Abstract
Acute heart failure (AHF) represents a major public health problem due to its high prevalence, high rates of mortality and readmissions and significant healthcare costs. Patients with AHF and low cardiac output represent a small subgroup of patients with very high mortality rates that require inotropic support to improve cardiac systolic function. Classical inotropic agents, such as β1-adrenergic agonists (dobutamine, dopamine) and phosphodiesterase III inhibitors (milrinone, enoximone) improve symptoms and hemodynamics by increasing free intracellular Ca2+ levels, but also increase myocardial O2 demands and exert arrhythmogenic effects. These actions explain why these drugs increase both short- and long-term mortality, particularly in patients with AHF and coronary artery disease. Thus, we need new inotropic agents that do not increase cytosolic Ca2+ or myocardial oxygen demands or produce arrhythmogenesis for the treatment of high-risk patients with (AHF) and low cardiac output. This review describes three new classes of investigational agents: levosimendan, a calcium sensitizer and potassium channel opener, istaroxime, the first new luso-inotropic agent and cardiac myosin activators.
Keywords: Inotropic drugs, acute heart failure, levosimendan, istaroxime, CK-1827452
Cardiovascular & Hematological Disorders-Drug Targets
Title: Investigational Positive Inotropic Agents for Acute Heart Failure
Volume: 9 Issue: 3
Author(s): Juan Tamargo, Ricardo Caballero, Ricardo Gomez, Adriana Barana, Irene Amoros and Eva Delpon
Affiliation:
Keywords: Inotropic drugs, acute heart failure, levosimendan, istaroxime, CK-1827452
Abstract: Acute heart failure (AHF) represents a major public health problem due to its high prevalence, high rates of mortality and readmissions and significant healthcare costs. Patients with AHF and low cardiac output represent a small subgroup of patients with very high mortality rates that require inotropic support to improve cardiac systolic function. Classical inotropic agents, such as β1-adrenergic agonists (dobutamine, dopamine) and phosphodiesterase III inhibitors (milrinone, enoximone) improve symptoms and hemodynamics by increasing free intracellular Ca2+ levels, but also increase myocardial O2 demands and exert arrhythmogenic effects. These actions explain why these drugs increase both short- and long-term mortality, particularly in patients with AHF and coronary artery disease. Thus, we need new inotropic agents that do not increase cytosolic Ca2+ or myocardial oxygen demands or produce arrhythmogenesis for the treatment of high-risk patients with (AHF) and low cardiac output. This review describes three new classes of investigational agents: levosimendan, a calcium sensitizer and potassium channel opener, istaroxime, the first new luso-inotropic agent and cardiac myosin activators.
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Cite this article as:
Tamargo Juan, Caballero Ricardo, Gomez Ricardo, Barana Adriana, Amoros Irene and Delpon Eva, Investigational Positive Inotropic Agents for Acute Heart Failure, Cardiovascular & Hematological Disorders-Drug Targets 2009; 9 (3) . https://dx.doi.org/10.2174/187152909789007070
DOI https://dx.doi.org/10.2174/187152909789007070 |
Print ISSN 1871-529X |
Publisher Name Bentham Science Publisher |
Online ISSN 2212-4063 |
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