Background & Epidemiology

• This is an ECG pattern with a high risk of sudden death/VF in patients with structurally normal hearts.

• Epidemiology

• Highly prevalent in SEA ethnic groups

• AKA "sudden unexplained nocturnal death syndrome" in the Phillipines, Bangungut, Lai Tai, Pokkuri Death Syndrome, etc…

• Genetic basis of disease, leads to familial association

• Males > females (8x)
• About 1:5000 prevalence

• Up to 20% of SCD in patients with structurally normal hearts

• Genetic basis consists of SCN5A cardiac sodium channel mutations affecting phase 0 of the cardiac AP. More than 500 pathogenic variations, generally autosomal dominant

Definition of BrS

The definition of BrS solely depends on characteristic EKG findings. EKG findings may be transient/concealed at the time of investigation. Checking V1 in more cranial positions (e.g. 2nd/3rd intercostal spaces) increases sensitivity in some patients. Prolonged EKG monitoring may help uncover only drug-induced type 1 pattern.

Type 1 (coved) is the only diagnostic pattern for BrS.

ST-segment elevation ≥2 mm in ≥1 right precordial lead (V1 to V3), followed by an rʹ-wave and a concave or straight ST segment. The descending ST segment crosses the isoelectric line and is followed by a negative and symmetric T-wave.

Type 2 (saddle-back) is only suggestive of BrS

ST-segment elevation ≥0.5 mm (generally ≥2 mm in V2) in ≥1 right precordial lead (V1 to V3), followed by a convex ST. The rʹ-wave may or may not overlap the J point, but it has a slow downward slope. The ST segment is followed by a positive T-wave in V2 and is of variable morphology in V1

To facilitate the differentiation of type 2 ECGs highly indicative of BrS from other Brugada-like patterns (such as athletes, pectus excavatum, and arrhythmogenic cardiomyopathy), several additional criteria have been suggested. These criteria utilize the triangle formed by the ascending and descending branch of the rʹ-wave

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β angle: A cut-off value ≥58° provided the best predictive values for conversion to a type 1 BrS pattern (73% positive and 87% negative values)

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Length of the base triangle of the rʹ-wave 5 mm below the maximum rise point: A cutoff value of 4 mm (≥4 mm in patients with BrS) demonstrated 96% specificity and 85% sensitivity (positive predictive value of 95% and negative predictive value 88%) for differentiating the BrS ECG pattern in BrS patients from the ECG pattern of healthy individuals

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Other criteria: The triangle base duration at the isoelectric line (>1.5 mm in patients with BrS) and the relationship between the triangle base at the isoelectric line and its height (>1.3 in BrS patients) may be distinguishing ECG patterns in BrS

Clinical Criteria:

occurring either spontaneously or after provocative drug test with intravenous administration of sodium-channel blockers (such as ajmaline, flecainide, procainamide, or pilsicainide)

Clinical Manifestations

• Syncope, seizures, nocturnal agonal breathing due to polymorphic VT or VF
• Can also present with SCD
• Can be completely asymptomatic as well, and never diagnosed
• These lethal arrhythmias generally present during rest/sleep, suggesting association with bradycardia/vagal events
• Fever is associated with symptoms as well
• Onset of symptoms during adulthood, with mean age of 41 +- 15 yrs
• Sex differences in presentation due to differential transmembrane ion current expression 2/2 testosterone expression

Pharmacological Tests/Diagnostic Tools

Sodium-channel blocker test should be performed in patients with diagnostic uncertainty/high suspicion of BrS. Continuous monitoring, positive when type 1 EKG is identified during the infusion. Stop when QRS > 130% of baseline width or there are frequent PVCs as there is a risk of ventricular arrhythmia.

• Most commonly uses IV ajmaline and flecainide, but procainamide could be considered.
• Continue monitoring until EKG reverts to baseline
• 25% of these tests are false-negative

Diagnosis of BrS

Old paradigm (< 2013) was that clinical symptoms needed to be present for the diagnosis, as well as a type 1 EKG. However, current (> 2013) diagnostic criteria are the classic type 1 EKG findings alone, either spontaneously or provoked with sodium channel blockade, without evidence of malignant arrhythmias.

Differential Diagnosis

1. RV conditions

2. RV ischemia, acute PE, compression of RVOT

3. RBBB, LVH, pectus excavatum, ARVC

4. Acquired BrS - propofol, tricyclic antidepressants, fluoxetine, lithium, trifluoperazine, antihistamines, and cocaine

Management

1. ICD placement is the definitive treatment. Indicated for symptomatic patients. In asymptomatic patients with a spontaneous type 1 pattern, the EPS can be used to assess the need for an ICD.
2. Quinidine is effective but highly toxic.
3. Ablation can be used to define and remove the arrhythmic electrophysiological substrate but this is less often done.
4. Education and lifestyle changes. Treat fevers, avoid contraindicated substances (propofol, tricyclic antidepressants, fluoxetine, lithium, trifluoperazine, antihistamines, and cocaine), etc.

References

1. Brugada J, Campuzano O, Arbelo E, Sarquella -Brugada Georgia, Brugada R. Present Status of Brugada Syndrome. Journal of the American College of Cardiology. 2018;72(9):1046-1059. doi:10.1016/j.jacc.2018.06.037
2. Brugada Syndrome • LITFL • ECG Library Diagnosis
3. Brugada Syndrome | Circulation: Arrhythmia and Electrophysiology (ahajournals.org)