Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors
William L. Border, Ritu Sachdeva, Kayla Stratton, Saro H. Armenian, Aarti Bhat, David E. Cox, Kasey J. Leger, Wendy M. Leisenring, Lillian R. Meacham, Karim Thomas Sadak, Shanthi Sivanandam, Paul C. Nathan, Eric J. Chow
Abstract
BACKGROUND: Childhood cancer survivors undergo serial echocardiograms to screen for cardiotoxicity. It is not clear whether small longitudinal changes in functional or structural parameters over time have clinical significance. OBJECTIVES: To assess the timing of changes in serial echocardiographic parameters in pediatric age childhood cancer survivors and to evaluate their associations with cardiomyopathy development. METHODS: We performed a multi-center retrospective case-control study of ≥1-year survivors following the end of cancer therapy. Cardiomyopathy cases (fractional shortening (FS) ≤28% or ejection fraction (EF) ≤50% on ≥2 occasions) were matched to controls (FS ≥30%, EF ≥55%, not on cardiac medications) by cumulative anthracycline and chest radiation dose, follow-up duration, and age at diagnosis. Digitally archived clinical surveillance echocardiograms were quantified in a central core lab, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2D, M-mode, pulsed wave Doppler and tissue Doppler imaging derived parameters across time between cases and controls. RESULTS: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n=181; controls, n=231) determined that indices of LV systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and LV size (end diastolic dimension z-scores) were significantly different between cases and controls, even four years prior to the development of cardiomyopathy. CONCLUSIONS: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric age childhood cancer survivors and are associated with the development of cardiomyopathy.