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Case Report/Case Series
December 2015

Brugada Syndrome Presenting as Polymorphic Ventricular Tachycardia–Ventricular Fibrillation Lasting 94 Seconds Recorded on an Ambulatory Monitor

Author Affiliations
  • 1Section of Cardiology, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire
JAMA Intern Med. 2015;175(12):1951-1954. doi:10.1001/jamainternmed.2015.5934
Abstract

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.

Introduction

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.

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 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, which occurred at 8:29 am, correlated with the event that prompted her second visit to the ED.

Figure 1.
A Single 94-Second Polymorphic Ventricular Tachycardia–Ventricular Fibrillation Event Captured on the Ambulatory Monitor (Continuous Recording Across 2 Pages)
A Single 94-Second Polymorphic Ventricular Tachycardia–Ventricular Fibrillation Event Captured on the Ambulatory Monitor (Continuous Recording Across 2 Pages)

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 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.

Figure 2.
The Initial 12-Lead Electrocardiogram From the Second Emergency Department Visit
The Initial 12-Lead Electrocardiogram From the Second Emergency Department Visit
Figure 3.
The 12-Lead Electrocardiogram After Flecainide Challenge
The 12-Lead Electrocardiogram After Flecainide Challenge

Subsequent genetic testing (Familion; Transgenomic Inc) did not reveal a known mutation for Brugada syndrome. 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 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 life-threatening 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 Long-term 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 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 remembered that the Brugada ECG pattern may be intermittently present, and a flecainide challenge should be considered in appropriate patients.1

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Article Information

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).

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.

Conflict of Interest Disclosures: None reported.

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