INTRODUCTION — 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:
●Brugada syndrome
●Congenital long QT syndrome (LQTS) (see "Congenital long QT syndrome: Epidemiology and clinical manifestations")
●Acquired LQTS with polymorphic ventricular tachycardia (VT) (see "Acquired long QT syndrome: Definitions, pathophysiology, and causes")
●Catecholaminergic polymorphic VT (see "Catecholaminergic polymorphic ventricular tachycardia")
●Idiopathic VT (see "Ventricular tachycardia in the absence of apparent structural heart disease")
●Idiopathic ventricular fibrillation
●Short QT syndrome (see "Short QT syndrome")
●Commotio cordis (see "Commotio cordis")
The prognosis and management of the Brugada syndrome, along with the approach to screening first-degree relatives, will be reviewed here. The epidemiology, pathogenesis, clinical manifestations, evaluation, and diagnosis of the Brugada syndrome, along with a discussion of the other causes of SCA in apparently normal hearts, are discussed elsewhere. (See "Approach to sudden cardiac arrest in the absence of apparent structural heart disease" and "Brugada syndrome: Epidemiology and pathogenesis" and "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".)
PROGNOSTIC FACTORS — The most important prognostic risk factor for patients with the Brugada electrocardiographic (ECG) pattern or Brugada syndrome appears to be a history of ventricular tachyarrhythmias leading to sudden cardiac arrest (SCA) or syncope. Other less powerful predictors of future events may include atrial fibrillation, male gender, and a family history of SCA. For most asymptomatic patients, and particularly for those with only a drug-induced type 1 Brugada pattern ECGs, close clinical follow-up may be sufficient for management given the low overall risk of arrhythmic events.
History of sudden cardiac arrest or syncope — Patients with a previous history of SCA and those with a history of syncope (unexplained syncope suggestive of a tachyarrhythmia) are at increased risk for subsequent arrhythmic events compared with asymptomatic individuals [1-6].
●In a series of 1029 patients (72 percent male; median age 45 years at diagnosis) with Brugada pattern ECG in the FINGER (France, Italy, Netherlands, Germany) Registry (including 654 asymptomatic patients, 313 with prior syncope, and 62 with prior SCA) who were followed for a median of 32 months, patients with either prior SCA or a history of syncope were significantly more likely to experience a future arrhythmic event compared with asymptomatic patients (hazard ratio [HR] 11 for prior SCA; 95% CI 4.8-24.3, and HR 3.4 for syncope; 95% CI 1.6-7.4) [5].
●Similarly, in a series of 334 patients with the Brugada ECG pattern (71 presenting after cardiac arrest [group A], 73 after syncope [group B], and 190 with asymptomatic ECG findings [group C]) who were followed for a mean of 33 months, a new arrhythmic event (SCA or ventricular tachyarrhythmia) occurred in 62 and 19 percent of group A and B patients, while only 8 percent of group C patients had a first arrhythmic event (figure 1) [3].
Atrial fibrillation — Atrial fibrillation (AF) appears to occur more commonly in patients with the Brugada ECG pattern than in the general population. Additionally, patients with the Brugada ECG pattern who experience AF have a higher risk of future ventricular tachyarrhythmias. In a series of 73 patients with Brugada syndrome, AF occurred in 10 (14 percent) [7]. Patients with AF had a higher incidence of syncope (60 versus 22 percent of patients without AF) and ventricular fibrillation (40 versus 14 percent).
Other risk markers — Male gender, family history of SCA, and inferolateral ECG abnormalities may also be markers of increased risk in patients with a Brugada pattern ECG [1,2,8-12].
Asymptomatic patients — The risk of SCA is much lower in asymptomatic patients with Brugada pattern ECGs, although subgroups of asymptomatic patients with increased risk can be identified [1-4].
●In a review that included 422 asymptomatic patients with type 1 Brugada pattern ECGs, two features that were important determinants of arrhythmic risk were the spontaneous presence of the type 1 ECG pattern (compared with type 1 ECG pattern following drug challenge) and inducible ventricular tachycardia on invasive electrophysiology (EP) testing (table 1) [2]. At a mean follow-up of 24 months, event rates for patients with a spontaneous type 1 ECG and positive and negative EP testing results were 14 and 1.8 percent, respectively. Patients with the type 1 ECG abnormality only after drug challenge had markedly lower event rates (4.5 and 0.5 percent for those with positive and negative EP testing results, respectively). Similar findings were reported in a separate cohort of 421 patients, including 343 diagnosed with Brugada ECG pattern following drug challenge; over a median follow-up of 63 months, arrhythmic event rates were significantly higher among patients with spontaneous type 1 ECG findings (2.3 versus 1.1 percent per year in patients with drug-induced Brugada pattern) [13].
●In the FINGER Brugada registry, which included 1029 patients with Brugada pattern ECGs, the overall event rate for asymptomatic patients was quite low (0.5 percent per year). Neither spontaneous type 1 ECG nor positive EP studies were significantly predictive of arrhythmic outcomes (0.8 versus 0.4 percent for spontaneous ECG and 1.1 versus 0.4 percent for positive EPS) [5].
●In a multicenter European cohort of 106 patients diagnosed with Brugada pattern ECG prior to 19 years of age (mean age 11 years; 80 patients [75 percent] asymptomatic at time of diagnosis), only 10 patients developed a life-threatening arrhythmia over a median follow-up of 54 months; symptoms at diagnosis and the presence of a spontaneous type 1 Brugada ECG pattern were the predictors of life-threatening arrhythmias [14].
TREATMENT — Treatment for patients diagnosed with the Brugada syndrome (Brugada pattern ECG plus symptoms) is primarily focused around prevention of sudden cardiac arrest (SCA) and the termination of any ventricular tachyarrhythmias with an implantable cardioverter-defibrillator (ICD) [15,16]. Fever should be promptly treated with antipyretic agents, and patients should avoid medications known to increase the risk of ventricular arrhythmias in patients with Brugada pattern ECG (including some antiarrhythmic drugs, psychotropic drugs, anesthetic agents, etc; a full list is available at www.brugadadrugs.org) [17,18]. Initial pharmacologic therapy for ventricular tachyarrhythmia prevention has been tried in the Brugada syndrome with relatively little success, so ICD implantation should be the first line therapy for nearly all patients. However, patients with the Brugada syndrome who experience recurrent ventricular arrhythmias resulting in ICD shocks may require therapy with an antiarrhythmic drug in an effort to reduce the frequency of ICD shocks.
We approach treatment of patients with the sudden unexpected nocturnal death syndrome (SUNDS, also called sudden unexpected death syndrome or SUDS) in an identical fashion as patients with Brugada syndrome. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Sudden unexpected nocturnal death syndrome'.)
In contrast to patients with the Brugada syndrome or SUNDS, asymptomatic patients with only the Brugada ECG pattern do not require any specific therapy. One exception to this is patients with a strong family history of sudden cardiac arrest; such patients who undergo risk stratification with an invasive electrophysiology (EP) study and are deemed to be at high risk of SCD may be candidates for an ICD, as discussed in a 2013 HRS/EHRA/APHRS expert consensus statement, though this approach remains controversial [19].
Symptomatic patients with Brugada syndrome
Our approach to treatment — For patients with the Brugada syndrome who have survived sudden cardiac arrest or those with a history of syncope that is felt to be due to ventricular tachyarrhythmias, we recommend implantation of an ICD rather than antiarrhythmic drug therapy. This recommendation is consistent with society guidelines published in 2013 and 2017 (algorithm 1) and endorsed by numerous professional societies worldwide [19,20]. Therapy with an ICD is well-documented to be safe and highly effective at terminating ventricular tachyarrhythmias, both in patients with the Brugada syndrome as well as other conditions associated with an increased risk of sudden cardiac death. (See 'ICD therapy' below and "Primary prevention of sudden cardiac death in patients with cardiomyopathy and heart failure with reduced LVEF" and "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".)
Antiarrhythmic drug therapy in patients with the Brugada syndrome who have survived sudden cardiac arrest or those with a history of syncope that is felt to be due to ventricular tachyarrhythmias may be considered in two circumstances (see 'Drug therapy' below):
●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, although catheter ablation is also an option.
●In patients with an ICD who have recurrent arrhythmias resulting in ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in the right ventricular outflow tract and right ventricular free wall. Therapy with quinidine or amiodarone is also an option [20]. (See 'Catheter ablation' below.)
Medications to avoid — Other than quinidine, class I antiarrhythmic drugs (table 2), particularly sodium channel blockers, may be deleterious and should not be used for therapy. Sodium channel blockers, such as flecainide, ajmaline, or procainamide, can transiently induce the characteristic type 1 ECG changes and are frequently used as part of a drug challenge to diagnose the Brugada ECG pattern [21-25]. In addition, sodium channel blockade can induce ventricular premature beats or VT in patients with Brugada syndrome, particularly in symptomatic patients (6 of 10 in one report) [26]. Certain psychotropic drugs can also cause sodium channel blockade and potentially precipitate arrhythmias, including tricyclic antidepressants, lithium, and oxcarbazepine, and these medications should be avoided. During anesthesia, procaine, bupivacaine, and prolonged propofol infusion, should also be avoided. A full list of drugs to be avoided can be found at www.brugadadrugs.org. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge'.)
ICD therapy — ICDs are safe and effective for terminating life-threatening arrhythmias in patients with the Brugada syndrome [19,22,27-29]. While several studies have looked at the effectiveness of ICD therapy specifically in patients with the Brugada syndrome, there are no randomized trials comparing ICDs with antiarrhythmic drug therapy (or no drug therapy) in patients with Brugada syndrome.
●The Survey on Arrhythmic Events in Brugada Syndrome (SABRUS) collected data from a large multicenter international cohort of 678 patients [28]. The study objective was to compare patients with aborted cardiac arrest (group A) with patients in whom the first arrhythmic event followed prophylactic ICD implantation (group B). Group B patients experienced an arrhythmic event almost seven years later and had a higher incidence of family history of sudden cardiac death and SCN5A mutations. Only 75 percent of patients who exhibited an arrhythmic event after receiving a prophylactic ICD complied with the 2013 class II indications, suggesting that efforts are still required for improving risk stratification to account for the 25 percent who did not.
●Among 258 patients with Brugada pattern ECG (62 percent with symptomatic Brugada syndrome) in a multicenter registry who received an ICD and were followed for an average of 2.5 years, 69 patients (27 percent) received at least one appropriate ICD shock during follow-up [22].
●In one series of 378 patients with type 1 Brugada ECG findings (spontaneous in 60 percent, inducible in 40 percent) in which 212 patients (56 percent) were symptomatic with Brugada syndrome at presentation, appropriate ICD therapy for arrhythmic events at 10 years occurred in 48 percent of patients who had a history of SCA and 19 percent of patient with syncope prior to ICD implantation [30]. Thus, in this heterogeneous cohort of BS patients, which included patients with a provocable (as opposed to spontaneous) type 1 Brugada pattern ECG, overall event rates remain high in patients with a history of syncope or SCA.
●In a series of 35 pediatric patients ≤20 years of age (mean age 14 years, 92 percent symptomatic) who underwent ICD implantation and were followed for an average of 88 months, nine patients (26 percent) received appropriate ICD therapy, seven patients (20 percent) experienced inappropriate shocks, and five patients (14 percent) had a device complication (three lead fractures, one lead dislodgement, and one pulse generator migration) [31].
●In a 2019 meta-analysis, which included 1539 patients from 28 nonrandomized studies (mean age 45 years, 18 percent female, 79 percent receiving the ICD for primary prevention) with a mean follow-up of 4.9 years, the rates of appropriate and inappropriate ICD shocks were similar (3.1 and 3.3 per 100 patient-years, respectively), with a very low cardiac mortality rate of 0.03 per 100 patient-years [32]. The rate of inappropriate therapies is similar to the rate reported (4.7 percent) in a review of patients with any inherited arrhythmia syndrome [33].
ICD therapy is also beneficial for patients with sudden unexpected nocturnal death syndrome (SUNDS). In the DEBUT trial, which randomized 66 patients who were considered definite or probable SUNDS survivors to treatment with an ICD or beta blockers, the trial was prematurely terminated after a mean follow-up of 24 months because of four deaths in the beta blocker arm, compared with none in the ICD arm [34]. Seven patients in the latter group had recurrent ventricular fibrillation (VF) that was appropriately terminated by the ICD.
Catheter ablation — We consider radiofrequency catheter ablation as an option for patients with a Brugada syndrome and significant arrhythmic burden in whom antiarrhythmic drugs have failed. Ablation may also be considered as first line therapy in patients with a large arrhythmia burden. Radiofrequency ablation of the right ventricular substrate in these patients should be performed at centers experienced in epicardial mapping and ablation.
Radiofrequency catheter ablation for ventricular arrhythmias in patients with the Brugada syndrome can effectively reduce the burden of ventricular arrhythmias and is endorsed as a treatment option (along with quinidine) for patients with or without an ICD who experience recurrent ventricular tachyarrhythmias [20]. In the largest single-cohort study of catheter ablation in 135 symptomatic patients with Brugada syndrome, epicardial mapping revealed large areas of arrhythmogenic substrate in the right ventricular epicardium over the right ventricular outflow tract and right ventricular free wall, and the size of these areas increased after administration of ajmaline [35]. Ablation of all areas of fractionated potentials lead to ECG normalization and rendered VT and VF noninducible in all patients. In a subsequent systematic review that included 22 nonrandomized studies (totaling 233 patients) of catheter ablation for symptomatic Brugada syndrome, the combination of epicardial and endocardial mapping with substrate ablation (180 patients) was the most successful technique, with over 98 percent of patients having elimination of the type I Brugada ECG changes and over 96 percent remaining free of VT at follow-up (ranging from 6 to 41 months) [36].
Drug therapy — Quinidine and amiodarone are two antiarrhythmic options for the treatment of ventricular tachyarrhythmias in patients with the Brugada syndrome who have recurrent arrhythmias resulting in ICD shocks, or for patients who are not candidates for (or refuse) ICD implantation [19,37,38]. In contrast to the known benefits of ICD for the termination of ventricular arrhythmias and prevention of sudden cardiac death (SCD), there are no proven pharmacologic treatments for preventing SCD in the Brugada syndrome, although there are data suggesting a benefit from quinidine and the efficacy of amiodarone is indirectly extrapolated from other ventricular tachyarrhythmia syndromes. While either drug may be effective, we suggest initial adjunctive therapy with quinidine for most patients, particularly younger patients in whom there is a desire to avoid the potential toxicities associated with long-term amiodarone.
We use the following doses when prescribing therapy with quinidine or amiodarone:
●Quinidine – 1 to 1.5 g/day of quinidine sulfate or 600 to 900 mg/day of hydroquinidine (not available in the US), typically divided into two or three equal daily doses. Small studies have suggested that lower doses of quinidine (300 to 600 mg/day) may be effective in some patients [38].
●Amiodarone – 200 mg daily after an appropriate initial loading dose (typically 400 mg twice or three times daily for one to two weeks).
Quinidine — The potential efficacy of quinidine has been illustrated only in small series of patients. In a report in which invasive EP testing was performed on 25 patients with Brugada pattern ECGs (15 symptomatic and 10 asymptomatic) before and after treatment with quinidine bisulfate (mean dose 1483±240 mg per day) [37], VF was inducible in all patients at baseline but in only three patients after quinidine loading. In the 19 patients who continued treatment with quinidine for an average of 56 months, none had a ventricular arrhythmia or syncope which appeared arrhythmic in origin. In another small study of 50 patients who completed a 36-month, double blind, placebo-controlled study of hydroquinidine (with crossover to the other group for all patients at 18 months), there were no arrhythmic events in the hydroquinidine group while on treatment, but 13 patients (26 percent) stopped treatment due to side effects [39]. The beneficial effect of quinidine is postulated to be mediated by blockade of Ito, the transient outward current, which increases heterogeneity and may promote ventricular premature beats that act as the trigger for ventricular tachycardia (VT)/VF [40].
Amiodarone — Amiodarone is the most effective agent for the prevention of ventricular tachyarrhythmias, although there are more potential side effects with its use than with most other antiarrhythmic agents, particularly in younger patients in whom therapy might be expected to last for decades. The efficacy of amiodarone is discussed in greater detail elsewhere. (See "Amiodarone: Clinical uses" and "Amiodarone: Adverse effects, potential toxicities, and approach to monitoring".)
Complications of therapy — Because patients with the Brugada syndrome who require ICD therapy are frequently relatively young, there are concerns regarding the long-term risk of ICD-related complications in this population [30,41]. Among a cohort of 378 patients with the Brugada syndrome (mean age 46 years, 82 percent male) who received an ICD and were followed for an average of 77 months, 37 percent experienced an inappropriate shock and 29 percent had a lead complication [30]. A 2019 meta-analysis reported an inappropriate ICD shock rate of 3.3 percent [32]. This highlights the importance of risk-benefit analysis and informed discussion with the patient prior to ICD placement, particularly for patients felt to be a low risk or for those who remain asymptomatic. In these patients, therapy with a subcutaneous ICD system may reduce the risk of lead complications, though this has not been studied in this population. (See "Subcutaneous implantable cardioverter defibrillators".)
Asymptomatic patients with the Brugada ECG pattern — For patients with the Brugada ECG pattern who are otherwise asymptomatic and have none of the criteria that would suggest Brugada syndrome (ie, no personal history of ventricular tachyarrhythmias or syncope suspected to be arrhythmic in origin, and no family history of sudden cardiac death or type 1 Brugada ECG pattern), we recommend no treatment. This recommendation, which is consistent with the 2017 AHA/ACC/HRS guidelines, is based on the relatively low incidence of sudden cardiac death or ventricular tachyarrhythmias in patients with only a Brugada pattern ECG, as well as the relatively high morbidity associated with ICD implantation or antiarrhythmic drug therapy [20]. Additionally, there are no randomized trials comparing ICDs with antiarrhythmic drug therapy (or no drug therapy) in asymptomatic patients with Brugada pattern ECGs.
While there are no randomized trials of therapies in asymptomatic patients with Brugada pattern ECGs, there are some data evaluating the use of an ICD or antiarrhythmic drugs in asymptomatic patients with a Brugada pattern ECG. In one series of 378 patients with type 1 Brugada ECG findings (spontaneous in 60 percent, inducible in 40 percent), which included 166 asymptomatic patients who received an ICD on the basis of an abnormal invasive EP study (139 patients) or a family history of SCD or nonsustained VT (24 patients), appropriate device therapy at 10 years occurred in 12 percent of asymptomatic patients [30]. In contrast, over 10 years, 37 percent of the cohort experienced an inappropriate shock, while 29 percent experienced ICD lead failure.
Recommendations of others — Based upon the high incidence of sudden cardiac arrest (SCA) in selected patients with the Brugada syndrome, several professional societies have discussed their approach to the treatment of patients with the Brugada syndrome [19,20,22,42].
●The 2013 Heart Rhythm Society/European Heart Rhythm Association/Asia Pacific Heart Rhythm Society (HRS/EHRA/APHRA) made the following recommendations [19]:
•ICD implantation was recommended (class I) for patients with Brugada syndrome who have survived SCA or who have documented spontaneous sustained VT.
•ICD implantation can be useful (class IIa) in patients with spontaneous type I Brugada pattern ECG with a history of syncope likely caused by ventricular arrhythmias.
•ICD implantation may be considered (class IIb) in patients with Brugada syndrome who develop VF during programmed stimulation during EP testing.
•ICD implantation is not indicated (class III) in asymptomatic patients with drug-induced type I Brugada pattern on the basis of a family history of SCA alone.
The HRS/EHRA/APHRS consensus statement also discusses the utility of quinidine for the treatment of electrical storm (class IIa); for the treatment of patients who have an indication for ICD therapy but are not candidates for, or refuse, ICD implantation (class IIa); and for prophylactic treatment of asymptomatic patients with spontaneous type I Brugada ECG pattern (class IIb) [19].
●The second consensus conference on Brugada syndrome, endorsed in 2005 by the HRS and the EHRA, recommended a somewhat more aggressive approach with ICD implantation for nearly all patients with the Brugada syndrome, including many with asymptomatic patients [22].
SCREENING OF 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. The clinical history should carefully screen for any prior episodes of syncope, and the 12-lead ECG should be carefully scrutinized for findings characteristic of the Brugada ECG pattern. 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. Because of relatively limited data regarding the best approach to screening in such patients, recommendations for screening in this setting are primarily based on expert opinion [20]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'ECG findings'.)
In contrast to screening with history and ECG, which we recommend for all first-degree relatives of patients with Brugada syndrome, we do not recommend universal genetic testing since the genetic heterogeneity of Brugada syndrome results in a low sensitivity for finding a mutation. Additionally, the clinical relevance of screening asymptomatic family members without known arrhythmias was called into question by a study of 2022 patients who underwent DNA sequencing including SCN5A and KCNH2 genes, among whom 63 persons were felt to have a potentially pathogenic mutation; there was no significant difference between patients with and without potentially pathogenic mutations in the frequency of arrhythmia diagnosis (17 versus 13 percent) or in the corrected QT interval (median 429 versus 439 milliseconds) [43]. However, there are situations in which genetic testing of the proband patient may allow for more efficient screening of family members (eg, large numbers of first-degree relatives), in which case we consider proceeding with the genetic testing as an adjunct to the clinical and serial ECG screening. This strategy would involve testing the proband, then performing targeted genetic testing of family members only if testing of the proband is positive for a known associated mutation.
Positive screening results — Screening may identify patients with both symptomatic Brugada syndrome as well as asymptomatic Brugada pattern ECGs:
●First-degree relatives with a history of syncope of suspected arrhythmic origin and a Brugada type I ECG meet the criteria for the diagnosis of Brugada syndrome and should be managed accordingly. (See 'Symptomatic patients with Brugada syndrome' above.)
●First-degree relatives with no history of syncope but a Brugada type I ECG are considered to have the Brugada pattern ECG and should be managed accordingly. (See 'Asymptomatic patients with the Brugada ECG pattern' above.)
Negative screening 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 'Frequency of repeat screening' below.)
Indeterminate screening 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'.)
●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 [25]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation", section on 'Drug challenge'.)
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.
Frequency of repeat screening — For first degree relatives of a patient with Brugada syndrome who initially screen negative, we repeat screening with a clinical history and ECG every one to two years, since a Brugada ECG may not develop until later in life. The frequency of screening can be decreased after the fifth decade of life, when the incidence of new onset Brugada syndrome is lower. However, lifelong vigilance for syncope is required in patients with a family history of Brugada.
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
●The most important prognostic risk factor for patients with the Brugada ECG pattern or Brugada syndrome appears to be a history of ventricular tachyarrhythmias leading to sudden cardiac arrest or syncope. The risk of SCA is much lower in asymptomatic patients with Brugada pattern ECGs, although subgroups of asymptomatic patients with increased risk can be identified. (See 'Prognostic factors' above.)
●Treatment for patients diagnosed with the Brugada syndrome is primarily focused around prevention of sudden cardiac arrest and the termination of any ventricular arrhythmias with an implantable cardioverter-defibrillator (ICD) (algorithm 1). (See 'Our approach to treatment' above.)
•For patients with the Brugada syndrome who have survived sudden cardiac arrest or those with a history of syncope which is felt to be due to ventricular tachyarrhythmias, we recommend implantation of an ICD rather than antiarrhythmic drug therapy (Grade 1A). (See 'ICD therapy' above.)
•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 'Drug therapy' above.)
•In patients with an ICD who have recurrent arrhythmias resulting in ICD shocks, we suggest catheter ablation of arrhythmogenic substrate in 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.)
•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 or type 1 Brugada ECG pattern), we recommend no treatment (Grade 1B). (See 'Asymptomatic patients with the Brugada ECG pattern' above.)
●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 of first-degree 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 one to two years, since a Brugada ECG may not develop until later in life. (See 'Frequency of repeat screening' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Ann Garlitski, MD, who contributed to earlier versions of this topic review.
