• maximal exercise tolerance (walking distance in the 6-minute walking test)
  
• peripheral oxygen saturation (SatO2)
  
• pulmonary-systemic ratio of arterial resistance (Rp:Rs)
  

• NYHA class
  
• increase in pulmonary reagibility by bosentan therapy
  
• normalisation of vasoactive mediators by bosentan therapy
  

Inclusion Criteria:

• Non-specific:

  • Written informed consent obtained

• Specific:

  • Age at least 18 years
  • Presence of cyanosis with < 93 % arterial oxygen saturation (measured by transcutaneous pulse oximetry)
  • 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 treatment)
  • Presence of PAH as diagnosed by invasive methods with Rp:Rs > 0.75 measured at rest, before testing of pulmonary vasodilatory reserve

  • One of the following diagnoses:

    • non-corrected large congenital shunting defect at atrial, ventricular or arterial level: PAPVD, ASD, SVD, VSD, AVSD, TAC, APW, PDA, or a combination of these.
    • Surgically corrected shunting defect (diagnoses as above) with significant residual defect
    • Other diagnoses with univentricular physiology/haemodynamics.

Exclusion Criteria:

• Non-specific:

  • pregnancy or lactation
  • women of child-bearing age who are sexually active without practising reliable methods of contraception
  • any disease or impairment that, in the opinion of the investigator, excludes a subject from participation
  • substance abuse (alcohol, medicines, drugs)
  • other medical, psychological or social circumstances that would adversely affect a patient's ability to participate adequately in the study or increase the risk to the patient or others in the case of participation.
  • insufficient compliance
  • subjects in whom MRI cannot be performed (contrast medium allergy, claustrophobia, cardiac pacemaker)
  • subjects who are not able to perform CPX

• Specific:

  • pulmonary hypertension of any aetiology other than those specified in the inclusion criteria
  • subjects with known intolerance of NO or iloprost or their constituents
  • acute decompensated heart failure within 7 days before the invasive procedure
  • haemodynamic instability that would increase the risk of pulmonary arterial reactivity testing
  • arterial hypotension
  • anaemia (Hb < 10 g/dl)
  • decompensated symptomatic polycythaemia
  • thrombocytopenia (< 50,000/μl)
  • secondary impairment of organic (renal, hepatic) function
  • other sources of pulmonary blood flow which render the measurement of the blood flow to the lungs and pulmonary vascular resistance impossible
  • obstruction of pulmonary blood outflow
  • left ventricular diseases
  • significant valvular diseases other than tricuspid or pulmonary regurgitation
  • pericardial constriction
  • history of stroke, myocardial infarction or life-threatening arrhythmia within 6 months before screening
  • bronchopulmonary dysplasia or other chronic lung diseases
  • history of significant pulmonary embolism
  • other relevant diseases (e.g. HIV infection)
  • trisomy 21
  • Prohibited concomitant medication: Any medication listed below which has not been discontinued at least 30 days prior to screening.
  • Unspecified or other significant medication (e.g. medication for diabetes or immunosuppression)
  • Unstable medication, recent changes in dosage regimen
  • Drugs to treat pulmonary hypertension (endothelin receptor antagonists, PDE-5 antagonists, prostanoids. (Specific pulmonary vasodilators during cardiac catheterisation are allowed.)
  • Other medication with vascular action
  • Medication that is not compatible with bosentan or that interferes with its metabolism (inhibitors of CYP2C9 or CYP3A4) or that, in the investigator's opinion, may interfere with bosentan treatment