Abstract
Elevated levels of inflammatory mediators have been identified in patients with heart failure, including heart failure with reduced and preserved ejection fraction, as well as acute decompensated heart failure. Moreover, experimental studies have shown repeatedly that activation of inflammation in the heart provokes left ventricular remodeling and left ventricular dysfunction. Nonetheless, phase III clinical trials that have attempted to antagonize inflammatory mediators have been negative with respect to the primary end points of the trials, and in some patients, resulted in worsening heart failure or death. The following review will discuss how recent developments in the field of innate immunity have advanced our understanding of the role of inflammation in the pathogenesis of heart failure and will discuss the negative outcomes of the existing clinical trials in light of this new information.
Keywords:
clinical trials; heart failure; inflammation; innate immunity.
© 2015 American Heart Association, Inc.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Adaptive Immunity
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Animals
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Anti-Inflammatory Agents / therapeutic use
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Antibodies, Monoclonal / therapeutic use
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Autoantibodies / immunology
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Autoimmune Diseases / immunology
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Biomarkers
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Clinical Trials, Phase III as Topic
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Cytokines / physiology*
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Dexamethasone / therapeutic use
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Heart Failure / drug therapy
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Heart Failure / etiology
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Heart Failure / immunology*
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Heart Failure / physiopathology
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Humans
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Immunity, Innate*
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Immunologic Factors / therapeutic use
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Immunosuppressive Agents / therapeutic use
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Inflammation / complications
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Inflammation / drug therapy
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Inflammation / immunology*
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Inflammation / physiopathology
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Models, Cardiovascular*
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Models, Immunological*
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Pentoxifylline / therapeutic use
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Randomized Controlled Trials as Topic
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Receptors, Pattern Recognition / immunology
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Receptors, Pattern Recognition / physiology
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Signal Transduction
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Thalidomide / therapeutic use
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Treatment Outcome
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / physiology
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Ventricular Dysfunction, Left / immunology
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Ventricular Dysfunction, Left / physiopathology
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Ventricular Remodeling / immunology
Substances
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Anti-Inflammatory Agents
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Antibodies, Monoclonal
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Autoantibodies
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Biomarkers
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Cytokines
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Immunologic Factors
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Immunosuppressive Agents
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Receptors, Pattern Recognition
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Tumor Necrosis Factor-alpha
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Thalidomide
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Dexamethasone
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Pentoxifylline