Regression of Myocardial Fibrosis After Aortic Valve Replacement (RELIEF-AS)

June 2, 2016 updated by: University College, London

REgression in Left Ventricular Interstitial Expansion and Fibrosis After Aortic Stenosis Surgery

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.

Study Overview

Status

Completed

Conditions

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

Enrollment (Actual)

181

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, W1G 8PH
        • The Heart Hospital, University College London Hospitals

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with severe aortic stenosis awaiting valve replacement recruited from cardiology outpatient department or as cardiology inpatients.

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cardiovascular death
Time Frame: 12 months
12 months
Major adverse cardiovascular events (MACE)
Time Frame: 12 months
MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional improvement
Time Frame: 12 months
Improvement in 6 minute walk test.
12 months
Regression of diffuse myocardial fibrosis
Time Frame: 12 months
Diffuse myocardial fibrosis measured by T1 mapping by CMR
12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
LV remodeling post AVR
Time Frame: 12 months
LV remodeling post AVR measured by CMR and transthoracic echocardiography.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University College, London

Investigators

  • Principal Investigator: James C Moon, MD, University College, London

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

December 1, 2015

Study Completion (Actual)

April 1, 2016

Study Registration Dates

First Submitted

June 24, 2014

First Submitted That Met QC Criteria

June 24, 2014

First Posted (Estimate)

June 25, 2014

Study Record Updates

Last Update Posted (Estimate)

June 3, 2016

Last Update Submitted That Met QC Criteria

June 2, 2016

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ReDA ID 07/0166

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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