The aim is to obtain sufficient data about aortic hemodynamics and motion in MFS patients in different disease stages (e.g. native aorta, after conventional surgery and after PEARS procedure) and while receiving different medical treatments, to…
ID
Source
Brief title
Condition
- Cardiac and vascular disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
There are three main study parameters end points
1. Any statistically significant differences in advanced MRI parameters between
MFS patients and healthy controls.
2. Any statistically significant differences in advanced MRI parameters between
MFS patients prior to compared to after PEARS procedure.
3. Any statistically significant differences in advanced MRI parameters within
MFS patients using either ARB, BB or a combination of both
Secondary outcome
1. Differences in advanced MRI parameters between MFS patients who have had
aortic root replacement and MFS patients with a native aorta.
2. Differences in advanced MRI parameters between MFS patients who have had
aortic root replacement and MFS patients with a native aorta.
3. Differences in advanced MRI parameters between high and low risk MFS
patients based on aortic sinus diameter >4.5cm and *4.5cm
4. Differences in advanced MRI parameters between MFS patients who have a HI
FBN1 mutation or a DN FBN1 mutation.
5. Differences in advanced MRI parameters between genders in MFS patients.
6. The correlation between regional WSS and elastic fibre thickness in resected
aorta tissue of MFS patients.
7. The correlation between biomechanical tissue stiffness and elastic fibre
thickness
8. Differences in the extracellular matrix of cultured Marfan muscle cells
based on mutation type.
9. Differences in exercise capacity, quantified as peak oxygen consumption
(peak VO2), within MFS patients using either ARB or BB.
10. Differences in quality of life and habitual physical activity within MFS
patients using either ARB or BB.
Background summary
Better understanding of aortic hemodynamics and motion in Marfan syndrome (MFS)
is required to ultimately improve indication criteria for surgical intervention
and provide optimal medication treatment. In-house developed cardiac magnetic
resonance imaging protocols allow us to acquire advanced and detailed
functional vascular parameters. The Personalised External Aortic Root Support
(PEARS) procedure is an emerging alternative for early surgical intervention on
the aorta root, with major benefits, mainly concerning perioperative risks. To
our knowledge evaluation of advanced MRI parameters in MFS after PEARS
procedure as well as in MFS patients who receive different medication
treatments has not previously been done. Currently, evidence for optimal
medicational treatment of Marfan Syndrome is limited and the effect of
medicinal treatment on exercise capacity is still incompletely understood.
Study objective
The aim is to obtain sufficient data about aortic hemodynamics and motion in
MFS patients in different disease stages (e.g. native aorta, after conventional
surgery and after PEARS procedure) and while receiving different medical
treatments, to improve our understanding of the pathophysiology of aortic
pathology in MFS.
Study design
Part observational and part interventional design with a longitudinal design
for a subgroup of patients.
Intervention
Administration of Metoprolol Losartan and a combination of both.
Study burden and risks
Most procedures are part of standard clinical care. Added burden of current
study is the addition of study sequences to the MRI investigation, which will
result in an increase of scan time of twenty to thirty minutes and 1-3
subsequent MRI sessions for a subgroup of patients after surgical intervention
and patients who receive different medication regimens. The nature and extent
of the burden and risks associated with the additional measurements
(cardiopulmonary exercise test (CPET), activity monitor and questionnaire)
performed in the medication arm are negligible since these measurements are
non-invasive. The risks of administering medication are no different than
standard use of these medications in this patient group.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Marfan Syndrome patients with a known Fibrilline-1 mutation
- Between 18-50 years of age
Healthy controls:
- Between 18-50 years of age
Exclusion criteria
A potential subject who meets any of the following criteria (both patients and
healthy controls) will be excluded from participation in this study:
- Contraindication for MR imaging
- Mental retardation
- Pregnancy, or planned pregnancy during study period
Additional exclusion criteria for the medication sub study:
- History of aorta surgery
- More than 50mg daily Metoprolol usage at baseline
- Contra-indication for Metoprolol and/or Losartan
- Contra-indication for cardiopulmonary exercise testing (table 1)
- Patients who use antihypertensive medication for the indication hypertension.
- Patients with a baseline systolic blood pressure >140 mmHg and/or diastolic
>90 mmHg.
Additional exclusion criteria healthy controls:
- History of aorta disease
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 | NL80821.018.22 |