Brief Title
Microvascular Dysfunction in Aortic Stenosis
Official Title
Prognostic Importance of Microvascular Dysfunction in Asymptomatic Patients With Aortic Stenosis (PRIMID-AS)
Brief Summary
Aortic stenosis (AS), or narrowing of the aortic valve, is the commonest condition requiring
valve surgery in the developed world. It is currently not known what determines who will go
on to develop symptoms. Exercise testing may be able to identify these patients better than
the severity of the narrowing itself, but with some limitations.
The purpose of this study is to compare whether MRI scanning or exercise testing can better
identify patients with AS who are likely to benefit from surgery.
Design: The investigators will measure blood flow to the heart muscle with MRI scanning and
perform exercise testing in 170 patients with AS and follow them for up to up to 2 years.
Expected outcomes: MRI scanning will more accurately identify those patients with AS who will
need surgery during this period. Anticipated Health Benefits: improved selection of patients
with AS who are likely to benefit from early surgery. This is likely to reduce deaths in such
patients.
Detailed Description
Surgical AVR remains the universally accepted management for symptomatic aortic stenosis
(AS). However, the best management of severe aortic stenosis, in the absence of symptoms,
remains one of the most controversial areas in modern Cardiology.
Exercise testing can identify asymptomatic patients with AS at increased risk, but with
limited specificity. In a BHF funded project, the investigators have identified that cardiac
MRI measured Myocardial Perfusion Reserve (MPR) may be a novel imaging biomarker in AS. MPR
was the only independent predictor of aerobic exercise capacity (peak VO2) in patients with
severe AS and was also inversely related to symptomatic status.
In this multi-centre, observational, cohort outcome study, the investigators will follow 175
patients with asymptomatic moderate to severe AS for a minimum of 12 months, and determine
whether MPR is a better predictor of outcome than exercise testing, elucidate the mechanisms
contributing to symptom development in AS and establish the determinants of MPR in AS.
Patients will be recruited from tertiary Cardiac centres, as well as regional hospitals.
Comprehensive CMR with adenosine stress to determine LV mass and function, focal and diffuse
fibrosis and MPR; cardiopulmonary exercise testing (peak VO2 and exercise symptoms); rest and
exercise echocardiography (AS severity, valve compliance) and NT-proBNP will be performed.
The study will be run in conjunction with the Glasgow CTU. Investigations will be analysed
blind to patient status and data will be entered in a validated database. Statistical
analysis will be performed under the supervision of Prof. Ian Ford. The relationship between
MPR and exercise testing with 1-year outcome will be analysed using logistic regression.
Paired comparisons of the specificities of the two approaches on the same dataset will be
carried out using McNemar's test.
The primary hypothesis is that MPR will be a better predictor of adverse outcome than
exercise testing.
Study Type
Observational
Primary Outcome
Typical AS Symptoms necessitating AVR.
Secondary Outcome
Individual components of primary composite outcome measures.
Condition
Aortic Stenosis
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
175
Start Date
April 2012
Completion Date
October 2014
Primary Completion Date
November 2013
Eligibility Criteria
Inclusion Criteria:
1. Moderate-severe aortic stenosis (2 or more of: AVA < 1.5cm2, peak PG >36mmHg or mean
PG > 25mmHg).
2. Asymptomatic.
3. Age > 18 years and < 85 years.
4. Prepared to consider AVR if symptoms develop.
5. Ability to perform bicycle exercise test
Exclusion Criteria:
1. History of CABG or MI within previous 6 months.
2. Severe valvular disease other than AS.
3. Previous Valve surgery
4. Persistent Atrial Fibrillation or Flutter
5. History of Heart Failure
6. Severe Asthma.
7. Severe renal impairment eGFR < 30ml/min.
8. Planned aortic valve replacement.
9. Significant LV systolic dysfunction (EF < 40%)
10. Any absolute contraindication to CMR
11. Any absolute contraindication to Adenosine
12. Participation in an Interventional Clinical Trial at Inclusion.
13. Other medical condition that limits life expectancy or precludes AVR.
14. Pregnancy
Gender
All
Ages
18 Years - 85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Gerry P McCann, MBChB, MD, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT01658345
Organization ID
87768
Responsible Party
Sponsor
Study Sponsor
University Hospitals, Leicester
Study Sponsor
Gerry P McCann, MBChB, MD, Principal Investigator, University of Leicester
Verification Date
February 2015