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Aortic StenosisRELIEF-ASNCT02174471

Regression of Myocardial Fibrosis After Aortic Valve Replacement

An observational study of Aortic Stenosis, run by University College, London at 1 site in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Aortic Stenosis
How many people
181 participants
Where
1 siteUnited Kingdom
Study dates
Oct 2012to Apr 2016
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

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

Who may be able to join

  • 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.

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

  • The Heart Hospital, University College London Hospitals

    London, W1G 8PH

Other trials in United Kingdom

About this study

Official title: 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.

Read the 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.

Conditions
Aortic Stenosis
Keywords
Aortic Stenosis, Aortic Valve Replacement, T1 Mapping, Extracellular Volume Fraction, Cardiovascular Magnetic Resonance, Diffuse Myocardial Fibrosis
Medical subject headings
Aortic Valve Stenosis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Cardiovascular death

    Measured: 12 months

  2. Major adverse cardiovascular events (MACE)

    MACE: hospitalisation with heart failure, chest pain, syncope, arrhythmia or stroke

    Measured: 12 months

Secondary outcomes (2)

  1. Functional improvement

    Improvement in 6 minute walk test.

    Measured: 12 months

  2. Regression of diffuse myocardial fibrosis

    Diffuse myocardial fibrosis measured by T1 mapping by CMR

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted25 Jun 2014 (estimated)
  2. Study startOct 2012
  3. Primary completionDec 2015
  4. Study completionApr 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
181 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02174471
Sponsor's protocol ID
ReDA ID 07/0166
Acronym
RELIEF-AS
Status last verified
May 2015
First submitted
24 Jun 2014
Last updated
3 Jun 2016
Results posted
No
Data monitoring committee
No

Publications

  • Flett AS, Hayward MP, Ashworth MT, Hansen MS, Taylor AM, Elliott PM, McGregor C, Moon JC. Equilibrium contrast cardiovascular magnetic resonance for the measurement of diffuse myocardial fibrosis: preliminary validation in humans. Circulation. 2010 Jul 13;122(2):138-44. doi: 10.1161/CIRCULATIONAHA.109.930636. Epub 2010 Jun 28.

    PubMed 20585010

  • Flett AS, Sado DM, Quarta G, Mirabel M, Pellerin D, Herrey AS, Hausenloy DJ, Ariti C, Yap J, Kolvekar S, Taylor AM, Moon JC. Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study. Eur Heart J Cardiovasc Imaging. 2012 Oct;13(10):819-26. doi: 10.1093/ehjci/jes102. Epub 2012 May 25.

    PubMed 22634740

  • Bhuva AN, Treibel TA, De Marvao A, Biffi C, Dawes TJW, Doumou G, Bai W, Patel K, Boubertakh R, Rueckert D, O'Regan DP, Hughes AD, Moon JC, Manisty CH. Sex and regional differences in myocardial plasticity in aortic stenosis are revealed by 3D model machine learning. Eur Heart J Cardiovasc Imaging. 2020 Apr 1;21(4):417-427. doi: 10.1093/ehjci/jez166.

    PubMed 31280289

  • Smith A, Moravcova S, Treibel TA, Colque-Navarro P, Mollby R, Moon JC, Hamilton-Davies C. Relationship between endotoxin core, staphylococcal and varicella antibody levels and outcome following aortic valve replacement surgery: a prospective observational study. Perioper Med (Lond). 2018 Sep 20;7:20. doi: 10.1186/s13741-018-0101-z. eCollection 2018.

    PubMed 30250733

  • Treibel TA, Kozor R, Schofield R, Benedetti G, Fontana M, Bhuva AN, Sheikh A, Lopez B, Gonzalez A, Manisty C, Lloyd G, Kellman P, Diez J, Moon JC. Reverse Myocardial Remodeling Following Valve Replacement in Patients With Aortic Stenosis. J Am Coll Cardiol. 2018 Feb 27;71(8):860-871. doi: 10.1016/j.jacc.2017.12.035.

    PubMed 29471937

  • Treibel TA, Kozor R, Fontana M, Torlasco C, Reant P, Badiani S, Espinoza M, Yap J, Diez J, Hughes AD, Lloyd G, Moon JC. Sex Dimorphism in the Myocardial Response to Aortic Stenosis. JACC Cardiovasc Imaging. 2018 Jul;11(7):962-973. doi: 10.1016/j.jcmg.2017.08.025. Epub 2017 Nov 15.

    PubMed 29153564

Questions about this trial

What is this clinical trial studying?

An observational study of Aortic Stenosis, run by University College, London at 1 site in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cardiovascular death (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02174471, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2016.

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