Brief Title
Regression of Myocardial Fibrosis After Aortic Valve Replacement
Official Title
REgression in Left Ventricular Interstitial Expansion and Fibrosis After Aortic Stenosis Surgery
Brief 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.
Study Type
Observational
Primary Outcome
Cardiovascular death
Secondary Outcome
Functional improvement
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
181
Start Date
October 2012
Completion Date
April 2016
Primary Completion Date
December 2015
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
Gender
All
Ages
18 Years - 90 Years
Accepts Healthy Volunteers
No
Contacts
James C Moon, MD, ,
Location Countries
United Kingdom
Location Countries
United Kingdom
Administrative Informations
NCT ID
NCT02174471
Organization ID
ReDA ID 07/0166
Responsible Party
Sponsor
Study Sponsor
University College, London
Study Sponsor
James C Moon, MD, Principal Investigator, University College, London
Verification Date
May 2015