Pathological Changes in the Cardiovascular System in Valvular Heart Disease

NCT06060171 | Unknown

• 1 other identifier: 134018
• Study Type: observational
• Target: 360
• Locations: 1 country
• Sites: 1

Brief Summary

An observational cohort study of patients recruited presenting with valvular heart disease. The specialized investigations will focus on myocardial remodelling and scar formation/regression and extracardiac micro- and macro-vascular sequelae of valvular heart disease (VHD). The aim is to investigate the natural history of VHD and its ensuing cardiac and extracardiac end organ effects, the impact of existing interventions and the long-term outcome. We hope to establish the underlying causative aetiology of known associated conditions (e.g. vascular dementia) and to determine if extracardiac changes may serve as early biomarkers of prognosis in VHD. Participants will attend for two visits at Barts Heart Centre or Chenies Mews Imaging Centre and will undergo a panel of tests including cross-sectional cardiac imaging, point-of-care microvascular assessment and blood tests. Patient outcome will be assessed by data linkage to hospital episode statistic (HES) data and ONS data (via NHS spine). We aim to identify determinants that will help to improve patient selection and timing of valve intervention based on advanced clinical, blood and/or imaging biomarkers.

Conditions

Valvular Heart Disease

Outcome Measures

Primary Outcomes (4)

• Multisystem study: Correlation between capillary density and stress myocardial blood flow in severe valve disease before intervention (at baseline)

  Single timepoint

• Multisystem study: Correlation between brain blood flow (arterial spin labelling) and stress myocardial blood flow in severe valve disease before intervention (at baseline)

  Single timepoint

• Intervention study: Change in stress myocardial blood flow from baseline to 6 months after aortic valve replacement

  Baseline and 6 months after surgery

• Intervention study: Correlation between functional capacity, measured by cardiopulmonary exercise testing and myocardial blood flow and fibrosis by cardiovascular magnetic resonance and histology at baseline and at 6 months after valve replacement

  Baseline and 6 months after surgery

Study Arms (3)

Natural history

Natural history of the three common valvular lesions; aortic stenosis, aortic regurgitation and mitral regurgitation. Patients with mild, moderate and severe valvular heart disease (VHD) will be followed up at 1-year to measure progression in remodelling (hypertrophy, ischaemic, scar).

Multisystem impact of VHD

Patients with severe symptomatic VHD will undergo non-invasive brain and cardiac magnetic resonance imaging (MRI) plus other non-invasive imaging tests to quantify small blood vessels across the cardiovascular system at baseline and at 6 months after surgical aortic valve replacement at which point a myocardial biopsy is taken.

Procedure: Aortic valve intervention

Response to intervention.

Patients with severe symptomatic VHD undergoing intervention will be followed up at 6 months to assess reverse remodelling after valve intervention. In those undergoing open-heart surgery, a myocardial biopsy will be taken to validate and complement non-invasive imaging.

Procedure: Aortic valve intervention

Interventions

Aortic valve intervention PROCEDURE

Surgical or transcatheter aortic valve intervention

Multisystem impact of VHD; Response to intervention.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Natural history cohort: Patients with three common valvular lesions: Aortic stenosis, aortic regurgitation and mitral regurgitation Multisystem impact of valvular heart disease: Patients with severe symptomatic valvular heart disease referred for surgery Response to intervention: Patients with severe symptomatic valvular heart disease undergoing intervention

You may qualify if:

• Age \> 18 years
• Able to provide written informed consent
• Mild, moderate or severe valvular heart disease (Natural history cohort), or severe valvular heart disease planned for surgical/transcatheter intervention (Intervention/Heart-Brain axis cohort).

You may not qualify if:

• Participants unwilling to consent.
• Needle phobic patients that would preclude blood taking
• Diagnosis of dilated or hypertrophic cardiomyopathy
• Pregnancy/breast feeding
• Inability to complete the protocol, other conditions that would prevent participation in the study.
• In severe VHD, no more than moderate valve disease other than primary lesion (AS / MR / AR)
• Participants that have more than moderate epicardial coronary disease (by CT or invasive coronary angiography) will be excluded.

Sponsors & Collaborators

• University College, London: lead
• British Heart Foundation: collaborator
• Horizon 2020 - European Commission: collaborator

Study Sites (1)

Barts Heart Centre

London, EC1A 7BE, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Septal myocardial biopsies Blood biomarkers

MeSH Terms

Conditions

Heart Valve Diseases

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Central Study Contacts

George D Thornton, MD

CONTACT

+4420 3465 5543; george.thornton@ucl.ac.uk

Thomas Treibel, MD PhD

CONTACT

thomas.treibel.12@ucl.ac.uk

Study Design

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

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 29, 2023
• Study Start: August 1, 2021
• Primary Completion: January 1, 2025
• Study Completion: January 1, 2025
• Last Updated: October 6, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)