Study of Effects of Sildenafil on Patients With Fontan Heart Circulation

Study Overview
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Brief Summary
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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
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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.

Official Title
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Response to Sildenafil in Patients With Fontan Physiology, A Pressure-volume Loop Analysis

Conditions
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Single Ventricle Heart Disease After Fontan Surgery

Intervention / Treatment
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* Diagnostic Test: Cardiac catheterization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of a congenital heart defect that leads to single ventricle physiology Previously performed Fontan surgery 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)

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dobutamine + Sildenafil<br>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.. | Diagnostic Test: Cardiac catheterization<br>* All patients will receive a dobutamine infusion during catheterization. Patients were 1:1 randomized to a single dose of 1 mg/kg of sildenafil (max dose of 20 mg) or placebo 30-90 min prior to beginning of catheterization.<br>|
| Placebo Comparator: Dobutamine + placebo<br>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.. | Diagnostic Test: Cardiac catheterization<br>* All patients will receive a dobutamine infusion during catheterization. Patients were 1:1 randomized to a single dose of 1 mg/kg of sildenafil (max dose of 20 mg) or placebo 30-90 min prior to beginning of catheterization.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End-systolic Elastance | end-systolic elastance (often abbreviated Ees or ESPVR) is a measure of contractility (systolic function) | 10 minutes after imitation of dobutamine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End-diastolic Pressure Volume Relationship | End-diastolic pressure volume relationship (EDPVR) is a measure of diastolic (relaxation) heart function | 10 minutes after imitation of dobutamine | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Single ventricle, Fontan, Sildenafil, Pressure-Volume Loops