Describe long-term changes in cardiorespiratory function and structure in a cohort of CTEPH and CTED patients treated with PEA and/or BPA in Denmark and the Netherlands.
ID
Source
Brief title
Condition
- Pulmonary vascular disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Main study parameters/endpoints: This is an observational study evaluating
determinants of a persistent response to BPA or PEA. Main study
parameter/endpoint is change in extracellular volume fraction after unloading
of the RV after PEA or BPA. This is measured calculated from pre and post
contrast T1 relaxation times measured by MR imaging.
Secondary outcome
- Change in RV function and volumes after PEA or BPA. This is measured by MR
imaging (RV ejection fraction, end diastolic volume, end systolic volume) and
right heart catheterization (end systolic elastance, RV-Arterial coupling)
- Change in lung perfusion defects before and after PEA measured by MR perfusion
- Change in serum levels of biomarkers of fibrosis and extracellular matrix
- Change in platelet transcriptomes
- Change in exercise capacity (peak oxygen uptake during cardiopulmonary
exercise testing, or CPET, and distance walked in 6 minutes) and gas exchange
during CPET (ventilatory efficiency, pulse oximetry)
- Change in quality of life
- Change in diffusion capacity
Background summary
Rationale: In chronic thromboembolic disease (CTED) and chronic thromboembolic
pulmonary hypertension (CTEPH), persistent thrombi after acute pulmonary
embolism occlude the pulmonary vasculature and cause persistent perfusion
defects in the lungs. Patients become symptomatic due to gas exchange
abnormalities and pressure overload of the right ventricle (RV), either at rest
or on exertion. A secondary pulmonary vasculopathy induced by high shear stress
in non-obstructed vessels can contribute to further cardiorespiratory
compromise. A diagnosis of CTEPH is a clear indication for interventional
treatment, consisting of pulmonary endarterectomy (PEA) or balloon pulmonary
angioplasty (BPA), or pharmacological treatment when PEA and BPA are not
possible or insufficient. Occluded vessels are opened by PEA and BPA and these
interventions are also believed to lead to (partial) reverse remodelling of the
lung vasculature and the RV. PEA and BPA can also be indicated for symptomatic
CTED patients, who have persistent emboli but no signs of pulmonary
hypertension. The early cardiorespiratory effects of BPA and PEA have been well
described and it has become clear that residual pressure overload, RV
dysfunction and gas exchange abnormalities are quite common. Little is known
about the subsequent clinical course of residual pulmonary vascular and RV
maladaptation after PEA and BPA. We have observed in our clinic both late
reversal of pulmonary vascular and RV remodelling and recurrent adverse
remodelling. We hypothesize that late reverse or adverse remodeling of the lung
vasculature and RV are critical determinants of long-term clinical outcome in
CTEPH and CTED. We also hypothesize that advanced imaging and biomarker
analysis will allow for a better understanding of determinants of treatment
success of PEA and BPA and that application of these methods will aid in
recognition of those patients requiring additional (pharmacological) treatment.
Study objective
Describe long-term changes in cardiorespiratory function and structure in a
cohort of CTEPH and CTED patients treated with PEA and/or BPA in Denmark and
the Netherlands.
Study design
Study design: Prospective cohort study. CTEPH/CTED patients who are evaluated
for invasive treatment with PEA or BPA will undergo structured follow up using
right heart catheterization, MR imaging, quality of life questionnaire,
spirometry test, exercise testing and blood sampling before PEA or BPA, and
again six and eighteen months after the last BPA session or day of surgery.
Study burden and risks
Nature and extent of the burden and risks associated with participation,
benefit and group relatedness: The study relies on information and results from
procedures that are part of the clinical routine for CTEPH and CTED patients.
This routine consists of the initial medical evaluation after referral and two
follow-up visits six and eighteen months after PEA surgery or the last BPA
procedure. Patients participating in the study will undergo an extended MR
imaging protocol to assess RV function and lung perfusion, which includes
administration of 0.3 mmol/kg of gadoterate meglumine contrast media. In rare
cases, gadoterate meglumine may induce an allergic reaction. The patients will
be informed about these risks and closely observed during the administration of
the contrast agent. Milder, rare side effects of gadoterate meglumine are
nausea, paraesthesias, skin irritation and headache. While a right heart
catheterization is routinely done 3-6 months after PEA or BPA to assess the
effects of the intervention, the 18 months* right heart catheterization is
currently only done in symptomatic patients (approximately one third of
patients). In the last 15 years we have performed about 250 right heart
catheterizations each year, with no significant complications. Occasionally,
patients experience a local hematoma at the site of venous access in the
internal jugular vein.
de Boelelaan 1117
Amsterdam 1007 MB
NL
de Boelelaan 1117
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of CTEPH or CTED (according to ESC/ERS guidelines (11))
- Scheduled for evaluation to determine possibility of PEA or BPA
- Age > 18
Exclusion criteria
- Pacemaker or other metal objects in the body
- Severe claustrophobia
- Severe renal insufficiency (eGFR < 30 mL/min)
- Allergy to gadolinium contrast
- Inability to provide informed consent
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 | NL60598.029.17 |