Defining a Noninvasive Signature for Pulmonary Vascular Remodeling in Group 3 PH
Bastiaan Driehuys
Summary
The main goal of this study is to develop a noninvasive signature for pulmonary vascular remodeling in Group 3 PH patients, using hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI). Such a signature may identify Group 3 PH responders to PAH-specific therapies. PAH's unique 129Xe MRI signature has been shown in previous studies. Past studies have lacked a pathologic "ground truth" correlate of these signatures, which could be provided by comparing them with the pathology of lung explant tissue from patients who have undergone a lung transplant. This signature could be validated in a cohort of patients with Group 3 PH in future studies.
Description
The objective of this study is to identify a 129Xe MRI signature associated with PAH-like pulmonary vascular remodeling, consisting of plexiform arteriopathy, smooth muscle cell proliferation, and vascular fibrosis, in IPF and COPD that could be used to identify potential responders vs non-responders to PAH-specific therapies. The central hypothesis is that similar mechanisms and pathways underlie pulmonary vascular remodeling in IPF-PH, COPD-PH, and PAH. However, only a subset of Group 3 PH patients display remodeling consistent with PAH, resulting in responder vs. non-responder phenotypes wh…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Age ≥ 18 years' old 2. Be on the lung transplant waiting list at Duke University Medical Center. 3. PH as defined by RHC - mPAP \> 20 mmHg, PVR \> 3 WU, PCWP \< 15 mmHg 4. Groups defined as: PAH: Clinical diagnosis of PAH (Group 1 PH) in the absence of severe chronic lung disease, left heart disease, chronic thromboembolism, sarcoidosis, sickle cell disease, or other causes of non-Group 1 PH. COPD-noPH: Clinical diagnosis of COPD in the absence of precapillary PH. COPD-PH: Clinical diagnosis of COPD with precapillary PH. IPF-noPH: Clinical diagnosis of I…
Interventions
- DrugHyperpolarized 129Xe
Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),
Location
- Duke University Medical CenterDurham, North Carolina