The goal of this study is to demonstrate the value of SAVI (both non-invasive and invasive) in patients with moderate aortic stenosis. The short-term objective will compare SAVI with standard resting indexes for symptom burden, functional capacity,…
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the evaluation of the SAVI metric as a risk predictor
compared to standard echocardiographic measurements like AVA and pressure
gradient at rest.
Secondary outcome
Secondary endpoints will include correlations between invasive and noninvasive
SAVI measurements to explore if stress assessment of the aortic valve can be
imaged non-invasively or if it requires invasive hemodynamic measurement. The
same will be done with the cardiac CT scans that will be analyzed to see if
computational fluid dynamics can simulate invasive SAVI. MRI will provide extra
information for cardiac volumes, stroke volume, extracellular volume and
grading of hypertrophy.
Background summary
Aortic stenosis (AS) has been increasing in prevalence in the developed world
due to a combination of an aging population and increasing lifespan. Surgical
aortic valve replacement (SAVR) and the recent development of transcatheter
aortic valve implantation (TAVI) have improved survival and symptoms for these
patients, with the exciting potential to help an even wider target population
due to advances that reduce procedural risk.
Due to clinical need and an approach based on surgical risk, much of the
existing physiologic recommendations for TAVI or SAVR have focused on clearly
symptomatic patients with severe AS at rest. Guidelines from the United States
and Europe recommend resting measurements of maximum velocity (Vmax), mean
transvalvular gradient (delta P), and aortic valve area (AVA) as well as
secondary parameters of AVA indexed to body surface area and the velocity ratio
(also called the dimensionless index). Recommendations for a valvular stress
test (typically with exercise or dobutamine) focus on a small minority with
reduced ventricular function. However, challenges and limitations exist with
our current severity classification for AS. For example, because stress-induced
symptoms and resting hemodynamic assessment may be discordant, some patients
may be inappropriately denied access to SAVR or TAVI.
Therefore, a rational hypothesis asks if routine valvular stress testing beyond
current guideline recommendations would identify a wider group of patients who
would benefit from TAVI but currently remain undertreated.
Study objective
The goal of this study is to demonstrate the value of SAVI (both non-invasive
and invasive) in patients with moderate aortic stenosis. The short-term
objective will compare SAVI with standard resting indexes for symptom burden,
functional capacity, and biomarkers. The long-term objective will associate
SAVI and standard resting indexes with clinical outcomes related to valvular
disease. We hypothesize that low SAVI (more marked AS during stress) will track
with more symptoms and a worse prognosis.
Study design
Clinical uncertainty exists regarding the need for invasive cardiac
catheterization in patients with moderate AS yet symptoms that could be related
to the valve. In some centers, such patients undergo coronary angiogram (CAG)
to ensure that non-invasive imaging has not underestimated valve severity and
to exclude significant coronary artery disease. In other centers, such patients
are managed conservatively. This very heterogeneity of practice highlights the
need for additional data that will be provided by this protocol. We anticipate
that some centers will consider a CAG as 'standard of care' while others will
perform it on a research basis. Each MEC/IRB can make this determination given
local practice patterns, and indeed it may differ among patients at a single
enrolling site.
The study will enroll an observational cohort. Potential subjects will be
identified by local investigators or a patient*s cardiologist through screening
echocardiography clinics. They will be invited to join the study with review of
inclusion/exclusion criteria and informed consent as approved by each local
MEC/IRB. After informed consent has been given, visits will be planned for the
catheterization with invasive SAVI measurements, non-invasive imaging (baseline
and stress echocardiography, cardiac CT scan, MRI scan), quality of life
questionnaire, and blood samples. A follow-up visit will be planned 1 year
after enrollment for a cardiac CT scan for valvular calcium scoring, 6-minute
walk test, blood samples, quality of life questionnaire, and echocardiography.
As a walk test, echocardiography, initial CT scan, MRI scan are routine
examinations for a patient with moderate AS, only the CT scan, questionnaire,
and blood samples are study investigations. Follow-up will be 5 years. The
initial catheterization will contain SAVI measurements that have been
investigated in two previous studies and are safe to use.
Study burden and risks
- possible adverse reaction to dobutamine
- allergic reaction to contrast fluid
- standard risks during heart catheterization
Michelangelolaan 2
Eindhoven 5623EJ
NL
Michelangelolaan 2
Eindhoven 5623EJ
NL
Listed location countries
Age
Inclusion criteria
1. Age >= 50 years
2. Moderate aortic stenosis confirmed in the past 3 months by standard
echocardiographic evaluation: aortic valve area >1.0 cm2 plus either maximal
velocity 2.5-3.9 m/s or mean gradient 15-39 mmHg
3. Ability to undergo exercise stress testing
4. Ability to understand and the willingness to provide written informed
consent
Exclusion criteria
1. Severe aortic stenosis
2. Percutaneous coronary intervention or coronary artery bypass grafting in the
past three months, or have revascularization planned in the near future
3. Known, unrevascularized, and severe coronary artery disease (for example a
90% diameter stenosis or FFR<0.7 in the proximal left anterior descending
artery)
4. Impaired left ventricular function (ejection fraction <50%)
5. Unicuspid, bicuspid, or non-calcified aortic valve observed during
echocardiography (note that later cusp fusion noted during study-related
cardiac imaging will not exclude a subject)
6. Severe aortic regurgitation, mitral valve disease, tricuspid regurgitation,
or a significant intracardiac shunt
7. Co-existing hypertrophic cardiomyopathy or severe septal hypertrophy >15mm
8. Persistent atrial fibrillation with uncontrolled ventricular response
9. Recent (within 6 weeks) acute coronary syndrome
10. Estimated glomerular filtration rate <=30 mL/min or end-stage renal disease
on replacement therapy (dialysis)
11. Severe COPD GOLD stage 3 or 4, home oxygen dependence, or >=2 pulmonary
inhalers (note that well-treated and stable asthma and GOLD stage 1 or 2 COPD
is permitted)
12. Severe comorbid condition with life expectancy <2 years
13. Prior adverse reaction to dobutamine
14. Severe iodine contrast allergy
15. Pregnancy
16. Severe pulmonary hypertension with systolic pulmonary artery pressure
greater than 50mmHg or isolated and symptomatic right ventricular failure
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 | NL74875.100.20 |