Cardiovascular & Hematological Disorders-Drug Targets

(Formerly Current Drug Targets - Cardiovascular & Hematological Disorders)

Garry X. Shen  
University of Manitoba
Winnipeg, MB
Canada

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Investigational Positive Inotropic Agents for Acute Heart Failure

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

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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Article Details

VOLUME: 9
ISSUE: 3
Year: 2009
Page: [193 - 205]
Pages: 13
DOI: 10.2174/187152909789007070
Price: $58