125 research outputs found
The innate immune system in chronic cardiomyopathy : a European Society of Cardiology (ESC) scientific statement from the Working Group on Myocardial Function of the ESC
Funded by Regione Campania CISI-Lab European Union Commission's Seventh Framework . Grant Number: 305507, 602904 FP7-Health-2013-Innovations-1. Grant Number: 602156 FWO Flanders, Belgium. Grant Number: FWO G080014 N European Union Horizon2020. Grant Number: UE LSHM-CT-05-018833, FNRS PDR T.0144.13 Bundesministerium für Bildung und Forschung. Grant Number: BMBF01 EO1004 Deutsche Forschungsgemeinschaft. Grant Number: SFB688 TP A10Peer reviewedPublisher PD
Treatments targeting inotropy
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.Peer reviewe
- …