title: Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.
abstract: OBJECTIVE
  To examine the utility and reliability of obtaining early echocardiographic measurements of left ventricular (LV) remodeling as well as blood biomarkers of cardiac injury in asymptomatic childhood cancer survivors at risk for LV dysfunction and congestive heart failure due to past exposure to anthracycline chemotherapy.
  
  
  METHODS
  Using a cross-sectional design, anthracycline-exposed childhood cancer survivors with preserved ejection fraction (EF; ≥50%) were evaluated using early echocardiographic indices and blood biomarkers of LV dysfunction. Survivors treated with ≥300 mg/m(2) anthracyclines [high risk (HR): n = 100] were compared with those treated with <300 mg/m(2) anthracyclines [low risk (LR): n = 50] and matched healthy controls (HC: n = 50). All echocardiograms were interpreted by an institutional cardiologist and a study cardiologist blinded to risk status.
  
  
  RESULTS
  Time from diagnosis was comparable for HR (12.0 years) and LR (13.2 years, P = 0.8) survivors. Echocardiograms: HR had lower LV thickness-dimension ratio (Z-score: HR: -0.62, LR: -0.03, HC: -0.02; P < 0.001), increased LV wall stress (HR: 66.7 g/cm(2), LR: 56.6 g/cm(2), HC: 54.2 g/cm(2); P < 0.01), and higher myocardial performance index (HR: 0.51, LR: 0.46, HC: 0.46; P < 0.01). Interobserver correlation (clinical/blinded reading) for all echocardiographic indices was excellent (range: R = 0.76-0.97, P < 0.001). Blood biomarkers: With the exception of NT-proBNP (r = 0.28, P < 0.01), there was no correlation between blood biomarkers (B-type natriuretic peptide, Troponin-T, ST-2, Galectin-3) and LV dysfunction.
  
  
  CONCLUSIONS
  Childhood cancer survivors with preserved EF 10+ years from anthracycline exposure had dose-dependent changes in echocardiographic markers of LV dysfunction.
authors.affiliation: Division of Outcomes Research, Department of Population Sciences; sarmenian@coh.org.
authors.forename: Saro H
authors.initials: SH
authors.lastname: Armenian
authors.affiliation: Division of Pediatric Cardiology, Department of Pediatrics and Communicable Diseases, C.S. Mott Children's Hospital, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Gelehrter
authors.affiliation: Division of Outcomes Research, Department of Population Sciences;
authors.forename: Tabitha
authors.initials: T
authors.lastname: Vase
authors.affiliation: Hematology, Oncology, Blood & Marrow Transplantation and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: Rajkumar
authors.initials: R
authors.lastname: Venkatramani
authors.affiliation: Division of Outcomes Research, Department of Population Sciences;
authors.forename: Wendy
authors.initials: W
authors.lastname: Landier
authors.affiliation: Division of Outcomes Research, Department of Population Sciences;
authors.forename: Karla D
authors.initials: KD
authors.lastname: Wilson
authors.affiliation: Division of Outcomes Research, Department of Population Sciences;
authors.forename: Claudia
authors.initials: C
authors.lastname: Herrera
authors.affiliation: Hematology, Oncology, Blood & Marrow Transplantation and.
authors.forename: Leah
authors.initials: L
authors.lastname: Reichman
authors.affiliation: Cardiology, Children's Hospital Los Angeles, Los Angeles; Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: John-David
authors.initials: JD
authors.lastname: Menteer
authors.affiliation: Hematology, Oncology, Blood & Marrow Transplantation and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: Leo
authors.initials: L
authors.lastname: Mascarenhas
authors.affiliation: Hematology, Oncology, Blood & Marrow Transplantation and Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California; and.
authors.forename: David R
authors.initials: DR
authors.lastname: Freyer
authors.affiliation: Department of Cardiology, City of Hope, Duarte; Divisions of.
authors.forename: Kalyanasundaram
authors.initials: K
authors.lastname: Venkataraman
authors.affiliation: Division of Outcomes Research, Department of Population Sciences;
authors.forename: Smita
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D004452:Echocardiography; D005260:Female; D006331:Heart Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D012307:Risk Factors; D017741:Survivors; D018487:Ventricular Dysfunction, Left / Q000175:diagnosis / Q000209:etiology; D020257:Ventricular Remodeling; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D015415:Biomarkers