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

Abstract

Background: Cardiovascular disease is the leading non-cancer cause of death among survivors of childhood cancer. Ejection fraction (EF) and fractional shortening (FS) are common echocardiographic measures of cardiac function. Newer analysis modalities, including radial displacement, may provide additional information about pre-clinical disease such as regional myocardial dysfunction. Methods: We compared mean radial displacement, EF, and FS among adult survivors of childhood cancer exposed to ≥ 250 mg/m2 of anthracyclines to age, sexmatched healthy controls. Survivors with a history of cardiac directed radiation, diabetes, or heart disease were excluded. Results: There were no differences in gender (35% male vs. 35% male, p=1.0) or current age (28.4 years (range18-50) vs. 28.7 years (range 18-50), p=0.94) between survivors and controls, respectively. Among survivors mean age at diagnosis was 12.5 (range 1-20) years, mean survival time 16 (range 5-30) years, and mean anthracycline exposure was 420 (range 300-645) mg/m2. FS (35.5% vs. 39.6%, p < 0.01) and radial displacement (5.6 mm vs. 6.7 mm, p = 0.02) were significantly lower in cancer survivors as compared to controls. EF showed a trend towards being lower in survivors versus controls (55.4% vs. 59.7%, p = 0.057). All echocardiographic measures were inversely related with dose of anthracyclines, though radial displacement was no longer significantly correlated with antrhacycline dose after controlling for survival time (p = 0.07) while EF remained correlated (p = 0.003). Conclusions: Novel and traditional measures of radial displacement, FS, and EF are lower in childhood cancer survivors in long-term follow-up compared to controls. Novel measures may add new information, but the potential clinical utility remains undetermined and requires further longitudinal study.