ArrhythmiaEPORVANCT03910725
Electrophysiological Phenotyping Of Patients at Risk of Ventricular Arrhythmia and Sudden Cardiac Death
An observational study of Arrhythmia and Sudden Cardiac Death, run by Imperial College London at 2 sites in United Kingdom.
Trial summary
Obesity, rheumatoid arthritis (RA) and gene-specific dilated cardiomyopathy (DCM) are common medical conditions. Small-scale studies have shown that these are associated with proarrhythmic changes on 12-lead electrocardiogram (ECG) and a higher risk of sudden cardiac death (SCD). Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Arrhythmia, Sudden Cardiac Death, Cardiomyopathy, Dilated
- What is being tested?
- Electrocardiographic imaging
- How many people
- 100 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 21 Nov 2019to 31 Dec 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients awaiting stapled bariatric surgery, without a history of or concomitant ischaemic or structural heart disease, arrhythmia or receiving anti-arrhythmic medication, will be recruited prospectively from the bariatric surgery preoperative assessment clinics. Similarly, patients with RA will be recruited prospectively from rheumatology clinics, prior to initiation of biologic or diseased modifying anti-rheumatic drugs. TTNtv-positive and -negative DCM patients an existing data registry will be recalled for this study. Healthy volunteers: will be recruited from our affiliated institutions who have given prior consent to be contacted for research.
Who may be able to join
- patients with obesity (BMI>40) who will undergo stapled bariatric surgery
- RA, prior to commencement of disease-modifying drugs
- TTNtv-positive or -negative DCM
- no known existing medical condition or health concerns i.e. healthy volunteers;
- aged 18 to 75 years, inclusive
Who cannot join
- aged under 18 or over 75 years;
- known HIV, hepatitis B \& C or vCJD infection;
- unable to provide verbal or signed written informed consent;
- pregnancy or positive urinary pregnancy test;
- breastfeeding
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites, 2 recruiting
- Recruiting
Imperial College London (Hammersmith campus)
London, W12 0NN
Fu Siong Ng, 02075943614, f.ng@imperial.ac.uk
Kiran Patel, 07563225319, kiran.patel@imperial.ac.uk
- Recruiting
St Mary's Hospital
London, W2 1NY
Fu Siong Ng, 02075943614, f.ng@imperial.ac.uk
Kiran Patel, 02075943614, kiran.patel@imperial.ac.uk
About this study
Official title: Electrophysiological Remodelling Secondary to Metabolic, Inflammatory and Cardiomyopathic Processes
Obesity, rheumatoid arthritis (RA) and gene-specific dilated cardiomyopathy (DCM) are common medical conditions. Small-scale studies have shown that these are associated with proarrhythmic changes on 12-lead electrocardiogram (ECG) and a higher risk of sudden cardiac death (SCD). However, these studies lack the deep electrophysiological phenotyping required to explain their observations. Electrocardiographic imaging (ECGi) is a non-invasive alternative to 12-lead ECG, by which epicardial potentials, electrograms and activation sequences can be recorded to study adverse electrophysiological modelling in greater depth and on a more focussed, subject-specific scale. Therefore, this study proposes to better define the risk of arrhythmia and understand the underlying adverse electrophysiological remodelling conferring this risk in three groups (obesity, RA and DCM). Firstly, data from two large, national repositories will be analysed to identify associations between routine clinical biomarkers and proarrhythmic 12-lead ECG parameters, to confirm adverse electrophysiological remodelling and a higher risk of arrhythmia. Secondly,ECGi will be performed before and after planned clinical intervention in obese and RA patients, and at baseline in titin-truncating variant (TTNtv)-positive and -negative DCM patients, to characterise the specific and potentially reversible conduction and repolarisation abnormalities that may underlie increased arrhythmic risk.
Read the detailed description
Sudden cardiac death (SCD) occurs in groups that are neither traditionally considered high-risk nor have been the subject of large-scale studies. These include obesity, inflammatory arthropathy and gene-specific cardiomyopathy. Existing data to explain higher risk of arrhythmia in these cohorts rely on 12-lead ECG and therefore lack in-depth electrophysiological phenotyping. The investigators have access to the two large national data repositories providing a wealth of data to study risks of arrhythmia on a scale larger than any previously published study. They also have a proven track record of utilising electrocardiographic imaging (ECGi) to conduct in-depth investigation of electrophysiological remodelling to better characterise arrhythmic risk.
ECGi is a validated, noninvasive method of acquiring body surface potential data using 252-electrodes and combining it with subjectspecific heart-torso geometry from crosssectional imaging. Using inverse solution mathematical algorithms, the ECGi system reconstructs epicardial unipolar electrograms and panoramic activation and potential maps over a single sinus beat, which is visualised on a digitised image of the subject's heart. Various studies have demonstrated the efficacy of ECGi to localise ventricular arrhythmias; more accurately calculate QT interval dispersion than 12-lead ECGs in obesity; and characterise ventricular tachycardia (VT) with intramural re-entry following myocardial infarction-induced scarring.
The study aims to confirm that obesity, RA and DCM are risk factors for arrhythmia and associated with electrophysiological remodelling manifest on 12-lead ECG, using large data repositories. The investigators will also perform electrocardiographic imaging (ECGi) to investigate and understand specific, and potentially reversible, conduction and repolarisation abnormalities conferring risk of arrhythmia in these cohorts using ECGi.
Hypotheses:
- Routine clinical biomarkers correlate with proarrhythmic 12-lead ECG parameters
- Adverse (proarrhythmic) electrophysiological remodelling can be quantified with ECGi
- Bariatric surgery reverses adverse electrophysiological remodelling in obesity
- Pharmacological therapy reverses adverse electrophysiological remodelling in RA
- TTNtv is associated with adverse electrophysiological remodelling in DCM
In-keeping with hypothesis 1, the study population will include participants from the UK biobank and Airwave Health Monitoring Study in which risk of arrhythmia will be defined. Participants in both data repositories provided informed consent for their data to be used for research.
With respect to hypotheses 2-5, the study will involve 3 distinct ECGi sub-studies, each in a well-defined cohort to identify specific, and potentially reversible, conduction and repolarisation abnormalities, and comparing the disease to healthy controls. These are:
- Obesity (BMI >40) ii. RA iii. TTNtv-positive and -negative DCM
- Conditions
- Arrhythmia, Sudden Cardiac Death, Cardiomyopathy, Dilated, Obesity, Inflammation
- Being tested
- Electrocardiographic imaging
- Keywords
- Arrhythmia, Cardiomyopathy, Dilated, Electrocardiographic imaging
- Medical subject headings
- Arrhythmias, Cardiac, Death, Sudden, Cardiac, Cardiomyopathy, Dilated, Obesity, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Electrocardiographic imagingOther
ECGi is a non-invasive body surface mapping technique that collects electrocardiographic data using 252 leads, and combines it with subject specific anatomic data acquired from cross sectional imaging to recreate epicardial electrograms.
| Study group | Role | What they receive |
|---|---|---|
| Obesity | Patients with BMI >40 awaiting stapled bariatric surgery, without a history of or concomitant ischaemic or structural heart disease, arrhythmia or receiving anti-arrhythmic medication, will be recruited prospectively from the bariatric surgery preoperative assessment clinics. Receives: Other: Electrocardiographic imaging | |
| Rheumatoid arthritis | Patients with RA without diagnosed or known ischaemic or structural heart disease, arrhythmia or receiving anti-arrhythmic medication will be recruited prospectively from rheumatology clinics, prior to initiation of biologic or diseased modifying anti-rheumatic drugs. Receives: Other: Electrocardiographic imaging | |
| Dilated cardiomyopathy | TTNtv-positive and -negative DCM patients from the Royal Brompton Hospital biobank have provided informed consent to be contacted for research Receives: Other: Electrocardiographic imaging |
What is being measured
The primary outcome is the main question the study is designed to answer.
Activation-recovery intervals
Electrocardiographic parameter
Measured: 30 months approximately ie at the end of the study
Conduction velocity
Electrocardiographic parameter
Measured: 30 months approximately ie at the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2019
- Study start21 Nov 2019
- Primary completion31 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ArrhythmiaStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London
- Responsible party
- Sponsor
- Investigators
- Fu Siong Ng, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03910725
- Sponsor's protocol ID
- 19HH4965
- Acronym
- EPORVA
- Status last verified
- Aug 2021
- First submitted
- 8 Apr 2019
- Last updated
- 25 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Only anonymised data will be shared amongst the research team. This includes electrocardiographic, imaging, demographic, biochemical and other clinical data.
Study at a glance
From the registry record, last updated by the sponsor on 25 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiological Remodelling Secondary to Metabolic, Inflammatory and Cardiomyopathic Processes
- ClinicalTrials.gov ID
- NCT03910725
- Acronym / sponsor ID
- EPORVA / 19HH4965
- Conditions
- Arrhythmia, Sudden Cardiac Death, Cardiomyopathy, Dilated, Obesity, Inflammation
- Keywords
- Arrhythmia, Cardiomyopathy, Dilated, Electrocardiographic imaging
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- University College, London
- Study start
- 21 Nov 2019 (actual)
- Primary completion
- 31 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 10 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Obesity, rheumatoid arthritis (RA) and gene-specific dilated cardiomyopathy (DCM) are common medical conditions. Small-scale studies have shown that these are associated with proarrhythmic changes on 12-lead electrocardiogram (ECG) and a higher risk of sudden cardiac death (SCD). However, these studies lack the deep electrophysiological phenotyping required to explain their observations. Electrocardiographic imaging (ECGi) is a non-invasive alternative to 12-lead ECG, by which epicardial potentials, electrograms and activation sequences can be recorded to study adverse electrophysiological modelling in greater depth and on a more focussed, subject-specific scale. Therefore, this study proposes to better define the risk of arrhythmia and understand the underlying adverse electrophysiological remodelling conferring this risk in three groups (obesity, RA and DCM). Firstly, data from two large, national repositories will be analysed to identify associations between routine clinical biomarkers and proarrhythmic 12-lead ECG parameters, to confirm adverse electrophysiological remodelling and a higher risk of arrhythmia. Secondly,ECGi will be performed before and after planned clinical intervention in obese and RA patients, and at baseline in titin-truncating variant (TTNtv)-positive and -negative DCM patients, to characterise the specific and potentially reversible conduction and repolarisation abnormalities that may underlie increased arrhythmic risk.
Detailed description
Sudden cardiac death (SCD) occurs in groups that are neither traditionally considered high-risk nor have been the subject of large-scale studies. These include obesity, inflammatory arthropathy and gene-specific cardiomyopathy. Existing data to explain higher risk of arrhythmia in these cohorts rely on 12-lead ECG and therefore lack in-depth electrophysiological phenotyping. The investigators have access to the two large national data repositories providing a wealth of data to study risks of arrhythmia on a scale larger than any previously published study. They also have a proven track record of utilising electrocardiographic imaging (ECGi) to conduct in-depth investigation of electrophysiological remodelling to better characterise arrhythmic risk.
ECGi is a validated, noninvasive method of acquiring body surface potential data using 252-electrodes and combining it with subjectspecific heart-torso geometry from crosssectional imaging. Using inverse solution mathematical algorithms, the ECGi system reconstructs epicardial unipolar electrograms and panoramic activation and potential maps over a single sinus beat, which is visualised on a digitised image of the subject's heart. Various studies have demonstrated the efficacy of ECGi to localise ventricular arrhythmias; more accurately calculate QT interval dispersion than 12-lead ECGs in obesity; and characterise ventricular tachycardia (VT) with intramural re-entry following myocardial infarction-induced scarring.
The study aims to confirm that obesity, RA and DCM are risk factors for arrhythmia and associated with electrophysiological remodelling manifest on 12-lead ECG, using large data repositories. The investigators will also perform electrocardiographic imaging (ECGi) to investigate and understand specific, and potentially reversible, conduction and repolarisation abnormalities conferring risk of arrhythmia in these cohorts using ECGi.
Hypotheses:
- Routine clinical biomarkers correlate with proarrhythmic 12-lead ECG parameters
- Adverse (proarrhythmic) electrophysiological remodelling can be quantified with ECGi
- Bariatric surgery reverses adverse electrophysiological remodelling in obesity
- Pharmacological therapy reverses adverse electrophysiological remodelling in RA
- TTNtv is associated with adverse electrophysiological remodelling in DCM
In-keeping with hypothesis 1, the study population will include participants from the UK biobank and Airwave Health Monitoring Study in which risk of arrhythmia will be defined. Participants in both data repositories provided informed consent for their data to be used for research.
With respect to hypotheses 2-5, the study will involve 3 distinct ECGi sub-studies, each in a well-defined cohort to identify specific, and potentially reversible, conduction and repolarisation abnormalities, and comparing the disease to healthy controls. These are:
- Obesity (BMI >40) ii. RA iii. TTNtv-positive and -negative DCM
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Obesity | – | Other: Electrocardiographic imagingPatients with BMI >40 awaiting stapled bariatric surgery, without a history of or concomitant ischaemic or structural heart disease, arrhythmia or receiving anti-arrhythmic medication, will be recruited prospectively from the bariatric surgery preoperative assessment clinics. |
| Rheumatoid arthritis | – | Other: Electrocardiographic imagingPatients with RA without diagnosed or known ischaemic or structural heart disease, arrhythmia or receiving anti-arrhythmic medication will be recruited prospectively from rheumatology clinics, prior to initiation of biologic or diseased modifying anti-rheumatic drugs. |
| Dilated cardiomyopathy | – | Other: Electrocardiographic imagingTTNtv-positive and -negative DCM patients from the Royal Brompton Hospital biobank have provided informed consent to be contacted for research |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients awaiting stapled bariatric surgery, without a history of or concomitant ischaemic or structural heart disease, arrhythmia or receiving anti-arrhythmic medication, will be recruited prospectively from the bariatric surgery preoperative assessment clinics. Similarly, patients with RA will be recruited prospectively from rheumatology clinics, prior to initiation of biologic or diseased modifying anti-rheumatic drugs. TTNtv-positive and -negative DCM patients an existing data registry will be recalled for this study. Healthy volunteers: will be recruited from our affiliated institutions who have given prior consent to be contacted for research.
Key inclusion criteria (5 listed)
- patients with obesity (BMI>40) who will undergo stapled bariatric surgery
- RA, prior to commencement of disease-modifying drugs
- TTNtv-positive or -negative DCM
- no known existing medical condition or health concerns i.e. healthy volunteers;
- aged 18 to 75 years, inclusive
Key exclusion criteria (5 listed)
- aged under 18 or over 75 years;
- known HIV, hepatitis B \& C or vCJD infection;
- unable to provide verbal or signed written informed consent;
- pregnancy or positive urinary pregnancy test;
- breastfeeding
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Electrocardiographic imagingECGi is a non-invasive body surface mapping technique that collects electrocardiographic data using 252 leads, and combines it with subject specific anatomic data acquired from cross sectional imaging to recreate epicardial electrograms. | Other | Dilated cardiomyopathy, Obesity, Rheumatoid arthritis |
Primary outcome
Activation-recovery intervals
Time frame: 30 months approximately ie at the end of the study
Electrocardiographic parameter
Conduction velocity
Time frame: 30 months approximately ie at the end of the study
Electrocardiographic parameter
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Aug 2021.
- Individual participant dataSharing planned: No. Only anonymised data will be shared amongst the research team. This includes electrocardiographic, imaging, demographic, biochemical and other clinical data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Fu Siong Ng principal investigator
Imperial College London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Arrhythmia and Sudden Cardiac Death, run by Imperial College London at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Fu Siong Ng, BSc MRCP PhD (+442075943614, f.ng@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Activation-recovery intervals (time frame: 30 months approximately ie at the end of the study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2021.