title: Effect of Sildenafil on Pressure-Volume Loop Measures of Ventricular Function in Fontan Patients.
abstract: Sildenafil has been reported to improve exercise capacity in Fontan patients, but the physiologic mechanisms behind these findings are not completely understood. The objective of this study was to study the acute effect of sildenafil on pressure-volume loop (PVL) measures of ventricular function in Fontan patients. Patients after Fontan operation who were presenting for a clinically indicated catheterization were enrolled. Patients were randomized in a double-blinded fashion to receive placebo (n = 9) or sildenafil (n = 10) 30-90 min prior to catheterization. PVLs were recorded using microconductance catheters at baseline and after infusion of dobutamine (10 mcg/kg/min). The primary outcome was change in ventriculoarterial (VA) coupling. For the entire cohort, VA coupling trended toward improvement with dobutamine (1.4 ± 0.4 to 1.8 ± 0.9, p = 0.07). End-systolic elastance showed improvement (2.6 ± 0.9 to 3.8 ± 1.4 mmHg m(2)/ml, p < 0.01) with dobutamine infusion. The cohorts had similar VA coupling at baseline (p = 0.32), but the sildenafil cohort trended toward having less of an improvement in VA coupling with dobutamine stress (p = 0.06). There were no differences between PVL measures of systolic or diastolic function between treatment groups, both at baseline and after dobutamine infusion. Patients with Fontan circulation had improved contractility and trended toward improvement in VA coupling with dobutamine stress. Acute sildenafil administration was not associated with improved PVL measurements of ventricular function in this population. These results suggest that clinical improvements seen with administration of sildenafil in Fontan patients are not associated with an acute improvement in ventricular function.
  
  
  BACKGROUND
  www.clinicaltrials.gov ; Clinicaltrials.gov Identifier: NCT01815502.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, MSC 915, Charleston, SC, 29425, USA. butts@musc.edu.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Butts
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, MSC 915, Charleston, SC, 29425, USA.
authors.forename: Shahryar M
authors.initials: SM
authors.lastname: Chowdhury
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, MSC 915, Charleston, SC, 29425, USA.
authors.forename: George H
authors.initials: GH
authors.lastname: Baker
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, MSC 915, Charleston, SC, 29425, USA.
authors.forename: Varsha
authors.initials: V
authors.lastname: Bandisode
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, MSC 915, Charleston, SC, 29425, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Savage
authors.affiliation: Division of Cardiology, Department of Pediatrics, Medical University of South Carolina, 165 Ashley Avenue, MSC 915, Charleston, SC, 29425, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Atz
mesh_terms: D000293:Adolescent; D058665:Adrenergic beta-1 Receptor Agonists / Q000008:administration & dosage; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D006328:Cardiac Catheterization; D002648:Child; D002675:Child, Preschool; D004280:Dobutamine / Q000008:administration & dosage; D004311:Double-Blind Method; D005260:Female; D018729:Fontan Procedure / Q000379:methods; D006801:Humans; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D058986:Phosphodiesterase 5 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000068677:Sildenafil Citrate / Q000009:adverse effects / Q000627:therapeutic use*; D016276:Ventricular Function / Q000187:drug effects*; D055815:Young Adult
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D058986:Phosphodiesterase 5 Inhibitors; D004280:Dobutamine; D000068677:Sildenafil Citrate
keywords: Fontan; Pressure–volume loop; Sildenafil; Single-ventricle heart disease