CASE REPORT

Brugada syndrome as a potential cardiac risk factor duringelectroconvulsive therapy (ECT)

CHRISTIAN LUCKHAUS1, MARCUS HENNERSDORF2, MICHAEL BELL3,

MARKUS W. AGELINK4, JURGEN ZIELASEK1 & JOACHIM CORDES1

1Department of Psychiatry and Psychotherapy, Heinrich-Heine-University, Duesseldorf, Germany, 2Department of

Cardiology, Pulmonology and Angiology, Heinrich-Heine-University, Duesseldorf, Germany, 3Department of General

Medicine, Elisabeth Hospital, Essen, Germany, and 4Department of Psychiatry, Psychotherapy and Psychosomatics,

Klinikum Herford, Herford, Germany

AbstractA case of asystole (�5 s) during electroconvulsive therapy (ECT) is reported in a patient who was subsequently diagnosedto have Brugada syndrome (BS). This hereditary sodium-channelopathy is characterized by typical, though intermittent,ECG abnormalities and carries a high risk of ventricular arrythmia and sudden cardiac death. The general occurence of BSis rare; however, it is more prevalent in men and in southeast Asian populations. As in the reported case, BS carriers maylack a telltale medical history and can present with normal ECG recordings. In these cases, BS can only be unmasked byrepeated ECG recordings over time or by specialist cardiological examinations. To our knowledge, BS, which was firstcharacterized in 1992, has not yet been in the focus of cardiac complications during ECT. However, as the presented caseillustrates, this syndrome should be considered as a rare but potentially severe cardiac risk factor in the context of ECT.

Key words: ECT, electroconvulsive therapy, side effects, Brugada syndrome, cardiac arrhythmia

Introduction

Modern ECT application in psychiatric patients

carries a low mortality rate of 2�10:100,000

(Shiwach et al. 1998). In a naturalistic study on

50 psychiatric patients undergoing electroconvulsive

therapy (ECT) asystoles (�2 s) during electrical

stimulation were detected in 48.7% of cases with

spontaneous recovery of heart beat in each case

(Hase et al. 2005). In elderly patients even higher

asystole rates under ECT (65.8%) were described

that were also not associated with an untoward

outcome (Burd and Kettl 1998). Accordingly,

temporary arrhythmias and repolarisation abnorm-

alities can occur in cardiologically healthy subjects

and are considered to be physiological side effects

of ECT (Abrahams 1992). In the rare case of a

lethal complication associated with this treatment,

arrhythmias, particularly asystole, are recognized to

be the most common cause. In reported cases of

asystole under ECT at least one of the following risk

factors has been identified (McCall 1996; Bhat et al.

2002):

� pre-existing ECG conduction deficits;

� unstable cardiac function;

� age�65 years;

� exposure to b-blockers or other sympatholytic

medication;

� exposure to acetylcholine esterase inhibitors;

� omission of anticholinergic pre-treatment;

� hypoxia.

A combination of sympatholytic and vagal stimula-

tory effects appears to be particularly prone to

produce asystole under ECT. This combination of

effects is physiologically given in the immediate post-

ictal period, making post-ictal asystole the most

frequent type of ECT related asystole. The other

common type is asystole immediately after a

subconvulsive stimulus, when the electric stimulus

exerts presumably direct vagal stimulation unop-

posed by neurogenic sympathomimetic effects,

Correspondence: Christian Luckhaus, MD, Department of Psychiatry and Psychotherapy, Heinrich-Heine-University, Bergische

Landstrasse 2, D-40629 Duesseldorf, Germany. Tel: �49 211 922 2741. Fax: �49 211 922 2745. E-mail: christian.luckhaus@lvr.de

The World Journal of Biological Psychiatry, 2008; 9(2): 150�153

(Received 5 February 2007; accepted 2 May 2007)

ISSN 1562-2975 print/ISSN 1814-1412 online # 2008 Taylor & Francis

DOI: 10.1080/15622970701432544

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which only occur during the seizure (McCall 1996;

Bhat et al. 2002).

Brugada syndrome has so far not been impli-

cated in the context of ECT-related asystole. This

hereditary cardiac sodium channelopathy has only

recently been chracterized clinically (Brugada and

Brugada 1992) and has been linked to mutations of

the SCN5A gene (Keller et al. 2002). Its clinical

hallmarks are (Bordacher et al. 2004; Junttila et al.

2004):

� typical ECG pattern of dynamic, sometimes

intermittent nature including partial right bun-

dle-branch block and ST segment elevation in

the right precordial leads V1�V3 (Brugada sign);

demasking effect of class Ia anti-arrhythmic

agents applied intravenously;

� presumably high risk of life-threatening ventri-

cular arrhythmias and sudden clinical death in

cases, who are symptomatic or have a positive

family history of Brugada syndrome;

� 8�9 times more common in men than women;

most prevalent in southeast Asian populations

(0.27% among 20�39-year-old males in a

Japanese population according to Atarashi

et al. 2001), presumably very rare in European

populations.

Case description

The following case description reports on a patient

without previously known cardiac abnormalities,

who developed asystole in first course ECT and

was later diagnosed with Brugada syndrome. The

patient gave his informed consent to the publication

of his case.

A 28-year-old male patient of mixed Indian and

German-Caucasian descent was admitted to a psy-

chiatric hospital for treatment due to rapid cycling as

part of a pre-existing severe bipolar affective disorder.

The past psychiatric history consisted of a

complicated twin birth with hypotrophy and

mild perinatal cyanosis necessitating postnatal in-

cubator treatment for 1 week. Also, a slight delay of

initial speech development was reported. During

early childhood a hyperactivity syndrome developed,

which was unresponsive to methylphenidate. There

was no persistence of an intellectual impairment or

any motor abnormalities. During adolescence the

full clinical picture of a bipolar affective disorder

became manifest. The past medical history revealed

a subtotal thyroidectomy because of an inactive

thyroidal nodule with consecutive l-thyroxine sub-

stitution. The patient had no history of cardiac

disease, arrhythmias or syncopes. His reported

family history was unremarkable for psychiatric or

cardiac disorders.

The current affective episode was characterised

by rapid cycling between severe manic states and

depressive stupor. Pharmacological treatments in-

cluding fluphenazine, diazepam, clozapine and

citalopram in high doses and lithium had been

ineffective, and the patient was on low dosed

clozapine (250 mg/day) and citalopram (20 mg/

day), only, at the time of ECT.

The entire pre-medication work-up revealed nor-

mal results including an unremarkable ECG and

normal serum electrolyte levels including potassium

(4.31 mM). Anaesthesia was carried out by i.v.

applications of atropine (0.5 mg), followed by pro-

pofol (150 mg) and succinylcholine (40 mg). Then,

as part of a titration scheme, a first electric stimulus

of 100.8 mC with a stimulus duration of 1.9 s, an

electric current of 0.9 A and 1-ms pulse width was

applied to the patient with right hemisphere elec-

trode placement using a ThymatronTM DG system.

The stimulus was subconvulsive and was immedi-

ately succeded by an asystole, which lasted some-

where between 5 and 8 s by clinical judgement

and then remitted spontaneously back into sinus

rhythm. Because of this arrhythmia the ECT proce-

dure was discontinued. For safety reasons, it was

decided to apply no further ECT, but to return to an

intensified drug treatment comprising high dose

clozapine, lamotrigine, valproic acid, melperone

and amitriptyline, finally bringing about a prolonged

recovery.

Regarding the unclear nature of asystole under

a subconvulsive electric stimulus, the patient re-

ceived a cardiological work-up. The resting ECG

and echocardiography were unremarkable. Exercise

ECG and 24-h ECG revealed some ventricular

extrasystoles, which were judged as not indicative

of a cardiac illness.

In a cardiological follow-up examination 1 year

later, a slight STelevation in V1 and an ascending ST

segment in V2�V5 became evident in the ECG. A

subsequent i.v. ajmaline challenge unmasked a tran-

siently progressive ST-elevation in V1 and V2 in the

absence of other changes, indicative of Brugada

syndrome (Figure 1). Programmed ventricular sti-

mulation during invasive electrophysiological study

confirmed this diagnosis. During this investigation

ventricular tachyarrhythmias with the need of defi-

brillation were inducible. As the patient was con-

sidered to be at high risk of malignant cardial

arrhythmias, he received an implantable cardioverter

defibrillator, the recommended treatment in Brugada

patients, who have become symptomatic once or who

have a positive family history (Bordachar et al. 2004).

ECT and Brugada syndrome 151

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Discussion

The reported case raises the question of whether

Brugada syndrome is associated with cardiac

complications during ECT. To our knowledge this

issue has not been covered before. The reported

patient had been asymptomatic regarding cardiac

events in the past and presented with normal ECG

recordings, despite later being diagnosed as having

Brugada syndrome. The observed arrhythmia under

first time ECT in this patient was asystole under a

subconvulsive ECT stimulus. This type of arrhyth-

mia is less known in Brugada syndrome, which is

mostly associated with tachyarrhythmias or ventri-

cular fibrillation due to sodium channel dysfunction

(Bordachar et al. 2004). The electrocardiographic

pattern of this arrhythmia is often not detectable

and can be unmasked by infusion of a sodium

channel blocker. The unmasking by ajmaline injec-

tion shows a sensitivity of up to 80% and a specificity

of up to 94% in families with mutations of the

cardiac sodium channel gene (SCN5A) (Hong et al.

2004). The ECT stimulus, on the other hand,

particularly if subconvulsive, presumably exerts a

strong unopposed vagal stimulus on the heart via

mucarinic receptors acting on potassium channels of

pace-making myocytes. It remains speculative, to

which result sodium channel dysfunction in Brugada

syndrome and excessive cholinergic stimulation by

ECT interact at the heart. The presented case raises

the possibility that asystole may occur in such a

constellation. As a confounding variable, propofol

application, as part of anaesthesia, may also have

compromised sodium channel function in the pre-

sented case, since this drug has sodium channel

blocking properties (Saint et al. 1998). On the other

hand, the administered atropine pre-medication may

have shortened the potential duration of asystole in

this case. The low dose medication of clozapine and

citalopram, that the patient received at the time, may

also have interacted at the cardiac level, as the ‘‘new

generation’’ antipsychotics and antidepressants also

have clinically important cardiac as well as vascular

effects (Agelink et al. 1998). Clozapine, in particu-

lar, is structurally similar to the tricyclic antidepres-

sants, which have anticholinergic and type 1A

antiarrhythmic properties that may cause bundle

branch blocks. Case reports have described electro-

cardiographic abnormalities, cardiomyopathy, and

fatal myocarditis associated with its use. Unex-

plained death in patients on clozapine therapy has

also been reported (Merrill et al. 2005). Bradycardia

has been reported with citalopram in therapeutic

doses. The inhibition of cardiac cation and vascular

calcium channels by citalopram may explain most

cardiovascular side effects observed occasionally

with this drug during chronic treatment (Pacher

et al. 2004).

In the end, it cannot be decided conclusively

whether in the present case Brugada syndrome was

the causative factor of asystole under ECT. Sub-

convulsive ECT stimulation per se and additional

drug effects, particularly by propofol, have to be

regarded as potential causes as well. Finally, there

Figure 1. ECG recording of presented case following an intrave-

nous application of ajmaline unmasking ST-elevations in right

pre-cordial leads (Brugada sign).

152 C. Luckhaus et al.

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remains some doubt whether the psychotropic drugs

that the patient received a year later at the time

of diagnosis of Brugada syndrome (i.e. clozapine,

lamotrigine, valproate, amitriptyline, melperon)

conferred to the then seen Brugada changes. This

possibility of drug-induced Brugada syndrome

(Thanacoody and Thomas 2005) could only have

been ruled out, if the patient had been drug-free at

the time of examination. However, because of the

potential severity of psychotic relapse this option was

judged unfeasible.

In summary, the presented case draws attention

to Brugada syndrome in the context of ECT

application in psychiatric patients. As the syndrome

is rare, elaborated cardiological work-ups on every

patient prior to undergoing ECT does neither seem

justified, nor feasible. However, in cases with pre-

vious unexplained cardiac events, a suggestive family

history or southeast Asian descent, a previously

undiagnosed Brugada syndrome can be a relevant

risk factor for arrhythmic complications under ECT

and should be ruled out by a specialist cardiological

examination before commencing this treatment.

Statement of interest

The authors have no conflict of interest with any

commercial or other associations in connection with

the submitted article.

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