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.

Cardiology Clinic Heart Institute Hadassah University Hospital Jerusalem Israel

Cardiology Clinic Rabin Medical Center Petah Tikva Israel

Cardiology Clinic University and Civil Hospital Brescia Italy

Cardiology Department Centro Hospitalar Lisboa Norte Hospital de Santa Maria Lisbon Portugal

Cardiothoracic Anaesthesiology and Intensive Care Department of Anaesthesiology and Intensive Care Medicine Institute for Clinical and Experimental Medicine Prague Czech Republic

Critical Care Proprietary Products Orion Pharma Espoo Finland

Département d'Anesthésie Réanimation Chirurgicale Hôpital Bichat Claude Bernard Université Paris Diderot Hôpitaux Uiversitaires Paris Nord Val de Seine Paris France

Department Cardiothoracic Anaesthesia Heart Centre Rigshospitalet Copenhagen Denmark

Department of Anaesthesia and Critical Care Medicine Cardiothoracic Anaesthesia and Intensive Care Azienda Ospedaliero Universitaria Pisana Pisa Italy

Department of Anesthesia and Surgical ICU University of Santiago de Compostela Santiago de Compostela Spain

Department of Anesthesiology and Intensive Care Medicine Institute of Clinical Sciences University of Gothenburg Sahlgrenska University Hospital Gothenburg Sweden

Department of Anesthesiology and Intensive Care Policlinico Umberto 1 University of Rome La Sapienza Rome Italy

Department of Anesthesiology and Intensive Care State Research Institute of Circulation Pathology Novosibirsk Russia

Department of Anesthesiology and Intensive Care Unit for Cardiac Surgery Patients Institute of Cardiology Kiev Ukraine

Department Of Cardiology Cumhuriyet University Sivas Turkey

Department of Cardiology G Gennimatas General Hospital Athens Greece

Department of Cardiology Sismanoglio and Amalia Fleming General Hospital Athens Greece

Department of Cardiology University Clinical Centre Ljubljana Ljubljana Slovenia

Department of Cardiovascular Respiratory Nephrology Anesthesiology and Geriatric Sciences Sapienza University of Rome Rome Italy

Department of Cardiovascular Sciences University of Leuven Leuven Belgium

Department of Intensive Cardiac Therapy Medical University Łodz Poland

Department of Intensive Care Radboud University Medical Center Nijmegen The Netherlands

Division of Clinical Physiology Department of Cardiology Faculty of Medicine University of Debrecen Debrecen Hungary

Emergency Cardiology Department University Hospital Center Zagreb Croatia

Emergency Medicine Helsinki University Helsinki University Hospital Helsinki Finland

Heart Failure Service Carmel Medical Center Haifa Israel

Heart Failure Unit Department of Cardiology National and Kapodistrian University of Athens Athens University Hospital Attikon Athens Greece

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

Innere Medizin 3 Universitätsklinik Innsbruck Innsbruck Austria

Intensive Care Unit Hospital de Sant Joan Despí Moisès Broggi Sant Joan Despí Barcelona Spain

Laboratory of Physiology University East Piedmont Novara Italy

Medizinische Klinik 2 Klinikum Weiden Weiden Germany

Section of Anaesthetics Pain Medicine and Intensive Care Imperial College London London UK

References provided by Crossref.org

Levosimendan Efficacy and Safety: 20 Years of SIMDAX in Clinical Use

Levosimendan Efficacy and Safety: 20 years of SIMDAX in Clinical Use

Short-Term Therapies for Treatment of Acute and Advanced Heart Failure-Why so Few Drugs Available in Clinical Use, Why Even Fewer in the Pipeline?

Use of Levosimendan in Intensive Care Unit Settings: An Opinion Paper