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
-
Matrix Metallopropteinases in Heart Failure
Current Topics in Medicinal Chemistry Drug Interactions between Non-Steroidal Anti-Inflammatory Drugs and Cardiovascular Treatments (Except Anti-Agregant Therapy)
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Novel Non-Steroidal Anti-Inflammatory Drugs: What we have Learned from Animal Studies
Current Drug Targets - Inflammation & Allergy Repositioning the Old Fungicide Ciclopirox for New Medical Uses
Current Pharmaceutical Design Regulation and Quantification of Cellular Mitochondrial Morphology and Content
Current Pharmaceutical Design Antimetastatic Activities and Mechanisms of Bisdioxopiperazine Compounds
Anti-Cancer Agents in Medicinal Chemistry IP6 (Inositol Hexaphosphate) as a Signaling Molecule
Current Signal Transduction Therapy Targeting the Ataxia Telangiectasia Mutated Protein in Cancer Therapy
Current Drug Targets Advances in the Researches on the Biological Activities and Inhibitors of Phosphatidylinositol 3-kinase
Anti-Cancer Agents in Medicinal Chemistry The Influence of Sex Hormones on Pulmonary Vascular Reactivity: Possible Vasodilator Therapies for the Treatment of Pulmonary Hypertension
Current Vascular Pharmacology Novel Methods of Genetic Modification of Human Pluripotent Stem Cells
Recent Patents on Regenerative Medicine Pioglitazone and Rosiglitazone: Effects of Treatment with a Thiazolidinedione on Lipids and Non Conventional Cardiovascular Risk Factors
Current Clinical Pharmacology Antiviral Therapy Targeting Viral Polymerase
Current Pharmaceutical Design Respiratory Hypoxia and Oxidative Stress in the Brain. Is the Endogenous Erythropoietin an Antioxidant?
Current Chemical Biology Progress and Prospects of Stem Cells in Treatment of Drug Resistant Tuberculosis
Current Respiratory Medicine Reviews Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones
Anti-Cancer Agents in Medicinal Chemistry Fatty Acid Amide Hydrolase: A Potential Target for Next Generation Therapeutics
Current Pharmaceutical Design Autophagy: For Better or for Worse, in Good Times or in Bad Times …
Current Molecular Medicine Recently Patented Applications of Homologous Cellular and Extracellular Agents as Therapeutics or Targets for the Prevention of Restenosis Post- Angioplasty
Recent Patents on Cardiovascular Drug Discovery (Pro)renin Receptor: Pathological Role and Therapeutic Potential in Primary Hypertension
Current Hypertension Reviews