Pathological Changes in the Cardiovascular System in Valvular Heart Disease (PATH-VHD)

Pathological Changes in the Cardiovascular System in Valvular Heart Disease: Validation of Non-invasive Markers

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.

Study Overview

• Status: Recruiting
• Conditions: Valvular Heart Disease
• Intervention / Treatment: Procedure: Aortic valve intervention

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: George D Thornton, MD; Phone Number: +4420 3465 5543; Email: george.thornton@ucl.ac.uk
• Study Contact Backup: Name: Thomas Treibel, MD PhD; Email: thomas.treibel.12@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • Barts Heart Centre
    • Contact: Thomas Treibel, MBBS PhD; Phone Number: 020 3416 5000; Email: thomas.treibel.12@ucl.ac.uk
    • Principal Investigator: Thomas A Treibel, MBBS PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• 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

Description

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 Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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; Surgical or transcatheter aortic valve intervention
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; Surgical or transcatheter aortic valve intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: British Heart Foundation; Horizon 2020 - European Commission

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: September 22, 2023
• First Submitted That Met QC Criteria: September 22, 2023
• First Posted (Actual): September 29, 2023

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 3, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases
• Other Study ID Numbers: 134018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No