The new england journal of
case records of the massachusetts general hospital
From the Department of Emergency Med-
icine (K.A.M.) and the Cardiology Division
(P.T.E.), Massachusetts General Hospital;
and the Division of Emergency Medicine
(K.A.M.) and the Department of Medicine
(P.T.E.), Harvard Medical School both
in Boston.
N Engl J Med 2005;353:2492-501.
Copyright 2005 Massachusetts Medical Society.
2492
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medicine
Founded by Richard C. Cabot
Nancy Lee Harris, m.d., Editor
Jo-Anne O. Shepard, m.d., Associate Editor Stacey M. Ellender, Assistant Editor
Sally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor
Case 37-2005: A 35-Year-Old Man
with Cardiac Arrest while Sleeping
Keith A. Marill, M.D. and Patrick T. Ellinor, M.D., Ph.D.
presentation of case
Dr. Alex Manini (Emergency Medicine): A 35-year-old man was brought to the emergen-
cy department of this hospital by ambulance after a cardiac arrest while sleeping.
According to his partner and his brother, the patient had been in good health. His
partner reported being awakened from sleep by a scream from the patient, who groaned
once and then became unresponsive, with agonal breathing and a bluish skin color.
The patients partner called 911 and initiated mouth-to-mouth rescue breathing, but
not chest compressions. Personnel from emergency medical services arrived at the scene
6 to 8 minutes later, approximately 11 minutes after the onset of the event. The techni-
cians found that the patient was in ventricular fibrillation. Electrical defibrillation was
performed eight times with an automated external defibrillator, with two doses (1 mg
each) of intravenously administered epinephrine, resulting in a return of spontaneous
circulation. During the resuscitation, the patient was orotracheally intubated without
premedication. During transport to the emergency department, a wide-complex tach-
ycardia (140 beats per minute) developed, and a continuous intravenously adminis-
tered lidocaine drip (2 mg per minute, with a 100-mg bolus) was initiated.
In the emergency department, the endotracheal tube was verified to be in the correct
position by qualitative assessment of end-tidal carbon dioxide (in which a portable de-
vice is attached to the endotracheal tube, with a yellow color change indicating that the
tube is in the trachea) and auscultation. Bilateral breathing sounds and peripheral
pulses were present and normal. The blood pressure was 110/60 mm Hg, the heart rate
was 75 beats per minute, the oxygen saturation was 100 percent while the patient was
being ventilated with 100 percent oxygen, and the temperature was 35.5C.
A physical examination revealed that the patient had a score on the Glasgow Coma
Scale of 5-T: eyes, 1 (no opening); verbal, T (could not be evaluated because of tracheal
intubation); and motor, 4 (withdrawal from pain). The scale ranges from 3 to 15, with
a score of 8 or less indicating coma. The pupils were equal, round, and reactive to light
(constricting from 4 to 2 mm). The results of an examination of the head and face were
normal, without evidence of trauma. There was no jugular venous distention or carotid
bruits. The chest was clear; examination of the heart revealed a regular rate and rhythm,
without murmurs, rubs, or gallops. The abdomen was soft and not distended, with nor-
n engl j med 353;23 www.nejm.org december 8, 2005
 case records of the massachusetts general hospital

mal bowel sounds. A rectal examination yielded
guaiac-negative stool. The arms and legs were well
perfused, with normal peripheral pulses.
On neurologic examination, the patient did not
follow commands or visually track the examiner.
His corneal reflexes were absent. His face was sym-
metric. Tone in both arms was slightly increased,
and both legs were rigid. He spontaneously moved
and withdrew both arms in response to noxious
stimuli. His legs were extended, and he did not with-
draw them in response to noxious stimuli. His toes
were turned down bilaterally.
An electrocardiogram (Fig. 1) revealed sinus
rhythm, with normal intervals and 3-mm ST-seg-
ment elevations in the inferior leads (II, III, and aVF)
as well as 1-mm ST-segment elevations in the later-
al leads (V5 and V6). Another electrocardiogram
with right-sided leads revealed no ST-segment ele-
vation in lead V4R.
An orogastric tube was placed, and minimal
gastric contents, which appeared normal, were man-
ually suctioned. Portable chest radiography revealed
that the endotracheal and orogastric tubes were in
appropriate positions and there was no evidence
of acute cardiopulmonary disease. Computed to-
mography (CT) of the head showed diffuse cerebral
swelling with loss or blurring of the junction of
gray matter with white matter, with no evidence of
intracranial hemorrhage. The results of a complete
blood count and measurements of prothrombin
time, renal function, and levels of electrolytes, cal-
cium, phosphorus, magnesium, creatine kinase,
and troponin T were normal, and a urine toxicolo-
gy screening was negative for cocaine and amphet-
amine metabolites. A serum toxicology screening
revealed the presence of pseudoephedrine but was
otherwise negative.
Shortly after the patients arrival, his partner ar-
rived at the emergency department and provided
the information that the patient had a history of
bipolar disorder and his only medication was di-
valproex sodium (1 g per day). He had no known
drug allergies. He drank alcohol occasionally, did
not smoke, and did not use illicit drugs. There was
no family history of sudden death or coronary artery
disease.
Aspirin (325 mg) was administered rectally.
Metoprolol (5-mg bolus) was given intravenously.
Unfractionated heparin was given as a 4000-U bo-
lus and then as a continuous infusion at a rate of
1000 U per hour. A bolus of eptifibatide, 13.5 mg
(180 g per kilogram of body weight), was delivered,
and a continuous infusion was established at a rate
of 150 g per minute (2 g per kilogram per minute).
The lidocaine drip was discontinued. A bolus of
amiodarone (150 mg) was administered over the
course of 10 minutes, followed by a continuous in-
fusion at a rate of 1 mg per minute.
After 20 minutes in the emergency department,
the patient remained hypotensive despite the ad-
ministration of normal saline (2 liters). Ultrasonog-
raphy, performed at the bedside by the chief resi-
dent in emergency medicine, was interpreted as
showing no pericardial effusion. A continuous in-
travenous infusion of dopamine was initiated to
maintain adequate blood pressures.
The cardiology service was consulted, and the
patient was transferred to the cardiac catheteriza-

A B

I aVR V1 V4 V1 V4

II aVL V2 V5 V2 V5

III aVF V3 V6
V3 V6

Figure 1. Electrocardiogram Obtained on Admission to the Emergency Department.

There is sinus rhythm (Panel A), with normal intervals and 3-mm ST-segment elevations in the inferior leads (II, III, and aVF) as well as
1-mm ST-segment elevations in the lateral leads (V5 and V6) (arrows). An electrocardiogram with right-sided leads (Panel B) shows no
ST-segment elevation in lead V4R (arrowhead).

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 The new england journal
tion laboratory. Coronary angiography revealed nor-
mal coronary arteries. Left ventriculography showed
an ejection fraction of 50 percent.
A diagnostic test was performed.
differential diagnosis
Dr. Keith A. Marill: This previously healthy young
man had a cardiac arrest while sleeping; his partner
had witnessed the event and had administered res-
cue breathing without chest compressions; despite
a response to defibrillation, the patient remained
hypotensive and did not regain consciousness. The
issues raised by this case include the management of
out-of-hospital cardiac arrest due to ventricular fi-
brillation both at the scene and in the emergency
department and the differential diagnosis of car-
diac arrest in a young patient.
management of cardiac arrest due to
ventricular fibrillation
Although mortality continues to be high, the con-
tinuum of the management of sudden death from
cardiac causes from cardiopulmonary resuscitation
by bystanders to the care provided by emergency
medical services, emergency departments, and in-
tensive care units continues to evolve with numer-
ous incremental scientific advances. This patient
was in ventricular fibrillation when first seen by
emergency-medical-services personnel. Ventricular
fibrillation is the most common cause of sudden
cardiac arrest and is the initial rhythm found in the
majority of people who survive cardiac arrest. Ven-
tricular fibrillation initially generates a coarse pat-
tern on an electrocardiographic tracing because of
quasiperiodic ventricular excitation. If the condi-
tion is left untreated, this pattern of ventricular fi-
brillation is usually followed by a predictable and
inexorable decay to a more disorganized state, with
energy dissolution and eventual asystole (Fig. 2).1,2
This decay is revealed on the surface electrocardio-
gram by progression from a coarse pattern to fine
deflections and increasing smoothness.
Care by bystanders is the first link in the chain
of survival as described by the American Heart As-
sociation. The most important initial action for a
bystander is to call for help from emergency medi-
cal services, as was done in this case. The next action
is to begin cardiopulmonary resuscitation (CPR),
which consists of chest compressions and artifi-
cial respirations. CPR slows the rate of decay from
coarse to fine ventricular fibrillation and improves
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of medicine
survival.3 Chest compressions are more important
than artificial respirations. Instruction of layper-
sons in both types of intervention can cause confu-
sion, and the interruption of chest compressions
to perform excessive artificial respirations may be
detrimental.4,5 This case exemplifies the tragic po-
tential for confusion by a layperson: the patient re-
ceived respirations but not chest compressions. If
available, an automatic external defibrillator should
be applied by trained bystanders. One of the pri-
mary challenges of the use of an automatic external
defibrillator in the community is determining the
optimal placement of the units. As in this case, the
majority of cardiac arrests occur at home, often in
patients with no history of cardiac disease; routine
installation of automatic external defibrillators in
homes is clearly not practical. The accurate identi-
fication of the majority of patients at risk for sud-
den death from cardiac causes and the reliable pre-
diction of serious adverse events continue to elude
physicians.
Personnel in emergency medical services have
the capability to perform defibrillation, but imme-
diate defibrillation, which was presumably done
in this case, may not always be the best choice. If
the patient has been in ventricular fibrillation for
more than four to five minutes, priming the car-
diac pump with a period of cardiopulmonary re-
suscitation before defibrillation is likely to be ben-
eficial.6 The rationale for this is a partial repletion
of myocardial oxygen tension and metabolic sub-
strates, allowing the resumption of organized con-
tractions after defibrillation. The optimal duration
of cardiopulmonary resuscitation before defibrilla-
tion remains uncertain. Electronic analysis of the
smoothness of the ventricular-fibrillation waveform
in animals has been shown to predict the effec-
tiveness of immediate defibrillation with an exter-
nal defibrillator, as compared with performing car-
diopulmonary resuscitation before defibrillation
an analysis that could be of use in the future to
direct therapy in humans when the onset time of
arrest is unknown.7
A patient such as the patient under discussion
with cardiac arrest associated with ventricular fi-
brillation will usually require definitive airway con-
trol with endotracheal intubation in the field or on
arrival to the emergency department; this proce-
dure was performed in the field in this case. Pa-
tients who have no response to initial defibrillation
attempts may benefit from vasopressor agents such
as epinephrine or vasopressin, or both; epineph-
december 8 , 2005
 case records of the massachusetts general hospital

A B
2

mV
0

2
0.0 0.5 1.0 1.5 2.0
Seconds
2

mV
0

2
0.0 0.5 1.0 1.5 2.0
Seconds

Figure 2. Electrophysiology of Ventricular Fibrillation.

A computer-generated two-dimensional model in four segments (Panel A) shows a cardiac scroll wave (arrow), which degenerates over time
into smaller wavelets (arrowheads). This phenomenon is associated with an initial coarse tracing of ventricular fibrillation on a representative
rhythm strip at 60 seconds after the onset of arrest (Panel B, top), which later becomes finer, over a period of 600 seconds (Panel B, bottom).
(Panel A is reprinted with permission from Weiss et al.,1 and Panel B is reprinted with permission from Angelos et al.2)

rine was used in this case when initial shocks were
unsuccessful. Although they have not been proved
to reduce mortality, these agents may improve cor-
onary-perfusion pressure, and their benefit may be
synergistic.8 The efficacy of antidysrhythmic agents
in improving outcomes by altering repolarization or
other electrophysiological characteristics remains
uncertain. Amiodarone may improve the return of
spontaneous circulation with defibrillation, but it
has not been proved to increase the likelihood of
survival to hospital discharge.9,10 The results of tri-
als of other agents that delay repolarization and
prolong the myocardial cellular refractory period,
such as bretylium and sotalol, have been disap-
pointing.11,12 In this patient, lidocaine was used in
the field to treat tachycardia with a wide QRS com-
plex, and amiodarone was substituted when he ar-
rived in the emergency department.
Patients such as this who remain comatose after
cardiac arrest may benefit from hypothermic thera-
py to improve the neurologic outcome.13,14 Tech-
niques to induce rapid hypothermia include chem-
ical paralysis to prevent shivering, external cooling,
and internal cooling with endovascular devices or
the infusion of cold saline or other solutions.15
differential diagnosis
of ventricular fibrillation
induced arrest
Although I am aware of the diagnosis in this case,
the differential diagnosis in a patient such as this
man, who presented to the emergency department
with ventricular fibrillation, is broad and includes
noncardiac disease and both primary nondysrhyth-
mic and dysrhythmic cardiac disease (Table 1).
noncardiac causes of ventricular
fibrillation
Respiratory causes including bronchospasm, aspi-
ration, or both should be considered, but these seem
unlikely to be the causes in this patient, who had no

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 The new england journal of medicine

history of dyspnea. Sleep apnea is associated with

Table 1. Causes of Ventricular FibrillationInduced
nocturnal cardiac arrest, but the patient had no
Cardiac Arrest.
known history of sleep disorder. Primary pulmo-
Noncardiac nary hypertension may lead to sudden death from
Respiratory cardiac causes, but generally only after the develop-
Bronchospasm ment of advanced congestive heart failure. Meta-
Aspiration bolic derangements of potassium, magnesium, cal-
Sleep apnea
cium, or glucose should be considered, and these
values should be checked. Seizure must be consid-
Primary pulmonary hypertension
ered, particularly in this patient, who groaned at
Pulmonary embolism
the onset of the event; however, there was no sup-
Metabolic or toxic porting historical or physical evidence of seizure,
Electrolyte disturbances including acute or prior tonicclonic activity, later-
Medications or drug ingestion al tongue laceration, or incontinence. An underly-
Environmental poisoning ing neurovascular event is possible, but a finding
Sepsis of symmetry on neurologic examination and the
Neurologic
absence of a lesion on CT scanning of the head re-
duce the likelihood.
Seizure
Toxic exposures must always be considered.
Cerebrovascular accident: intracranial hemorrhage
or ischemic stroke
This patient was taking divalproex sodium, a dimer
of valproic acid, and had evidence of the deconges-
Cardiac
tant pseudoephedrine in his serum. Divalproex so-
Structural heart disease
dium would not be expected to cause cardiac ar-
Myocardial ischemia or infarction due to coronary ar- rest, but pseudoephedrine ingestion, coupled with
tery disease
exercise, has been associated with supraventricular
Cardiomyopathy
tachycardia.16 The patient was noted to have a blu-
Dilated ish hue, which raises the slight possibility of met-
Hypertrophic hemoglobinemia or sulfhemoglobinemia, which
Arrhythmogenic right ventricular cardiomyopathy could be caused by a number of medications. The
or dysplasia possibility of an overdose of a cyclic antidepres-
Aortic stenosis sant drug should always be explored, particularly
Aortic dissection in a patient with a history of psychiatric illness. An
Pericardial tamponade overdose of stimulants such as cocaine or amphet-
Congenital heart disease amine is possible. Patients who have had an over-
Myocarditis
dose of narcotic drugs or a benzodiazepine gener-
ally present with depression of respirations and
No structural heart disease
mental status as the primary features. Exposure to
Catecholaminergic polymorphic ventricular tachycar-
dia and right ventricular outflow tract tachy-
an environmental toxin, such as carbon monoxide,
cardia is also possible; however, the patients partner had
Mechanical (commotio cordis) or electrical accidents no medical symptoms.
Preexcitation
Overwhelming sepsis, such as with streptococ-
cal infection, can lead to cardiac arrest and persis-
Heart block
tent hypotension, even in a formerly healthy person.
Drug-induced QT prolongation with torsades de
pointes
Conditions that obstruct blood flow, such as spon-
taneous pneumothorax with secondary elevated in-
Channelopathies
trathoracic tension, and pulmonary embolism more
Long-QT syndrome
typically lead to pulseless electrical activity rather
Short-QT syndrome than ventricular fibrillation. There was no evidence
Brugada syndrome of external hemorrhage, but the possibility of an
internal vascular catastrophe such as rupture of the

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 case records of the massachusetts general hospital
aorta or other major vessel should be investigated.
This would be of particular concern in a young adult
patient if the physical features suggest the presence
of Marfans syndrome.
cardiac causes of ventricular fibrillation
A primarily nondysrhythmic cardiac event such as
acute myocardial infarction can lead to abrupt pump
failure, secondary ventricular fibrillation, or both.
This patients initial electrocardiogram was sug-
gestive of inferolateral myocardial infarction, with
ST-segment elevation in the inferior limb and later-
al chest leads and reciprocal ST-segment depres-
sion in the septal chest leads V1 and V2. Cardiac
arrest due to acute valvular failure would be an un-
likely cause of ventricular fibrillation, unless it was
associated with ascending aortic dissection or acute
myocardial infarction. Cardiologic causes of ob-
struction to blood flow include cardiac tampon-
ade, aortic stenosis, and hypertrophic obstructive
cardiomyopathy. Traumatic pericardial tamponade
is more likely than nontraumatic pericardial tam-
ponade to cause cardiac arrest because of the rapid
accumulation of blood in the pericardial sac. This
patient had no known history of trauma. Aortic ste-
nosis and hypertrophic obstructive cardiomyopa-
thy usually cause symptoms including dyspnea,
chest pain, and sudden death on exertion rather
than at rest. Sudden death in patients with hyper-
trophic obstructive cardiomyopathy is primarily
due to an increased risk of ventricular fibrillation,
not obstruction of flow, but this typically occurs
during exertion. Patients with a congenital ana-
tomical heart disease, such as tetralogy of Fallot, or
those in whom such a defect has been repaired,
may be at increased risk for sudden death from car-
diac causes. This patients arrest occurred while he
was sleeping, and he had no history of congenital
heart disease.
Primary dysrhythmic causes of sudden death
from cardiac causes may or may not be associated
with structural cardiac disease. Coronary artery dis-
ease is the most important structural cause of ven-
tricular fibrillation and may lead to this condition
as a result of acute plaque rupture, localized ische-
mia, and myocardial infarction. Myocardial scar
formation owing to prior myocardial infarction
causes sustained ventricular tachycardia, which
can degenerate to ventricular fibrillation. Dilated
cardiomyopathy from any cause increases the risk
of ventricular fibrillation and ventricular tachycar-
dia, including bundle-branch reentry. Patients with
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myocardial diseases such as hypertrophic cardio-
myopathy and arrhythmogenic right ventricular
dysplasia are at increased risk for ventricular fibril-
lationinduced arrest. Cardiac catheterization of
this patient revealed no evidence of coronary artery
disease and an unremarkable left ventriculogram,
although the results of right ventriculography were
not described.
There are a variety of exercise-induced nonstruc-
tural conditions associated with ventricular tachy-
dysrhythmias and possible sudden death, including
right ventricular outflow tract ventricular tachycar-
dia, catecholaminergic polymorphic ventricular
tachycardia, and commotio cordis, or blunt chest-
wall trauma. Since this patients arrest occurred
during sleep, conditions unrelated to exercise are
probably more important in understanding his
event.
Patients with viral myocarditis can present with
ventricular fibrillation and elevations of the ST
segment and enzyme levels despite having nor-
mal coronary arteries. However, this patient had
no preceding symptoms of viral infection or chest
pain. Ventricular fibrillation may be caused by a va-
riety of other infections, including bacterial endo-
carditis and Chagas disease, which is associated
with right bundle-branch block. In this case, there
was no history of injection-drug use, recent dental
manipulation, valvular heart disease, fevers, or trav-
el to suggest the presence of bacterial endocardi-
tis or Chagas disease. The WolffParkinsonWhite
syndrome is associated with atrial fibrillation and
potentially unstable high-frequency ventricular exci-
tation through conduction by the accessory path-
way. The PR interval and QRS upstroke on this
patients electrocardiogram were normal and not
suggestive of the presence of the WolffParkinson
White syndrome and ventricular preexcitation.
Polymorphic ventricular tachycardia in association
with a prolonged QT interval during sinus rhythm,
termed torsades de pointes, can occur in young
adults as a result of either congenital or acquired
derangements. The QT interval in this patient was
normal.
The understanding of cardiac ion-channel dis-
eases is advancing rapidly, and diseases of the so-
dium, potassium, and calcium channels can lead
to syndromes associated with short and long QT
intervals and to sudden death.17-19 Fatal dysrhyth-
mias may occur with activity (long-QT syndrome,
variant 1) or rest (long-QT syndrome, variant 3), de-
pending on the disease variant. The Brugada syn-
december 8, 2005 2497
 The new england journal of medicine

drome, a disease ascribed primarily to the cardiac
sodium channel, causes sudden death, often noc-
turnal, in young men with no structural heart dis-
ease. The electrocardiographic pattern in patients
with this syndrome is characterized by complete
or incomplete right bundle-branch block, with
downsloping, early ST-segment elevation in the an-
terior precordial electrocardiographic leads. This
patients initial electrocardiogram did not show
the typical features; however, the right-sided elec-
trocardiogram is suggestive of the presence of the
Brugada syndrome. With the Brugada syndrome as
with other abnormalities of conduction, such as
the long-QT syndromes and the WolffParkinson
White syndrome, manifestations of the conduction
abnormality can vary considerably on the resting
electrocardiogram as a function of the autonomic
and physiologic milieu.

A Sodium channel within cell membrane B Active sodium channel Inactive sodium channel
Voltage-sensing
segments
Central pore
Na+ Selectivity filter

Cell Selectivity filter

membrane

Activation
gate
Central pore
Inactivation gate
Inactivation gate

I II III IV Domains
4340delA=
premature stop
R1432G R1623Q
T1304M T1620M
R1644H

Cell
Extracellular membrane

S6
S1 S2 S3 S4 S5

Intracellular E1784K
T1645M
IVS7+4insAA L567Q T632M D1790G
N1325S R1512W
NH2 KPQ 1795insD
Brugada syndrome 1505-1507
A1924T
Long-QT syndrome COOH
LQT3 and Brugada syndrome

Figure 3. The Cardiac Sodium Channel with Some Sites of Mutations Associated with the Brugada Syndrome and the Long-QT Syndrome.
Panel A shows the three-dimensional configuration of the cardiac sodium-channel pore. Panel B shows an active and an inactive sodium
channel. A linear map of the protein (Panel C) shows the four transmembrane domains (I, II, III, and IV) and the sites of common mutations.
Protein mutations associated with the Brugada syndrome are shown in purple; those causing the long-QT syndrome are in red, and yellow is
associated with both the long-QT syndrome, variant 3 (LQT3), and the Brugada syndrome. The S4 segments of each domain are colored pink
to signify their overall positive charge and instrumental role in sensing the transmembrane voltage.

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 case records of the massachusetts general hospital

the brugada syndrome istics of a pattern of right bundle-branch block and

The Brugada syndrome is an autosomal dominant
disease caused by a variety of mutations of the car-
diac sodium-channel genes. Different defects of
the same gene, SCN5A, are also responsible for
long-QT syndrome, variant 3. Although there are
many remaining questions, substantial progress
has been made in understanding the structure and
function of the sodium channel protein resulting
from this gene (Fig. 3).20,21 Defects associated
with the Brugada syndrome lead to premature in-
activation and other loss-of-function abnormali-
ties of the cardiac sodium channel. Differential
manifestation of a specific conducting defect with-
in and between the ventricular epicardium and en-
docardium leads to heterogeneous cellular repo-
larization across the myocardium and the potential
for reentrant ventricular tachydysrhythmias such
as polymorphic ventricular tachycardia and ventric-
ular fibrillation.22 The disease appears to be preva-
lent in Southeast Asian populations and is at least
partly responsible for the nocturnal sudden death
described as lai tai (death during sleep) in Thai-
land, bangungut (to rise and moan during sleep
and then die) in the Philippines, and pokkuri (un-
expected sudden death from cardiac causes at night)
in Japan.23 The clinical manifestations are nine
times as common among men as among women,
often first occurring in the third or fourth decade of
life and in patients at rest or during sleep.
The diagnosis of the Brugada syndrome is made
on the basis of the electrocardiographic character-
an elevation at the J point that is greater than 2 mm,
with a slowly descending ST segment in conjunc-
tion with flat or negative T waves in the right pre-
cordial leads V1, V2, or V3. In addition, there would
be a history of syncope, inducible polymorphic
ventricular tachycardia or ventricular fibrillation, or
sudden death from cardiac causes in the patient or
a family member and no obvious structural cause
of sudden death.24,25 The electrocardiographic mor-
phology associated with the Brugada syndrome var-
ies in individual patients, decreasing in prominence
with sympathetic stimulation and exercise and in-
creasing with body temperature and the adminis-
tration of class I antidysrhythmic agents, which
variably decrease sodium-channel conduction.26,27
Thus, the diagnostic test in this case should be a
repeated electrocardiogram.
dr. keith marills diagnosis
The Brugada syndrome.
diagnostic discussion
Dr. Manini: A second electrocardiogram was ob-
tained (Fig. 4), which demonstrated downsloping
ST-segment elevations in leads V1 and V2 with a pat-
tern of partial right bundle-branch block. Straight
down sloping of the ST segment in V1 and a saddle
appearance of the ST segment in V2 were suggestive
of known variants of the Brugada syndrome pattern.

A B

V1
I aVR V1 V4

II aVL V2 V5 V2

III aVF V3 V6 V3

Figure 4. Additional Electrocardiograms.

An electrocardiogram obtained approximately seven hours after the first (Panel A) shows a pattern of incomplete right bundle-branch block
and downsloping ST-segment elevation in the anterior septal leads V1 and V2, consistent with patterns associated with the Brugada syn-
drome. Classically, in the Brugada syndrome, the ST segment in these leads is coved, showing upward concavity. This patients electrocar-
diogram shows two common variants of ST-segment morphology: a straight downward ST segment in lead V 1 (arrow) and a saddle-shaped
ST segment in lead V2 (arrowhead). An electrocardiogram obtained the next day (Panel B), 31 hours after the initial tracing, shows more clas-
sic coving of the ST segment in lead V2 (arrow).

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 The new england journal of medicine

On the basis of the electrocardiographic find- consultant, but it was deferred because the patient
ings, in concert with the clinical circumstances, a had purposeful movements and was not unequivo-
diagnosis of the Brugada syndrome was made. cally comatose and because the procedure carries
some risk. A cooling blanket and acetaminophen
discussion of management were used to maintain euthermia. Follow-up brain
magnetic resonance imaging revealed changes con-
Dr. Marill: This patient did not have a family history sistent with the presence of anoxic brain injury. On
of cardiac dysrhythmias or sudden death but had a the second hospital day, bloody diarrhea occurred
ventricular fibrillationinduced cardiac arrest, no and an abdominal CT performed with contrast ma-
evident structural cause, and on a repeated electro- terial showed changes consistent with the pres-
cardiogram, findings characteristic of the Brugada ence of ischemic colitis. On the third day, the pa-
syndrome. If he recovers from this episode, what tient remained comatose and did not respond to
are the prognosis and management options? stimuli; the prognosis for a neurologic recovery
The likelihood of sudden death from cardiac was thought to be poor. After the clinicians con-
causes in patients with the Brugada syndrome in- sulted with the patients family, life support was
creases with a history of syncope or cardiac arrest, withdrawn and the patient died. An autopsy was
a spontaneous as opposed to drug-inducible not performed.
abnormality on electrocardiography, male sex, and Dr. Patrick T. Ellinor : It was recommended that
probably, the potential to induce ventricular tachy- all the patients first-degree relatives be screened
dysrhythmias with programmed electrical stimula- for the Brugada syndrome. The patients 32-year-
tion.28-30 This patients history clearly puts him at old brother had no cardiac symptoms. His evalua-
high risk for a recurrence. Primary therapy for all tion, which included the results of a stress test per-
symptomatic patients with the Brugada syndrome formed a few months earlier for atypical chest pain,
is an automatic implantable cardioverterdefibril- a resting electrocardiogram, and an echocardio-
lator. His family members should be evaluated for gram, was normal. There were no inducible ST-seg-
evidence of the Brugada syndrome. Testing involves ment abnormalities present after the infusion of
electrocardiography, followed by repeated electro- procainamide. To my knowledge, the parents have
cardiography in the electrophysiology laboratory not been evaluated. The only identified cause of the
after challenge with a sodium-channelblocking Brugada syndrome is an abnormality in the cardiac
agent such as procainamide if the initial tracing is sodium channel; however, mutations in this gene
normal; programmed electrical stimulation may appear to account for only one third of the cases.
be helpful for diagnosis and assessment of the risk Testing for mutations in this gene is commercially
of tachydysrhythmia if the electrocardiogram shows available, but a negative result would not be help-
abnormalities. The approach to an asymptomatic ful. As part of a research protocol in our laboratory,
patient remains challenging.28-30 the cardiac sodium channel SCN5A was analyzed
Dr. Manini: The patient was transferred to the and no mutation was identified in this patient.
cardiac intensive care unit in critical condition. The Dr. Marill reports owning equity in Medtronic and in Johnson &
placement of an automatic implantable cardiover- Johnson/Guidant.
We are indebted to Dr. David F. Brown for his assistance with this
terdefibrillator was deferred until the extent of his discussion and to Drs. Josep Brugada and William Catterall for their
neurologic recovery could be determined. Induc- generous contributions to the manuscript figures.
tion of hypothermia was considered by a neurology

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