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

Abstract

Tumor necrosis factor inhibitors (anti-TNFs) are widely used therapies for the treatment of inflammatory bowel diseases (IBD); however, their administration is not risk-free. Heart failure (HF), although rare, is a potential adverse event related to administration of these medications. However, the exact mechanism of development of HF remains obscure. TNFα is found in both healthy and damaged hearts. Its effects are concentration- and receptor-dependent, promoting either cardio-protection or cardiomyocyte apoptosis. Experimental rat models with TNFα receptor knockout showed increased survival rates, less reactive oxygen species formation, and improved diastolic left ventricle pressure. However, clinical trials employing anti-TNF therapy to treat HF had disappointing results, suggesting abolishment of the cardioprotective properties of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation. Thus, patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy. This review aims to discuss adverse events associated with the administration of anti-TNF therapy, with a focus on HF, and propose some approaches to avoid cardiac adverse events in patients with IBD.

Keywords: Adverse event; Heart failure; Inflammatory bowel disease; TNFα receptor; Tumor necrosis factor inhibitors.

Figure 1

Clinical profiles of acute heart failure. Patients with acute heart failure present differently at admission depending on the degree of congestion and hypoperfusion of the tissues. Such profile differentiation provides guided treatment with better outcomes.

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.