title: Impaired exercise capacity and left ventricular function in long-term adult survivors of childhood acute lymphoblastic leukemia.
abstract: BACKGROUND
  Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk for late cardiotoxic effects of cancer treatment, but conflicting evidence exists on the effects of anthracyclines on left ventricular (LV) diastolic function and exercise capacity.
  
  
  METHODS
  We performed a cross-sectional study with comprehensive echocardiography in 138 adult survivors of childhood ALL, median 23.4 years after diagnosis. Pulsed tissue Doppler measurements of early diastolic mitral annular velocities (e') were used for the assessment of diastolic function, and compared to 138 matched controls. Of the survivors, 133 also performed ergospirometry measuring peak oxygen uptake (VO2 max). Associations between cancer treatment, LV function, and VO2 max were analyzed.
  
  
  RESULTS
  The survivor group had lower e' values than controls (e' septal 11.0 vs. 12.6 cm/s, P < 0.001), but the difference was confined to the subgroup of anthracycline treated survivors (median cumulative dose 120 mg/m(2) ). Anthracycline exposure was inversely correlated with e' (regression coefficient -1.581, P=0.009). Reduced VO2 max/kg occurred in 47% of the survivors, but more often in anthracycline treated survivors (56%) than anthracycline naïve survivors (17%, P<0.001). Anthracycline exposure was inversely correlated with VO2 max/kg (regression coefficient -3.084, P = 0.05 in multivariate analysis). Furthermore, associations were observed between measures of LV function and VO2 max/kg, and e' was the best predictor of VO2 max/kg (standardized coefficient 0.355, P < 0.001 in multivariate analysis).
  
  
  CONCLUSIONS
  Adult survivors of childhood ALL have increased risk for impaired LV diastolic function and impaired exercise capacity, both associated with previous anthracycline exposure. Furthermore, there is an association between LV diastolic function and exercise capacity.
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Department of Medicine, Innlandet Hospital Trust, Elverum, Norway.
authors.forename: Jon R
authors.initials: JR
authors.lastname: Christiansen
authors.affiliation: Department of Pediatric Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Adriani
authors.initials: A
authors.lastname: Kanellopoulos
authors.affiliation: Department of Respiratory Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: May B
authors.initials: MB
authors.lastname: Lund
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Richard
authors.initials: R
authors.lastname: Massey
authors.affiliation: Department of Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Levanger, Norway.|Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Håvard
authors.initials: H
authors.lastname: Dalen
authors.affiliation: National Resource Centre for Late Effects after Cancer Treatment, Oslo University Hospital, Radiumhospitalet, Oslo, Norway.
authors.forename: Cecilie E
authors.initials: CE
authors.lastname: Kiserud
authors.affiliation: Department of Pediatric Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: Ellen
authors.initials: E
authors.lastname: Ruud
authors.affiliation: Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Svend
authors.initials: S
authors.lastname: Aakhus
mesh_terms: D000293:Adolescent; D000328:Adult; D018943:Anthracyclines / Q000009:adverse effects* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D066126:Cardiotoxicity; D003430:Cross-Sectional Studies; D004452:Echocardiography; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption / Q000187:drug effects; D010809:Physical Fitness / Q000502:physiology*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D017741:Survivors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced*; D016277:Ventricular Function, Left / Q000502:physiology; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents
keywords: cardiotoxicity; childhood cancer survivors; diastolic; dysfunction; exercise capacity; leukemia