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

Dimitrios Farmakis, Julian Alvarez, Tuvia Ben Gal, Dulce Brito, Francesco Fedele, Candida Fonseca, Anthony C Gordon, Israel Gotsman, Elena Grossini, Fabio Guarracino, Veli-Pekka Harjola, Yaron Hellman, Leo Heunks, Visnja Ivancan, Apostolos Karavidas, Matti Kivikko, Vladimir Lomivorotov, Dan Longrois, Josep Masip, Marco Metra & 15 others Andrea Morelli, Maria Nikolaou, Zoltán Papp, Alexander Parkhomenko, Gerhard Poelzl, Piero Pollesello, Hanne Berg Ravn, Steffen Rex, Hynek Riha, Sven-Erik Ricksten, Robert H G Schwinger, Bojan Vrtovec, M Birhan Yilmaz, Marzenna Zielinska, John Parissis

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)303-12
Number of pages10
JournalInternational Journal of Cardiology
Volume222
DOIs
Publication statusPublished - 1 Nov 2016

Cite this

Farmakis, Dimitrios ; Alvarez, Julian ; Gal, Tuvia Ben ; Brito, Dulce ; Fedele, Francesco ; Fonseca, Candida ; Gordon, Anthony C ; Gotsman, Israel ; Grossini, Elena ; Guarracino, Fabio ; Harjola, Veli-Pekka ; Hellman, Yaron ; Heunks, Leo ; Ivancan, Visnja ; Karavidas, Apostolos ; Kivikko, Matti ; Lomivorotov, Vladimir ; Longrois, Dan ; Masip, Josep ; Metra, Marco ; Morelli, Andrea ; Nikolaou, Maria ; Papp, Zoltán ; Parkhomenko, Alexander ; Poelzl, Gerhard ; Pollesello, Piero ; Ravn, Hanne Berg ; Rex, Steffen ; Riha, Hynek ; Ricksten, Sven-Erik ; Schwinger, Robert H G ; Vrtovec, Bojan ; Yilmaz, M Birhan ; Zielinska, Marzenna ; Parissis, John. / Levosimendan beyond inotropy and acute heart failure : Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper. In: International Journal of Cardiology. 2016 ; Vol. 222. pp. 303-12.
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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.",
keywords = "Journal Article, Review",
author = "Dimitrios Farmakis and Julian Alvarez and Gal, {Tuvia Ben} and Dulce Brito and Francesco Fedele and Candida Fonseca and Gordon, {Anthony C} and Israel Gotsman and Elena Grossini and Fabio Guarracino and Veli-Pekka Harjola and Yaron Hellman and Leo Heunks and Visnja Ivancan and Apostolos Karavidas and Matti Kivikko and Vladimir Lomivorotov and Dan Longrois and Josep Masip and Marco Metra and Andrea Morelli and Maria Nikolaou and Zolt{\'a}n Papp and Alexander Parkhomenko and Gerhard Poelzl and Piero Pollesello and Ravn, {Hanne Berg} and Steffen Rex and Hynek Riha and Sven-Erik Ricksten and Schwinger, {Robert H G} and Bojan Vrtovec and Yilmaz, {M Birhan} and Marzenna Zielinska and John Parissis",
note = "Copyright {\circledC} 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.ijcard.2016.07.202",
language = "English",
volume = "222",
pages = "303--12",
journal = "International Journal of Cardiology",
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Farmakis, D, Alvarez, J, Gal, TB, Brito, D, Fedele, F, Fonseca, C, Gordon, AC, Gotsman, I, Grossini, E, Guarracino, F, Harjola, V-P, Hellman, Y, Heunks, L, Ivancan, V, Karavidas, A, Kivikko, M, Lomivorotov, V, Longrois, D, Masip, J, Metra, M, Morelli, A, Nikolaou, M, Papp, Z, Parkhomenko, A, Poelzl, G, Pollesello, P, Ravn, HB, Rex, S, Riha, H, Ricksten, S-E, Schwinger, RHG, Vrtovec, B, Yilmaz, MB, Zielinska, M & Parissis, J 2016, 'Levosimendan beyond inotropy and acute heart failure: Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper' International Journal of Cardiology, vol. 222, pp. 303-12. https://doi.org/10.1016/j.ijcard.2016.07.202

Levosimendan beyond inotropy and acute heart failure : Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper. / Farmakis, Dimitrios; Alvarez, Julian; Gal, Tuvia Ben; Brito, Dulce; Fedele, Francesco; Fonseca, Candida; Gordon, Anthony C; Gotsman, Israel; Grossini, Elena; Guarracino, Fabio; Harjola, Veli-Pekka; Hellman, Yaron; Heunks, Leo; Ivancan, Visnja; Karavidas, Apostolos; Kivikko, Matti; Lomivorotov, Vladimir; Longrois, Dan; Masip, Josep; Metra, Marco; Morelli, Andrea; Nikolaou, Maria; Papp, Zoltán; Parkhomenko, Alexander; Poelzl, Gerhard; Pollesello, Piero; Ravn, Hanne Berg; Rex, Steffen; Riha, Hynek; Ricksten, Sven-Erik; Schwinger, Robert H G; Vrtovec, Bojan; Yilmaz, M Birhan; Zielinska, Marzenna; Parissis, John.

In: International Journal of Cardiology, Vol. 222, 01.11.2016, p. 303-12.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Levosimendan beyond inotropy and acute heart failure

T2 - Evidence of pleiotropic effects on the heart and other organs: An expert panel position paper

AU - Farmakis, Dimitrios

AU - Alvarez, Julian

AU - Gal, Tuvia Ben

AU - Brito, Dulce

AU - Fedele, Francesco

AU - Fonseca, Candida

AU - Gordon, Anthony C

AU - Gotsman, Israel

AU - Grossini, Elena

AU - Guarracino, Fabio

AU - Harjola, Veli-Pekka

AU - Hellman, Yaron

AU - Heunks, Leo

AU - Ivancan, Visnja

AU - Karavidas, Apostolos

AU - Kivikko, Matti

AU - Lomivorotov, Vladimir

AU - Longrois, Dan

AU - Masip, Josep

AU - Metra, Marco

AU - Morelli, Andrea

AU - Nikolaou, Maria

AU - Papp, Zoltán

AU - Parkhomenko, Alexander

AU - Poelzl, Gerhard

AU - Pollesello, Piero

AU - Ravn, Hanne Berg

AU - Rex, Steffen

AU - Riha, Hynek

AU - Ricksten, Sven-Erik

AU - Schwinger, Robert H G

AU - Vrtovec, Bojan

AU - Yilmaz, M Birhan

AU - Zielinska, Marzenna

AU - Parissis, John

N1 - Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

KW - Journal Article

KW - Review

U2 - 10.1016/j.ijcard.2016.07.202

DO - 10.1016/j.ijcard.2016.07.202

M3 - Article

VL - 222

SP - 303

EP - 312

JO - International Journal of Cardiology

JF - International Journal of Cardiology

SN - 0167-5273

ER -