Brugada Syndrome

Context

Sudden cardiac death (SCD) accounts for 15–20 % of all deaths worldwide and is a cause for major concern¹.

Causes of SCD differ among the various age groups. In the younger person, the most common causes are cardiomyopathies, channelopathies, illicit drug use, and myocarditis².

Definition

Brugada syndrome is an autosomal dominant genetic disorder, with a male preponderance, characterized by abnormal findings on the electrocardiogram (ECG) along with an increased risk of ventricular tachyarrhythmias and sudden cardiac death³.

Typical ECG changes are that of ST-segment elevation in V1 and/or V2 with a coved ST-segment, sometimes described as a pseudo right bundle branch block⁴.

The exact pathophysiology is not clearly understood but various mechanisms have been found. Genetic analysis has led to the identification of certain causative mutations in the specific genes, which encode for subunits of a cardiac sodium channel.

The problematic sodium channels in the myocardium, reduce sodium inflow currents, and shorten the duration of the action potentials. This makes the heart more susceptible to arrhythmias⁵.

Learning bite

Brugada syndrome is a genetic sodium channelopathy resulting in cardiac dysrhythmias that can lead to sudden cardiac death.

For patients presenting with syncope the first step of clinical assessment in a detailed history. This history is ideally taken not only from the patient themselves, but also from a bystander or witness to the event. Teasing out the presence of a prodrome, existence of myoclonic jerking or tonic-clonic seizure activity, bladder or bowel incontinence, or existence of a post ictal phase can help to discern a seizure from syncope. Presence of a fever, recreational drug or alcohol use is also important in helping to risk stratify and formulate a differential diagnosis.

A detailed family history must also be undertaken to ascertain if any first degree relatives has had SCD, or Brugada syndrome.

Clinical examination for these patients is often completely normal. It is important to ensure a thorough cardiovascular and neurological exam however, to exclude other causes for syncope.

Occasionally a patient may present with viral type symptoms or fever (or even routinely on health screening) and an opportunistic ECG will reveal Brugada pattern. In this case discussion should occur with cardiology for further work-up to assess for presence of Brugada syndrome.

Learning bite

A detailed history should be taken in anyone presenting with syncope including a thorough family history for unexplained cardiac death.

Bedside Investigations

Capillary blood glucose – To be performed in any patient with altered mental status or transient loss of consciousness.

Electrolytes – Low potassium levels have been associated with SCD in patients with Brugada syndrome⁷.

A 12-lead electrocardiogram (ECG) – This is essential for the diagnosis of Brugada syndrome. However, a normal ECG does not rule out Brugada syndrome⁸.

An ECG consistent with the Brugada pattern requires a referral and further workup by a cardiologist.

There are 3 patterns observed in the ECG.

Special tests

All patients with suspected Brugada syndrome, based on the combination of symptoms and typical Brugada pattern ECG changes require an evaluation to exclude underlying structural heart disease.

Tests for identifying structural heart diseases: Echocardiogram and cardiac magnetic resonance imaging (MRI) may be undertaken as part of the full workup.

Provocation/ Challenge test: This is a test where Class I anti-arrhythmic medications (sodium channel blockers) are administered by cardiologists in an electrophysiological laboratory under controlled settings. Commonly used drugs are flecainide, procainamide, and ajmaline.

Learning bite

A typical ECG and a detailed history are important for the diagnosis of Brugada Syndrome. It is important to know that a normal ECG does not exclude the diagnosis of Brugada syndrome.

General Management

Patients with suspected or confirmed brugada syndrome should ideally be on continuous cardiac monitoring to allow treatment of any arrhythmia promptly (following ALS guidelines).

If a patient presents with syncope and a precipitating cause such as fever is suspected, then it is important to aggressively treat this to prevent malignant arrhythmias.

Patients with suspected Brugada syndrome (typical ECG and symtpoms) should be admitted with ongoing telemetry monitoring.

In patients with Brugada pattern (no symptoms), obtain a cardiology consultation to decide on appropriate management; admit or discharge for outpatient management e.g. provocative testing.

When treating patients with known Brugada, consider if drugs prescribed for other illnesses are safe. Drugs to avoid include antidepressants, antiarrhythmics (especially from Class 1), some local anesthetics, and propofol. For more information, refer to Brugadadrugs.org.

Specific Management

Implantable cardioverter defibrillator (ICD) implantation is recommended in the following¹⁰:

1. Survivors of a cardiac arrest and/or
2. Patients with documented spontaneous sustained ventricular tachycardia.

Learning bite

Control precipitating factors such as fever and monitor the patient closely. Refer to a cardiologist early for definitive therapy- ICD implantation.

Typical ECG features of Brugada syndrome fluctuate and might only manifest in the presence of fever, drugs, or tachycardia. ECG patterns are also known to change with time and age.

Performing a 12-lead ECG with the precordial leads (V1 and V2) higher up in the second or third intercostal space or using bipolar chest leads are techniques known to accentuate these abnormalities and should be performed when there is doubt about the diagnosis.

The diagnosis of Brugada syndrome is only established if the patients’ ECG converts to a Type 1 ECG pattern (if originally Type 2) upon provocation by drugs.

1. Srinivasan NT, Schilling RJ. Sudden Cardiac Death and Arrhythmias. Arrhythm Electrophysiol Rev. 2018 Jun;7(2):111-117.
2. Priori SG, Blomström-Lundqvist C, Mazzanti A, Blom N, Borggrefe M, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: 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). European Heart Journal. 2015;36(41):2793–867.
3. Brugada J, Campuzano O, Arbelo E, et al. Present Status of Brugada Syndrome: JACC State-of-the-Art Review. J Am Coll Cardiol. 2018 Aug 28;72(9):1046-1059.
4. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. 1992 Nov 15;20(6):1391-6.
5. Podrid PJ. Pathophysiology and etiology of sudden cardiac arrest. UpToDate. Accessed July 12 2022].
6. Brugada J. Management of patients with a Brugada ECG pattern [Internet]. European Society of Cardiology. Vol. 7, N° 24, 2009. [Accessed Aug 15 2022].
7. Araki T, Konno T, Itoh H, Ino H, Shimizu M. Brugada syndrome with ventricular tachycardia and fibrillation related to hypokalemia. Circ J. 2003 Jan;67(1):93-5.
8. Brugada Syndrome: ECG, clinical features and Management; In Clinical ECG Interpretation. [Internet]. ECG & ECHO. 2021 [Accessed July 12 2022].
9. National Institute for Health and Care Excellence. Transient loss of consciousness (‘blackouts’) in over 16s: Guidance. NICE Clinical guideline [CG109]. [Accessed July 12 2022].
10. Wylie JV. Brugada syndrome: Clinical presentation, diagnosis, and evaluation. UpToDate. [Accessed July 14 2022].
11. Brugadadrugs.org. [Accessed July 12 2022].
12. Image 1 and 3: Larkin J, Cadogan M, Cadogan J. Brugada syndrome [Internet]. Life in the Fast Lane • LITFL. 2022 [Accessed July 21 2022].