Dysregulation of Lipid Metabolism and Right Ventricular Function in PAH

Study Overview
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Brief Summary
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Right ventricular (RV) failure is the predominant cause of death in pulmonary arterial hypertension (PAH). No RV-specific therapies are available, in part because the underlying mechanisms of RV dysfunction are poorly understood. Given the heart's preference for fatty acids (FA) as an energy source, a deeper understanding of FA metabolism may shed light on RV adaptation to elevated afterload in PAH. The purpose of this study is to test the hypothesis that defects in fatty acid metabolism are common in PAH and contribute to RV failure. The investigators will measure peripheral and transcardiac lipid and glucose metabolites in PAH patients in comparison with patients with pulmonary venous hypertension and no evidence of pulmonary hypertension. The investigators will also correlate metabolites with concurrent measurement of right ventricular function.

Official Title
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Dysregulation of Lipid Metabolism and Right Ventricular Function in PAH

Conditions
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Pulmonary Arterial Hypertension

Intervention / Treatment
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* Procedure: Blood Sampling
* Other: Cardiac MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old Scheduled to undergo cardiac catheterization (right ± left heart catheterization) and/or electrophysiology study in the VHVI cardiac catheterization laboratory (CCL)/electrophysiology laboratory (EP lab) Hemoglobin value ≥ 10 g/dL or hematocrit of ≥ 30% (measured on clinically-indicated blood draw within 30 days or a point-of-care measurement in CCL/EP Laboratory if clinically-indicated value is not available) Exclusion Criteria: Any individual that is anemic and has a hemoglobin value < 10 g/dL and hematocrit of < 30% will be excluded from the study. If a physician performing the procedure believes that performing the extra steps and /or acquiring the additional blood samples will delay or otherwise compromise participants' care, he/she can abandon acquisition of those data at his/her discretion. Contraindication to cardiac MRI (applies only to patients undergoing CMR as part of this protocol). Implanted ferromagnetic material Glomerular filtration rate < 60mL/min (measured on clinically-indicated blood draw within 30 days of CMR or a point-of-care measurement in the CMR Laboratory if clinically-indicated GFR is not available)

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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No

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>Clinical diagnosis of pulmonary arterial hypertension | Procedure: Blood Sampling<br> <br> Other: Cardiac MRI<br> <br> |
| Healthy subjects and patients with other causes of PH<br>Patients referred for right heart catheterization who do not have PAH | Procedure: Blood Sampling<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral blood oleoylcarnitine in PAH versus control |  | At time of clinic visit, within 24 hrs prior to right heart catheritization | 
| Percent change across the cardiac circulation of oleate and the glucose/lactate ratio. | The combination of these findings will indicate if there is a decreased reliance on FAO and and increased glycolysis | At time of right heart catheterization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of oleoylcarnitine, other acylcarnitines and free fatty acids with the homeostatic index of insulin resistance, tricuspid annular plane systolic excursion, and six minute walk distance |  | At time of clinic visit, within 24hrs prior to right heart catheritization | 
| Correlation of the trans-cardiac gradient of oleate and lactate/glucose with right ventricular ejection fraction on cardiac MRI and six minute walk distance. |  | At time of right heart catheterization | 
| Measurement of trans-cardiac acylcarnitines |  | At time of right heart catheterization | 
| Measurement of trans-cardiac and trans-pulmonary glucose metabolites |  | At time of right heart catheterization | 
| Measurement of trans-cardiac and trans-pulmonary lipid metabolites |  | At time of right heart catheterization | 
| Measurement of trans-cardiac and trans-pulmonary amino acid metabolites |  | At time of right heart catheterization |