Pulmonary hypertension due to chronich thromboembolism healthy volunteers I27.0 I27.2
Conditions
Interventions
Group 1: HPAH patients
all subjects will receive a single assessment (cross-sectional study) of sclinical data and laboratory asssessment of gene activity
Group 2: Healthy volunteers
Group 3: IPAH patients
Group 4: CTEPH pa
Sponsors
Thoraxklinik am Universitätsklinikum Heidelberg
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: All participants (PAH patients, healthy plant carriers, healthy controls): - Age of majority - Capacity to give consent - Written informed consent PAH patients - Mean pulmonary arterial pressure (mPAP) =25 mmHg, pulmonary vascular resistance =3 WU, pulmonary arterial occlusion pressure (PAWP) =15 mmHg. HPAH patients - Molecularly detected (probable) pathogenic variant in a PAH gene. IPAH patients - Guideline diagnosis of IPAH SSc-APAH patients - Rheumatologically confirmed systemic sclerosis according to the American College of Rheumatology / European League against Rheumatism criteria Other APAH patients - Guideline diagnosis of APAH PAH patients with comorbidities. - Age =65 years - Either at least three of these cardiac/metabolic comorbidities: systemic arterial hypertension, coronary artery disease, diabetes mellitus, BMI =30 kg/m2, left atrial enlargement, atrial fibrillation; - And/Or: pulmonary comorbidities such as chronic obstructive pulmonary disease (COPD) or interstitial lung disease with (near) normal lung function parameters: forced expiratory volume in one second (FEV1) =60%, forced vital capacity =70% CTEPH patients - Guideline diagnosis of CTEPH. Healthy variant carriers - Presence of hereditary PAH diagnosis (HPAH) in a close relative. - Proven genetic variant predisposing to PAH - No evidence of pulmonary hypertension in screening examination including echocardiography Healthy controls - Age- and sex-matched group in relation to the IPAH patients - Blood collection after informed consent or - Participants of the Lung Biobank Heidelberg of the Translational Research Section, Thoraxklinik Heidelberg, and Platform Biobanking & Data Management of the German Center for Lung Research (DZL)
Exclusion criteria
Exclusion criteria: All (PAH patients, healthy variant carriers, healthy controls): - Pregnancy, lactation - Acute infection PAH patients with comorbidities. - Significant lung disease: COPD with FEV1 <60% pred, IPF with FVC <70% pred, CT =20% fibrosis. Healthy controls - Significant cardiac or pulmonary disease - Acute malignant tumor disease - Comorbidities that may be triggered by the BMPR2 pathway: Brachydactyly, short stature, hemochromatosis (BMPR1B, BMP9); microphthalamia (BMP4); Myhre syndrome (SMAD4); craniosynastosis (SMAD6); proximal symphalangism/multiple synostoses syndrome (Noggin); sclerosteosis (Sclerostin), Loeys-Dietz syndrome (SMAD3).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| BMPR2 mRNA expression in HPAH patients (positive control) and healthy study participants (negative control) compared with IPAH, CTEPH patients, patients with systemic sclerosis-associated PAH (SSc-APAH), healthy BMPR2 plant carriers, and PAH patients with comorbidities. | — |
Secondary
| Measure | Time frame |
|---|---|
| - mRNA expression and protein expression of additional BMPR2 pathway partners including ligands, co-receptors, cytoplasmic pathway proteins and downstream regulated genes in the above patients/study participants including additional PH subsets. - Characterization of cell populations in blood - Correlation of experimental results with routinely collected clinical data from patients or data collected from family members for screening purposes. These include, but are not limited to: - Exercise capacity: 6-minute walk distance with Borg scale, exercise capacity in recumbent ergometer (watts)¸ respiratory economy (EqO2, EqCO2); - Echocardiographic parameters at rest and during exercise: systolic pulmonary arterial pressure (sPAP, mmHg), right ventricular area (RV area, cm²) and right atrial area (RA area, cm²), tricuspid annular plane systolic excursion (TAPSE), Tei index, left ventricular ejection fraction (LVEF, %), RV pump function (qualitative), LV pump function (qualitative); - WHO functional class; - Maximal oxygen uptake (VO2 peak) during exercise and other spiroergometry parameters and pulmonary function parameters; - Laboratory parameters that may be markers of right heart strain such as NTproBNP; - Blood gas analysis: oxygen partial pressure, carbon dioxide partial pressure, blood oxygen saturation (SaO2), supplemental oxygen administration (yes/no). - Safety parameters such as long-term ECG, blood pressure, heart rate, ECG; - Documentation of frequency, cause and duration of inpatient stays; | — |
Countries
Germany
Contacts
Public ContactChristina A. Eichstaedt
Thoraxklinik Heidelberg gGmbH
Outcome results
None listed