The Clinical Assessment Of Subclinical Anthracycline-induced Cardiotoxicity By Two-dimentional Speckle Tracking Imaging

【Background】With advances in cancer treatment,the survival time of patients with malignant tumors had been significantly prolonged.However,the cardiotoxicity caused by chemotherapy had seriously affected the quality of life of cancer survivors.Anthracyclines were the first-line chemotherapy drugs for non-hodgkin’s lymphoma.Most occult cardiotoxicity had no clinical manifestations before the onset of symptoms of heart failure.Echocardiography was the most commonly used technique for clinical monitoring of cardiac toxicity of anthracyclines due to its simplicity and economy.Left ventricular ejection fraction（LVEF）,was the most commonly used indicator for monitoring cardiac function in patients undergoing chemotherapy.However LVEF had a poor sensitivity.Therefore,its use in monitoring occult cardiotoxicity had some limitations.Ultrasound two-dimensional speckle tracking imging（2D-STI）was a new technology developed rapidly in recent years,which could qualitatively and quantitatively display myocardial motion speed,strai,strain rate and so on.Compared with traditional echocardiography parameters,it could more sensitively identify occultive myocardial damage,especially the two-dimensional strain parameter（LV GLS）.ESC,ASE,EACVI and other academic guidelines recommended LV GLS as one of the central function monitoring indexes during chemotherapy follow-up.At present,the monitoring of cardiac function in patients with chemotherapy was mainly focused on the left ventricle,but less on the right ventricle.Therefore this study used2D-STI technology and conventional echocardiographic parameters to monitor changes in left and right ventricular function during chemotherapy,observed the changes in the parameters related to the accumulation of anthracycline doses in order to find the value of these parameters in predicting early cardiotoxicity and the correlation between these parameters and the cumulative dose of anthracyclines,and tried to find an early and sensitive indicator to identify the occult myocardial injury caused by anthracyclines.【Methods】A total of 52 patients who were initially diagnosed with non-hodgkin’s lymphoma by pathology from October 2018 to January 2020,and completed 6 cycles of R-CHOP chemotherapy were enrolled.Echocardiography was performed at baseline（T₀）and during 1-6 cycles chemotherapy(T_1-6)within 24 hours after each cycle.Two-dimensional traditional echocardiographic parameters were measured:left ventricular end diastolic diameter（LVEDd）,interventricular septal end-diastolic thickness（IVSd）,left ventricular posterior wall end-diastolic thickness（LVWPd）,end-systolic anteroposterior diameter of left atrial（LA-ap）,end-diastolic right ventricular basement transverse diameter（RVD-B）,end-diastolic right ventricular transverse diameter（RVD-M）,and right ventricle fractional area change（FAC）.Simpson method to measure left ventricular ejection fraction（LVEF）,left atrial volume（LAV）.M-type echocardiography to measure tricuspid annulus plane systolic excursion（TAPSE）.Pulse Doppler measurement of the peak E-velocity of the mitral valve during early diastole and the peak A-velocity of the late diastole to calculate the E/A ratio.Tissue Doppler measurement of peak velocities of mitral annulus ventricular septal movement in early diastole e’,peak velocity of ventricular septal movement in late diastole a’,calculated E/e’.Simultaneously measured the isovolumetric relaxtion time（IRT）,isovolumic contraction time（ICT）,and ejection time（ET）,and calculated the left ventricular Tei index,Tei index=（IRT+ICT）/ET.Two-dimensional speckle tracking imaging was used to analyze the left ventriclar global longitudinal strain（LV GLS）and the right ventriclar global longitudinal strain（RV GLS）and right ventricular free wall global longitudinal strain value（RV FWLS）.According to the European Society of Cardiology（ESC）,cardiotoxicity was defined as a decrease of baseline LVEF>10%,to a value below the lower limit of normal（considered as an LVEF<50%）.【Results】Compared with the baseline,LV GLS absolute value had a significant decrease since the end of the second cycle of chemotherapy（T₂）（P<0.01）,which was also negatively associated with the cumulative dose of anthracycline（spearman rho=-0.563,P<0.01）.Ventricular septal Tei index increased significantly from the end of the third cycle of chemotherapy（T₃）（P<0.05）,and was positively correlated with the cumulative dose of anthracycline（spearman rho=0.295,P<0.01）.The absolute values of RV GLS and RV FWLS significantly declined from the end of the fourth cycle of chemotherapy（T₄）（P<0.05）,which was negatively correlated with the cumulative dose of anthracycline（spearman rho=-0.230,-0.228,P<0.01）.E/e’increased significantly from the end of the fifth cycle of chemotherapy（T₅）（P<0.05）,which was correlated with the cumulative dose of anthracycline（spearman rho=0.226,P<0.01）.LVEF,e’,TAPSE and RV FAC showed a significant impaired untill the end of the sixth cycle of chemotherapy（T₆）（P<0.05）,which was negatively correlated with the cumulative dose of anthracycline,but the correlation was small.During all 6 cycles of chemotherapy and at the end of chemotherapy,no significant symptoms of heart failure were observed in all subjects.According to the recent position paper of the European Society of Cardiology（ESC）,a total of 5patients developed cardiotoxicity（decrease of baseline LVEF>10%,to a value below the lower limit of normal）.Logistic regression analysis found that the occurrence of anthracycline cardiotoxicity was not related to gender,age,diabetes,hypertension,body surface area,BMI,ACEI,calcium channel antagonists,and ARB administration.A LV GLS absolute value decrease of>15%was an independent predictor of anthracycline cardiotoxicity（P=0.004）,with a sensitivity of 83.3%and a specificity of 95%.【Conclusion】The golbal longitudinal strain value based on the two-dimensional speckle tracking imaging could effectively identify the left and right ventricular mild injury caused by anthracyclines.Tei index and left ventricular diastolic function index E/e’could detect the left ventricular function changes caused by anthracyclines earlier than2D LVEF.A decrease in left ventricular GLS of>15%was an independent predictor of anthracycline cardiotoxicity.