An upcoming study from Vanderbilt University Medical Center in Nashville, Tennessee, will evaluate patients with pulmonary arterial hypertension (PAH), genetically susceptible individuals with BMPR2 gene mutations, and healthy individuals to determine risk and resilience factors and their association with outcomes.

The study is expected to start on November 1, 2022, and the estimated primary completion date is August 31, 2026.

The observational, prospective cohort study will enroll up to 150 participants aged 15 to 80 years, including patients diagnosed with idiopathic or heritable PAH, healthy participants with a known BMPR2 gene mutation and normal pulmonary pressure and functioning (unaffected mutation carriers), and healthy controls.

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Given that BMPR2 mutations are present in 30% of patients with PAH but clinical penetrance is only 20%, the authors see a unique opportunity to explore the determinants of PAH and its outcomes among unaffected mutation carriers compared with patients and healthy controls.

Read more about PAH etiology

Primary outcome measures include changes in: quality of life as measured by the emphasis-10 questionnaire or the Pediatric Quality of Life Inventory Version 4.0; 6-minute walk distance; diffusing capacity for carbon monoxide on the Pulmonary Function Test; cardiac functioning as measured by several echocardiogram tests; daily step count; resting heart rate; intensity of activity; hospitalizations related to PAH; medication regimen; deaths; and lung transplantations.

The research team proposes clinical and molecular phenotyping of the participants at multiple time points to identify static and dynamic features of PAH progression and resilience. Serial clinical, proteomic, and gene expression profiles of patients will be combined with bioinformatic and network medicine analyses to identify proteins and RNAs associated with cardiac and respiratory functioning and outcomes.

Once the possible risk and resilience factors are defined, the researchers will develop explanatory models to test in validation cohorts, with the aim of identifying risk and resilience signatures associated with progression and clinical outcomes in patients with PAH. Ultimately, the team hopes to advance current care standards to more personalized medicine and surveillance in PAH.


Risk and resilience in pulmonary arterial hypertension and genetically susceptible individuals (RARE-PAH). October 18, 2022. Updated October 26, 2022. Accessed October 27, 2022.