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

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.

Cinnamomum zeylanicum Blume (Ceylon cinnamon) bark extract attenuates doxorubicin induced cardiotoxicity in Wistar rats.

Anti-tumour efficacy of doxorubicin is hindered by the cumulative dose-dependent cardiotoxicity induced by reactive oxygen species during its metabolism. As Cinnamomum zeylanicum has proven antioxidant potential, objective of this study was to investigate the cardioprotective activity of Cinnamomum bark extract against doxorubicin induced cardiotoxicity in Wistar rats. Physicochemical and phytochemical analysis was carried out and dose response effect and the cardioprotective activity of Cinnamomum were determined in vivo. 180 mg/kg dexrazoxane was used as the positive control. Plant extracts were free of heavy metals and toxic phytoconstituents. In vivo study carried out in Wistar rats revealed a significant increase (p < 0.05) in cardiac troponin I, NT-pro brain natriuretic peptide, AST and LDH concentrations in the doxorubicin control group (18 mg/kg) compared to the normal control. Rats pre-treated with the optimum dosage of Cinnmamomum (2.0 g/kg) showed a significant reduction (p < 0.05) in all above parameters compared to the doxorubicin control. A significant reduction was observed in the total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activity while the lipid peroxidation and myeloperoxidase activity were significantly increased in the doxorubicin control group compared to the normal control (p < 0.05). Pre-treatment with Cinnamomum bark showed a significant decrease in lipid peroxidation, myeloperoxidase activity and significant increase in rest of the parameters compared to the doxorubicin control (p < 0.05). Histopathological analysis revealed a preserved appearance of the myocardium and lesser degree of cellular changes of necrosis in rats pre-treated with Cinnamomum extract. In conclusion, Cinnamomum bark extract has the potential to significantly reduce doxorubicin induced oxidative stress and inflammation in Wistar rats.

Anthracycline-Induced Cardiotoxicity in Breast Cancer Patients from Southern Sri Lanka: An Echocardiographic Analysis.

Anthracycline-induced cardiotoxicity has never been investigated in Sri Lanka. Therefore, this study was conducted to determine the prevalence of anthracycline-induced cardiotoxicity in breast cancer patients using echocardiographic findings. A prospective cohort study was performed. All newly diagnosed breast cancer patients who were administered with anthracycline and cyclophosphamide (AC schedule) for the first time were enrolled in the study. In the hospital setting, anthracycline is administered only as a combination therapy, and only this combination was selected to limit the effect of other cardiotoxic chemotherapy agents. Records of echocardiography were obtained: one day before anthracycline chemotherapy (baseline), one day after the first chemotherapy dose, one day after the last chemotherapy dose, and six months after the completion of anthracycline chemotherapy. Following parameters were recorded from the echocardiography results: ejection fraction (EF, %), fractioning shortening (FS, %), posterior wall thickness, left ventricle (PWT, mm), the thickness of interventricular septum (IVS, mm), left ventricular end-diastolic diameter (LVEDD, mm), and left ventricular end-systolic diameter (LVESD, mm). Statistical analysis of the echocardiography results was performed using ANOVA at four stages. A p value <0.05 was considered significant. Subclinical cardiac dysfunction was defined as a fall of EF >10% during the follow-up echocardiography. There was no significant change (p > 0.05) between the baseline echocardiographic parameters and one day after the 1st anthracycline dose. However, significant differences (p < 0.05) were observed between the baseline echocardiographic parameters and one day after the last anthracycline dose and six months after the completion of anthracycline therapy with a gradual and progressive deterioration in functional parameters including EF, FS, PWT, and IVS over time. There were 65 patients out of 196 (33.16%) who developed subclinical cardiac dysfunction six months after the completion of anthracycline chemotherapy. The prevalence of subclinical anthracycline-induced cardiotoxicity was relatively higher in these patients. An equation was also developed based on left ventricular ejection fraction (LVEF) to predict the anthracycline-induced cardiotoxicity of a patient six months after the completion of anthracycline chemotherapy. We believe that this will help in the monitoring of patients who undergo anthracycline therapy for cardiotoxicity. It is recommended to carry out a long-term follow-up to detect early-onset chronic progressive cardiotoxicity in all patients who were treated with anthracycline therapy.