Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

Study Overview
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Brief Summary
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Pulmonary hypertension is common in patients with aortic stenosis and is associated with worse operative and long-term outcomes. Sildenafil has been shown to reduce pulmonary artery pressure and improve exercise performance in patients with left-sided heart failure, but this has not been tested in patients with aortic stenosis. We hypothesize that Sildenafil will produce a clinically significant decrease in pulmonary artery pressure in patients with severe aortic stenosis. The dose of Sildenafil that produces a significant decrease in pulmonary artery pressure will be safe and well tolerated in patients with and without a depressed ejection fraction.

Detailed Description
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Patients with severe aortic stenosis referred for a clinically ordered right and left heart catheterization will be eligible. Twenty subjects will be enrolled: 10 patients will receive 40mg and 10 patients will receive 80mg; each dose will be equally distributed among those with preserved (≥50%) and reduced (<50%) EF. Subjects will get a baseline echo prior to the heart catheterization. Baseline invasive hemodynamic measurements will be performed using a Swan Ganz catheter. A single oral dose of sildenafil will then be administered (40mg or 80mg), followed by invasive hemodynamic measurements at 30 and 60 minutes. Also at 60 minutes, limited echocardiographic images will be obtained.

Official Title
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Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis

Conditions
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Aortic Stenosis

Intervention / Treatment
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* Drug: Sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe aortic stenosis (AVA < 1.0 cm2) Referred for a clinically ordered right and left heart catheterization 18 years of age and older Able and willing to comply with all requirements of the study Exclusion Criteria: Nitrate use within 24 hours SBP < 110 mmHg or MAP < 75 mmHg Severe mitral regurgitation Severe aortic regurgitation Increased risk of priapism Retinal or optic nerve problems or unexplained visual disturbance Alpha antagonists or cytochrome P450 3A4 inhibitors use within 24 hours Current or recent (≤ 30 days) acute coronary syndrome O2 sat < 90% on room air Females that are pregnant or believe they may be pregnant Any condition which the PI determines will place the subject at increased risk or is likely to yield unreliable hemodynamic data Unwilling to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 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: Sildenafil 40mg or 80mg<br>A single oral dose of Sildenafil (either 40mg or 80mg) will be administered to a participant after baseline hemodynamics are measured in the catheterization lab. Each dose will be equally distributed among those with preserved (≥50%) and reduced (<50%) EF. | Drug: Sildenafil<br>* Single oral dose of 40mg or 80mg of Sildenafil<br>* Other names: Viagra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Mean Pulmonary Artery Pressure in the Whole Cohort. |  | Baseline and 60 minutes after drug administered | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in Pulmonary Vascular Resistance in the Whole Cohort. |  | Baseline and 60 minutes after drug administered | 
| Percent Change in Cardiac Index. | Cardiac index is cardiac output divided by body surface area. | Baseline and 60 minutes after drug administered | 
| Load Independent Index of Diastolic Filling. | Measurements of the load independent index of diastolic filling were made with the parameterized diastolic filling formalism as previously described and validated with the use of transmitral Doppler E waves recorded during different respiratory states (regular breathing and held expiration and inspiration). | Baseline and 60 minutes after drug administered | 
| Global Longitudinal Strain | Global longitudinal strain was measured at baseline and 60 minutes after drug administration. | Baseline and 60 minutes after drug administered | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aortic valve stenosis, Sildenafil, Phosphodiesterase inhibitors, Hypertension, Pulmonary