Treatments targeting inotropy: A position paper of the Committees on Translational Research and Acute Heart Failure of the Heart Failure Association of the European Society of Cardiology. (8th October 2018)

• Record Type: Journal Article
• Authors: Maack, Christoph; Eschenhagen, Thomas; Hamdani, Nazha; Heinzel, Frank R; Lyon, Alexander R; Manstein, Dietmar J; Metzger, Joseph; Papp, Zoltán; 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; Ristić, Arsen; Ruschitzka, Frank; Seferović, Petar M; Skouri, Hadi; Zimmermann, Wolfram H; Mebazaa, Alexandre;
• Is Part Of: European heart journal. Volume 40:Number 44(2019)
• Page Start: 3626
• Page End: 3644
• Publication Date: 2018-10-08
• Subjects: Heart failure -- Acute decompensated heart failure -- Inotropes -- Cardiogenic shock -- Excitation–contraction coupling -- Calcium -- Sarcomeres -- Mitochondria -- Energetics -- Adrenergic receptors -- Contractility -- Levosimendan -- Omecamtiv mecarbil -- Nitroxyl; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehy600
• Languages: English
• ISSNs: 0195-668X

Abstract

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 Ca 2+ . 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.