Treatments targeting inotropy

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Maack , C , Eschenhagen , T , Hamdani , N , Heinzel , F R , Lyon , A R , Manstein , D J , Metzger , J , Papp , Z , Tocchetti , C G , Yilmaz , M B , Anker , S D , Balligand , J-L , Bauersachs , J , Brutsaert , D , Carrier , L , Chlopicki , S , Cleland , J G , de Boer , R A , Dietl , A , Fischmeister , R , Harjola , V-P , Heymans , S , Hilfiker-Kleiner , D , Holzmeister , J , de Keulenaer , G , Limongelli , G , Linke , W A , Lund , L H , Masip , J , Metra , M , Mueller , C , Pieske , B , Ponikowski , P , Ristic , A , Ruschitzka , F , Seferovic , P M , Skouri , H , Zimmermann , W H & Mebazaa , A 2019 , ' Treatments targeting inotropy ' , European Heart Journal , vol. 40 , no. 44 , pp. 3626-3640 . https://doi.org/10.1093/eurheartj/ehy600

Title: Treatments targeting inotropy
Author: Maack, Christoph; Eschenhagen, Thomas; Hamdani, Nazha; Heinzel, Frank R.; Lyon, Alexander R.; Manstein, Dietmar J.; Metzger, Joseph; Papp, Zoltan; Tocchetti, Carlo G.; Yilmaz, M. Birhan; Anker, Stefan D.; Balligand, Jean-Luc; Bauersachs, Johann; Brutsaert, Dirk; Carrier, Lucie; Chlopicki, Stefan; Cleland, John G.; de Boer, Rudolf A.; Dietl, Alexander; Fischmeister, Rodolphe; Harjola, Veli-Pekka; Heymans, Stephane; Hilfiker-Kleiner, Denise; Holzmeister, Johannes; de Keulenaer, Gilles; Limongelli, Giuseppe; Linke, Wolfgang A.; Lund, Lars H.; Masip, Josep; Metra, Marco; Mueller, Christian; Pieske, Burkert; Ponikowski, Piotr; Ristic, Arsen; Ruschitzka, Frank; Seferovic, Petar M.; Skouri, Hadi; Zimmermann, Wolfram H.; Mebazaa, Alexandre
Contributor: University of Helsinki, HUS Emergency Medicine and Services
Date: 2019-11-21
Language: eng
Number of pages: 15
Belongs to series: European Heart Journal
ISSN: 0195-668X
URI: http://hdl.handle.net/10138/309687
Abstract: Acute heart failure (HF) and in particular, cardiogenic shock are associated with high morbidity and mortality. A therapeutic dilemma is that the use of positive inotropic agents, such as catecholamines or phosphodiesterase-inhibitors, is associated with increased mortality. Newer drugs, such as levosimendan or omecamtiv mecarbil, target sarcomeres to improve systolic function putatively without elevating intracellular Ca2+. Although meta-analyses of smaller trials suggested that levosimendan is associated with a better outcome than dobutamine, larger comparative trials failed to confirm this observation. For omecamtiv mecarbil, Phase II clinical trials suggest a favourable haemodynamic profile in patients with acute and chronic HF, and a Phase III morbidity/mortality trial in patients with chronic HF has recently begun. Here, we review the pathophysiological basis of systolic dysfunction in patients with HF and the mechanisms through which different inotropic agents improve cardiac function. Since adenosine triphosphate and reactive oxygen species production in mitochondria are intimately linked to the processes of excitation-contraction coupling, we also discuss the impact of inotropic agents on mitochondrial bioenergetics and redox regulation. Therefore, this position paper should help identify novel targets for treatments that could not only safely improve systolic and diastolic function acutely, but potentially also myocardial structure and function over a longer-term.
Subject: Heart failure
Acute decompensated heart failure
Inotropes
Cardiogenic shock
Excitation-contraction coupling
Calcium
Sarcomeres
Mitochondria
Energetics
Adrenergic receptors
Contractility
Levosimendan
Omecamtiv mecarbil
Nitroxyl
3121 General medicine, internal medicine and other clinical medicine
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