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Cardiovascular & Hematological Disorders-Drug Targets

Editor-in-Chief

ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

Investigational Positive Inotropic Agents for Acute Heart Failure

Author(s): Juan Tamargo, Ricardo Caballero, Ricardo Gomez, Adriana Barana, Irene Amoros and Eva Delpon

Volume 9, Issue 3, 2009

Page: [193 - 205] Pages: 13

DOI: 10.2174/187152909789007070

Price: $65

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


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