Comprehensive Echocardiographic Detection of Treatment-Related Cardiac Dysfunction in Adult Survivors of Childhood Cancer: Results From the St. Jude Lifetime Cohort Study

J Am Coll Cardiol. 2015 Jun 16;65(23):2511-22. doi: 10.1016/j.jacc.2015.04.013.

Abstract

Background: Treatment-related cardiac death is the primary, noncancer cause of mortality in adult survivors of childhood malignancies. Early detection of cardiac dysfunction may identify a high-risk subset of survivors for early intervention.

Objectives: This study sought to determine the prevalence of cardiac dysfunction in adult survivors of childhood malignancies.

Methods: Echocardiographic assessment included 3-dimensional (3D) left ventricular ejection fraction (LVEF), global longitudinal and circumferential myocardial strain, and diastolic function, graded per American Society of Echocardiography guidelines in 1,820 adult (median age 31 years; range: 18 to 65 years) survivors of childhood cancer (median time from diagnosis 23 years; range: 10 to 48 years) exposed to anthracycline chemotherapy (n = 1,050), chest-directed radiotherapy (n = 306), or both (n = 464).

Results: Only 5.8% of survivors had abnormal 3D LVEFs (<50%). However, 32.1% of survivors with normal 3D LVEFs had evidence of cardiac dysfunction by global longitudinal strain (28%), American Society of Echocardiography-graded diastolic assessment (8.7%), or both. Abnormal global longitudinal strain was associated with chest-directed radiotherapy at 1 to 19.9 Gy (rate ratio [RR]: 1.38; 95% confidence interval [CI]: 1.14 to 1.66), 20 to 29.9 Gy (RR: 1.65; 95% CI: 1.31 to 2.08), and >30 Gy (RR: 2.39; 95% CI: 1.79 to 3.18) and anthracycline dose > 300 mg/m(2) (RR: 1.72; 95% CI: 1.31 to 2.26). Survivors with metabolic syndrome were twice as likely to have abnormal global longitudinal strain (RR: 1.94; 95% CI: 1.66 to 2.28) and abnormal diastolic function (RR: 1.68; 95% CI: 1.39 to 2.03) but not abnormal 3D LVEFs (RR: 1.07; 95% CI: 0.74 to 1.53).

Conclusions: Abnormal global longitudinal strain and diastolic function are more prevalent than reduced 3D LVEF and are associated with treatment exposure. They may identify a subset of survivors at higher risk for poor clinical cardiac outcomes who may benefit from early medical intervention.

Keywords: cardiomyopathy; cardiotoxicity; heart failure; late effects; screening; strain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Antibiotics, Antineoplastic / adverse effects*
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / diagnostic imaging*
  • Cardiovascular Diseases / epidemiology
  • Child
  • Child, Preschool
  • Cohort Studies
  • Echocardiography, Three-Dimensional* / trends
  • Female
  • Follow-Up Studies
  • Humans
  • Infant
  • Infant, Newborn
  • Longitudinal Studies
  • Male
  • Neoplasms / drug therapy*
  • Neoplasms / epidemiology
  • Stroke Volume / drug effects
  • Stroke Volume / physiology
  • Survivors*
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Antibiotics, Antineoplastic