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Gene Transfer for Ischemic Heart Failure in a Preclinical Model
07:35

Gene Transfer for Ischemic Heart Failure in a Preclinical Model

Published on: May 15, 2011

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Targeted anticytokine therapy and the failing heart

Douglas L Mann1

  • 1Winters Center for Heart Failure Research, Cardiology Section, Department of Medicine, Michael E. DeBakey Veterans Administration Medical Center and Baylor College of Medicine, Houston, Texas 77030, USA. dmann@bcm.tmc.edu

The American Journal of Cardiology
|June 1, 2005
PubMed

Insights

Targeting tumor necrosis factor (TNF) to treat chronic heart failure (CHF) worsened patient outcomes. This review examines why anti-TNF therapies failed and suggests future research directions for CHF treatment.

Area of Science:

  • Cardiology
  • Immunology
  • Pathophysiology

Background:

  • Proinflammatory mediators are implicated in chronic heart failure (CHF) development and progression.
  • Sustained expression of these mediators in CHF models highlighted their pathophysiologic role.
  • This led to clinical trials targeting tumor necrosis factor (TNF) in moderate-to-advanced CHF.

Purpose of the Study:

  • To review the outcomes of clinical trials targeting TNF in CHF.
  • To understand the implications of these negative trial results.
  • To explore future research avenues for CHF pathogenesis and treatment.

Main Methods:

  • Review of multicenter clinical trials using targeted approaches to neutralize TNF in CHF patients.
  • Analysis of data from preclinical and clinical CHF models.
  • Synthesis of findings from negative clinical trials.

Main Results:

  • Targeted neutralization of TNF in patients with moderate-to-advanced CHF resulted in worsening of the condition.
  • The clinical trials failed to demonstrate a benefit and indicated potential harm.
  • These outcomes challenge the presumed role of TNF as a primary driver in CHF pathogenesis.

Conclusions:

  • The role of proinflammatory cytokines, specifically TNF, in CHF pathogenesis requires re-evaluation.
  • Negative clinical trial results necessitate a shift in research focus.
  • Future research should explore alternative pathways and therapeutic strategies for CHF.

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