Assess BMP10 secretion in patients with pulmonary arterial hypertension and its effect on right ventricular adaptation to pressure overload.
ID
Source
Brief title
Condition
- Cardiac valve disorders
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
BMP10 levels measured in bloodsamples and conditioned medium of right atrial
cardiomyocytes
Secondary outcome
* BMP10 activity plasma vs. serum
* Importance of location of the blood sampling (right atrium vs. venous
puncture) on BMP10 activity
Background summary
Bone morphogenetic protein (BMP) signalling is essential for cardiac
development. The ligand BMP10 is uniquely expressed by cardiomyocytes and
steers cardiomyocyte proliferation and differentiation. In the adult heart,
BMP10 is highly expressed in the right atrium, which is under high stress in
patients with pulmonary arterial hypertension. Hence, the stressed right atrium
may release increased amounts of BMP10, thereby disturbing the right
ventricular response to pressure overload.
Study objective
Assess BMP10 secretion in patients with pulmonary arterial hypertension and its
effect on right ventricular adaptation to pressure overload.
Study design
Observational study
Study burden and risks
Aim 1: BMP10 secretion by right atrial cardiomyocytes
During cardiac valve surgery or pulmonary endarterectomy, patients are placed
on a cardiopulmonary bypass. Central venous cannulation for cardiopulmonary
bypass is accomplished by cannulation of the right atrial appendage. For this
part of the study, we want to obtain a biopsy of the right atrium during this
procedure. Possible additional risk for this procedure will be bleeding and
scar formation. However, as this biopsy will be performed in a setting with an
experienced cardio-thoracic surgeon present, this risk is considered minimal.
Aim 2: BMP10 release as a bio-assay of right heart failure
During regular clinical follow-up patients undergo right heart catheterization
and magnetic resonance imaging. During the right heart catheterization, blood
samples will be withdrawn from the catheter. In addition, a venous blood sample
will be withdrawn to determine if right atrial blood sampling is really
essential for quantification.
De Boelelaan 1117
Amsterdam 1081 HV
NL
De Boelelaan 1117
Amsterdam 1081 HV
NL
Listed location countries
Age
Inclusion criteria
Aim 1: BMP10 secretion by right atrial cardiomyocytes
Inclusion criteria patients:
- Patients with chronic thrombo-embolic pulmonary hypertension (CTEPH)
- Undergoing pulmonary endarterectomy, Inclusion criteria controls:
- Patients undergoing cardiac surgery and put on the heart-lung machine, Aim 2:
BMP10 release as a bio-assay of right heart failure, Inclusion criteria
patients:
- Idiopathic PAH (Invasively assessed mean pulmonary artery pressure >25 mmHg,
pulmonary artery wedge pressure <15 mmHg)
- Right heart catheterization and magnetic resonance imaging < 1 year before
participation
- Age > 18 years, Inclusion criteria controls:
- Age >18 years
- Age and sex-matched to patients
- We will include 10 subjects with a BMPR2 mutation without Pulmonary
Hypertension
Exclusion criteria
Aim 1: BMP10 secretion by right atrial cardiomyocytes, Exclusion criteria
patients:
- Age < 18 years, Exclusion criteria controls:
- Pulmonary hypertension (according to European Society of Cardiology
guidelines: echocardiography, tricuspid regurgitation peak velocity * 2.8
m/sec, estimated systolic pulmonary artery pressure * 36 mmHg and no additional
echocardiographic signs of pulmonary hypertension)(13)
- RV dysfunction (TAPSE < 16 mm)(13)
- RV (annulus) dilatation (RV end-diastolic diameter > 42 mm (base))(13)
- Tricuspid valve replacement or tricuspid annuloplasty
- Dilated right atrium or RA dysfunction (e.g. related to atrial fibrillation,
congenital abnormalities; cut-off values: area > 18 cm2)
- Age < 18 years, Aim 2: BMP10 release as a bio-assay of right heart failure,
Exclusion criteria patients:
- Pregnancy
- Claustrophobia
- Pacemaker, Exclusion criteria controls:
- Pulmonary hypertension (Invasively assessed mean pulmonary artery pressure >
25 mmHg)
- Increased pulmonary artery wedge pressure (>15 mmHg)
- Tricuspid valve dysfunction
- RV dysfunction
- Dilated right atrium or RA dysfunction (e.g. related to atrial fibrillation,
congenital abnormalities)
- Previous cardiac surgery
- Age < 18 years
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 | NL60827.029.17 |