Single Ventricle Heart Disease After Fontan Surgery
Conditions
Keywords
Single ventricle, Fontan, Sildenafil, Pressure-Volume Loops
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.
Interventions
DIAGNOSTIC_TESTCardiac catheterization
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.
Sponsors
American Heart Association
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 40 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Ventricular-arterial Coupling | 10 minutes after imitation of dobutamine | Ventricular-arterial coupling is a measure of efficiency of ventricular work in response to the work created by the vascular tree |
| Preload Augmentation | 10 minutes after imitation of dobutamine | Preload augmentation is a measure of how quickly the heart fills with blood during exercise |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sildenafil Sildenafil will be given an one time dose 30 to 90 minutes prior to 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: Patients will receive a dobutamine infusion during catheterization. | 10 |
| Sugar Pill Patients will be given a one time dose of sugar pill 30 to 90 minutes prior to 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..
Dobutamine: Patients will receive a dobutamine infusion during catheterization. | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Sildenafil | Sugar Pill | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 10 Participants | 10 Participants | 20 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10 years | 8 years | 8 years |
| Race/Ethnicity, Customized Hispanic | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Not Hispanic | 9 Participants | 10 Participants | 19 Participants |
| Region of Enrollment United States | 10 participants | 10 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 0 / 10 | 0 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
End-systolic Elastance
end-systolic elastance (often abbreviated Ees or ESPVR) is a measure of contractility (systolic function)
Time frame: 10 minutes after imitation of dobutamine
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil | End-systolic Elastance | 0.85 Ees in mmHg/ml/m2 |
| Sugar Pill | End-systolic Elastance | 1.8 Ees in mmHg/ml/m2 |
Secondary
End-diastolic Pressure Volume Relationship
End-diastolic pressure volume relationship (EDPVR) is a measure of diastolic (relaxation) heart function
Time frame: 10 minutes after imitation of dobutamine
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil | End-diastolic Pressure Volume Relationship | 499 mmHg/ms |
| Sugar Pill | End-diastolic Pressure Volume Relationship | 953 mmHg/ms |
Other Pre-specified
Preload Augmentation
Preload augmentation is a measure of how quickly the heart fills with blood during exercise
Time frame: 10 minutes after imitation of dobutamine
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil | Preload Augmentation | 0.04 ml/m^2 |
| Sugar Pill | Preload Augmentation | 0.08 ml/m^2 |
Other Pre-specified
Ventricular-arterial Coupling
Ventricular-arterial coupling is a measure of efficiency of ventricular work in response to the work created by the vascular tree
Time frame: 10 minutes after imitation of dobutamine
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sildenafil | Ventricular-arterial Coupling | 0.01 ratio |
| Sugar Pill | Ventricular-arterial Coupling | 0.86 ratio |