Regression of Myocardial Fibrosis After Aortic Valve Replacement

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

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