Brugada Syndrome and CK Elevation: Management Approach
Direct Answer
CK elevation in Brugada syndrome patients is not a primary feature of the syndrome itself and should prompt immediate evaluation for alternative causes, particularly rhabdomyolysis, drug toxicity, or metabolic derangements that can unmask Brugada patterns—while simultaneously addressing any acute triggers that could precipitate life-threatening arrhythmias.
Understanding the Clinical Context
CK Elevation is Not a Feature of Brugada Syndrome
- Brugada syndrome is a primary electrical disorder characterized by coved ST-segment elevation in right precordial leads (V1-V3) with increased risk of sudden cardiac death in patients with structurally normal hearts 1.
- The syndrome involves ion channel dysfunction, predominantly SCN5A mutations affecting cardiac sodium channels, not myocardial injury that would elevate CK 1.
When CK Elevation Occurs: Consider Brugada Phenocopies
- Rhabdomyolysis with hyperkalemia can produce ECG patterns identical to congenital Brugada syndrome (Brugada phenocopies), which resolve when the underlying metabolic derangement is corrected 2.
- A case report documented a patient with heroin overdose, severe rhabdomyolysis (elevated CK), acute renal failure, and hyperkalemia (K+ 7.2 mmol/L) who presented with Brugada-like ECG changes in V1-V2 that resolved after bicarbonate administration and potassium normalization 2.
Immediate Management Algorithm
Step 1: Identify and Treat Reversible Causes
Check for metabolic triggers:
- Measure serum potassium, creatinine, and CK levels immediately 2.
- Severe hyperkalemia can produce Brugada phenocopy patterns that resolve with correction 2.
- Rhabdomyolysis requires aggressive IV hydration and monitoring for acute kidney injury 2.
Screen for toxic exposures:
- Cocaine, excessive alcohol, heroin, and other substances can both elevate CK and unmask/trigger Brugada patterns 1.
- These agents should be avoided in confirmed Brugada patients 1.
Step 2: Assess for Fever
- Fever is a critical trigger for ventricular fibrillation in Brugada syndrome and warrants early, aggressive antipyretic treatment 1.
- Fever triggered 27% of life-threatening arrhythmic events in pediatric Brugada patients 3.
- Even if CK elevation suggests another process (e.g., infection with myositis), aggressive fever management is mandatory 1, 4.
Step 3: Review Medication List
- Psychotropic medications, anesthetic agents, and sodium channel blockers can precipitate arrhythmias and should be discontinued if present 1.
- Refer to www.brugadadrugs.org for comprehensive drug avoidance list 1.
Risk Stratification in True Brugada Syndrome
High-Risk Features Requiring ICD
If the patient has confirmed Brugada syndrome (not phenocopy), assess:
- Spontaneous type 1 ECG pattern + recent syncope presumed due to ventricular arrhythmia = ICD indicated 4.
- Spontaneous type 1 pattern and symptoms at diagnosis are the strongest predictors of life-threatening arrhythmias 3.
- Annual arrhythmic event rates: 13.5% in cardiac arrest survivors, 3.2% in syncope patients, 1% in asymptomatic patients 4.
Alternative to ICD
- Quinidine is recommended for patients who decline or are not candidates for ICD (Class I recommendation) 4.
- A series showed no deaths during mean follow-up over 9 years with quinidine, though adverse effects occurred in 38% 1.
Distinguishing True Brugada from Phenocopy
Confirm Diagnosis with Proper ECG Technique
- Use high electrode positioning in second and third intercostal spaces to improve detection of type 1 pattern 1, 4.
- Type 1 pattern: coved ST-segment elevation ≥2 mm in V1 and/or V2 with negative T-waves 4.
Key Distinguishing Features
- True Brugada syndrome: ECG pattern may be intermittent, triggered by fever or vagotonic states, with family history of sudden death <50 years 5.
- Brugada phenocopy: ECG pattern resolves completely when the inciting medical condition (hyperkalemia, drug toxicity, rhabdomyolysis) is corrected 2.
Genetic Testing Considerations
- SCN5A mutations account for 20-30% of phenotype-positive Brugada cases 1, 4.
- In one pediatric study, all 9 patients with life-threatening arrhythmias who underwent genetic testing were genotype-positive, while 17 SCN5A-negative patients remained asymptomatic 3.
- Negative genetic testing does not exclude Brugada syndrome, as diagnosis is primarily clinical and electrocardiographic 1.
Practical Clinical Pitfalls
Common Mistake: Assuming CK Elevation is Cardiac-Specific
- CK elevation with Brugada-pattern ECG should trigger evaluation for rhabdomyolysis, not myocardial infarction, as Brugada patients have structurally normal hearts 1, 2.
Common Mistake: Failing to Aggressively Treat Fever
- Fever is a well-established trigger for sudden death in Brugada syndrome and requires immediate antipyretic therapy 1, 4, 3.
Common Mistake: Overlooking Drug-Induced Patterns
- Sodium channel blockers used for diagnostic provocation can cause marked QRS widening and should be terminated if ventricular arrhythmias develop 1.
Follow-Up Management
If Brugada Phenocopy (CK elevation with reversible cause):
- Serial ECGs to document resolution of Brugada pattern after metabolic correction 2.
- No long-term Brugada-specific therapy needed if pattern completely resolves 2.