01	Not yet recruiting
A Clinical Study on Levosimendan Improvement of Prognosis of ARDS Patients by Optimizing Pulmonary Hemodynamics [NCT04020003]	Phase 3	120 participants (Anticipated)	Interventional	2019-07-01	Recruiting
Preoperative Levosimendan in Patients With Heart Failure Undergoing Elective Noncardiac Surgery: A Randomized, Placebocontrolled Trial. SIMPLE Study [NCT01022983]	Phase 4	0 participants (Actual)	Interventional	2011-04-30	Withdrawn(stopped due to Not finding patients for including)
LEVOSIMENDAN to Facilitate Weaning From ECMO in Severe Cardiogenic Shock Patients [NCT04728932]	Phase 3	206 participants (Anticipated)	Interventional	2021-08-27	Recruiting
[NCT00695929]		50 participants (Anticipated)	Interventional	2008-07-31	Completed
Phase 2 Prospective, Randomized, Double-Blind Pilot Study on Cardiac Output Following Corrective Open Heart Surgery in Children Less Than One Year: Use of Levosimendan Versus Milrinone. [NCT00549107]	Phase 2	40 participants (Anticipated)	Interventional	2007-09-30	Recruiting
Levosimendan Pre-Treatment in Patients Undergoing Coronary Artery Bypass Graft Surgery: a Double-Blind, Single Center, Prospective, Randomized, Placebo-Controlled Trial [NCT00610350]	Phase 4	100 participants (Actual)	Interventional	2005-01-31	Completed
Renal Effects of Levosimendan in Patients Admitted With Acute Decompensated Heart Failure [NCT00527059]	Phase 4	21 participants (Anticipated)	Interventional	2007-10-31	Not yet recruiting
Levosimendan and Inhaled Nitric Oxide for Resuscitating the Microcirculation in Septic Shock. A Randomized Controlled Trial [NCT00800306]	Phase 2	40 participants (Actual)	Interventional	2007-11-30	Completed
Efficacy of Levosimendan in Cardiac Failure After Heart Valve Surgery [NCT00154115]	Phase 4	200 participants (Anticipated)	Interventional	2005-03-31	Completed
Efficacy and Safety of Pulsed Infusions of Levosimendan in Outpatients With Advanced Heart Failure - A Multicenter, Double-blind, Placebo Controlled Prospective Trial With Two Arms [NCT01065194]	Phase 3	120 participants (Anticipated)	Interventional	2009-08-31	Recruiting
The Effects of Levosimendan on Renal Function in Patients With Low Ejection Fraction Undergoing Mitral Valve Surgery. [NCT01969071]	Phase 4	140 participants (Actual)	Interventional	2009-07-31	Completed
[NCT02012946]	Phase 4	40 participants (Anticipated)	Interventional	2013-12-31	Not yet recruiting
A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effectiveness and Safety of Levosimendan in Patients With Severe Aortic Stenosis and Heart Failure Undergoing Transcatheter Aortic Valve Replacement [NCT04573049]	Phase 4	124 participants (Anticipated)	Interventional	2020-09-01	Recruiting
Levosimendan to Reduce Mortality in High Risk Cardiac Surgery Patients. A Multicentre Randomized Controlled Trial [NCT00994825]	Phase 4	1,000 participants (Anticipated)	Interventional	2009-11-30	Completed
Interest of Levosimendan in Reducing Weaning Failures of ExtraCorporeal Life Support - ECLS. Randomized, Controlled, Multicenter, Double-blind, Multicenter Clinical Trial [NCT04158674]	Phase 3	210 participants (Anticipated)	Interventional	2020-02-24	Recruiting
Rationale and Design of a Multicenter Randomized Trial of Levosimendan to Reduce Low Cardiac Output Syndrome in Low Ejection Fraction (≤ 35%) Cardiac Surgery Patients. Spanish Randomized Clinical Trial on Levosimendan (SPARTANS Study) [NCT04179604]	Phase 2/Phase 3	300 participants (Anticipated)	Interventional	2020-06-17	Recruiting
Multicenter, Double-blind, Placebo-controlled Randomized Trial to Evaluate the Efficacy and Safety of Intravenous Administration of Intermittent Doses of Levosimendan in Ambulatory Patients With Advanced CHF: the LION-HEART Study [NCT01536132]	Phase 4	70 participants (Actual)	Interventional	2010-04-30	Completed
Effects of Levosimendan on Cellular Metabolic Alterations in Patients With Septic Shock: A Randomised Controlled Study [NCT02963454]		50 participants (Anticipated)	Interventional	2011-01-31	Recruiting
Efficacy of Levosimendan in the Critically Ill Patients With Unstable Hemodynamics (the LICI Study) - A Double Blind Randomized Pilot Study [NCT00093301]	Phase 2/Phase 3	40 participants	Interventional	2004-10-31	Recruiting
Using Transesophageal Echocardiography to Evaluate the Effect of Levosimendan on Patients With Acute Respiratory Distress Syndrome Associated With Right Ventricular Dysfunction During Mechanical Ventilation [NCT05768230]	Phase 2/Phase 3	58 participants (Anticipated)	Interventional	2023-03-22	Not yet recruiting
Levosimendan In Ambulatory Heart Failure Patients [NCT04705337]	Phase 4	350 participants (Anticipated)	Interventional	2021-01-01	Not yet recruiting
[NCT02275013]		159 participants (Actual)	Observational	2006-01-31	Completed
Interest of Levosimendan Preconditioning for Cardiac Surgery Under CEC in Heart Failure Patients With Impaired Ejection Fraction [NCT06021587]		300 participants (Anticipated)	Observational	2023-07-01	Recruiting
Preoperative Infusion of Levosimendan in High Risk Cardiac Surgery Patients: A Retrospective Study [NCT04635293]		100 participants (Actual)	Interventional	2012-01-01	Completed
Levosimendan Administration in High Risk Cardiac Surgery Patients With Pulmonary Hypertension [NCT04599816]		45 participants (Actual)	Interventional	2020-10-17	Completed
Effect of Levosimendan on Left Ventricular Systolic Function and Heart Failure After PCI in Patients With Acute Anterior Myocardial Infarction-- Multicenter Prospective Randomized Controlled Trial [NCT04970238]	Phase 4	500 participants (Anticipated)	Interventional	2021-10-31	Enrolling by invitation
Effect of Early Use of Levosimendan Versus Placebo on Top of a Conventional Strategy of Inotrope Use on a Combined Morbidity-mortality Endpoint in Patients With Cardiogenic Shock [NCT04020263]	Phase 3	610 participants (Anticipated)	Interventional	2019-12-01	Not yet recruiting
Safety and Efficacy of Levosimendan in Patients With Acute Myocardial Infarction Complicated by Symptomatic Left Ventricular Failure. [NCT00324766]	Phase 4	61 participants (Actual)	Interventional	2006-06-30	Completed
Effects of Peroral Levosimendan in the Prevention of Further Hospitalisations in Patients With Chronic Heart Failure. A Randomised, Phase II, Double-Blind, Placebo-Controlled, Multi-Centre, Parallel-Group Study [NCT00130884]	Phase 2	300 participants	Interventional	2005-03-31	Completed
Impact of Levosimendan Pretreatment on Weaning From Cardiopulmonary Bypass (CPB) in Patients With Diminished Left Ventricular Function Before Coronary Artery Bypass Grafting (CABG) [NCT00130871]	Phase 2	60 participants	Interventional	2004-01-31	Completed
Pharmacokinetics and Pharmacodynamics of Levosimendan During Cardiac Surgery [NCT00166127]	Phase 3	1 participants (Actual)	Interventional	2005-05-31	Terminated(stopped due to Unable to renegotiate an expired contract w/sponsor providing study med)
The Effect of Perioperative LevosIMendan Administration on Postoperative N-terminal pRo Brain Natriuretic Peptide Concentration in Patients With Increased cardiOVascular Risk Factors Undergoing Noncardiac surgEry - A Double-blinded Randomized Clinical Tri [NCT04329624]	Phase 3	230 participants (Anticipated)	Interventional	2020-10-10	Recruiting
Efficacy and Safety of Short-term Intravenous Treatment With Simdax® Versus Dobutrex® in Decompensated Heart Failure Patients Treated With Beta-receptor Blocking Agents. [NCT00219388]	Phase 4	60 participants	Interventional	2002-11-30	Completed
Randomized, Multicenter Evaluation of Intravenous Levosimendan Efficacy Versus Placebo in the Short Term Treatment of Decompensated Chronic Heart Failure: the REVIVE II Study. [NCT00048425]	Phase 3	600 participants	Interventional	2002-09-30	Completed
Early Management Strategies of Acute Heart Failure for Patients With NSTEMI [NCT03189901]	Phase 4	470 participants (Anticipated)	Interventional	2017-07-01	Enrolling by invitation
Survival of Patients With Acute Heart Failure in Need of Intravenous Inotropic Support: a Multicentre, Parallel-Group, Randomised, Double-Blind, Double-Dummy Study of Levosimendan Versus Dobutamine in Patients With Acute Heart Failure. [NCT00348504]	Phase 3	1,300 participants	Interventional	2003-03-31	Completed
Intracoronary Administration of Levosimendan in Cardiac Surgery Patients [NCT01500785]	Phase 4	50 participants (Actual)	Interventional	2018-06-15	Terminated(stopped due to Change of schedule)
Myocardial Hemodynamic Effects of Levosimendan [NCT00585104]	Phase 2	10 participants (Actual)	Interventional	2006-09-30	Completed
Postoperative Prolonged Vasoactive-inotropic Support and Levosimendan Use After Lung Transplantation: a Retrospective Analysis of Risk Factors and Impact on Outcomes [NCT05702333]		150 participants (Actual)	Observational	2017-02-01	Completed
Levosimendan Versus Placebo Before Tricuspid Valve Surgery in Patients With Right Ventricular Dysfunction [NCT05233202]	Phase 3	230 participants (Anticipated)	Interventional	2023-01-23	Recruiting
Acute and Chronic Protective Effects of Peri-interventional Administration of Levosimendan in ST Elevation Myocardial Infarctions [NCT03022877]		0 participants (Actual)	Interventional	2017-06-30	Withdrawn(stopped due to Rationale obsolete)
What Are the Changes in Cardiac Deformation Variables and Hemodynamic Parameters Following Changes in Cardiac Loading Conditions and After Administration of Two Different Inotropic Drugs. [NCT02408003]		30 participants (Actual)	Interventional	2014-03-31	Completed
Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET) [NCT02261948]	Phase 4	42 participants (Actual)	Interventional	2012-09-30	Completed
The Effect of Levosimendan Versus Its Combination to Magnesium Sulphate on Spinal Cord Protection Guided by NIRS in Infants Undergoing Coarctectomy: A Randomized Controlled Study. [NCT04330755]	Phase 4	40 participants (Actual)	Interventional	2021-02-04	Completed
Levosimendan and Global Longitudinal Strain Assessment in Cardiogenic Shock Sepsis (GLASSES 1): a Study Protocol for an Observational Study [NCT04141410]		35 participants (Anticipated)	Observational	2019-10-21	Recruiting
Levosimendan Versus Adrenaline in Patients With Low Left Ventricular Function Undergoing Elective On-Pump Coronary Artery Bypass Graft Surgery. A Randomized Controlled Study [NCT05222256]		52 participants (Anticipated)	Interventional	2022-03-31	Not yet recruiting
Effects of Levosimendan on Systolic Deformation and Diastolic Function in Patients Eligible for Aortic Valve Replacement With Left Ventricular Hypertrophy [NCT01188369]	Phase 4	20 participants (Actual)	Interventional	2010-09-30	Terminated(stopped due to Terminated prematurely due to high incidence of postoperative atrial fibrillation.)
Phase I Study of Two Inodilators in Neonates Undergoing Cardiovascular Surgery [NCT01576094]	Phase 1/Phase 2	20 participants (Actual)	Interventional	2009-11-30	Completed
Comparison of the Administration of Levosimendan and Placebo in the Preparation of Critical Patients for Heart Surgery [NCT01595737]	Phase 4	30 participants (Actual)	Interventional	2011-02-28	Completed
Assessment and Hemodynamic Response in CABG After Cardiopulmonary Bypass Using Intraoperative Transesophegeal Echocardiography [NCT01616069]	Phase 4	81 participants (Actual)	Interventional	2012-02-29	Completed
Repetitive Levosimendan Infusion for Patients With Advanced Chronic Heart Failure [NCT03437226]	Phase 3	264 participants (Anticipated)	Interventional	2018-03-08	Recruiting
Preoperative Optimization Levosimendan in Heart Failure Patients Undergoing Hip Fracture [NCT02972918]		19 participants (Actual)	Observational	2014-05-31	Completed
Efficacy and Clinical Outcomes of Levosimendan in E-CPR [NCT05730907]		100 participants (Anticipated)	Observational	2023-02-20	Recruiting
Expanded Access Protocol; Intermediate Size Protocol: Levosimendan Compassionate Use in Pediatric Patients With Advanced Decompensated Heart Failure Who Are Refractory to Standard Therapy [NCT02973620]		0 participants	Expanded Access		No longer available
Effects of ODM-109 on Respiratory Function in Patients With ALS. A Randomized, Double Blind, Placebo-controlled, Cross-over, 3-period, Multicenter Study With Open-label Follow-up Extension [NCT02487407]	Phase 2	66 participants (Actual)	Interventional	2015-07-31	Completed
Perioperative Use of Levosimendan in Patients With Impaired Right Ventricular Function Undergoing Cardiac Surgery With Cardiopulmonary Bypass [NCT05063370]	Phase 2	40 participants (Actual)	Interventional	2021-08-18	Active, not recruiting
Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension [NCT04718350]		40 participants (Anticipated)	Interventional	2021-01-27	Recruiting
Prospective, Randomized, Monocenter, Double Blind, Placebo-controlled Study to Investigate the Efficacy and Safety of Levosimendan in Intensive Care Patients With Acute Kidney Injury [NCT01720030]	Phase 2/Phase 3	68 participants (Actual)	Interventional	2016-09-30	Active, not recruiting
Effects of Levosimendan on Diaphragm Function in Mechanically Ventilated Patients [NCT01721434]	Phase 2/Phase 3	42 participants (Anticipated)	Interventional	2012-09-30	Recruiting
Impact of Levosimendan Preconditioning on Critical Care and In-hospital Lengths of Stay After Cardiac Surgery With Bypass Surgery [NCT05685537]		120 participants (Anticipated)	Observational	2022-12-15	Recruiting
Levosimendan Improves Heart Failure Through Regulating 3 Cardiac Specific miRNAs (miR-660-3p, miR-665 and miR-1285-3p) in Patients With Refractory Heart Failure (NYHA III-IV) [NCT04950569]	Phase 4	136 participants (Anticipated)	Interventional	2020-10-29	Recruiting
Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock [NCT04917497]		43 participants (Actual)	Observational	2011-06-30	Completed
A Double-Blind, Randomized, Placebo-Controlled Study of Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery Requiring Cardiopulmonary Bypass [NCT02025621]	Phase 3	882 participants (Actual)	Interventional	2014-07-31	Completed
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

Trial	Outcome
NCT00585104 (1) [back to overview]	Change in Left Ventricular End-diastolic Pressure (LVEDP) Using Pressure-volume Catheter.
NCT01188369 (1) [back to overview]	E/E'(Unitless)
NCT02025621 (7) [back to overview]	Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (Days)
NCT02025621 (7) [back to overview]	Incidence of Low Cardiac Output Syndrome (LCOS)
NCT02025621 (7) [back to overview]	Number of Dual Efficacy Endpoint Events
NCT02025621 (7) [back to overview]	Number of Quad Efficacy Endpoint Events
NCT02025621 (7) [back to overview]	Occurrence of All-cause Mortality From Randomization Through Day 90
NCT02025621 (7) [back to overview]	Postoperative Use of Secondary Inotrope
NCT02025621 (7) [back to overview]	Rehospitalization for Any Cause Through Day 30
NCT02261948 (3) [back to overview]	Change in DLCO (Diffusion Lung CO)
NCT02261948 (3) [back to overview]	Change in Peak VO2 (Oxygen Consumption )
NCT02261948 (3) [back to overview]	Changes in VE/VCO2
NCT03505021 (6) [back to overview]	Change From Baseline in Respiratory Function of ALSFRS-R at 48 Weeks
NCT03505021 (6) [back to overview]	Change From the Baseline in Clinical Global Impression CGI at 48 Weeks
NCT03505021 (6) [back to overview]	Combined Assessment of Function and Survival Through 48 Weeks
NCT03505021 (6) [back to overview]	Supine Borg Category Ratio 10 Scale at 12 Weeks
NCT03505021 (6) [back to overview]	Supine Slow Vital Capacity (SVC)
NCT03505021 (6) [back to overview]	Time to Respiratory Event Through 48 Weeks
NCT03948178 (13) [back to overview]	Adverse Events Recording
NCT03948178 (13) [back to overview]	Health Care Service Use During the Study (Days Spent in an Institutional Facility)
NCT03948178 (13) [back to overview]	Health Care Service Use During the Study(Stays in Hospital)
NCT03948178 (13) [back to overview]	Health Care Service Use During the Study(Visits to the Emergency Room)
NCT03948178 (13) [back to overview]	Need for Respiratory Support Device
NCT03948178 (13) [back to overview]	Number of Subjects Requiring Health and Home Care Resource Use
NCT03948178 (13) [back to overview]	12-lead Electrocardiogram Assessments
NCT03948178 (13) [back to overview]	Borg Category Ratio 10 Scale (CR 10)
NCT03948178 (13) [back to overview]	Disease Progression
NCT03948178 (13) [back to overview]	Pulse/Heart Rate Assessment
NCT03948178 (13) [back to overview]	Revised ALS Functional Rating Scale (ALSFRS-R)
NCT03948178 (13) [back to overview]	Subject's Status for Tracheostomy and Survival
NCT03948178 (13) [back to overview]	Supine Slow Vital Capacity (SVC)

Change in Left Ventricular End-diastolic Pressure (LVEDP) Using Pressure-volume Catheter.

Left ventricular end-diastolic pressure (LVEDP) recorded from CD Leycom ConductNT software analysis. (NCT00585104)
Timeframe: From baseline to 30-minutes after levosimendan started.

Intervention	mmHg (Mean)
Levosimendan, Compare Heart Function and Metabolism	5.67

Intervention	Participants (Count of Participants)
	Baseline abnormal ECG	Week 2 abnormal ECG	Week 4 abnormal ECG	Month 3 abnormal ECG	Month 6 abnormal ECG	End-of study abnormal ECG
Levosimendan	69	56	43	27	11	36

Intervention	units on a scale (Mean)
	Baseline in Borg score Supine position	Change from baseline in Borg score supine at week 2	chenge from baseline in Borg score week 4	Change from baseline in Borg score supine at month 3	Change from baseline in Borg score supine at month 6	Change from baseline in Borg score supine at end of study	Baseline Borg score sitting	Change from baseline in Borg score sitting at week 2	Change from baseline in Borg score sitting at week 4	Change from baseline in Borg score sitting at month 3	Change from baseline in Borg score sitting month 6	Change from baseline in Borg score sitting at end of study
Levosimendan	2.52	0.15	0.40	0.54	1.61	1.58	2.19	0.01	0.34	0.61	1.2	1.07

Intervention	Participants (Count of Participants)
	Total withdrawal due to sponsor terminating the study	Number of withdrawals due to disease progression
Levosimendan	164	30

Intervention	beats per minute (bpm) (Mean)
	Change in pulse rate at week 2	Change in pulse rate at 4 weeks	Change in pulse rate at week 6	chnage in pulse rate at Month 3	Change in pulse rate at month 6	Change in pulse rate at end-of-study	Change in Heart rate at week 2	Change in Heart rate at week 4	Change in heart rate at Month 3	Change in heart rate at month 6	Change in heart rate at end-of-study	Baseline supine pulse rate	Baseline supine heart rate
Levosimendan	7.0	10.0	8.5	10.4	12.8	3.5	9.1	12.8	12.6	15.0	5.3	75.8	73.5

Intervention	Score on a scale (Mean)
	Change from baseline in respiratory function ALSFR-S at end of study	Baseline respiratory ALSFRS-R
Levosimendan	-1.2	9.4

Intervention	Participants (Count of Participants)
	Number of participants who died from baseline to end of the study treatment	Number of participants requiring tracheostomy from baseline to the end of the study treatment
Levosimendan	5	0

Intervention	% of predicted normal (Mean)
	Change from baseline in supine SVC at week 2	Change from baseline in supine SVC at week 4	Change from baseline in supine SVC at month 3	Change from baseline in supine SVC at month 6	Change from baseline in supine SVC at the end of the study	Change from baseline in sitting SVC at week 2	Change from baseline in sitting SVC at week 4	Change from baseline in sitting SVC month 3	Change from baseline in sitting SVC month 6	Change from baseline in sitting SVC at the end of the study	Baseline Supine SVC (% predicted normal	Baseline Sitting SVC (% predicted normal)
Levosimendan	1.5	0.8	-3.5	-5.3	-5.6	1.4	2.1	-1.9	-6.1	-7.3	54.4	61.4

Intervention	Score on a scale/month (Least Squares Mean)
Levosimendan	-0.191
Placebo for Levosimendan	-0.205

Intervention	Scores on a rank scale (Least Squares Mean)
Levosimendan	239.85
Placebo for Levosimendan	229.16

Intervention	percentage (Least Squares Mean)
Levosimendan	-6.731
Placebo for Levosimendan	-6.988

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Studies (1,240)

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Research Demand Index: 27.60

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Clinical Trials (91)

Trial Overview

Trial Outcomes

Change in Left Ventricular End-diastolic Pressure (LVEDP) Using Pressure-volume Catheter.

E/E'(Unitless)

Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (Days)

Incidence of Low Cardiac Output Syndrome (LCOS)

Number of Dual Efficacy Endpoint Events

Number of Quad Efficacy Endpoint Events

Occurrence of All-cause Mortality From Randomization Through Day 90

Postoperative Use of Secondary Inotrope

Rehospitalization for Any Cause Through Day 30

Change in DLCO (Diffusion Lung CO)

Change in Peak VO2 (Oxygen Consumption )

Changes in VE/VCO2

Change From Baseline in Respiratory Function of ALSFRS-R at 48 Weeks

Change From the Baseline in Clinical Global Impression CGI at 48 Weeks

Combined Assessment of Function and Survival Through 48 Weeks

Supine Borg Category Ratio 10 Scale at 12 Weeks

Supine Slow Vital Capacity (SVC)

Time to Respiratory Event Through 48 Weeks

Adverse Events Recording

Health Care Service Use During the Study (Days Spent in an Institutional Facility)

Health Care Service Use During the Study(Stays in Hospital)

Health Care Service Use During the Study(Visits to the Emergency Room)

Need for Respiratory Support Device

Number of Subjects Requiring Health and Home Care Resource Use

12-lead Electrocardiogram Assessments

Borg Category Ratio 10 Scale (CR 10)

Disease Progression

Pulse/Heart Rate Assessment

Revised ALS Functional Rating Scale (ALSFRS-R)

Subject's Status for Tracheostomy and Survival

Supine Slow Vital Capacity (SVC)

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