Acute Reversible Heart Failure Caused by Coronary Vasoconstriction due to Continuous 5-Fluorouracil Combination Chemotherapy

Abstract

We present the case of a 51-year-old male patient who received adjuvant chemotherapy consisting of oxaliplatin, bolus and continuous 5-fluorouracil (5-FU) and leucovorin after anterior resection because of locally advanced rectal cancer. Preoperative chemotherapy with capecitabine (an oral 5-FU prodrug) had been well tolerated. Two days after initiation of the first course of chemotherapy, the patient reported typical chest pain. The ECG showed ST elevations and prominent T waves in almost all leads. Due to suspicion of a high-risk acute coronary syndrome, an urgent cardiac catheterization was performed. It showed a generally reduced coronary flow with multiple significant stenoses (including the ostia of the left and right coronary artery), as well as a highly reduced left ventricular function with diffuse hypokinesia. Due to the meanwhile completely stable situation of the patient after medical acute coronary syndrome treatment, no ad hoc intervention was performed to allow further discussion of the optimal management. Thereafter, the patient remained clinically asymptomatic, without any rise in cardiac necrosis parameters; only NT-pro-BNP was significantly elevated. A control cardiac catheterization 2 days later revealed a restored normal coronary artery flow with only coronary calcifications without significant stenoses, as well as a normal left ventricular ejection fraction. Cardiovascular symptoms occurred on the second day of continuous 5-FU treatment. As cardiotoxic effects seem to appear more frequently under continuous application of 5-FU, compared to the earlier established 5-FU bolus regimens, treating medical oncologists should pay special attention to occurring cardiac symptoms and immediately interrupt 5-FU chemotherapy and start a cardiologic work-up.

Acute reversible left ventricular systolic dysfunction associated with 5-fluorouracil therapy: a rare and increasingly recognised cardiotoxicity of a commonly used drug

“…Additionally, the presence of these features in the setting of drug use, excludes the diagnosis of SCM, per Gothenburg Criteria 38. A similar presentation of reversible global hypokinesis associated with 5-FU has been previously described,39–45 and these cases do not meet the strict definition of SCM (table 1). Thus, these reports of 5-FU-related global hypokinesia, make us think about our current understanding of the underlying mechanism for this cardiotoxicity.…”

Evaluation of cardioprotective activity of Lepidium sativum seed powder in albino rats treated with 5-fluorouracil

“…The mechanisms of 5-FU-induced cardiotoxicity are hemorrhagic infarction, myocardial inflammatory reaction with interstitial fibrosis; arterial endothelial injury followed by thrombosis (Bertolini et al, 2001); increased metabolism leading to depletion of ATP, increased levels of superoxide anion and a decreased antioxidant capacity; arterial vasoconstriction and altered plasma levels of substances involved in coagulation and fibrinolysis (Dechant et al, 2012). Oxidative stress causes cellular damage, coronary artery spasm and the decreased affinity of RBCs to transfer oxygen, resulting in myocardial ischemia, cardiac arrest and sudden death (Polk et al, 2014).…”

A comparison of cardiomyocyte cytotoxic mechanisms for 5-fluorouracil and its pro-drug capecitabine

“…It was also reported that 5-FU has direct toxic effects on vascular endothelium that involves endothelial nitric oxide synthase (NOS) and causes coronary spasms and endothelium-independent vasoconstriction through protein kinase C (Dechant et al, 2012;Lieutaud et al, 1996).…”