5-Fluorouracil increases the number and complexity of premature complexes in the heart: a prospective study using ambulatory ECG monitoring

Abstract

The cardiac toxicity of LV5FU2 (de Gramont) regimen which is a widely used chemotherapy regimen in gastrointestinal system cancers is not well defined. We aimed to evaluate the impact of this regimen on cardiac rhythm. Two Holter ECG recordings were obtained in all patients with gastrointestinal system cancers treated with LV5FU2 regimen as first-line chemotherapy (one before and the second during the first 24 h of chemotherapy). Records were reviewed for the heart rate, rhythm, atrial premature complexes (APC), ventricular premature complexes (VPC), grades according to Lown-Wolf grading system and ST segment changes. Holter ECG recordings were evaluated in 27 patients. In the baseline evaluation, neither clinical symptom nor ST segment changes were observed. During the treatment period, chest pain was observed in two patients without any cardiac enzyme and ST segment changes. Moreover, a decrease in mean heart rate, and an increase in the number and complexity of premature complexes secondary to treatment were observed. The mean heart rate, APC per hour and VPC per hour (+/-SD) before vs. during treatment were, respectively, 93.1+/-16.4 vs. 81.6+/-12.7 (p=0.001), 18.9+/-54.0 vs. 45.3+/-53.8 vs. (p=0.049) and 12.7+/-29.6 vs. 38.1+/-42.1 (p=0.002). LV5FU2 regimen leads to a decrease in mean heart rate and a significant increase in APC and VPC which may lead to serious arrhythmias. These effects must be better understood for a safer administration of this useful and widely used drug regimen.

Clinical and Electrocardiography Changes in Patients Treated with Capecitabine

“…Cardiac toxicity of capecitabine is as important as its use, as it is commonly and easily used when 5-FU is contraindicated [5]. For example, the incidence of 5-FU-induced cardiac toxicity is reported to be 1.2–18.0%, whereas the incidence of capecitabine-induced cardiac toxicity is yet to be reported [21,22]. …”

“…5-FU-induced cardiac toxicity can be easily determined based on the typical ECG findings combined with chest pain, palpitations, nausea and sweating [9]. Another important testing method is the use of a Holter monitor [22]. In patients who had previously received a chemotherapy regimen with anthracycline or transtuzumab, or mediastinal radiotherapy, the cardiac toxicity risk increases with the usage of antimetabolite group chemotherapy medications.…”

“…The usage of ECHO and the treadmill stress test, which are found effective in reduction of morbidity and mortality rates in patients treated with fluoropyrimidine, in the pretreatment phase and during monitoring, takes an important place in the diagnosis and treatment of cardiac diseases which constitute a significant problem for cancer patients, whose lifespan is extended through developing cancer treatments [6,7,22]. In our study, ECHO and the treadmill stress test were not routinely applied to each patient in pretreatment assessment.…”

The Need for Routine Monitoring of Cardiac Function in Patients Receiving 5-Fluorouracil Infusion

“…Common electrocardiogram changes, related symptoms, and possible diagnosis can be found in Table 1. A Holter monitor is considered more sensitive than a regular electrocardiogram because it permits the registration of cardiac activity for a long period of time (Yilmaz et al, 2007). A Holter monitor is considered more sensitive than a regular electrocardiogram because it permits the registration of cardiac activity for a long period of time (Yilmaz et al, 2007).…”

Ventricular ectopy - all bad?

“…In this issue of the International Journal , Yilmaz et al. (1) present data from their study of the arrhythmogenic potential of the chemotherapeutic agent 5‐Fluorouracil (5FU). Their investigation raises further questions in this area and also highlights the complexity of risk stratification with ventricular ectopy.…”