title: Diffuse myocardial fibrosis by T1-mapping in children with subclinical anthracycline cardiotoxicity: relationship to exercise capacity, cumulative dose and remodeling.
abstract: BACKGROUND
  The late cardiotoxic effects of anthracycline chemotherapy influence morbidity and mortality in the growing population of childhood cancer survivors. Even with lower anthracycline doses, evidence of adverse cardiac remodeling and reduced exercise capacity exist. We aim to examine the relationship between cardiac structure, function and cardiovascular magnetic resonance (CMR) tissue characteristics with chemotherapy dose and exercise capacity in childhood cancer survivors.
  
  
  METHODS
  Thirty patients (15 ± 3 years), at least 2 years following anthracycline treatment, underwent CMR, echocardiography, and cardiopulmonary exercise testing (peak VO(2)). CMR measured ventricular function, mass, T(1) and T(2) values, and myocardial extracellular volume fraction, ECV, a measure of diffuse fibrosis based on changes in myocardial T1 values pre- and post-gadolinium. Cardiac function was also assessed with conventional and speckle tracking echocardiography.
  
  
  RESULTS
  Patients had normal LVEF (59 ± 7%) but peak VO(2) was 17% lower than age-predicted normal values and were correlated with anthracycline dose (r = -0.49). Increased ECV correlated with decreased mass/volume ratio (r = -0.64), decreased LV wall thickness/height ratio (r = -0.72), lower peak VO(2)(r = -0.52), and higher cumulative dose (r = 0.40). Echocardiographic measures of systolic and diastolic function were reduced compared to normal values (p < 0.01), but had no relation to ECV, peak VO(2) or cumulative dose.
  
  
  CONCLUSIONS
  Myocardial T1 and ECV were found to be early tissue markers of ventricular remodeling that may represent diffuse fibrosis in children with normal ejection fraction post anthracycline therapy, and are related to cumulative dose, exercise capacity and myocardial wall thinning.
authors.affiliation: Department of Pediatrics, Stollery Children's Hospital, University of Alberta, Edmonton, AB, Canada. etham@ualberta.ca
authors.forename: Edythe B
authors.initials: EB
authors.lastname: Tham
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Haykowsky
authors.forename: Kelvin
authors.initials: K
authors.lastname: Chow
authors.forename: Maria
authors.initials: M
authors.lastname: Spavor
authors.forename: Sachie
authors.initials: S
authors.lastname: Kaneko
authors.forename: Nee S
authors.initials: NS
authors.lastname: Khoo
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Pagano
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Mackie
authors.forename: Richard B
authors.initials: RB
authors.lastname: Thompson
mesh_terms: D000293:Adolescent; D018943:Anthracyclines / Q000009:adverse effects*; D002648:Child; D003287:Contrast Media; D003430:Cross-Sectional Studies; D004452:Echocardiography; D004719:Endomyocardial Fibrosis / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology*; D005080:Exercise Test; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D010100:Oxygen / Q000097:blood; D010807:Physical Endurance / Q000502:physiology*; D012307:Risk Factors; D017741:Survivors; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D018943:Anthracyclines; D003287:Contrast Media; D019786:Gadolinium DTPA; D010100:Oxygen