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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Effect of Endothelin Receptor Antagonist Bosentan in Glucose Metabolism of the Myocardium and Coronary Dependant Endothelial Vasoreactivity Measured by 18F-FDG PET / CT and 82Rb PET / CT in Patients With PAH or CTEPH

Conditions
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Myocardial Dysfunction, Endothelial Dysfunction

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of each method of imaging for assessment of myocardial metabolism | On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax) | Baseline | 
| Analysis of each method of imaging for assessment of myocardial metabolism | myocardial ventricular right maximum standardized uptake value (SUVmax) on the images of au 18F-FDG PET/CT | at 4 weeks after start of treatment | 
| Analysis of each method of imaging for assessment of myocardial metabolism | On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax) | at 6 weeks after start of treatment | 
| Analysis of each method of imaging for assessment of myocardial metabolism | On the images of au 18F-FDG PET/CT : myocardial ventricular right maximum standardized uptake value (SUVmax) | at 12 weeks after start of treatment | 
| On the images 82Rb PET/CT rest MBF | myocardial blood flow (MBF in mL/min/g) at rest | Baseline | 
| On the images 82Rb PET/CT rest MBF | myocardial blood flow (MBF in mL/min/g) at rest | at 4 weeks after start of treatment | 
| On the images 82Rb PET/CT rest MBF | myocardial blood flow (MBF in mL/min/g) at rest | at 6 weeks after start of treatment | 
| On the images 82Rb PET/CT rest MBF | myocardial blood flow (MBF in mL/min/g) at rest | at 12 weeks after start of treatment | 
| On the images 82Rb PET/CT stress MBF | myocardial blood flow (MBF in mL/min/g) at pharmacological stress | Baseline | 
| On the images 82Rb PET/CT stress MBF | myocardial blood flow (MBF in mL/min/g) at pharmacological stress | at 4 weeks after start of treatment | 
| On the images 82Rb PET/CT stress MBF | myocardial blood flow (MBF in mL/min/g) at pharmacological stress | at 6 weeks after start of treatment | 
| On the images 82Rb PET/CT stress MBF | myocardial blood flow (MBF in mL/min/g) at pharmacological stress | at 12 weeks after start of treatment | 
| On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF | myocardial blood flow (MBF in mL/min/g) at cold test | Baseline | 
| On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF | myocardial blood flow (MBF in mL/min/g) at cold test | at 4 weeks after start of treatment | 
| On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF | myocardial blood flow (MBF in mL/min/g) at cold test | at 6 weeks after start of treatment | 
| On the images 82Rb PET/CT, analysis of endothelial dysfunction cold test MBF | myocardial blood flow (MBF in mL/min/g) at cold test | at 12 weeks after start of treatment | 
| Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction | On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax) | Baseline | 
| Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction | On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax) | at 4 weeks after start of treatment | 
| Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction | On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax) | at 6 weeks after start of treatment | 
| Analysis of each method of imaging for assessment of myocardial metabolism and endothelial dysfunction | On the images of au 18F-FDG PET/CT : myocardial ventricular left maximum standardized uptake value (SUVmax) | at 12 weeks after start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of right heart catheterization parameters PAP | pulmonary arterial pressure (PAP) | at screening | 
| Analysis of right heart catheterization parameters PAP | PAP | at 12 weeks after start of treatment | 
| Analysis of right heart catheterization parameters RAP | right atrial pressure (RAP) | at screening | 
| Analysis of right heart catheterization parameters RAP | RAP | at 12 weeks after start of treatment | 
| Analysis of right heart catheterization parameters PWP | pulmonary wedge pressure (PWP) | at screening | 
| Analysis of right heart catheterization parameters PWP | PWP | at 12 weeks after start of treatment | 
| Analysis of clinical parameters NYHA | NYHA classification | at screening | 
| Analysis of clinical parameters NYHA | New York Heart Association (NYHA) classification | at 12 weeks after start of treatment | 
| Analysis of clinical parameters 6-min walk test | 6-minute walk test | at screening | 
| Analysis of clinical parameters 6-min walk test | 6-minute walk test | at 12 weeks after start of treatment | 
| Analysis of clinical parameters LFT | Results of lung function tests | at screening | 
| Analysis of clinical parameters LFT | Results of lung function tests | at 12 weeks after start of treatment | 
| Analysis of clinical parameters NT-pro-BNP | plasmatic N terminal - pro - Brain Natriuretic Peptide (NT-pro-BNP) | at screening | 
| Analysis of clinical parameters NT-pro-BNP | plasmatic NT-pro-BNP | at 12 weeks after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelin receptor antagonist (ERA), pulmonary artery hypertension (PAH),, 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT, Rubidium-82 (82Rb) PET/CT