Clinical trial NCT05026112: The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy
Official title: The Arrhythmogenic Potential of Midwall Septal Fibrosis in Dilated Cardiomyopathy: a Combined ECGI and CMR Investigative Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Dilated Cardiomyopathy
Lead sponsor: University College, London
Sponsor class: OTHER
First posted: 2021-08-30
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with dilated cardiomyopathy, with and without midwall septal fibrosis on previous CMR

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.


Eligibility criteria: 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).

Primary outcomes:
measure: The relationship between the electrical and structural substrate in DCM
timeFrame: 2 years
Secondary outcomes:
measure: Comparison of epicardial activation and conduction patterns via ECGI
timeFrame: 2 years
measure: Comparison of MSF+DCM, MSF-DCM and controls' electromechanical function of the heart via modelling
timeFrame: 2 years
measure: Personalised simulation of risk of malignant ventricular arrhythmia
timeFrame: 2 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Royal Free Hospital NHS Trust (RFH)
Study officials:
affiliation: University College, London
name: Gabriella Captur, PhD
role: PRINCIPAL_INVESTIGATOR
References: