Abstract 4361008: Longitudinal Echocardiographic Assessment of Subacute Cardiotoxicity in a Prospective Cohort of Adolescents and Young Adults with Sarcoma Treated with High-Dose Doxorubicin

Introduction: Anthracycline-induced cardiomyopathy is a significant cause of morbidity and mortality among adolescents and young adults (AYAs) with sarcoma. Latency between myocardial injury, dysfunction, and symptoms delays diagnosis and may affect reversibility of myocardial damage. This study aims to identify subacute, longitudinal echocardiographic changes following high-dose doxorubicin (Dox) exposure in AYAs with sarcoma that may predict development of cardiomyopathy. Methods: AYAs (age 15-39) with sarcoma treated at a tertiary cancer center from 2018-2022 were prospectively enrolled. Echocardiograms (echo)s were done prior to, one and two years after Dox exposure. Study cardiologists performed standardized interpretation. Results: Of 75 patients, 56 completed at least 2 of the 3 study echos and were included in this analysis (median age 24.1 years [IQR, 17.6−30.5], median BMI 24.6 [IQR, 21.6−32.5], 84% white, 41% female). Median cumulative Dox dose was 450 [IQR, 370−450] mg/m2 with 95% of patients receiving >250mg/m2 and 75% receiving dexrazoxane. From baseline to 1 year, there were significant absolute changes in LVEF (-2.73±4.3%), GLS (1.37±2.56%), septal e’ (-1.75±2.48cm/s), lateral e’ (-2.78±3.44cm/s), MPI ave (0.03±0.11), LVEDVi (-3.88±13.67 ml/m2) and TAPSE (-0.2±0.5cm). The changes remained significant at year 2. No significant changes were noted in wall thickness, left atrial volume or PWT/LVEDD. At one year, 6% of patients developed a significant drop in LVEF (>10%), 27% developed >15% relative drop in LV GLS, 44% developed >20% drop in lateral e’ and 35% developed >20% drop in septal e’. Among baseline variables, smoking history was associated with significant echo changes (OR 11.3, 95% CI [2.0-64.3]). Dexrazoxane was not associated with preservation of LV systolic and diastolic function or strain but this finding should be interpreted in the context of a small sample size. Conclusions: A significant proportion of AYAs with sarcoma treated with high-dose Dox have worsened LV systolic and diastolic function, as well as strain 1 year post treatment. Beyond LVEF, which has been traditionally used to define cancer therapy related cardiac dysfunction, use of diastolic function and strain may be valuable for risk stratification and diagnosis of subacute Dox-induced myocardial injury. Larger, prospective studies with longer follow up are needed to determine if these early echo abnormalities translate into subsequent cardiomyopathy or heart failure.