Author + information
- Received December 9, 2014
- Revision received March 24, 2015
- Accepted April 7, 2015
- Published online June 16, 2015.
- Gregory T. Armstrong, MD, MSCE∗∗ (, )
- Vijaya M. Joshi, MD†,
- Kirsten K. Ness, PhD∗,
- Thomas H. Marwick, MBBS, PhD, MPH‡,
- Nan Zhang, MS§,
- DeoKumar Srivastava, PhD§,
- Brian P. Griffin, MD‖,
- Richard A. Grimm, DO‖,
- James Thomas, MD¶,
- Dermot Phelan, MD, PhD‖,
- Patrick Collier, MD, PhD‖,
- Kevin R. Krull, PhD∗,
- Daniel A. Mulrooney, MD, MS#,
- Daniel M. Green, MD∗,
- Melissa M. Hudson, MD#,
- Leslie L. Robison, PhD∗ and
- Juan Carlos Plana, MD∗∗
- ∗Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, Tennessee
- †Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee
- ‡Menzies Research Institute, University of Tasmania, Hobart, Australia
- §Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee
- ‖Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, Ohio
- ¶Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago, Illinois
- #Department of Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee
- ∗∗Baylor College of Medicine, Houston, Texas
- ↵∗Reprint requests and correspondence:
Dr. Gregory T. Armstrong, St. Jude Children’s Research Hospital, Department of Epidemiology & Cancer Control, 262 Danny Thomas Place, Mail Stop 735, Memphis, Tennessee 38105.
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.
Support to St. Jude Children’s Research Hospital was provided by Cancer Center Support grant CA21765 (R. Gilbertson, principal investigator) and the American Lebanese-Syrian Associated Charities.
Dr. Marwick has received research grants from General Electric (>$50,000); and equipment support from Siemens and Philips. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
This research was previously presented at the 2014 annual meeting of the American Society of Clinical Oncology. Rick Nishimura, MD, served as Guest Editor for this paper.
- Received December 9, 2014.
- Revision received March 24, 2015.
- Accepted April 7, 2015.
- American College of Cardiology Foundation