Cardiac function in 5-year survivors of childhood cancer: a long-term follow-up study

Arch Intern Med. 2010 Jul 26;170(14):1247-55. doi: 10.1001/archinternmed.2010.233.


Background: Childhood cancer survivors (CCSs) have an increased risk of morbidity and mortality. We evaluated the prevalence and determinants of left ventricular (LV) dysfunction in a large cohort of long-term CCSs treated with different potentially cardiotoxic therapies.

Methods: The study cohort consisted of all adult 5-year CCSs who were treated with potentially cardiotoxic therapies and who visited our late effects outpatient clinic. Echocardiography was performed in patients who had received anthracyclines, cardiac irradiation, high-dose cyclophosphamide, or high-dose ifosfamide. Detailed treatment data were registered. Both multivariate linear and logistic regression analyses were performed.

Results: Of 601 eligible CCSs, 525 (87%) had an echocardiogram performed, of which 514 were evaluable for assessment of the LV shortening fraction (LVSF). The median overall LVSF in the whole group of CCSs was 33.1% (range, 13.0%-56.0%). Subclinical cardiac dysfunction (LVSF <30%) was identified in 139 patients (27%). In a multivariate linear regression model, LVSF was reduced with younger age at diagnosis, higher cumulative anthracycline dose, and radiation to the thorax. High-dose cyclophosphamide and ifosfamide were not associated with a reduction of LVSF. Vincristine sulfate was associated with a nonsignificant decrease of cardiac function (P = .07). Epirubicin hydrochloride was as cardiotoxic as doxorubicin when corrected for tumor efficacy, and daunorubicin hydrochloride seemed less cardiotoxic.

Conclusions: A high percentage (27%) of young adult CCSs have an abnormal cardiac function. The strongest predictors of subclinical cardiac dysfunction are anthracycline dose, cardiac irradiation, and younger age at diagnosis. There is a suggestion that daunorubicin is less cardiotoxic than other anthracyclines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anthracyclines / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Child
  • Child, Preschool
  • Cohort Studies
  • Doxorubicin / adverse effects
  • Echocardiography
  • Epirubicin / adverse effects
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Linear Models
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Neoplasms / drug therapy*
  • Neoplasms / radiotherapy*
  • Netherlands / epidemiology
  • Prevalence
  • Prospective Studies
  • Risk Factors
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / diagnosis
  • Ventricular Dysfunction, Left / epidemiology*
  • Ventricular Dysfunction, Left / etiology*


  • Anthracyclines
  • Epirubicin
  • Doxorubicin