Brugada syndrome: Prognosis, management, and approach to screening

Authors:
John V Wylie, MD, FACC
Ann C Garlitski, MD, FACC, FHRS
Section Editors:
Scott Manaker, MD, PhD
Samuel Asirvatham, MD
Deputy Editor:
Brian C Downey, MD, FACC
Contributor Disclosures
All topics are updated as new evidence becomes available and our peer review
process is complete.
Literature review current through: Apr 2020. | This topic last updated: Jul 24, 2019.

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, causes, and pathophysiology")
●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 heart failure and
cardiomyopathy" 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 therapy with quinidine, although amiodarone is also an
option for these patients [20]. Alternatively, catheter ablation may be an option
for some patients. (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.

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 [19,35,36]. 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 [36].
●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) [35],
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 [37]. 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 [38].

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".)

Catheter 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, which increased after administration of ajmaline [39].
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) [40].

These data support the use of radiofrequency ablation as an option for patients with
a significant arrhythmic burden in whom antiarrhythmic drugs have failed and may be
considered as first line in patients with a large arrhythmia burden. We consider
ablation of the right ventricular substrate in these patients at centers experienced in
epicardial mapping and ablation.

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 therapy with quinidine, although amiodarone is also an
option for these patients (Grade 2C). Catheter ablation of arrhythmogenic
substrate in the right ventricular outflow tract and right ventricular free wall
is also an option in some patients. (See 'Drug therapy' 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.)
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