Vasospastic Angina Accompanied by Brugada-TypeElectrocardiographic Abnormalities

MASAOMI CHINUSHI, M.D., YUUKO KUROE, M.D., EIICH ITO, M.D.,MINORU TAGAWA, M.D., and YOSHIFUSA AIZAWA, M.D.

From the First Department of Internal Medicine, Niigata University School of Medicine, Niigata, Japan

Brugada Syndrome and Vasospastic Angina. We present two patients with vasospasticangina and Brugada-type ECG abnormalities. The � rst patient complained of chest pain, andtransient ST segment elevation was con� rmed on ECG. Coronary angiogram showed no organicstenosis. The second patient had syncopal episodes following anginal chest pain, and the samesymptoms were reproduced by intracoronary acetylcholine injection that induced vasospasm. Inboth patients, ECG at rest showed ST segment elevation in leads V1 and V2 and a right bundlebranch block pattern that were accentuated by a Class I antiarrhythmic drug. Ventricular � bril-lation also was induced by programmed electrical stimulation. Susceptibility to ventricular � bril-lation can be modulated by the interaction of coronary vasospasm with Brugada syndrome or viceversa; therefore, it is important to study the clinical implications of the coexistence of the twodiseases in such patients. (J Cardiovasc Electrophysiol, Vol. 12, pp. 108-111, January 2001)

vasospastic angina, Brugada syndrome, ventricular tachyarrhythmia

Introduction

Vasospastic angina and Brugada syndrome are prev-alent in Asian countries and can cause sudden cardiacdeath from ventricular tachyarrhythmia.1 ,2 These dis-eases are considered an independent category of cardio-vascular disease, but the coexistence of vasospastic an-gina and Brugada syndrome in the same patient may bepossible and the susceptibility to ventricular tachyar-rhythmia may be exaggerated.3 ,4

We report two patients who suffer from both vaso-spastic angina and Brugada syndrome. Their originalsymptoms were considered to be due to coronary vaso-spasm, but ventricular � brillation (VF) also was inducedby programmed electrical stimulation.

Case Reports

Patient 1

In March 1999, a 50-year-old man was referred to ourhospital for evaluation of chest pain that developed earlyin the day once or twice a week. The chest pain usuallylasted for 10 to 20 minutes, and sublingual nitrate ad-

ministration was effective in relieving the chest pain. TheECG obtained when the patient complained of chest painat bed rest demonstrated transient ST segment elevation(Fig. 1). After the patient took a nitrate tablet, the chestpain disappeared within 5 minutes and ST segment re-turned to the basal level within 15 minutes. He did nothave episodes of syncope, palpitation, or a history ofcardiovascular diseases, and no medication had beenprescribed. Cardiac events or sudden death were notobserved in members of his family.

On admission to our hospital, results of a two-dimen-sional echocardiogram and thallium cardiac scintigramwere normal. Twelve-lead ECG at rest showed normalsinus rhythm, but coved-type ST segment elevation anda right bundle branch block pattern were noted in leadsV1 to V3 (Fig. 2A). ST segment elevation was accentu-ated by intravenous administration of � ecainide and at-tenuated by isoproterenol infusion (Figs. 2B and 2C).3 ,5

Standard cardiac catheterization was performed forexamination of coronary artery disease. The intracardiacpressure study was normal, and left ventriculogramshowed normal ventricular contraction. The coronaryangiogram did not show any stenotic segments. A prov-ocation test for coronary spasms was not performedbecause nitrate was effective for treating his chest painand the chest pain was concomitant with transient STsegment elevation. He was diagnosed as having vaso-spastic angina.

Programmed electrical stimulation then was at-tempted to study the inducibility of VF because we foundBrugada-type ECG abnormalities. When double ventric-

Address for correspondence: Masaomi Chinushi, M.D., First Depart-ment of Internal Medicine, Niigata University School of Medicine,1-754 Asahimachi Niigata 951-8510, Japan. E-mail: chinushi@med.niigata-u.ac.jp

Manuscript received 23 March 2000; Accepted for publication 28September 2000.

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Reprinted with permission fromJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Volume 12, No. 1, January 2001

Copyright ©2001 by Futura Publishing Company, Inc., Armonk, NY 10504-0418

ular extrastimuli at coupling intervals . 180 msec wereapplied from the right ventricle, VF was induced twiceand electrical de� brillation was required to terminateeach VF (Fig. 2D). Neither AV conduction abnormalitiesnor a rate-dependent right bundle branch block wereobserved. He was diagnosed as also having Brugadasyndrome. A de� brillator device was recommended, buthe refused the treatment. He has been treated with cal-cium antagonist alone, and his condition has remainedstable as of September 2000.

Patient 2

The patient was a 68-year-old man who had severalepisodes of syncopal attack following angina-like chestpain. He did not have a history of cardiovascular dis-eases, and no medication had been prescribed. No car-diac events or sudden death were observed in membersof his family.

On admission to our hospital, results of his physicaland neurologic examinations were normal, and bloodanalysis showed no abnormalities. Twelve-lead ECG atrest showed normal sinus rhythm, but mild saddleback-

type ST segment elevation and a right bundle branchblock-like pattern were noted in leads V1 and V2 (Fig.3A). ST segment elevation was accentuated by � ecainidebut attenuated by isoproterenol infusion (Figs. 3B and3C). Results of a two-dimensional echocardiogram andthallium cardiac scintigram were normal.

During cardiac catheterization, the intracardiac pres-sure values were normal and the left ventriculogramshowed normal ventricular contraction. The coronaryangiogram revealed no stenotic lesions, but administra-tion of acetylcholine 100 m g into the left coronary arteryresulted in ST segment elevation in leads I, aVL, and V3to V6 (Fig. 3D). The patient complained of chest painthat was the same as he had previously experienced.Coronary angiography showed complete occlusion of theleft circum� ex and major diagonal arteries. The coronaryspasms and his chest pain were soon relieved by intra-coronary nitrate injection, and bradyarrhythmia or tachy-arrhythmia was not observed during the provocation test.

Electrophysiologic study later demonstrated normalAV conduction and lack of a rate-dependent right bundlebranch block. However, VF was induced twice by doubleventricular extrastimuli at coupling intervals . 180 msec.

Figure 1. ECG recording from patient 1. When the patient complained of chest pain in the morning (06:25), channel 1 (close to lead V5) andchannel 2 (close to lead II) leads showed ST segment elevation. After the patient took a nitrate tablet, the chest pain disappeared and the elevatedST segment returned to the basal level within 5 minutes (06:35). See text for details.

Chinushi et al. Brugada Syndrome and Vasospastic Angina 109

He was considered to have both vasospastic angina andBrugada syndrome. Because his syncopal attacks couldnot be related to coronary vasospasm alone, de� brillatortreatment was recommended, but he did not accept im-plantation of the device. A calcium antagonist was ad-ministered, and neither syncopal attacks nor anginalchest pain have recurred during the follow-up period of34 months.

Discussion

In the present two patients, vasospastic angina wasindicated: chest pain and transient ST segment elevationon ECG monitoring in the � rst patient, and coronaryvasospasm induction by intracoronary acetylcholine inthe second patient. Ef� cacy of a calcium antagonist insuppressing further episodes of chest pain supported thediagnosis that these patients suffered from vasospasticangina. Because an intracoronary acetylcholine test wasnot attempted in the � rst patient, the direct demonstrationof vasospasm was not available. Although the patient’ shistory of episodes of chest pain and the transient aggra-vation of ST segment elevation were suggestive of cor-onary artery spasm in this patient, transient aggravation

of ST segment elevation in a few leads should not beclaimed as evidence of vasospasm because ST segmentelevation may be variable in patients with Brugada syn-drome.3 ,5 Our case showed transient ST segment eleva-tion (about 15 min) in two ECG leads (close to II and V5)(Fig. 1). In the second patient, bradyarrhythmia or tachy-arrhythmia may have developed following coronaryspasms and could have caused his syncopal attacks, butthis was not con� rmed at the time of catheterization.However, the ECGs from both patients showed Brugada-type abnormalities that might have caused the syncopalattacks. Thus far, we have been unable to con� rm VF dueto Brugada syndrome, but VF was reproducibly inducedby nonaggressive programmed electrical stimulation inthe two patients using extrastimuli with a coupling in-terval . 180 msec.6 Based on reports from the litera-ture,5 ,7 de� brillator implantation is safer for preventingpossible clinical manifestation of VF. However, the in-dication for de� brillator treatment remains controversial,because the � rst patient did not have syncopal episodesand syncope could be explained by coronary vasospasmsin the second patient.

The incidence of the coexistence of vasospastic an-gina and Brugada syndrome is not known and, to our

Figure 2. Twelve-lead ECG from patient 1. (A) ECG obtained in the control state shows coved-type ST segment elevation in leads V1 to V3.Intravenous administration of � ecainide accentuated ST elevation (B), whereas isoproterenol injection attenuated the ECG abnormalities (C).Ventricular extrastimuli from the apex of the right ventricle induced ventricular � brillation in the control state (D).

110 Journal of Cardiovascular Electrophysiology Vol. 12, No. 1, January 2001

knowledge, patients suffering from the two diseases havenot been reported. The coexistence of vasospastic anginaand Brugada syndrome in our patients may be incidental.Recent experimental studies revealed that an arrhythmo-genic substrate of Brugada syndrome was based on thedifferent characteristics of repolarization within the lay-ers of the right ventricle,4 and coronary spasms have thepotential to alter conduction properties and repolariza-tion in certain areas, thus modifying the arrhythmoge-nicity of Brugada syndrome. Although rare, we need topay attention to the coexistence of vasospastic anginaand Brugada syndrome, both of which are well known toinitiate lethal arrhythmia, and to further study the clinicalimplications in such patients.

References

1. Brugada P, Brugada J: Right bundle branch block, persistent ST seg-ment elevation and sudden cardiac death: A distinct clinical and elec-trocardiographic syndrome. J Am Coll Cardiol 1992;20:1391-1396.

2. MacAlpin RN: Cardiac arrest and sudden unexpected death invariant angina: Complications of coronary spasm that can occur inthe absence of severe organic coronary stenosis. Am Heart J 1993;125:1011-1017.

3. Miyazaki T, Mitamura H, Miyoshi S, Soejima K, Aizawa Y, OgawaS: Autonomic and antiarrhythmic drug modulation of ST segmentelevation in patients with Brugada syndrome. J Am Coll Cardiol1996;27:1061-1070.

4. Yan GX, Antzelevitch C: Cellular basis for the Brugada syndromeand other mechanisms of arrhythmogenesis associated with ST-segment elevation. Circulation 1999;100:1660-1666.

5. Brugada J, Brugada P: Further characterization of the syndrome ofright bundle branch block, ST segment elevation, and sudden car-diac death. J Cardiovasc Electrophysiol 1997;8:325-331.

6. Aizawa Y, Naitoh N, Washizuka T, Takahashi K, Uchiyama H,Shiba M, Shibata A: Electrophysiological � ndings in idiopathicrecurrent ventricular � brillation: Special reference to mode of in-duction, drug testing, and long-term outcomes. PACE 1996;19:929-939.

7. Brugada J, Brugada R, Brugada P: Right bundle branch block andST-segment elevation in leads V1 through V3 a marker for suddendeath in patients without demonstrable structural heart disease.Circulation 1998;97:457-460.

Figure 3. Twelve-lead ECG from patient 2. (A) ECG obtained at admission shows saddleback-type mild ST segment elevation in leads V1 and V2.Flecainide accentuated ST segment elevation (B), whereas isoproterenol diminished the abnormalities (C). When acetylcholine 100 m g wasadministered into the left coronary artery, the ECG in leads I, aVL, and V3 to V6 revealed ST segment elevation (D), and coronary spasms weredemonstrated by coronary angiography.

Chinushi et al. Brugada Syndrome and Vasospastic Angina 111