TY - JOUR

T1 - Myocardial Ischemia Induced by 5-Fluorouracil

T2 - A Prospective Electrocardiographic and Cardiac Biomarker Study

AU - Dyhl-Polk, Anne

AU - Schou, Morten

AU - Vistisen, Kirsten K.

AU - Sillesen, Anne Sophie

AU - Serup-Hansen, Eva

AU - Faber, Jens

AU - Klausen, Tobias W.

AU - Bojesen, Stig E.

AU - Vaage-Nilsen, Merete

AU - Nielsen, Dorte L.

PY - 2021

Y1 - 2021

N2 - Background: Cardiotoxicity induced by 5-fluorouracil (5-FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5-FU to increase our understanding of the cardiotoxicity. Subjects, Materials, and Methods: Patients with colorectal or anal cancer that received first-time treatment with 5-FU-based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12-lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5-FU treatment (intervention). Results: A total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5-FU infusion (14.1%) than before (3.7%; p =.001). The ischemic burden per day (p =.001), the number of ST depression episodes per day (p =.003), and the total duration of ischemic episodes per day (p =.003) were higher during the first 5-FU infusion than before, as was plasma copeptin (p <.001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5-FU treatment. Conclusion: 5-FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5-FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%–6% of the patients developed acute coronary syndromes during treatment with 5-FU. Implications for Practice: Symptomatic 5-fluorouracil (5-FU) cardiotoxicity occurs in 0.6%–19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5-FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5-FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5-FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5-FU.

AB - Background: Cardiotoxicity induced by 5-fluorouracil (5-FU) is well known but poorly understood. In this study, we undertook ECG recording (Holter) and analyses of the biomarkers troponin and copeptin in patients receiving 5-FU to increase our understanding of the cardiotoxicity. Subjects, Materials, and Methods: Patients with colorectal or anal cancer that received first-time treatment with 5-FU-based chemotherapy were prospectively included. Holter recording, clinical evaluation, 12-lead electrocardiogram, and assessment of plasma concentrations of troponin I and copeptin were performed before (control) and during 5-FU treatment (intervention). Results: A total of 108 patients were included, 82 with colorectal and 26 with anal cancer. The proportion of patients with myocardial ischemia on Holter recording was significantly higher during the first 5-FU infusion (14.1%) than before (3.7%; p =.001). The ischemic burden per day (p =.001), the number of ST depression episodes per day (p =.003), and the total duration of ischemic episodes per day (p =.003) were higher during the first 5-FU infusion than before, as was plasma copeptin (p <.001), whereas plasma troponin I was similar (p > 0.999). Six patients (5.6%) developed acute coronary syndromes and two (1.8%) developed symptomatic arrhythmias during 5-FU treatment. Conclusion: 5-FU infusion is associated with an increase in the number of patients with myocardial ischemia on Holter recording. According to biomarker analyses, 5-FU is associated with an increase in copeptin, but rarely with increases in cardiac troponin I. However, 5%–6% of the patients developed acute coronary syndromes during treatment with 5-FU. Implications for Practice: Symptomatic 5-fluorouracil (5-FU) cardiotoxicity occurs in 0.6%–19% of patients treated with this drug, but a small electrocardiographic (Holter) study has revealed silent myocardial ischemia in asymptomatic patients, suggesting a more prevalent subclinical cardiac influence. This study demonstrated a significant increase in the number of patients with myocardial ischemia on Holter recording during 5-FU treatment and an increase in ischemic burden. Cardiac biomarker analyses suggested that 5-FU infusion results in endogenous stress (increased copeptin) but rarely induces myocyte injury (no change in troponin). These findings suggest a more prevalent cardiac influence from 5-FU and that Holter recording is an important tool in the evaluation of patients with suspected cardiotoxicity from 5-FU.

KW - 5-Flourouracil

KW - Anal cancer

KW - Cardiotoxicity

KW - Colorectal cancer

KW - Myocardial ischemia

U2 - 10.1002/onco.13536

DO - 10.1002/onco.13536

M3 - Journal article

C2 - 32959474

AN - SCOPUS:85092176300

VL - 26

SP - e403-e413

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 3

ER -