Brugada syndrome (BrS) is an inherited autosomal dominant cardiac channelopathy characterized by coved-type ST-segment elevation ≥2 mm in the right precordial leads (V1–V2) and an increased risk of sudden cardiac death (SCD) from ventricular fibrillation (VF), predominantly affecting males in their 3rd–4th decade of life. [1-2] Prevalence is estimated at 1 in 2,000 worldwide, with higher prevalence in Southeast Asia, and BrS may account for 18–28% of unexplained sudden deaths. [1]
The following figure from the 2017 AHA/ACC/HRS Guidelines illustrates the risk stratification and management algorithm for BrS:
1. History
- Syncope: Characterize as exertional vs. rest/sleep-related; BrS syncope typically occurs at rest, during sleep, or with vagal tone [4]
- Cardiac arrest or resuscitated SCD: Prior episodes of VF or aborted SCA
- Nocturnal agonal respirations: Witnessed by bed partner — a classic presentation [5]
- Palpitations, chest discomfort, seizure-like episodes (may represent self-terminating polymorphic VT) [6]
- Timing: Events cluster at night or during rest; fever is a critical trigger [7-8]
- Triggers: Recent febrile illness, heavy meals, alcohol binge, new medications (especially sodium channel blockers, TCAs, cocaine) [4][9]
- Important negatives: Absence of exertional syncope (which favors LQTS/CPVT/HCM over BrS), absence of structural heart disease symptoms
2. Alarm Features
- Cardiac arrest or witnessed VF — highest risk category (~10–15%/year recurrence) [10]
- Syncope at rest or during sleep with spontaneous type 1 ECG (~2.3%/year event rate) [1]
- Fever with new Brugada ECG pattern — can precipitate VF, especially in children [2][11]
- VF storm / recurrent ICD shocks — requires urgent intensification with IV isoproterenol acutely, then quinidine or catheter ablation [4][12]
- Nocturnal agonal breathing reported by family members [5]
- Family history of unexplained sudden death <45 years — warrants urgent evaluation of the patient
3. Medications
Medications to AVOID (comprehensive list at brugadadrugs.org): [4][9][13]
- Class IA/IC antiarrhythmics: Flecainide, propafenone, procainamide (except for diagnostic challenge under monitored conditions)
- Tricyclic antidepressants: Amitriptyline, nortriptyline, imipramine, desipramine [14]
- Psychotropics: Lithium, trifluoperazine, fluoxetine [2]
- Anesthetics: Propofol, bupivacaine [14]
- Recreational substances: Cocaine, cannabis, excessive alcohol [9][13]
- Antihistamines (certain first-generation agents) [2]
Treatments
- Quinidine (Class Ia, also blocks Ito): First-line pharmacologic therapy; no SCD observed in long-term follow-up, though adverse effects in ~38% [4][15]
- Isoproterenol IV: Acute management of VF storm [12]
- Antipyretics (acetaminophen, ibuprofen): Aggressive use for any fever [9][11]
Contraindicated in VF storm: Procainamide (worsens sodium channel blockade) [14]
4. Diet
- Avoid heavy meals: Large meals (especially late evening) increase vagal tone and may trigger arrhythmias [11]
- Avoid excessive alcohol: Alcohol intoxication can precipitate syncopal events and unmask the Brugada ECG pattern [9]
- Hydration: Maintain adequate hydration to prevent electrolyte disturbances (hypokalemia, metabolic acidosis can unmask BrS pattern) [9]
5. Review of Systems
- Cardiovascular: Syncope, presyncope, palpitations, chest discomfort, nocturnal agonal breathing
- Neurologic: Seizure-like episodes (may be misdiagnosed epilepsy from self-terminating VT/VF) [5]
- Constitutional: Recent febrile illness, night sweats
- Psychiatric: Current psychotropic medications (TCAs, lithium, SSRIs)
- Substance use: Cocaine, cannabis, alcohol use patterns [9]
- Family: Any unexplained deaths, drowning, single-vehicle accidents, SIDS in family
6. Collateral History and Family History
- Witnessed events: Bed partner or family members should be asked about nocturnal agonal respirations, seizure-like activity during sleep, or witnessed cardiac arrest [5]
- Family history of SCD: Present in ~26% of affected patients; however, a positive family history alone is not a significant predictor of adverse events in the proband [4][16]
- Autosomal dominant inheritance with variable penetrance; >90% of symptomatic patients are male [7]
- Cascade screening: First-degree relatives should be offered ECG screening and potentially sodium channel blocker challenge and/or genetic testing [12]
- Ethnic background: Higher prevalence in Southeast Asian populations (linked to sudden unexplained nocturnal death syndrome — SUNDS/Lai Tai/Bangungut) [1]
7. Risk Factors
- Male sex: >90% of symptomatic patients [7]
- Age 30–50 years: Peak presentation in 3rd–4th decade [1]
- Southeast Asian descent [1]
- Fever: Critical modifiable trigger, especially in children [2][11]
- Vagotonic states: Rest, sleep, postprandial period [4]
- Sodium channel–blocking drugs, cocaine, alcohol [4]
- SCN5A mutation carriers (~20–30% of phenotype-positive patients) [5][8]
- Spontaneous type 1 ECG pattern: Strongest ECG predictor of events [15]
8. Differential Diagnosis
Before diagnosing BrS, Brugada phenocopies and other causes of right precordial ST elevation must be excluded: [2][17]
- Acute MI / RV ischemia: ST elevation typically in different distribution; troponin positive
- Pulmonary embolism: Acute RV strain pattern; clinical context of DVT risk
- Arrhythmogenic right ventricular cardiomyopathy (ARVC): Structural RV abnormalities on imaging; epsilon waves; overlapping ECG features [2][18]
- Pericarditis/myocarditis: Diffuse ST elevation, PR depression; inflammatory markers elevated
- Hyperkalemia: Peaked T waves, widened QRS; check BMP
- Hypercalcemia: Shortened QT interval [6]
- Hypothermia: Osborn (J) waves can mimic Brugada pattern [6]
- Pectus excavatum: Mechanical compression of RVOT [17]
- Mediastinal tumor: RVOT compression [18]
- Early repolarization syndrome: Benign variant, especially in young males [6]
- RBBB: Atypical RBBB can mimic type 2 pattern [17]
- Drug intoxication: TCA overdose, cocaine [6]
Key distinguishing features of phenocopies: identifiable underlying condition, pattern resolves with treatment of the condition, negative sodium channel blocker challenge, no family history of SCD [2]
9. Past Medical History
- Prior syncope episodes (especially at rest/sleep)
- Prior cardiac arrest or resuscitated SCD
- History of atrial fibrillation (associated with BrS in some patients) [17]
- Sinus node dysfunction or conduction disease (AV block, intraventricular conduction delay) [19]
- Prior febrile convulsions in childhood (may have been unrecognized BrS events)
- Existing ICD or prior device-related complications
- Psychiatric history and current psychotropic medications
10. Physical Exam
- Often entirely normal — BrS patients typically have structurally normal hearts [7]
- Vital signs: Check for fever (trigger); bradycardia (vagal tone increases risk)
- Cardiac auscultation: Usually normal; no murmurs expected
- Chest wall: Pectus excavatum (can cause Brugada-like ECG pattern and should be noted) [17]
- Neurologic exam: Assess for post-ictal state if seizure-like presentation
- Signs of substance use: Cocaine, alcohol intoxication
11. Lab Studies
- Basic metabolic panel: Rule out hyperkalemia, hypercalcemia, metabolic acidosis (all can unmask BrS pattern) [9]
- Troponin: Rule out acute myocardial ischemia/infarction
- Toxicology screen: Cocaine, TCA levels if overdose suspected [14]
- Thyroid function: Hyperthyroidism can affect cardiac conduction
- Inflammatory markers (CRP, ESR): If myocarditis/pericarditis suspected
- Genetic testing: SCN5A sequencing (yield ~20–30%); useful for cascade family screening but does not change risk stratification [1][8]
12. Imaging
- Echocardiogram: First-line to exclude structural heart disease; typically normal in BrS. Important to rule out ARVC, pectus-related compression, and other structural mimics [7]
- Cardiac MRI: If ARVC is suspected (fibrofatty replacement of RV myocardium); emerging evidence suggests subtle RVOT structural abnormalities may exist in BrS [15]
- CT chest: If mediastinal mass or PE suspected
- CT angiography / coronary angiography: If acute coronary syndrome cannot be excluded
- Imaging is not required for diagnosis if the clinical and ECG picture is classic
13. Special Tests
- Sodium channel blocker challenge[2][8]
- Programmed ventricular stimulation (PVS): May be considered (Class IIb) in asymptomatic patients with spontaneous type 1 ECG for risk stratification; specificity decreases with triple extrastimuli; value remains controversial [8][12]
- Shanghai Score: Proposed scoring system integrating ECG, clinical, and family history features for diagnosis when provocative testing is positive [1]
- Signal-averaged ECG: Late potentials may be supportive [17]
- Holter monitoring: To detect intermittent type 1 pattern, nocturnal ST changes, or atrial arrhythmias [14]
14. ECG
The ECG is the cornerstone of diagnosis: [2]
- Type 1 ("coved") — DIAGNOSTIC: ≥2 mm coved ST elevation in ≥1 right precordial lead (V1–V2), followed by negative T wave. This is the only pattern diagnostic for BrS [2]
- Type 2 ("saddleback") — SUGGESTIVE only: ≥0.5 mm ST elevation with convex morphology and positive T wave in V2; requires conversion to type 1 with sodium channel blocker challenge to confirm diagnosis [2]
- High lead placement: Record V1–V2 in the 2nd and 3rd intercostal spaces (high parasternal leads) to improve sensitivity [8]
- Dynamic nature: The ECG pattern can be intermittent and may be normal at baseline; repeat ECGs and provocative testing may be needed [5][7]
- QRS fragmentation: Seen in a minority; associated with increased risk [4]
- Conduction abnormalities: First-degree AV block, left axis deviation, prolonged HV interval may be present [17]
- Atrial fibrillation: Associated finding in some patients [17]
Dangerous ECG patterns to recognize
- Spontaneous type 1 pattern + syncope = highest risk [15]
- Type 1 pattern unmasked by fever = urgent management needed [2]
- Polymorphic VT / VF on monitor = immediate defibrillation
15. Assessment
Severity stratification (annual VT/VF risk): [10][15][20]
- Prior cardiac arrest: ~10–15%/year — highest risk
- Arrhythmic syncope + spontaneous type 1 ECG: ~2.3%/year
- Asymptomatic + spontaneous type 1 ECG: ~1–9%/year (controversial)
- Asymptomatic + drug-induced type 1 ECG only: ≤0.4%/year — lowest risk
Typical presentation: Young male, syncope or cardiac arrest at rest/during sleep, structurally normal heart, type 1 Brugada ECG [1][7]
Atypical presentations: Pediatric onset (rare but aggressive), female patients, seizure-like episodes, nocturnal agonal breathing, fever-triggered events [2][5]
Complications: SCD, recurrent VF storms, ICD-related complications (inappropriate shocks, lead fracture — significant concern given young age at implantation) [20]
16. Treatment Plan
Acute stabilization (ED/ICU)
- VF/cardiac arrest: Standard ACLS; defibrillation is definitive
- VF storm: IV isoproterenol (augments calcium current, suppresses VF); avoid procainamide [12][14]
- Fever-triggered events: Aggressive antipyretics (acetaminophen 1g IV/PO) + active cooling [9][11]
- Correct electrolyte abnormalities (K⁺, Ca²⁺, acidosis) [9]
- Discontinue all offending medications immediately [14]
Definitive therapy (per 2017 AHA/ACC/HRS Guidelines): [4][12]
- ICD implantation (Class I): Spontaneous type 1 ECG + cardiac arrest, sustained VA, or arrhythmic syncope
- Quinidine (Class I): For recurrent ICD shocks, VF storm, or when ICD is refused/not feasible; also used in pediatric patients [4][15]
- Catheter ablation (Class I for recurrent VF): Epicardial ablation of RVOT substrate can eliminate type 1 pattern in >75% and markedly reduce VF recurrence [4]
- Observation only (Class I): Asymptomatic patients with drug-induced-only type 1 ECG [12]
All patients: Counsel on trigger avoidance — drugs (brugadadrugs.org), fever, alcohol, cocaine, heavy meals [4][9]
17. Disposition
Admit (telemetry/ICU)
- Cardiac arrest survivor or documented sustained VT/VF
- Syncope with spontaneous type 1 Brugada ECG
- VF storm or recurrent ICD shocks
- Fever with new or known Brugada pattern (monitor until afebrile and ECG stable)
- Active drug intoxication unmasking Brugada pattern (TCA, cocaine) [14]
Observation
Discharge criteria
- Asymptomatic with drug-induced-only type 1 ECG after appropriate counseling [12]
- Known BrS patient with stable ICD, no acute triggers, and no new symptoms
- Fever-triggered pattern that has resolved with antipyretics and patient is afebrile
Specialist consultation triggers
- Electrophysiology: All newly diagnosed or suspected BrS patients
- Genetics: For genetic counseling and cascade family screening [12]
- Pediatric cardiology: Any pediatric presentation [19]
18. Follow Up / Return Precautions
Follow-up timing
- Electrophysiology follow-up within 1–2 weeks for newly diagnosed patients
- ICD patients: Device check per manufacturer schedule (typically every 3–6 months) [20]
- Annual cardiology follow-up for all BrS patients
Return precautions — seek immediate care for
- Syncope or near-syncope (especially at rest or during sleep)
- Palpitations with lightheadedness
- ICD shock (appropriate or inappropriate)
- Fever >38°C — take antipyretics immediately and present to ED if unable to control [9][13]
- Nocturnal agonal breathing witnessed by family
Patient counseling
- Register at brugadadrugs.org and check all new prescriptions against the drug list [9]
- Avoid cocaine, excessive alcohol, and cannabis [9][11]
- Inform all healthcare providers (including dentists and anesthesiologists) of diagnosis [2]
- Family members should be trained in CPR and AED use
- First-degree relatives should undergo ECG screening [12]
- Genetic counseling recommended for family planning [1]
Expected course: BrS is a lifelong condition. With appropriate trigger avoidance and ICD placement when indicated, long-term survival is excellent. The 10-year survival rate of cardiac arrest survivors with ICD is high, though ICD-related complications (inappropriate shocks, lead issues) are a significant concern given the young age of most patients. [13][20]
References
1. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the State of Genetic Testing for Cardiac Diseases. — Wilde AAM, Semsarian C, Márquez MF, et al. Heart Rhythm. 2022.
2. Present Status of Brugada Syndrome: JACC State-of-the-Art Review. — Brugada J, Campuzano O, Arbelo E, Sarquella-Brugada G, Brugada R. Journal of the American College of Cardiology. 2018.
3. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. — Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. Journal of the American College of Cardiology. 2018.
4. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. — Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. Journal of the American College of Cardiology. 2018.
5. Cardiomyopathy in Children: Classification and Diagnosis: A Scientific Statement From the American Heart Association. — Lipshultz SE, Law YM, Asante-Korang A, et al. Circulation. 2019.
6. Brugada Syndrome. — Brugada R, Campuzano O, Sarquella-Brugada G, et al GeneReviews® [Internet]. 2022.
7. 2012 ACCF/AHA/HRS Focused Update Incorporated Into the ACCF/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. — Epstein AE, DiMarco JP, Ellenbogen KA, et al. Journal of the American College of Cardiology. 2013.
8. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. — Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. Heart Rhythm. 2018.
9. Brugada Syndrome. — Krahn AD, Behr ER, Hamilton R, et al. JACC. Clinical Electrophysiology. 2022.
10. Inherited Heart Diseases. — Antoni Bayés De Luna, Miquel Fiol‐Sala, Antoni Bayés‐Genís, et al. Clinical Electrocardiography. 2021.
11. 2024 HRS Expert Consensus Statement on Arrhythmias in the Athlete: Evaluation, Treatment, and Return to Play. — Lampert R, Chung EH, Ackerman MJ, et al. Heart Rhythm. 2024.
12. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. — Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. Heart Rhythm. 2018.
13. Out-of-Hospital Cardiac Arrest in Apparently Healthy, Young Adults. — Tseng ZH, Nakasuka K. The Journal of the American Medical Association. 2025.
14. Drug-Induced Arrhythmias: A Scientific Statement From the American Heart Association. — Tisdale JE, Chung MK, Campbell KB, et al. Circulation. 2020.
15. Precision Medicine Approaches to Cardiac Arrhythmias: JACC Focus Seminar 4/5. — Giudicessi JR, Ackerman MJ, Fatkin D, Kovacic JC. Journal of the American College of Cardiology. 2021.
16. Sudden Death in the Young: Information for the Primary Care Provider. — Erickson CC, Salerno JC, Berger S, et al. Pediatrics. 2021.
17. HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients With Inherited Primary Arrhythmia Syndromes: Document Endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. — Priori SG, Wilde AA, Horie M, et al. Heart Rhythm. 2013.
18. ST-Segment Elevation in Conditions Other Than Acute Myocardial Infarction. — Wang K, Asinger RW, Marriott HJ. The New England Journal of Medicine. 2003.
19. 2021 PACES Expert Consensus Statement on the Indications and Management of Cardiovascular Implantable Electronic Devices in Pediatric Patients. — Writing Committee Members, Shah MJ, Silka MJ, et al. Heart Rhythm. 2021.
20. Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long-Term Follow-Up. — Hernandez-Ojeda J, Arbelo E, Borras R, et al. Journal of the American College of Cardiology. 2017.