Congestive Heart Failure as a Side Effect of Using Infliximab in the Treatment of Crohn`s Disease
BACKGROUND: The main biological agents used to treat Crohn's disease (CD) are anti-TNF agents. Despite its safety profile, the medication is not exempt from side effects such as infections, malignancy and cardiovascular complications such as heart failure (HF). The objective of this study is to report the case of a patient with CD who developed heart failure after the use of Infliximab (IFX).
METHODS: Case study of a CD outpatient who developed HF after use of IFX. Anamnesis, physical examination, laboratory and imaging data were obtained by consulting their electronic medical records.
RESULTS: A 50-year old female patient with a history of hypertension, diabetes and cholecystectomy, was admitted in 2016 with abdominal pain, diarrhea and weight loss of 25 kg in 6 months. Colonoscopy showed ulcers and intense inflammatory process with stenosis of the ileocecal valve. Anatomopathological evidenced nonspecific inflammatory infiltrate. Enterotomography revealed terminal ileum and jejunum wall thickening with fibrotic stenosis. The patient underwent ileotiflectomy with ileo-ascending anastomosis. During the surgery, severe thickening of 70 cm of the ileum associated with mesenteric infiltration was observed. Surgical specimen confirmed the diagnosis of CD (stenosing phenotype). The patient started IFX and azathioprine. After four months, she started having dyspnea, orthopnea and paroxysmal nocturnal dyspnea that gradually got worse until 8 months after initiation of clinical treatment. Echocardiography revealed biventricular dysfunction, moderate insufficiency, ejection fraction of 36% and moderate pericardial effusion (19 mm). IFX was discontinued and the patient started treatment for HF with diuretics. Improvement of symptoms and improvement of cardiac function were demonstrated in a new echocardiogram. The patient will start another class of biological treatment for CD.
CONCLUSION: Anti-TNFs exert intracellular effects by binding two receptors: TNFR1 and TNFR2, with the first mediating proinflammatory and pro-apoptotic signals and the last related to survival pathways. Its biological activity varies with its concentration. The increase of TNF- ? concentration after anti-TNF treatment is a common phenomenon, which may explain its cardiotoxic effect. However, it is unclear whether cardiotoxicity is observed under all conditions in which it is increased or only in patients with HF. Reverse signaling is another mechanism responsible for its cardiotoxic effects, where the transmembrane TNF produced by heart cells would act as a receptor for anti-TNF, serving as a signal for the production of more TNF- ? in the tissue, and increasing its cardiotoxicity. In healthy people, increased TNF-? levels predict the risk of developing cardiovascular disease and are an independent predictor of the survival of HF in asymptomatic patients without prior acute myocardial infarction and mortality. The patient probably already had a lesion due to hypertension and IFX use prevented TNFR2 binding, inhibiting the cardioprotective action of this receptor when activated. Anti-TNFs may trigger HF in predisposed patients. The reported case supports the need to investigate risk factors of HF and to consider the risk-benefit of introducing this therapy in patients with inflammatory bowel disease.
