Natural History Study of Biomarkers in Pulmonary Arterial Hypertension

• ELIGIBILITY:

The study will enroll subjects with confirmed and suspected NYHA/WHO Group 1 PH (68) as well as age and sex matched control subjects. Subjects must be at least 18 years of age and must be able to provide informed, written consent for participation in this study. There is no exclusion based on race or sex.

INCLUSION AND EXCLUSION CRITERIA FOR PAH SUBJECTS:

Inclusion Criteria:

The following parameters on RHC are required to meet the hemodynamic definition of PAH (NYHA/WHO Group I PH):

• mean pulmonary artery pressure of > 25 mmHg at rest,
• pulmonary capillary wedge pressure of \< 15 mmHg (or a left ventricular end-diastolic pressure of \< 12 mmHg), and
• pulmonary vascular resistance of > 3 Wood units (240 dyn s cm-5).

For patients with suspected PAH (Group I PH) who have not undergone a RHC and/or additional testing to confirm the diagnosis, this testing will be completed as clinically indicated under a procedural consent. If clinically indicated (diagnostic) testing indicates that the subject with suspected PAH does not in fact meet standard criteria for PAH (Group I PH), then the subject will be removed from the study.

Exclusion Criteria:

• Pregnant or breastfeeding women (all women of childbearing potential will be required to have a screening urine or blood pregnancy test)
• Age less than 18 years
• Inability to provide informed written consent for participation in the study

INCLUSION AND EXCLUSION CRITERIA FOR HEALTHY CONTROL SUBJECTS:

Inclusion Criteria for Control Subjects

Any healthy man or woman who is the appropriate age and sex for matching to a PAH patient

• Must be eligible for MRI and Gadolinium Based MRI studies
• Must be eligible for CT and Iodine Based Contrast CT studies

Exclusion Criteria for Healthy Control Subjects

• Current pregnancy or breastfeeding (All women of childbearing potential will be required to have a screening urine or blood pregnancy test)
• Electrocardiographic evidence of clinically relevant heart disease
• Symptoms of coronary or cardiac insufficiency
• More than one major risk factor for coronary artery disease (excluding age and sex)
• Obesity (defined as a body mass index > 30 kg/m\^2)
• History of underlying conditions/risk factors associated with pulmonary hypertension such as collagen vascular disease, HIV infection, use of appetite suppressants, chronic liver disease or cirrhosis of the liver, chronic thromboembolic disease, congenital heart defects, hypoxemia and/or significant pulmonary parenchymal disease
• Systemic hypertension that is not well controlled (i.e. blood pressure at the time of screening >140/90 mmHg in adults \< 60 years old or >150/90 mmHg in adults 60 years or older) on medications. Subjects taking > 2 anti-hypertensive medications will be excluded irrespective of their current blood pressure at time of screening
• Anemia, thrombocytopenia or coagulopathy
• Renal insufficiency (defined as an estimated glomerular filtration rate of \< 60 mL/min/1.73m\^2 of body surface area)
• Active tobacco use (> 6 months) in the past ten years, any tobacco use within 3 months prior to the screening evaluation or any tobacco use prior to completion of the study
• Inability to provide informed written consent for participation in the study

• History of recreational drug use with the exception of marijuana (as long as marijuana use was > 3 months from the time of study screening).

  • Volunteers may be excluded if in the opinion of the study investigators they have a condition that may adversely affect the outcome of the study or the safety of the volunteer.

Exclusion Criteria for MRI in Healthy Control Subjects and Subjects with PAH

These contraindications include but are not limited to the following devices or conditions:

1. Implanted cardiac pacemaker or defibrillator
2. Cochlear Implants
3. Ocular foreign body (e.g. metal shavings)
4. Embedded shrapnel fragments
5. Central nervous system aneurysm clips
6. Implanted neural stimulator
7. Any implanted device that is incompatible with MRI
8. Unsatisfactory performance status as judged by the referring physician such that the subject could not tolerate an MRI scan. Examples of medical conditions that would not be accepted would include unstable angina and severe dyspnea at rest
9. Subjects requiring monitored sedation for MRI studies
10. Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.)
11. Subjects with severe back-pain or motion disorders who will be unable to tolerate supine positioning within the MRI scanner and hold still for the duration of the examination.

Exclusion Criteria for Gadolinium Based MRI Studies Only:

1. History of severe allergic reaction to gadolinium contrast agents despite pre- medication with diphenhydramine and prednisone
2. Chronic kidney disease (an estimated glomerular filtration rate of \< 60 mL/min/1.73m\^2 of body surface area)

Exclusion Criteria for Cardiac Computed Tomography in Healthy Control Subjects and Subjects with PAH:

1) Subjects with a condition precluding entry into the scanner (e.g. morbid

obesity, claustrophobia, etc.)

Exclusion Criteria for Iodine Based Contrast CTA Studies Only:

1. Serum creatinine > 1.4 mg/dL
2. History of multiple myeloma
3. Use of metformin-containing products less than 24 hours prior to contrast administration
4. History of significant allergic reaction to CTA contrast agents despite pre-medication with diphenhydramine and prednisone