Spontaneous Alternans in Brugada ST-Segment Morphology Within Minutes

Written By: Sam Savage

Published Date: August 13, 2008 Last Edited: August 13, 2008

By Ariyarajah, Vignendra Smith, Hugh; Hodge, Steve; Khadem, Aliasghar

Abstract Brugada syndrome is an inherited, life-threatening, cardiac channelopathy where the electrocardiogram (ECG) characteristically depicts a classic pattern of complete or incomplete right bundlebranch block with ST-segment elevation in the right precordial leads V^sub 1^ to V^sub 3^. These, almost inalienable, ECG patterns may be dynamic, where changes may resolve to baseline or one particular type may evolve into another. Such alternans has been described with fever, electrolyte imbalances, atrial pacing, glucose and/or insulin administration, psychotropic drugs, beta-adrenergic blocker use, class IA and IC antiarrhythmic provocation testing, such as with ajmaline, procainamide, or flecainide, and even large meals, that is, “full stomach sign.” However, spontaneous alternans between the different types of Brugada ECG patterns (types) have not been reported within minutes, in the absence of previously described precipitating factors. We present a novel case where classic, type 2, Brugada-like ECG pattern evolved spontaneously to type 1 before returning to type 2 within minutes of presentation.

Keywords: Brugada syndrome; Type 1; Type 2; Spontaneous alternans

Introduction

Brugada syndrome, first described in 1992 by Pedro and Josep Brugada,1 is an autosomal dominant, life-threatening, cardiac channelopathy where the electrocardiogram (ECG) characteristically depicts a classic pattern of complete or incomplete right bundle- branch block with ST-segment elevation in the right precordial leads V^sub 1^ to V^sub 3^ (Fig. 1). Three distinct types of Brugada-like ECG patterns have been described. In type 1, the ST-segment elevation is 2 mm and descends with an upward convexity to an inverted T wave (Fig. IA).2 This is the classic Brugada type and is often referred to as the “coved-type” Brugada pattern. The type 2 and type 3 patterns demonstrate J-point elevation and have a “saddleback-type” Brugada ST-T wave configuration where the elevated ST segment descends toward the baseline, then rises again to an upright or biphasic T wave. The ST segment is elevated 1 mm in type 2 and less than 1 mm in type 3 (Fig. IB and C).2 These, almost inalienable, ECG patterns may be dynamic, where changes may resolve to baseline or one particular type may evolve into another. Such altemans has been described with fever,3 electrolyte imbalances,4 atrial pacing,5 glucose and/ or insulin administration,5 psychotropic drugs,6 beta-adrenergic blocker use,7’8 class IA and IC antiarrhythmic provocation testing, such as with ajmaline, procainamide, or flecainide,9’10 and even large meals, that is, “full stomach sign.”11 However, spontaneous alternans between the different types of Brugada ECG patterns (types) have not been reported within minutes, in the absence of previously described precipitating factors. We present a novel case where classic type 2 Brugada-like ECG pattern evolved spontaneously to type 1 before returning to type 2 within minutes of presentation.

Case scenario

A previously healthy, 43-year-old, afebrile, Filipino male, who was not on any medications, presented to the emergency department of a peripheral community hospital with chest discomfort. The Brugada- like ST-segment elevations on his ECG (Fig. 2) were misdiagnosed as acute myocardial infarction, and he was given thrombolytic therapy. However, his symptoms did not resolve. Despite negative cardiac enzyme markers and normal serum biochemistry, he then underwent coronary artery angiography. Only when the coronary angiogram showed nonocclusive normal coronary anatomy, a potential arrhythmogenic conduction abnormality was considered.

Fig. 1. Types of Brugada-type ECG patterns.

When the patient’s medical information was reviewed by the arrhythmia service, in the absence of other potential causes for such ECG findings (Table I),2 Brugada syndrome was diagnosed. Interestingly, this patient’s serial ECGs demonstrated spontaneous alternans between the different types of Brugada-like ECG patterns within minutes of each other (Fig. 2). Classic “saddleback-type” patterns of type 2 Brugada-like ECG pattern changed spontaneously to “coved-type” type 1 and subsequently reverted to type 2 within minutes, without drug provocation and in the absence of known factors that could induce change. These spontaneous changes occurred repeatedly, even before beta-adrenergic blocker administration. The patient has been scheduled for electrophysiologic assessment.12

Fig. 2. Evolution from type 2 to type 1 Brugada-type ECG pattern in our patient. A, August 14, 2007, 1840 hours-after administration of sublingual nitroglycerine. B, August 14, 2007, 1853 hours-after administration of aspirin and more sublingual nitroglycerine. C, August 14, 2007, 1923 hours-after administration of more sublingual nitroglycerine and thrombolytic therapy. D, August 14, 2007, 2019 hours-after administration of intravenous beta-adrenergic blocker.

Table 1

Differential diagnosis for the ECG pattern (ie, ST-segment elevation in the right precordial leads)

Discussion

Chest pain is an unusual presentation of Brugada syndrome.2 Syncope and cardiac arrest are, by far, the most common clinical manifestations associated with this disease.2 Because sudden unexplained nocturnal death syndrome or “SUNOS”13 is similarly associated with nocturnal death and can be preceded by nightmares with nocturnal thrashing, these syndromes that are sometimes mistaken for seizures are thought to be phenotypically, genetically, and functionally the same entity.13 Indeed, in several Southeast Asian populations, where it is endemic, it is known by various names such as Bangungut (to rise and moan in sleep) in the Philippines, Lai Tai (death during sleep) in Thailand, and Pokkuri (unexpected sudden death at night) in Japan.14

Brugada syndrome has a male preponderance and usually affects men aged 30 to 50 years.2 Commonly, patients have a structurally normal heart. However, in 30% of patients and families with Brugada syndrome, mutations in the SCN5A gene, which encodes for the voltage- gated cardiac fast sodium channel, have been thought to be the culprit abnormality.2 The resultant inhomogeneities in epicardial and endocardia! action potentials from reduced sodium current flow allows the transient outward current to predominate, primarily in the superior portion of the anterior right ventricular myocytes, where this phenomenon is most strongly expressed.2 This manifests as ST-segment elevation in precordial leads V^sub 1^ to V^sub 3^ in the setting of a complete or incomplete right bundle-branch block pattern.

Fazelifar et al15 reported spontaneous alternans in Brugada-type ECG patterns between type 1 (coved type) and type 2 (saddleback type), particularly in lead V^sub 2^, after permanent implantable pacemaker failure. However, these changes did not occur within minutes. Moreover, in that case, such ECG changes were only noted when the R-R interval changed. They noted the saddleback pattern with decreased R-R interval and coved type pattern with increased R- R interval. Our patient clearly did not have significant change in the R-R interval. During a 40 +- 19-month followup, where 124 consecutive patients with Brugada-type ECG patterns were studied, Ikeda et al16 showed that spontaneous ST-segment change was noted in 41 patients (33%); 28 had manifestation, augmentation, or normalization of ST-segment elevation, 12 had a change from saddleback type to coved type, or vice versa, and 9 had visible alternans on continuous ECG monitoring. However, these observations did not occur within minutes as noted with our patient. The authors however showed that spontaneous change in STsegment elevation was most significant (relative hazard, 9.2; P = .036) among the risk indices for subsequent events that were evaluated such as family history of sudden death, syncopal episodes, spontaneous coved-type ST-segment elevation, and late potentials. Because such changes occurred frequently after a large meal, Ikeda et al11 also later demonstrated that the “full stomach test” could be used to identify high-risk Brugada syndrome patients.

T-wave alternans in Brugada syndrome has also been shown to occur with administration of sodium channel blockers, glucose, and atrial pacing.5 Miyazaki et al7 observed that intravenous isoproterenol consistently reduced ST-segment elevation by >/=0.1 mV or greater for 80 milliseconds after the J point in their patients with Brugada syndrome. They also observed that selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented the ST-segment elevation, whereas alpha-adrenoceptor blockade reduced the ST-segment elevation. Aouate et al8 also presented a case where intentional propranolol overdose resulted in unmasking of the typical coved-type Brugada ECG pattern. Our patient, however, did not receive beta- or alpha-adrenergic blocker therapy while the ST- segment elevations evolved. It is also unknown what the exact role of sublingual nitroglycerine would be in this scenario, although alteration in Brugada ECG pattern after nitroglycerine has been described.17 In addition, there have been no known reports of such ECG change induced by thrombolytic therapy. Although it is unlikely that thrombolytic therapy had any effect on these ECG changes, interestingly, these changes occurred only after or at the time of its administration. Further study is certainly warranted to perhaps ascertain novel factors that may contribute to this phenomenon. Acknowledgment

We thank Maureen Kuppe, CAS, for preparing the figures.

References

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13. Vatta M, Dumaine R, Varghese G, et al. Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNOS), a disease allelic to Brugada syndrome. Hum MoI Genet 2002;! 1:337.

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17. Matsuo K, Shimizu W, Kurita T, Inagaki M, Aihara N, Kamakura S. Dynamic changes of 12-lead electrocardiograms in a patient with Brugada syndrome. J Cardiovasc Electrophysiol 1998;9:508.

Vignendra Ariyarajah, MD,* Hugh Smith, MD, Steve Hodge, MD, Aliasghar Khadem, MD

Division of Cardiology, Department of Medicine, St Boniface General Hospital, University of Manitoba, Winnipeg, Manitoba, USA

Received 29 August 2007; accepted 15 November 2007

* Corresponding author. WRHA/SBGH Cardiac Sciences Program, Bergen Cardiac Care Centre, Winnipeg, MB R2H 2A6, USA. Tel: +1 204 510 2235; fax: +1 204233 9162.

E-mail address: [email protected]

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