Presentation: Adult with Brugada syndrome

A 34-year-old male is admitted to intensive care following an out-of-hospital cardiac arrest, which he survived following successful use of a community defibrillator. His resting electrocardiogram (ECG) is noted to have an incomplete right bundle branch block as well as a coved ST elevation of 3mm in V1–V2 with a negative T-wave.

Genomic testing should be considered in the following scenarios.

• A firm clinical diagnosis of Brugada syndrome and/or sodium channel disease as indicated by:
  • a spontaneous type 1 (‘coved-type’) ST-segment elevation – characterised by ST-segment elevation ≥2mm (0.2mV) in ≥1 right precordial leads (V1–V3) positioned in the fourth, third or second intercostal space;
  • a suspicion of a sodium channel disease such as atrial arrhythmias, sinus node dysfunction, conduction disease and/or QT prolongation (these criteria are predominantly found in children and young people); or
  • a type 1 ST-segment elevation unmasked using a sodium channel blocker and either:
    • • a documented ventricular fibrillation or polymorphic ventricular tachycardia;
      • a syncope of probable arrhythmic cause;
      • a family history of sudden cardiac death at under 45 years of age with negative autopsy;
      • coved-type ECGs in family members;
      • a nocturnal agonal respiration; or
      • premature atrial arrhythmias at under 30 years of age.
• Clinical evaluation in young probands and cascade testing in families will incorporate assessments for other features of sodium channel disease, such as:
• • sinus node disease;
• • atrial arrhythmias;
• • conduction disease;
• • dilated cardiomyopathy; and
• • long QT syndrome (of LQT3 subtype).
• These sodium channel diseases may coexist with or supplant types one, two or three Brugada ECG patterns.
• Brugada ECG patterns may be present even in patients with a negative sodium channel genotype.
• Testing should be carried out in parallel with expert phenotypic assessment – for example, in an inherited cardiac conditions (ICC) clinic – and with support from clinical genetics services. Note that testing may occasionally be appropriate outside these criteria, following discussion in an ICC multidisciplinary team meeting.

• Consult the National Genomic Test Directory. From here you can access the rare and inherited disease eligibility criteria for information about individual tests and their associated eligibility criteria. You can also access a spreadsheet containing details of all available tests.
• To find out which genes are included on different gene panels, see the NHS Genomic Medicine Service (GMS) signed-off panels resource.
• If eligibility criteria are met, discuss the case with or refer it to your local ICC service for genomic testing and family screening. You will need to provide details confirming that the patient fulfils the criteria.
• If the patient fulfils diagnostic criteria as detailed in published guidelines that differ from the eligibility criteria in the test directory, it is appropriate to refer to an ICC clinic for further assessment.
• The relevant clinical indication for Brugada syndrome is:
  • R128 Brugada syndrome and cardiac sodium channel disease: This indication comprises small gene panel sequencing, and multiplex ligation-dependent probe amplification (MLPA) or equivalent.
• For tests that do not include whole genome sequencing, you will need to:
  • complete a test order form and consent (record of discussion) form, available from your local Genomic Laboratory Hub; and
  • include details of the phenotype in the test order form (refer to human phenotype ontology (HPO) terms or the clinical summary) as well as the appropriate panel name(s) with associated R number.
• These tests are DNA based, and an EDTA sample (purple-topped tube) is required.
• Information about patient eligibility and test indications was correct at the time of writing. When requesting a test, please refer to the National Genomic Test Directory to confirm the right test for your patient.

For clinicians

• European Society of Cardiology: Brugada syndrome and sports activity: From history to risk stratification
• NHS England: National Genomic Test Directory

References:

• Zeppenfeld K, Tfelt-Hansen J, de Riva M and others. ‘2022 ESC guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: Developed by the task force for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death of the European Society of Cardiology (ESC) endorsed by the Association for European Paediatric and Congenital Cardiology (AEPC)’. European Heart Journal 2022: volume 43, issue 40, pages 3,997–4,126. DOI: 10.1093/eurheartj/ehac262

For patients

• Arrhythmia Alliance: Brugada syndrome
• British Heart Foundation: Brugada syndrome
• British Heart Foundation: Life with sudden arrhythmic death syndrome
• Cardiac Risk in the Young
• myheart: Brugada syndrome
• NHS Health A to Z: Brugada syndrome
• SADS Foundation: Brugada syndrome