The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy

Study Overview
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Brief Summary
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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.

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

Conditions
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Dilated Cardiomyopathy

Intervention / Treatment
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* Diagnostic Test: ECG-Imaging
* Diagnostic Test: Cardiac MRI scan


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| DCM with MSF (MSF+)<br>Patients with dilated cardiomyopathy and midwall septal fibrosis identified in a previous cardiac MRI scan | Diagnostic Test: ECG-Imaging<br>* ECG imaging acquisition<br>Diagnostic Test: Cardiac MRI scan<br>* Cardiac MRI scan<br>|
| DCM without MSF (MSF-)<br>Patients with dilated cardiomyopathy but without midwall septal fibrosis on previous cardiac MRI scan | Diagnostic Test: ECG-Imaging<br>* ECG imaging acquisition<br>Diagnostic Test: Cardiac MRI scan<br>* Cardiac MRI scan<br>|
| Control - MSF+<br>Control healthy volunteers (HV) to the MSF+ cohort | Diagnostic Test: ECG-Imaging<br>* ECG imaging acquisition<br>Diagnostic Test: Cardiac MRI scan<br>* Cardiac MRI scan<br>|
| Control - MSF-<br>Control healthy volunteers (HV) to the MSF- cohort | Diagnostic Test: ECG-Imaging<br>* ECG imaging acquisition<br>Diagnostic Test: Cardiac MRI scan<br>* Cardiac MRI scan<br>|

What is the study measuring?
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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 |