Cardiac Metabolic Remodeling After Pulmonary Vasodilator Therapy in Pulmonary Arterial Hypertension: A Pilot Study

Study Overview
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Brief Summary
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Pulmonary arterial hypertension(PAH) is associated with the development of right heart failure. In the setting of heart failure, the heart shifts to increasing dependence on glucose metabolism. In this study, the investigators will perform cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) scans to measure glucose metabolism in the heart before and after initiation of pulmonary vasodilator therapy for pulmonary arterial hypertension.

Detailed Description
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Pulmonary arterial hypertension is associated with the development of right heart failure. In the setting of heart failure, the heart shifts to increasing dependence on glucose metabolism. In this study, the investigators will perform cardiac positron emission tomography/magnetic resonance imaging (PET/MRI) scans to measure glucose metabolism in the heart before and after initiation of pulmonary vasodilator therapy for pulmonary arterial hypertension. By utilizing a rest-exercise protocol and continuous PET imaging acquisition, we can capture real-time changes in glucose uptake in the heart in response to acute exercise. By coupling these measures of dynamic glucose utilization with MRI-based cardiac function, we will determine cardiac metabolic efficiency.

Official Title
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Cardiac Metabolic Remodeling After Pulmonary Vasodilator Therapy in Pulmonary Arterial Hypertension: A Pilot Study

Conditions
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Pulmonary Arterial Hypertension, Right-Sided Heart Failure

Intervention / Treatment
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* Other: PET/MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: World Health Organization(WHO) group PAH secondary into idiopathic pulmonary arterial hypertension(IPAH) or connective tissue disease associated pulmonary arterial hypertension (CTDPAH) New York Heart Association (NYHA) classification I - III heart failure Vasodilator therapy naive Able to provide informed consent Exclusion Criteria: Metabolic disorders such as uncontrolled diabetes (A1c > 8%) that may interfere with FDG uptake Baseline 6-minute walk distance (6MWD) < 400 feet or NYHA class IV heart failure Musculoskeletal abnormalities that would prevent exercise Contraindications to MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: PET/MRI|Positron Emission Tomograph/Magnetic Resonance Imaging - participants will undergo PET/MRI prior to initiation of pulmonary vasodilator therapy and again 4-6 months after initiation of therapy|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to augment glucose uptake (substrate flexibility), defined as change in rate of glucose uptake from rest to exercise | Substrate flexibility is defined as the change in myocardial to blood pool glucose uptake rate from rest to exercise. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in substrate flexibility after initiation of pulmonary vasodilator therapy | Substrate flexibility is defined as the change in myocardial to blood pool glucose uptake rate from rest to exercise. Substrate flexibility before and after pulmonary vasodilator therapy will be compared. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary arterial hypertension, right-sided heart failure, metabolism, PET/MRI