bosentan in myocardium metabolism and perfusion measured by 18f-fdg and 82rb pet/ct on pah and cteph

Conditions: Myocardial Dysfunction; Endothelial Dysfunction

Summary: 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 \ 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

Keywords: endothelin receptor antagonist (era) pulmonary artery hypertension (pah), 18f-2-fluoro-2-deoxy-d-glucose (18f-fdg) pet/ct rubidium-82 (82rb) pet/ct