What is the diagnostic approach for a patient suspected of having Brugada syndrome, presenting with symptoms such as syncope, palpitations, or chest pain, and potentially a family history of sudden cardiac death?

Diagnosis of Brugada Syndrome

Brugada syndrome is diagnosed by identifying a spontaneous type 1 ECG pattern (coved ST-segment elevation ≥2 mm in leads V1 and/or V2 with negative T-waves) in the absence of structural heart disease, particularly when accompanied by symptoms such as syncope, cardiac arrest, or a family history of sudden cardiac death. 1, 2

ECG Diagnostic Criteria

The cornerstone of diagnosis is the electrocardiogram:

• Type 1 Brugada pattern consists of coved ST-segment elevation ≥2 mm in right precordial leads V1 and/or V2, followed by a negative T-wave with no isoelectric separation 2, 1
• Position ECG leads in the second and third intercostal spaces (higher than standard placement) to improve detection sensitivity 3, 2
• The ECG pattern is dynamic and may be intermittent—it can appear and disappear spontaneously, requiring serial ECGs for diagnosis 1, 2
• A single normal ECG does not exclude the diagnosis 2

Critical distinction: Spontaneous type 1 pattern carries significantly worse prognosis than drug-induced pattern 2

Provocative Testing When ECG is Non-Diagnostic

If clinical suspicion exists but baseline ECG is normal or shows only type 2/3 pattern:

• Perform sodium channel blocker challenge using ajmaline, flecainide, procainamide, or pilsicainide 1, 2
• This unmasks the type 1 pattern in patients with concealed forms 1, 4
• Terminate the test immediately if ventricular arrhythmias, marked QRS widening (>130% of baseline), or type 1 pattern develops 2

Important caveat: Drug-induced pattern alone in asymptomatic patients indicates low risk and does not require chronic therapy 2

Clinical Context and History

Obtain detailed history focusing on:

• Personal symptoms: Syncope (especially at rest/sleep or with fever), aborted sudden cardiac death, documented ventricular arrhythmias, or unexplained seizures 1, 5
• Family history: Sudden cardiac death before age 50, unexplained drowning, Brugada syndrome diagnosis in relatives 1, 2
• Triggers: Episodes occurring during fever, vagotonic states (rest, sleep), or after certain medications 3, 2

Risk stratification based on presentation:

• Cardiac arrest survivors: 13.5% annual arrhythmic event rate 3, 6
• Syncope patients: 3.2% annual event rate 3, 6
• Asymptomatic patients: 1% annual event rate 3, 6

Syncope with spontaneous type 1 pattern confers 6-fold higher cardiac arrest risk compared to asymptomatic patients 2

Excluding Structural Heart Disease

Essential to rule out alternative diagnoses:

• Echocardiography to exclude structural abnormalities, particularly right ventricular abnormalities 1, 7
• Cardiac MRI may be needed to definitively exclude arrhythmogenic right ventricular cardiomyopathy or subtle structural disease 7
• Coronary angiography if acute coronary syndrome is in differential (particularly in older patients) 7

Genetic Testing and Family Screening

Genetic evaluation has limited diagnostic utility but important implications:

• SCN5A mutations account for only 20-30% of clinically diagnosed cases 3, 6, 2
• Negative genetic testing does not exclude Brugada syndrome—diagnosis remains primarily clinical and electrocardiographic 6, 5
• Genetic counseling and testing are reasonable (Class IIa) to facilitate cascade screening of first-degree relatives 1, 3
• In pediatric cohorts, all patients with life-threatening arrhythmias who underwent genetic testing were genotype-positive, while SCN5A-negative patients remained asymptomatic 5

Diagnostic Algorithm

Step 1: Obtain 12-lead ECG with standard and high precordial lead placement (V1-V2 in 2nd/3rd intercostal space) 3, 2

Step 2: If type 1 pattern present spontaneously → Diagnosis confirmed (proceed to risk stratification) 1, 2

Step 3: If ECG non-diagnostic but high clinical suspicion (syncope, family history, cardiac arrest) → Perform sodium channel blocker challenge 1

Step 4: Exclude structural heart disease with echocardiography ± cardiac MRI 1, 7

Step 5: Obtain serial ECGs, as pattern may be intermittent 1, 2

Step 6: Consider genetic testing for family screening purposes, not for diagnosis confirmation 1, 3

Common Pitfalls

The ECG pattern can be unmasked or exacerbated by:

• Fever (aggressive antipyretic treatment is critical) 3, 6, 5
• Sodium channel blocking drugs (antiarrhythmics, certain psychotropics, anesthetics) 3, 6
• Excessive alcohol intake 3, 6
• Cocaine use 3

The pattern can be normalized by:

• Beta-adrenergic stimulation 4
• Changes in autonomic tone 4

Do not rely on a single ECG—the pattern fluctuates and may require multiple recordings or Holter monitoring to capture 1, 2

In symptomatic patients (syncope, cardiac arrest) with spontaneous type 1 pattern, ICD implantation is Class I recommendation 1, 3, though this represents management rather than diagnosis.