Professionals
Background
Brugada syndrome (BrS) is an inherited arrhythmogenic disorder characterized by coved-type ST-segment elevation in the right precordial leads, associated with increased risk of sudden death. It is genetically and clinically heterogeneous, presenting typically in the fourth or fifth decade of life.
The prevalence of BrS in the pediatric population is low compared with the adult population. However, over the last 5-10 years there has been growing evidence in the literature of disease onset during childhood.
Most pediatric BrS cases are asymptomatic. However, there are a number of patients who become symptomatic with a variety of conduction abnormalities, including life threatening ventricular arrhythmias and sudden cardiac death. This early disease expression may be precipitated by diverse factors, including genetic substrates, hormonal shifts, and unidentified environmental triggers.
Purpose and Significance of
the Pediatric Brugada Registry
The diagnosis and management of BrS among young patients remains challenging. Under the mentorship of Prof. Pedro Brugada, Cecilia Gonzalez Corcia has investigated the clinical characteristics, risk factors and prognosis of pediatric BrS. Based on a 30-year prospective database, initiated with the first pediatric BrS diagnosis, our team has elucidated the disease spectrum within young populations, identified prognostic markers for future arrhythmic events, and formulated clinical algorithms for high-risk patient identification. However, there are still many gaps in our understanding of the disease.
The aim of this project is to sustain an international pediatric BrS registry bringing together cases from different world regions, genetic characteristics and environmental backgrounds. We strongly believe that this objective can only be fulfilled with the support of many of our community members working in various parts of the world. By fostering dialogue, sharing insights, and pooling resources, we aspire to unravel the pathophysiological underpinnings of pediatric BrS and forge tailored approaches to patient care.
Our vision supports a collective collaboration within the medical and patient community, transcending geographical boundaries. Together, let us embark on this journey toward enhanced understanding, improved management, and, ultimately, brighter futures for children and families affected by BrS.
DOWNLOAD OUR PROTOCOL
For more details, download our Handbook for Participating Centres:
"Pediatric Brugada Registry: An International Initiative for Risk Assessment and Management".
Content Index
Registry Design and Methods
This project is a multicentre observational study consisting of two phases:
- An initial retrospective enrolment of patients presenting with paediatric Brugada syndrome, followed by
- A prospective observational follow up of the cohort.
Patient selection and inclusion criteria
- Group 1: Phenotypic positive (disregarding genotype) patients < 20 years of age at diagnosis that presented with spontaneous or drug induced Brugada type I electrocardiogram. An electrocardiogram should be considered diagnostic of Brugada syndrome if a coved type ST elevation ≥ 2 mm was documented in ≥ 1 lead from V1–V2, in a standard or a superior position (up to the second intercostal space).
- For the patients included via a retrospective identification, data will be entered as per availability in the medical records.
- In the case of newly diagnosed patients, we propose direct inclusion in the registry following an initial evaluation proposal.
- Group 2: Genotypic positive (with negative phenotypic expression) patients < 20 years of age at diagnosis of the pathogenic mutation, even if no phenotypic expression in terms of symptoms or characteristic ECG pattern.
Initial evaluation
Detailed information on patient demographic data, family history, medical history, and events of atrial or ventricular arrhythmia, severe syncope or SD will be obtained in retrospective.
On inclusion on the registry, we request an update of
1- physical examination
2- personal and family medical history (including pedigree and family tree)
3- baseline 12 lead ECG (trying to include the most representative, diagnostic or severe tracings in the case of restrospective inclusion)
4- baseline heart imaging (echocardiography and/or cMRI) to exclude underlying structural cardiac abnormalities
5- provocative test in cases of normal baseline electrocardiogram (optional).
6- 24hs Holter monitoring +/- treadmill exercise test (optional)
7- electrophysiological study with atrial and ventricular stimulation protocol (optional). Inclusion of data related to atrial or ventricular substrate ablation, if present.
8- genetic testing (when feasible)
Tests characteristics
12 lead electrocardiograms: All baseline and drug-induced 12-lead electrocardiograms should be recorded at a paper speed of 25 mm/s and amplitude of 10 mm/mV, with the right precordial leads positioned at the sternal margin of the second, third and fourth intercostal space according to the prescribed guidelines (8). All electrocardiograms should be analyzed with measurement of PR intervals, QRS durations, and QTc intervals (determined using Bazett’s formula), by averaging hand-measurements on three consecutive beats. Maximal ST-segment elevations should be measured at the J point in the right precordial leads (V1–V3), and analyses of ST-segment elevation were performed in leads V1 and V
- Provocation test: to be performed in young patients suspected of having Brugada syndrome, in the case of a normal baseline ECG. The test should be performed with intravenous ajmaline, procanaminde or flecainide according to the investigator’s discretion and access to these drugs at individual centres. Refer to Table I for standardized drug administration according to present guidelines. All ECGs should be analyzed before, during an after drug administration, with measurement of PR intervals, QRS durations, and QTc intervals (determined using Bazett’s formula), by averaging hand-measurements on three consecutive beats. Maximal ST-segment elevations should be measured at the J point in the right precordial leads (V1–V3), and analyses of ST-segment elevation should be performed in leads V1 and V2.
We suggest performing 12 lead ECG monitoring during the test with printing performed every minute.
We recommend immediate termination of the drug infusion when/if:
- Presence of diagnostic type I ECG
- QRS prolongation > 30% above baseline
- high-degree atrio-ventricular block
- sustained ventricular arrhythmias
In all these circumstances, immediate administration of intravenous isoprotenerol (that should be always be ready before the start of the provocative test) helps improve intrinsic conduction, and avoid rhythm degeneration into sustained ventricular arrhythmias.
In patients < 5 years of age, we recommend performing the provocative test under sedation with a single intravenous dose of propofol.
- EP study: optional evaluation. When performed as per centre’s protocols, electrophysiological studies should include measurements of baseline intervals, sinus node recovery time, corrected sinus node recovery time, and sino-atrial conduction time (11). The atrio-ventricular conduction system can be evaluated by measuring the Wenckebach cycle length and the atrio-ventricular nodal effective refractory period in each case. We also recommend performing an atrial and ventricular stimulation protocol from 2 right ventricular sites (including the RVOT) up to S3 at CL 200ms. We recommend performing the studies under general anesthesia.
- Genetic test: optional evaluation. When feasible, specifically analysis of the SCN5A gene sequence, or any comprehensive genetic panel performed in the patient. In mutation-positive index cases, the young family members should be screened for specific genetic mutations.
Specific information on the following parameters is of main importance:
- History of syncope
- History of SCD
- Evidence of events of ventricular arrhythmias (VT or VF)
- Evidence of events of atrial arrhythmias (sustained ectopic atrial tachycardia, AF or A Fib)
- Evidence of conduction abnormalities
- Evidence of SND
Prospective Follow-up
Yearly clinical visit with:
- 12 lead electrocardiogram
- 12 lead electrocardiogram during fever (axillar temperature > 38°C) °
- Holter at diagnosis and every 2 years
- Internal loop recorder (ILR) tracing readings (if present) *
- ICD memory readings (if present)*
- We recommend giving the patient a letter to present to the Emergency Department on arrival describing his condition and requesting the to perform a 12- lead ECG with high V1-V2 leads (refer to Appendix for sample of letter)
* ILR and ICD implant are determined by clinicians choice. In case of implantation, the tracking will be included in the database.
Identification of potentially lethal events
During the follow-up period, potentially lethal event (primary outcomes) should be identified as follows:
- SCD or severe syncope
- Events of sustained ventricular tachycardia or ventricular fibrillation during electrocardiograms, Hospital monitoring, Holter monitoring, implantable loop recorder, implantable cardioverter-defibrillator memory
- Appropriate ICD shocks with tracings recorded in the device’s memory.
Identification of electrical disease expression
During the follow-up period, progression of the electrical disease manifestation (secondary outcomes) should be identified as follows:
- Spontaneous/ Fever induced type I BrS pattern in a 12 lead ECG
- Recorded evidence of onset of SND and/or atrial arrhythmias
- Recorded evidence of no-sustained ventricular arrhythmias
- Evidence of new onset of electrical conduction abnormalities
Participating Centre
Participating centres involved in the care of children and adolescents with BrS are invited to join the registry. Patients can be enrolled by pediatric or adult electrophysiologists, pediatric or adult cardiologists, or nurse practitioners (or equivalent qualifications in different areas of the world).
Steps to become a participating Centre
1- Contact the Coordinating Centre
Please contact M Cecilia Gonzalez Corcia who will be able to assist you with obtaining ethical approval and data sharing agreement (if required).
Contact details: cecilia.gonzalez-corcia.med@ssss.gouv.qc.ca
Telephone contact: +1 514 518 4311
2- Obtain Ethical Approval and DSA
Principal investigators at each site must ensure that the REB/IRB certificate of Initial Approval is obtained for this study.
You will need the following items to obtain REB/IRB approval:
Study protocol | Appendix page 30
Study invitation letter | Appendix page 38
Consent forms | Appendix page 39
Sample letter for ED | Appendix page 48
Data Collection tool | Appendix page 49
A DSA may be required for some centres in order for data to be transmitted between the coordinating and participating centres. If this is the case, the PI her team will act as liaisons to connect the contract offices between sites, and provide the necessary study documents and ethical approval certificates.
3- Forward Documents to Coordinating Centre
Once ethical approval has been obtained, please forward your REB/IRB approval certificate, approved study documents and DSA (if applicable) to the PI
Participating Centre Site Initation
Dr Cecilia Gonzalez Corcia will arrange for a site initiation call with the site investigator and/or their representative once the centre is ready to begin conducting the study.
During this telephone conversation, any question concerning the study specificities will be addressed including:
- Study documents
- Recruitment plan
- Patient enrolment and follow-up details
- Consenting procedures
- Data entry via Redcap
Site Initation Checklist
Patient Screening and Enrolment
Procedure:
- Identify potential study participants based upon the specific inclusion/exclusion criteria via chart review (pre-screening).
- Determine parent/guardian interest in study participation of eligible infant. This could occur at their next clinic visit.
- Obtain consent and place original signed consent in the patient’s chart.
PARTICIPATING CENTRE
If you are a participating center involved in the care of children and adolescents with Brugada Syndrome (BrS), we invite you to join the registry. Patients can be enrolled by pediatric or adult electrophysiologists, pediatric or adult cardiologists, or nurse practitioners (or individuals with equivalent qualifications in different regions of the world). If you are interested in participating in the registry, please contact Dr Cecilia Gonzalez Corcia and her team who will be able to assist you with obtaining ethical approval and data sharing agreement (if required).
COORDINATING CENTRE
Please contact Dr Cecilia Gonzalez Corcia and her team
who will be able to assist you with obtaining ethical approval
and data sharing agreement (if required).
COORDINATING CENTRE
Please contact Dr Cecilia Gonzalez Corcia and her team who will be able to assist you with obtaining ethical approval and data sharing agreement (if required).
