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Prospective longitudinal assessment of late anthracycline cardiotoxicity after childhood cancer: the role of diastolic function
  1. I Dorup1,
  2. G Levitt2,
  3. I Sullivan3,
  4. K Sorensen1
  1. 1Department of Cardiology, Aarhus University Hospital (SKS), Aarhus N, Denmark
  2. 2Department of Haematology/Oncology, Great Ormond Street Hospital for Children NHS Trust, London, UK
  3. 3Department of Cardiology, Great Ormond Street Hospital for Children NHS Trust
  1. Correspondence to:
    Dr Inge Dorup
    Department of Cardiology B, Aarhus University Hospital (SKS), Brendstrupgaardsvej, DK-8200 Aarhus N, Denmark;

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Anthracyclines are highly effective in the treatment of childhood malignancies, but are potentially cardiotoxic at all dose ranges. Early studies suggested that as many as 65% of acute lymphoblastic leukaemia (ALL) survivors have subclinical abnormalities of left ventricular (LV) systolic function at medium term follow up. More recent reports have shown that the prevalence of cardiac abnormalities is much lower with cumulative anthracycline doses of less than 250–300 mg/m2.1–4

It has been suggested that diastolic changes precede systolic dysfunction in various conditions and predict later deterioration. Similarly, LV restriction has been suggested to be a late functional event after anthracycline exposure. Most reports of anthracycline cardiotoxicity are cross-sectional studies of heterogeneous diagnostic groups receiving various anthracycline schedules.5 We obtained prospective longitudinal diastolic data in two well defined cohorts of long term survivors of ALL and Wilms’ tumor (WT) and compared this to systolic function. Both cohorts underwent echocardiographic evaluation in 1991–92 and again in 1995–96.


The original cohort consisted of 120 ALL survivors, comprising a convenience sample of 40 survivors from each of three treatment groups receiving a total dose of 90, 180 or 270 mg/m2 of daunorubicin. Initially, 106 of these subjects underwent investigation of diastolic filling on average 6.2 years after anthracyline treatment, and 94 patients underwent follow up leaving comparative diastolic data available in 88 patients.

From 110 WT patients treated between 1970 and 1990, 90 underwent investigation of diastolic filling in 1991–92, and 78 were reinvestigated in 1995–96, on average 6.7 years and 11.1 years after treatment, respectively. Of these, 66 subjects had complete comparative diastolic data sets. Mean cumulative doxorubicin dose at first study was 303 (79) mg/m2.

One hundred healthy children and adolescents were studied on a single occasion using identical echocardiographic methods.

LV diastolic …

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