Special Feature

The Brugada Syndrome

By William J. Brady, MD and Amal Mattu, MD

Introduction

The Brugada syndrome is a recently described cardiac disorder involving patients with structurally normal hearts who lack coronary artery disease and experience ventricular dysrhythmias.1-3 These patients present with sudden cardiac death, as well as characteristic electrocardiographic abnormalities when in sinus rhythm, including right bundle-branch block (RBBB) pattern and right precordial ST segment elevation (STE). In fact, this syndrome likely accounts for approximately 50% of patients with sudden death who lack organic heart disease.3 Brugada and Brugada initially described this presentation in 1992; they characterized the syndrome in a series of patients with the classic electrocardiographic findings who survived recurrent episodes of sudden cardiac death.1 Contrary to earlier reports focusing entirely on young Asian males, the Brugada syndrome is encountered in patients of multiple ethnic groups, in both genders, and in all age groups.2,4-6 It is, however, found to a significantly greater extent in Asian males, likely due to increased genetic transmission in these ethnic groupings.7

Clinical Spectrum

Patients with the Brugada syndrome experience symptomatic ventricular dysrhythmias, most often polymorphic ventricular tachycardia which degenerates into ventricular fibrillation.2 Patients present across a spectrum of initial severity, ranging from a history of syncope in the patient with normal sinus rhythm, to incessant, malignant ventricular dysrhythmia in the individual with active cardiac arrest. If the dysrhythmia is self-terminating, the patient will note dizziness or complain of syncope; in such instances, the clinician must be familiar with the "resting" electrocardiographic findings of RBBB and right precordial STE when the patient is in normal sinus rhythm. Alternatively, if the dysrhythmia continues, it ultimately will degenerate into ventricular fibrillation.

A familial occurrence has been observed in a segment of patients with the Brugada syndrome, suggesting a genetic component to the disease. Recent studies have confirmed a genetic predisposition; mutations in the gene SCN5A (which encodes for the cardiac sodium channel) have been identified in patients with the Brugada syndrome.2,8-10 The mutation produces an improperly functioning sodium channel. This sodium channel malfunction is intensified by increasing body temperature, is precipitated by certain drugs (particularly agents which effect the cardiac sodium channels), and is enhanced by various autonomic disturbances.11,12

Individuals with a family history of sudden cardiac death who demonstrate RBBB with right precordial ST segment elevation should be considered as possible Brugada syndrome patients. The clinician must realize that malignant ventricular dysrhythmias occur in up to one-third of initially asymptomatic patients within two years of the initial discovery of the syndrome features.7

ECG Findings in the Brugada Syndrome

The classic electrocardiographic findings include RBBB and STE in the right precordial leads (V1 to V3). (See Figures 1-3.) With increased physician awareness of the syndrome, variants in the original electrocardiographic presentations have been described. These variations, in fact, reflect minimal alteration from the original presentations. Patients may demonstrate an incomplete RBBB, STE in a more limited distribution (leads V1 to V2), and various forms of STE. Two types of STE morphologies have been described in the right precordial leads: convex ("coved") and concave ("saddle-type").3,4,13 (See Figures 2 and 3.) The electrocardiographic changes in the Brugada syndrome are not constant; in fact, these abnormalities have been known to change over time—ranging from alterations in the previously noted pattern to complete resolution.3,13 Dysrhythmias in the Brugada syndrome include ventricular tachycardia (monomorphic and polymorphic) and ventricular fibrillation; polymorphic ventricular tachycardia is the predominant form of ventricular tachycardia seen in this patient group. No electrocardiographic features are diagnostic of the Brugada syndrome when the patient is in a ventricular dysrhythmia.

Treatment and Disposition

Urgent therapy involves electrical defibrillation and other cardiorespiratory support; antiarrhythmic agents have proven to be of little benefit in the resuscitation phase of management. Furthermore, antiarrhythmic agents are of minimal value in chronic therapy.2,7

Admission to the hospital or same-day cardiology consultation are recommended. Electrophysiologic testing will confirm the diagnosis with induction of ventricular dysrhythmia. Further confirmation of the diagnosis is made by accentuation of the ST segment elevation with type I antiarrhythmic agents in the electrophysiology laboratory. Once the diagnosis is confirmed, patients must be treated with placement of an automatic internal cardioverter-defibrillator (AICD). With placement of an AICD, mortality has been avoided in all cases thus far.7 The reported mortality without appropriate therapy is approximately 30% within two years after the index presentation.2

Dr. Brady, Associate Professor of Emergency Medicine and Internal Medicine, Vice Chair, Emergency Medicine University of Virginia, Charlottesville, is on the Editorial Board of Emergency Medicine Alert. Dr. Mattu is assistant professor, Department of Surgery/Division of Emergency Medicine, University of Maryland, Baltimore.

References

1. Brugada P, et al. Right bundle-branch block, persistent ST segment elevation and sudden cardiac death: A distinct clinical and electrocardiographic syndrome. J Am Coll Cardiol 1992;20:1391-1396.

2. Brugada P, et al. The Brugada syndrome. Curr Cardiol Reports 2000;2:507-514.

3. Alings M, et al. "Brugada" syndrome—clinical data and suggested pathophysiological mechanism. Circulation 1999;99:666-673.

4. Monroe MH, et al. Two-year case collection of the Brugada syndrome electrocardiogram patterns at a large teaching hospital. Clin Cardiol 2000;23:849-851.

5. Hermida J, et al. Prevalence of the Brugada syndrome in an apparently healthy population. Amer J Cardiol 2000;86:91-94.

6. Priori SG, et al. Brugada syndrome and sudden cardiac death in children. Lancet 2000;355:808-809.

7. Brugada J, et al. The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death—The Brugada syndrome. Europace 1999;1: 156-166.

8. Chen Q, et al. Genetic basis and molecular mechanisms for idiopathic ventricular fibrillation. Nature 1998;392:293-296.

9. Bezzina C, et al. A single Na+ channel mutation causing both long-QT and Brugada syndrome. Circ Res 1999;85:1206-1213.

10. Rook MB, et al. Human SCN5A gene mutations alter cardiac sodium channel kinetics and are associated with the Brugada syndrome. Cardiovasc Res 1999;44: 507-517.

11. Goethals P, et al. Drug-induced Brugada syndrome. Acta Cardiol 1998;53:157-160.

12. Sao N, et al. A case of idiopathic ventricular fibrillation with possible mechanism of autonomic dysfunction. Jpn J Electrocardiol 1994;14:206-217.

13. Furuhashi M, et al. Prevalence of asymptomatic ST segment elevation in right precordial leads with right bundle branch block (Brugada-type ST shift) among the general Japanese population. Heart 2001;86:161-166.