Chemotherapy regime based on 5-fluorouracil (5-FU) are frequently administered in the treatment of gastro-intestinal malignancies, especially colorectal carcinomas. A potential severe side effect of 5-FU is cardiotoxicity with often presents with chest pain related to coronary vasospasm. More serious cardiotoxicity, including dilated cardiomyopathy, ventricular arrhythmia and sudden cardiac death has also reported in the literature.
We present a 40-years-old man with stage IV colon adenocarcinoma with metastases. The patient had no history, or risk factors, of cardiac disease. The patient was started on palliative chemotherapy with FOLFOXIRI (Leucovorin/Irinotecan/Fluorouracil). Approximately 24 h into receiving the first infusional dose of 5-FU the patient developed progressive chest pain. Electrocardiography (ECG) revealed sinus tachycardia without repolarization changes. Cardiac biomarkers indicated a moderate elevated troponin (430-580 ng/L). Echocardiogram revealed severely reduced left ventricular function with an ejection fraction (EF) of 23%. Subsequently, the patient developed a hemodynamic instability treated with noradrenaline and dobutamine, but the patient remained in cardiogenic shock. The patient was transferred to cardiac surgery for ECMO placement. Despite ECMO placement the patient was hemodinamically unstable, it was necessary to position also IMPELLA and IABP. The improvement was very slow and the ventricular function returned to normal after 5 days. A subsequent cardiac MRI showed delayed enhancement with diffuse subepicardial distribution (non-ischaemic pattern).
Our case emphasizes the importance of early recognition of this rare complication and prompt cessation of 5-FU, as cardiac dysfunction in this context is potentially reversible. The precise mechanism remains unclear, but several mechanisms have been proposed including coronary vasospasm, direct toxicity to the myocardium, endothelial dysfunction. It should be noted that these mechanisms were elucidated though animal modeling, case reports, and small clinical studies.