The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy (DCM-MSF)

The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy: a Combined ECGI and CMR Investigative Study

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.

Study Overview

• Status: Recruiting
• Conditions: Dilated Cardiomyopathy
• Intervention / Treatment: Diagnostic test: ECG-Imaging; Diagnostic test: Cardiac MRI scan

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: Fiona Chan, MBBS; Phone Number: 02076705702; Email: f.chan@ucl.ac.uk
• Study Contact Backup: Name: Gabriella Captur, PhD; Phone Number: 02076705702; Email: gabriella.captur@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • Royal Free Hospital NHS Trust (RFH)
    • Contact: Fiona Chan, MBBS; Phone Number: 02076705702; Email: f.chan@ucl.ac.uk
    • Principal Investigator: Dr Gabriella Captur, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

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

Description

Inclusion Criteria:

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

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
DCM with MSF (MSF+); Patients with dilated cardiomyopathy and midwall septal fibrosis identified in a previous cardiac MRI scan	Diagnostic test: ECG-Imaging; ECG imaging acquisition; Diagnostic test: Cardiac MRI scan; 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; ECG imaging acquisition; Diagnostic test: Cardiac MRI scan; Cardiac MRI scan
Control - MSF+; Control healthy volunteers (HV) to the MSF+ cohort	Diagnostic test: ECG-Imaging; ECG imaging acquisition; Diagnostic test: Cardiac MRI scan; Cardiac MRI scan
Control - MSF-; Control healthy volunteers (HV) to the MSF- cohort	Diagnostic test: ECG-Imaging; ECG imaging acquisition; Diagnostic test: Cardiac MRI scan; Cardiac MRI scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of epicardial activation and conduction patterns via ECGI	The investigators will compare participants with MSF+DCM, MSF-DCM and controls in terms 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	The investigators will compare MSF+DCM, MSF-DCM and controls in terms of Electromechanical function of the heart (via 4-dimensional computational models)	2 years
Personalised simulation of risk of malignant ventricular arrhythmia	Applying and exploring simulation methodology to establish predictions for likely propensity to malignant VA (personalised simulations of risk) between MSF+DCM, MSF-DCM and controls groups	2 years

Collaborators and Investigators

• Sponsor: University College, London
• Investigators: Principal Investigator: Gabriella Captur, PhD, University College, London

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: August 23, 2021
• First Submitted That Met QC Criteria: August 23, 2021
• First Posted (Actual): August 30, 2021

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Cardiomegaly; Laminopathies; Cardiomyopathies; Cardiomyopathy, Dilated
• Other Study ID Numbers: 143656

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