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Brugada Syndrome

Quick Summary

Definition: An inherited arrhythmia syndrome defined by a spontaneous or provoked type 1 coved ST-segment elevation pattern in the right precordial leads, predisposing to ventricular arrhythmias and sudden death, after exclusion of phenocopies and structural heart disease.[1][4][2]

  • 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: Aborted cardiac arrest, documented sustained ventricular arrhythmia, and arrhythmic syncope with a spontaneous Type 1 ECG are strongest; family history and inducible VF are adjunctive/controversial, not standalone ICD indications
  • First-line Mx: Avoid triggers (fever, sodium-channel blockers, Brugada-risk drugs - check brugadadrugs.org); ICD for cardiac-arrest survivors or selected high-risk patients after specialist assessment; quinidine in selected scenarios or 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 diagnostic Type 1 ECG pattern reflects reduced conduction reserve in the RVOT, mediated by reduced sodium current and structural/fibrotic changes; interpret in clinical context and exclude phenocopies
  • 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 (reported ranges; perform only in a specialist EP lab with continuous monitoring and resuscitation facilities)
  • 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]

Older, selected-cohort estimates have attributed 4–12% of all sudden cardiac deaths and up to 20% of sudden deaths in structurally normal hearts to Brugada syndrome; these figures come from historical, non-representative series and should be treated as indicative rather than dependable contemporary population estimates[4]

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)

Testing not recommended (Class III):

  • 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] (management recommendations are covered in the Treatments section; genetic testing is covered in the Genetic Testing tab).

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 when spontaneous in the appropriate context, after excluding phenocopies and structural disease. If seen only after drug provocation, interpret alongside clinical and family features and current diagnostic criteria (see above)
  • 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

1. General measures:

  • 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)
  • Genetic counselling and family cascade testing, see the Genetic Testing page

2. 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[6]
    • 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)
  • Cilostazol (phosphodiesterase-3 inhibitor): an alternative to quinidine where quinidine is unavailable, not tolerated, or contraindicated[1]
  • 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

3. Device therapy / catheter ablation:

  • ICD therapy:
    • Secondary prevention after cardiac arrest (Class I indication)
    • Primary prevention controversial - see risk stratification
    • ICD is the therapy with the strongest evidence for preventing SCD in Brugada syndrome[1]
  • 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:

  • Programmed electrical stimulation (EPS)-induced VF has limited and controversial incremental value for risk stratification and should not be used as a stand-alone ICD indication; it may be considered in selected asymptomatic individuals with a spontaneous type-1 pattern as part of a broader risk assessment
  • 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

Pregnancy in Brugada syndrome - generally lower event rate, individualized

Reported arrhythmic event rates during pregnancy in Brugada syndrome are low, and some case-series data have suggested a lower rate than outside pregnancy, but this should be described cautiously rather than framed as pregnancy being reliably "protective" for an individual patient; risk should still be assessed on the individual's phenotype (spontaneous vs drug-induced Type 1 pattern), symptom history and ICD status.[1][5]

Baseline assessment: 12-lead ECG with high precordial leads, review of prior Type 1 pattern documentation and ICD status if present. Sodium-channel-blocker provocation testing is not a routine part of pregnancy assessment, it carries its own risk and should only be used for the same diagnostic indications as outside pregnancy, not repeated purely because a patient is pregnant.

Fever: fever remains a recognised VF trigger in Brugada syndrome and should be treated promptly with antipyretics; this applies in pregnancy as it does otherwise.

Medication safety: check individual drugs against a current Brugada drug-safety list (e.g. BrugadaDrugs.org) and the BNF/SmPC for pregnancy safety, rather than applying a blanket avoidance of entire antibiotic classes (macrolides, fluoroquinolones) or NSAIDs; some agents within these classes carry stronger evidence of risk than others, and pregnancy-specific safety must also be checked.

Delivery and postpartum: mode of delivery is normally obstetric unless the individual's cardiac status requires otherwise; an ICD or prior cardiac arrest may warrant delivery at a centre with cardiology input. Postpartum follow-up (including ECG timing) should be individualized rather than a fixed six-week rule for every patient.

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

  • Genetic testing has low yield (~20-30%) but still recommended[1]
  • Type 2/3 patterns alone are NOT diagnostic - need provocation test
  • Screen first-degree relatives with ECG (high precordial leads, consider drug challenge)
  • Lead placement matters - record V1-V3 in 2nd and 3rd intercostal spaces
  • Avoid drugs that can induce/worsen Brugada pattern (www.brugadadrugs.org)[1]
  • Fever can trigger VF - treat aggressively with antipyretics[1]
  • EPS VF inducibility should not be used as a stand-alone ICD indication given its limited and controversial incremental value; it may be considered in selected asymptomatic patients with a spontaneous type-1 pattern[1]
  • Asymptomatic drug-induced Type 1 pattern - ICD generally NOT indicated
  • Reported arrhythmic event rates during pregnancy are generally low, but risk should still be individualized rather than assumed to be reliably lowered by pregnancy

References & Review Date

Last reviewed: July 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)90253-J
  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/ehad295
  4. Narasimhan B, et al. Brugada syndrome. Nat Rev Dis Primers. 2025;11:38. PubMed
  5. 2025 ESC Guidelines for the management of cardiovascular disease during pregnancy. Eur Heart J. 2025. doi:10.1093/eurheartj/ehaf193
  6. Joint Formulary Committee. British National Formulary (BNF), quinidine, isoprenaline monographs. bnf.nice.org.uk