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Research
Case Report/Case Series
Brugada Syndrome Presenting as Polymorphic Ventricular
Tachycardia–Ventricular Fibrillation Lasting 94 Seconds
Recorded on an Ambulatory Monitor
Christopher R. Russo, MD; Terrence D. Welch, MD; Rajbir S. Sangha, MD; Mark L. Greenberg, MD
IMPORTANCE Cardiac arrhythmias are common causes of syncope. Brugada syndrome is an
uncommon but serious genetic arrhythmia disorder that can be unmasked by medicines
causing sodium channel blockade.
OBSERVATIONS This report documents a case of Brugada syndrome and polymorphic
ventricular tachycardia–ventricular fibrillation not initially recognized in a patient taking
nortriptyline and experiencing syncope. It also illustrates one of the longest episodes of
ventricular fibrillation recorded on an ambulatory monitor (94 seconds). Although the
baseline electrocardiogram did not demonstrate a typical appearance for Brugada syndrome,
provocative testing with flecainide in this patient with documented polymorphic ventricular
tachycardia revealed a Brugada electrocardiogram pattern.
CONCLUSIONS AND RELEVANCE Vigilance should be maintained for arrhythmia substrates
such as Brugada syndrome in patients with typical symptoms when they are prescribed
membrane-active medicines. Long-term ambulatory rhythm monitors can provide useful
information in these cases, especially when symptoms are infrequent.
JAMA Intern Med. 2015;175(12):1951-1954. doi:10.1001/jamainternmed.2015.5934
Published online October 26, 2015.
C
ardiac arrhythmias are common causes of syncope.
Brugada syndrome is an uncommon but serious
genetic arrhythmia disorder that can be unmasked by
medicines causing sodium channel blockade.
Report of a Case
A woman in her 40s with a history of severe depression and
a diagnosis of apparent generalized seizure disorder presented to the emergency department (ED) after a syncopal
episode. She had lost consciousness at home, and when she
regained consciousness, her husband brought her to the ED.
At presentation, she was alert and asymptomatic. She
described an extensive history of palpitations and presyncope previously investigated with a Holter monitor, echocardiogram, tilt-table test, and nuclear cardiac stress test
with no remarkable findings. Several years earlier, she had
experienced a grand mal seizure and undergone 2 electroencephalography (EEG) tests, the results of which did not
indicate epilepsy. There was no family history of sudden
cardiac death. Her only medication was nortriptyline for
depression.
Findings of physical examination and a comprehensive
laboratory workup were unremarkable. Sinus tachycardia
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Author Affiliations: Section of
Cardiology, Dartmouth Hitchcock
Medical Center, Lebanon,
New Hampshire.
Corresponding Author: Rajbir S.
Sangha, MD, Section of Cardiology,
Dartmouth Hitchcock Medical Center,
Geisel School of Medicine at
Dartmouth, One Medical Center Dr,
Lebanon, NH 03756 (Rajbir.S.Sangha
@hitchcock.org).
was present on electrocardiogram (ECG), with a QTc of 500
milliseconds (heart rate–corrected [Bazett formula] QT 374,
milliseconds; sinus rate, 107 bpm) without significant
ST-segment changes. Monitoring in the ED revealed sinus
tachycardia and no arrhythmias. She was discharged with
an ambulatory patch recording device for extended ambulatory cardiac rhythm monitoring.
Two days later, she was again seen in the ED with
another profound episode of syncope and what appeared
to be a seizure. She had no clear recollection of the event,
but her spouse reported that she had prolonged loss of
consciousness with associated shaking activity of her
arms. She was wearing the monitoring patch at the time
of the episode. Findings of her evaluation in the ED were
again unremarkable, and she was discharged to home to
continue ambulatory monitoring and with plans for an
outpatient EEG.
After 14 days, the ambulatory monitor was mailed in to
the manufacturer. There were 4 prolonged episodes of polymorphic ventricular tachycardia–ventricular fibrillation
(PVT-VF), with the longest 2 episodes being approximately
94 seconds (Figure 1) and 38 seconds. Immediate admission
to the cardiology service was arranged, and urgent evaluation performed. Although the patient diary only reported a
“seizure” with the more brief episode, the longer episode,
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Research Case Report/Case Series
Ventricular Tachycardia–Fibrillation Recorded on an Ambulatory Monitor
Figure 1. A Single 94-Second Polymorphic Ventricular Tachycardia–Ventricular Fibrillation Event
Captured on the Ambulatory Monitor (Continuous Recording Across 2 Pages)
400 ms
Figure 2. The Initial 12-Lead Electrocardiogram From the Second Emergency Department Visit
aVR
V1
V4
aVL
V2
V5
aVF
V3
V6
which occurred at 8:29 AM, correlated with the event that
prompted her second visit to the ED.
The cardiac evaluation included an ECG (Figure 2),
echocardiography, cardiac magnetic resonance imaging,
and coronary angiography, all of which revealed nothing
remarkable. Review of all available prior ECGs showed no
consistent evidence of prolongation of her QTc interval,
with the exception of her earlier ECG in the ED, where her
baseline QT was likely overcorrected in the setting of a sinus
1952
tachycardia. Because of concern for Brugada syndrome, a
flecainide challenge was then performed. After a single
400-mg oral dose of flecainide, the ECG revealed a type I
Brugada pattern (Figure 3). She was diagnosed with Brugada
syndrome and received a subcutaneous implantable
cardioverter-defibrillator (ICD). Her nortriptyline treatment
was discontinued.
Subsequent genetic testing (Familion; Transgenomic
Inc) did not reveal a known mutation for Brugada syn-
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Ventricular Tachycardia–Fibrillation Recorded on an Ambulatory Monitor
Case Report/Case Series Research
Figure 3. The 12-Lead Electrocardiogram After Flecainide Challenge
aVR
V1
V4
aVL
V2
V5
aVF
V3
V6
drome. The patient had no further syncopal events or symptoms. Ambulatory monitoring was repeated with no significant arrhythmias noted, and the subcutaneous ICD did not
deliver any therapeutic pulses in over a year of follow-up.
Discussion
The Brugada pattern on ECG is characterized by a peculiar
form of ST segment elevation in leads V1-V3. When the ECG
pattern is accompanied by other criteria (eg, personal history of syncope, ventricular arrhythmias, suspicious family
history), Brugada syndrome can be diagnosed. In some
countries, Brugada syndrome may be the second most common cause of death in young adults,1 with sudden cardiac
death as the first presentation of the condition. Mutations in
the cardiac sodium channel SCN genes appear to predominate, although changes in potassium, calcium, and trafficking genes have also been described. Typical ECG manifestations include a pseudo–right bundle branch block pattern
and ST-segment elevation in the right precordial leads.
These abnormalities may be transient and become manifest
only with stimuli such as fever, electrolyte abnormalities, or
medications such as tricyclic antidepressants or sodium
channel blockers. Findings of routine cardiac imaging are
usually normal.
Although a case of Brugada syndrome with 2 minutes
and 41 seconds of spontaneously terminating ventricular
fibrillation has been recorded on an implantable monitor,2
the present case is, to our knowledge, the longest known
wearable ambulatory rhythm recording of PVT-VF in a nonresuscitated patient who survived to ICD placement with
normal neurologic function. On the basis of her history and
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prior episodes of prolonged syncope, this patient had been
presumed to have a seizure disorder. Limited reports in the
literature suggest that spontaneous conversion of lifethreatening ventricular tachyarrhythmias is more common
in young women without structural heart disease, torsade
de pointes as the VT mechanism, and patients taking class I
antiarrhythmic drugs.3 The formation of stable rotors identifies patients who are likely to need defibrillation.4 Longterm wearable ambulatory rhythm monitors can now provide 2 to 4 weeks of continuous monitoring, which may
allow a more thorough evaluation for arrhythmia.5
In the present case, Brugada syndrome was the likely
cause of episodes of convulsive syncope misdiagnosed as a
seizure disorder. It is not uncommon for infrequent arrhythmia substrates to be misdiagnosed as seizures. There is a
known association between epilepsy and sudden death, and
there appears to be an association between epilepsy, Long
QT syndrome, and Brugada syndrome. Sudden unexpected
death in epilepsy has a reported incidence as high as 2.65
per 1000 patient years.6 In the present case, the use of nortriptyline may have contributed to the development of syncope from ventricular tachyarrhythmias.7 Nortriptyline is a
tricyclic antidepressant with sodium channel blocking properties; such medicines should be avoided in the setting of
Brugada syndrome.8
Conclusions
This case highlights the importance of definitively excluding
cardiac arrhythmias in patients with unexplained syncope or
seizurelike episodes and also the need to conduct an exhaustive search for the cause of ventricular tachyarrhythmias in
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Research Case Report/Case Series
Ventricular Tachycardia–Fibrillation Recorded on an Ambulatory Monitor
these cases. Longer-term ambulatory monitoring can be of
value. Genetic testing can be helpful, but it has a low sensitivity and was not helpful in the present case. It should be
ARTICLE INFORMATION
Accepted for Publication: September 8, 2015.
Published Online: October 26, 2015.
doi:10.1001/jamainternmed.2015.5934.
Author Contributions: While Drs Sangha and
Greenberg had full access to all of the data in the
study and take responsibility for the integrity of the
data and the accuracy of the data analysis, all
authors contributed equally to this article.
Study concept and design: Russo, Welch, Sangha.
Acquisition, analysis, or interpretation of data:
Greenberg.
Drafting of the manuscript: Russo, Welch, Sangha.
Critical revision of the manuscript for important
intellectual content: Welch, Sangha, Greenberg.
Administrative, technical, or material support:
Russo, Greenberg.
Study supervision: Sangha, Greenberg.
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remembered that the Brugada ECG pattern may be intermittently present, and a flecainide challenge should be considered in appropriate patients.1
Conflict of Interest Disclosures: None reported.
from self-terminating episodes in humans. J Am Coll
Cardiol. 2014;63(24):2712-2721.
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Electrocardiographic patch devices and
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stability separates sustained ventricular fibrillation
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Accessed September 16, 2015.
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