Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

Phase 4

Completed

Brief Summary: The study will investigate the cardiovascular effects of sildenafil on patients with Fontan circulation. Recent studies suggest that sildenafil may improve exercise in patients with Fontan circulation. However, why this occurs is not known. The study will used specialized catheters to measure pressure and volume. The measure of pressure and volume leads to more detailed analysis of heart function. Patients will receive either sugar pill or sildenafil prior to catheterization. It is believed that sildenafil will improve relaxation and contraction of the heart.

Detailed Description: Modifications to surgical procedures and medical treatment have led to a rapidly declining mortality rates in patients with single-ventricle heart disease (SV). However, SV patients still suffer from lower quality of life, decreased exercise capacity, worse neurodevelopmental outcomes and many other morbidities. While patients with SV circulation only make a small portion of all congenital heart diseases, 2-4 %, they require a great deal of resource utilization.

Standard medical treatments for adult heart failure have not had the same success in the SV population. Phosphodiesterase 5 (PDE5) inhibitors have recently become a frequently used medication class in patients with SV heart disease to treat pulmonary hypertension, heart failure, as well as "Fontan" failure (i.e., plastic bronchitis and protein-losing enteropathy). While there have been findings of improved measures of exercise capacity and some reports of improved symptoms of heart failure, the physiologic mechanisms behind these findings are not completely understood. There have been reports, indicating that the phosphodiesterase five inhibitors improve ventricular function in biventricular circulation patients and animal models. The aim of our study was to investigate the effect of acute PDE5 inhibition on ventricular function in SV patients after the final palliative surgery, the Fontan procedure.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

The use of phosphodiesterase type 5 (PDE5) inhibitors at the time of catheterization of within 1 month of catheterization
- Unstable arrhythmia at the time of catheterization
- History of unstable arrhythmia within 2 months of catheterization
- Venous, arterial or cardiac malformation that precludes the proper placement of a microconductance catheter
- Allergy to sildenafil or previous significant adverse reaction to sildenafil (e.g. hypotension)

Arm && Interventions

Group	Intervention	Description
Dobutamine + Sildenafil	Cardiac catheterization	Sildenafil will be given an one time dose 30 to 90 minutes prior to cardiac catheterization. Sildenafil will be given at a dose 1 milligram per kilogram with a maximum of 20 milligrams. During the catheterization patients will have specialized catheter placed in the heart that measures pressure and volume simultaneously. The patients will undergo an infusion of dobutamine up to 10 micrograms per kilogram per minute to mimic exercise for up to ten minutes..
Dobutamine + placebo	Cardiac catheterization	Patients will be given a one time dose of sugar pill 30 to 90 minutes prior to cardiac catheterization.During the catheterization patients will have specialized catheter placed in the heart that measures pressure and volume simultaneously. The patients will undergo an infusion of dobutamine up to 10 micrograms per kilogram per minute to mimic exercise for up to ten minutes..

Primary Outcome Measures

Name	Time	Method
End-systolic Elastance	10 minutes after imitation of dobutamine	end-systolic elastance (often abbreviated Ees or ESPVR) is a measure of contractility (systolic function)

Secondary Outcome Measures

Name	Time	Method
End-diastolic Pressure Volume Relationship	10 minutes after imitation of dobutamine	End-diastolic pressure volume relationship (EDPVR) is a measure of diastolic (relaxation) heart function