PURPOSE: Portopulmonary hypertension occurs in 6-15% of advanced cirrhosis patients undergoing evaluation for orthotopic liver transplantation. Pulmonary arterial hypertension (PAH) increases peri-operative cardiovascular mortality and is an absolute contraindication when patients have a mean pulmonary arterial pressure (mPAP) > 40mmHg. Most reports have used parenteral prostanoid therapy to treat PAH in these patients; drug therapy is complex and many patients are interested in alternatives.
METHODS: The study received IRB approval as an anonymous retrsopective chart review. All patients receiveing sildenafil from 2003-2006 for a catheter-confirmed diagnosis of PAH in the setting of cirrhosis were included. Risks and potential benefits of sildenafil therapy were explained to patients, and all patients agreed to a trial of the drug. Sildenafil was generally started at 25 mg TID and advanced to 50 TID although individual doses were higher; after Revatio approval, subjects were generally started at 20 mg TID. WHO/NYHA functional class, six minute walk, and right heart catheterizations were followed serially. Repeated measures t-test was used to assess statistical significance.
RESULTS: 7 patients received sildenafil therapy. Patients tolerated the therapy well, reporting only mild adverse reactions attributable to drug. Follow-up catheterization showed hemodynamic improvement in all patients. Patients experienced a mean reduction in MPAP of 11 mmHg (p<0.0025) and mean PVR reduction of 287 dynes/sec/cm-5 (p<0.0001). 5 of 7 patients achieved an mPAP of < 35 mm Hg within 3 months (sufficient hemodynamic improvement to be listed although none has had transplantation.) Six-minute-walk test performance improved in some individuals but the group mean difference did not acheive significance.
CONCLUSION: Sildenafil therapy was well tolerated and improved hemodynamics sufficiently to allow for transplant listing. Although open label, these results compare favorably with similar reports about epoprostenol.
CLINICAL IMPLICATIONS: Oral sildenafil therapy is much simpler than parenteral prostanoids, especially in patients with significant cirrhosis-related morbidity. Our results suggest similar efficacy. The field should undertake a large-scale trial of a phospho-diesterase-5 inhibitor in this subset of PAH patients.
DISCLOSURE: Michael Gough, University grant monies Salary support for research in vascular biology of pulmonary hypertension; Grant monies (from sources other than industry) Parker B Francis Fellowship to RJW for pulmonary arterial hypertension; Grant monies (from industry related sources) RJW is a site PI for Lilly/ICOS (tadalafil) and United Therapeutics (treprostinil). He was a site PI for Myogen (ARIES-1).; Shareholder None; Employee None; Fiduciary position (of any organization, association, society, etc, other than ACCP None; Consultant fee, speaker bureau, advisory committee, etc. Consultant for Actelion, CoTherix, and United. CME Speaking with grants funded by Actelion. Non-CME Speaking for Actelion.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose, Sildenafil is approved for PAH but there are no therapies specifically labeled for portopulmonary hypertension. We will make this clear on the poster.