Brugada syndrome: Clinical presentation, diagnosis, and evaluation
- John V Wylie, MD, FACC
John V Wylie, MD, FACC
- Assistant Professor of Medicine
- Tufts Medical School
- Ann C Garlitski, MD, FACC, FHRS
Ann C Garlitski, MD, FACC, FHRS
- Assistant Professor of Medicine
- Hofstra North Shore-LIJ School of Medicine
- Hofstra University
- Section Editors
- Scott Manaker, MD, PhD
Scott Manaker, MD, PhD
- Section Editor — Critical Care
- Professor of Medicine
- University of Pennsylvania School of Medicine
- Samuel Asirvatham, MD
Samuel Asirvatham, MD
- Section Editor — Long QT Syndrome
- Professor of Medicine and Pediatrics
- Mayo Clinic College of Medicine
The vast majority of cases of sudden cardiac arrest (SCA) and sudden cardiac death (SCD) are caused by ventricular tachyarrhythmias, with most of these associated with structural heart disease, particularly coronary heart disease. SCA in the apparently normal heart is an uncommon occurrence, accounting for only 5 to 10 percent of SCA cases. (See "Pathophysiology and etiology of sudden cardiac arrest".)
Some causes of SCA in patients with apparently normal hearts have been identified and include:
●Congenital long QT syndrome (LQTS) (see "Clinical features of congenital long QT syndrome")
●Acquired LQTS with polymorphic ventricular tachycardia (VT) (see "Acquired long QT syndrome")To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- 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: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932.
- Rodríguez-Mañero M, Namdar M, Sarkozy A, et al. Prevalence, clinical characteristics and management of atrial fibrillation in patients with Brugada syndrome. Am J Cardiol 2013; 111:362.
- Atarashi H, Ogawa S, Harumi K, et al. Characteristics of patients with right bundle branch block and ST-segment elevation in right precordial leads. Idiopathic Ventricular Fibrillation Investigators. Am J Cardiol 1996; 78:581.
- Matsuo K, Kurita T, Inagaki M, et al. The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome. Eur Heart J 1999; 20:465.
- Rodríguez-Mañero M, Sacher F, de Asmundis C, et al. Monomorphic ventricular tachycardia in patients with Brugada syndrome: A multicenter retrospective study. Heart Rhythm 2016; 13:669.
- Corrado D, Basso C, Buja G, et al. Right bundle branch block, right precordial st-segment elevation, and sudden death in young people. Circulation 2001; 103:710.
- Kakishita M, Kurita T, Matsuo K, et al. Mode of onset of ventricular fibrillation in patients with Brugada syndrome detected by implantable cardioverter defibrillator therapy. J Am Coll Cardiol 2000; 36:1646.
- Sacher F, Arsac F, Wilton SB, et al. Syncope in Brugada syndrome patients: prevalence, characteristics, and outcome. Heart Rhythm 2012; 9:1272.
- Bordachar P, Reuter S, Garrigue S, et al. Incidence, clinical implications and prognosis of atrial arrhythmias in Brugada syndrome. Eur Heart J 2004; 25:879.
- Morita H, Kusano-Fukushima K, Nagase S, et al. Atrial fibrillation and atrial vulnerability in patients with Brugada syndrome. J Am Coll Cardiol 2002; 40:1437.
- Kusano KF, Taniyama M, Nakamura K, et al. Atrial fibrillation in patients with Brugada syndrome relationships of gene mutation, electrophysiology, and clinical backgrounds. J Am Coll Cardiol 2008; 51:1169.
- Giustetto C, Cerrato N, Gribaudo E, et al. Atrial fibrillation in a large population with Brugada electrocardiographic pattern: prevalence, management, and correlation with prognosis. Heart Rhythm 2014; 11:259.
- Macedo PG, Brugada J, Leinveber P, et al. Sleep-disordered breathing in patients with the Brugada syndrome. Am J Cardiol 2011; 107:709.
- Kirschner RH, Eckner FA, Baron RC. The cardiac pathology of sudden, unexplained nocturnal death in Southeast Asian refugees. JAMA 1986; 256:2700.
- Gotoh K. A histopathological study on the conduction system of the so-called "Pokkuri disease" (sudden unexpected cardiac death of unknown origin in Japan). Jpn Circ J 1976; 40:753.
- Nademanee K, Veerakul G, Nimmannit S, et al. Arrhythmogenic marker for the sudden unexplained death syndrome in Thai men. Circulation 1997; 96:2595.
- 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.
- Vatta M, Dumaine R, Varghese G, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet 2002; 11:337.
- Probst V, Denjoy I, Meregalli PG, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007; 115:2042.
- Conte G, de Asmundis C, Ciconte G, et al. Follow-up from childhood to adulthood of individuals with family history of Brugada syndrome and normal electrocardiograms. JAMA 2014; 312:2039.
- Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J 2002; 23:1648.
- Bayés de Luna A, Brugada J, Baranchuk A, et al. Current electrocardiographic criteria for diagnosis of Brugada pattern: a consensus report. J Electrocardiol 2012; 45:433.
- Batchvarov VN, Govindan M, Macfarlane P, et al. Diagnostic utility of bipolar precordial leads during ajmaline testing for suspected Brugada syndrome. Heart Rhythm 2010; 7:208.
- Sangwatanaroj S, Prechawat S, Sunsaneewitayakul B, et al. New electrocardiographic leads and the procainamide test for the detection of the Brugada sign in sudden unexplained death syndrome survivors and their relatives. Eur Heart J 2001; 22:2290.
- Miyamoto K, Yokokawa M, Tanaka K, et al. Diagnostic and prognostic value of a type 1 Brugada electrocardiogram at higher (third or second) V1 to V2 recording in men with Brugada syndrome. Am J Cardiol 2007; 99:53.
- Alings M, Wilde A. "Brugada" syndrome: clinical data and suggested pathophysiological mechanism. Circulation 1999; 99:666.
- Chevallier S, Forclaz A, Tenkorang J, et al. New electrocardiographic criteria for discriminating between Brugada types 2 and 3 patterns and incomplete right bundle branch block. J Am Coll Cardiol 2011; 58:2290.
- Gottschalk BH, Garcia-Niebla J, Anselm DD, et al. Methods for Improving the Diagnosis of a Brugada ECG Pattern. Ann Noninvasive Electrocardiol 2016; 21:210.
- Pitzalis MV, Anaclerio M, Iacoviello M, et al. QT-interval prolongation in right precordial leads: an additional electrocardiographic hallmark of Brugada syndrome. J Am Coll Cardiol 2003; 42:1632.
- Bezzina C, Veldkamp MW, van Den Berg MP, et al. A single Na(+) channel mutation causing both long-QT and Brugada syndromes. Circ Res 1999; 85:1206.
- Clancy CE, Rudy Y. Na(+) channel mutation that causes both Brugada and long-QT syndrome phenotypes: a simulation study of mechanism. Circulation 2002; 105:1208.
- Grant AO, Carboni MP, Neplioueva V, et al. Long QT syndrome, Brugada syndrome, and conduction system disease are linked to a single sodium channel mutation. J Clin Invest 2002; 110:1201.
- Veltmann C, Schimpf R, Echternach C, et al. A prospective study on spontaneous fluctuations between diagnostic and non-diagnostic ECGs in Brugada syndrome: implications for correct phenotyping and risk stratification. Eur Heart J 2006; 27:2544.
- Cerrato N, Giustetto C, Gribaudo E, et al. Prevalence of type 1 brugada electrocardiographic pattern evaluated by twelve-lead twenty-four-hour holter monitoring. Am J Cardiol 2015; 115:52.
- Adler A, Topaz G, Heller K, et al. Fever-induced Brugada pattern: how common is it and what does it mean? Heart Rhythm 2013; 10:1375.
- Amin AS, Meregalli PG, Bardai A, et al. Fever increases the risk for cardiac arrest in the Brugada syndrome. Ann Intern Med 2008; 149:216.
- Krishnan SC, Josephson ME. ST segment elevation induced by class IC antiarrhythmic agents: underlying electrophysiologic mechanisms and insights into drug-induced proarrhythmia. J Cardiovasc Electrophysiol 1998; 9:1167.
- Brugada R, Brugada J, Antzelevitch C, et al. Sodium channel blockers identify risk for sudden death in patients with ST-segment elevation and right bundle branch block but structurally normal hearts. Circulation 2000; 101:510.
- Hong K, Brugada J, Oliva A, et al. Value of electrocardiographic parameters and ajmaline test in the diagnosis of Brugada syndrome caused by SCN5A mutations. Circulation 2004; 110:3023.
- Darbar D, Yang T, Churchwell K, et al. Unmasking of brugada syndrome by lithium. Circulation 2005; 112:1527.
- Konigstein M, Rosso R, Topaz G, et al. Drug-induced Brugada syndrome: Clinical characteristics and risk factors. Heart Rhythm 2016; 13:1083.
- Postema PG, Wolpert C, Amin AS, et al. Drugs and Brugada syndrome patients: review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org). Heart Rhythm 2009; 6:1335.
- Antzelevitch C, Yan GX, Ackerman MJ, et al. J-Wave syndromes expert consensus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 2016; 13:e295.
- Gray B, Behr ER. New Insights Into the Genetic Basis of Inherited Arrhythmia Syndromes. Circ Cardiovasc Genet 2016; 9:569.
- 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; 31:1357.
- Huang Z, Patel C, Li W, et al. Role of signal-averaged electrocardiograms in arrhythmic risk stratification of patients with Brugada syndrome: a prospective study. Heart Rhythm 2009; 6:1156.
- Tatsumi H, Takagi M, Nakagawa E, et al. Risk stratification in patients with Brugada syndrome: analysis of daily fluctuations in 12-lead electrocardiogram (ECG) and signal-averaged electrocardiogram (SAECG). J Cardiovasc Electrophysiol 2006; 17:705.
- Papavassiliu T, Veltmann C, Doesch C, et al. Spontaneous type 1 electrocardiographic pattern is associated with cardiovascular magnetic resonance imaging changes in Brugada syndrome. Heart Rhythm 2010; 7:1790.
- Priori SG, Napolitano C, Gasparini M, et al. Clinical and genetic heterogeneity of right bundle branch block and ST-segment elevation syndrome: A prospective evaluation of 52 families. Circulation 2000; 102:2509.
- Morita H, Morita ST, Nagase S, et al. Ventricular arrhythmia induced by sodium channel blocker in patients with Brugada syndrome. J Am Coll Cardiol 2003; 42:1624.
- Gasparini M, Priori SG, Mantica M, et al. Flecainide test in Brugada syndrome: a reproducible but risky tool. Pacing Clin Electrophysiol 2003; 26:338.
- Conte G, Sieira J, Sarkozy A, et al. Life-threatening ventricular arrhythmias during ajmaline challenge in patients with Brugada syndrome: incidence, clinical features, and prognosis. Heart Rhythm 2013; 10:1869.
- Calvo D, Rubín JM, Pérez D, et al. Time-dependent responses to provocative testing with flecainide in the diagnosis of Brugada syndrome. Heart Rhythm 2015; 12:350.
- Adler A, Rosso R, Chorin E, et al. Risk stratification in Brugada syndrome: Clinical characteristics, electrocardiographic parameters, and auxiliary testing. Heart Rhythm 2016; 13:299.
- Calò L, Giustetto C, Martino A, et al. A New Electrocardiographic Marker of Sudden Death in Brugada Syndrome: The S-Wave in Lead I. J Am Coll Cardiol 2016; 67:1427.
- 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.
- Gussak I, Antzelevitch C, Bjerregaard P, et al. The Brugada syndrome: clinical, electrophysiologic and genetic aspects. J Am Coll Cardiol 1999; 33:5.
- 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.
- Brugada P, Brugada R, Mont L, et al. Natural history of Brugada syndrome: the prognostic value of programmed electrical stimulation of the heart. J Cardiovasc Electrophysiol 2003; 14:455.
- Probst V, Veltmann C, Eckardt L, et al. Long-term prognosis of patients diagnosed with Brugada syndrome: Results from the FINGER Brugada Syndrome Registry. Circulation 2010; 121:635.
- Priori SG, Gasparini M, Napolitano C, et al. Risk stratification in Brugada syndrome: results of the PRELUDE (PRogrammed ELectrical stimUlation preDictive valuE) registry. J Am Coll Cardiol 2012; 59:37.
- Sroubek J, Probst V, Mazzanti A, et al. Programmed Ventricular Stimulation for Risk Stratification in the Brugada Syndrome: A Pooled Analysis. Circulation 2016; 133:622.
- Letsas KP, Liu T, Shao Q, et al. Meta-Analysis on Risk Stratification of Asymptomatic Individuals With the Brugada Phenotype. Am J Cardiol 2015; 116:98.
- Miura D, Nakamura K, Ohe T. Update on genetic analysis in Brugada syndrome. Heart Rhythm 2008; 5:1495.
- CLINICAL PRESENTATION
- Definition of Brugada pattern versus Brugada syndrome
- Sudden cardiac arrest and syncope
- Atrial fibrillation
- Nocturnal agonal respiration
- Sudden unexpected nocturnal death syndrome
- Features in children
- ECG findings
- - Type 1 versus Type 2
- - Variation of ECG findings over time
- - Provoking factors
- Medications and toxins
- 2013 HRS/EHRA/APHRS criteria
- 2005 HRS/EHRA criteria
- EVALUATION AND RISK STRATIFICATION
- Our approach to evaluation and risk stratification
- Testing for underlying heart disease
- Drug challenge
- - Drug challenge procedure
- Signal-averaged ECG
- 12-lead ECG
- Electrophysiology testing
- Genetic testing
- DIFFERENTIAL DIAGNOSIS
- Differential diagnosis of Brugada pattern ECG findings
- - Brugada ECG pattern in ARVC
- Differential diagnosis for VT or sudden death with a structurally normal heart
- SUMMARY AND RECOMMENDATIONS