title: Comprehensive Echocardiographic Detection of Treatment-Related Cardiac Dysfunction in Adult Survivors of Childhood Cancer: Results From the St. Jude Lifetime Cohort Study.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee. Electronic address: greg.armstrong@stjude.org.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Armstrong
authors.affiliation: Department of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: Vijaya M
authors.initials: VM
authors.lastname: Joshi
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Kirsten K
authors.initials: KK
authors.lastname: Ness
authors.affiliation: Menzies Research Institute, University of Tasmania, Hobart, Australia.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Marwick
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: DeoKumar
authors.initials: D
authors.lastname: Srivastava
authors.affiliation: Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Griffin
authors.affiliation: Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Grimm
authors.affiliation: Bluhm Cardiovascular Institute, Northwestern Memorial Hospital, Chicago, Illinois.
authors.forename: James
authors.initials: J
authors.lastname: Thomas
authors.affiliation: Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Dermot
authors.initials: D
authors.lastname: Phelan
authors.affiliation: Department of Cardiovascular Medicine, The Cleveland Clinic, Cleveland, Ohio.
authors.forename: Patrick
authors.initials: P
authors.lastname: Collier
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Krull
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Mulrooney
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Green
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Melissa M
authors.initials: MM
authors.lastname: Hudson
authors.affiliation: Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Robison
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Plana
mesh_terms: D000293:Adolescent; D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging* / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D019560:Echocardiography, Three-Dimensional / Q000639:trends; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008137:Longitudinal Studies; D008297:Male; D009369:Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D017741:Survivors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000903:Antibiotics, Antineoplastic
keywords: cardiomyopathy; cardiotoxicity; heart failure; late effects; screening; strain