Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients

Study Overview
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Brief Summary
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The study involves documenting the effects of inhaled nitric oxide upon ventricular-arterial coupling in patients with congenital heart disease and passive pulmonary blood flow. Consenting patients undergoing a clinically-indicated cardiac catheterization will be given inhaled nitric oxide for 10 minutes while intraventricular pressure-volume analysis will be make via conduction catheters.

Detailed Description
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Patients with complex congenital heart disease and single ventricle physiology typically undergo a staged surgical palliation to a situation where the single ventricle is recruited as the systemic pumping chamber and some (following a Glenn surgery) or all (following a Fontan surgery) systemic venous return flows passively to the lungs. While this physiology eliminates ventricular volume loading and normalizes systemic arterial oxygen saturations, there remain a number of physiologic burdens that limit functional capacity and life expectancy. Evidence suggests that this surgical imposition of the systemic and pulmonary vascular beds in series results in ventricular loading conditions that adversely affect ventricular function. At present, there exist limited means by which to mitigate these burdens, however, new therapies directed at reducing total pulmonary resistance may favorably affect patients with this physiology by reducing systemic venous pressures and improving both ventricular preload and afterload. One such therapy is inhaled nitric oxide (iNO), which is a selective pulmonary vasodilator that has been shown to reduce total pulmonary resistance and improve systemic venous pressures in this patient population. However limited data exist regarding the affects of pulmonary vasodilators like iNO on ventricular loading and ventricular-arterial coupling. This study proposes to assess the effects of pulmonary vasodilator therapy upon ventricular loading and ventricular-arterial coupling in single ventricle patients with passive pulmonary blood flow presenting for elective cardiac catheterization. The study components include obtaining routine (they would be obtained as a part of the clinically-indicated catheterization) hemodynamic measurements with hi-fidelity catheters rather than standard fluid-filled catheters, as well as simultaneous additional measurements with the same catheters at rest and during administration of iNO.

Official Title
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The Effect of Selective Pulmonary Vasodilation on Ventricular Afterload and Ventricular-arterial Coupling in Patients With Fontan Physiology and Validation of Echocardiographic Measures of Systolic and Diastolic Function.

Conditions
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Congenital Heart Disease, Fontan

Intervention / Treatment
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* Drug: inhaled nitric oxide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All consecutive patients with single ventricle hearts having passive pulmonary blood flow presenting to the cardiac catheterization laboratory for clinically indicated cardiac catheterization. Exclusion Criteria: Patients with coarctation of the aorta or known bilateral femoral arterial obstruction Patients with known severe systemic venous/Fontan obstruction Patients already receiving sildenafil or other vasodilator therapy

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: inhaled nitric oxide<br> | Drug: inhaled nitric oxide<br>* 20 parts per million (ppm) of inhaled nitric oxide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective arterial elastance (Ea) | Patients will undergo hemodynamic evaluation while receiving inhaled nitric oxide. After the measurements are made the nitric oxide will be discontinued. The primary outcome is the change in effective arterial elastance, a value obtained from ventricular pressure-volume assessment, before and while receiving nitric oxide. | Acute, approximately 10-15 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nitric oxide, ventricular-arterial coupling, congenital heart disease