Three-Dimensional Left Ventricle Strain Echocardiography in the Detection of Anthracycline Cardiotoxicity in Children with Acute Lymphoblastic Leukemia-Retrospective Case-Control Analysis and Relation to the Cardiotoxicity Risk Factors Assessment.
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BACKGROUND/OBJECTIVES: Acute lymphoblastic leukemia (ALL) treatment is effective but involves the use of cardiotoxic anthracyclines. Data on three-dimensional (3D) strain echocardiography utility in the monitoring of acute and early-onset cardiotoxicity in children with ALL are scarce. The aim was to assess the left ventricular function in 3D strain echocardiography in children with ALL treated with anthracyclines in reference to a healthy cohort and to assess risk factors of possible subclinical cardiotoxicity. METHODS: For this study, medical records from between May 2023 and December 2024 were retrospectively analyzed, and the echocardiographic data were reassessed. The study group consisted of children diagnosed and treated for ALL for at least 6 months with the use of daunorubicin and doxorubicin (or only with daunorubicin) who underwent routine cardiological evaluation with 3D echocardiography in >6 months and <2 years from the beginning of treatment. The echocardiographic records were reassessed offline to analyze the left ventricle 3D global longitudinal (GLS 3D), circumferential (GCS 3D) and radial (GRS 3D) strain. The results were compared with the results of 24 apparently healthy peers matched by sex and age. A set of models was developed to test literature-based subclinical cardiotoxicity determinants in relation to the obtained 3D strain values. RESULTS: The study group consisted of 42 children (22 males and 20 females) aged 2-17 years (mean 7.7 ± 4.1 years) treated for ALL. The median time from the first anthracycline dose was 0.59 (IQR1 = 0.5; IQR3 = 0.96) years with a cumulative equivalent anthracycline dose of 158.2 ± 78.0 (min. 48.0-max. 451.8) mg/m2. Statistically significant differences between study and control groups were observed in terms of LVEF 3D (53.9 ± 4.4% vs. 59.1 ± 5.8%, p < 0.001), GLS 3D (-21.8 ± 4.2% vs. -25.2 ± 3.6%, p < 0.001), GCS 3D (-22.3 ± 3.8% vs. -27.3 ± 4.7%, p < 0.001) and GRS 3D (37.1 ± 5.0% vs. 44.6 ± 5.7%, p < 0.001). None of the previously described cardiotoxicity risk factors-age at the diagnosis, sex, age at treatment initiation, body surface area (BSA) at treatment initiation, time since treatment initiation, ALL subtype, total anthracycline dose and doxorubicin treatment-were statistically significant in the GLS or GCS models. CONCLUSIONS: GLS 3D, GCS 3D and GRS 3D of the left ventricle may be sensitive indicators of myocardial dysfunction in children with ALL treated with anthracyclines. The relation of the previously described cardiotoxicity risk factors to the 3D strain values and myocardial dysfunction is inconclusive; further studies are warranted.