Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: Results from the St. Jude Lifetime Cohort Study

Gregory T. Armstrong*, Vijaya M. Joshi, Kirsten K. Ness, Thomas H. Marwick, Nan Zhang, Deokumar Srivastava, Brian P. Griffin, Richard A. Grimm, James Thomas, Dermot Phelan, Patrick Collier, Kevin R. Krull, Daniel A. Mulrooney, Daniel M. Green, Melissa M. Hudson, Leslie L. Robison, Juan Carlos Plana

*Corresponding author for this work

Research output: Contribution to journalArticle

114 Scopus citations

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/m2 (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.

Original languageEnglish (US)
Pages (from-to)2511-2522
Number of pages12
JournalJournal of the American College of Cardiology
Volume65
Issue number23
DOIs
StatePublished - Jun 16 2015

Keywords

  • cardiomyopathy
  • cardiotoxicity
  • heart failure
  • late effects
  • screening
  • strain

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Armstrong, G. T., Joshi, V. M., Ness, K. K., Marwick, T. H., Zhang, N., Srivastava, D., Griffin, B. P., Grimm, R. A., Thomas, J., Phelan, D., Collier, P., Krull, K. R., Mulrooney, D. A., Green, D. M., Hudson, M. M., Robison, L. L., & Plana, J. C. (2015). Comprehensive echocardiographic detection of treatment-related cardiac dysfunction in adult survivors of childhood cancer: Results from the St. Jude Lifetime Cohort Study. Journal of the American College of Cardiology, 65(23), 2511-2522. https://doi.org/10.1016/j.jacc.2015.04.013