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Clinical implications of tumour necrosis factor α antagonism in patients with congestive heart failure
  1. Guillermo Torre-Amione,
  2. Sonny S Stetson,
  3. John A Farmer
  1. Department of Medicine, Section of Cardiology, Winters Center for Heart Failure Research, USA
  1. Dr G Torre-Amione, Baylor College of Medicine, Section of Cardiology, 6550 Fannin, MS: SM1901, Houston, TX 77030, USA.

https://doi.org/10.1136/ard.58.2008.i103

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    Tumour necrosis factor (TNF) α is a pro-inflammatory cytokine that is produced by the heart under certain forms of stress. Patients with advanced heart failure have increased levels of circulating TNFα1 but more importantly, TNFα can produce left ventricular remodelling, pulmonary oedema and cardiomyopathy in human subjects.2 ,3 Therefore, increased production of TNFα may play a contributory part in the pathogenesis of heart failure.

    The evidence supporting the importance of TNFα in heart failure stems from the following observations: Firstly, increased levels of circulating TNFα occur on patients with Class III-IV heart failure.4 ,5 Secondly, in a sub-study of the Studies On Left Ventricular Dysfunction (SOLVD) we showed that patients who became symptomatic with respect to heart failure had progressively higher circulating TNFα levels.5 Thirdly, TNFα is elaborated in the failing heart in response to pressure or volume overload, physiological stimuli for TNFα production in heart failure patients.6 And finally, strong experimental support comes from the observations that transgenic mice over-expressing TNFα in cardiac tissue develop dilated cardiomyopathy and die prematurely. In this review, we will discuss the human and experimental evidence that supports a causative role of TNFα in heart failure and discuss the clinical implications of TNFα antagonism in patients with congestive heart failure.

    TNFα in cardiac function

    Two important clinical observations led to the initial investigations of the role of TNFα in cardiac function. Firstly, as TNFα was a mediator of cachexia and patients with advanced heart failure manifest profound metabolic abnormalities and the syndrome of cachexia, it was reasonable to suggest that TNFα may be increased in patients with advanced heart failure. Indeed, the initial report on patients with advanced heart failure demonstrated that approximately 30–40% of patients with advanced heart failure have increased circulating TNFα levels.1 Secondly, it has long been …

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