eMedicine Specialties > Cardiology > Arrhythmias

Brugada Syndrome: Differential Diagnoses & Workup

Author: Jose M Dizon, MD, Associate Professor of Medicine and Surgery, Clinical Electrophysiology Laboratory, Division of Cardiology, Columbia University; Consulting Staff, Department of Medicine, New York-Presbyterian Hospital, Columbia University Medical Center
Coauthor(s): Deepak Saluja, MD, Fellow in Clinical Cardiac Electrophysiology, New York Presbyterian Hospital, Columbia Campus; Hugues Abriel, MD, PhD, Director, Department of Clinical Research, University of Bern, Switzerland
Contributor Information and Disclosures

Updated: Aug 24, 2009

Differential Diagnoses

Arrhythmogenic Right Ventricular Dysplasia (ARVD)
Hypothermia
Pericarditis, Acute
Pulmonary Embolism

Other Problems to Be Considered

The differential diagnosis of sudden cardiac death in an otherwise presumably healthy subject is varied, but includes such entities as acute cardiac ischemia due to atherosclerosis or coronary anomaly, hypertrophic cardiomyopathy, catecholaminergic polymorphic ventricular tachycardia, long QT syndrome, and arrhythmogenic right ventricular cardiomyopathy (ARVC). Many of these entities can be differentiated on the basis of history and physical examination. Occasionally, however, there is overlap that requires special consideration. 

The differential diagnosis of right precordial ST-segment elevation is as follows.9,18

Atypical right bundle branch block
Left ventricular hypertrophy
Early repolarization
Acute pericarditis
Acute myocardial ischemia or infarction
Prinzmetal angina
Pulmonary embolism
Dissecting aortic aneurysm
Mediastinal tumor or hemopericardium compressing the right ventricular outflow tract (RVOT)
Arrhythmogenic right ventricular dysplasia and/or cardiomyopathy
Various abnormalities of the central and autonomic nervous systems
Overdose of a heterocyclic antidepressant
Cocaine intoxication
Duchenne muscular dystrophy
Friedreich ataxia
Thiamine deficiency
Hypercalcemia
Hyperkalemia
Hypothermia
Pectus excavatum
Effects of athletic training

Workup

Laboratory Studies

  • Check serum potassium and calcium levels in patients presenting with ST-segment elevation in the right precordial leads because both hypercalcemia and hyperkalemia may generate an ECG pattern similar to that of Brugada syndrome.
  • Laboratory markers, such as creatine kinase-MB (CK-MB) and troponin, should be checked in patients who have acute symptoms compatible with a coronary artery syndrome.
  • Patients with high likelihood of the disease may be genetically tested for a mutation in SCN5A, which codes for the alpha subunit Nav 1.5 of the cardiac sodium channel.
    • The results of this test support the clinical diagnosis and are important for the early identification of family members at potential risk.
    • Mutations in SCN5A are found in only about 20-30% of index cases.

Imaging Studies

Echocardiography and/or MRI should be performed mainly to exclude arrhythmogenic right ventricular cardiomyopathy and also to assess for other potential causes of arrhythmias, such as hypertrophic cardiomyopathy, unsuspected myocardial injury, myocarditis, or aberrant coronary origins.

Other Tests

  • Exercise stress testing may suppress ECG changes and arrhythmias.
  • ECG: Three ECG patterns have been described in Brugada syndrome18 (see Media file 2).
ECG Patterns in Brugada Syndrome

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Table
CharacteristicType 1Type 2Type 3
J wave amplitude (mm)>2 mm>2 mm>2 mm
T waveNegativePositive or biphasicPositive
ST-T configurationCoved-typeSaddlebackSaddleback
ST segment, terminal portionGradually descendingElevated by
>1 mm		Elevated by
<1 mm
CharacteristicType 1Type 2Type 3
J wave amplitude (mm)>2 mm>2 mm>2 mm
T waveNegativePositive or biphasicPositive
ST-T configurationCoved-typeSaddlebackSaddleback
ST segment, terminal portionGradually descendingElevated by
>1 mm		Elevated by
<1 mm


  • Recently, the QRS duration on 12-lead ECG has been suggested as a risk marker for vulnerability to dangerous arrhythmias.19,20
  • Signal-averaged ECG: Arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome may be difficult to differentiate in some cases. Late potentials on signal-averaged ECG may reveal the fibrofatty degeneration of the right ventricle seen in ARVC.
  • Challenge with sodium channel blockers: In some patients, the intravenous administration of drugs that block sodium channels may unmask or modify the ECG pattern, aiding in diagnosis and/or risk stratification in some individuals.
    • Flecainide 2 mg/kg (maximum 150 mg) over 10 minutes, procainamide 10 mg/kg over 10 minutes, ajmaline 1 mg/kg over 5 minutes, or pilsicainide 1 mg/kg over 10 minutes may unmask or exaggerate the ST-segment elevation.
    • The sensitivity and specificity of this test is not yet confirmed.
    • This challenge should be performed with continuous cardiac monitoring and in a setting equipped for resuscitation.
    • In patients with a normal baseline ECG, the results are positive when the drug generates a J wave with an absolute amplitude of 2 mm or more in leads V1, V2, and/or V3 with or without an RBBB.
    • This drug test should not be performed in patients with a type 1 ECG pattern (see Table above) because it adds no information to that obtained with other tests.
    • In patients with the type 2 or 3 patterns, the drug challenge is recommended to clarify the diagnosis.9
    • Administration of the drug should be stopped when the result is positive, when ventricular arrhythmia occurs, or when QRS widening of greater than 30% is observed.
    • Isoproterenol and sodium lactate may be effective as antidotes if the sodium channel blocker induces an arrhythmia.

Procedures

Some investigators use electrophysiologic study (EPS) to determine the inducibility of arrhythmias in an effort to risk-stratify patients with  Brugada syndrome. However, the predictive value of this approach is debated. In 2002, Priori21 reported poor predictive value, whereas in 2001, Brugada22 showed that inducibility may be a good predictor of outcome. A study by Gehi concluded that EPS was not of use in guiding the management of patients with Brugada syndrome.23

More on Brugada Syndrome

Overview: Brugada Syndrome
Differential Diagnoses & Workup: Brugada Syndrome
Treatment & Medication: Brugada Syndrome
Follow-up: Brugada Syndrome
Multimedia: Brugada Syndrome
References
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References

  1. Frustaci A, Priori SG, Pieroni M, et al. Cardiac histological substrate in patients with clinical phenotype of Brugada syndrome. Circulation. Dec 13 2005;112(24):3680-7. [Medline].

  2. Martini B, Nava A, Thiene G, et al. Ventricular fibrillation without apparent heart disease: description of six cases. Am Heart J. Dec 1989;118(6):1203-9. [Medline].

  3. Brugada J, Brugada R, Brugada P. Determinants of sudden cardiac death in individuals with the electrocardiographic pattern of Brugada syndrome and no previous cardiac arrest. Circulation. Dec 23 2003;108(25):3092-6. [Medline].

  4. Brugada P, Brugada J. Right bundle branch block, persistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome. A multicenter report. J Am Coll Cardiol. Nov 15 1992;20(6):1391-6. [Medline].

  5. Vorobiof G, Kroening D, Hall B, et al. Brugada syndrome with marked conduction disease: dual implications of a SCN5A mutation. Pacing Clin Electrophysiol. May 2008;31(5):630-4. [Medline].

  6. Kusano KF, Taniyama M, Nakamura K, Miura D, Banba K, Nagase S, et al. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol. Mar 25 2008;51(12):1169-75. [Medline].

  7. Alings M, Wilde A. "Brugada" syndrome: clinical data and suggested pathophysiological mechanism. Circulation. Feb 9 1999;99(5):666-73. [Medline].

  8. Meregalli PG, Wilde AA, Tan HL. Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more?. Cardiovasc Res. Aug 15 2005;67(3):367-78. [Medline].

  9. Antzelevitch C, Brugada P, Brugada J, et al. Brugada syndrome: from cell to bedside. Curr Probl Cardiol. Jan 2005;30(1):9-54. [Medline].

  10. Nagase S, Kusano KF, Morita H, et al. Longer repolarization in the epicardium at the right ventricular outflow tract causes type 1 electrocardiogram in patients with Brugada syndrome. J Am Coll Cardiol. Mar 25 2008;51(12):1154-61. [Medline].

  11. Donohue D, Tehrani F, Jamehdor R, et al. The prevalence of Brugada ECG in adult patients in a large university hospital in the western United States. Am Heart Hosp J. Winter 2008;6(1):48-50. [Medline].

  12. Nademanee K, Veerakul G, Nimmannit S, et al. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation. Oct 21 1997;96(8):2595-600. [Medline].

  13. [Guideline] Antzelevitch C, Brugada P, Borggrefe M, et al. Brugada syndrome: report of the second consensus conference: endorsed by the Heart Rhythm Society and the European Heart Rhythm Association. Circulation. Feb 8 2005;111(5):659-70. [Medline].

  14. Bezzina CR, Shimizu W, Yang P, et al. Common sodium channel promoter haplotype in asian subjects underlies variability in cardiac conduction. Circulation. Jan 24 2006;113(3):338-44. [Medline].

  15. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation. Jan 30 2007;115(4):442-9. [Medline].

  16. London B, Michalec M, Mehdi H, Zhu X, Kerchner L, Sanyal S, et al. Mutation in glycerol-3-phosphate dehydrogenase 1 like gene (GPD1-L) decreases cardiac Na+ current and causes inherited arrhythmias. Circulation. Nov 13 2007;116(20):2260-8. [Medline].

  17. Watanabe H, Koopmann TT, Le Scouarnec S, Yang T, Ingram CR, Schott JJ. Sodium channel beta1 subunit mutations associated with Brugada syndrome and cardiac conduction disease in humans. J Clin Invest. Jun 2008;118(6):2260-8. [Medline].

  18. Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome: consensus report. Circulation. Nov 5 2002;106(19):2514-9. [Medline].

  19. Takagi M, Yokoyama Y, Aonuma K, Aihara N, Hiraoka M. Clinical characteristics and risk stratification in symptomatic and asymptomatic patients with brugada syndrome: multicenter study in Japan. J Cardiovasc Electrophysiol. Dec 2007;18(12):1244-51. [Medline].

  20. Junttila MJ, Brugada P, Hong K, et al. Differences in 12-lead electrocardiogram between symptomatic and asymptomatic Brugada syndrome patients. J Cardiovasc Electrophysiol. Apr 2008;19(4):380-3. [Medline].

  21. Priori SG, Napolitano C, Gasparini M, et al. Natural history of Brugada syndrome: insights for risk stratification and management. Circulation. Mar 19 2002;105(11):1342-7. [Medline].

  22. Brugada P, Geelen P, Brugada R, et al. Prognostic value of electrophysiologic investigations in Brugada syndrome. J Cardiovasc Electrophysiol. Sep 2001;12(9):1004-7. [Medline].

  23. Gehi AK, Duong TD, Metz LD, et al. Risk stratification of individuals with the Brugada electrocardiogram: a meta-analysis. J Cardiovasc Electrophysiol. Jun 2006;17(6):577-83. [Medline].

  24. Pelliccia A, Fagard R, Bjornstad HH, et al. Recommendations for competitive sports participation in athletes with cardiovascular disease: a consensus document from the Study Group of Sports Cardiology of the Working Group of Cardiac Rehabilitation and Exercise Physiology and the Working Group of Myocardial and Pericardial Diseases of the European Society of Cardiology. Eur Heart J. Jul 2005;26(14):1422-45. [Medline].

  25. Márquez MF, Salica G, Hermosillo AG, Pastelín G, Gómez-Flores J, Nava S, et al. Ionic basis of pharmacological therapy in Brugada syndrome. J Cardiovasc Electrophysiol. Feb 2007;18(2):234-40. [Medline].

  26. Márquez MF, Salica G, Hermosillo AG, Pastelín G, Cárdenas M. Drug therapy in Brugada syndrome. Curr Drug Targets Cardiovasc Haematol Disord. Oct 2005;5(5):409-17. [Medline].

  27. Yang F, Hanon S, Lam P, Schweitzer P. Quinidine revisited. Am J Med. Apr 2009;122(4):317-21. [Medline].

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Further Reading

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Keywords

Brugada syndrome, idiopathic ventricular fibrillation, idiopathic VFib, ventricular tachyarrhythmias, syncope, cardiac arrest, sudden death, sudden unexpected nocturnal death syndrome, SUNDS, SCN5A mutation, sodium channel blockers, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, heterocyclic antidepressants, glucose and insulin, hyperkalemia, hypokalemia, hypercalcemia, alcohol intoxication, cocaine intoxication

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Contributor Information and Disclosures

Author

Jose M Dizon, MD, Associate Professor of Medicine and Surgery, Clinical Electrophysiology Laboratory, Division of Cardiology, Columbia University; Consulting Staff, Department of Medicine, New York-Presbyterian Hospital, Columbia University Medical Center
Jose M Dizon, MD is a member of the following medical societies: American College of Cardiology and Heart Rhythm Society
Disclosure: Nothing to disclose.

Coauthor(s)

Deepak Saluja, MD, Fellow in Clinical Cardiac Electrophysiology, New York Presbyterian Hospital, Columbia Campus
Deepak Saluja, MD is a member of the following medical societies: Alpha Omega Alpha and Phi Beta Kappa
Disclosure: Nothing to disclose.

Hugues Abriel, MD, PhD, Director, Department of Clinical Research, University of Bern, Switzerland
Disclosure: Nothing to disclose.

Medical Editor

Justin D Pearlman, MD, PhD, ME, MA, Director of Advanced Cardiovascular Imaging, Professor of Medicine, Professor of Radiology, Adjunct Professor, Thayer Bioengineering and Computer Science, Dartmouth-Hitchcock Medical Center
Justin D Pearlman, MD, PhD, ME, MA is a member of the following medical societies: American College of Cardiology, American College of Physicians, American Federation for Medical Research, International Society for Magnetic Resonance in Medicine, and Radiological Society of North America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Ronald J Oudiz, MD, FACP, FACC, Associate Professor of Medicine, Division of Cardiology, The David Geffen School of Medicine at UCLA; Director, Liu Center for Pulmonary Hypertension, LA Biomedical Research Institute at Harbor-UCLA Medical Center
Ronald J Oudiz, MD, FACP, FACC is a member of the following medical societies: American College of Cardiology, American College of Chest Physicians, American College of Physicians, American Heart Association, and American Thoracic Society
Disclosure: Actelion Grant/research funds Clinical Trials + honoraria; Encysive Grant/research funds Clinical Trials + honoraria; Gilead Grant/research funds Clinical Trials + honoraria; Pfizer Grant/research funds Clinical Trials + honoraria; United Therapeutics Grant/research funds Clinical Trials + honoraria; Lilly Grant/research funds Clinical Trials + honoraria; LungRx  Clinical Trials + honoraria

CME Editor

Amer Suleman, MD, Consultant in Electrophysiology and Cardiovascular Medicine, Department of Internal Medicine, Division of Cardiology, Medical City Dallas Hospital
Amer Suleman, MD is a member of the following medical societies: American College of Physicians, American Heart Association, American Institute of Stress, American Society of Hypertension, Federation of American Societies for Experimental Biology, Royal Society of Medicine, and Society of Cardiac Angiography and Interventions
Disclosure: Nothing to disclose.

Chief Editor

Jeffrey N Rottman, MD, Professor of Medicine and Pharmacology, Director, Clinical Cardiac Electrophysiology Fellowship Program, Vanderbilt University School of Medicine; Chief, Department of Cardiology, Nashville Veterans Affairs Medical Center
Jeffrey N Rottman, MD is a member of the following medical societies: American Heart Association and North American Society of Pacing and Electrophysiology (NASPE)
Disclosure: Nothing to disclose.

 
 
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