Subacute Anthracycline-Related Cardiotoxicity in Adolescent and Young Adult Patients of Sarcoma: A Prospective Echocardiographic Study

Adolescent and young adult patients aged 15 to 39 years with a diagnosis of sarcoma who were scheduled to receive high-dose Dox (≥300 mg/m²) at a single tertiary cancer center between 2018 and 2022 were prospectively enrolled. The study (PA18-0462) was approved by the Institutional Review Board, and written informed consent was obtained from all participants or their legally authorized guardians as appropriate. Transthoracic echocardiograms were performed at baseline (prior to initiation of Dox therapy) and at predefined follow-up time points at one and two years after treatment initiation. All studies were conducted by certified sonographers in accordance with the American Society of Echocardiography guidelines for performing a comprehensive transthoracic echocardiographic examination. Image interpretation was performed by a single board-certified cardiologist blinded to clinical data and in accordance with American Society of Echocardiography interpretation standards. The primary composite endpoint was the development of subacute cardiotoxicity, defined for the purposes of this study as: i. reduction in LVEF by >10 percentage points from baseline or an absolute LVEF <50%, or ii. >10% decrease in the LVWT/D ratio at one and two years after Dox exposure compared with baseline. Secondary endpoints included longitudinal changes in echocardiographic indices of cardiac structure, chamber volumes, left and right ventricular systolic function, diastolic function, and myocardial deformation. Changes were assessed across three intervals: baseline to one year, one to two years, and baseline to two years. Echocardiographic measures were also compared with published age- and sex-specific normative values from the general population.