Genetics, Hypertension, Pulmonary, Pathophysiology, Pulmonary Arterial Hypertension
Conditions
Keywords
Pulmonary Arterial Hypertension, Prognostic factors, Signal transduction, Genetics
Brief summary
The objectives of the current study are to identify and evaluate new prognostic non-invasive and serological markers in patients with pulmonary hypertension. The focus will be on L-arginine metabolism and to clarify its influence on endothelial function.
Detailed description
The objectives of the current study are to identify and evaluate new prognostic non-invasive and serological markers in patients with pulmonary hypertension. The focus will be on L-arginine metabolism and to clarify its influence on endothelial function. The investigators also want to evaluate differences in plasma concentrations of L-arginine/NO metabolites and non-invasively assessed endothelial function based on specific PH-therapy. Furthermore, the investigators aim to transfer the results gained from the investigators study population to in-vitro systems in order to carefully characterize the involved signal transduction pathways. Thereby the investigators hope to identify potentially new therapeutic targets in PH or patient subgroups preferably benefitting from established therapeutic options.
Interventions
DEVICEEndoPAT measurement
EndoPAT (Itamar Medical Ltd, Ceasarea, Isreal) quantifies the endothelium-mediated changes in vascular tone, elicited by a 5-minute occlusion of the brachial artery (using a standard blood pressure cuff). When the cuff is released, the surge of blood flow causes an endothelium-dependent Flow Mediated Dilatation (FMD). The dilatation, manifested as Reactive Hyperemia, is captured by EndoPAT as an increase in the PAT Signal amplitude. A post-occlusion to pre-occlusion ratio is calculated by the EndoPAT software, providing the EndoPAT index. EndoPAT is FDA-cleared and CE-marked.
BIOLOGICALBlood Test
It is hypothesized that L-arginine/NO-metabolites are altered in pulmonary hypertension depending on disease severity. Moreover, polymorphisms in L-arginine/NO-metabolism modifying factors may influence disease severity. Analysis will be performed following established/published protocols after isolation from whole blood.
Sponsors
Pfizer
Actelion
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* proven PH (by right heart catheterization, PAP \>25 mmHg, within last 12 months) * age \>18 years * Dana Point classification I or IV (all subgroups) * declaration of consent
Exclusion criteria
* Pulmonary Hypertension not proven by right heart catheterization * Eisenmenger's syndrome/reaction * PH other than Dana Point I and IV * alcohol or drug abuse * non-compliance due to any cause (e.g. severe psychiatric disorder)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Differences of endothelial function regarding disease class and severity | 0, 3, 6, 9 and 12 months | 1. Quantification of L-arginine metabolites in whole blood 2. PAT-Ratio as non-invasively assessed endothelial function by EndoPAT2000-Device (Itamar Medical Ltd., Caesarea, Israel) 0 months = Time of Inclusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of endothelial function with established prognostic factors | 0,3,6,9 and 12 months | L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of proBNP as well as capillary pCO2, 6-minute walk distance and NYHA/WHO functional class. |
| Correlation of endothelial function with possible prognostic factors | 0,3,6,9 and 12 months | L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of various enzymes as well as lung function. |
| Correlation of endothelial function with changes in pulmonary hemodynamics | 0,3,6,9 and 12 months | L-arginine metabolite concentrations and PAT-Ratio correlated with PAPm, RAP, PVR (assessed by right heart catheterization within 12 months prior to inclusion) and echocardiographical parameters RVSP, TAPSE and TEI. |
| Correlation of polymorphisms in L-arginine metabolism genes with disease severity | 0 months | — |
| Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites) | 0 months | — |
| Correlation of L-arginine metabolites with pulmonary vascular signaling | 0 months | In vitro evaluation of human pulmonary vasculature cells signaling and proliferation by altered L-arginine metabolite levels. |
Countries
Germany
Outcome results
None listed