NCT04627987

Brief Summary

Aortic stenosis (AS) is caused by narrowing of one of the main heart valves. Replacing the valve is the only treatment to prevent the heart from failing or death. The timing of replacement is currently often too late - half of patients are left with permanent scarring and a quarter die within 3.5 years. Studies are underway to see if earlier replacement makes a difference. But for those with scarring of the heart, there is currently no tailored treatment. I want to change this by understanding why and how patients with scar are dying and what the investigators can do to prevent this. In this study, the investigators will use a heart scan (MRI) to detect scarring before valve replacement. After replacement, patients will receive a tiny monitor (paper clip size), which the investigators inject underneath the skin. This monitor continuously checks the heartbeat and can detect increased body fluid due to heart failure. The investigators will monitor patients for an average of 3 years to see if scarring is linked to abnormal heart rhythms and heart failure. Once the investigators know how and why, the investigators can target patients with available medications and design studies using specialised treatments, eg defibrillator implantation, to protect patients with scar from dying.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
192

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Mar 2021

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 6, 2020

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 13, 2020

Completed
4 months until next milestone

Study Start

First participant enrolled

March 23, 2021

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2025

Completed
Last Updated

April 30, 2021

Status Verified

April 1, 2021

Enrollment Period

4.7 years

First QC Date

November 6, 2020

Last Update Submit

April 27, 2021

Conditions

Keywords

Late gadolinium enhancementTissue characterisationArrhythmiaSudden cardiac deathHeart failureAortic stenosisMyocardial remodelling

Outcome Measures

Primary Outcomes (2)

  • Heart failure death or hospitalisation for heart failure.

    5 years after aortic valve replacement

  • Burden of non-sustained VT

    As assessed on implantable cardiac monitor (approximate battery life 2.5 years)

    2.5 years after aortic valve replacement.

Secondary Outcomes (5)

  • All-cause mortality (all-cause and cardiovascular via NHS spine/death registration)

    5 years after aortic valve replacement

  • change in functional capacity (6-minute walk test)

    At 6 weeks and 12 months after aortic valve replacement.

  • Heart failure symptoms

    At 6 weeks and 12 months post aortic valve surgery

  • Heart failure symptoms

    At 6 weeks and 12 months post aortic valve surgery

  • Burden of other serious arrhythmias requiring change in management

    2.5 years after aortic valve replacement

Study Arms (1)

Main study

Patients with severe, symptomatic aortic stenosis will be recruited and followed up with primary outcome of heart failure death and hospitalisation (n=192). Of these, 170 will have an implantable cardiac monitor placed to detect presence and burden of non-sustained VT.

Diagnostic Test: Cardiac MRI scanDiagnostic Test: Serum biomarkers (High sensitivity troponin, NT-proBNPProcedure: Implantable Loop RecorderDiagnostic Test: 6 minute walk testDiagnostic Test: Echocardiogram

Interventions

Cardiac MRI scanDIAGNOSTIC_TEST

Cardiac MRI scan pre- and post- aortic valve replacement to assess degree of left ventricular remodelling, fibrosis and myocardial blood flow.

Main study

Blood tests looking evidence of cardiac structural remodelling and function.

Main study

Determine post-AVR arrhythmia burden

Main study
6 minute walk testDIAGNOSTIC_TEST

Validated assessment of functional capacity - distance walked over 6 minute time frame.

Main study
EchocardiogramDIAGNOSTIC_TEST

Ultrasound assessment of heart structure and function. Standard of care in valve surgery pathway.

Main study

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

This is a prospective single centre, observational cohort study of patients with symptomatic severe AS (n=192) undergoing clinically indicated AVR (surgical or transcatheter) and multiparametric assessment by CMR prior to AVR.

You may qualify if:

  • Patients with symptomatic severe aortic stenosis referred for surgical or transcatheter AVR (one out of: effective orifice area \[EOA\] \<1.0 cm2 , indexed EOA of 0.6cm/m2, peak velocity \>4.0 m/s or mean gradient \>40mmHg).

You may not qualify if:

  • More than moderate valve disease other than AS
  • Diagnosis of dilated or hypertrophic cardiomyopathy, pregnancy/breast feeding
  • eGFR \<30ml/min, CMR incompatible devices
  • Inability to complete the protocol
  • Other conditions that would prevent participation in the study.
  • Adenosine perfusion will not be performed in patients with AV block, severe asthma/COPD or LVEF\<40%.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Barts Heart Centre

London, EC1A 7BE, United Kingdom

RECRUITING

Related Publications (1)

  • Bennett J, Thornton GD, Nitsche C, Gama FF, Aziminia N, Gul U, Shetye A, Kellman P, Davies RH, Moon JC, Treibel TA; Barts Valve and Imaging Group. Left Ventricular Hypertrophy in Aortic Stenosis: Early Cell and Matrix Regression 2 Months Post-Aortic Valve Replacement. Circ Cardiovasc Imaging. 2024 Dec;17(12):e017425. doi: 10.1161/CIRCIMAGING.124.017425. Epub 2024 Dec 4.

Biospecimen

Retention: SAMPLES WITHOUT DNA

Myocardial biopsy

MeSH Terms

Conditions

Aortic Valve StenosisHeart FailureArrhythmias, CardiacDeath, Sudden, Cardiac

Interventions

Walk TestEchocardiography

Condition Hierarchy (Ancestors)

Aortic Valve DiseaseHeart Valve DiseasesHeart DiseasesCardiovascular DiseasesVentricular Outflow ObstructionPathologic ProcessesPathological Conditions, Signs and SymptomsHeart ArrestDeath, SuddenDeath

Intervention Hierarchy (Ancestors)

Exercise TestHeart Function TestsDiagnostic Techniques, CardiovascularDiagnostic Techniques and ProceduresDiagnosisCardiac Imaging TechniquesDiagnostic ImagingUltrasonography

Central Study Contacts

Thomas A Treibel, MBBS PhD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 6, 2020

First Posted

November 13, 2020

Study Start

March 23, 2021

Primary Completion

December 1, 2025

Study Completion

December 1, 2025

Last Updated

April 30, 2021

Record last verified: 2021-04

Locations