Preoperative Levosimendan Administration in Heart Transplant Patients with Severe Hepatic and Renal Impairment: A Retrospective Study.

BACKGROUND The cardio-renal syndrome and hepatic impairment play a critical role in end-stage heart failure (HF). Levosimendan is an effective inotropic agent used to maintain cardiac output similar to classic cardiotonic like dobutamine/dopamine. This current research aims to investigate the clinical outcomes of levosimendan and dobutamine/dopamine in Chinese heart transplant awaiting patients with severe hepatic or renal impairment. METHODS We performed a retrospective analysis of 568 heart transplant awaiting individuals with severe hepatic or renal impairment who treated with levosimendan or dobutamine/dopamine in our institution between January 2015 and December 2020. Univariate Cox proportional hazard models and Kaplan-Meier survival curves were applied. The primary endpoint was defined as death included inhospital mortality and the mortality at 30 days, 90 days, 180 days and 1 year after heart transplantation. RESULTS There were no significant differences in mortality rate at 30, 90, 180 days and 1 years after heart transplantation between the levosimendan and non-levosimendan groups, or between subgroups of patients with severe hepatic impairment or renal impairment. The results were consistent before and after propensity score matching. CONCLUSIONS In the population with advanced heart failure awaiting heart transplantation, levosimendan did not increase short- or long-term mortality rates after surgery compared to dobutamine/dopamine, regardless of their hepatic or renal function. Severe hepatic or renal impairment were not necessarily considered a contraindication for levosimendan in these patients.

[1]  S. Ricksten,et al.  Effects of levosimendan on renal blood flow and glomerular filtration in patients with acute kidney injury after cardiac surgery: a double blind, randomized placebo-controlled study , 2021, Critical Care.

[2]  Changqing Zhu,et al.  Renoprotective effects of levosimendan on acute kidney injury following cardiac arrest via anti‐inflammation, anti‐apoptosis, and ERK activation , 2021, FEBS open bio.

[3]  Ravi B. Patel,et al.  Kidney Function and Outcomes in Patients Hospitalized with Heart Failure. , 2021, Journal of the American College of Cardiology.

[4]  W. Ho,et al.  Levosimendan use in patients with acute heart failure and reduced ejection fraction with or without severe renal dysfunction in critical cardiac care units: a multi-institution database study , 2021, Annals of Intensive Care.

[5]  A. Israni,et al.  OPTN/SRTR 2019 Annual Data Report: Heart , 2021, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[6]  R. Sherer,et al.  Remdesivir Use in the Setting of Severe Renal Impairment: A Theoretical Concern or Real Risk? , 2020, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[7]  M. Kearney,et al.  Association of heart failure and its comorbidities with loss of life expectancy , 2020, Heart.

[8]  L. Garrido-Sanchez,et al.  Renal and Neurologic Benefit of Levosimendan vs Dobutamine in Patients With Low Cardiac Output Syndrome After Cardiac Surgery: Clinical Trial FIM-BGC-2014-01 , 2020, Frontiers in Pharmacology.

[9]  K. Gauvreau,et al.  Long-Term Survival After Heart Transplantation at Centers Stratified by Short-Term Performance. , 2019, Circulation. Heart failure.

[10]  Yuan-qiang Lu,et al.  Multiorgan Drug Action of Levosimendan in Critical Illnesses , 2019, BioMed research international.

[11]  A. Zangrillo,et al.  Effect of Levosimendan on Renal Outcome in Cardiac Surgery Patients With Chronic Kidney Disease and Perioperative Cardiovascular Dysfunction: A Substudy of a Multicenter Randomized Trial. , 2018, Journal of cardiothoracic and vascular anesthesia.

[12]  M. Asif A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites. , 2018, Mini-Reviews in Medical Chemistry.

[13]  E. Bollano,et al.  Differential Effects of Levosimendan and Dobutamine on Glomerular Filtration Rate in Patients With Heart Failure and Renal Impairment:A Randomized Double‐Blind Controlled Trial , 2018, Journal of the American Heart Association.

[14]  N. Brunetti,et al.  Liver disease and heart failure: Back and forth. , 2017, European journal of internal medicine.

[15]  G. Filippatos,et al.  Heart failure and kidney dysfunction: epidemiology, mechanisms and management , 2016, Nature Reviews Nephrology.

[16]  J. Foley,et al.  Comparison of vildagliptin and sitagliptin in patients with type 2 diabetes and severe renal impairment: a randomised clinical trial , 2015, Diabetologia.

[17]  A. Abdelrahman,et al.  Molecular mechanisms contributing to the protective effect of levosimendan in liver ischemia-reperfusion injury. , 2014, European journal of pharmacology.

[18]  L. Stevenson,et al.  Quantifying the effect of cardiorenal syndrome on mortality after left ventricular assist device implant. , 2013, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[19]  F. Despas,et al.  Pharmacology of levosimendan: inotropic, vasodilatory and cardioprotective effects , 2013, Journal of clinical pharmacy and therapeutics.

[20]  B. Massie,et al.  Effect of levosimendan on the short-term clinical course of patients with acutely decompensated heart failure. , 2013, JACC. Heart failure.

[21]  M. Yılmaz,et al.  Effect of levosimendan in patients with severe systolic heart failure and worsening renal function. , 2012, Arquivos brasileiros de cardiologia.

[22]  I. O. Erroz,et al.  Treatment of Acute Heart Failure Using Levosimendan for a Patient With Dilated Cardiomyopathy, Chronic Renal Failure, and Hypertension , 2011, Pediatric Cardiology.

[23]  S. Ramalingam,et al.  Phase I study of vorinostat in patients with advanced solid tumors and hepatic dysfunction: a National Cancer Institute Organ Dysfunction Working Group study. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  P. Pentikäinen,et al.  Pharmacokinetics of Intravenous Levosimendan and Its Metabolites in Subjects With Hepatic Impairment , 2008, Journal of clinical pharmacology.

[25]  Pingfu Fu,et al.  Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of renal dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[26]  M. Bunc,et al.  Levosimendan improves renal function in patients with advanced chronic heart failure awaiting cardiac transplantation. , 2007, Journal of cardiac failure.

[27]  J. Doroshow,et al.  Dose-Escalating and Pharmacologic Study of Oxaliplatin in Adult Cancer Patients with Impaired Hepatic Function: A National Cancer Institute Organ Dysfunction Working Group Study , 2007, Clinical Cancer Research.

[28]  A. Cohen-Solal,et al.  Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. , 2007, JAMA.

[29]  C. Stefanadis,et al.  Levosimendan: beyond its simple inotropic effect in heart failure. , 2007, Pharmacology & therapeutics.

[30]  G. Filippatos,et al.  Effects of levosimendan versus dobutamine on inflammatory and apoptotic pathways in acutely decompensated chronic heart failure. , 2006, The American journal of cardiology.

[31]  G. Filippatos,et al.  Levosimendan for the treatment of acute heart failure syndromes , 2005, Expert Opinion on Pharmacotherapy.

[32]  E. Foster,et al.  Effects of Intravenous Levosimendan on Human Coronary Vasomotor Regulation, Left Ventricular Wall Stress, and Myocardial Oxygen Uptake , 2005, Circulation.

[33]  P. Pentikäinen,et al.  Pharmacokinetics of levosimendan and its circulating metabolites in patients with heart failure after an extended continuous infusion of levosimendan. , 2004, British journal of clinical pharmacology.

[34]  J. Cleland,et al.  Efficacy and safety of intravenous levosimendan compared with dobutamine in severe low-output heart failure (the LIDO study): a randomised double-blind trial , 2002, The Lancet.

[35]  M. Nieminen,et al.  Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. , 1998, European heart journal.

[36]  F. Gilsanz,et al.  Levosimendan as a treatment for acute renal failure associated with cardiogenic shock after hip fracture. , 2017, Brazilian journal of anesthesiology.

[37]  J. Doroshow,et al.  Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  P. Pentikäinen,et al.  Effect of Severe Renal Failure and Haemodialysis on the Pharmacokinetics of Levosimendan and Its Metabolites , 2007, Clinical pharmacokinetics.

[39]  H. Iida,et al.  Myocardial efficiency during levosimendan infusion in congestive heart failure , 2000, Clinical pharmacology and therapeutics.