Bosentan in Myocardium Metabolism and Perfusion Measured by 18F-FDG and 82Rb PET/CT on PAH and CTEPH

The purpose of this study is to assess the effect of bosentan on the myocardial metabolism and the dependent endothelial coronary vasomotoricity in patients presenting a PAH.

Hypothesis : Bosentan may improve right ventricular function by decreasing myocardial stress and glucose metabolism. Patients may benefit from images with 18F-FDG PET / CT and 82Rb PET / CT for an earlier assessment and optimal management of PAH.

Patients refered to the hospital for a right heart catheterization for a PAH suspected at the echocardiography will be presented with the protocol.If inclusion/exclusion criteria are fulfilled all the procedures will be planned. At the screening visit the patient will have a right heart catheterization and an echocardiography. After a maximum of 4 weeks each patient will have 18F-FDG and 82Rb PET/CTs before start of treatment with Bosentan. These PET/CTs together with an echocardiography will be repeated at 6 and 12 weeks after start of treatment with bosentan.

Finally a right heart catheterization will be planned at 12 weeks after start of treatment with bosentan as a routine procedure.

Eligibility Criteria:
Inclusion Criteria:

* Patients with chronic PAH (PH group 1 Dana Point / stages 2 à 4 according to NYHA classification, defined by a mean arterial pulmonary pressure \>25 millimeter of mercury (mmHg) at rest, an occlusion arterial pulmonary pressure \<15 millimeter of mercury (mmHg) and vascular pulmonary resistance \>240 dyn.s.cm-5 for which a treatment with bosentan is indicated Or Patients with CTEPH not candidate for a pulmonary endarterectomy or patient with residual CTEPH after pulmonary endarterectomy (PH group 4 Dana Point / stages 2 to 4 according to NYHA classification) and for which a treatment with bosentan is indicated
* Indication to perform a right heart catheterization in the context of PAH suspected during cardiac ultrasound
* Age from 18 to 80 years old, male and female
* Karnofsky index ≥80%
* Informed consent signed

Exclusion Criteria:

* Patients with PAH stages 2,3 or 5 of Dana Point
* Patients with a contra-indication to adenosine including severe uncontrolled asthma, severe uncontrolled chronic obstructive pulmonary disease, 2nd or 3rd degree atrioventricular block without pacemaker,
* Patients with a contraindication to Bosentan, i.e :hypersensibility to the product, hepatic failure Child Pugh B or C, aminotransferases \>3 times normal value (N),association with cyclosporine A or glibenclamide
* Pregnancy, female of child-bearing potential not using any acceptable contraceptive method, breastfeeding
* Atrial fibrillation (Ventricular Ejection Fraction (VEF) not evaluable at echography)
* Karnofsky index \<80%
* Impossibility to obtain informed consent signed
* Left cardiopathies that can be responsible of post-capillar hypertension
* Involvement in another clinical study with an unregistered drug within 30 days prior to this specific study and during the entire course of the study
* Inability to comply with study procedures (linguistic problem, psychiatric problems, dementia, confusional state)
* Known or suspected non compliance drug or alcohol abuse
* Left heart assessment : diastolic and systolic function and valvular structures to exclude a cardiac pathology