-1992, linked to SCN5A mutation
-May be unmasked or modulated by: sodium channel blockers (procainamide), fever, vagotonic
agents, adrenergic agonists, adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination
of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity.
-Mean age of sudden death 41 +/- 15 years, usually occur at night.
Responsible for 4% of all sudden deaths and 20% of sudden deaths in structurally normal hearts
Prevalence: 5/10 000
In a Japanese study, Brugada type I was observed in 12/10 000 inhabitants. Types 2 and 3
(non-diagnostic) in 58/10 000 inhabitants.
-20% if Brugada patients develop SVT (AFib in 10-20% of cases, also AVNRT and WPW).
-Brugada is also associated with prolonged SNRT, slowed atrial conduction and atrial standstill.

Type 1 Brugada Coved ST elevation > 2 mm followed by a negative T wave in >1 right
precordial lead (V1 to V3) in the presence or absence of a sodium channel-blocker, and in conjunction
with one of the following (isolated cases have been reported in left precordial and inferior leads):
   -Polymorphic VT
   -Family history of SCD at < 45 years old
   -Coved type ECGs in family members
   -Inducible VT by EPS
   -Nocturnal agonal respiration
-Drug challenge is generally not performed in asymptomatic patients displaying the type 1 ECG
because the additional diagnostic and prognostic values are unclear and there is a risk of arrhythmias.
-Shift of right precordial leads (V1 and V2) to
2nd intercostal space unmasks type 1 sometimes.

   -Atypical RBBB
   -Early repolarization
   -Acute Pericarditis
   -Acute MI
   -Pulmonary Embolism
   -Prinzmetal Angina
   -Dissecting aortic aneurysm
   -Duchenne's Muscular Dystrophy
   -Thiamin deficiency
   -Hypercalcemia / Hyperkalemia / Hypothermia
ARVD/C (click on link)
   -Pectus Excavatum
   -Mechanical compression of the RVOT (mediastinal tumor, hemopericardium)
   -Post DC-CV (?)
   -Athlete's ECG (ST upslope rather than downslope, unaffected by pharmacologic challenge)
Type 2 Brugada Saddleback appearance with a high takeoff ST elevation > 2 mm,
a trough displaying > 1 mm ST elevation, and then either a positive or a biphasic T wave.

Type 3 Brugada either a saddleback or coved appearance with an ST-segment
elevation of < 1 mm.

Types 2 and 3 are not diagnostic of Brugada Syndrome. The diagnosis is made when
either type 2 or 3 are present on > 1 right precordial lead at baseline ECG and convert to
a diagnostic type 1 after a sodium channel blocker challenge with one or more of the
criteria mentioned in
blue above.

Acute myocardial infarction or ischemia from vasospasm involving the RVOT mimics
ST-segment elevation similar to that in Brugada syndrome.
This effect is likely the result of a depression of calcium channel current
(ICa) and the
activation of ATP-sensitive potassium channel current (
IK-ATP) during ischemia, and it
suggests that patients with congenital and possibly acquired forms of Brugada syndrome
may be at a higher risk for ischemia-related sudden cardiac death.
-Diagnostic type 1 develops
-ST segment in type 2 increases by > 2 mm
-PVCs or other arrhythmias develop
-QRS widens by > 130% from baseline
Antidotes: Isoproterenol and Na+ Lactate

-Patients initially presenting with aborted sudden death are at the highest risk for a recurrence: 69% at 54 months of follow-up (Brugada data)
-Patients presenting with
syncope and a spontaneously appearing type 1 ECG have a recurrence rate of 19% at 26-36 months of follow-up.
-Patients with a spontaneous type-I ECG who are
asymptomatic have an 8% occurrence of cardiac events.
This adverse prognosis was not observed in a population of similar size by
Priori et al, although the diagnostic criteria applied in the 2 studies may have been
different in that the report by Priori et al does not specify a requirement for a coved-type ECG (type 1) in 1 precordial leads as a means to diagnose Brugada

Taken together, the data indicate that asymptomatic Brugada patients at highest risk are men with inducible VT/VF and a
spontaneously elevated ST segment (type 1 ECG).

Combined ECG markers remain to be tested in a prospective trial:
Atarashi et al used the width of the S wave and the ST-segment elevation magnitude
Morita et al used the combined ST-segment elevation and the presence of late potentials

EPS: Brugada et al suggested that among asymptomatic patients, the inducibility of VT/VF during EPS may forecast risk. Studies by Priori et al, Kanda et
al, and Eckardt et al, however, failed to find an association between inducibility and recurrence of VT/VF among both asymptomatic and symptomatic patients
with Brugada syndrome. (
Nademanee: Prognostic value of EPS in Brugada).  These discrepancies may result from differences in patient characteristics and the
use of non-standardized or noncomparable stimulation protocols. The adverse prognosis and higher predictive value of inducibility by Brugada et al may, at
least in part, be due to more demanding criteria for diagnosing patients with Brugada syndrome. It is noteworthy that programmed electrical stimulation–induced
VF is observed in
6% to 9% (Viskin et al) of apparently healthy individuals and may represent a false-positive and nonspecific response, particularly when
aggressive stimulation protocols are used.
A protocol involving up to 3 extrastimuli applied to the right ventricular apex at cycle lengths 200 ms is recommended. If not inducible from
the right ventricular apex, then stimulation may be applied to the RVOT.

A recent study by Brugada et al reported on 547 individuals diagnosed with Brugada syndrome who had had no previous cardiac arrest. In 124 patients, the
abnormal ECG was identified after 1 episode of syncope, and in 423 individuals, the abnormal ECG was identified during routine ECG screening or during
study because they were family members of patients with the syndrome. Structural disease was ruled out in all patients. This study, which evaluated the
clinical outcome of the largest population of patients with Brugada syndrome thus far reported, reached the following conclusions:
                     1. Patients have a relatively high risk for sudden arrhythmic death, even in the absence of a history of cardiac arrest:
8.2% experienced sudden death or at least one documented episode of VF during a mean follow-up of 24-33 months.
                     Individuals with a
spontaneously abnormal type 1 ECG carried a 7.7-fold higher risk of developing an arrhythmic
                     event during a lifetime as compared with individuals in whom the ECG diagnostic of Brugada syndrome was
                     evident only after sodium channel blocker challenge.
  2. Male gender is another risk factor for sudden death. Men had a 5.5-fold higher risk of sudden death than did women.
  3. Programmed EPS that induces a sustained ventricular arrhythmia is the strongest marker of risk,
                     associated with an
8-fold higher risk of (aborted) sudden death than in non-inducible patients.
                     4. Familial forms of the disease are not associated with a worse prognosis than are sporadic cases.

THERAPY  Currently the ICD is the only proven effective treatment for the disease. Of 690 patient included in a Multicenter Registry of which 258
received an ICD because of suspected high risk of SCD. (mean age 42 +- 13.5 years, 81.3% men, 62% symptomatic, 48.4% with a family history of sudden
death or a familial Brugada ECG pattern, 76.7% had inducible VT/VF during EPS).
During a mean follow-up of 2.5 years, 26.7% of patients had an
appropriate defibrillation. The cumulative efficacy of the device was 18%, 24%, 32%, 36%, and 38% at 1, 2, 3, 4, and 5 years of follow-up.
Antiarrhythmic agents such as amiodarone and B-blockers have been shown to be ineffective. Class IC antiarrhythmic drugs (eg, flecainide and
propafenone) and class IA agents (eg, procainamide) are contraindicated for reasons enumerated previously. Specific
class IA agents such as Quinidine
and tedisamil, however, may exert a therapeutic action because of their I
to-blocking properties. Because the presence of a prominent transient outward current,
to, in the right ventricle is at the heart of the mechanism underlying Brugada syndrome, any agent that inhibits this current may be protective. Cardioselective
and I
to-specific blockers are not available. The only agent on the US market with significant Ito-blocking properties is Quinidine.

Studies have shown Quinidine to be effective in restoring the epicardial action potential dome, thus normalizing the ST segment and preventing phase 2
reentry and polymorphic VT in experimental models of Brugada syndrome. Clinical evidence of the effectiveness of quinidine in normalizing ST-segment
elevation in patients with Brugada syndrome has been reported (
Belhassen et al., Alings et al.). Although clinical trials designed to assess the efficacy
of this agent are limited.
Relatively high doses of Quinidine are recommended (1200 to 1500 mg/d). Agents that boost the L-type calcium current, such
as isoproterenol, may be useful as well. Both types of agents (
Ito blocker and agents that augment ICa) have been shown to be effective in normalizing ST-
segment elevation in patients with Brugada syndrome and in controlling “electrical storms,” particularly in children. Other than the studies by Belhassen and
coworkers involving quinidine, none have as yet demonstrated long-term efficacy in the prevention of sudden cardiac death.

The most recent addition to the pharmacological armamentarium is a phosphodiesterase III inhibitor,
Cilostazol, which normalizes the ST segment most likely
by augmenting the calcium current (I
Ca), as well as by reducing Ito secondary to an increase in heart rate.

An experimental antiarrhythmic agent,
Tedisamil, with potent action to block Ito among other outward currents has been suggested as a therapeutic candidate.
Tedisamil may be more potent than quinidine because it lacks the relatively strong inward current–blocking actions of quinidine.
Type 2 or type 3 pattern should be distinguished from incomplete RBBB, present in 3%
of the population. In this study from Lausanne, 38 patients with either type 2 or type 3 Brugada
pattern that were referred for an antiarrhythmic drug challenge (AAD) were included. Before
AAD, 2 angles were measured from ECG leads V1 and/or V2 showing incomplete RBBB:
1) Alpha, the angle between a vertical line and the downslope of the r' wave
2) Beta, the angle between the upslope of the S-wave and the downslope of the r' wave.

Beta's optimal cutoff value was 58°, which yielded a PPV of 73% and a NPV of 87% for
conversion to type 1 pattern on AAD;
Alpha was slightly less sensitive and specific compared
with Beta When the angles were combined with QRS duration, it tended to improve discrimination.

New ECG Criteria for distinguishing between Brugada type 2 and 3 JACC 2011 Stephane
From ACC 2012 Guidelines: The Brugada syndrome is characterized by ST-segment elevation across the right precordial leads in association with a high risk of SCD
(16,422–425). Although the Brugada pattern ECG most commonly shows J-point segment elevation in leads V1 to V3 and right bundle-branch block, the ECG pattern can be
intermittent (16). Less commonly, the J-point elevation occurs in the inferior leads (16). Patients with the Brugada syndrome have a structurally normal heart with a primary
channelopathy (16,426). This is transmitted with an
autosomal dominant pattern of inheritance, and more than 90% of those affected are male. The genetic basis for the
Brugada syndrome involves the cardiac sodium channel gene (SCN5A) (16,426).
Brugada Sd: syncope and this ECG pattern of STE in V1-V3 slope down nice to ski on. > 1 first degree relative with this ECG pattern. Or this ECG pattern and a
+ Brugada genetic test.

Type I: ski slope.
Type II: saddle back.
Type III: less saddle back.
Drugs to bring out this ECG pattern.
Ajmaline in europe and procainamide/flecainide in US. Or reposition of right precordial leads and move them up in
second ICS.
High lead ECG as good as procainamide drug challenge. Na channel responsible for phase 0. Loss of function of BrS1 is most common
genetically identifiable cause of BrS but not most common cause. Explains only
20-30% of BrS1 by SCN5A mutation. Second most common cause is mutation
Ca channel CACNA1C 5-10% responsible. 65% of BrS is genetically elusive.
When ICD?
if syncope + spontaneous ECG
if aborted cardiac arrest and type I ECG pattern

Asymptomatic with type I ECG. No role for EPS

Only disease in cardiology with clear role for
Quinidine. It's not a strong Na channel blocker. It blocks the ITO phase 1 channel. Fever is brugada  trigger.
The ECG shows a RBBB pattern with secondary ST-T changes in the precordial leads, 'type 3' Brugada pattern.

Only a 'type 1' pattern (spontaneous or drug-induced) with >2 mm of 'coved' ST elevation in at least 1 anterior precordial lead meets criteria for diagnosis,
based on our most up-to-date consensus document.
A 'type 2' and 'type 3' ECG may raise clinical suspicion, but they do not make the diagnosis. For a patient with an indeterminate ECG, the easiest, safest, and
most practical option is to repeat the 12-lead ECG with V1 and V2 in the 2nd or 3rd intercostal space. If this converts the ECG into a 'type 1' ECG, you're
done. If it doesn't, you're next option is drug challenge.
Typically, we administer
procainamide 10 mg/kg over 10 minutes or flecainide 400 mg PO once, monitoring for ST segment changes for 3-4 hours.
If the drug challenge is unequivocally positive (see ECG 2 below). What next? EP study gets a 'IIb' recommendation based on registry data that calls into
question the predictive value of inducible VT/VF (from the 2013 HRS Consensus Document on Inherited Primary Arrhythmia Syndromes). At the minimum,
asymptomatic Brugada patients should be counseled to avoid drugs with sodium channel blocking properties (, to treat fever aggressively
with anti-pyretic drugs, to avoid carbohydrate laden meals, and to avoid heavy alcohol intake. Brugada is not associated with exercise-induced VT/VF, so there
is no reason to limit physical activity.
FINGER Registry
: The cardiac event rate per year was 7.7% in patients with
aborted SCD, 1.9% in patients with syncope, and 0.5% in asymptomatic patients.
Symptoms and spontaneous type 1 ECG were predictors of arrhythmic events,
whereas gender, familial history of SCD, inducibility of ventricular

 VT/VF inducibility by EPS was unable to identify high-risk
patients, whereas the presence of a spontaneous type I ECG, history of
syncope, ventricular effective refractory period 200 ms, and QRS fragmentation
seem useful to identify candidates for prophylactic ICD
beneficial in Brugada by blockade of the Ito inward current
HRS April 2017 Fa-Po Chung et al (Taipei)
ICD is recommended for patients with BrS who experience cardiac arrest or spontaneous sustained VT with or without syncope
Disappointing efficacy and side effects of antiarrhythmic drugs makes that catheter ablation is an alternative strategy
Ventricular arrhythmias are often triggered by PVCs and RFA targeting triggers originating from the arborization of the RV Purkinje system and RVOT could be
an effective strategy in preventing recurrence of VT
Nademanee et al demonstrated the effectiveness of ablating the arrhythmogenic substrate at the RVOT epicardium on decreasing the VT/VF burden HR 2011
Wazni et al JACC 2006 demonstrated that ablation of epicardial abnormal substrates at anterior free wall and RVOT after flecainide testing could eliminate BrS
Fever is most common trigger of BrS phenotype and VT/VF (hot baths in Japan contribute to syncope and SCD in BrS patients)

Brs Definition: Coved ST elevation > 2 mV followed by T wave inversion in  1 or more precordial leads V1-V3 in 2nd, 3rd, or 4th intercsotal space

Brugada syndrome is an inherited arrhythmia syndrome but increasing evidence suggests that the Brugada ECG pattern is a marker of subtle cardiac structural
abnormalities. This evidence includes:
. Histopathological findings of right ventricular fibro-fatty infiltration similar to arrhythmogenic right ventricular cardiomyopathy in Brugada syndrome victims.
. Conduction delay and QRS fragmentation during electrophysiological studies in Brugada syndrome patients.
. Cardiac magnetic resonance studies demonstrating increased right ventricular volumes and reduced right ventricular function in Brugada syndrome patients.

The diagnosis in an individual requires the presence of the Brugada ECG pattern as described above (type 1) with at least one of the
recognized diagnostic criteria: syncope, prior cardiac arrest, documented or inducible polymorphic ventricular tachycardia or ventricular
fibrillation, a family historyof sudden death ,45 years old, or type 1 Brugada pattern and/or nocturnal agonal respiration

According to presently accepted criteria, patients are diagnosed with “drug-induced Brugada syndrome” when they have the following
electrocardiographic and clinical features.
B. Type I (coved type) 2 mm St-segment elevation with or without documented arrhythmias following intravenous infusion of propofol.

What do we know about clinical characteristics that predispose patients to develop drug-induced proarrhythmic events?
. Women are more likely to develop drug-induced long QT syndrome and males are more likely to develop drug-induced Brugada syndrome

The following medications have been reported to cause drug induced Brugada syndrome:
Drugs that block the depolarizing sodium (INa) current.

What do we know about the value of electrocardiographic screening to detect patients who are at increased risk of drug-induced Brugada
syndrome if eventually treated with medications known to cause this complication?

Electrocardiographic screening is complicated by the fact that subtle ST-segment elevation is seen in approximately 10% of healthy adults.

What do we know about the prognosis of patients with drug-induced Brugada syndrome?

. Approximately 10% of patients with drug induced Brugada syndrome reported so far developed ventricular fibrillation.