Download pdf - Original Article Clinical observations of supraventricular ...Clinical observations of supraventricular arrhythmias in patients with brugada syndrome Bing Liu, Chengjun Guo, Dongping

Int J Clin Exp Med 2015;8(8):14520-14526www.ijcem.com /ISSN:1940-5901/IJCEM0008425

Original ArticleClinical observations of supraventricular arrhythmias in patients with brugada syndrome

Bing Liu, Chengjun Guo, Dongping Fang, Jinping Guo

Department of Cardiology, Beijng Anzhen Hospital, Capital University of Medical Sciences, Beijing, China

Received March 25, 2015; Accepted June 4, 2015; Epub August 15, 2015; Published August 30, 2015

Abstract: Objective: To study various types of supraventricular arrhythmias in patients with Brugada Syndrome. Methods: Forty six patients with ECG of spontaneous type Brugada and with ventricular and/or supraventricular tachyarrhythmia, without structural heart diseases which were excluded by echocardiography, underwent 24 h-Holter recording, electrophysiological study and/or radiofrequency ablation. Results: There were thirty-nine male and seven female (mean age 37.44 years) among total forty-six patients. Twenty one patients had family histories of tachycardia, twentythree patients experienced episodes of syncope, and three patients were resuscitated from cardiac arrest. One patient had ventricular fibrillation and third degree atrioventricular block, eleven patients had polymorphic ventricular tachycardia and five patients had monomorphic ventricular tachycardia. Fourteen patients had atrial tachyarrhythmia, paroxysmal supraventricular tachycardia was found in five patients including four Wolf-Parkinson-White syndrome, two patients hadventricular tachycardia and third degree atrioventricular block, one of them had atrial fibrillation, two patients had both supraventricular tachycardia and ventricular tachycardia, three patients had both atrial tachyarrhythmia and supraventricular tachycardia, two third degree atrioventricular block patients had atrial flutter, one patienthad both atrial tachyrhythmia and ventricular tachycardia. Radiofrequency bla-tion was performed in thirty-nine patients and succeed in thirty-two, four patients were implanted with pacemakers, and four patients had implantable cardioverter defibrillators. Conclusion: In addition to ventricular tachycardia and ventricular fibrillation, patients with Brugada syndrome exhibit various supraventricular tachyarrhythmia and third degree atrioventricular block. In patients with Brugada syndrome, the dysfunction of the cardiac ion channel, which related to mutation of cardiac sodium channelgene, is not limited in His Purkinje system and ventricular myocar-dium, but also in the atrium and atrioventricular node, which may serves as a cause of dispersion of repolarization and phase 2 reentry leading to various arrhythmias.

Keywords: Brugada syndrome, cardiac arrhythmia, conduction abnormality, atrioventricular block, supraventricu-lar tachyarrhythmia

Introduction

Brugada syndrome (BS) is an autosomal domi-nant genetic disease characterized by dome-typed or saddle-shaped ST segment elevation in V1~V3 leads, with diagram in V1 lead resemb-lingthat of right bundle branch block [1, 2]. Patients suffer from paroxysmal palpitations, syncope, or ventricular fibrillation (VF) which leads to sudden unexplained nocturnaldeath [3]. The current study found that BSis associ-ated with dysfunction of the sodium channel caused by mutation of the SCN5A gene which encodes α subunit of cardiac sodium channel [4]. Since BS is causedby mutation of cardiac sodium channel gene, then the sodium channel

dysfunction should not be limited to ventricular muscle, other parts of the myocardium should also have this problem which will trigger a vari-ety of arrhythmias. Current studies focuses mostly on the mechanism of BS complicated ventricular tachycardia (VT) and ventricular fibrillation, not many reports on supraventricu-lar arrhythmia. Here we reported the clinical observation results of 46 cases of BS patients complicated with various types of arrhythmias.

Materials and methods

Patients who visited our hospital between March 1998 to March 2007 suffering from heart palpitations, syncope and nocturnal dys-

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Supraventricular arrhythmias of brugada syndromepatients

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pnea were selected for routine ECG study. If found to have ST segment elevationin leads V1~V3, excluded organic heart disease and elec-trolyte imbalance by physical examination, blood biochemical tests, echocardiogra-phy and coronary angiography, diagnosed with the “Expert Consensus Recommendations” about BS diagnosis and treatment revised in 2005 as a diagnostic criterion [5]. Spontaneous type I Brugada syndrome was diagnosed direct-ly by the combination of ECG changes with his-tory of illness and familyhistory; Type II and IIIBrugada syndrome was diagnosed with initial ECG with induced ECG changes in the precor-dial leads inPropafenone stimulation test; Induced type I Brugada syndrome was diag-nosed with the combination of ECG changes with history of illness and family history. For all BS patients, routine ECG and Holter were per-formed to observe the types of arrhythmia, and for some patients,conventional electrophysiol-ogy and radiofrequency ablation were per-formed following the protocol described in the literature [6]. Permanent cardiac pacemakers were implanted in patient with symptomatic third-degree atrioventricular block, and implant-able cardioverter defibrillators (ICD) were implanted in patients with cardiac arrest and

who could afford the cost. In this study, the term supraventricular arrhythmia means atrial arrhythmia or arrhythmia caused by atrioventricular bypass and dual atrioventricular node pathways, and paroxysmal supraventricular tachycardia (PSVT) means supraventricular tachycar-diacaused by atrioventricular bypass and dual atrioventricular node pathways.

Results

Total forty-six cases who met the BS diagnostic criteria were treated during the nine-year periods as above men-tioned, with thirty-nine males and seven females, and ages ranging from twelve to sixty-six years old (37.44 ± 14.52). Twenty-one cases have a family history, and twenty-three cases have history of syncope, including three cases undergo-ing cardiopulmonary resuscitation (Table 1). Among the total forty-six cases, there arefive cases complicated with paroxys-mal supraventricular tachycardia (PSVT,

Table 1. Clinical characteristics of patients with Brugada SyndromeClinical characteristics Number of casesTotal number of patients 46Male 39Female 7History of illnessPalpitation 43Syncope 23Cardiopulmonary resuscitation 3Family history 21TreatmentsElectrophysiology exam + RFA 35Electrophysiology exam + RFA + pace maker 3Electrophysiology exam + ICD 3Electrophysiology exam + RFA + ICD 1Electrophysiology exam 1Pace maker 1Follow-up 2Follow-up time (5.25±2.37) yearsNote: ICD=implantable cardioverter defibrillators; RFA=radiofrequency ablation.

with four cases of dominant WPW syndrome, Figure 1); two cases of PSVT coexisting withVT; three cases of PSVT coexisting with atrial flutter (AFL); fourteen cases of atrial tachycardia (AT) coexisting withAFL and atrial fibrillation (AF); two cases of AT coexisting with third-degree atrioventricular block; one case of AT coexisting with VT; eleven cases of polymorphic VT; five-cases of monomorphic VT; one case of ventric-ular fibrillation (VF) electrical storm coexisting with third-degree atrioventricular block; one-case of VT coexisting withthird-degree atrioven-tricular block; one case of VTcoexisting with third degree atrioventricular block and AF. There are total ten cases (21.74%, Table 2) coexisting withPSVT (with/without other types of arrthymia) among the forty-six BS cases, six of which wereconfirmed as paroxysmal atrio-ventricular reentrant tachycardia (AVRT, 13.04%), and the rest fourwere confirmed as paroxysmal atrioventricular nodal reentrant tachycardia (AVNRT, 8.70%. Figure 2 by electro-physiological examination. There are twenty-two cases concurrent with rapid atrial arrhyth-mia (47.83%, Figure 3), including eighteen cases of atrial flutter and atrial fibrillation (39.13%, Figure 4), seventeen cases of which were treated with radiofrequency ablation with


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success in eleven cases, and three cases had recurrence of the arrhythmia during follow-ups. There are five cases concurrent with three-degree atrioventricular block (10.87%). There are twenty-two cases (47.83%) concurrent with rapid ventricular arrhythmias (with or without

other types ofarrhythmia). There are different degrees ofintraventricular block in all forty-six cases. Thirty-nine cases underwent radiofre-quency ablation with success in thirty-two cases, four cases were implanted with implant-able cardiac pacemakers, one case underwent

Figure 1. ECG in a patient with Brugada syndrome coexisting within intermittent WPW syndrome. Patient is a 37-year-old male, with arrows indicating the oblique ST segment in V1lead, and ST segment elevation in V2leads inversely down during pre-excitation.

Table 2. Clinical characteristics of PSVT in patients with Brugada syndrome

ID Age/gender Palpitation Syncope CPR Family history Arrthymia SVT type/VT and AF origin Treatment/follow-up (years)

1 34/F + - - - PSVT AVRT RFA/42 59/M + - - + PSVT/AF AVNRT/PV RFA/73 45/M + - - - PSVT/VT AVNRT/RVOT RFA/4.54 42/M + - - + PSVT/AF AVNRT/PV RFA/75 48/M + + - + PSVT/AFL LAVRT RFA/76 47/F + - - - PSVT AVNRT RFA/3.57 37/F + + - - PSVT/VT AVRT/RT, His B. RFA/48 42/M + - - - PSVT AVRT RFA/59 25/M + - - - PSVT AVRT RFA/4.510 36/M + - - - PSVT AVRT RFA/5Note: F=female; M=male; AFL=Atrial flutter; AF=Atrial fibrillation; RFA=radiofrequencyablation; AVRT=atrioventricular reentrant tachycardia; AVNRT=atrioventricular nodal reentrant tachycardia; RVOT=Right ventricular outflow tract; RV=Right ventricle; PV=Pulmonary vein; PSVT=paroxysmal supraventricular tachycardia; VT=Ventricular tachycardia; CPR=Cardiopulmonary resusci-tation; His B.=His bundle.


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Figure 2. ECG in a patient with Brugada syndrome coexisting withatrioventricular nodal reentrant tachycardia.Pa-tient is a 42-year-old male, with sinus rhythm (left) and atrioventricular nodal reentrant tachycardia at onset (Right).

Figure 3. ECG in a patient with Brugada syndrome coexisting withatrial tachycardia. Patient is 36-year-old male.


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electrophysiological examination alone, and four cases were implanted with ICDs. There is one case of paroxysmal atrial tachycardia showing concurrence of BS and short QT syn-drome (SQTS) (Figure 5).

Discussion

Clinically, BS usually coexists with malignant ventricular arrhythmias, with sudden cardiac death as the initial presentation in some cases, and has become the focus of clinical studies recently. In our study, among total forty-six BS cases, there are thirty-two cases complicated by rapid atrial arrhythmia and/orparoxysmal supraventricular tachycardia and atrioventricu-lar block, few such studies have been reported in the literature.

Our data confirm that, besides ventricular tachycardia and ventricular fibrillation, BS patients can also be complicated by non-ven-tricular arrhythmias, including atrial flutter and atrial fibrillation (39.13%), AVRT (13.04%) and AVNRT (8.70%). Two or more types of arrhyth-mias can coexist. In 1999, Anzelevitchet al reported only 10% of BS patients were compli-

cated with paroxysmal atrial fibrillation, but recent studies have shown that the concur-rence rate can be as high as 39%, which is simi-lar to the results inour study [7].

The present studies suggest that the mecha-nism of arrhythmia in BS patients is dysfunc-tion of the sodium channel in the cell membran-ecaused by gene mutation, such as accelerat-ed inactivation or decelerated reactivation, which results in loss of the action potential (AP) dome. This loss is, however, heterogeneous, generating epicardial dispersion of repolariza-tion. This dispersion creates a vulnerable win-dow, which allows phase 2 reentry to cause a premature impulse, which triggers VT/VF based on reentry between transmural layers [8, 9]. Since BS is caused by mutation of the cardiac sodium channelgene, then the above men-tioned mechanisms of increase of repolariza-tion dispersion and reentry can also existin atrial and atrioventricular node cells, which per-haps help to explain the pathogenesis of atrial tachy-arrhythmias and AVNRT in BS patients [10]. Increases in tension of Vagus nerve and hemodynamic changes caused by supraven-

Figure 4. ECG in a patient with Brugada syndrome coexisting withatrial flutter. Patient is a 50-year-old male.


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Figure 5. ECG in a patient with Brugada syndrome coexisting with short QT syn-drome. Patient is a 19-year-old male. A. Standard lead ECG. The heart rate is 85 beats/min, QT interval is 280 mS, with ST segment almost completely lost, and high and sharp symmetrical T waves on the right chest leads. B. Dynamic ECG showing atrial tachycardia.

tricular tachy-arrhythmias can be inducing fac-tors forventricular tachy-cardia and ventricular fibrillation in BS patients. The mechanism for con-currence of BS with AVRT is currently unknown [11], and it is suggested that electrophysiological examination and drug provo-cation test should be per-formed in WPW syndrome patients with history of sudden death in order to detect BS. In our study, there areforty-six cases (100%) coexisting with intraventricular block, and five cases coexisting with third degree atrio-ventricular block, indicat-ing that conduction de- lays exist in atrium, atrio-ventricular junction and ventricle, and conduction delay may be associated with tachy-arrhythmias, which provides a new idea for pathogenesis of concurrent tachyarrhyth-mia in BS patients.

There are few studies published for non-ventric-ular arrhythmias in BS patients, thus it is possi-ble that a large number of concurrent supraventric-ular arrhythmias in BS patients have long been neglected. In clinical, in addition to ventricular tachy-arrhythmias, non-ventricular arrhythmias such as atrial flutter, atri-al fibrillation, AVNRT or even AVRT and third degree atrioventricular block should also be con-sidered as reasons to cause palpitations and syncope in BS patients. In BS patients with syn-cope likely caused by


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supraventricular tachy-arrhythmia, atrial stimu-lation should be performed during electrophysi-ological examination to induce such arrhyth-mia. Incases of BS concurrent with supraven-tricular tachycardia, radiofrequency ablation should be the preferred treatment; the use of IC antiarrhythmic drugsshould be avoided. In BS patients with syncope, an ICD with supraven-tricular tachycardia recognition function should be chosen to avoid false discharge [12].

Studies have found that BS can coexist with SQTS suggesting that BS is possibly a polygenic disease. The currently known three causative genes for SQTS, KCNH2, KCNQ1 and KCNJ2 can all encode cardiac potassium channels [13], the abnormalities of which can cause-shortening of QT interval. But BS and SQTS coexistence case was not found in our study.

Disclosure of conflict of interest

None.

Address correspondence to: Chengjun Guo, Depart- ment of Cardiology, Beijng Anzhen Hospital, Capital University of Medical Sciences, No.2, Anzhen Road, Chaoyang District, Beijing 100029, China. Tel: 86-010-64456132; E-mail: [email protected]

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