Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease: A review of the literature

Figure 2 Mechanisms of heart failure caused by the use of anti-tumor necrosis factor agents. Tumor necrosis factor (TNF)-α is found in both healthy and damaged hearts and its effects are concentration dependent via two pathways: The survivor activating factor enhancement pathway working at low concentrations and the death-promoting pathway working at high concentrations. In addition to the concentration, its repercussion in the muscle depends on the receptor to which TNFα-1 (TNFR1) and -2 (TNFR2) binds, with the latter being cardioprotective. Thus, it is suggested that the development/worsening of heart failure in patients using anti-TNF is due to a suppression of the cardioprotective concentration of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation or also to selective cytotoxicity.