An observational study in Arrhythmogenic Right Ventricular Dysplasia, Brugada Syndrome and Cardiac Channelopathy, sponsored by St. George's Hospital, London. Recruiting at 1 site in United Kingdom. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-08.
Sponsored by St. George's Hospital, London · Observational
Every week in the UK, 12 apparently healthy and fit individuals under the age of 35 die suddenly, a tragic event known as sudden cardiac death (SCD). The investigators have shown that heritable cardiac disorders affect the distribution of proteins at the cardiac cell-cell junctions, the areas where cardiac cells are mechanically and electrically coupled. This knowledge has helped the investigators diagnose specific heart disorders in individuals thus reducing the risk and incidence of SCD. Yet, the primary material required is a heart sample. A heart biopsy is an invasive process that comes with risks and is not performed unless absolutely necessary. And it is impossible to obtain a heart sample from an individual that may be carrying a disease-causing mutation (and hence be at risk of SCD) but does not yet show evidence of disease manifestation. The investigators recently showed that buccal cells show changes in protein distribution equivalent to those exhibited by the heart,hence providing them with a surrogate tissue for the myocardium. The investigators aim to use buccal smears as a means to identify those at risk of SCD. Patients regularly seen at the cardiology clinics at St. George's Hospital can participate in the study. The investigators shall take a buccal smear simply by rubbing a soft brush at the inside of their cheek and smearing it on a slide. Most individuals willing to participate in the study will only have to provide the investigators with a sample once. However, in selected cases (for instance, if the patients show disease progression or have a change in medication) they may be asked to provide the investigators with a subsequent sample during one of their scheduled follow-up visits. The process takes only a few seconds, is totally risk- and pain-free and it is anticipated to have great implications in diagnosis and patient management.
Exfoliated buccal mucosa cells have been used as a source of material for various genetic tests and in studies of oral cancer but their use in studies of cardiovascular disease has been limited. Previous applications have included analysis of telomere length in buccal cells from patients with ischemic heart failure and measurements of intracellular magnesium levels in patients undergoing radiofrequency catheter ablation for atrial fibrillation. To the best of the investigators' knowledge, their study published at Circulation Arrhythmia and Electrophysiology 9(2) in 2016, was the first analysis of buccal mucosa cells in patients with a heritable form of heart disease. This analysis included 39 patients diagnosed with arrhythmogenic cardiomyopathy (ACM), a primary myocardial disease characterized by an unusually high burden of arrhythmias and sudden cardiac death as well as 15 carriers of disease-causing mutations without overt disease manifestation. In a subsequent analysis (unpublished data), 55 additional individuals affected by ACM were sampled and the positive predictive value of our approach in diagnosing the disease was 91.9%. Although highly arrhythmogenic, ACM is a relatively rare disorder. The investigators are now at a position to apply this simple, totally risk-free approach to help identify those individuals at risk of SCD due to more common forms of heritable arrhythmic disorders including the cardiac channelopathies. The cardiologists at St. George's University of London evaluate more than 100 families of SCD victims per year for diagnosis and risk assessment. The large number of individuals evaluated at this single site provides the unprecedented opportunity to use this novel diagnostic approach to aid significant numbers of those at risk of developing life-threatening arrhythmias. There are no risks or potential discomfort associated with the study for the volunteer participants. The outcomes, however, may prove highly beneficial for prevention of SCD, timely and accurate diagnosis and management of arrhythmic disorders.
The study participants will just be asked to open their mouth. A study team member will rub a soft brush a few times at the inside of their cheek and smear the brush on a microscopy slide. The slide will be sprayed with 70% ethanol to preserve the material and taken to the research laboratory where it will be subjected to immunostaining to study the distribution of key proteins. The patient will have a total of 4 smears taken (2 from each cheek). For the majority of the patients, only a single sampling will be enough which will take place during one of their regular follow-up appointments at the cardiology clinic. There is no pain and no discomfort associated with the procedure and it lasts only a few seconds. In selected cases, however, if for instance the investigators want to use the buccal smear to evaluate the effect of a novel drug treatment on protein distribution, the patient might be asked to provide the study team with another sample, again during one of his scheduled regular follow-up visits
48 studies on the registry are indexed under Arrhythmogenic Right Ventricular Dysplasia; 28 are open to participants now.
This study's planned enrollment of 26 is below the median of 320 across 33 observational studies indexed under Arrhythmogenic Right Ventricular Dysplasia.
Browse Arrhythmogenic Right Ventricular Dysplasia studies →St. George's Hospital, London is the lead sponsor of 7 studies on the registry; 3 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Participants will include individuals that have arrhythmic disorders or are being evaluated for arrhythmic disorders due to a family history of sudden cardiac death at the cardiology center of St George's.
Inclusion Criteria:• Participants will include patients diagnosed with a heritable arrhythmic disorder (including arrhythmogenic, hypertrophic and dilated cardiomyopathy, cardiac sarcoidosis as well as cardiac channelopathies; Long syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) followed at the Inherited Cardiac Conditions (ICC) service of St. George's University Hospitals NHS Foundation Trust.
Exclusion Criteria:• Children under 18 years of age
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will include patients diagnosed with a heritable arrhythmic disorder (including arrhythmogenic, hypertrophic and dilated cardiomyopathy, cardiac sarcoidosis as well as cardiac channelopathies; Long QT syndrome, Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia) followed at the Inherited Cardiac Conditions (ICC) service of St. George's University Hospitals NHS Foundation Trust as well as family members of victims of SCD evaluated at the same clinic for risk assessment and diagnosis.
Diagnostic Test: obtaining a buccal smear sample
A sample will be taken from the inside of the participants' cheeks using a soft brush
Alteration of Key Protein Distribution
We recruit individuals that have propensity to an arrhythmic disorder (ie. they are carriers of disease-causing mutations) or they have been already diagnosed with a heritable heart condition. The primary outcome measure is whether key proteins show altered localization in the eligible participants. We are reporting the number of participants that did show altered protein distribution at baseline. There is no unit of measurement for this outcome. Cheek smears are subjected to immunofluorescence staining and examined under a confocal microscope. The technique has been optimized to show a binary outcome: a protein is either at its normal location or not.
Time frame: This is a longitudinal study. Each participant will provide cheek smears at recruitment to assess baseline protein distribution. Thereafter, each participant will be asked to provide follow-up samples every 6 months for the duration of the study.
Correlation of Protein Distribution With Participants' Genotype
A potential secondary outcome of the research is whether the investigators can correlate protein distribution in the buccal mucosa with specific genotypes. The investigators' preliminary results on the cohort of patients with ACM suggest that mutations in different genes result in different protein distribution patterns within the buccal mucosa. Being able to predict the gene bearing the disease-causing mutation will significantly reduce the time and cost of genetic sequencing. Identifying the specific gene underlying a heritable arrhythmic disorder is of pivotal importance as increasingly developing genotype/phenotype correlations help individualized risk identification and patient management.
Time frame: This is a longitudinal study. Each participant will provide cheek smears at recruitment to assess baseline protein distribution. Thereafter, each participant will be asked to provide follow-up samples every 6 months for the duration of the study.
Correlation of Treatments With Cx43 Distribution
Another potential outcome has to do with the effect changes in the patients' treatment plans may have on Cx43 distribution. Cx43 is the major gap junction protein responsible for the electrical coupling of the cells. It has been shown that patients with arrhythmic disorders show decreased distribution of Cx43 at the cell borders in their hearts and this has been associated with an increased risk for arrhythmias. The investigators' preliminary studies show that patients with cardiomyopathies show Cx43 remodeling in their buccal mucosa. If a patient seen at the arrhythmia service of St. George's shows Cx43 remodeling during initial sampling and in a follow-up visit his clinical care team deems necessary to change his treatment plan the investigators would like to study Cx43 distribution again during one of his/hers follow up visits. If the new treatment plan results in restoration of Cx43, this finding may be an indication of successful arrhythmia management.
Time frame: This is a longitudinal study. Each participant will provide cheek smears at recruitment to assess baseline protein distribution. Thereafter, each participant will be asked to provide follow-up samples every 6 months for the duration of the study.
| Milestone | Predisposed for Heritable Cardiac Disorder |
|---|---|
| Started | 26 |
| Completed | 26 |
| Not completed | 0 |
We recruit individuals that have propensity to an arrhythmic disorder (ie. they are carriers of disease-causing mutations) or they have been already diagnosed with a heritable heart condition. The primary outcome measure is whether key proteins show altered localization in the eligible participants. We are reporting the number of participants that did show altered protein distribution at baseline. There is no unit of measurement for this outcome. Cheek smears are subjected to immunofluorescence staining and examined under a confocal microscope. The technique has been optimized to show a binary outcome: a protein is either at its normal location or not.
| Participants | Predisposed for Heritable Cardiac Disorder |
|---|---|
| Alteration of Key Protein Distribution | 26 |
A potential secondary outcome of the research is whether the investigators can correlate protein distribution in the buccal mucosa with specific genotypes. The investigators' preliminary results on the cohort of patients with ACM suggest that mutations in different genes result in different protein distribution patterns within the buccal mucosa. Being able to predict the gene bearing the disease-causing mutation will significantly reduce the time and cost of genetic sequencing. Identifying the specific gene underlying a heritable arrhythmic disorder is of pivotal importance as increasingly developing genotype/phenotype correlations help individualized risk identification and patient management.
Results for this outcome have not been posted.
Another potential outcome has to do with the effect changes in the patients' treatment plans may have on Cx43 distribution. Cx43 is the major gap junction protein responsible for the electrical coupling of the cells. It has been shown that patients with arrhythmic disorders show decreased distribution of Cx43 at the cell borders in their hearts and this has been associated with an increased risk for arrhythmias. The investigators' preliminary studies show that patients with cardiomyopathies show Cx43 remodeling in their buccal mucosa. If a patient seen at the arrhythmia service of St. George's shows Cx43 remodeling during initial sampling and in a follow-up visit his clinical care team deems necessary to change his treatment plan the investigators would like to study Cx43 distribution again during one of his/hers follow up visits. If the new treatment plan results in restoration of Cx43, this finding may be an indication of successful arrhythmia management.
Results for this outcome have not been posted.
Collected over through study completion an average of 1 year. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Predisposed for Heritable Cardiac Disorder | 0/18 (0%) | 0/18 (0%) | 0/18 (0%) |
| Event | Predisposed for Heritable Cardiac Disorder |
|---|---|
| no adverse events recorded†Congenital, familial and genetic disorders | 0/18 |
| Age, Categorical(Participants) | Patients With Arrhythmic Disorders |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 18 |
| >=65 years | 0 |
| Age, Continuous(years) | Patients With Arrhythmic Disorders |
|---|---|
| Mean | 32 ± 6 |
| Sex: Female, Male(Participants) | Patients With Arrhythmic Disorders |
|---|---|
| Female | 6 |
| Male | 12 |
| Ethnicity (NIH/OMB)(Participants) | Patients With Arrhythmic Disorders |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 18 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(Participants) | Patients With Arrhythmic Disorders |
|---|---|
| United Kingdom | 18 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Undecided
Ran from Oct 2017 to primary completion in Mar 2024, 77 months.
Results were first posted in Feb 2025, 10 months after primary completion.
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Arrhythmogenic Right Ventricular Dysplasia →
St. George's Hospital, London