The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy

NCT05026112 | Unknown

• 1 other identifier: 143656
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Midwall septal fibrosis (MSF) is a common structural abnormality in non-ischaemic dilated cardiomyopathy (DCM). Its presence is believed to increase the risk of malignant ventricular arrhythmias (VA), but the mechanism of arrhythmogenicity is not known. This is particularly relevant in DCM patients with MSF and mid-range left ventricular ejection fraction (LVEF) as they do not currently fulfil criteria for a primary prevention implantable cardioverter-defibrillator (ICD) insertion. Access to the epicardium for electrical measurements of the heart can enhance the understanding of arrhythmogenicity in DCM, however direct epicardial access is invasive. Instead, the investigators will non-invasively combine high resolution 256-lead ECG imaging (ECGI) and latest generation cardiovascular magnetic resonance (CMR) to study the hearts of 60 DCM patients with and without MSF regardless of LVEF, and 60 matched healthy volunteers. The investigators recently invented the re-usable and CMR-safe SMART-ECGI vest technology for this purpose. Using supercomputers, the investigators will fuse the collected ECGI/CMR data and run electromechanical simulations of whole-heart activation to non-invasively measure each participant's personalised risk of malignant VA induction. By panoramically mapping the DCM heart in a single beat, the investigators aim to elucidate how MSF perturbs the cardiac activation front and how this could lead to life-threatening VA. This has the potential to change the method by which cardiologists risk stratify patients with DCM.

Conditions

Dilated Cardiomyopathy

Outcome Measures

Primary Outcomes (1)

• The relationship between the electrical and structural substrate in DCM

  The investigators will describe the relationship between the electrical and structural substrate in DCM across the spectrum of left ventricular dysfunction.

  2 years

Secondary Outcomes (3)

• Comparison of epicardial activation and conduction patterns via ECGI

  2 years

• Comparison of MSF+DCM, MSF-DCM and controls' electromechanical function of the heart via modelling

  2 years

• Personalised simulation of risk of malignant ventricular arrhythmia

  2 years

Study Arms (4)

DCM with MSF (MSF+)

Patients with dilated cardiomyopathy and midwall septal fibrosis identified in a previous cardiac MRI scan

Diagnostic Test: ECG-Imaging; Diagnostic Test: Cardiac MRI scan

DCM without MSF (MSF-)

Patients with dilated cardiomyopathy but without midwall septal fibrosis on previous cardiac MRI scan

Diagnostic Test: ECG-Imaging; Diagnostic Test: Cardiac MRI scan

Control - MSF+

Control healthy volunteers (HV) to the MSF+ cohort

Diagnostic Test: ECG-Imaging; Diagnostic Test: Cardiac MRI scan

Control - MSF-

Control healthy volunteers (HV) to the MSF- cohort

Diagnostic Test: ECG-Imaging; Diagnostic Test: Cardiac MRI scan

Interventions

ECG-Imaging DIAGNOSTIC_TEST

ECG imaging acquisition

Control - MSF+; Control - MSF-; DCM with MSF (MSF+); DCM without MSF (MSF-)

Cardiac MRI scan DIAGNOSTIC_TEST

Cardiac MRI scan

Control - MSF+; Control - MSF-; DCM with MSF (MSF+); DCM without MSF (MSF-)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with dilated cardiomyopathy, with and without midwall septal fibrosis on previous CMR

You may qualify if:

• Adults with dilated cardiomyopathy
• With and without midwall septal fibrosis on previous CMR

You may not qualify if:

• Needle-phobic patients that would preclude cannulation for contrast injection and blood taking
• anyone unwilling to consent
• anyone with a conventional contraindication for CMR
• anyone with any condition precluding full participation in the study such as DCM patients with infarct-pattern LGE, or subepicardial LGE or non-septal midwall fibrosis (participants with small volume right ventricular insertion point LGE will not be excluded).

Sponsors & Collaborators

• University College, London: lead

Study Sites (1)

Royal Free Hospital NHS Trust (RFH)

London, United Kingdom

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample collection - for storage of DNA, RNA, small molecule analysis, and blood cells for human induced pluripotent cells. Urine sample collection for small molecule analysis

MeSH Terms

Conditions

Cardiomyopathy, Dilated

Condition Hierarchy (Ancestors)

Cardiomegaly; Heart Diseases; Cardiovascular Diseases; Cardiomyopathies; Laminopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Gabriella Captur, PhD

  University College, London

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Fiona Chan, MBBS

CONTACT

02076705702; f.chan@ucl.ac.uk

Gabriella Captur, PhD

CONTACT

02076705702; gabriella.captur@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: August 23, 2021
• First Posted: August 30, 2021
• Study Start: October 1, 2021
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2024
• Last Updated: March 31, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)