Maack, Christoph and Eschenhagen, Thomas and Hamdani, Nazha and Heinzel, Frank R. and Lyon, Alexander R. and Manstein, Dietmar J. and Metzger, Joseph and Papp, Zoltan and Tocchetti, Carlo G. and Yilmaz, M. Birhan and Anker, Stefan D. and Balligand, Jean-Luc and Bauersachs, Johann and Brutsaert, Dirk and Carrier, Lucie and Chlopicki, Stefan and Cleland, John G. and de Boer, Rudolf A. and Dietl, Alexander and Fischmeister, Rodolphe and Harjola, Veli-Pekka and Heymans, Stephane and Hilfiker-Kleiner, Denise and Holzmeister, Johannes and de Keulenaer, Gilles and Limongelli, Giuseppe and Linke, Wolfgang A. and Lund, Lars H. and Masip, Josep and Metra, Marco and Mueller, Christian and Pieske, Burkert and Ponikowski, Piotr and Ristic, Arsen and Ruschitzka, Frank and Seferovic, Petar M. and Skouri, Hadi and Zimmermann, Wolfram H. and Mebazaa, Alexandre (2019) Treatments targeting inotropy. EUROPEAN HEART JOURNAL, 40 (44). pp. 3626-3640. ISSN 0195-668X, 1522-9645
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; Heart failure; Acute decompensated heart failure; Inotropes; Cardiogenic shock; Excitation-contraction coupling; Calcium; Sarcomeres; Mitochondria; Energetics; Adrenergic receptors; Contractility; Levosimendan; Omecamtiv mecarbil; Nitroxyl |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin II |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Mar 2020 08:51 |
| Last Modified: | 24 Mar 2020 08:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/25811 |
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