Brugada syndrome

At a glance

• An inherited sodium channel disease of a structurally normal-looking heart that causes polymorphic VT and VF, often at rest or asleep.
• Diagnosis rests on a spontaneous type 1 ECG pattern in V1 or V2. A saddleback (type 2) pattern isn't enough.
• Typical patient: a man in his 30s or 40s, often of Southeast Asian background, with syncope or arrest at night or during a fever.
• ICD for those who have had an arrest, sustained VT or arrhythmic syncope. Everyone gets trigger advice: treat fever, avoid listed drugs, limit alcohol.

Genetics and pathophysiology

• Autosomal dominant with incomplete penetrance. SCN5A loss-of-function variants are found in about 20% of probands and are the only definite single-gene cause (APHRS-led J-wave consensus 2026). Much of the remaining risk is polygenic.
• Reduced sodium current in the right ventricular outflow tract epicardium, plus subtle epicardial fibrosis there, produces the ST elevation and the substrate for VF.
• Sodium current falls further with fever, sodium channel blockers and high vagal tone, which is why events cluster at night, after large meals and with fever.
• Male predominance of about 8 to 10:1, probably from testosterone effects on repolarisation currents.

Recognition

ECG patterns

Pattern	Appearance (V1 to V2)	Diagnostic?
Type 1 (coved)	ST elevation ≥2 mm, convex upwards, descending into a negative T wave	Yes, if spontaneous
Type 2 (saddleback)	ST elevation with a trough then a positive or biphasic T wave	No. Needs conversion to type 1

• Record high right precordial leads: move V1 and V2 up to the 2nd and 3rd intercostal spaces. This raises the yield and is accepted by ESC 2022.
• The pattern is dynamic. A normal ECG today doesn't exclude it. Repeat ECGs, especially during fever.
• Other findings: first-degree AV block, AF in 10 to 20%, sinus node dysfunction.

Clinical presentation

• Arrhythmic syncope: sudden, little prodrome, often at rest or asleep.
• Nocturnal agonal respiration reported by a bed partner.
• Cardiac arrest or sudden death, historically called sudden unexplained nocturnal death syndrome in Southeast Asia.
• An incidental pattern on an ECG done for another reason. Many patients never have an event.

Pitfall: syncope in Brugada syndrome is often reflex syncope. A clear vasovagal prodrome and trigger carry much lower risk than abrupt syncope at rest.

Diagnostic criteria (ESC 2022)

• Spontaneous type 1 pattern with no other heart disease: diagnostic (Class I).
• Survivor of VF or polymorphic VT with type 1 induced by sodium channel blocker or fever: diagnostic (Class I).
• Drug-induced type 1 plus one of arrhythmic syncope or nocturnal agonal respiration, a family history of Brugada syndrome, or sudden death in a relative under 45 with a negative autopsy: should be considered (IIa).
• Drug-induced type 1 alone: may be considered (IIb). Sodium channel blocker challenges have false positives.

The Shanghai score (2016 J-wave consensus) weights ECG, clinical history, family history and genetics: 3.5 or more is probable or definite Brugada syndrome. A spontaneous type 1 pattern alone scores 3.5; a drug-induced one scores 2.

Mimics (Brugada phenocopies)

Cause	Clue
Atypical RBBB, athlete's ECG	Broad terminal S in lead I and V6; ST pattern not coved
ARVC	Epsilon waves, T inversion beyond V3, RV dilatation on MRI
Hyperkalaemia, hypercalcaemia	Electrolytes; resolves with correction
TCA or other sodium channel blocker overdose	Broad QRS, terminal R in aVR; see ventricular tachycardia
Acute RV ischaemia, PE, pericarditis, pectus excavatum	Clinical context and imaging
High lead placement in a normal person	Repeat with correct placement

Investigations

• 12-lead ECG with high precordial leads, repeated, and an ECG during any fever.
• Echo and usually cardiac MRI to exclude structural disease (ARVC especially).
• Sodium channel blocker challenge when the pattern is type 2 or the clinical suspicion is high. Ajmaline is the most sensitive agent internationally, but in Australia IV flecainide is the usual agent; ajmaline isn't registered here and is obtained through the TGA Special Access Scheme in a few centres. Done with full resuscitation facilities. Not done if a spontaneous type 1 pattern has already been seen (Class III).
• Genetic testing for SCN5A in the proband, with genetic counselling. A pathogenic variant enables cascade testing, but a negative result in a relative doesn't rule out the disease.
• Electrophysiology study may be considered in asymptomatic patients with a spontaneous type 1 pattern (IIb). Its predictive value is debated.
• Holter or implantable loop recorder when syncope is unexplained.

Management

Everyone

• Treat fever promptly with paracetamol; ECG during febrile illness.
• Avoid drugs on the BrugadaDrugs.org list: class IC antiarrhythmics, TCAs, lithium, some anaesthetic agents (bupivacaine, propofol infusions) and others. Give the patient a written list and a medical alert.
• Avoid cocaine, cannabis and excess alcohol, and very large meals.
• Tell the anaesthetist before any procedure.

Risk-based treatment (ESC 2022)

Situation	Recommendation
Cardiac arrest survivor or documented spontaneous sustained VT	ICD (Class I)
Spontaneous type 1 with arrhythmic syncope	ICD should be considered (IIa)
Asymptomatic, spontaneous type 1	Consider EP study; ICD may be considered if VF is inducible with up to two extrastimuli (IIb)
Asymptomatic, drug-induced type 1 only	No ICD on family history alone (Class III). Trigger advice and follow-up
Qualifies for ICD but declines or has a contraindication, or recurrent shocks	Quinidine (IIa)
Electrical storm	IV isoprenaline (IIa)
Recurrent appropriate shocks despite drugs	Epicardial substrate ablation of the RVOT (IIa)

• Electrical storm: IV isoprenaline, which suppresses VF by raising heart rate and calcium current. Amiodarone doesn't help. Class IC drugs and other pure sodium channel blockers make it worse; quinidine (class IA, but an Ito blocker) is the exception, given orally once stable.
• Quinidine blocks the transient outward current. Gastrointestinal upset, thrombocytopenia and QT prolongation limit it. It isn't registered in Australia and is supplied through the Special Access Scheme.
• Ablation: the 2026 J-wave consensus calls epicardial substrate ablation transformative, citing durable VF suppression in registries and limited randomised data. That consensus is APHRS-led, and ESC 2022 still restricts ablation to recurrent shocks despite drugs.
• ICD complications (inappropriate shocks, lead problems) matter because most patients are young and will carry the device for decades. Subcutaneous ICDs suit many as they rarely need pacing, after ECG screening (ideally including exercise or a drug challenge), which fails more often in Brugada syndrome because of the dynamic ECG and T-wave oversensing.

Family screening and genetics

• First-degree relatives need a clinical ECG (with high leads), a review of symptoms and, if the proband has a pathogenic SCN5A variant, cascade genetic testing.
• Relatives with a normal ECG and negative genotype for a known familial variant can be reassured. Without a known variant, a normal ECG doesn't exclude the disease; a drug challenge may be offered after counselling.
• Children of a proband have a 50% chance of inheriting a familial variant. Fever is a particular trigger in children.
• Under the Commonwealth law passed in April 2026, life insurers can't ask for or use genetic test results (or whether someone has been tested) for decisions from 8 October 2026. They can still use family history, a diagnosis, signs or symptoms. This removes a common reason relatives declined testing.

Special populations and Australian points

• Pregnancy: generally well tolerated. Treat fever, avoid listed drugs (check local anaesthetics for epidurals), and plan delivery with obstetrics, anaesthesia and cardiology. Continue the ICD.
• Older patients: a new Brugada pattern in an older person warrants a search for a cause (drugs, electrolytes, ischaemia) before a genetic label. Events after 60 are uncommon.
• Driving (Austroads 2022): ICD rules apply as in ventricular tachycardia. Syncope needs specialist assessment before return to driving.
• Southeast Asian communities in Australia carry higher prevalence. Ask about sudden nocturnal death in the family.
• Sport: most asymptomatic patients can exercise after specialist review. Exercise rarely triggers events, but post-exercise vagal tone and hyperthermia can.

Pitfalls

• Diagnosing Brugada syndrome from a saddleback pattern or from a single ECG with V1 placed too high.
• Missing fever as the trigger, or giving a febrile patient a TCA or lithium without checking the ECG.
• Reading a TCA overdose ECG as Brugada syndrome (or the reverse). Check the QRS width and aVR.
• Offering an ICD to an asymptomatic patient with only a drug-induced pattern.
• Using amiodarone or flecainide in a Brugada electrical storm. Give isoprenaline.
• Reassuring relatives because the proband's gene test was negative.