Brugada Syndrome

It’s Friday night, and you get a second in between patients. You are dreaming of sipping a Mai Tai by the beach, when your dream is quickly brought to an end. A 35-year-old young man walks into the ED, complaining of an episode of “passing out” after a few drinks. “Mai Tai’s?” you ask. “Oh no, just vodka,” he says. Oh, come on, you tell yourself, as you sign up for him and order an ECG and fingerstick. You think he just must have had a bit too much, and you casually hop over the stretcher-lined hallway to get a history.

He surprisingly does not seem intoxicated and has no significant past medical history. He says he had three shots of vodka, and after about an hour, “passed out”. This occurred about 4 hours prior. He felt light-headed and had palpitations just prior to the event. He does not recall how long he was down, although his friends mentioned about one to two minutes. He was not confused afterward, did not report any pain or weakness, but he did feel a bit light-headed. This has happened to him twice over the past 4 years, and both times were during alcohol intake.

His physical exam including neurologic/cerebellar function is within normal limits. His fingerstick is 110. You get his ECG back as you are talking and “aha”…

1. What do you see, and why does it concern you?

ST segment elevation in V₁-V₃ with corresponding inverted T waves
This is concerning for possible Brugada Syndrome

2. What is Brugada Syndrome?

Brugada syndrome is a disorder caused by a mutation in a cardiac sodium channel gene, SCN5A,⁽¹⁾ causing conduction abnormalities and dysrhythmias.
In Southeast Asia, it has been connected with a known phenomenon called SUNDS – Sudden and Unexpected Death during Sleep. In Thailand, studies have shown a Brugada-like ECG in 16 of 27 men, referred for a phenomenon called “Lai Tai” – or death during sleep.⁽¹⁾
It is associated with ventricular fibrillation and sudden cardiac death, often in otherwise healthy young adults without known structural heart disease.

3. How does it present?

Clinically, it can present with ventricular fibrillation, aborted sudden cardiac death (more common at night or during sleep), syncope, palpitations, chest pain or discomfort, or nocturnal agonal respiration.⁽²⁾
ECG changes and clinical manifestations can be transient and unmasked or altered by various factors, some of which include alcohol intake, fever, ischemia, hypothermia, hypokalemia, DC cardioversion, cocaine, and various drugs listed below:⁽¹⁾
- Sodium channel blockers
- Alpha-adrenergic agonists
- Beta blockers
- Tricyclic antidepressants
- First generation antihistamines – i.e diphenhydramine, chlorpheniramine
- Vagotonic drugs – i.e nitrates
- Lithium

4. How common is Brugada Syndrome, and who gets it?

The prevalence of Brugada Syndrome is estimated at 1-5 per 10,000 people worldwide, more common in men, and is even higher (greater than 5 per 10,000 people) in South-East Asia, particularly in Thailand and the Philippines where it is considered one of the major causes of death in young people.⁽¹⁾
Given that it is often concealed, masked, or missed, the actual prevalence may vary from the numbers above.
The mean age at sudden death due to the syndrome is 41 years, and the age range for diagnosis ranges from 2 days to 84 years,^(1,3)

5. How do you diagnose Brugada Syndrome?

Although there are three ECG phenotypes classically associated with Brugada Syndrome, only Type I is truly diagnostic.
Type I: Coved ST segment elevation greater than or equal to 2 mm followed by negative T wave.
Type II: Saddle-back appearance with initial ST segment elevation greater than or equal to 2 mm. This is followed by an elevated trough in the ST segment greater than or equal to 1 mm and then, in turn, a positive or bi-phasic T wave.
Type III: Saddle-back or coved appearance with ST segment elevation of less than 1 mm.
A diagnosis of Brugada syndrome is definitively made when a Type I ECG is present in more than one precordial lead, either in the presence or absence of a sodium channel blocker, in conjunction with at least one of the following:
- ventricular fibrillation
- polymorphic ventricular tachycardia
- family history of sudden cardiac death at less than 45 years of age
- similar coved ECG types in family members
- syncope
- nocturnal agonal respiration
- inducible VT with programmed electrical stimulation⁽¹⁾
Doing the 12-lead ECG with leads V1-V2 (right precordial leads) in a superior position, using a sodium channel blocker challenge to help unmask ECG characteristics, and imaging to rule out structural heart disease may aid in diagnosis.

6. What is your differential?

In a young patient without known structural heart disease, several conditions can predispose to tachydysrythmias.
- Long QT Syndrome: QTc greater than 440-450 ms in men, and greater than 460 ms in women
- Ventricular Pre-excitation Syndromes/Accessory Conduction Pathways:
  - Wolf-Parkinson White – Shortening of PR interval less than 120 ms, widened QRS, “delta wave” – slurred upstroke of initial part of R wave
  - Lown-Ganong-Levine Syndrome – Shortening of PR interval less than 120 ms, but no delta wave.
- Hypertrophic Cardiomyopathy: Left ventricular hypertrophy and/or prominent Q waves in leads II, III, aVF, V₅, and V₆

7. How will you manage this patient?

Given the presence of syncope and a diagnostic Type I Brugada pattern on ECG, this patient should be presumed to have Brugada Syndrome
Initial emergency management, ABCs, and cardiac monitoring should be applied to all patients while in the ED. ACLS protocol should be applied to patient’s in ventricular tachycardia, ventricular fibrillation, and cardiac arrest.
Cardiology should be involved, on an inpatient or outpatient basis, depending on your patient’s disposition. Given that our patient is symptomatic (presenting with syncopal episodes) and has a diagnostic Type I ECG, he should be admitted to telemetry with cardiology consult for implantable cardioverter defibrillator (ICD) placement.
Currently, an ICD is the only definitive management.
In patients with a diagnostic ECG presenting with aborted sudden cardiac death, ICD placement is generally recommended given high risk for recurrence.
In an asymptomatic patient with a type I ECG or any stable patient with a type II or Type III ECG, it may be reasonable to follow closely in an outpatient setting, with risk stratification and electrophysiological studies.⁽³⁾

Resources:

Antzelevitch C. Brugada Syndrome . Pacing Clinical Electrophysiology 2006; 29(10): 1130–59.
MDedge [Internet]. MDedge. [cited 2017 Aug 7];Available from: http://www.mdedge.com/emed-journal/dsm/7862/cardiology/brugada-syndrome
Brugada Syndrome [Internet]. LITFL • Life in the Fast Lane Medical Blog. 2016 [cited 2017 Aug 7];Available from: https://lifeinthefastlane.com/what-is-brugada-syndrome/
Brugada Syndrome [Internet]. Practice Essentials, Background, Pathophysiology. 2017 [cited 2017 Aug 7];Available from: http://emedicine.medscape.com/article/163751-overview
Toscano J. Review of Important ECG Findings in Patients with Syncope . American Journal of Clinical Medicine 9(2):92–6.