Indian Pacing Electrophysiol. J.

ISSN 0972-6292


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Indian Pacing Electrophysiol. J. 2007;7(2):73-76                      Editorial

Approach to the asymptomatic patients with Brugada syndrome

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Masahiko Takagi, MD, Ph.D, Hiroaki Tatsumi, MD, and Minoru Yoshiyama, MD, Ph.D

Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 5458585, Japan

Address for correspondence: Masahiko Takagi, MD, Ph.D, Department of Internal Medicine and Cardiology, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka 5458585, Japan. E-mail: m7424580@msic.med.osaka-cu.ac.jp

Abstract

            Brugada syndrome is an arrhythmogenic disease characterized by an ECG pattern of coved-type ST segment elevation in the right precordial leads and an increased risk of sudden cardiac death (SCD) as a result of polymorphic ventricular tachyarrhythmia or ventricular fibrillation (VF). Data from large patient studies and a meta-analysis of previous reports have shown that patients with a history of syncope or SCD and a spontaneous type 1 Brugada ECG are at high risk for SCD. However, risk stratification of asymptomatic patients with Brugada type ECG is still a challenge. In particular, the use of electrophysiological study (EPS) for risk stratification remains controversial. Although some investigators have reported the possibility of use of EPS for distinguishing between high- and low-risk patients with Brugada type ECG, no precise predictor of risk for SCD in asymptomatic patients has yet been determined. The approach to treatment of these patients is thus still unclear. Large clinical prospective studies with uniform diagnostic criteria and protocols for EPS as well as extended follow-up periods of over ten years are required for prediction of SCD.

Key Words: Brugada syndrome, asymptomatic, sudden cardiac death, risk stratification


            Since its description in 19921, Brugada syndrome has been the focus of many clinical and research investigations as one of the leading causes of sudden cardiac death (SCD) in young adults. Recent large prospective studies have indicated that symptomatic patients with at least one episode of syncope or documented VF are at high risk of malignant ventricular tachyarrhythmias because of the high rate of recurrence of VF2-4. On the basis of this evidence, recommendations for treatment of this syndrome were described in the recently published consensus report5. The report recommends that symptomatic patients displaying type 1 (coved-type ST segment elevation ≥ 0.2 mV followed by a negative T wave) Brugada type ECG (either spontaneously or after sodium channel blockade) who present with aborted SCD and related symptoms such as syncope, seizure, or nocturnal agonal respiration should undergo placement of an implantable cardioverter defibrillator (ICD) after non-cardiac causes have been ruled out. However, risk stratification of asymptomatic patients with Brugada ECG is still a challenge.
 
Risk stratification of asymptomatic patients with Brugada ECG

            Some reports have noted the natural history of asymptomatic patients with Brugada type ECG. Data from the largest patient series have shown that 8% of patients without previous cardiac arrest had SCD or documented ventricular fibrillation during a mean follow-up of 24 months4. In that study, patients with syncope and family members of patients with Brugada syndrome were included. The risk of these events was highest in patients who were men, had suffered syncope, had a spontaneously abnormal type 1 Brugada type ECG, and had inducible ventricular tachyarrhythmias during electrophysiological study (EPS). Priori et al. found that 14% of patients with spontaneously abnormal Brugada type ECG (ST segment elevation ≥ 0.2 mV; whether type 1 ECG was observed was not specified) without previous syncope suffered cardiac arrest during a mean follow-up of 34 months, and that patients with spontaneously abnormal Brugada type ECG had relatively high risk of SCD2. In their study, family members of patients (35%) with Brugada syndrome were included. However, other studies reported a much lower risk of these events in asymptomatic patients6-9. Eckardt et al. found that only 0.8% of patients without previous cardiac arrest or syncope had SCD and documented ventricular fibrillation during a mean follow-up of 40 months6. They also reported that one of the significant predictors for risk of SCD was a spontaneously abnormal type 1 Brugada type ECG. In the three Japanese studies, as well, although numbers of patients were relatively small and diagnostic criteria differed (not all patients had type 1 ECG), only 0.4 - 0.5% of sporadic patients without previous cardiac arrest or syncope had SCD per year7-9.
            These findings suggest that, although the risk of SCD in sporadic asymptomatic patients may be much lower, a spontaneously abnormal type 1 Brugada ECG might be a predictor for SCD in these patients.
            Recent studies have suggested that combined noninvasive ECG markers may be helpful in risk stratification. Atarashi et al. reported the feasibility of risk stratification using the width of the S wave and ST segment elevation magnitude in the right precordial leads on surface ECG10. Some reports noted that signal-averaged ECG (SAECG) has been useful for identifying patients at high risk11,12. Other studies have suggested that circadian and daily fluctuations in ECG and SAECG could be useful for distinguishing between high- and low-risk patients13-15. The value of these markers in combination remains to be tested in a large prospective study.

Role of electrophysiological study in risk stratification

            The predictive value of inducibility of sustained ventricular arrhythmias during EPS is still controversial. Although Brugada et al. have supported the value of EPS based on the results for the largest series of patients4, two other large studies have not confirmed their findings2,6. Recently, Gehi et al. performed a meta-analysis of prognostic studies of patients with Brugada syndrome16. The results of their meta-analysis did not support the value of EPS as a predictor of cardiac events. The heterogeneity found in the value of EPS for risk stratification may be due to methodological differences in stimulation protocols and/or criteria for positive EPS2,6. A standard methodology is needed to determine the value of EPS for risk stratification in patients with Brugada syndrome17.

Therapeutic approach to asymptomatic patients with Brugada type ECG

            Currently, implantation of an ICD is the only effective treatment for this syndrome. However, various other treatments have been attempted to prevent SCD. Quinidine has been shown to be effective for prevention of SCD18-20. Tedisamil and isoproterenol have been reported to normalize the ST segment elevation in patients with this syndrome21,22. The phosphodiesterase III inhibitor, cilostazol, has also recently been reported to be useful23. However, the long-term efficacy of these treatments in preventing SCD is still unclear.
            For symptomatic patients with type 1 Brugada ECG (either spontaneously or after sodium channel blockade), ICD implantation is recommended in the report of the second consensus conference5. With regard to treatment of asymptomatic patients, the indications for use of ICD remain controversial. The report of the second consensus conference recommends ICD implantation for asymptomatic patients with a family history of SCD, type 1 Brugada ECG (either spontaneously or after sodium channel blockade), and inducible ventricular tachyarrhythmias during EPS. However, the meta-analysis of prognostic studies of patients with Brugada syndrome by Gehi et al. did not support the value of EPS and family history of SCD as predictors of cardiac events. For asymptomatic patients with spontaneous type 1 Brugada ECG without family history of SCD, the indications for treatment remain unclear, since the value of EPS is still controversial, as noted above. Asymptomatic patients with type 1 Brugada ECG after sodium channel blockade and without family history of SCD appear to be at low risk for SCD2.  Treatment is currently not recommended for these patients.
            There has been some lack of uniformity in the diagnostic criteria and protocols for EPS, and follow-up periods have been limited. Large clinical prospective studies with uniform diagnostic criteria and protocols for EPS as well as extended follow-up periods of over ten years are required for prediction risk of SCD in asymptomatic patients with Brugada syndrome.

References

1. 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;20:1391-1396.

2. Priori SG, Napolitano C, Gasparini M, et al.: Natural history of Brugada syndrome: insight for risk stratification and management. Circulation 2002;105:1342-1347.

3. Brugada J, Brugada R, Antzelevitch C, et al.: Long-term follow-up of individuals with the electrocardiographic pattern of right bundle-branch block and ST-segment elevation in precordial leads V1 to V3. Circulation 2002;105:73-78.

4. 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 2003;108:3092-3096.

5. 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 2005;111:659-670.

6. Eckardt L, Probst V, Smits JPP, et al.: Long-term prognosis of individuals with right precordial ST-segment-elevation Brugada syndrome. Circulation 2005;111:257-263.

7. Matsuo K, Akahoshi M, Nakashima E, et al.: The prevalence incidence and prognostic value of the Brugada-type electrocardiogram: A population-based study of four decades. J Am Coll Cardiol 2001;38:765-770.

8. Atarashi H, Ogawa S, Harumi K, et al.: Three-year follow-up of patients with right bundle branch block and ST-segment elevation in right precordial leads: Japanese Registry of Brugada Syndrome. Idiopathic Ventricular Fibrillation Investigators. J Am Coll Cardiol 2001;37:1916-1920.

9. Miyasaka Y, Tsuji H, Yamada K, et al.: Prevalence and mortality of the Brugada-type electrocardiogram in one city in Japan. J Am Coll Cardiol 2001;38:771-774.

10. Atarashi H, Ogawa S: Idiopathic Ventricular Fibrillation Investigator: New ECG criteria for high-risk Brugada syndrome. Circ J, 2003;67:8-10.

11. Ajiro Y, Hagiwara N, Kasanuki H: Assessment of markers for identifying patients at risk for life-threatening arrhythmic events in Brugada syndrome. J Cardiovasc Electrophysiol 2005;16:45-51.

12. Ikeda T, Sakurada H, Sakabe K, et al.: Assessment of noninvasive markers in identifying patients at risk in the Brugada syndrome: insight into risk stratification. J Am Coll Cardiol 2001;37:1628-1634.

13. Mizumaki K, Fujiki A, Tsuneda T, et al.: Vagal activity modulates spontaneous augmentation of ST elevation in the daily life of patients with Brugada syndrome. J Cardiovasc Electrophysiol 2004;15:667-673.

14. Ikeda T, Abe A, Yasu S, et al.: The full stomach test as a novel diagnostic technique for identifying patients at risk of Brugada syndrome. J Cardiovasc Electrophysiol 2006;17:602-607.

15. Tatsumi H, Takagi M, Nakagawa E, et al.: Risk stratification in patients with Brugada syndrome: Analysis of daily fluctuation in 12-lead electrocardiogram and signal-averaged electrocardiogram. J Cardiovasc Electrophysiol 2006;17:705-711.

16. Gehi AK, Duong TD, Metz LD, et al.: Risk stratification of individuals with the Brugada Electrocardiogram: A meta-analysis. J Cardiovasc Electrophysiol 2006;17:577-583.

17. Priori SG, Napolitano C: Should patients with an asymptomatic Brugada electrocardiogram undergo pharmacological and electrophysiological testing? Circulation 2005;112:285-291.

18. Belhassen B, Viskin S, Fish R, et al.: Effects of electrophysiologic-guided therapy with Class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome. J Cardiovasc Electrophysiol 1999;10:1301-1312.

19. Belhassen B, Viskin S, Antzelevitch C.:The Brugada syndrome: is an implantable cardioverter defibrillator the only therapeutic option? Pacing Clin Electrophysiol 2002;25:1634-1640.

20. Alings M, Dekker L, Sadee A, et al.: Quinidine induced electrocardiographic normalization in two patients with Brugada syndrome. Pacing Clin Electrophysiol 2001;24:1420-1422.

21. Antzelevitch C.:The Brugada syndrome: ionic basis and arrhythmia mechanisms. J Cardiovasc Electrophysiol 2001;12:268-272.

22. Tanaka H, Kinoshita O, Uchikawa S, et al.: Successful prevention of recurrent ventricular fibrillation by intravenous isoproterenol in a patient with Brugada syndrome. Pacing Clin Electrophysiol 2001;24:1293-1294.

23. Tsuchiya T, Ashikaga K, Honda T, et al.: Prevention of ventricular fibrillation by cilostazol, an oral phosphodiesterase inhibitor, in a patient with Brugada syndrome. J Cardiovasc Electrophysiol 2002;13:698-701.

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