Microvascular Dysfunction in Aortic Stenosis
Condition: Aortic Stenosis
MeSH terms: Aortic Valve Stenosis; Constriction, Pathologic
Study type: Observational

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.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Cardiology outpatients department and echocardiography department.
      
Biospecimen description: 
      With consent, a blood sample (up to 50ml) will be drawn and banked for prospective research
      studies. All research projects will be related to cardiovascular disease and approved by the
      Trial Steering Committee (TSC) or a committee delegated this responsibility by the TSC.

      All tissue will be collected, stored and disposed of in accordance with the Codes of Practice
      as laid out by the Human Tissue Authority.
    
Keywords: aortic stenosis; asymptomatic; microvascular dysfunction; Cardiac MRI