3D strain echocardiography in detection of subclinical left ventricle dysfunction as a marker of early-onset anthracycline cardiotoxicity among children treated for acute lymphoblastic leukemia

Background The predominant malignancy in the pediatric population is acute lymphoblastic leukemia(ALL). Although survival rates are encouraging, the ALL therapeutic regimen includes cardiotoxic anthracyclines. The cardiotoxicity related to anthracycline use is detected in speckle tracing echocardiography among adult childhood cancer survivors and adult oncological patients. The data for children on detection of early-onset anthracycline-related cardiac dysfunction is lacking. Aim To assess left ventricle function in 3D strain echocardiography among children treated for ALL and detection of early-onset anthracycline cardiotoxicity after induction and intensification therapy completion. Methods In this prospective study, consecutive pediatric patients diagnosed with ALL were enrolled. Transthoracic echocardiography was conducted following diagnosis and prior to the initiation of anthracycline therapy (first assessment), and after the completion of induction and intensification therapy (second assessment). Three-dimensional echocardiographic recordings were analyzed offline using the 4D LV-Analysis software to evaluate left ventricular ejection fraction(3D-LVEF), global longitudinal strain(3D-LV-GLS), global circumferential strain(3D-LV-GCS), and radial strain(3D-LV-GRS). Results from the second assessment of the study group were compared with a control group consisting of age-matched healthy children. Interobserver reliability of the data was assessed by two echocardiographers. Results The study cohort comprised 26 children(12 females, 14 males) aged between 1-16 years(mean age 5,9±3,7years). Among these, 23(85%) children were diagnosed with ALL type C, and 25(96%) were treated according to the AIEOP BMF 2017 protocol. The mean interval between the first and second echocardiographic assessments was 212 days(7 months). The cumulative dose of doxorubicin administered was 181,7± 62mg/m², with 8 children receiving a dose >200 mg/m² and one child >300 mg/m². Statistically significant differences between the first and the second echocardiography were observed 3D-LVEF(59,7±7,3% vs. 53,2±4,2%,p=0,004), 3D-LV-GLS(-23,3±5,3% vs -20,2±3,2%,p=0,031) and 3D-LV-GCS(-26,4±6,0% vs. -21,8±3,2%,p=0,012), the difference in 3D-LV-GRS was not statistically significant. The decrease of >15% from first assessment was observed in 9(35%) in 3D-LVGLS, 12(46%) in 3D-LVGCS and only in 3(12%) patients in 3D-LVGRS. In comparison with the control group the differences were observed in 3D-LVEF(53,2±4,2% vs. 60,7±5,8%,p<0,001), 3D-LV-GLS(-20,2±3,6% vs. -24,9±3,9%,p<0,001) and 3D-LV-GCS (21,8±3,2% vs. -28,2±4,5%, p<0,001) as well as in 3D-LV-GRS(-35,4±4,6% vs. -45,1±5,9%,p<0,001). Conclusions 3D echocardiography with speckle tracing may be sensitive method in detection of early anthracycline-related cardiac dysfunction in children treated for ALL. Early detection of subclinical cardiotoxicity may enable implementation of cardioprotective measures and treatment.Table 1- results Figure 1- protocol