Pathological Changes in the Cardiovascular System in Valvular Heart Disease

Recruiting

• Conditions: Valvular Heart Disease
• Interventions: Procedure: Aortic valve intervention

• Registration Number: NCT06060171
• Lead Sponsor: University College, London

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-08-01
• Status Verified: 2023-09
• Study First Submitted: 2023-09-22
• Study First Submitted QC: 2023-09-22
• Study First Posted: 2023-09-29
• Last Update Submitted: 2023-10-03
• Last Update Posted: 2023-10-06
• Primary Completion: 2025-01-01
• Study Completion: 2025-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 360

Inclusion Criteria

• 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).

Exclusion Criteria

• 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)

Exclusion for the Heart-Brain-Axis Study:

• Participants that have more than moderate epicardial coronary disease (by CT or invasive coronary angiography) will be excluded.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Multisystem impact of VHD	Aortic valve intervention	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.
Response to intervention.	Aortic valve 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.

Primary Outcome Measures

Name	Time	Method
Multisystem study: Correlation between capillary density and stress myocardial blood flow in severe valve disease before intervention (at baseline)	Single timepoint
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
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

Trial Locations

Locations (1)

Barts Heart Centre; 🇬🇧 London, United Kingdom