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Brugada Syndrome

Quick Summary

Definition: An inherited arrhythmia syndrome defined by coved-type ST-segment elevation in the right precordial leads, predisposing to ventricular arrhythmias and sudden death in a structurally normal heart.[1]

  • Prevalence: 1-5 in 10,000 (higher in Southeast Asia), male predominant 8-10:1[4]
  • Key gene: SCN5A (20-30% of cases, sodium channel loss-of-function) - 70% genetically elusive
  • Hallmark: Type 1 Brugada ECG pattern (coved ST elevation ≥2mm in V1-V2), VF/SCD, typically 30-40s
  • High-risk markers: Prior cardiac arrest/syncope, spontaneous Type 1 ECG, inducible VF, family history SCD
  • First-line Mx: ICD if high-risk, avoid triggers (fever, Na-blockers, drugs - check brugadadrugs.org), quinidine if ICD declined

Aetiology

Monogenic (Mendelian): SCN5A in only ~20–30%, the lowest of the channelopathies[1]

Acquired: Brugada phenocopies (fever, drugs, electrolyte/metabolic disturbance) can produce a Type-1 pattern and must be excluded[4]

Complex (likely polygenic): ~70% gene-elusive, now viewed as oligogenic/polygenic with a conduction/structural substrate[4]

Genetics

Inheritance: Autosomal dominant with incomplete penetrance (15–35%, highly variable); strong male predominance (8–10:1, ~91.3% of cases in men). Polygenic, over 100 contributive mutations described; up to 70% of families have no definitive genetic mutation (Narasimhan et al, Nat Rev Dis Primers 2025)[4]

Genetic yield: Only ~20–30% (SCN5A identified), lowest of all channelopathies. 70% are genetically elusive. SCN5A is the only definitively causative gene; all others are uncertain or modulatory.

Key gene:

  • SCN5A (~20–30%), Nav1.5 sodium channel loss-of-function (reduced RVOT conduction reserve → ST elevation); autosomal dominant; male-predominant expression. SCN5A carriers have higher risk of VA during sodium channel blocker test (SCBT), predictive of test-induced arrhythmia (Wilde et al 2023, EHJ)[3]

Why is BrS polygenic/genetically complex?

  • The pathognomonic Type 1 ECG reflects reduced conduction reserve in the RVOT, mediated by reduced sodium current AND structural/fibrotic changes
  • Multiple common genetic variants (polygenic risk) contribute, higher aggregate burden increases SCBT-induced arrhythmia risk
  • Sex hormones (testosterone) likely modulate expression, BrP absent in prepubertal males; may resolve after therapeutic orchiectomy
  • Geographical variation: highest prevalence in Thailand (second only to road accidents as cause of death in young men); known locally as "Lai Tai" (death during sleep)[4]
Sodium Channel Blocker Test (SCBT): Pitfalls (Wilde et al, EHJ 2023)[3]

SCBT (ajmaline, flecainide, procainamide) is used to unmask Type 1 BrP in patients with non-diagnostic baseline ECG.

  • Sensitivity: Ajmaline 76–100% (best); flecainide ~68%; procainamide lower
  • Key pitfall, Specificity: Drug-induced Type 1 ECG alone is NOT sufficient for BrS diagnosis (revised since 2016). Additional clinical criteria required (Shanghai score): prior VF/VT, syncope, family history SCD, family BrS. A positive SCBT in isolation ≠ BrS.
  • Contraindication: Do NOT perform SCBT in asymptomatic patients with Type 2 Brugada pattern and no family history of BrS/SCD
  • Safety: Malignant VA (VF, sustained VT) occurs in 0–10.7% (mean ~1.4%), higher risk if spontaneous Type 1 ECG, prolonged baseline conduction intervals, or pathogenic SCN5A variant
  • New use: SCBT increasingly used to delineate arrhythmogenic substrate during ablation procedures

Prevalence

~1 in 2,000 individuals (higher in Southeast Asia, highest prevalence in Thailand, Japan, Taiwan)[4]

Male predominance (8–10:1 male:female ratio); SCN5A variants account for 20–30% of cases in European populations but only 8–20% in Asian populations[4]

Accounts for 4–12% of all sudden cardiac deaths; up to 20% of sudden deaths in individuals with structurally normal hearts

Ethnic variation (Narasimhan et al, Nat Rev Dis Primers 2025[4]): Asian populations more often present with spontaneous Type 1 Brugada pattern (71.1% vs 56% in Western populations), with higher rates of aborted SCD; however family history of SCD is less common in Asian populations (12.8% vs 24.5%). SCN5A loss-of-function mutations more prevalent in Western populations (40.1% vs 13.2% in Asian cohorts).

Fever trigger: Arrhythmic events during febrile episodes occur in ~6% of patients; fever accelerates sodium channel inactivation, particularly in SCN5A variant carriers, treat ALL fevers aggressively with antipyretics

Diagnosis

ESC 2022 Guidelines - Brugada Syndrome[1]

Diagnostic Criteria (ESC 2022):

BrS is diagnosed (Class I) if:

  1. Spontaneous type 1 Brugada ECG pattern + no other heart disease, OR
  2. Survived cardiac arrest due to VF/polymorphic VT + type 1 Brugada ECG induced by sodium channel blocker or fever + no other heart disease

BrS should be considered (Class IIa) if:

  • No other heart disease + induced type 1 pattern + at least one of:
    • Arrhythmic syncope or nocturnal agonal respiration
    • Family history of BrS
    • Family history of sudden death (<45 years) with negative autopsy

BrS may be considered (Class IIb) if:

  • Induced type 1 Brugada ECG alone (without additional features)

General Recommendations (Class I):

  • Avoidance of drugs that induce ST-elevation (brugadadrugs.org)
  • Avoidance of cocaine, cannabis, excessive alcohol
  • Treatment of fever with antipyretics
  • ICD for cardiac arrest survivors or documented VF/sustained VT

Genetic Testing (Class I):

  • SCN5A gene testing recommended for probands with BrS

Advanced Therapies:

  • Quinidine: Effective in reducing arrhythmia inducibility and ICD shocks
  • Cilostazol: Alternative to quinidine (phosphodiesterase-3 inhibitor)
  • Isoproterenol: Can suppress electrical storm
  • Catheter ablation: Epicardial RVOT ablation can suppress VF in >75% of patients with recurrent events

Class III (NOT recommended):

  • Sodium channel blocker test in patients with prior type I Brugada pattern

Reference: Zeppenfeld K et al. 2022 ESC Guidelines for management of patients with ventricular arrhythmias and prevention of sudden cardiac death. Eur Heart J 2022;43:3997-4126[1]

Diagnostic Criteria:

  • Type 1 Brugada pattern on ECG (spontaneous or drug-induced)
  • ST-segment elevation ≥2mm in ≥1 right precordial lead (V1-V3)
  • Coved-type ST elevation followed by negative T-wave

ECG Patterns:

  • Type 1: Coved ST elevation ≥2mm, negative T-wave (diagnostic)
  • Type 2: Saddle-back pattern, ST elevation ≥0.5mm (suggestive, not diagnostic)
  • Type 3: Either pattern but ST elevation <2mm (not diagnostic)

Clinical Features:

  • Often asymptomatic (ECG finding on screening)
  • Syncope (typically at rest or during sleep)
  • Nocturnal agonal respiration
  • Sudden cardiac arrest (VF)
  • Events often occur with fever

Investigations

First-line:

  • 12-lead ECG with high precordial lead placement (2nd/3rd intercostal space)
  • Repeat ECGs (pattern can be intermittent)
  • ECG during febrile illness (can unmask Type 1 pattern)

Provocation test, Sodium Channel Blocker Test (SCBT) (Wilde et al, EHJ 2023)[3]:

  • Ajmaline (preferred in Europe, most sensitive ~100%); flecainide (68%); procainamide (less potent); pilsicainide (Asia)
  • Must be performed in specialist centre with full resuscitation capability, malignant VA (VF/sustained VT) in ~1.4% (range 0–10.7%)
  • A positive SCBT alone is NOT diagnostic of BrS (current modified Shanghai criteria), additional clinical criteria required in absence of spontaneous Type 1 ECG
  • DO NOT perform SCBT in asymptomatic patients with Type 2 Brugada pattern and no family history of BrS or SCD
  • Higher risk of SCBT-induced VA: spontaneous Type 1 pattern, prolonged baseline conduction intervals, pathogenic SCN5A variant
  • New use: SCBT during EP study to delineate arrhythmogenic substrate for ablation

Electrophysiology study:

  • Controversial role in risk stratification
  • VF inducibility does NOT reliably predict events
  • Generally NOT recommended for routine risk stratification

Exclude structural heart disease:

  • Echocardiography (structurally normal heart in Brugada)
  • Consider cardiac MRI if any doubt

Treatments

Lifestyle modifications:

  • Avoid drugs that can trigger Brugada pattern (www.brugadadrugs.org)
  • Treat fever aggressively with antipyretics (fever can precipitate VF)
  • Avoid excessive alcohol
  • Avoid large meals (vagal stimulation can unmask pattern)

ICD therapy:

  • Secondary prevention after cardiac arrest (Class I indication)
  • Primary prevention controversial - see risk stratification
  • ICD is ONLY therapy proven to prevent SCD[1]

Medical therapy (limited evidence):

  • Quinidine bisulfate[1], Ito (transient outward current) blocker; normalises ST elevation and suppresses VF triggers.
    • Start 200–250 mg three times daily → target 400–500 mg three times daily (total 1200–1500 mg/day)
    • UK: Available as quinidine bisulfate 200 mg tablets (unlicensed/SPECIALS), source via specialist pharmacy; monitor QTc (paradoxical QT prolongation), diarrhoea, thrombocytopenia
    • Indications: ICD contraindicated/declined; recurrent appropriate ICD shocks despite VF storm management; electrical storm bridging
    • Check quinidine level if toxicity suspected (target 2–5 mcg/ml)
  • Isoprenaline (isoproterenol) IV, for electrical storm / VF storm:
    • 0.5–2 mcg/min IV infusion, titrated to achieve target HR 90–110 bpm
    • Maximum 5 mcg/min in refractory storm; deliver in HDU/ICU setting with continuous monitoring
    • Mechanism: ↑cAMP → augments Ito/ICa-L balance → reduces ST elevation and VF triggers
    • Use as bridge to quinidine or ablation; wean slowly once arrhythmia suppressed

Catheter ablation:

  • For recurrent VF/ICD shocks
  • Target RVOT epicardium
  • Emerging therapy; long-term efficacy uncertain
Related Resources

Complications

  • Polymorphic VT and VF: leading to sudden death, characteristically at rest or during sleep and provoked by fever[1]
  • Electrical storm: recurrent VF, managed distinctly (isoproterenol, quinidine)
  • Atrial fibrillation: common, and can be the first manifestation
  • Inappropriate ICD shocks.

Risk Stratification

High-risk (ICD recommended):

  • Cardiac arrest survivor (secondary prevention)
  • Spontaneous Type 1 ECG pattern + syncope likely due to VT/VF

Intermediate risk (ICD may be considered - shared decision-making):

  • Spontaneous Type 1 ECG + family history of SCD <45 years
  • Drug-induced Type 1 ECG + syncope
  • Spontaneous Type 1 ECG pattern only (asymptomatic)

Lower risk (no ICD):

  • Asymptomatic with drug-induced Type 1 pattern only
  • Type 2 or 3 pattern

Important notes on risk stratification:

  • EPS-induced VF does NOT predict spontaneous events - NOT recommended for routine risk stratification
  • Spontaneous Type 1 pattern higher risk than drug-induced
  • Male sex associated with higher risk
  • History of syncope/cardiac arrest in patient or family is key risk factor

Pregnancy Management

ESC 2018 Pregnancy Guidelines - Brugada Syndrome (mWHO Class II-III)

PRECONCEPTION COUNSELLING:

  • Risk stratification:
    • Asymptomatic, Type 1 pattern, no family history of SCD: mWHO II (low-moderate risk)
    • Prior cardiac arrest, recurrent syncope, ICD: mWHO II-III (moderate-high risk)
    • Extremely rare in women (male:female 8-10:1) - most women are genotype-positive, phenotype-negative
  • Pregnancy-specific physiology:
    • Progesterone may have PROTECTIVE effect (shortens action potential duration, reduces arrhythmic substrate)
    • Pregnancy appears PROTECTIVE - very few reported arrhythmic events during pregnancy
    • Testosterone amplifies Brugada phenotype (explains male predominance); estrogen protective
  • Baseline assessment:
    • 12-lead ECG (high precordial leads V1-V3 in 2nd/3rd intercostal spaces)
    • Drug provocation test if not previously done (ajmaline/flecainide/procainamide)
    • Document baseline Type 1 pattern presence (spontaneous vs drug-induced)
    • ICD interrogation if present (programming, battery, lead integrity)
  • Medications:
    • Generally no chronic medications required for Brugada (unlike LQTS)
    • Quinidine if recurrent VF/ICD shocks - limited pregnancy data but used if essential
    • Avoid: All sodium channel blockers, many antidepressants, antihistamines (check www.brugadadrugs.org)
  • Genetic counselling: 50% transmission risk; predominantly affects males in family[4]

PREGNANCY MANAGEMENT:

  • Monitoring frequency:
    • Each trimester cardiology review if asymptomatic
    • ECG each visit (Type 1 pattern may become less prominent in pregnancy - progesterone protective)
    • More frequent if ICD present or history of arrhythmic events
  • Low arrhythmic risk in pregnancy:
    • Pregnancy appears protective due to hormonal changes
    • Very few case reports of VF during pregnancy
    • Most women have minimal symptoms
  • Fever management - CRITICAL:
    • Fever is major VF trigger - treat aggressively
    • Paracetamol (acetaminophen) 1g QDS at first sign of fever (safe in pregnancy)
    • Cooling measures (tepid sponging)
    • If infection suspected: Treat promptly but check antibiotic safety (avoid macrolides, fluoroquinolones)
  • Medication safety:
    • Check ALL medications against www.brugadadrugs.org before prescribing
    • Common pregnancy medications to AVOID: Ondansetron (antiemetic), many antidepressants
    • Safe alternatives: Metoclopramide, cyclizine for nausea
  • ICD management:
    • Safe during pregnancy
    • Review quarterly (increased metabolic demands)
    • Patient to report any shocks immediately

LABOUR & DELIVERY:

  • Delivery planning:
    • Tertiary centre if ICD or prior cardiac arrest
    • Standard obstetric unit acceptable if asymptomatic, no ICD
    • External defibrillator immediately available
  • Mode of delivery:
    • Vaginal delivery preferred (pregnancy protective, low risk)
    • Caesarean section only for obstetric indications
  • Anaesthesia:
    • Epidural SAFE and preferred
    • Bupivacaine commonly used - SAFE (despite being amide local anaesthetic)
    • AVOID: Propofol (reported to unmask Brugada pattern in some cases; use with caution)
    • GA if needed: Use agents with minimal cardiac sodium channel effects
  • Intrapartum monitoring:
    • Continuous ECG monitoring
    • Temperature monitoring - aggressively treat any fever
    • Defibrillator immediately available
  • Pain management:
    • Good pain control important (stress reduction)
    • Paracetamol safe
    • Avoid NSAIDs if possible (theoretical risk, limited data)

POSTPARTUM:

  • Hormonal withdrawal:
    • Falling progesterone may theoretically increase risk
    • However, clinical data shows continued low risk postpartum
    • Monitor 24 hours if ICD or prior arrhythmic events
  • Fever vigilance:
    • Postpartum infection risk - monitor temperature
    • Treat fever immediately with paracetamol
    • Safe antibiotics: Penicillins, cephalosporins (avoid macrolides, fluoroquinolones)
  • No specific medications needed postpartum (unless quinidine for recurrent VF)
  • Contraception: All methods safe
  • Breastfeeding: Safe and encouraged
  • Follow-up: Standard cardiology follow-up; ECG at 6 weeks

KEY SAFETY MESSAGES:

  • Fever = VF trigger: Treat aggressively with paracetamol at first sign
  • Check ALL drugs: Many common medications contraindicated (www.brugadadrugs.org)
  • Pregnancy appears protective: Arrhythmic risk lower than baseline in most women
  • Male predominance: Female carriers often phenotype-negative; pregnancy safe in vast majority

OVERALL PROGNOSIS:

  • Pregnancy in Brugada syndrome is generally LOW RISK
  • Protective hormonal effects during pregnancy
  • Main risk is inadvertent exposure to contraindicated drugs or untreated fever
  • Excellent maternal and fetal outcomes expected with appropriate precautions

Follow-up

Pragmatic surveillance approach informed by ESC 2022 Ventricular Arrhythmia guidelines (which do not mandate fixed monitoring intervals)[1].

Advanced / complicated = spontaneous type-1 pattern with syncope or documented arrhythmia, prior aborted SCD, or appropriate ICD therapy.

Genotype-positive / phenotype-negative (G+/P−) = a confirmed pathogenic-variant carrier with no overt disease expression yet.

Genotype+ / Phenotype−Uncomplicated / StableAdvanced / Complicated
FrequencyPeriodic (low penetrance)AnnualEvery 6 months
Clinical reviewFever-management & drug-avoidance adviceSyncope, palpitations, fever-management educationAs above + device interrogation
ECGPeriodic (incl. high lead placement)Annual 12-lead (incl. high lead placement)Each visit
Holter / ambulatoryAs indicatedPeriodic (AF, conduction, arrhythmia)As indicated
Family screening–Cascade ECG ± drug challenge / genetics–

Disclaimer: This table is general guidance based on published guidelines and does not replace clinical judgement. The responsible clinician is accountable for determining the appropriate, individualised follow-up plan for each patient.

Key Points

  • Avoid drugs that can induce/worsen Brugada pattern (www.brugadadrugs.org)[1]
  • Screen first-degree relatives with ECG (high precordial leads, consider drug challenge)
  • Fever can trigger VF - treat aggressively with antipyretics[1]
  • Do NOT use EPS VF inducibility to guide ICD decision (poor predictive value)[1]
  • Asymptomatic drug-induced Type 1 pattern - ICD generally NOT indicated
  • Type 2/3 patterns alone are NOT diagnostic - need provocation test
  • Genetic testing has low yield (~20-30%) but still recommended[1]
  • Lead placement matters - record V1-V3 in 2nd and 3rd intercostal spaces
  • Pregnancy generally LOW RISK due to protective hormonal effects

References & Review Date

Last reviewed: June 2026

  1. Zeppenfeld K, et al. 2022 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. Eur Heart J. 2022;43(40):3997–4126. doi:10.1093/eurheartj/ehac262
  2. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol. 1992;20(6):1391–1396. doi:10.1016/0735-1097(92)90400-X
  3. Wilde AAM, et al. Use, misuse, and pitfalls of the drug challenge test in the diagnosis of Brugada syndrome. Eur Heart J. 2023;44(25):2427–2439. doi:10.1093/eurheartj/ehad103
  4. Narasimhan B, et al. Brugada syndrome. Nat Rev Dis Primers. 2025;11:38. PubMed
  5. Regitz-Zagrosek V, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165–3241. doi:10.1093/eurheartj/ehy340
  6. Joint Formulary Committee. British National Formulary (BNF), quinidine, isoprenaline monographs. bnf.nice.org.uk