Regression of Myocardial Fibrosis After Aortic Valve Replacement

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* Severe aortic stenosis (1 or more of: aortic valve area \< 1.0cm2, peak pressure gradient \>64mmHg, or mean pressure gradient \> 40mmHg).
* Symptomatic.
* Age \> 18 years and \< 90 years.

Exclusion Criteria:

* Severe valvular disease other than AS.
* Previous Valve surgery
* Severe renal impairment eGFR \< 30ml/min.
* Any absolute contraindication to CMR
* Other medical condition that limits life expectancy or precludes AVR.
* Pregnancy