Brugada syndrome

Background

Genetic condition associated with arrhythmia (polymorphic VT) and sudden cardiac death that was originally described in adolescent males in southeast Asia
Described in 1992 by Pedro and Josep Brugada
- Initially described in 1988 by Nava, with the first complete description in 1989 by Martini, Nava, Thiene, et al. (PMID: 2589161)
- Individuals thought to be usually healthy with structurally normal hearts
- Primarily an electrical problem (sodium channelopathy)
- Increasing literature demonstrates that there may actually be structural abnormalities that are technically difficult to diagnose
First onset of symptoms (VT, VF, syncope, sudden death)
- 41 ± 15 years on average for VF episodes
- Arrhythmias reported from 2-84 years
  - May occur at rest or sleep, especially 12am – 6am
    - during ↑ vagal tone
- Fever and hot ambient temperature bring out the ECG findings and PVT/VF episodes
  - Treat fevers aggressively
- Type Ia and Ic medications increase the ECG findings
  - (questionable if increases arrhythmias)
- A reported cause of SIDS or sudden cardiac death in young children
- Positive family history in 20-30%
More common than you may realize!
- ~ 4% of ALL sudden deaths
- 20% of sudden death in patients with structurally normal hearts
- A leading cause of death in patients < 40 years of age
- Identified in all ethnic groups, both males and females
Mortality
- Early data: ~ 10% per year if not treated with internal cardioverter-defibrillator (ICD, only effective treatment)
- New data showing VF episodes and mortality rates are probably lower
  - Most risk associated with Type I (coved) pattern
- Isoproterenol and quinidine may decrease incidence
  - Quinidine not shown to improve outcomes and is not easily available
  - Isoproterenol may be helpful in arrhythmic storm

ECG interpretation of Brugada pattern: type 1 (coved) is pathognomonic, but type 2 (saddle-back) requires checking lead placement (negative P in V1 or biphasic P in V2 are too high) and measuring the base of the triangle (>4mm measured 5mm from the apex of r’)
Treat reversible causes of Brugada phenocopy (eg hyperkalemia, RV/anterior ischemia)
Diagnosis, management and risk stratification of Brugada syndrome: treat fever and stop inciting meds/drugs; type 1 patients who are symptomatic (arrest, nonvagal syncope, seizure, agonal breathing) require ICD, and asymptomatic patients can be referred for provocative testing

"3 types"

3types

Look closely at leads V1 & V2
- RBBB or IRBBB pattern
- ST segment elevation
  - Type 1 – “Coved-type” (more sensitive and specific)
  - Type 2 – Saddleback with ST segment elevation
  - Type 3 – Saddle ST morphology without ST segment elevation
Type 1 “coved-type” pattern is much more concerning, type 2 & 3 less worrisome in more recent literature
Moving the V1-V2 leads one interspace higher may increase the abnormality
ECG findings can come and go
More commonly present around the time of the arrhythmia
- Fever/hot ambient temperature can bring out the ECG findings

hyperkalaemia as mimic

Diagnosis

Shanghai score

Electrophysiology study (EPS) – sodium channel blocker test (SCBT)

Used to unmask ECG findings in patients with a suspected BrS with a nondiagnostic ECG at baseline
- Also used to identify arrhythmogenic focus for ablation procedures
- Sensitivity and specificity remain elusive, not considered a “gold standard test”
  - Sensitivity of the test is dependent on the actual drug used for the test (availability may be limited in certain settings)
  - Typically only be performed when there is clinical suspicion, as there is ~ 5% of false positives in healthy patients. The life changing consequences of false positive tests must be carefully considered

Management

All patients with suspected BrS

Avoid potential triggers for VF and sudden cardiac death
- Certain drugs (www.brugadadrugs.org)
- Advise against excessive alcohol consumption or large meals
- Aggressively treat fever with antipyretics
Use the Shanghai score system

BrS with VTs or arrhythmic storm

Consider acute treatment with isoproterenol or quinidine
Avoid acute treatment with amiodarone or procainamide (sodium channel-blockers) as them may cause serious harm
Aggressively correct triggers (fever, electrolyte disturbances)

Symptomatic BrS (cardiac arrest, arrhythmic syncope, or documented sustained VT/VF)

Advise ICD therapy (Class I recommendation)
- Benefits in the lowest risk patients remains questionable (balance with risk of device related complications and high prevalence of inappropriate shocks)
Consider Quinidine if ICD refused, contraindicated, or insufficient (frequent shocks)

Questionably symptomatic BrS (unexplained syncope, nonspecific symptoms, etc.)

Consider ICD with spontaneous type-1 ECG, or an implantable loop recorder when risk of sudden cardiac death is low (class IIa recommendation)
Consider Quinidine if ICD refused, contraindicated, or insufficient (frequent shocks)

Asymptomatic patients with Brugada pattern ECG

Majority of patients with the Brugada ECG pattern are asymptomatic until the occurrence of an event.
- Current guidelines are not clear on how best to manage these patients as many are young with long life expectancy and risk of ICD implantation may be equal to or greater than intrinsic risk of disease
- ICDs are generally not recommended in asymptomatic patients without a spontaneous type 1 ECG pattern. Instead, the focus is on close follow up and avoidance of triggers
- The most recent studies (PMID: 37830188, 36516610) show a relatively low incidence of arrhythmic events in asymptomatic patients, and arrhythmic risk seems even lower in drug induced-only Brugada ECG pattern vs. a spontaneous type 1 coved ECG pattern
- Only clear risk factor for ventricular arrhythmias is the spontaneous type-1 coved ECG pattern
  - EP studies (i.e., SCBT) may have value to identify higher risk subgroups that may need intervention, consult closely with your local electrophysiologist
    - SCBT for those with spontaneous or fever induced Type-1 ECG patterns may be reasonable to further estimate arrhythmic risk in certain patients
      - Value of positive EP study (inducible VF or sustained VT) remains unclear
      - Most patients with positive tests are typically offered an ICD, but the test has limited sensitivity and specificity, so shared decision making is important
    - Close monitoring (i.e., serial ECGs, Holter monitoring, loop recorders, etc.) may be preferred in drug induced-only ECG patterns looking closely for missed spontaneous type-1 ECG patterns which may be intermittent

References

Sudden Cardiac Death - Brugada Syndrome ECG Cases EM Cases

Marsman EMJ, Postema PG, Remme CA. Brugada syndrome: update and future perspectives. Heart. 2022 May;108(9):668-675. Epub 2021 Oct 14. PMID: 34649929.

Wilde AAM, Amin AS, Morita H, et al. Use, misuse, and pitfalls of the drug challenge test in the diagnosis of the Brugada syndrome. Eur Heart J. 2023 Jul 14;44(27):2427-2439. PMID: 37345279.