Electrocardiographic and biochemical analysis of anthracycline induced cardiotoxicity in breast cancer patients from Southern Sri Lanka

Abstract

Background: The clinical application of anthracycline chemotherapy is hindered due to the cumulative dose-dependent cardiotoxicity followed by the oxidative stress initiated during the mechanism of action of anthracyclines. Due to a lack of prevalence data regarding anthracycline-induced cardiotoxicity in Sri Lanka, this study was conducted to determine the prevalence of cardiotoxicity among breast cancer patients in Southern Sri Lanka in terms of electrocardiographic and cardiac biomarker investigations.

Methods: A cross-sectional study with longitudinal follow-up was conducted among 196 cancer patients at the Teaching Hospital, Karapitiya, Sri Lanka to determine the incidence of acute and early-onset chronic cardiotoxicity. Data on electrocardiography and cardiac biomarkers were collected from each patient, one day before anthracycline (doxorubicin and epirubicin) chemotherapy, one day after the first dose, one day and six months after the last dose of anthracycline chemotherapy.

Results: Prevalence of sub-clinical anthracycline-induced cardiotoxicity six months after the completion of anthracycline chemotherapy was significantly higher (p < 0.05) and there were strong, significant (p < 0.05) associations among echocardiography, electrocardiography measurements and cardiac biomarkers including troponin I and N-terminal pro-brain natriuretic peptides. The cumulative anthracycline dose, > 350 mg/m² was the most significant risk factor associated with the sub-clinical cardiotoxicity in breast cancer patients under study.

Conclusion: Since these results confirmed the unavoidable cardiotoxic changes following anthracycline chemotherapy, it is recommended to carry out long-term follow-ups in all patients who were treated with anthracycline therapy to increase their quality of life as cancer survivors.

Keywords: Anthracycline; Breast cancer patients; Cardiotoxicity; Electrocardiography; NT-proBNP; Troponin I.

Fig. 1

Sample of standard ECG paper which shows the scale of voltage in vertical axis and time in the horizontal axis. (Extracted from http://www.medicine.mcgill.ca/physio/vlab/cardio/introecg.htm)

Fig. 2

Comparison of echocardiographic parameters among the four time points. Baseline; One day prior to anthracycline chemotherapy, FTP I; One day after 1^st dose of anthracycline chemotherapy, FTP II; One day after last dose of anthracycline chemotherapy, FTP III; Six months after completion of anthracycline chemotherapy. All values are expressed as mean ± SD (n = 196). p values *˂ 0.05, **˂ 0.01, ***˂0.001 compared to the baseline readings. (Paired t-test was applied to compare echocardiographic parameters between the baseline and one day and six months after the completion of anthracycline chemotherapy). FTP; Follow up time point, EF; ejection fraction, FS; fractioning shortening, PWT, LV; posterior wall thickness (left ventricle), IVS, LV; thickness of inter-ventricular septum (left ventricle), LVEDD; left ventricular end diastolic diameter, LVESD; left ventricular end systolic diameter, SD; standard deviation

Fig. 3

Percentage of patients with PR interval changes in milli seconds compared to the baseline PR interval. PR0; PR interval reading at the baseline. PR1; PR interval reading one day after the first dose of anthracycline chemotherapy (FTP I). PR2; PR interval reading one day after the last dose of anthracycline chemotherapy (FTP II). PR3; PR interval reading six months after the completion of anthracycline chemotherapy (FTP III). FTP; Follow up time point

Fig. 4

Percentage of patients with QRS duration changes in milli seconds compared to the baseline QRS duration. QRS0; QRS duration reading at the baseline. QRS1; QRS duration reading one day after the first dose of anthracycline chemotherapy (FTP I). QRS2; QRS duration reading one day after the last dose of anthracycline chemotherapy (FTP II). QRS3; QRS duration reading six months after the completion of anthracycline chemotherapy (FTP III). FTP; Follow up time point

Fig. 5

Percentage of patients with QTc interval changes in milli seconds compared to the baseline QTc interval. QT0; QTc interval reading at the baseline. QT1; QTc interval reading one day after the first dose of anthracycline chemotherapy (FTP I). QT2; QTc interval reading one day after the last dose of anthracycline chemotherapy (FTP II). QT3; QTc interval reading six months after the completion of anthracycline chemotherapy (FTP III)