asymptomatic patients with Brugada ECG findings have a low risk of future arrhythmic events. There is some evidence that electrophysiology testing combined with myocardial substrate electroanatomic mapping may be a way to more accurately predict inducible arrhythmias [69]; however, this has not been well studied. Insertable cardiac monitor For patients who have nonspecific symptoms for Brugada syndrome (eg, neurocardiogenic syncope, palpitations, or presyncope), the risk of life- threatening arrythmia may be uncertain; in such patients, an insertable cardiac monitor (ICM) may help elucidate a diagnosis. A registry study of 50 patients with Brugada syndrome treated with ICM demonstrated a 22 percent diagnostic yield [70]. The majority of these events were bradyarrhythmias, and only one patient had a concerning ventricular arrhythmia (nonsustained polymorphic ventricular tachycardia) [70]. (See "Ambulatory ECG monitoring", section on 'Insertable cardiac monitor'.) Genetic testing Genetic testing for a mutation in the SCN5A gene or other causative genetic variant should be performed in asymptomatic patients with a Brugada pattern ECG only when a definitive mutation has been identified within the family proband. The genetic and clinical heterogeneity of Brugada syndrome limit the utility of genetic testing, as the absence of a mutation in SCN5A or other pathogenic variant does not exclude Brugada syndrome, and the presence of such a variant does not confirm the diagnosis of Brugada syndrome. (See "Brugada syndrome or pattern: Management and approach to screening of relatives", section on 'Screening relatives'.) ALTERNATIVE APPROACHES AND OTHER GUIDELINE GROUPS Because of the clinical variability in presentation and the different ECG manifestations that can be seen in Brugada syndrome, diagnostic criteria have been proposed by professional societies https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 13/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate from both Europe and North America [3,14,39]. In 2013, three major professional societies, the Heart Rhythm Society (HRS), the European Heart Rhythm Association (EHRA), and the Asia Pacific Heart Rhythm Society (APHRS), jointly issued an expert consensus statement on inherited arrhythmia syndromes, which included updated diagnostic criteria for Brugada syndrome [3]. We broadly agree with this statement that suggests that Brugada syndrome should be "definitively diagnosed" with symptoms, and the presence of type I Brugada pattern ECG changes in at least one right precordial lead (specifically V1 or V2), either spontaneously or following drug challenge with a sodium channel blocker, using standard or superior ECG lead placement. (See 'Drug challenge for type 2 or equivocal ECG' above.) For a patient with type I Brugada pattern ECG findings who is otherwise asymptomatic, clinical findings that would support the diagnosis of Brugada syndrome include the following: Presence of first-degree atrioventricular block and left axis deviation on the ECG Atrial fibrillation (see 'Palpitations' above) Late potentials seen on signal-averaged ECG (SAECG) (see "Signal-averaged electrocardiogram: Overview of technical aspects and clinical applications") Fragmented QRS complex ST-T wave alternans with spontaneous ventricular premature beats in a left bundle branch block pattern on prolonged ECG recording Ventricular refractory period <200 milliseconds and HV (His bundle to ventricular myocardium) interval >60 milliseconds during invasive electrophysiology study Absence of structural heart disease, including myocardial ischemia We agree with the 2013 HRS/EHRA/APHRS consensus statement, which updated the 2005 criteria, but the original criteria continue to be frequently cited in clinical practice and more specifically define criteria to diagnose Brugada syndrome [14]. This includes the appearance of type 1 ST-segment elevation (coved type) in more than one right precordial lead (V1 to V2) in the presence or absence of a sodium channel blocker, plus at least one of the following: Documented ventricular fibrillation Polymorphic ventricular tachycardia Family history of sudden cardiac death at less than 45 years of age Family history of type 1 Brugada pattern ECG changes Inducible ventricular tachycardia during electrophysiology study Unexplained syncope suggestive of a tachyarrhythmia Nocturnal agonal respiration https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 14/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate DIFFERENTIAL DIAGNOSIS The differential diagnosis of Brugada syndrome includes conditions that have similar ECG findings with Brugada syndrome and/or conditions that have clinical features consistent with ventricular arrhythmia. Conditions with ECG similar to Brugada pattern The differential diagnosis for Brugada pattern ECG changes includes other conditions that result in apparent conduction and ST- segment abnormalities in leads V1 to V2 on the ECG. Arrhythmogenic right ventricular dysplasia The Brugada pattern on ECG can be seen as an early subclinical manifestation of arrhythmogenic right ventricular cardiomyopathy (ARVC) [64]. ARVC is a genetic disorder, usually autosomal dominant, that primarily involves the right ventricle, as the right ventricular myocardium is typically replaced by fat, with scattered residual myocardial cells and fibrous tissue. (See "Arrhythmogenic right ventricular cardiomyopathy: Pathogenesis and genetics".) A study of 96 victims of sudden cardiac death who were 35 years and had a baseline ECG available suggested an association between ARVC and the Brugada pattern on ECG [8]. Right precordial ST-segment elevation with or without right bundle branch block was present in 13 percent of patients; at autopsy, all but one had ARVC. However, this study was from southern Italy, where ARVC has a high prevalence and is an important cause of sudden cardiac death. Furthermore, mutations in SCN5A have not been described in ARVC but are a recognized cause of Brugada syndrome. (See "Brugada syndrome: Epidemiology and pathogenesis", section on 'SCN5A'.) Patients with ARVC often have abnormalities in the right ventricle that can be seen on echocardiography or cardiac magnetic resonance imaging. In contrast, the vast majority of patients with Brugada syndrome do not have apparent structural heart disease on routine imaging studies [14]. (See "Arrhythmogenic right ventricular cardiomyopathy: Diagnostic evaluation and diagnosis", section on 'Diagnostic evaluation'.) Other causes of ST changes in V1 to V2 These include: Right bundle branch block (see "Right bundle branch block", section on 'ECG findings and diagnosis') Early repolarization (see "Early repolarization", section on 'ECG findings') Acute pericarditis (see "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram') https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 15/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Acute myocardial ischemia or infarction (see "Electrocardiogram in the diagnosis of myocardial ischemia and infarction") Left ventricular hypertrophy (see "Left ventricular hypertrophy: Clinical findings and ECG diagnosis") Pectus excavatum (see "Pectus excavatum: Etiology and evaluation", section on 'Cardiac function') Hypothermia (see "ECG tutorial: Miscellaneous diagnoses", section on 'Hypothermia') Blunt chest trauma (eg, driver in an motor vehicle accident) Conditions causing ventricular arrythmia and no structural heart disease The differential diagnosis of Brugada syndrome includes a broad range of conditions in which there are clinical manifestations of ventricular tachyarrhythmias (ie, sudden cardiac death, syncope) and no apparent cardiac structural abnormalities. Congenital long QT syndrome (LQTS) Patients with a documented or suspected ventricular arrhythmia associated with prolongation of the QT interval are more likely to have LQTS than Brugada syndrome. Congenital LQTS should be suspected if the patient has no acquired cause of a long QT such as medications of electrolyte imbalance. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations".) Acquired LQTS with polymorphic ventricular tachycardia This diagnosis should be considered if the patient has a QTc prolongation or has been exposed to medications or other triggers, such as electrolyte imbalance, that may prolong the QT interval. Similarly, patients with ventricular tachycardia or sudden cardiac death whose QT interval is markedly shortened are more likely to have short QT syndrome. (See "Acquired long QT syndrome: Definitions, pathophysiology, and causes".) Short QT syndrome Patients with a documented or suspected ventricular arrhythmia associated with a short QT interval (usually <360 milliseconds with a range of 220 to 360 milliseconds) are more likely to have a short QT interval rather than Brugada syndrome. (See "Short QT syndrome".) Catecholaminergic polymorphic ventricular tachycardia Patients who experience ventricular tachycardia or sudden cardiac death in the setting of exertion are more likely to have catecholaminergic polymorphic ventricular tachycardia than Brugada syndrome, in which symptomatic tachyarrhythmias are more likely to occur at rest. (See "Catecholaminergic polymorphic ventricular tachycardia".) Commotio cordis Patients with ventricular tachycardia or sudden cardiac death immediately following blunt chest trauma are more likely to have experienced commotio cordis than Brugada https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 16/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate syndrome. Commonly, the blunt trauma is experienced during a sporting event by a projectile object (eg, baseball or hockey puck) traveling at a velocity greater than 20 miles per hour. Often, the patient collapses within two to three seconds of impact. (See "Commotio cordis".) Idiopathic ventricular tachycardia or fibrillation If patients undergo a thorough evaluation for Brugada syndrome and are not found to have spontaneous or drug-induced ECG findings consistent with Brugada syndrome or any other cause of ventricular arrythmia in the absence of structural heart disease, it is possible that idiopathic ventricular tachycardia or ventricular fibrillation are present. It is important to note that both of these are diagnoses of exclusion. (See "Ventricular tachycardia in the absence of apparent structural heart disease" and "Approach to sudden cardiac arrest in the absence of apparent structural heart disease", section on 'Idiopathic VF'.) PEDIATRIC PATIENTS Brugada syndrome is rarely diagnosed in children. In the largest international multicenter registry (SABRUS) of patients with Brugada syndrome with a documented first arrhythmic event, only 0.8 percent of patients were <16 years. [71]. Demographic features In a report from the SABRUS cohort, which included 57 patients age 20 years, pediatric patients (age 12 years) were more likely than adolescents (age 13 to 20 years) to be female (42 versus 13 percent) [72]. Clinical diagnosis and natural history The majority of children diagnosed with Brugada syndrome are identified based on family screening, whereas a smaller subset presented with a clinical event consistent with ventricular arrhythmia. This was illustrated in a cohort of 30 children with Brugada syndrome (mean age eight years) diagnosed at 13 referral centers in Europe [73]. In this study, 17 of 30 were diagnosed based on family screening, 10 had prior unexplained syncope, and one presented with aborted sudden cardiac death. The following are more common among pediatric compared with adolescent patients [72]: Spontaneous type I Brugada ECG pattern (81 versus 52 percent), Fever associated with their arrhythmic event (54 versus 7 percent). Recurrent events earlier Drug challenge Repeat ajmaline challenge following the development of puberty (in patients with a negative result prior to puberty) has been shown to unmask the Brugada https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 17/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate ECG pattern in asymptomatic relatives of Brugada syndrome patients [74]. (See 'Drug challenge for type 2 or equivocal ECG' above.) SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes".) SUMMARY AND RECOMMENDATIONS Background Brugada syndrome is a genetic disorder that can cause life-threatening ventricular tachyarrhythmias and thereby sudden cardiac arrest and sudden cardiac death; patients have abnormal findings on the surface electrocardiogram (ECG) but do not usually have any apparent cardiac structural abnormalities. (See 'Introduction' above.) Clinical manifestations Brugada syndrome is generally diagnosed between 22 and 65 years of age; it is rarely diagnosed in children. Most clinical manifestations of Brugada syndrome are related to life-threatening ventricular arrhythmias, most often ventricular fibrillation or polymorphic ventricular tachycardia. Patients may also present with syncope, palpitations, atrial fibrillation, nocturnal agonal respiration, or sudden unexpected nocturnal death. (See 'Clinical presentation' above.) Diagnostic evaluation Initial steps In all patients, we take a medical history, perform 12-lead ECG, and rule out any structural causes of heart disease. (See 'Initial steps to diagnose Brugada syndrome' above and 'Diagnostic evaluation' above.) Drug challenge if ECG is type 2 or equivocal If the initial evaluation for a patient does not reveal structural heart disease or myocardial ischemia, and the patient has spontaneous type 2 Brugada pattern or other equivocal ECG changes, we perform a drug challenge using a sodium channel blocker in an attempt to elicit the type 1 Brugada ECG pattern. (See 'Drug challenge for type 2 or equivocal ECG' above.) Further risk stratification in those with a negative drug challenge In patients with intermediate risk factors for Brugada syndrome, we undertake risk stratification in order to establish a diagnosis and decide therapy. (See 'Risk stratification for those with uncertain diagnosis' above.) https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 18/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate We suggest first evaluating with a signal-averaged ECG (SAECG) rather than other tests. If this test is negative, the likelihood of Brugada syndrome is much lower. (See 'Signal-averaged ECG (SAECG)' above.) If the SAECG is positive, we further evaluate with electrophysiologic testing for further risk stratification. (See 'Electrophysiology testing' above.) In some patients, we may use an insertable cardiac monitor (ICM) if there is suspicion of ventricular arrythmia that would indicate a diagnosis of Brugada syndrome, but this has not been yet confirmed. (See 'Insertable cardiac monitor' above.) Genetic testing for a mutation in the SCN5A gene or other causative genetic variant should be performed in asymptomatic patients with a Brugada pattern ECG only when a definitive mutation has been identified within the family proband. (See 'Genetic testing' above.) Differential diagnosis The differential diagnosis of Brugada syndrome includes conditions that have similar ECG findings with Brugada syndrome and/or conditions that have clinical features consistent with ventricular arrhythmia. (See 'Differential diagnosis' above.) Pediatric patients The majority of children diagnosed with Brugada syndrome are identified based on family screening, whereas a smaller subset presented with a clinical event consistent with ventricular arrhythmia. Pediatric patients are more likely to have a spontaneous type I Brugada ECG pattern and fever associated with their arrhythmic events. (See 'Pediatric patients' above.) 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Age of First Arrhythmic Event in Brugada Syndrome: Data From the SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) in 678 Patients. Circ Arrhythm Electrophysiol 2017; 10. 72. Michowitz Y, Milman A, Andorin A, et al. Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome. J Am Coll Cardiol 2019; 73:1756. 73. Probst V, Denjoy I, Meregalli PG, et al. Clinical aspects and prognosis of Brugada syndrome in children. Circulation 2007; 115:2042. 74. 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. Topic 106759 Version 31.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 25/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate GRAPHICS 12-lead electrocardiogram Brugada pattern Patient with Brugada pattern ECG. Note the presence of pseudo-right bundle branch block and persistent ST segment elevation in leads V1 to V2. ECG: electrocardiogram Courtesy of Ann C Garlitski, MD, FACC, FHRS. Graphic 122897 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 26/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Sinus tachycardia with ST segment changes due to fever in an 11- month-old child with Brugada syndrome (A) Electrocardiography demonstrating sinus tachycardia and ST segment changes triggered by fever in an 11-month-old child with Brugada syndrome. (B) Electrocardiography reverts to normal with the resolution of fever in the same patient. Graphic 100119 Version 3.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 27/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Drugs that can induce Brugada-like patterns on the surface electrocardiogram (ECG) Antiarrhythmic or antianginal drugs Cardiac sodium channel blockers (some have been used for drug challenge in patients with Brugada type 2 or 3 ECG pattern) Class IC drugs (flecainide, pilsicainide, propafenone) Class IA drugs (ajmaline, procainamide, disopyramide, cibenzoline) Lithium Calcium channel blockers Beta blockers Nitrates Nicorandil (a potassium channel opener) Psychotropic drugs Tricyclic antidepressants Amitriptyline Nortriptyline Desipramine Clomipramine Tetracyclic antidepressants Maprotiline Phenothiazines Perphenazine Cyamemazine Selective serotonin reuptake inhibitors Fluoxetine Other Dimenhydrinate Cocaine intoxication Alcohol intoxication Adapted from: 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. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 28/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Graphic 73611 Version 5.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 29/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Diagnostic approach to patients with intermediate or high suspicion for Brugada syndrome* ECG: electrocardiogram; VT: ventricular tachycardia. Brugada syndrome is suspected based on the combination of symptoms and typical Brugada pattern ECG changes (either type 1 or 2). Refer to related UpToDate content for further information. This is usually done with stress testing, echocardiography, and sometimes with cardiac magnetic resonance imaging. The presence of structural heart disease makes Brugada syndrome less likely and points to the structural heart disease as the probable diagnosis. A drug challenge typically involves giving a sodium channel- blocking medicine in an attempt to elicit the type 1 Brugada ECG pattern. Refer to related UpToDate content for further information. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 30/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Tests such as electrophysiologic studies and signal-averaged ECG can be used for further risk stratification and evaluation. Refer to related UpToDate content for further information. Graphic 141729 Version 1.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 31/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate ECG patterns of Brugada syndrome in leads V1-V2 (A) This typical coved pattern present in V1-V2 shows the following: 1. At the end of QRS, an ascending and quick slope with a high take-off 2 mm followed by concave or rectilinear downsloping ST. There are few cases of coved pattern with a high take-off between 1 and 2 mm. 2. There is no clear r' wave. 3. The high take-off often does not correspond with the J point. 4. At 40 milliseconds of high take-off, the decrease in amplitude of ST is 4 mm. In RBBB and athletes, it is much higher. 5. ST at high take-off N ST at 40 milliseconds N ST at 80 milliseconds. 6. ST is followed by negative and symmetric T wave. 7. The duration of QRS is longer than in RBBB, and there is a mismatch between V1 and V6. (B) This typical saddle-back pattern present in V1-V2 shows the following: 1. High take-off of r' (that often does not coincide with J point) 2 mm. 2. Descending arm of r' coincides with beginning of ST (often is not well seen). 3. Minimum ST ascent 0.5 mm. 4. ST is followed by positive T wave in V2 (T peak N ST minimum N 0) and of variable morphology in V1. 5. The characteristics of triangle formed by r' allow to define different criteria useful for diagnosis. angle. Duration of the base of the triangle of r' at 5 mm from the high take- off greater than 3.5 mm. 6. The duration of QRS is longer in BrP type 2 than in other cases with r' in V1, and there is a mismatch between V1 and V6. RBBB: right bundle branch block. https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 32/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Reproduced from: Bay s 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. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 91152 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 33/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Patterns of ST abnormalities in leads V1 to V3 in Brugada syndrome* Feature Type 1 Type 2 2 mm 2 mm J wave amplitude T wave Negative Positive or biphasic ST-T configuration Coved type Saddle back Elevated 1 mm ST segment (terminal portion) Gradually descending ECG: electrocardiographic. In contemporary studies of Brugada syndrome, the focus has generally been on ECG findings in leads V1 and V2 only. Modi ed with permission from: Wilde AA, Antzelevitch C, Borggrefe M, et al. Proposed diagnostic criteria for the Brugada syndrome. Eur Heart J 2002; 23:1648. Copyright 2002 Elsevier Science. Graphic 71258 Version 7.0 https://www.uptodate.com/contents/brugada-syndrome-clinical-presentation-diagnosis-and-evaluation/print 34/40 7/6/23, 11:28 AM Brugada syndrome: Clinical presentation, diagnosis, and evaluation - UpToDate Electrocardiogram (ECG) showing common right bundle branch block (RBBB) Electrocardiogram showing characteristic changes in the precordial leads in complete RBBB. The asynchronous activation of the two