Obesity Predisposes Anthracycline-Treated Survivors of Childhood and Adolescent Cancers to Subclinical Cardiac Dysfunction

Anthracyclines are effective chemotherapeutics used in approximately 60% of pediatric cancer cases but have a well-documented risk of cardiotoxicity. Existing cardiotoxicity risk calculators do not include cardiovascular risk factors present at the time of diagnosis. The goal of this study is to leverage the advanced sensitivity of strain echocardiography to identify pre-existing risk factors for early subclinical cardiac dysfunction among anthracycline-exposed pediatric patients. We identified 115 pediatric patients with cancer who were treated with an anthracycline between 2013 and 2019. Peak longitudinal left ventricular strain was retroactively calculated on 495 surveillance echocardiograms via the TOMTEC AutoSTRAIN software. Cox proportional hazards models were employed to identify risk factors for abnormal longitudinal strain (> - 16%) following anthracycline treatment. High anthracycline dose (>= 250 mg/m(2) doxorubicin equivalents) and obesity at the time of diagnosis (BMI > 95th percentile-for-age) were both significant predictors of abnormal strain with hazard ratios of 2.79, 95% CI (1.07-7.25), and 3.85, 95% CI (1.42-10.48), respectively. Among pediatric cancer survivors, patients who are obese at the time of diagnosis are at an increased risk of sub-clinical cardiac dysfunction following anthracycline exposure. Future studies should explore the incidence of symptomatic cardiomyopathy 10-15 years post-treatment among patients with early subclinical cardiac dysfunction.