Right Ventricular Metabolism in Pulmonary Arterial Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to use non-invasive imaging to determine the metabolic phenotype of the right ventricle in patients with pulmonary arterial hypertension across a spectrum of disease severity.

Detailed Description
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Current medical therapy for pulmonary arterial hypertension (PAH) is aimed at reducing pulmonary vascular resistance (PVR) but not ameliorating right ventricular (RV) failure, the major cause of death. There are no RV-specific therapies currently available for PAH, in part because the pathophysiology of RV failure is poorly understood. The investigators hypothesize that the RV in PAH develops a distinct metabolic pattern characterized by increased glycolysis, impaired oxidative metabolism and lipid deposition, which are associated with RV failure. Specific Aim 1. To test the hypothesis that the RV in human PAH exhibits lipid deposition, increased glycolysis and impaired fatty acid oxidation. The investigators will measure RV oxidative metabolism and glycolysis in PAH patients and controls using positron emission tomography 11C acetate and [18F]fluoro-deoxy-D-glucose imaging and measure myocardial lipid accumulation using magnetic resonance spectroscopy imaging. Specific Aim 2. To test the hypothesis that an abnormal RV metabolic profile is associated with RV dysfunction and reduced exercise capacity in PAH. PET and MRS findings will be correlated with RV function, patient exercise capacity and a blood metabolic profile.

Official Title
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Metabolic Intervention in the Right Ventricle in Pulmonary Arterial Hypertension

Conditions
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Healthy, Pulmonary Arterial Hypertension

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Heritable or idiopathic PAH 18 years or older Able to give informed consent Exclusion Criteria: Pregnancy Type 1 diabetes mellitus Prednisone use PAH associated with any condition other than idiopathic or heritable Implanted ferromagnetic material incompatible with MRI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pulmonary Arterial Hypertension<br>Patients diagnosed with idiopathic or heritable pulmonary arterial hypertension according to consensus guidelines. RV oxidative metabolism and glycolysis will be measured using PET 11C acetate and [18F]fluoro-deoxy-Dglucose (FDG) imaging and measure myocardial lipid accumulation using MRS imaging. | |
| Subjects without cardiopulmonary disease<br>Subjects without known cardiopulmonary disease. RV oxidative metabolism and glycolysis will be measured using PET 11C acetate and [18F]fluoro-deoxy-Dglucose (FDG) imaging and measure myocardial lipid accumulation using MRS imaging | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right ventricular oxygen consumption divided by the rate pressure product | kmono divided by the rate pressure product (heart rate X systolic blood pressure) | At time of C11 acetate PET scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Right ventricular oxygen consumption (kmono) |  | At time of C11 acetate PET scan | 
| Right ventricular glucose uptake (standardized uptake value) |  | At time of 18-FDG PET scan | 
| Percent myocardial triglyceride content | Percent of myocardial triglyceride measured in the interventricular septum | At time of cardiac magnetic resonance imaging | 
| Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with right ventricular function |  | Day 1 | 
| Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with six minute walk distance |  | Day 1 | 
| Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with plasma metabolic profile |  | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pulmonary arterial hypertension, Right ventricle, Right ventricular function, Metabolism, Non-invasive imaging, Healthy Subjects