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Treatments targeting inotropy
- Source :
- European heart journal, Eur Heart J, European Heart Journal, 40(44), 3626-3644. Oxford University Press, European heart journal, Vol. 40, no. 44, p. 3626-3644 (2019)
- Publication Year :
- 2019
-
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.
- Subjects :
- Inotrope
Acute decompensated heart failure
Phosphodiesterase Inhibitors
Swine
Levosimendan
030204 cardiovascular system & hematology
Omecamtiv mecarbil
Contractility
Antioxidants
Placebos
0302 clinical medicine
Catecholamines
Diastole
Dobutamine
Inotropes
Urea
Adrenergic receptors
1102 Cardiorespiratory Medicine and Haematology
Excitation Contraction Coupling
Clinical Trials as Topic
Cardiogenic shock
3. Good health
Receptors, Adrenergic
Mitochondria
Acute Disease
Models, Animal
Cardiology
Nitrogen Oxides
Cardiology and Cardiovascular Medicine
Oxidation-Reduction
medicine.drug
Cardiac function curve
Sarcomeres
medicine.medical_specialty
Cardiotonic Agents
Systole
Shock, Cardiogenic
Heart failure
03 medical and health sciences
Special Article
Dogs
Internal medicine
Energetics
medicine
Animals
Humans
Simendan
business.industry
030229 sport sciences
medicine.disease
Myocardial Contraction
Excitation-contraction coupling
Cardiovascular System & Hematology
3121 General medicine, internal medicine and other clinical medicine
Case-Control Studies
Nitroxyl
Calcium
Human medicine
business
Energy Metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0195668X
- Database :
- OpenAIRE
- Journal :
- European heart journal
- Accession number :
- edsair.doi.dedup.....046ee915c5f51c9fa308eff3927520f7