Pulmonary Artery Remodelling With Bosentan

Inclusion Criteria : · Men or women >18 years of age.·

• Symptomatic (modified NYHA class III) iPAH or PAH-SSc·
• PAH confirmed by right heart catheterization performed within 3 months before enrolment mPAP > 25 mmHg, PCWP < 15 mmHg and PVR > 3 mmHg/l/min.
• Women of childbearing potential must have a negative pre-treatment pregnancy test and use a reliable method of contraception during study treatment and for 3 months after study treatment termination.
• Bosentan naïve patients

Exclusion Criteria : · PAH other than iPAH or PAH-SSc

• Significant vasoreactivity during right heart catheterization defined as a fall in mPAP to < 40 mmHg with a decrease >= 10 mmHg and with a normal cardiac index (>= 2.5 l/min.m2)· Severe obstructive lung disease: FEV1/FVC < 0.5
• Severe restrictive lung disease: TLC < 0.7 of normal predicted value
• Hemoglobin <75% of the lower limit of the normal range· Systolic blood pressure < 85 mmHg
• Body weight < 40 kg
• Pregnancy or breast-feeding
• Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C.
• Baseline aminotransferases, i.e., aspartate aminotransferases (AST) and/or alanine aminotransferases (ALT) > 3 times the upper limit of the normal (ULN) range.
• Treatment for iPAH or PAH-SSc within 1 month before start of study treatment, excluding warfarin and acute administration of vasodilators for vascular reactivity testing during heart catheterization.
• Treatment with epoprostenol or other prostacyclin analogs for iPAH or PAH-SSc within 1 month before start of study treatment
• Treatment with glibenclamide (glyburide), fluconazole ketoconazole or ritonavir within 1 week before start of study treatment.
• Current treatment with cyclosporine A or tacrolimus
• Hypersensitivity to bosentan or any of the excipients of its formulation.
• Patient who received an investigational drug (such as sildenafil) within 3 months before start of study treatment
• Conditions that prevent compliance with the protocol or adherence to therapy.