title: Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper.
abstract: Levosimendan is a positive inotrope with vasodilating properties (inodilator) indicated for decompensated heart failure (HF) patients with low cardiac output. Accumulated evidence supports several pleiotropic effects of levosimendan beyond inotropy, the heart and decompensated HF. Those effects are not readily explained by cardiac function enhancement and seem to be related to additional properties of the drug such as anti-inflammatory, anti-oxidative and anti-apoptotic ones. Mechanistic and proof-of-concept studies are still required to clarify the underlying mechanisms involved, while properly designed clinical trials are warranted to translate preclinical or early-phase clinical data into more robust clinical evidence. The present position paper, derived by a panel of 35 experts in the field of cardiology, cardiac anesthesiology, intensive care medicine, cardiac physiology, and cardiovascular pharmacology from 22 European countries, compiles the existing evidence on the pleiotropic effects of levosimendan, identifies potential novel areas of clinical application and defines the corresponding gaps in evidence and the required research efforts to address those gaps.
authors: Heart Failure Unit, Department of Cardiology, National and Kapodistrian University of Athens, Athens University Hospital Attikon, Athens, Greece. Electronic address: dimitrios_farmakis@yahoo.com.
authors: Dimitrios
authors: D
authors: Farmakis
authors: Department of Anesthesia and Surgical ICU, University of Santiago de Compostela, Santiago de Compostela, Spain.
authors: Julian
authors: J
authors: Alvarez
authors: Cardiology Clinic Rabin Medical Center, Petah Tikva, Israel.
authors: Tuvia Ben
authors: TB
authors: Gal
authors: Cardiology Department Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.
authors: Dulce
authors: D
authors: Brito
authors: Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.
authors: Francesco
authors: F
authors: Fedele
authors: Heart Failure Unit, Department of Internal Medicine, Hospital São Francico Xavier, Centro Hospitalar Lisboa Ocidental, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
authors: Candida
authors: C
authors: Fonseca
authors: Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
authors: Anthony C
authors: AC
authors: Gordon
authors: Cardiology Clinic, Heart Institute, Hadassah University Hospital Jerusalem, Israel.
authors: Israel
authors: I
authors: Gotsman
authors: Laboratory of Physiology, University East Piedmont, Novara, Italy.
authors: Elena
authors: E
authors: Grossini
authors: Department of Anaesthesia and Critical Care Medicine, Cardiothoracic Anaesthesia and Intensive Care, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
authors: Fabio
authors: F
authors: Guarracino
authors: Emergency Medicine, Helsinki University, Helsinki University Hospital, Helsinki, Finland.
authors: Veli-Pekka
authors: VP
authors: Harjola
authors: Heart Failure Service, Carmel Medical Center, Haifa, Israel.
authors: Yaron
authors: Y
authors: Hellman
authors: Department of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands.
authors: Leo
authors: L
authors: Heunks
authors: Emergency Cardiology Department, University Hospital Center, Zagreb, Croatia.
authors: Visnja
authors: V
authors: Ivancan
authors: Department of Cardiology, G. Gennimatas General Hospital, Athens, Greece.
authors: Apostolos
authors: A
authors: Karavidas
authors: Critical Care Proprietary Products, Orion Pharma, Espoo, Finland.
authors: Matti
authors: M
authors: Kivikko
authors: Department of Anesthesiology and Intensive Care, State Research Institute of Circulation Pathology, Novosibirsk, Russia.
authors: Vladimir
authors: V
authors: Lomivorotov
authors: Département d'Anesthésie Réanimation Chirurgicale, Hôpital Bichat-Claude Bernard, Université Paris-Diderot, Hôpitaux Uiversitaires Paris Nord Val de Seine, Paris, France.
authors: Dan
authors: D
authors: Longrois
authors: Intensive Care Unit, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, Spain.
authors: Josep
authors: J
authors: Masip
authors: Cardiology Clinic, University and Civil Hospital, Brescia, Italy.
authors: Marco
authors: M
authors: Metra
authors: Department of Anesthesiology and Intensive Care, Policlinico "Umberto I" University of Rome "La Sapienza", Rome, Italy.
authors: Andrea
authors: A
authors: Morelli
authors: Department of Cardiology, Sismanoglio and Amalia Fleming General Hospital, Athens, Greece.
authors: Maria
authors: M
authors: Nikolaou
authors: Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
authors: Zoltán
authors: Z
authors: Papp
authors: Department of Anesthesiology and Intensive Care Unit for Cardiac Surgery Patients, Institute of Cardiology, Kiev, Ukraine.
authors: Alexander
authors: A
authors: Parkhomenko
authors: Innere Medizin III, Universitätsklinik Innsbruck, , Innsbruck, Austria.
authors: Gerhard
authors: G
authors: Poelzl
authors: Critical Care Proprietary Products, Orion Pharma, Espoo, Finland.
authors: Piero
authors: P
authors: Pollesello
authors: Department Cardiothoracic Anaesthesia, Heart Centre, Rigshospitalet, Copenhagen, , Denmark.
authors: Hanne Berg
authors: HB
authors: Ravn
authors: Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
authors: Steffen
authors: S
authors: Rex
authors: Cardiothoracic Anaesthesiology and Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors: Hynek
authors: H
authors: Riha
authors: Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors: Sven-Erik
authors: SE
authors: Ricksten
authors: Medizinische Klinik II, Klinikum Weiden, Weiden, Germany.
authors: Robert H G
authors: RHG
authors: Schwinger
authors: Department of Cardiology, University Clinical Centre Ljubljana, Ljubljana, Slovenia.
authors: Bojan
authors: B
authors: Vrtovec
authors: Department Of Cardiology, Cumhuriyet University, Sivas, Turkey.
authors: M Birhan
authors: MB
authors: Yilmaz
authors: Department of Intensive Cardiac Therapy, Medical University, Łodz, Poland.
authors: Marzenna
authors: M
authors: Zielinska
authors: Heart Failure Unit, Department of Cardiology, National and Kapodistrian University of Athens, Athens University Hospital Attikon, Athens, Greece.
authors: John
authors: J
authors: Parissis
mesh_terms: D000208:Acute Disease; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic / Q000379:methods / Q000592:standards; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D000077464:Simendan; D016896:Treatment Outcome
chemical_list: D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D000077464:Simendan
keywords: Cardiogenic shock; Cardioprotection; Heart failure; Inotropes; Levosimendan; Organ protection