Clinical implications of tumour necrosis factor α antagonism in patients with congestive heart failure

The experimental and clinical evidence that demonstrates the effect of TNFα in heart failure patients continues to accumulate. It is well established that increased concentrations of TNFα appear in the circulation of heart failure patients and that the levels may have prognostic significance. Also, increased TNFα levels may be responsible for the decreased expression of myocardial TNF receptors observed in failing myocardium. Along with these clinical data, it has been clearly demonstrated that increased levels of TNFα lead to cardiomyopathy and eventually death in experimental animals; therefore, it is reasonable to assume that increased concentrations of TNFα in heart failure patients may be detrimental to cardiac function. In support of this concept we found that cardiac TNFα concentrations were significantly reduced in heart failure patients treated with LVADs; a form of mechanical support that leads to improved cardiac function. The hypothesis that TNFα contributes to the pathogenesis of heart failure has recently been tested at the clinical level. The results of specific TNFα antagonism in symptomatic heart failure patients demonstrate that anti-TNFα treatment is safe and it may be effective. This hypothesis is currently being tested in a large randomised multicentre study that is expected to be complete in the next couple of years. Perhaps the most important aspect of the ongoing research on the role of cytokines in heart failure is that the recognition of ongoing activation of inflammatory mediators provides new targets for therapeutic intervention.