2 or equivocal ECG'.) Management based on screening result The management of first-degree relatives of patients with Brugada syndrome depends on the results of screening. Positive results Screening may identify patients with both symptomatic Brugada syndrome and asymptomatic Brugada pattern ECGs. The management of relatives at this https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 12/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate point is similar to other patients determined to have suspected or confirmed Brugada syndrome. (See 'Risk factors for arrhythmia or sudden cardiac arrest' above and 'Management' above.) Negative results Screening may identify patients in whom Brugada syndrome (and Brugada pattern ECG) can be confidently excluded: First-degree relatives with no history of syncope and a normal ECG are considered to have a negative screening result. These patients should undergo repeat screening with a clinical history and ECG every one to two years until at least the fifth decade of life, since a Brugada ECG may not develop until later in life. (See 'Screening relatives' above.) Indeterminate results Screening may identify patients in whom Brugada syndrome (and Brugada pattern ECG) can neither be diagnosed nor confidently excluded. In such patients, additional testing or ongoing surveillance is needed. First-degree relatives with a history of syncope of suspected arrhythmic origin and a type 2 Brugada ECG pattern or a normal ECG should undergo drug-challenge testing. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) First-degree relatives with a concerning history of syncope but a normal-appearing ECG have an indeterminate screening result but may continue to have a high suspicion for the Brugada syndrome. Such patients should have ongoing screening with serial ECGs performed over three to four visits over the course of one to two years. First-degree relatives with indeterminate screening should also be considered for provocative testing with a pharmacologic challenge. A negative drug challenge has a specificity of 94 percent and negative predictive value of 83 percent in a similar population, and therefore a negative test makes Brugada syndrome unlikely, and ongoing screening is not mandatory in such patients [20]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge for type 2 or equivocal ECG'.) Since the diagnostic ECG changes of Brugada syndrome can appear later in life (in the fourth and fifth decade), symptomatic younger patients (ie, in their teens or 20s) with a first-degree relative with Brugada syndrome should continue to receive annual screening ECGs. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 13/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 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" and "Society guideline links: Cardiac implantable electronic devices".) SUMMARY AND RECOMMENDATIONS Risk factors for arrythmia of sudden cardiac arrest (SCA) The most important prognostic risk factors for patients with the Brugada electrocardiogram (ECG) pattern or Brugada syndrome are history of prior SCA, syncope from ventricular tachyarrhythmia, and/or documented sustained ventricular tachycardia. The risk of having a later ventricular arrhythmia is much lower in asymptomatic patients with Brugada pattern ECGs, although subgroups of asymptomatic patients with increased risk can be identified. (See 'Risk factors for arrhythmia or sudden cardiac arrest' above.) General measures If a patient has Brugada pattern ECG or Brugada syndrome, we counsel them to treat fevers with antipyretics, to avoid medications that provoke Brugada ECG changes, and to avoid excessive alcohol consumption. (See 'General measures in all patients' above.) Management of high-risk patients Treatment for patients diagnosed with the Brugada syndrome is primarily focused on prevention of SCA ( algorithm 1). (See 'Initial therapy with implantable cardiac defibrillator' above.) Initial therapy For patients with the Brugada syndrome who have survived SCA or those with a history of syncope from ventricular tachyarrhythmias, we recommend implantation of an implantable cardioverter-defibrillator (ICD) rather than antiarrhythmic drug therapy (Grade 1A). (See 'Initial therapy with implantable cardiac defibrillator' above.) Alternative initial therapy with antiarrhythmics In patients who refuse ICD implantation or are not considered a candidate for ICD implantation due to reduced life expectancy or significant comorbidities, we suggest initial therapy with either quinidine or amiodarone (Grade 2C). (See 'Alternative initial therapy with antiarrythmics' above.) High arrhythmic burden In patients with an ICD who have recurrent arrhythmias resulting in ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 14/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate the right ventricular outflow tract and right ventricular free wall. (Grade 2C). Therapy with quinidine or amiodarone is also an option. (See 'Catheter ablation' above.) Intermediate-risk patients For these patients, we perform shared decision-making and consider further risk stratification with signal-averaged ECG, electrophysiologic study, and possibly other tests in order to further guide therapy. (See 'Intermediate-risk patients' above and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Risk stratification for those with uncertain diagnosis'.) Patients with Brugada pattern ECG who are asymptomatic For patients with the Brugada ECG pattern who are otherwise asymptomatic and have none of the criteria that would suggest Brugada syndrome (ie, family history of sudden cardiac death [SCD] or type 1 Brugada ECG pattern), we recommend no treatment (Grade 1B). (See 'Intermediate-risk patients' above.) In these patients, we perform general measures. (See 'General measures in all patients' above.) First-degree relatives Since Brugada syndrome follows an autosomal dominant genetic pattern with variable penetrance, all first-degree relatives of patients with confirmed Brugada syndrome should undergo screening with a clinical history and 12-lead ECG. While provocative pharmacologic testing and genetic testing are available, we do not proceed with these tests as part of the screening process for the majority of patients. (See 'Screening relatives' above.) For first-degree relatives of a patient with Brugada syndrome who initially screen negative, we repeat screening with a clinical history and ECG every year, since a Brugada ECG may not develop until later in life. ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Ann Garlitski, MD, who contributed to earlier versions of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 15/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate 1. 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. 2. Probst V, Veltmann C, Eckardt L, et al. 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Long-term efficacy of low doses of quinidine on malignant arrhythmias in Brugada syndrome with an implantable cardioverter-defibrillator: a case series and literature review. Heart Rhythm 2012; 9:1995. 35. Yan GX, Antzelevitch C. Cellular basis for the Brugada syndrome and other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999; 100:1660. 36. Belhassen B, Glick A, Viskin S. Efficacy of quinidine in high-risk patients with Brugada syndrome. Circulation 2004; 110:1731. 37. Andorin A, Gourraud JB, Mansourati J, et al. The QUIDAM study: Hydroquinidine therapy for the management of Brugada syndrome patients at high arrhythmic risk. Heart Rhythm 2017; 14:1147. 38. Fernandes GC, Fernandes A, Cardoso R, et al. Ablation strategies for the management of symptomatic Brugada syndrome: A systematic review. Heart Rhythm 2018; 15:1140. 39. Pappone C, Brugada J, Vicedomini G, et al. Electrical Substrate Elimination in 135 Consecutive Patients With Brugada Syndrome. 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J Cardiovasc Electrophysiol 2014; 25:522. 42. Van Driest SL, Wells QS, Stallings S, et al. Association of Arrhythmia-Related Genetic Variants With Phenotypes Documented in Electronic Medical Records. JAMA 2016; 315:47. Topic 106760 Version 26.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 19/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate GRAPHICS 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. https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 20/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate RBBB: right bundle branch block. 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-or-pattern-management-and-approach-to-screening-of-relatives/print 21/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Outcome of patients with Brugada syndrome depends upon the clinical presentation In a study of 334 patients with the Brugada syndrome, the incidence of arrhythmic events (sudden cardiac death or documented ventricular fibrillation) during follow-up depended upon the clinical presentation. The outcome was best for those who were asymptomatic and presented with an abnormal ECG, intermediate for those presenting with syncope, and worst in patients with aborted sudden cardiac death. ECG: electrocardiogram. Data from: Brugada J, Brugada R, Antzelevitch C, et al. Circulation 2002; 105:73. Graphic 80714 Version 4.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 22/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Revised (2018) Vaughan Williams classification of antiarrhythmic drugs abridged table Class 0 (HCN channel blockers) Ivabradine Class I (voltage-gated Na+ channel blockers) Class Ia (intermediate dissociation): Quinidine, ajmaline, disopyramide, procainamide Class Ib (rapid dissociation): Lidocaine, mexilitine Class Ic (slow dissociation): Propafenone, flecainide Class Id (late current): Ranolazine Class II (autonomic inhibitors and activators) Class IIa (beta blockers): Nonselective: carvedilol, propranolol, nadolol Selective: atenolol, bisoprolol, betaxolol, celiprolol, esmolol, metoprolol Class IIb (nonselective beta agonists): Isoproterenol Class IIc (muscarinic M2 receptor inhibitors): Atropine, anisodamine, hyoscine, scopolamine Class IId (muscarinic M2 receptor activators): Carbachol, pilocarpine, methacholine, digoxin Class IIe (adenosine A1 receptor activators): Adenosine Class III (K+ channel blockers and openers) Class IIIa (voltage dependent K+ channel blockers): Ambasilide, amiodarone, dronedarone, dofetilide, ibutilide, sotalol, vernakalant Class IIIb (metabolically dependent K+ channel openers): https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 23/26 7/6/23, 11:27 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Nicorandil, pinacidil Class IV (Ca++ handling modulators) Class IVa (surface membrane Ca++ channel blockers): Bepridil, diltiazem, verapamil Class IVb (intracellular Ca++ channel blockers): Flecainide, propafenone Class V (mechanosensitive channel blockers): No approved medications Class VI (gap junction channel blockers) No approved medications Class VII (upstream target modulators) Angiotensin converting enzyme inhibitors Angiotensin receptor blockers Omega-3 fatty acids Statins HCN: hyperpolarization-activated cyclic nucleotide-gated; Na: sodium; K: potassium; Ca: calcium. Graphic 120433 Version 3.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 24/26 7/6/23, 11:28 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Consensus recommendations for implantable cardioverter-defibrillators (ICDs) in patients diagnosed with Brugada syndrome ECG: electrocardiogram; EP: electrophysiology; ICD: implantable cardioverter-defibrillator; SCD: sudden cardiac death; VF: ventricular fibrillation; VT: ventricular tachycardia. Reproduced from: Priori S, Wilde A, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes. Heart Rhythm 2013; 10:1932. Illustration used with the permission of Elsevier Inc. All rights reserved. Graphic 99533 Version 2.0 https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 25/26 7/6/23, 11:28 AM Brugada syndrome or pattern: Management and approach to screening of relatives - UpToDate Contributor Disclosures John V Wylie, MD, FACC No relevant financial relationship(s) with ineligible companies to disclose. Samuel Asirvatham, MD Grant/Research/Clinical Trial Support: Medtronic [Defibrillators]; St Jude's [Sudden Cardiac Death]. Consultant/Advisory Boards: BioTronik [Defibrillators]; Boston Scientific [Sudden Cardiac Death]. All of the relevant financial relationships listed have been mitigated. Nisha Parikh, MD, MPH No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/brugada-syndrome-or-pattern-management-and-approach-to-screening-of-relatives/print 26/26