Early anthracycline cardiotoxicity in adolescents and young adults with sarcoma: a prospective echocardiographic study

Adolescents and young adults (AYAs) with sarcomas often receive high-dose doxorubicin (Dox), but data on early cardiotoxicity in this population are limited.

To prospectively evaluate early echocardiographic changes in AYAs with sarcoma treated with high-dose Dox.

AYAs (15–39 years) with sarcoma treated at a tertiary cancer centre (2018–22) were prospectively enroled. Echocardiograms were performed at baseline, 1 and 2 years after cancer therapy initiation and interpreted by a single cardiologist. The primary endpoint was a >10% absolute reduction in left ventricular ejection fraction (LVEF), an absolute LVEF <50%, or >10% decrease in LV wall thickness/dimension (LVWT/D) ratio from baseline. Secondary endpoints included longitudinal changes in cardiac structure, chamber volumes, systolic and diastolic function, and strain.

Of 70 patients, 56 completed at least two of three study echocardiograms (median age 22.6 [IQR, 17.6–30.5] years; 41% female, 84% white). Median cumulative Dox dose was 450 (IQR, 370–450) mg/m²; 75% received dexrazoxane. The primary endpoint was met by 44.4% at 1 year and 27.5% at 2 years, driven primarily by LVWT/D ratio decline (37% at 1 year, 25% at 2 years), while significant LVEF decline was observed in 11.1% and 2.5%, respectively. Significant absolute changes at 1 year included LVEF (−2.73 ± 4.3%, P < .001), global longitudinal strain magnitude (−1.37 ± 2.56%, P = .002), septal e′ (−1.75 ± 2.48 cm/s, P < .001), and lateral e′ (−2.78 ± 3.44 cm/s, P < .001), persisting at 2 years. One patient (1.8%) developed ventricular fibrillation and heart failure with reduced ejection fraction, with LVEF recovery within 1 year.

Over one-third of AYAs with sarcoma met the primary endpoint at 1 year, with half of these abnormalities persisting at 2 years, primarily driven by LVWT/D ratio reductions. Subclinical changes in strain and diastolic function were observed, reflecting the broad cardiac impact of high-dose Dox in this population.