TranspulmonarY Estrogen Gradient and Estrogen Receptors (TYEGER) in PAH

Pulmonary arterial hypertension (PAH) is a disease characterized by elevated pressures in the blood vessels of the lungs that is not caused by another disease processes. More specifically, it is defined by a mean pulmonary artery pressure \> 25 mm Hg, a pulmonary vascular resistance \> 3 Wood Units (WU), and a normal pulmonary capillary wedge pressure in the absence of other etiology of pulmonary hypertension. The underlying mechanism of the disease in still unknown, but marked changes to the small arteries in the lungs have been observed. These changes include thickening of vessel walls and clot formation -- making the vessels less capable of gas exchange. Currently, PAH therapies focus on dilating the "good" remaining vessels that haven't been altered by this disease process; however, this therapy does not cure the disease. Survival remains low despite progress. There is growing human and experimental evidence supporting the concept that estrogens and estrogen receptors in the lungs are involved in the process that leads to PAH. As mentioned above, no current therapies attack the cause of PAH; they only act to dilate remaining "good" vessels which can reduce the burden of the disease, but not cure it. Thus, there is a critical need for novel therapeutics, as recently highlighted by a National Institute of Health workshop on pulmonary vascular diseases which called for the exploration of novel therapeutic approaches. None of the current FDA-approved treatments for PAH target estrogen or estrogen receptors. Despite the evidence supporting the concept that estrogens and estrogen receptors in the lungs contribute to PAH, no human studies investigate the estrogen level and the amount of estrogen receptors within the lungs of patients with PAH and their potential associations with current disease severity or 1 year outcomes including survival after 1 year, functional status, etc. Investigators hypothesize that a subset of PAH patients will have higher levels of estrogen and estrogen receptors in their lungs which would make them good candidates for novel therapies that block estrogen in hopes of halting the disease process. Update 12/31/2024: This record was updated to reflect the actual status of the research: * The study was observational, as the 18F-FES PET was not an interventional procedure, but was planned to be used as an estrogen receptor (ESR)-specific PET tracer to determine lung ESR density. * Zero participants were enrolled. Due to Covid-19, we utilized 66 serum samples from another study to test the hypothesis that among PAH patients, transpulmonary (TP) E2 gradient associates with a more severe hemodynamic profile and worse 1 year outcomes.