Download Sudden Cardiac Death BRUGADA SYNDROME

Sudden Cardiac Arrest
BRUGADA SYNDROME
Carlo Francisco S. Gochuico, M.D.
August 14, 2008
OBJECTIVES
• To present a case of sudden cardiac arrest
in a young male
• To discuss the approach and management
of Brugada syndrome
General Data
•
•
•
•
J.D.
28 year old
Male
Filipino
Chief Complaint
Loss of consciousness
History of Present Illness
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One hour PTA
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Found unconscious
Seen with upward rolling of eyeballs,
stiffening of extremities, and salivary
pooling
Lasted 3 to 5 minutes
Regained full consciousness with no
recollection of the incident
Was able to drink, sit on a chair, and
talk with parents
No slurring of speech, no extremity
weakness, no chest pain
History of Present Illness

Five minutes after
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Recurrence of stiffening
of extremities and
upward rolling of
eyeballs
Rushed to MMC ER
During transit, he
remained unconscious
Events at ER
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Quicklook showed
cyanosis
BP 0 HR 0
GCS 3 E1V1M1
Initial tracing at ER at
1:42 AM
Chest compressions and
bag mask ventilation
Defibrillation at 200
joules
Epinephrine 1mg IV
Intubated and advised
ICU admission
CXRAY, stat5 and ABG
12 L EKG 8-1-08 2:16 AM post defibrillation
CRBBB
PR interval 0.16 sec
QT interval 0.36 sec
Events at ER
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2:33 AM at ER
Systolic BP170
Pulse 80s
regular
Post CP arrest
Events at ER
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2:47 AM
Episode of
stiffening of
extremities
chest
compression
and
defibrillation
at 200 joules
Events at ER
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2:52 AM
Post defibrillation
BP 120/80
Pulse 80s
Amiodarone drip
started
Cardiac enzymes
Referred to
neurology
Admitted to ICU
Review of Systems
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General: no fever, fatigue, weight loss
Skin: no rashes, jaundice, ecchymoses,
petechiae
Head: no recent head injury, headache,
dizziness
Eyes: no blurring of vision, redness, pain
Ears: no tinnitus, vertigo, earache,
discharge
Review of Systems
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Nose: no colds, nasal congestion, discharge
Mouth: no sore throat, hoarseness
Neck: no pain, lumps, mass, stiffness
Respiratory: no cough, dyspnea, wheezing,
hemoptysis
Cardiac: no chest pain, palpitations,
orthopnea, PND, edema, recent chest
trauma
Review of Systems
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Gastrointestinal: no nausea, vomiting,
regurgitation, dysphagia, hematemesis,
abdominal pain, change in frequency and
characteristic of stools
Urinary: no hematuria, dysuria, oliguria,
polyuria, urgency, hesitancy
Vascular: no claudication, varicose veins, leg
cramps
Musculoskeletal: no myalgia, arthralgia, and
swelling
Review of Systems
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Hematologic: no anemia, pallor, easy
bruising or bleeding
Endocrine: no heat or cold intolerance,
no excessive thirst or hunger
Psychiatric: no depression,
nervousness
Past Medical History
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No history of HPN, DM, and BA
PTB, treated for 6 months
No previous seizure disorder, no
known neurologic and cardiac
problems
Had a history of syncope during early
childhood and another one a year ago,
no work-ups were done
Family History
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(+) HPN in paternal side
(-) DM, BA, stroke, cancer
No seizure disorder
Personal and Social
History
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Occasional smoker
Occasional alcoholic beverage drinker
Denies illicit drug use
PHYSICAL EXAMINATION
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Conscious, restless, intubated
BP 120/80 HR 80 regular RR 20 assisted
afebrile
Warm moist skin, no active dermatoses, no
jaundice
Anicteric sclerae, pink palpebral
conjunctivae, pupils 2-3 mm ERTL OU
No visible anterior neck mass, no neck vein
distention, no carotid bruit
No cervical lymphadenopathies
PHYSICAL EXAMINATION
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Equal chest expansion, no retractions, no rales,
wheezes, crackles
Adynamic precordium, AB at 5th LICS MCL, regular
rhythm, S1>S2 at base, S2>S1 at apex, no extra
heart sounds, no murmurs
Abdomen flabby, normoactive bowel sounds, soft,
no guarding, no direct and rebound tenderness, no
hepatosplenomegaly
No costovertebral angle tenderness
No pedal edema
Pulses full and equal
PHYSICAL EXAMINATION
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GCS 11 E4V1 (intubated) M6
No papilledema
Full and equal EOM
No facial asymmetry
Intact doll’s eye movement, gag and corneal
reflexes
Direct tendon reflexes normal
Motor and Sensory: intact
Localizes to pain and temperature
No babinski, kernig’s, and brudzinski
Salient Features
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28 M Filipino
Loss of consciouness
at night during sleep
2 episodes of
stiffening of
extremities
Post CP arrest 2x
(VFib)
No fever, headache,
chest pain, weakness
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History of syncope 2x
Positive family history
of cardiac disease
No illicit drug use
Differential Diagnosis
Loss of consciousness
Neurologic
Seizure Disorder
Cerebrovascular Accident
Cardiac
Structural
Primary physiologic abnormality
Differential Diagnosis
Neurologic
Seizure
Cerebrovascular accident
No previous history
CBC electrolytes
glucose toxicology
liver and
renal function test
CT, EEG
Imaging (CT)
Loss of consciousness
Neurologic
Seizure Disorder
Cerebrovascular Accident
Cardiac
Structural
Primary physiologic abnormality
Differential Diagnosis
Cardiac
Structural heart disease
Non-structural heart disease
Differential Diagnosis
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Structural heart diseases
– Ischemic heart disease
– Non-ischemic cardiomyopathies
– Valvular heart diseases
– Arrhythmogenic right ventricular dysplasia
Primary electrophysiologic abnormalities
– Long QT syndrome
– Brugada syndrome
Ischemia

Cardiac arrest due to ventricular
arrhythmias may be due to chronic
scar or to acute MI/ischemia. A
chronic infarct scar can serve as the
focus for reentrant ventricular
tachyarrhythmias
Non-ischemic
cardiomyopathies
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represent the second largest group of
patients who experience SCD
Dilated cardiomyopathy is usually
characterized by ventricular dilatation,
initially usually of the left ventricle
(LV), with myocyte hypertrophy and
diminished systolic function
Hypertrophic
cardiomyopathy (HCM)

an autosomal-dominant, incompletely
penetrant genetic disorder resulting
from a mutation in one of the many
(>45) genes encoding proteins of the
cardiac muscle sarcomere
Echo of HCM
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Small LV cavity due to marked hypertrophy of
the myocardium and encroachment into the LV
cavity
Reduced septal motion and thickening during
systole, particularly of the upper septum, due
to the disarray of the myofibrillar architecture
and abnormal contractile function
Reduced rate of closure of the mitral valve in
mid diastole due to a decrease in LV
compliance Left atrial enlargement
Cardiac
Non-structural heart disease
Structural heart disease
Primary physiologic abnormality
Course in the Ward
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1st Hospital day in the ICU (1230 PM)
Repeat 12L EKG done
– Rsr’ pattern
– ST elevation in lead V1-V3
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2D echo – N LVD EF69% Normal LA and RA
dimensions
Normal MV, TV, AV, PV
Mild MR, TR
Normal left ventricular diastolic function indices
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FIo2 adjusted to 0.35
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Course in the Ward
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ICU at 1500H
T-piece placed and repeat ABG done
Referred to cardiology EPS
Thyroid function test requested
Quinidine bisulfate started
Course in the Ward
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ICU at 1750 H
Patient extubated
4th Hospital day
Transferred to regular room
Quinidine 200mg/tab adjusted to 1 ½
tablets in the morning and evening,
and 1 tablet at lunchtime
Course in the Ward
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5th hospital day
Repeat 12 L EKG
– Normal
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Discharged on 6th hospital day
Follow-up after 1 week
• CXRAY Aug
1, 2008
• Lungs are
clear
• Heart is
magnified
• ET in place
with tip at
carina
• Cranial CT
Scan
Aug 1, 08
• Normal
noncontrast
CT of the
brain
• EEG
• Normal
2D ECHOCARDIOGRAPHY
August 1, 2008
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Normal left ventricular dimension with
normal wall motion and contractility.
Computed LV EF 69%
Normal left and right atrial dimensions
Normal mitral, aortic, tricuspid, and
pulmonic valves
Mild MR, TR
Normal left ventricular diastolic
function indices
Repeat 12 L EKG 8-1-08 12:30 PM IRBBB
PR interval 0.16 sec
QT interval 0.40 sec
Laboratory Results and Ancillary Procedures
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Stat 5
Na 137
K 2.7
Hgb 16.7
Hct 49
Glucose (random)
245 mg/dL
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CBC
Hgb 16.8
Hct 50.2
WBC 14.21
–
–
–
–
–
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seg54
lymph36
eos4
mono5
Baso1
Platelet 204000
Laboratory Results and Ancillary Procedures
Cardiac enzymes
CK total 165 U/L
CPK MB 1.4 ng/mL
Troponin I 0 ng/mL
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PTT
patient 27.3
control 27.6
PT
patient 11.1
control 11.7
activity 115.6%
INR 0.94
Laboratory Results and Ancillary Procedures
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SPEC 23
Na 137
K 3.6
Cl 103
calcium 9.78
BUN 13
creatinine 1.1
HDL 46
trig 119
LDL 166
cholesterol 245
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glucose 120
CPK 506
LDH 262
ALT 185
AST 82
alkaline
phosphatase 148
Laboratory Results and Ancillary Procedures
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Routine urinalysis
Yellow hazy
PH 6
spgr 1.020
+3 protein
trace sugar
negative ketones, nitrites,
leucocyte esterase
+1 blood
rbc 2/hpf
wbc 2/hpf
epith 10/hpf
Bact 15/hpf
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Thyroid Function Test
TSH 0.037
(0.27-3.75)
FT3 4.419
(4.2-12)
FT4 17.815
(8.8-33)
Laboratory Results and Ancillary Procedures
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ABG
Post intubation
PO2 426.2
PH 7.34
PCO2 41
HCO3 22.1
O2 sat 99.8
AC mode 100%
FiO2 VT 420
Laboratory Results and Ancillary Procedures
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ABG
5 PM
PO2 169.1
PH 7.39
PCO2 37.3
HCO3 22.5
O2 sat 99.1
inline neb via T piece 35% FiO2
Repeat 12 L EKG 8-6-08 9:54 AM Normal
PR interval 0.20 sec
QT interval 0.44 sec
DISCUSSION
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Sudden cardiac death (SCD) is an
unexpected death due to cardiac causes,
heralded by loss of consciousness occurring
in a short time period (generally within 1
hour of symptom onset)
Most cases are due to cardiac arrhythmias
such as VF or VT which is responsible for
50-80% of cases
Sudden Cardiac Death
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Most cases of SCD occur in patients with
structural abnormalities in the heart,
related to either a prior MI, coronary
artery disease, cardiomyopathies
Valvular diseases such as aortic stenosis
are associated with increased risk of SCD
Acute inflammatory and infiltrative
disorders, such as myocarditis, provide a
sustained risk of SCD
Sudden Cardiac Death
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Less commonly, SCD happens in
patients who may not have apparent
structural disease
These conditions are usually inherited
arrhythmia syndromes or primary
electrophysiologic abnormalities
Primary Electrophysiologic
Abnormalities
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This generally represents a group of
abnormalities in which patients have
no apparent structural heart disease
but have a primary electrophysiologic
abnormality that predisposes them to
VF or VT
Brugada syndrome, Long QT
syndrome
Brugada Syndrome
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A cardiac disease caused by an
inherited ion channelopathy associated
with a propensity to develop
ventricular fibrillation (VF)
Reported as early as 1953 but was
first described as a distinct clinical
entity associated with a high risk of
sudden cardiac death in 1992
Brugada Syndrome
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In the 1980s, the Centers for Disease
Control and Prevention reported a high
incidence of sudden death in young
immigrants from Southeast Asia.
For natives, it is known as lai tai (death
during sleep) in Thailand, bangungut
(sudden death during sleep) in the
Philippines, and pokkuri (unexpected
sudden death at night) in Japan
Brugada Syndrome
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Familial disease with an autosomal dominant
mode of transmission, with incomplete
penetrance and an incidence ranging between
5 and 66 per 10 000
In Southeast Asia where it is endemic, it is
distinguished by a male predominance (8:1
male:female ratio) and the appearance of
arrhythmic events at an average age of 40
years (range: 1 to 77 years)
Brugada Syndrome

The syndrome typically manifests
during adulthood, with a mean age of
sudden death of 41 +/- 15 years. The
youngest patient clinically diagnosed
with the syndrome is 2 days old and
the oldest is 84 years old
Brugada Syndrome: Report of the Second Consensus
Conference Circulation 2005
Brugada Syndrome
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It is thought that it may cause 4 to 10
sudden deaths per 10,000 inhabitants in
Southeast Asia annually, making it the
second most common cause of natural
death in men aged younger than 40 years
In endemic countries, it has been estimated
to cause at least 4% of all sudden deaths
and at least 20% of all sudden cardiac
deaths in patients with structurally normal
hearts.
Orphanet Journal of Rare Diseases 2006
Brugada Syndrome
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The prevalence of BrS in the general
population is unknown. The suggested
prevalence ranges from 5/1,000
(Caucasians) to 14/1,000 (Japanese)
In Laos, it causes an estimated 1
sudden death per 1000 inhabitants per
year, and in Thailand, unexpected
sudden death is the most common
cause of natural death in young people
Brugada Syndrome
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It has been linked to a genetic mutation located on
the SCN5A gene on chromosome 3 p21-23, which
codes for the α subunit of the cardiomyocyte
sodium ion channels
This mutation leads to either complete loss of
channel function or an accelerated recovery from
activation
This can generate heterogeneity of repolarization
and increase the chance of intramyocardial re-entry
circuits, which may induce ventricular
tachyarrhythmias

Genetic mutations detected so far in the
Brugada syndrome result in defective
myocardial sodium channels that reduce
sodium inflow currents, resulting in shorterthan-normal action potentials
Brugada Syndrome
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It can also present atrial fibrillation,
which is present in 10% to 20% of
cases
Potential clinical manifestations
dizziness, palpitations, syncope, and
sudden cardiac death
ECG abnormalities constitute the
hallmark of Brugada syndrome
Circadian pattern
VF and sudden death in
Brugada syndrome usually
occur at rest and at night
Modulating and precipitating factors
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The ECG manifestations of congenital
Brugada syndrome are often concealed but
can be unmasked or modulated by:
Sodium channel blockers, a febrile state,
vagotonic agents, alpha and beta
adrenergic agonists, tricyclic or tetracyclic
antidepressants, a combination of glucose
and insulin, hyperkalemia, hypokalemia,
hypercalcemia, and alcohol and cocaine
toxicity
Brugada Syndrome
Electrocardiographic Characteristics
The J wave is a deflection that appears in the ECG as a late delta wave following the
QRS or as a small secondary R wave (R'). Also referred to as the Osborn wave
Brugada Syndrome

Electrocardiographic Characteristics
Type1 is characterized
by a prominent coved
ST-segment elevation
displaying J wave
amplitude or STsegment elevation 2
mm or 0.2 mV at its
peak followed by a
negative T-wave, with
little or no isoelectric
separation
Proposed Diagnostic Criteria for the
Brugada Syndrome: Consensus
Report Circulation 2002
Brugada Syndrome
Brugada Syndrome

Electrocardiographic Characteristics
Type 2 also has a high
take-off STsegment
elevation, but in this case,
J wave amplitude (2 mm)
gives rise to a gradually
descending ST-segment
elevation (remaining 1
mm above the baseline),
followed by a positive or
biphasic T-wave that
results in a saddle back
configuration
Proposed Diagnostic Criteria for the
Brugada Syndrome: Consensus Report
Circulation 2002
Brugada Syndrome
Electrocardiographic Characteristics

Type 3 is a right
precordial STsegment elevation
of 1 mm of saddle
back type, coved
type, or both
Proposed Diagnostic Criteria for the
Brugada Syndrome: Consensus Report
Circulation 2002
Brugada Syndrome
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report
Circulation 2002
Brugada Syndrome: Report of the Second
Consensus Conference Circulation 2002
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It can be established in the presence of:
ST-segment elevation (type 1) in more than one
right precordial lead (V1 to V3), and one of the
following:
Documented ventricular fibrillation; self terminating
polymorphic ventricular tachycardia; a family history
of sudden cardiac death (<45 years); coved type
ECGs in family members; electrophysiological
inducibility; syncope
There should be no other factors that can account
for the ECG abnormality
Brugada Syndrome: Report of the Second
Consensus Conference


Appearance of type 2 ST-segment elevation
("saddleback type") in more than one right
precordial lead upon challenge with a sodium
channel blocker.
A drug-induced ST-segment elevation to a
value >2 mm should raise the possibility of
Brugada syndrome when one or more clinical
criteria are present
Brugada Syndrome: Report of the Second
Consensus Conference

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
Appearance of type 3 ST segment elevation in more
than one lead under baseline conditions with
conversion to type 1 after challenge with a sodium
channel blocker is considered equivalent to case 1
above
Drug-induced conversion of type 3 to type 2 is not
considered diagnostic
Characteristic EKG morphologies recorded within
the first few hours after resuscitation cannot be
taken as diagnostic
Drug Challenge


Drug challenge should be
performed while the patient is
continuously monitored and
with defibrillator and
advanced coronary life
support facilities close at
hand
Drug administration should
be stopped when the test is
positive and/or when
ventricular arrhythmias,
including ventricular
premature complexes, are
evident, or when significant
QRS widening (30%) is
observed
Type 2 and type 3 ECGs, the test is
recommended to clarify the diagnosis.
Conversion of a type 2 or 3 ECG to a
type 1 is considered positive
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report
Circulation 2002
Differential Diagnosis
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Acute myocardial ischemia
Acute myocarditis
Tricyclic antidepressant overdose
Cocaine intoxication
Arrhythmogenic right ventricular
dysplasia
Long QT syndrome
Arrhythmogenic right ventricular
dysplasia
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Discrimination between BrS and ARVC may be
particularly difficult because ARVC may at times
mimic BrS
Before the diagnosis Brugada syndrome is made,
a serious attempt should be taken to exclude
ARVC.
Drug challenge with sodium channel blockers
may be useful in discriminating between these 2
disease
Proposed Diagnostic Criteria for the Brugada Syndrome: Consensus Report Circulation 2002
Long QT syndrome
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There is an alteration in the function of a
myocellular channel protein that regulates
the potassium flux during electrical
repolarization
Clinical course is variable, some remain
aymptomatic and some develop syncope
and sudden death
Risk is impacted by factors such as
hypokalemia, emotional extremes, and
vigorous physical activity
Long QT syndrome

involve an abnormal repolarization of the
heart causes differences in the
"refractoriness" of the myocytes leading to
re-entrant ventricular arrhythmias
Long QT syndrome

A commonly used criterion to diagnose
LQTS is the LQTS "diagnostic score“.
Its based on several criteria giving
points to each. With 4 or more points
the probability is high for LQTS, and
with 1 or less point the probability is
low. Two or 3 points indicates
intermediate probability.
Long QT syndrome

QTc (Defined as QT interval / square root of RR interval)
– >= 480 msec - 3 points
– 460-470 msec - 2 points
– 450 msec and male gender - 1 point
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Torsade de Pointes ventricular tachycardia - 2 points
T wave alternans - 1 point
Notched T wave in at least 3 leads - 1 point
Low heart rate for age (children) - 0.5 points
Syncope (one cannot receive points both for syncope and Torsades de
pointes)
– With stress - 2 points
– Without stress - 1 point

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Congenital deafness - 0.5 points
Family history (the same family member cannot be counted for LQTS and
sudden death)
– Other family members with definite LQTS - 1 point
– Sudden death in immediate family (members before the age 30) - 0.5 points
Long QT syndrome
Long QT syndrome
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
Beta blockers are the first choice in
treating Long QT syndrome
The only effective form of arrhythmia
termination in individuals with LQTS is
placement of an implantable
cardioverter-defibrillator (ICD). ICD
are commonly used in patients with
syncopes despite beta blocker therapy,
and in patients who have experienced
a cardiac arrest.
Brugada: Risk stratification

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Brugada et al found
that patients initially
presenting with aborted
sudden death are at the
highest risk for a
recurrence (69%)
Those presenting with
syncope and a
spontaneously
appearing type 1 ECG
have a recurrence rate
of 19%
Men had a 5.5-fold
higher risk of sudden
death than did women
Brugada Syndrome
Indication for ICD implantation
Brugada Syndrome Report of the Second Consensus Conference
Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association
Brugada Syndrome
Indication for ICD implantation
Brugada Syndrome Report of the Second Consensus Conference
Endorsed by the Heart Rhythm Society and the European Heart Rhythm Association
Outcome After Implantation of a CardioverterDefibrillator in Patients With Brugada Syndrome
A Multicenter Study Circulation 2006


In this large Brugada syndrome population,
a low incidence of arrhythmic events was
found, with an annual event rate of 2.6%
during a follow-up of 3 years
Device-related complications (8.9%/year).
Inappropriate shocks were 2.5 times more
frequent than appropriate ones
Efficacy of Quinidine in High-Risk Patients With
Brugada Syndrome
Bernard Belhassen, MD; Aharon Glick, MD; Sami Viskin, MD
Circulation 2004

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Quinidine depresses Ito current, which may play
an important role in the arrhythmogenesis of this
disease
It prevented VF induction in 22 of the 25 patients
(88%)
The effective quinidine serum blood levels
rangedfrom 1.29 to 5.2 mg/L (meanSD, 2.650.99
mg/L)
Quinidine
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May exert its beneficial effects in Brugada
syndrome by inhibiting Ito, thereby restoring
electrical homogeneity
In addition, quinidine prolongs ventricular
refractoriness
Finally, the anticholinergic effect of quinidine
might contribute to its antiarrhythmic efficacy
in the Brugada syndrome
Despite these hypotheses, the basis for
quinidine efficacy in this setting remains to be
elucidated
Study shows the following:
 First, quinidine is highly effective (88%
success rate) for preventing VF induction in
patients with inducible VF
 Second, it also appears to be effective in
preventing spontaneous VF, with no
arrhythmic events observed during a mean
SD follow-up of 56-67 months
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
Third, the drug could be chronically
tolerated with therapeutic effectiveness in
16 study patients (64%)
Fourth, no proarrhythmic event occurred in
any treated patient despite QT prolongation.
Finally, although quinidine related side
effects (thrombocytopenia, diarrhea,
esophagitis, allergic reaction, aggravation of
sinus node dysfunction) were common, they
were always transient and invariably
resolved after drug discontinuation
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