title: Impact of vitamin C on endothelial function and exercise capacity in patients with a Fontan circulation.
abstract: OBJECTIVE
  To evaluate the impact of antioxidant therapy on functional health status in Fontan-palliated patients. Design.  Prospective, randomized, double-blind, placebo-controlled trial.
  
  
  METHODS
  Fifty-three generally asymptomatic Fontan patients.
  
  
  METHODS
  Patients were randomized to receive either high-dose ascorbic acid (vitamin C) or placebo for 4 weeks.
  
  
  METHODS
  Peripheral vascular function, as measured with endothelium-dependent digital pulse amplitude testing (EndoPAT), and exercise capacity were assessed before and after study drug treatment. Primary outcome measures included the EndoPAT index and peripheral arterial tonometry (PAT) ratio, both validated markers of vascular function. Secondary outcome measures included peak oxygen consumption and work.
  
  
  RESULTS
  Twenty-three vitamin C- and 21 placebo-assigned subjects completed the protocol (83%). Median age and time from Fontan completion were 15 (interquartile range [IQR] 11.7-18.2) and 11.9 years (IQR 9.0-15.7), respectively. Right ventricular morphology was dominant in 30 (57%). Outcome measures were similar between groups at baseline. Among all subjects, vitamin C therapy was not associated with a statistical improvement in either primary or secondary outcome measures. In subjects with abnormal vascular function at baseline, compared with placebo, vitamin C therapy more frequently resulted in normalization of the EndoPAT index (45% vs. 17%) and PAT ratio (38% vs. 13%).
  
  
  CONCLUSIONS
  Short-term therapy with vitamin C does not alter endothelial function or exercise capacity in an asymptomatic Fontan population overall. Vitamin C may provide benefit to a subset of Fontan patients with abnormal vascular function.
authors.affiliation: Division of Cardiology, Department of Pediatrics, C.S. Mott Children's Hospital, University of Michigan Health System, Ann Arbor, MI, USA. bryan.goldstein@cchmc.org
authors.forename: Bryan H
authors.initials: BH
authors.lastname: Goldstein
authors.forename: Angela M
authors.initials: AM
authors.lastname: Sandelin
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Golbus
authors.forename: Nicole
authors.initials: N
authors.lastname: Warnke
authors.forename: Lindsay
authors.initials: L
authors.lastname: Gooding
authors.forename: Karen K
authors.initials: KK
authors.lastname: King
authors.forename: Janet E
authors.initials: JE
authors.lastname: Donohue
authors.forename: Sunkyung
authors.initials: S
authors.lastname: Yu
authors.forename: James G
authors.initials: JG
authors.lastname: Gurney
authors.forename: Caren S
authors.initials: CS
authors.lastname: Goldberg
authors.forename: Albert P
authors.initials: AP
authors.lastname: Rocchini
authors.forename: John R
authors.initials: JR
authors.lastname: Charpie
mesh_terms: D000293:Adolescent; D000704:Analysis of Variance; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002648:Child; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects*; D005260:Female; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000503:physiopathology / Q000601:surgery*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D008365:Manometry; D055118:Medication Adherence; D008824:Michigan; D010101:Oxygen Consumption / Q000187:drug effects; D010166:Palliative Care; D011237:Predictive Value of Tests; D011446:Prospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid