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
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
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%.
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.
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.