Targeted anticytokine therapy and the failing heart

Recent studies have identified the importance of proinflammatory mediators in the development and progression of chronic heart failure (CHF). The growing appreciation of the pathophysiologic consequences of sustained expression of proinflammatory mediators in preclinical and clinical CHF models culminated in a series of multicenter clinical trials that used targeted approaches to neutralize tumor necrosis factor in patients with moderate-to-advanced CHF. However, these targeted approaches have resulted in worsening CHF, thereby raising a number of important questions about what role, if any, proinflammatory cytokines play in the pathogenesis of CHF. This review summarizes what has been learned from the negative clinical trials, as well as the potential direction of future research in this area.