Evaluation of the BMPR2-Activin Signaling Pathway as a Key Mediator in Group II Pulmonary Hypertension. BREATHE-PH Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 150
- Locations
- 1
- Primary Endpoint
- Pulmonary vascular resistence
Study Overview
Brief Summary
Previous data from our group showed reduced BMPR2 isoform A in pulmonary hypertension associated with left heart disease (PH-LHD) of valvular origin.
Focusing on dysregulation of the BMPR2-activin pathway, a key regulator of vascular homeostasis, this project uses a multimodal approach combining molecular biology, advanced cardiac imaging, and histology.
Its aim is to determine the role of the BMPR2-activin pathway in the development and regression of PH-LHD.
We will conduct a prospective observational study with 1-year follow-up in 150 heart failure patients of different etiologies undergoing hemodynamic assessment.
Clinical parameters, biomarkers, molecular profiles, and hemodynamic/echocardiographic variables will be analyzed.
A nested substudy in 40 heart transplant candidates will include thoracic CT for vascular morphometric analysis and histological correlation in explanted hearts versus healthy controls.
We will also assess reversibility of vascular remodeling one year after transplantation.
Results may redefine PH-LHD classification, enable phenotypic precision-medicine models, guide targeted therapies such as activin inhibitors, and refine transplant criteria in combined pulmonary hypertension.
Detailed Description
This is a longitudinal observational study involving patients with heart failure (HF), including a substudy of advanced HF patients awaiting heart transplantation (BREATHE-CT).
The main cohort will include 150 HF patients of diverse etiologies undergoing invasive hemodynamic assessment by right heart catheterization.
Approximately 70 patients are expected to have PH-LHD and 80 will not. Eligible participants include advanced HF patients assessed for heart transplantation or ventricular assist devices, patients hospitalized for severe acute HF decompensation, and those undergoing pre-valvular intervention evaluation. The BREATHE-CT substudy will include 40 advanced HF patients selected from the main cohort and listed for heart transplantation.
Eligibility requires fulfillment of inclusion criteria and written informed consent.
Advanced HF and pulmonary hypertension classification will follow current European Society of Cardiology guidelines.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Older that 18 years
- •Heart failled patients with clinical indication for invasive hemodynamic assessment
- •Written consent
Exclusion Criteria
- •Refulsl to sign the infomred consent
- •Presence of iodinated contrast allergy
- •Ineligibility for HT (for BREATHE-CT substudy)
Outcomes
Primary Outcomes
Pulmonary vascular resistence
Time Frame: 12 months
Pulmonary vascular resistence will be assesed 12 months after inclussion
BMPR2 -activin expression
Time Frame: 12 months
BMPR2-activine pathway will be determinaned to correlate with PH
Secondary Outcomes
No secondary outcomes reported
Investigators
Javier Bermejo Thomas
Research Group Leader
Hospital General Universitario Gregorio Marañon