Inclusion Criteria:

Non-specific:

1. Written informed consent obtained.
2. No participation in another AMG driven study attendancing this treatment protocol

Specific:

1. Age at least 14 years
2. Presence of cyanosis with < 93 % arterial oxygen saturation (measured by transcutaneous pulse oximetry)
3. Clinical indication for the invasive diagnostic procedures planned for the study is given; this is evaluated on the basis of observation before, during and after medicinal therapy)
4. Presence of PAH as diagnosed by invasive methods with Rp:Rs > 0.5 measured at rest, before testing of pulmonary vasodilatory reserve

5. One of the following diagnoses:

   1. non-corrected large congenital shunting defect at atrial, ventricular or arterial level:

      • PAPVD
      • ASD
      • SVD
      • VSD
      • AVSD
      • TAC
      • APW
      • PDA
      • combinations thereof.
   2. Surgically corrected shunting defect (diagnoses as above) with significant residual defect
   3. Other diagnoses with univentricular physiology/ hemodynamics.

Exclusion Criteria:

Non-specific:

1. pregnancy or lactation
2. women of child-bearing age who are sexually active without practising highly effective methods of contraception
3. any diseases or impairment that, in the opinion of the investigator exclude a subject from participation
4. substance abuse (alcohol, medicines, drugs)
5. other medical, psychological or social circumstances that would adversely affect a patient's ability to participate reliably in the study or increase the risk to themselves or others if they participated
6. insufficient compliance
7. missing willingness to storaging and transferring pseudonymous disease data within this study.
8. subjects who are not able to perform Cardio-Pulmonary Exercise Testing (CPX).

Specific:

1. pulmonary hypertension secondary to any etiology other than those specified in the inclusion criteria
2. subjects with known intolerance of NO and iloprost or their constituents
3. acute decompensated heart failure within the 7 days before the invasive diagnostic procedure
4. clinically significant haemoptysis within the last 6 months
5. hemodynamic instability which would represent an unjustifiable risk during testing of pulmonary arterial vasoreagibility
6. arterial hypotension (as defined by age-specific values)
7. anemia (Hb < 10 g/dl)
8. decompensated symptomatic policythemia; (details: 4.2.2. exclusion criteria)
9. thrombocytopenia (< 50.000/µl)

10. secondary impairment of organic function:

    • impairment of renal function (GFR < 30 ml/min/1,73 m2 BSA)
    • impairment of hepatic function (ALT and/or AST > 3 x ULN and bilirubin ≥ 2 mg/dl)

11. other sources of pulmonary blood flow which prohibit measurement of the blood flow into the lungs and therefore of the pulmonary vascular resistance:

    • Glenn
    • BT shunt
    • significant number of MAPCAs; (details: 4.2.2. exclusion criteria)

12. Obstruction of pulmonary blood outflow:

    • obstruction of pulmonary venous return
    • mitral valve dysfunction

13. Left heart diseases:

    • aortic or mitral valve disease (more severe than "mild")
    • restrictive or congestive cardiomyopathy
    • PCWP/LVEDP > 15 mmHg
    • symptomatic coronary artery disease
14. Significant valvular diseases other than tricuspid or pulmonary regurgitation (these are not exclusion criteria; details: 4.2.2. exclusion criteria).
15. Pericardial constriction
16. History of stroke, myocardial infarction or life-threatening arrhythmia within the 6 months before screening
17. Bronchopulmonary dysplasia (BPD) and other chronic lung diseases
18. History of significant pulmonary embolism
19. Other relevant diseases (e.g. HIV, diabetes mellitus requiring medical treatment)
20. Subjects with trisomy 21 (reproducibility of 6-MWT and CPX doubtful; communication as to side effects and subjective quality of life doubtful)

21. all contraindications against the study medication (see also "4.2.3 concomitant medication")

    • hypersensitivity against the active ingredients as well as supplementaries
    • patients who lost vision on one eye due to a non arteriitic anterior ischaemic neuropathy of the opticus (NAION).

Prohibited concomitant medication:

Any medication listed below which has not been discontinued at least 30 days prior to screening. Specific pulmonary vasodilators during cardiac catheterization are allowed.

1. Unspecified concomitant medication
2. Other significant medication (a.o. chronic intake of systemic immunosuppression as e.g. systemic glucocorticoids, cytostatic drugs, ciclosporin)

3. Instable medication (details: 4.2.5 prohibited concomitant medication):

   • begin of a new medication regimen within the last 30 days before screening
   • change in the dosage of existing medication within the last 7 days before cardiac catheterization

4. Existing anti-pulmonary hypertensive medication (in any form) with:

   • PDE-5 antagonists (e.g. sildenafil)
   • prostanoids (e.g. iloprost, prostacyclin, beraprost) In case the patient is stable and on Bosentan therapy at least for 6 months. Bosentan (Tracleer®) is unprohibited as concomitant medication.

5. Other medication with vascular action:

   • alpha blockers
   • L-arginin (acts through NO axis)
   • ritonavir, nicorandil (act through K+ channels)

6. Medication that is not compatible with sildenafil or interferes with the metabolism:

   • cytochrome P450-CYP2C9 and CYP3A4 inhibitors (e.g. erythromycin/ketoconazole/itraconazole/protease inhibitors)
   • any existing medication that, in the opinion of the investigator, may interfere with sildenafil treatment.