Sildenafil and Pulmonary Artery Pressure
Sildenafil and Pulmonary Artery Pressure
The purpose of the study is to see if the administration of sildenafil (Viagra) in patients
 with portopulmonary hypertension could be a safe and effective treatment.

 Portopulmonary hypertension (PTPH) is a special type of pulmonary hypertension. Pulmonary
 hypertension is high blood pressure in the pulmonary arteries that carry unoxygenated blood
 from the right ventricle of the heart to the lungs. Pulmonary hypertension results from
 constriction, or tightening, of the blood vessels that supply blood to the lungs.
 Consequently, it becomes difficult for blood to pass through the lungs, making it harder for
 the heart to pump blood forward. This stress on the heart leads to enlargement of the heart
 and eventually fluid can build up in the liver and tissues, such as in the legs. Affected
 patients can sometimes notice increasing shortness of breath and dizziness.

 There is a growing body of evidence suggesting a potential therapeutic role for this
 sildenafil in patients with primary pulmonary hypertension. Studies are ongoing regarding
 this area.

 Our hypothesis is that chronic oral sildenafil will successfully reduce pulmonary artery
 pressures by at least 25% (reduction in mean pulmonary artery pressure) and could be an
 effective treatment for PTPH, especially in candidates for liver transplantation

 Primary Hypothesis To measure the effects of a single dose of sildenafil on pulmonary
 arterial pressure in patients with PTPH

 Secondary Hypothesis To measure the effects of chronic (3 month) treatment with sildenafil on
 pulmonary arterial pressure, safety, and tolerability in patients with PTPH
This is a single center (only takes place at University of Chicago), open-label (doctor and
 subject know that the subject is taking the experimental drut), pilot study to evaluate the
 effects of sildenafil on pulmonary artery pressures in patients with portopulmonary
 hypertension.

 Patients who are diagnosed with PTPH after having routine care right heart catheterization
 will be asked if they are interested in participating. Approximately ten subjects will be
 enrolled. Subjects will undergo the following experimental procedures as part of their
 participation in this study: blood laboratory tests, medical history, physical exam, inhaled
 nitric oxide test, study drug (sildenafil) administration, and a pill count.

 Sildenafil will be given to these patients 3 times a day for a 12 week period to see if the
 study drug can lower their pulmonary artery pressures by at least 25%.
Inclusion Criteria:

 Candidates for enrollment in this clinical trial are limited to adult patients diagnosed
 with severe portopulmonary hypertension (PTPH). Specifically, other causes of pulmonary
 hypertension (PH) such as left ventricular dysfunction, valvular heart disease, chronic
 lung disease, chronic thromboembolic disease, chronic hypoxemia, rheumatologic conditions,
 and significant untreated obstructive sleep apnea will be excluded in the usual fashion in
 patients with underlying portal hypertension and usually cirrhosis. The diagnosis of
 pulmonary hypertension will be confirmed by invasive hemodynamic measurements (i.e. right
 heart catheterization) and severe PH is defined as a mean pulmonary artery pressure (MPAP)
 >35 mmHg. If evidence of right ventricular (RV) dysfunction is present (RV dilation,
 reduced RV ejection fraction (EF), or elevated RV end-diastolic pressure (>10 mmHg) and the
 MPAP is 30-35 mmHg, then the patient may be enrolled.

 Study participants will be selected from those patients referred for hemodynamic assessment
 of pulmonary hypertension, such as potential liver transplant recipients. They must be
 capable of giving informed consent. The University of Chicago referring physician will be
 contacted for concurrence of agreement.

 Exclusion Criteria:

 Patients with pulmonary arterial hypertension, but not portopulmonary hypertension will be
 excluded. Patients will be excluded from consideration if they do not have severe PTPH, if
 invasive hemodynamic assessment is contraindicated, or if there are any contraindications
 to sildenafil. Patients with unstable coronary syndromes or otherwise significant
 unrevascularized coronary artery disease and myocardial ischemia as determined by cardiac
 stress testing and/or coronary angiography will also be excluded. Moribund patients will
 not be considered for enrollment.