We hypothesize that the development of a follow-up program of unaffected mutation carriers will lead to early identification of disease and in the development of strategies to prevent the development of disease and successful treatment.
ID
Source
Brief title
Condition
- Heart failures
- Chromosomal abnormalities, gene alterations and gene variants
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Platelet markers (RNA profiles)
-Metabolites and cytokines markers
-Exosome markers
-Change in mean pulmonary artery pressure (mPAP)
-Change in cardiac output (CO)
-Change in right atrial pressure (RAP)
-Change in right ventricular ejection fraction (RVEF) (%)
-Change in right ventricular end diastolic volume (RVEDV) (ml)
-Change in right ventricular end systolic volume (RVESV) (ml)
-Change in CPET markers: maximal work (VE), peak oxygen consumption (VO2),
maximal oxygen pulse (O2-pulse), VO2 max, anaerobic threshold (AT), ventilation
for a given volume of carbon dioxide production (VE/VCO2-slope) and the
end-tidal CO2 tension (PET-CO2).
-Change in 6 minute walking distance
- Changes in pulmonary vasculature
Density and abscence of pulmonary vasculature
Abnormal or abberant morphology of pulmonary vasculature
Secondary outcome
non
Background summary
Idiopathic and heritable forms of PAH (IPAH and HPAH, respectively) are rare
diseases that severely limit life expectancy. In recent years, the role of
BMPR2 signaling in vascular function and biology has become much better
defined. The abnormal pressure response to exercise in BMPR2 mutation carriers
suggests that the pulmonary circulation is abnormal even in the subclinical
stage. Because of the large vascular reserve capacity of the lung, pulmonary
hypertension at rest is thought to develop only after destruction of at least
two thirds of the total vascular bed.
Study objective
We hypothesize that the development of a follow-up program of unaffected
mutation carriers will lead to early identification of disease and in the
development of strategies to prevent the development of disease and successful
treatment.
Study design
Prospective observational cohort study
Study burden and risks
-RHC (right heart catherization)
Because RHC are part of our routine clinical assessment protocol a baseline and
during regular one-year follow-up assessment, the present study requires one
RHC measurement per patient and unaffected carrier at baseline. RHC performed
in experienced centres has low morbidity (1.1%) and mortality rates (0.055%)
[21]. We consider that the additional measurements are justified by an expected
improvement of patients clinical symptoms, quality of life and survival by our
goal oriented therapeutic approach in order to preserve/improve RV function
during long term follow-up. Furthermore, the results of the present study could
be of great value in order to improve the treatment strategy for PAH patients
worldwide.
-Liquid biopsy
Venous punction will be done by highly qualified medical doctors of the
Department of Pulmonology VUmc. Occasionally punction can cause a hematoma. The
total amount of blood withdrawn will be 80 ml per patient for the complete
study. The time taken for the procedure will take 10 min.
Drawing of blood by venous punction is a regular diagnostic technique and will
be conducted in compliance with the safety guidelines of the department
regarding the procedure.
-Cardiac MRI and cardiac echo are safe procedure with risk associated with
participation
-Cardio Pulmonary exercise testing (CPET) is safe and routinely used at our
department for patients with PAH and unaffected carriers. There is a small risk
of cardiac ischemia during exercise. Therefore we will use ECG-monitoring
during exercise and subjects obtained permission for the CPET after approval by
a pulmonologist.
- Contrast CT thorax
The risks associated with contrast fluid are allergic reaction or anaphylaxis
in severe cases. Both are very rare and can be treated medicamentally by our
expertised research group withouth permanent damage, even in cases of
anaphylaxis.
De Boelelaan 117 1117
Amsterdam 1081HV
NL
De Boelelaan 117 1117
Amsterdam 1081HV
NL
Listed location countries
Age
Inclusion criteria
1. Diagnosis of idiopathic PAH, according to ESC/ERS guidelines (ref: Galie ERJ
2015)
Or
Unaffected BMPR2 or other mutation carrier or other mutations associated with
PAH
Or
Healthy relative of heritable PAH patient not carrying the disease causing
mutation
2. Age >18 and <80 years
3. Able to understand and willing to sign the Informed Consent Form
Exclusion criteria
- Pregnant subjects
- Claustrophobia
- Inability to provide informed consent
- In case of PAH patients: TLC < 70%pred or radiographic evidence of
interstitial lung disease
- In case of BMPR2 mutation carriers and family control subjects, one or more
of the following: abnormal spirometry, TLC < 70%, echocardiographic evidence of
pulmonary hypertension
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL61732.029.17 |