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Int J Cardiol. 2016 Nov 1;222:303-312. doi: 10.1016/j.ijcard.2016.07.202. Epub 2016 Jul 29.

Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper.

Author information

1
Heart Failure Unit, Department of Cardiology, National and Kapodistrian University of Athens, Athens University Hospital Attikon, Athens, Greece. Electronic address: dimitrios_farmakis@yahoo.com.
2
Department of Anesthesia and Surgical ICU, University of Santiago de Compostela, Santiago de Compostela, Spain.
3
Cardiology Clinic Rabin Medical Center, Petah Tikva, Israel.
4
Cardiology Department Centro Hospitalar Lisboa Norte, Hospital de Santa Maria, Lisbon, Portugal.
5
Department of Cardiovascular, Respiratory, Nephrology, Anesthesiology and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.
6
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.
7
Section of Anaesthetics, Pain Medicine and Intensive Care, Imperial College London, London, UK.
8
Cardiology Clinic, Heart Institute, Hadassah University Hospital Jerusalem, Israel.
9
Laboratory of Physiology, University East Piedmont, Novara, Italy.
10
Department of Anaesthesia and Critical Care Medicine, Cardiothoracic Anaesthesia and Intensive Care, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy.
11
Emergency Medicine, Helsinki University, Helsinki University Hospital, Helsinki, Finland.
12
Heart Failure Service, Carmel Medical Center, Haifa, Israel.
13
Department of Intensive Care, Radboud University Medical Center, Nijmegen, The Netherlands.
14
Emergency Cardiology Department, University Hospital Center, Zagreb, Croatia.
15
Department of Cardiology, G. Gennimatas General Hospital, Athens, Greece.
16
Critical Care Proprietary Products, Orion Pharma, Espoo, Finland.
17
Department of Anesthesiology and Intensive Care, State Research Institute of Circulation Pathology, Novosibirsk, Russia.
18
Département d'Anesthésie Réanimation Chirurgicale, Hôpital Bichat-Claude Bernard, Université Paris-Diderot, Hôpitaux Uiversitaires Paris Nord Val de Seine, Paris, France.
19
Intensive Care Unit, Hospital de Sant Joan Despí Moisès Broggi, Sant Joan Despí, Barcelona, Spain.
20
Cardiology Clinic, University and Civil Hospital, Brescia, Italy.
21
Department of Anesthesiology and Intensive Care, Policlinico "Umberto I" University of Rome "La Sapienza", Rome, Italy.
22
Department of Cardiology, Sismanoglio and Amalia Fleming General Hospital, Athens, Greece.
23
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
24
Department of Anesthesiology and Intensive Care Unit for Cardiac Surgery Patients, Institute of Cardiology, Kiev, Ukraine.
25
Innere Medizin III, Universitätsklinik Innsbruck, , Innsbruck, Austria.
26
Department Cardiothoracic Anaesthesia, Heart Centre, Rigshospitalet, Copenhagen, , Denmark.
27
Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
28
Cardiothoracic Anaesthesiology and Intensive Care, Department of Anaesthesiology and Intensive Care Medicine, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
29
Department of Anesthesiology and Intensive Care Medicine, Institute of Clinical Sciences, University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden.
30
Medizinische Klinik II, Klinikum Weiden, Weiden, Germany.
31
Department of Cardiology, University Clinical Centre Ljubljana, Ljubljana, Slovenia.
32
Department Of Cardiology, Cumhuriyet University, Sivas, Turkey.
33
Department of Intensive Cardiac Therapy, Medical University, Łodz, Poland.
34
Heart Failure Unit, Department of Cardiology, National and Kapodistrian University of Athens, Athens University Hospital Attikon, Athens, Greece.

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.

KEYWORDS:

Cardiogenic shock; Cardioprotection; Heart failure; Inotropes; Levosimendan; Organ protection

PMID:
27498374
DOI:
10.1016/j.ijcard.2016.07.202
[Indexed for MEDLINE]
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