title: Impact of sildenafil on echocardiographic indices of myocardial performance after the Fontan operation.
abstract: The objective of this study was describe the impact of sildenafil on echocardiographic measures of myocardial performance in children and young adults with a functional single-ventricle physiology late after Fontan surgery. A double-blind, placebo-controlled, crossover trial was conducted in children and young adults after the Fontan operation at a single pediatric center. Subjects were randomized to receive placebo or sildenafil (20 mg tid) for 6 weeks. After a 6-week washout period, subjects were crossed for an additional 6 weeks. Each subject underwent an echocardiogram at the start and finish of each phase. A total of 27 subjects completed study testing at a mean age of 14.9 years and a mean time from Fontan surgery of 11.3 years. After sildenafil, subjects demonstrated improvement in their myocardial performance index (MPI; -0.051; 95% CI -0.095, -0.0077; p 0.02) and in the product of the velocity time integral (VTI) of the dominant outflow tract and the heart rate (HR; 110 cm × bpm; 95% CI 7.5, 220; p = 0.04). Measures of diastolic performance, including inflow velocities, myocardial velocities, and the ratio of blood pool velocity to myocardial velocity during passive inflow, did not change. In this cohort, there were significant improvements in both the MPI and the product of the VTI × HR after 6 weeks of treatment with sildenafil. These findings suggest that sildenafil may be a useful therapy to improve or maintain ventricular performance in select patients after the Fontan operation.
authors.affiliation: Division of Cardiology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. goldbergda@email.chop.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldberg
authors.forename: Benjamin
authors.initials: B
authors.lastname: French
authors.forename: Anita L
authors.initials: AL
authors.lastname: Szwast
authors.forename: Michael G
authors.initials: MG
authors.lastname: McBride
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Marino
authors.forename: Nicole
authors.initials: N
authors.lastname: Mirarchi
authors.forename: Brian D
authors.initials: BD
authors.lastname: Hanna
authors.forename: Gil
authors.initials: G
authors.lastname: Wernovsky
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Paridon
authors.forename: Jack
authors.initials: J
authors.lastname: Rychik
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D015415:Biomarkers / Q000097:blood; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004452:Echocardiography; D005260:Female; D018729:Fontan Procedure; D006330:Heart Defects, Congenital / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000601:surgery*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D016014:Linear Models; D008297:Male; D010101:Oxygen Consumption / Q000502:physiology; D058986:Phosphodiesterase 5 Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010919:Placebos; D011687:Purines / Q000008:administration & dosage / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D010919:Placebos; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate