The Cardiac Electrical Activity Injury Caused By Epirubicin Chemotherapy For Breast Cancer Patients With Diabetes

Objective: In recent years, the incidence of breast cancer increased yearby year.In the developed cities of China such as Beijing, Shanghai, Tianjin,breast cancer accounts for the first incidence of women, to become the greatestthreat to women’s health.Anthracycline-based chemotherapy plays animportant role in the treatment of breast cancer, but the cardiotoxicity causedby it often limits its anti-cancer efficacy, is becoming a hot research in recentyears. According to the WHO’s classification standard of common adversereaction caused by anti-cancer drugs, the assessment of cardiotoxicity isdivided into three aspects: rhythm, heart function and pericarditis.Theventricular diastolic or contraction function change caused by anthracycline isrelatively late stage, the positive rate is low in short-term observation andcardiac electrophysiological changes appear earlier, and the positive rate ishigh. Among the indicators of cardiac electrophysiological activity,correctedQT interval (QTc interval) and heart rate variability (HRV) have relativelyhigh specificity and repeatability, they are used to monitor changes in theelectrical activity of the heart is better than QRS wave, arrhythmia, ST-Tchanges, etc. According to statistics, there are up to16%of the breast cancerpatients are also suffering from diabetes. At present,across home andabroad,studies of the cardiotoxicity risk for the diabetic breast cancer patientsreceiving anthracycline are still very few. Test in this paper by comparing theQTc interval and HRV between the female breast cancer patients with diabetesand the patients without diabetes, to assess the toxic effects of cardiacelectrophysiological activities caused by the clinical commonly usedchemotherapy for breast cancer,and to clear diabetes whether can increasethe cardiotoxicity caused by anthracycline, and to provide evidence forclinical. Methods: This study recruited25cases of female breast cancer patientswith diabetes from May2012to September2013at Breast Center of4thhospital of Hebei Medical University, set to diabetes group, and25age-matched cases of female breast cancer patients without diabetes, set ascontrol group.All patients were confirmed of primary breast cancer bysurgical treatment and postoperative pathology and received chemotherapywith EC plan (E: Epirubicin; C: Cyclophosphamide)4-6cycles, experimentalobservation of the first four cycles.Before and after4cycles of thechemotherapy,all patients were examined by12-lead electrocardiogram and24-hour dynamic electrocardiogram. All diabetic patients withoutcomplications such as coronary heart disease, cardiac insufficiency,arrhythmia, hypertension, kidney disease, etc.Diabetes duration <10years, theaverage (3.43+2.58) years. Before the chemotherapy,all of the patients didnot received any other chemotherapy drugs and radiation therapy,and wereconfirmed without cardiopulmonary disease, EF value50%or higher, noserious damage to liver and kidney function,no anemia, no hyperthyroidism orhypothyroidism, no serious electrolyte disorder, no prolong QT interphase andprotect neurological drugs within1week.In order to test the results withoutinterference, all patients did not use protecting myocardial drugs. Analysis ofthe change of QTc interphase and HRV between the diabetes group and thecontrol group before and after the chemotherapy. The indexes of HRV include:(1) Time domain indexes:①SDNN(standard deviation of all normal-to-normalintervals);②SDANN(standard deviation of the average of allnormal-to-normal intervals in all5-minute intervals);③RMSSD(root meansquare of differences between adjacent normal-to-normal intervals);④pNN50(percent of NN50in the total number of normal-to-normal intervals);(2)Frequency domain indexes:①LF (low frequency of0.04~0.15Hz) reflectingthe activity of sympathetic nerve and vagus nerve;②HF (high frequency of0.15~0.40Hz), reflecting the activity of the vagus nerve,③LF/HF (the ratioof low frequency band and high frequency band), reflecting the balance of thesympathetic nerve and the vagus nerve. Results: All of the patients during the chemotherapy had no cardicinsufficiency of clinical manifestations.Three patients had a brief arrhythmia,no dealing with it.After the chemotherapy, we did not see obvious anomaliesin hemoglobin,electrolyte and thyroid function.1、There were no significant differences in age and body mass index betweenthe diabetes group and the control group(P>0.05).2、Comparison between the two groups in QTc interphase: QTc interphase ofthe diabetes group and the control group were all significantly longer afterchemotherapy(P<0.01). Before the chemotherapy,QTc interphase was nostatistically significant difference between the diabetes group and the controlgroup (P>0.05). After the chemotherapy,QTc interphase was statisticallysignificant difference between the diabetes group and the control group(P<0.01). Clearly, the diabetes group’s QTc interphase prolong is moreobvious.3、Comparison between the two groups in HRV:SDNN,SDANN,RMSSD,pNN50,LF and HF of the diabetes group and the control group were all reducedafter the chemotherapy, and the LF/HF ratio was all increased after thechemotherapy(P<0.01).Before the chemotherapy,SDNN,SDANN,RMSSD,pNN50,LF and HF were lower in the diabetes group compared with the controlgroup, and the LF/HF ratio was higher(P<0.01);The reduce of SDNN,SDANN，LF,HF and the LF/HF ratio after the chemotherapy was bigger in the diabetesgroup compared with the control group(P<0.01);and the reduce of RMSSDand pNN50after the chemotherapy were no difference(P>0.05).The testshows that anthracycline-based chemotherapy causes autonomic nervedysfunction, sympathetic nerve and vagus nerve tension decreases, and thevagus nerve tension reducing is more obvious, sympathetic relative advantageat this time.Diabetes patients already have autonomic nerve function disorderbefore the chemotherapy, and more obvious after the chemotherapy.Conclusion:1Epirubicin chemotherapy can lead to ventricular repolarization latency andautonomic nerve dysfunction of the breast cancer patients. 2Diabetes increases the electrical injury caused by epirubicin chemotherapy.