Regression of Myocardial Fibrosis After Aortic Valve Replacement
Condition: Aortic Stenosis
MeSH terms: Aortic Valve Stenosis; Fibrosis; Constriction, Pathologic
Study type: Observational

Summary: 
      Aortic stenosis (AS) is the most common valvular heart condition in the United Kingdom and
      the Western world. Surgery for severe AS prior to symptom onset is controversial.
      Conventionally changes in valve area and gradient are used to time intervention but
      myocardial changes may be more predictive of surgical need.

      This study aims to elucidate the role of diffuse myocardial fibrosis as a prognostic marker,
      implementing a novel, non-invasive MRI technique to measure it.

      Design: The investigators will measure diffuse myocardial fibrosis in 150 patients with
      severe narrowing of the aortic valve before and one year after valve replacement. Expected
      outcomes: Diffuse myocardial fibrosis measured by MRI scanning will predict outcome after
      surgery in aortic stenosis. Anticipated Health Benefits: Identify patients with higher post
      operative morbidity and mortality, who may benefit from earlier valve replacement.
    

Detailed description: 
      Surgery for severe aortic stenosis (AS) prior to symptom onset is controversial.
      Conventionally changes in valve area and gradient are used to time intervention but
      myocardial changes may be more predictive of surgical need. This study aims to elucidate the
      role of diffuse myocardial fibrosis as a prognostic marker, implementing a novel,
      non-invasive technique to measure it.

      AS is the most common valvular heart condition in the United Kingdom and the Western world.
      Its prevalence rises with age - about 3% aged over 75 have severe AS. During a period of
      progressive valve narrowing, the left ventricle (LV) adapts to the increased pressure with
      increasing concentric muscle hypertrophy. However, eventually this remodelling becomes
      maladaptive and the LV less compliant, leading to symptoms (breathlessness, chest pain, and
      loss of consciousness). This heralds a significant increase in morbidity and mortality.
      Consequently aortic valve replacement (AVR) in symptomatic patients is a Class I indication.
      In most asymptomatic patients however, prophylactic surgery is controversial: the risk of
      surgery is thought to be greater than watchful waiting, although there is no randomised data
      to support this approach. Conversely, diffuse myocardial fibrosis is thought to play a key
      role in functional deterioration, symptom development and possibly outcome in AS.
      Unfortunately, assessment of AS severity, including hemodynamic parameters such as peak
      velocity and mean gradient, poorly predict symptom development and/or optimal timing of
      surgery.

      A non-invasive technique to quantify diffuse myocardial fibrosis against the gold standard of
      myocardial biopsy has been developed and validated in patients with AS: Cardiovascular
      magnetic resonance (CMR) with T1 mapping uses the extracellular tracer gadolinium to measure
      the extracellular volume (ECV), which closely reflects the degree of diffuse fibrosis. An
      important observation in a previous cohort (Flett et al European Heart Journal Cardiovascular
      Imaging 2012) was the fate of patients with severe fibrosis: they were more symptomatic at
      baseline, improved the most post-operatively and yet carried a trend towards increased
      mortality at six months. To unravel this, this study aims to track diffuse fibrosis in the
      RELIEF-AS study with a larger cohort (n=150) and for longer (12 months) to understand how to
      use diffuse fibrosis as a prognostic marker.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with severe aortic stenosis awaiting valve replacement recruited from cardiology
        outpatient department or as cardiology inpatients.
      
Biospecimen description: 
      Serum and Plasma; myocardial biopsy obtained intra-operatively.
    
Keywords: Aortic Stenosis; Aortic Valve Replacement; T1 Mapping; Extracellular Volume Fraction; Cardiovascular Magnetic Resonance; Diffuse Myocardial Fibrosis