Brugada Phenocopy: Conditions That Mimic Brugada ECG Pattern - A Critical Care Perspective

Dr Neeraj Manikath , claude.ai

Abstract

Background: Brugada phenocopy refers to clinical conditions that produce electrocardiographic patterns resembling Brugada syndrome but lack the underlying genetic basis and associated arrhythmic risk. Recognition of these conditions is crucial in the critical care setting where acute reversible causes are common.

Objective: To provide a comprehensive review of conditions causing Brugada phenocopy, with emphasis on critical care presentations, diagnostic approaches, and management strategies.

Methods: Systematic review of literature from 1992-2024 examining conditions that mimic Brugada ECG patterns.

Results: Brugada phenocopy encompasses a diverse spectrum of acquired conditions including metabolic disturbances, drug toxicities, mechanical factors, and acute illness states. Unlike true Brugada syndrome, these patterns are typically reversible with treatment of the underlying condition.

Conclusions: Critical care physicians must maintain high clinical suspicion for Brugada phenocopy in patients presenting with characteristic ECG changes, as prompt recognition and treatment of reversible causes can prevent inappropriate interventions and improve outcomes.

Keywords: Brugada phenocopy, electrocardiography, critical care, channelopathy, sudden cardiac death

Introduction

Brugada syndrome, first described by Pedro and Josep Brugada in 1992, is an inherited channelopathy characterized by a distinctive electrocardiographic pattern and increased risk of sudden cardiac death¹. The syndrome is defined by a coved-type ST-segment elevation ≥2mm in leads V1-V3, often accompanied by right bundle branch block morphology². However, similar ECG patterns can be observed in various acquired conditions, termed "Brugada phenocopy" by Baranchuk et al. in 2012³.

The distinction between true Brugada syndrome and Brugada phenocopy is critical, particularly in the intensive care unit where acute reversible conditions are prevalent. Misdiagnosis can lead to inappropriate implantable cardioverter-defibrillator (ICD) placement, unnecessary family screening, and failure to address treatable underlying pathology⁴.

This review examines the spectrum of conditions causing Brugada phenocopy, with particular emphasis on presentations encountered in critical care medicine.

Definition and Diagnostic Criteria

Brugada Phenocopy Definition

Brugada phenocopy is defined as a clinical condition that exhibits an ECG pattern identical or similar to Brugada syndrome but differs in the following aspects³:

Reversibility: ECG pattern normalizes with resolution of the underlying condition
No genetic basis: Absence of mutations in genes associated with Brugada syndrome
Different clinical presentation: Often associated with acute illness rather than idiopathic presentation
Lower arrhythmic risk: Generally not associated with increased sudden cardiac death risk

ECG Criteria

The characteristic ECG pattern includes:

Coved-type ST-segment elevation ≥2mm in leads V1-V3
Right bundle branch block pattern (may be incomplete)
QRS duration typically <120ms in phenocopy (vs often >120ms in true Brugada)
T-wave inversion in right precordial leads

🔹 Clinical Pearl:

The key distinguishing feature is reversibility - Brugada phenocopy ECG changes resolve when the underlying condition is treated, unlike true Brugada syndrome where the pattern may be persistent or only unmasked by provocative testing.

Classification of Brugada Phenocopy

Category 1: Metabolic and Electrolyte Disturbances

Hyperkalemia

Hyperkalemia is the most commonly reported cause of Brugada phenocopy⁵. The mechanism involves:

Enhanced potassium efflux during phase 1 of the cardiac action potential
Predominant effect on right ventricular epicardium
Creates transmural voltage gradient resembling Brugada pattern

Critical Care Relevance:

Common in acute kidney injury, rhabdomyolysis, tumor lysis syndrome
ECG changes may precede life-threatening arrhythmias
Pattern typically reverses with potassium normalization

Hyponatremia

Severe hyponatremia (typically <120 mEq/L) can produce Brugada-like patterns through:

Altered sodium channel function
Reduced sodium current during depolarization
Enhanced repolarization heterogeneity⁶

Hyperthermia

Fever and hyperthermia unmask Brugada patterns by:

Temperature-dependent sodium channel dysfunction
Enhanced transient outward potassium current (Ito)
Mechanism similar to flecainide challenge test⁷

🔹 Clinical Hack:

Always check core temperature in patients with new Brugada-like patterns - even mild fever (38-39°C) can unmask these changes in susceptible individuals.

Category 2: Pharmacological Causes

Sodium Channel Blockers

Class IA Antiarrhythmics:

Procainamide, quinidine, disopyramide
Dose-dependent effect
Particularly pronounced in overdose situations⁸

Class IC Antiarrhythmics:

Flecainide, propafenone
Used diagnostically in Brugada syndrome but can cause phenocopy in overdose

Other Sodium Channel Blockers:

Tricyclic antidepressants (amitriptyline, imipramine)
Local anesthetics (lidocaine, bupivacaine)
Antihistamines (diphenhydramine in overdose)

Calcium Channel Blockers

Primarily verapamil and diltiazem
Mechanism involves indirect effects on sodium channels
More common with intravenous administration⁹

Novel Agents

Recent case reports describe Brugada phenocopy with:

Propofol (particularly in prolonged infusions)¹⁰
Cannabis (likely related to cannabinoid receptor effects)¹¹
Cocaine (sodium channel blockade)¹²

🔹 Oyster:

Propofol-induced Brugada phenocopy is an under-recognized phenomenon in the ICU. Consider this diagnosis in sedated patients developing new right precordial ST elevation, especially with prolonged high-dose infusions.

Category 3: Mechanical and Structural Causes

Right Ventricular Outflow Tract Obstruction

Pulmonary embolism
Right heart catheterization
Pneumothorax (particularly tension pneumothorax)
Mechanical ventilation with high PEEP¹³

Mechanism:

Acute increase in right heart pressures
Altered ventricular activation sequence
Mechanical compression effects on conduction system

Pectus Excavatum

Mechanical compression of right ventricle
More pronounced in severe cases
Pattern may fluctuate with position¹⁴

Category 4: Ischemic Causes

Acute Coronary Syndromes

Right coronary artery occlusion
Acute anterior STEMI with right ventricular involvement
Mechanism involves regional ischemia affecting right ventricular conduction¹⁵

🔹 Clinical Pearl:

Always obtain a 15-lead ECG (including V7-V9 and right-sided leads) in patients with Brugada-like patterns to exclude acute coronary syndromes, particularly RCA occlusion.

Category 5: Infectious and Inflammatory

Myocarditis

Viral, bacterial, or autoimmune etiology
Inflammatory infiltration affects conduction system
May be associated with elevated troponins and imaging abnormalities¹⁶

COVID-19

Emerging reports of Brugada phenocopy in COVID-19 patients
Likely multifactorial: direct viral effects, cytokine storm, hypoxemia¹⁷

Category 6: Miscellaneous Conditions

Central Nervous System Pathology

Subarachnoid hemorrhage
Traumatic brain injury
Mechanism involves autonomic nervous system dysfunction¹⁸

Hypothyroidism

Severe hypothyroidism or myxedema coma
Affects sodium channel expression and function¹⁹

Diagnostic Approach in Critical Care

Initial Assessment

History:

Recent medication changes or overdoses
Symptoms of metabolic disturbances
Family history of sudden cardiac death
Previous ECGs for comparison

Physical Examination:

Signs of acute illness or toxicity
Evidence of mechanical factors (chest trauma, recent procedures)
Neurological status

Laboratory Evaluation

Essential Tests:

Complete metabolic panel (electrolytes, renal function)
Arterial blood gas analysis
Thyroid function tests
Toxicology screen
Cardiac biomarkers

Advanced Testing (if indicated):

Drug levels (digoxin, antiarrhythmics)
Inflammatory markers (CRP, ESR)
Blood cultures

Imaging Studies

Echocardiography:

Assess right heart function and pressures
Evaluate for structural abnormalities
Regional wall motion abnormalities

Chest Imaging:

Rule out pneumothorax, pulmonary embolism
Assess for pectus deformity
Pulmonary edema or infection

Advanced Imaging (selected cases):

CT pulmonary angiogram for PE
Cardiac MRI for myocarditis evaluation

🔹 Clinical Hack:

Create a "Brugada Phenocopy Checklist" for your ICU: 1) Check K+, Na+, temperature 2) Review medications 3) Assess for mechanical factors 4) Obtain echo 5) Compare to old ECGs. Most causes will be identified with this systematic approach.

Differential Diagnosis

True Brugada Syndrome vs. Phenocopy

Feature	True Brugada	Brugada Phenocopy
Onset	Often lifelong/genetic	Acute with underlying condition
Reversibility	Persistent or inducible	Resolves with treatment
Family History	Often positive	Typically negative
Arrhythmic Risk	High (3-15% annually)	Low (related to underlying condition)
QRS Duration	Often >120ms	Usually <120ms
Response to Fever	Pattern enhanced	May cause pattern
Genetic Testing	May be positive	Negative

Other Considerations

Right Bundle Branch Block:

May coexist but lacks ST elevation
Usually has different morphology

Arrhythmogenic Right Ventricular Cardiomyopathy:

May have similar ECG changes
Usually associated with structural abnormalities on imaging
Epsilon waves may be present

Acute Pericarditis:

Widespread ST elevation (not limited to V1-V3)
PR depression
Associated clinical syndrome

Management Strategies

Acute Management

Immediate Priorities:

Stabilize the patient: Address hemodynamic compromise
Identify and treat underlying cause: Based on systematic evaluation
Monitor for arrhythmias: Continuous cardiac monitoring
Avoid triggers: Discontinue offending medications

Specific Interventions by Category

Metabolic Correction

Hyperkalemia:

Emergent treatment if K+ >6.5 mEq/L or ECG changes
Calcium gluconate, insulin/glucose, beta-agonists
Definitive treatment: dialysis if severe

Hyponatremia:

Careful correction (avoid osmotic demyelination)
3% saline for severe symptomatic cases
Rate: <10-12 mEq/L in 24 hours

Temperature Management:

Active cooling for hyperthermia
Target normothermia
Treat underlying infection

Drug-Induced Cases

Discontinue offending agent
Supportive care for overdoses
Consider specific antidotes (e.g., sodium bicarbonate for TCA overdose)
Enhanced elimination if appropriate (dialysis for certain drugs)

Mechanical Causes

Treat pneumothorax: Chest tube placement
Pulmonary embolism: Anticoagulation, thrombolysis, or embolectomy
Optimize ventilator settings: Reduce PEEP if causing compression

🔹 Clinical Pearl:

For drug-induced Brugada phenocopy, the ECG pattern may persist for several half-lives after drug discontinuation. Don't rush to diagnose true Brugada syndrome if the pattern doesn't immediately resolve.

Long-term Management

True Brugada Syndrome Ruled Out

No ICD indicated based on phenocopy alone
Family screening not necessary
Focus on preventing recurrence of underlying condition
Patient education about triggers to avoid

Uncertain Cases

Cardiology consultation
Consider genetic counseling and testing
Pharmacological challenge testing (flecainide or ajmaline) may be considered after acute phase resolution
Family screening may be appropriate pending genetic results

Prognosis and Outcomes

Short-term Prognosis

Generally excellent when underlying condition is identified and treated
Arrhythmic risk is related to the underlying pathology rather than the ECG pattern itself
ECG normalization typically occurs within hours to days of treatment

Long-term Outcomes

Recurrence risk: Depends on prevention of underlying condition
Arrhythmic risk: Not elevated compared to baseline population
Quality of life: Generally not affected by the ECG pattern itself

🔹 Oyster:

Some patients with Brugada phenocopy may have underlying genetic susceptibility that predisposes them to manifest the pattern when stressed. Consider genetic counseling in recurrent cases or those with subtle family histories.

Special Populations

Pediatric Considerations

Fever is the most common trigger in children²⁰
Dehydration and electrolyte disturbances more common
Family history becomes more relevant
Different drug exposure patterns

Elderly Patients

Higher prevalence of polypharmacy
More susceptible to electrolyte disturbances
Underlying structural heart disease more common
Consider age-related changes in drug metabolism

Pregnancy

Physiological changes may influence presentation
Drug safety considerations for treatment
Hemodynamic changes may affect pattern
Genetic counseling implications for offspring

Future Directions and Research

Genetic Insights

Investigation of modifier genes that predispose to phenocopy
Polygenic risk scores for pattern development
Pharmacogenomics of drug-induced patterns

Diagnostic Advances

Artificial intelligence: Machine learning algorithms for pattern recognition
Advanced imaging: High-resolution mapping of electrical activity
Biomarkers: Novel markers to distinguish phenocopy from true syndrome

Therapeutic Innovations

Personalized medicine: Tailored treatments based on genetic profiles
Novel antiarrhythmics: Drugs with reduced proarrhythmic potential
Gene therapy: Potential future applications

Clinical Pearls and Practical Tips

🔹 Key Clinical Pearls:

"When in doubt, look for reversible causes" - The vast majority of Brugada-like patterns in the ICU are phenocopies
"Temperature matters" - Even mild fever can unmask patterns; always check core temperature
"Timing is everything" - Acute onset with concurrent illness strongly suggests phenocopy
"Potassium is king" - Hyperkalemia is the most common cause of Brugada phenocopy
"Right heart pressure" - Consider mechanical causes, especially after procedures or with respiratory distress

🔹 Practical Hacks:

"The Phenocopy Protocol":
- Step 1: Check electrolytes (especially K+)
- Step 2: Review medications and timing
- Step 3: Assess temperature
- Step 4: Look for mechanical factors
- Step 5: Compare to old ECGs
"The 24-48 Hour Rule": If ECG pattern doesn't improve within 48 hours of treating the presumed cause, consider true Brugada syndrome
"The Family History Filter": Strong family history of sudden death shifts probability toward true Brugada syndrome

🔹 Common Pitfalls:

Rushing to ICD placement without adequate evaluation for reversible causes
Overlooking drug interactions that may predispose to phenocopy
Ignoring subtle metabolic abnormalities (e.g., mild hyperkalemia in renal dysfunction)
Failing to repeat ECGs after treatment intervention

Conclusion

Brugada phenocopy represents a diverse group of acquired conditions that can mimic the ECG pattern of Brugada syndrome. For critical care physicians, recognition of these patterns and their underlying causes is essential for appropriate patient management. The key distinguishing features include acute onset in the setting of illness, reversibility with treatment of the underlying condition, and generally lower arrhythmic risk compared to true Brugada syndrome.

A systematic approach to evaluation, focusing on metabolic disturbances, drug effects, and mechanical factors, will identify the majority of cases. Prompt recognition and treatment of reversible causes can prevent inappropriate interventions and improve patient outcomes. As our understanding of these conditions continues to evolve, the critical care physician plays a vital role in the initial recognition and management of patients with Brugada phenocopy.

The distinction between phenocopy and true Brugada syndrome has profound implications for patient management, family counseling, and long-term prognosis. By maintaining high clinical suspicion and following a systematic diagnostic approach, critical care physicians can effectively manage these challenging cases and contribute to improved patient outcomes.

References

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.
Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference. Heart Rhythm. 2005;2(4):429-440.
Baranchuk A, Nguyen T, Ryu MH, et al. Brugada phenocopy: new terminology and proposed classification. Ann Noninvasive Electrocardiol. 2012;17(4):299-314.
Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm. 2013;10(12):1932-1963.
Ryu MH, Stephan Gooden E, Malik S, et al. Hyperkalemia-induced Brugada phenocopy: a systematic review. Europace. 2016;18(9):1289-1293.
García-Niebla J, Llontop-García P, Valle-Racero JI, et al. Technical mistakes during the acquisition of the electrocardiogram. Ann Noninvasive Electrocardiol. 2009;14(4):389-403.
Amin AS, Meregalli PG, Bardai A, et al. Fever increases the risk for cardiac arrest in the Brugada syndrome. Ann Intern Med. 2008;149(4):216-218.
Ortega-Carnicer J, Bertos-Polo J, Gutierrez-Tirado C. Aborted sudden death, transient Brugada pattern, and wide QRS dysrhythmias after massive cocaine ingestion. J Electrocardiol. 2001;34(4):345-349.
Korantzopoulos P, Liu T, Li G, et al. Brugada phenocopy due to a combination of calcium and sodium channel blocking agents. Cardiol J. 2010;17(1):73-75.
Cornara S, Somaschini A, Dembinski G, et al. Propofol and the Brugada syndrome: a dangerous relationship? Intensive Care Med. 2013;39(10):1827-1828.
Letsas KP, Efremidis M, Kounas SP, et al. MDMA-induced Brugada-type electrocardiographic pattern. Basic Clin Pharmacol Toxicol. 2009;105(6):424-427.
Rollin A, Maury P, Bongard V, et al. Prevalence, prognosis, and identification of the concealed form of the Brugada syndrome. Am J Cardiol. 2007;99(12):1677-1682.
Littmann L, Monroe MH, Kerns WP 2nd, et al. Brugada syndrome and "Brugada sign": clinical spectrum with a guide for the clinician. Am Heart J. 2003;145(5):768-778.
Calo L, Giustetto C, Martino A, et al. A new electrocardiographic marker to identify patients with Brugada syndrome: the S-wave in lead I. J Am Coll Cardiol. 2016;68(25):2704-2714.
Richter S, Sarkozy A, Paparella G, et al. Number of electrocardiogram leads displaying the diagnostic coved-type pattern in Brugada syndrome: a diagnostic consensus criterion to be revised. Eur Heart J. 2010;31(11):1357-1364.
Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation. 2005;112(24):3680-3687.
McCullough SA, Goyal P, Krishnan U, et al. Electrocardiographic findings in coronavirus disease-19: insights on mortality and underlying myocardial processes. J Card Fail. 2020;26(7):626-632.
Sugimura Y, Ishikawa T, Matsushita K, et al. Brugada-type electrocardiographic changes in acute central nervous system disorders. Circ J. 2008;72(4):694-696.
Dorr M, Wolff B, Grabow H, et al. Hypothyroidism and Brugada-like electrocardiographic pattern. Am J Cardiol. 2006;97(12):1793-1794.
Skinner JR, Chung SK, Nel CA, et al. Brugada syndrome masquerading as febrile seizures. Pediatrics. 2007;119(5):e1206-e1211.

Conflicts of Interest: None declared
Funding: None

Wednesday, September 17, 2025