Longitudinal Changes in Echocardiographic Parameters of Cardiac Function in Pediatric Cancer Survivors

OBJECTIVES: The purpose of this study was to assess the timing of changes in serial echocardiographic parameters in pediatric cancer survivors and to evaluate their associations with cardiomyopathy development. BACKGROUND: Pediatric 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. METHODS: This is a multicenter, 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 control subjects (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 laboratory, blinded to patient characteristics. Using mixed models with interaction terms between time and case status, we estimated the least square mean differences of 2-dimensional, M-mode, pulsed wave Doppler, and tissue Doppler imaging–derived parameters over time between cases and control subjects. RESULTS: We identified 50 matched case-control pairs from 5 centers. Analysis of 412 echocardiograms (cases, n = 181; control subjects, n = 231) determined that indices of left ventricular systolic function (FS, biplane EF), diastolic function (mitral E/A ratio), and left ventricular size (end-diastolic dimension z-scores) were significantly different between cases and control subjects, even 4 years prior to the development of cardiomyopathy. CONCLUSIONS: Longitudinal changes in cardiac functional parameters can occur relatively early in pediatric cancer survivors and are associated with the development of cardiomyopathy.