Evaluation of traditional and novel measures of cardiac function to detect anthracycline-induced cardiotoxicity in survivors of childhood cancer

Purpose: Cardiovascular disease is the leading noncancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function, but newer imaging modalities may provide additional information about preclinical disease. This study aimed to evaluate these modalities in detection of anthracycline-induced cardiac toxicity. Methods: We compared mean radial displacement, EF, and FS among 17 adult survivors of childhood cancer exposed to ≥ 300 mg/m² of anthracyclines to 17 age- and sex-matched healthy controls. Survivors with a history of cardiac-directed radiation, diabetes, or heart disease were excluded. Results: Survivors (35 % male), mostly with history of treatment for a solid tumor, had a median age at diagnosis of 15 years (1-20) and 27 years (18-50) at evaluation. Median anthracycline exposure was 440 (range 300-645) mg/m². FS (35.5 vs. 39.6 %, p < 0.01) and radial displacement (5.6 vs. 6.7 mm, p = 0.02) were significantly lower in survivors compared to controls, respectively. Although the mean EF was lower in survivors versus controls (55.4 vs. 59.7 %), it was not statistically significant (p = 0.057). All echocardiographic measures were inversely associated with anthracycline dose, though radial displacement was no longer significantly correlated with anthracycline dose after controlling for survival time (p = 0.07), while EF remained correlated (p = 0.003). Implications for Cancer Survivors: Radial displacement, EF, and FS are lower in childhood cancer survivors compared to controls. In this study, radial displacement added no new information beyond the traditional measures, but clinical utility remains undetermined and requires further longitudinal study.