Please select the eligibility criteria that correspond to the clinical trial below.
Title: Acute Hemodynamic Effects of Sildenafil in Patients With Severe Aortic Stenosis
Brief Summary: 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.


Options:
A: Inclusion Criteria:

* Participant in Apex 2 high altitude expedition

Exclusion Criteria:

* Previous history of high altitude pulmonary edema
B: Inclusion Criteria:

* Clinical diagnosis of IPF
* Diffusing capacity of the lung (DLCO) level less than 35% (adjusted for hemoglobin)

Exclusion Criteria:

* Current enrollment in another investigational study
* Six-minute walk distance of less than 50 meters at screening or study entry
* Difference of greater than 15% between the screening and study entry 6-minute walk distance
* Acute or long-term impairment other than dyspnea (e.g., angina pectoris, intermittent claudication) that limits the ability to comply with the 6-minute walk test or other study requirements
* Forced Expiratory Volume 1-second (FEV1)/forced vital capacity (FVC) ratio of less than 0.65 after bronchodilator use
* Extent of emphysema greater than the extent of fibrotic change (e.g., honeycombing, reticular changes) on high-resolution computed tomography (HRCT) scan
* Acute heart attack within the 6 months prior to study entry
* Nitrate use
* Hypersensitivity to sildenafil or any component of the formulation
* Presence of aortic stenosis (AS)
* Life-threatening arrhythmia within 1 month of study entry
* Diabetes mellitus requiring insulin therapy
* Second-degree or third-degree atrioventricular (AV) block on electrocardiogram
* Severe chronic heart failure, defined by left ventricular ejection fraction (LVEF) of less than 25%
* Presence of idiopathic hypertrophic subaortic stenosis (IHSS)
* Hypotension (i.e., systolic blood pressure \[SBP\] less than 100 mm Hg or diastolic blood pressure \[DBP\] less than 50 mm Hg)
* Uncontrolled systemic hypertension (i.e., SBP greater than 180 mm Hg or DBP greater than 100 mm Hg)
* Known penile deformities or conditions (e.g., sickle cell anemia, multiple myeloma, leukemia) that may predispose participant to priapism
* Aspartate aminotransferase (AST), serum glutamic pyruvic transaminase (SGPT), alanine aminotransferase (ALT), or serum glutamic oxaloacetic transaminase (SGOT) greater than three times the upper limit of normal range
* Kidney impairment (i.e., creatinine clearance less than 30 mL/minute)
* Current drug or alcohol dependence
* Retinitis pigmentosa
* History of vision loss
* History of nonarteritic ischemic optic neuropathy
* Recently initiated pulmonary rehabilitation within 30 days of study entry. Participants will be prohibited from starting pulmonary rehabilitation during the study. Participants who are currently undergoing maintenance pulmonary rehabilitation at study entry will be asked to maintain their levels of rehabilitation for the duration of the study.
* Use of any investigational therapy as part of a clinical trial for any medical condition within 30 days of study entry
* Start or change in dose of treatment for IPF investigational agent (e.g., interferon gamma-1b, pirfenidone, etanercept, N-acetylcysteine, any other investigational agent intended to treat IPF), corticosteroids, or cytotoxic agents within 30 days of study entry
* Use of certain medications. More information about this criterion can be found in the study protocol.
* Treatment for pulmonary hypertension with prostaglandins (e.g., epoprostenol, treprostinil), endothelin-1 antagonists (e.g., bosentan, sitaxsentan, ambrisentan), or any other phosphodiesterase inhibitor (e.g., tadalafil, vardenafil) within 30 days of study entry
* Addition or discontinuation of calcium channel blockers, digitalis, diuretics, or vasodilators within 30 days of study entry (dosage must be stable for 7 days prior to study entry \[except for diuretics\])
* Currently on the waiting list for a lung transplant
* Use of L-arginine supplements
* Use of grapefruit juice or St. John's wort
* Pregnant or breastfeeding
* Resting saturation of peripheral oxygen (SpO2) (i.e., oxygen saturation measured using pulse oximetry) less than 92% with 6 liters of supplemental oxygen
C: 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
D: Inclusion Criteria:

* Clinical diagnosis of IPF
* 40-85 years of age
* 6-minute walk distance 150-500 m
* FVC 40-90% predicted
* DLCO 30-90% predicted

Exclusion Criteria:

* Severe pulmonary hypertension
* Severe heart failure
* FEV1/FVC \< 0.7

Answer: C