5-Fluorouracil Cardiotoxicity: Known But Unknown.
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ABSTRACT:
SUBMITTER: Brell JM
PROVIDER: S-EPMC8352191 | biostudies-literature | 2021 Mar
REPOSITORIES: biostudies-literature
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Project description:5-Fluorouracil (5-FU) is a chemotherapeutic agent frequently used for the treatment of solid tumors. In a few cases, 5-FU can be associated with coronary vasospasm, cardiac ischemia, or life-threatening arrhythmias. Recognition of 5-FU cardiotoxicity is clinically important as after the rapid sensation of therapy, cardiotoxicity can be completely reversible, and on the other hand, readministration may lead to serious damage of the heart and even death. A 70-year-old male came to the emergency department (ED) with chest pain which started while receiving an infusion of 5-FU. The patient did not have a personal history or risk factors of coronary artery disease and his electrocardiogram (ECG) before starting chemotherapy was completely normal. In the ED, his ECG had ischemic changes, troponin was elevated, and echocardiogram showed anterior wall hypokinesis. However, emergent coronary angiogram did not reveal any acute coronary occlusion. 5-FU-induced cardiotoxicity was suspected; the patient was admitted to a progressive care unit for close monitoring and infusion of calcium channel blockers was initiated. The patient's symptoms and ECG findings gradually resolved, and two days later on discharge, patient was chest pain free and ECG was normal. This case supports the vasospastic hypothesis of 5-FU cardiac toxicity, describes its clinical course, and emphasizes the importance of better awareness and early recognition of the rare side effect as it may allow physicians to reduce the risk of life-threatening complications.
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Project description:BackgroundCardiotoxicity is a serious side effect to treatment with 5-fluorouracil (5-FU), but the underlying mechanisms are not fully understood. The objective of this systematic review was to evaluate the pathophysiology of 5-FU- induced cardiotoxicity.MethodsWe systematically searched PubMed for articles in English using the search terms: 5-FU OR 5-fluorouracil OR capecitabine AND cardiotoxicity. Papers evaluating the pathophysiology of this cardiotoxicity were included.ResultsWe identified 27 articles of 26 studies concerning the pathophysiology of 5-FU-induced cardiotoxicity. The studies demonstrated 5-FU-induced: hemorrhagic infarction, interstitial fibrosis and inflammatory reaction in the myocardium; damage of the arterial endothelium followed by platelet aggregation; increased myocardial energy metabolism and depletion of high energy phosphate compounds; increased superoxide anion levels and a reduced antioxidant capacity; vasoconstriction of arteries; changes in red blood cell (RBC) structure, function and metabolism; alterations in plasma levels of substances involved in coagulation and fibrinolysis and increased endothelin-1 levels and N-terminal-pro brain natriuretic peptide levels. Based on these findings the proposed mechanisms are: endothelial injury followed by thrombosis, increased metabolism leading to energy depletion and ischemia, oxidative stress causing cellular damage, coronary artery spasm leading to myocardial ischemia and diminished ability of RBCs to transfer oxygen resulting in myocardial ischemia.ConclusionsThere is no evidence for a single mechanism responsible for 5-FU-induced cardiotoxicity, and the underlying mechanisms might be multifactorial. Further research is needed to elucidate the pathogenesis of this side effect.
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