title: Impaired Left Ventricular Reserve in Childhood Cancer Survivors Treated With Anthracycline Therapy.
abstract: BACKGROUND
  Childhood cancer survivors show evidence of diffuse myocardial fibrosis that is related to exercise capacity. The mechanism of reduced exercise tolerance in anthracycline cardiotoxicity remains unclear. We explored the determinants of exercise intolerance by evaluating left ventricular (LV) distensibility and functional reserve.
  
  
  METHODS
  Patients (n = 22) and healthy controls (n = 10) underwent two-dimensional echocardiography while supine, upright, and during cycle exercise. LV distensibility was measured as the change in end-diastolic cavity area (EDCA) from supine to the upright position. LV functional reserve was assessed during peak exercise, and measured as the exercise-induced change in systolic circumferential strain rate (SR) and early-diastolic SR (EDSR). The peak rate of oxygen consumption was measured by indirect calorimetry.
  
  
  RESULTS
  Median age of patients was 16 years (range 8-19) and controls 14 years (range 8-19). Median time since anthracycline therapy was 6 years (range 2-16). Peak oxygen consumption was significantly lower in patients compared to controls (35 ml/kg/min [28-60] vs. 45 ml/kg/min [44-53], P = 0.005). Transitioning from the supine position to the upright position caused a similar reduction in LV EDCA, suggesting similar LV distensibility between patients (-22% [-46 to -4]) and controls (-20% [-46 to -3], P = 0.3). However, during exercise, both systolic SR and EDSR reserve were significantly impaired in patients (∆SR: 93% [14-308], ∆EDSR: -4.5% [-88 to 121]) compared to controls (∆SR: 128% [54-230], P = 0.046; ∆EDSR: 74% [22-234], P = 0.02).
  
  
  CONCLUSIONS
  Our findings suggest that impaired LV contractility and functional reserve play a role in the reduced exercise capacity in anthracycline cardiotoxicity rather than LV distensibility.
authors: Division of Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors: Sachie
authors: S
authors: Kaneko
authors: Division of Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors: Edythe B
authors: EB
authors: Tham
authors: College of Nursing and Health Innovation, University of Texas, Arlington, Texas.
authors: Mark J
authors: MJ
authors: Haykowsky
authors: Division of Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors: Maria
authors: M
authors: Spavor
authors: Division of Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors: Nee S
authors: NS
authors: Khoo
authors: Division of Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors: Andrew S
authors: AS
authors: Mackie
authors: Division of Cardiology, Stollery Children's Hospital, Edmonton, Alberta, Canada.
authors: Jeffrey F
authors: JF
authors: Smallhorn
authors: Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada.
authors: Richard B
authors: RB
authors: Thompson
authors: College of Nursing and Health Innovation, University of Texas, Arlington, Texas.
authors: Michael D
authors: MD
authors: Nelson
mesh_terms: D000293:Adolescent; D018943:Anthracyclines / Q000009:adverse effects*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D066126:Cardiotoxicity / Q000209:etiology*; D002648:Child; D004452:Echocardiography; D005080:Exercise Test; D005260:Female; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy; D010101:Oxygen Consumption / Q000187:drug effects; D017741:Survivors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000000981:diagnostic imaging; D016277:Ventricular Function, Left / Q000187:drug effects; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents
keywords: cardiomyopathy; diastolic function; echocardiography; exercise testing; strain imaging