Natural History Study of Biomarkers in Pulmonary Arterial Hypertension

Prior treatment

• 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
• Cochlear Implants
• Use of metformin-containing products less than 24 hours prior to contrast administration

Other illness

• Electrocardiographic evidence of clinically relevant heart disease
• Symptoms of coronary or cardiac insufficiency
• 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
• Renal insufficiency (defined as an estimated glomerular filtration rate of \< 60 mL/min/1.73m\^2 of body surface area)
• 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.
• These contraindications include but are not limited to the following devices or conditions:
• Implanted cardiac pacemaker or defibrillator
• 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
• Subjects with a condition precluding entry into the scanner (e.g. morbid obesity, claustrophobia, etc.)
• 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.
• History of severe allergic reaction to gadolinium contrast agents despite pre- medication with diphenhydramine and prednisone
• Chronic kidney disease (an estimated glomerular filtration rate of \< 60 mL/min/1.73m\^2 of body surface area)
• 1\) Subjects with a condition precluding entry into the scanner (e.g. morbid
• History of multiple myeloma
• History of significant allergic reaction to CTA contrast agents despite pre-medication with diphenhydramine and prednisone

Lab values

• Serum creatinine \> 1.4 mg/dL

Age

• Age less than 18 years
• More than one major risk factor for coronary artery disease (excluding age and sex)
• 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

Other

• Pregnant or breastfeeding women (all women of childbearing potential will be required to have a screening urine or blood pregnancy test)
• Inability to provide informed written consent for participation in the study
  • INCLUSION AND 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)
• Obesity (defined as a body mass index \> 30 kg/m\^2)
• Anemia, thrombocytopenia or coagulopathy
• Inability to provide informed written consent for participation in the study
• Ocular foreign body (e.g. metal shavings)
• Embedded shrapnel fragments
• Central nervous system aneurysm clips
• Implanted neural stimulator
• Any implanted device that is incompatible with MRI
• Subjects requiring monitored sedation for MRI studies
• obesity, claustrophobia, etc.)

• 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.
• 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

Criteria the registry did not label

• 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: