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.
Export Options
About this article
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 |
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Mast Cells and Inflammatory Heart Disease: Potential Drug Targets
Cardiovascular & Hematological Disorders-Drug Targets Utilization of Evidence-Based Secondary Prevention Medications at the Time of Discharge in Patients with Acute Coronary Syndrome (ACS) in Qatar
Current Vascular Pharmacology Genes Involved in Hereditary Hearing Impairment
Current Genomics Molecular Predictors of Drug-induced Prolongation of the QT Interval
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Geriatric Evaluation of Oncological Elderly Patients
Anti-Cancer Agents in Medicinal Chemistry Renin-Angiotensin-Aldosterone System Antagonists and the Prevention of Type 2 Diabetes Mellitus
Current Pharmaceutical Design Intra-Renal Hemodynamic Changes After Habitual Physical Activity in Patients with Chronic Kidney Disease
Current Pharmaceutical Design Biology of Transforming Growth Factor-β Signaling
Current Pharmaceutical Biotechnology Update to Medicinal Chemistry of Nicotinamide in the Treatment of Ischemia and Reperfusion
Medicinal Chemistry Reviews - Online (Discontinued) Signaling Epicenters: The Role of Caveolae and Caveolins in Volatile Anesthetic Induced Cardiac Protection
Current Pharmaceutical Design Advanced Techniques for Penetration Enhancement in Transdermal Drug Delivery System
Current Drug Delivery Current Indications for Infective Endocarditis Antibiotic Prophylaxis
Infectious Disorders - Drug Targets An Expedient Synthesis of CMF-019: (S)-5-Methyl-3-{1-(pentan-3-yl)-2- (thiophen-2-ylmethyl)-1H-benzo[d]imidazole-5-carboxamido}hexanoic Acid, a Potent Apelin Receptor (APJ) Agonist
Medicinal Chemistry Angiotensin II, Cell Proliferation and Angiogenesis Regulator: Biologic and Therapeutic Implications in Cancer
Current Vascular Pharmacology Relevance of Sphingolipids in the Pleiotropic Protective Effects of High-Density Lipoproteins
Current Pharmaceutical Design Infants and Children with Tachycardia: Natural History and Drug Administration
Current Pharmaceutical Design Strategies for Enhancing Progenitor Cell Mobilization and Function in Diabetes
Current Vascular Pharmacology Mechanisms of Drug Induced QT Interval Prolongation
Current Drug Safety Understanding the Molecular and Cellular Changes Behind Aortic Valve Stenosis
Current Pharmaceutical Biotechnology Bone Morphogenetic Protein-Smad Pathway as Drug Targets for Osteoporosis and Cancer Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets