Microvascular Dysfunction in Aortic Stenosis

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

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

Responsible Party

Sponsor

Study Sponsor

University Hospitals, Leicester

Study Sponsor

Gerry P McCann, MBChB, MD, Principal Investigator, University of Leicester

Verification Date

February 2015