Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study

1. All participants will undergo a baseline liver magnetic resonance elastography. The
patients with liver stiffness score >2.5 kiloPascal (KPa) [Normal: ≤2.5 KPa] will be
enrolled in the study.

2. In addition to a baseline liver MRE, all participants will undergo cardiac MRI,
transthoracic echocardiogram (TTE), FibroSure® (alpha-2 macroglobulin, haptoglobulin,
gamma-glutamyltransferase, bilirubin, apolipoprotein A1, and alanine transaminase), and
chemistry panel.

3. This will be a double blinded placebo control study design. All participants will be
randomized 1:1 to sildenafil or placebo for a total of 12 months therapy.

4. Sildenafil will be initiated at 5 mg 3 times per day for the first week, and titrated to
10 mg 3 times per day for the second week and 20 mg 3 times per day from the 3rd week to
the end of the study period. The patients will be required to check their pulse rate and
blood pressure daily during the first month of drug therapy. Patient who experience
hypotension (blood pressure < 90/50 plus symptoms such as dizziness) during dose
titration will be asked to remain on the previous tolerated dose. Patients who cannot
tolerate 10 mg 3 times daily will be asked to withdraw from the study and will be asked
to continue checking their blood pressure for three days after stopping the medication.

5. After 12 months (+/- 2 weeks) of therapy, all imaging studies (liver MRE, cardiac MRI,
TTE) and blood tests (FibroSure® and chemistry panel) will be repeated. A final liver
MRE and FibroSure will be performed at 18 months (+/- 2 weeks) for the participants
whose 18 months follow-up still falls within the study period.

6. Adverse event and compliance monitoring: During the first month of enrollment
(initiation and dose titration), adverse events will be collected by subject report and
by weekly telephone interview with dedicated research personnel. For the rest of the
study period, adverse events will be collected by subject report and by monthly
telephone interview with dedicated research personnel. The research personnel will be
responsible for sending out the monthly supply of medications and obtaining a count of
the remaining number pills as a measure of compliance. All participants will be provided
with a pamphlet containing all the side effects of sildenafil, and contact information
of research team for reporting any adverse event of concerns about the study.

Inclusion criteria:

- All adult Fontan patients who have no contraindications for magnetic resonance imaging
(MRI) will be eligible for the study.

Exclusion criteria:

- Subjects with implantable pacemakers

- Residual cardiac lesions (severe ventricular dysfunction, severe atrioventricular
valve regurgitation, Fontan baffle or conduit obstruction)

- Viral hepatitis

- Severe renal dysfunction

- History of sildenafil use in the six months prior to study enrollment

- Ongoing sildenafil therapy

- Patients currently taking nitrates

- Hypotension at baseline (BP <90/50 mmHg)

- Pulmonary veno-occlusive disease

- Hearing/vision impairment

- Pulmonary hypertension due to sickle cell disease

- Women of child-bearing potential with a positive pregnancy test will additionally be
excluded