Cardiac arrest related to coronary spasm in patients with variant angina: a three-case study

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1 Journal of nternal Medicine 2002; 252: CASE REPORT Cardiac arrest related to coronary spasm in patients with variant angina: a three-case study W. SENUK, T. MULAREK-KUBZDELA, M. GRYGER, S. GRAJEK & A. CEŚLŃSK From the Cardiology Department, Karol Marcinkowski University School of Medical Sciences, Poznań, Poland Abstract. Seniuk W, Mularek-Kubzdela T, Grygier M, Grajek S, Cieśliński A (Karol Marcinkowski University School of Medical Sciences, Poznań, Poland). Cardiac arrest related to coronary spasm in patients with variant angina: a three-case study (Case report). J ntern Med 2002; 252: We present three patients with variant angina pectoris and episodes of cardiac arrest. All of them had typical clinical symptoms, ST-segment changes in electrocardiogram, and coronary artery spasm confirmed by arteriography. They were treated with high doses of calcium antagonists and nitrates. An automatic cardioverter-defibrillator was implanted in the patient who developed ventricular fibrillation despite therapy with calcium antagonists. n another patient a DDD pacemaker was implanted because of high-degree atrioventricular block. Keywords: calcium channel blockers, cardiac arrest, variant angina pectoris. ntroduction Vasospastic angina was first described in 1959 by Prinzmetal et al. [1]. They described a type of angina pectoris with typical thoracic pain that usually occurred in the morning, at rest. The vasospastic pathomechanism of this disturbance in coronary arteries, proposed by Prinzmetal, was confirmed by arteriographic techniques. n some patients with the diagnosis of variant angina, dangerous complications such as myocardial infarction, high-degree atrioventricular blocks, ventricular tachycardia and fibrillation or electromechanical dissociation, which can lead to sudden death, are observed during the attack of ischaemia. We present three patients with variant angina and cardiac arrest who were successfully resuscitated and then managed in different ways. Patient 1 A 51-year-old man was hospitalized because of retrosternal squeezing chest pain for 2 h, with a 5-day history of nausea, dyspnoea and retrosternal discomfort. At admission to the hospital a physical examination revealed a pale, sweaty man with a blood pressure of 130/90 mmhg. The electrocardiogram (ECG) presented ST-segment elevation and negative T-wave in lead, and, with sinus rhythm of 51 beats min )1 (Fig. 1). Nitroglycerin in a dose of 10 lg min )1, heparin infusion, aspirin in a dose of 75 mg day )1, diltiazem in a dose of 240 mg day )1 and amlodipine in a dose of 20 mg day )1 were started. After switching medications pain disappeared for about 12 h. Coronary arteriography showed a nonsignificant stenosis (<35%) in the central part of the left anterior descending coronary artery. The other arteries and the left ventricular arteriogram were normal. A very severe retrosternal pain occurred some hours after arteriography. Several episodes of sustained and nonsustained ventricular tachycardia treated with xylocaine accompanied the pain. Between episodes of ventricular tachycardia, advanced and degree atrioventricular block appeared, so temporary endocavital pacing was immediately initiated. n the next few minutes, three episodes of ventricular fibrillation occurred. All of them were successfully defibrillated. The dose of nitroglycerin was increased up to 30 lg min )1 and the dose of diltiazem up to 360 mg day )1 and amlodipine in a dose of 368 Ó 2002 Blackwell Science Ltd

2 CASE REPORT: CARDAC ARREST RELATED TO CORONARY SPASM 369 Fig. 1 ECG of the first patient with ST-segment elevation and negative T-wave in lead, and. 20 mg day )1 was continued. Amiodarone was started in a dose of 200 mg, four times a day. This therapy gave symptomatic relief. Coronary examination performed 4 days after the cardiac arrest was the same as before, but an injection of the contrast substance to the right coronary artery, induced diffuse, severe spasm of the vessel (Fig. 2a), very severe chest pain and ST-segment depression with negative T-wave in leads,, (Fig. 3). After intravenous administration of 0.7 mg of nitroglycerin occlusion disappeared (Fig. 2b). Seven days later, because of recurrences of high-degree atrioventricular block episodes, a DDD pacemaker was implanted. No more episodes of angina or cardiac arrhythmias were detected. The patient was discharged from the hospital in a good condition. For ambulatory treatment, diltiazem in a dose of 360 mg day )1, amlodipine in a dose of 20 mg day )1, isosorbide mononitrate in a dose of 100 mg day )1, amiodarone in a dose of 200 mg day )1 and aspirin in a dose of 75 mg were prescribed. During the 6-month period of observation the patient remains asymptomatic. No disturbances of the rhythm were observed. Fig. 2 The right coronary artery after intravenous administration of contrast substance: (a) a severe, diffuse spasm; (b) intravenous administration of 0.7 mg of nitroglycerin relieved occlusion.

3 370 W. SENUK et al. (a) (b) Fig. 3 ECG during pain episode (a) and without pain (b) ST-segment changes. Patient 2 A 52-year-old woman was admitted to another hospital because of angina at rest of 1 week duration. She had suffered from the morning attacks of angina at rest for 5 years and from arterial hypertension for 10 years. Because of the repeated episodes of morning angina at rest, despite medical treatment, the patient was transferred to our hospital. The ECG recorded during the morning pain episode and an hour later, when angina attack passed, showed typical changes of ST-segment (Fig. 4). n our hospital physical examination was normal, except for a blood pressure of 160/ 100 mmhg. The resting ECG was normal. Diltiazem in a dose of 240 mg day )1, nitroglycerin and heparin infusion and aspirin in a dose of 75 mg were administrated. Coronary arteriography showed parietal irregularities in the left anterior descending coronary artery and in the circumflex coronary artery. The other arteries and the left ventricular arteriogram were normal. During intravenous administration of the first dose of the contrast substance, the spasm of the left main coronary artery appeared. ntravenous administration of 0.2 mg of nitroglycerin relieved occlusion. The therapy with calcium antagonists and nitroglycerin in a dose of 40 mg day )1 per os was continued. Two days later, despite the medical treatment, a very severe chest pain, followed by cardiac arrest in the mechanism of electromechanical dissociation, appeared. Resuscitation was successful. There were not any significant changes in cardiac enzymes. Diltiazem was continued in a dose of 240 mg day )1, amlodipine was added in a dose of 20 mg day )1 and long-acting nitrate at high dose was started: isosorbide mononitrate 100 mg day )1. The angina completely disappeared. A 24-h Holter ECG examination did not reveal any significant ST-segment changes and arrhythmias. Ten days after the cardiac arrest, the patient was discharged from the hospital in good condition. For ambulatory treatment, diltiazem in a dose of 240 mg day )1, amlodipine in a dose of 20 mg day )1, isosorbide mononitrate in a dose of 100 mg day )1 and aspirin in a dose of 75 mg were prescribed. The patient remained asymptomatic with regular pharmacological treatment. When she stopped calcium antagonists for 2 days only, the episode of angina occurred. As the patient came back to regular, earlier prescribed medical treatment, she remained asymptomatic during a follow-up period of 6 months.

4 CASE REPORT: CARDAC ARREST RELATED TO CORONARY SPASM 371 (a) (b) V1 V1 V2 V2 V3 V3 V4 V4 V5 V5 V6 V6 Fig. 4 ST-segment changes: (a) ECG during angina attack, at 8.30 a.m.; (b) ECG after pain episode, at 9.50 a.m.

5 372 W. SENUK et al. Patient 3 A 49-year-old man with a history of non-q wave inferior and posterior infarction and two cardiac arrests was hospitalized earlier elsewhere with a 2-week history of angina at rest. During the episodes of angina, in ECG, ST-segment elevations in leads, and were observed (Fig. 5). Usually angina was relieved in a few minutes by sublingual nitroglycerin. Because of repeated episodes of angina at rest, despite medical treatment, the patient was referred to our Department. Physical examination and resting ECG were normal, except for a blood pressure of 140/90 mmhg. Troponin test was negative. Diltiazem in a dose of 360 mg day )1, nitroglycerin and heparin infusion and aspirin in a dose of 75 mg were administrated. Coronary arteriography showed stenosis of 45% in a proximal segment of the left anterior descending coronary artery and parietal irregularities in the right coronary artery. During arteriography a transient spasm of the right coronary artery was observed. About 12 h after coronary arteriography, ventricular fibrillation occurred, without any preceding arrhythmias or ST-segment shifts. Cardiopulmonary resuscitation was successful. After cardiac arrest the doses of calcium antagonists were increased. Diltiazem was continued in a dose of 360 mg day )1 and amlodipine was added in a dose of 20 mg day )1. Amiodarone was started, at first in a bolus of 600 mg, and then in a dose of 800 mg day )1. Long acting nitrate at high dose was also started: isosorbide mononitrate in a dose of 100 mg day )1. The echocardiography showed akinesis of inferior wall and hipokinesis of posterior wall. Because of episodes of the cardiac arrest in a mechanism of ventricular fibrillation, despite pharmacological treatment with calcium antagonists and nitrates, and lack of any significant abnormalities in arteriography, we implanted an automatic cardioverter-defibrillator (CD). The patient was discharged from the hospital with sinus rhythm at (a) (b) Fig. 5 ECG changes during pain episode (a) and a few minutes later (b), without pain.

6 CASE REPORT: CARDAC ARREST RELATED TO CORONARY SPASM beats min )1. For ambulatory treatment, diltiazem in a dose of 360 mg day )1, amlodipine in a dose of 20 mg day )1, isosorbide mononitrate in a dose of 100 mg day )1, amiodarone in a dose of 200 mg day )1 and aspirin in a dose of 75 mg were prescribed. During the 6-month period of observation the patient remained asymptomatic. Discussion We have presented three patients with diagnosed Prinzmetal s angina who developed cardiac arrest in a mechanism of ventricular fibrillation or electromechanical dissociation. n our patients the presumptive diagnosis of Prinzmetal s angina was made by demonstrating transient ST-segment elevation during pain episodes, which usually occurred at rest (Figs 1, 4 and 5). The final diagnosis was confirmed by visualization of coronary spasm at arteriography (Fig. 6). The presumptive diagnosis of variant angina is made when the patient has angina in association with transient ST-segment elevation, both of which resolve spontaneously or with nitroglycerin [2 6]. According to the literature, coronary arteriography is recommended in all patients with Prinzmetal s angina [2, 3, 7]. When coronary arteriogram is normal or shows only nonobstructive plaques and if transient ST-segment elevation can be demonstrated in association with discomfort, the diagnosis of Prinzmetal s angina can be made and no further tests are necessary [2, 3, 5]. A 24-h ambulatory ECG may be helpful in demonstrating ST-segment elevation [2, 3, 8, 9]. According to Onaka et al. [9], 22 of 30 patients (73%) with diagnosed variant angina demonstrated ST-segment elevation during monitoring. n the patient in whom the diagnosis of variant angina is elusive, for instance in the absence of ST-segment elevation that accompanies chest discomfort, various provocative tests (methylergonovine [10], acetylcholine [11], methacholine [12]) can be employed in an attempt to induce coronary artery spasm that can be visualized angiographically and is accompanied by ST-segment elevation [2, 3]. Provocative tests can cause refractory coronary spasm requiring intracoronary nitroglycerin for relief or sometimes there is also need for an intracoronary calcium antagonist or emergency percutaneous transluminal coronary angioplasty, so the tests should be conducted in a catheterization laboratory [13]. Hyperventilation [14, 15], exercise [16], or exposure to cold [17] are other provocative tests [2, 3, 14]. A provocative test with acetylcholine or methylergonovine may not necessarily be performed in hyperventilation test-positive patients because the specificity of hyperventilation is 100% Fig. 6 Diagnosis of Prinzmetal s angina.

7 374 W. SENUK et al. for coronary spasm [14]. These patients are at high risk for lethal arrhythmias and multivessel spasm [14]. According to the literature [5, 6, 18 21] calcium antagonists and nitrates are very effective in preventing coronary artery spasm in patients with variant angina. They act in different mechanisms and that is why the vasodilatory effect of these two classes of drugs is additive. Usually, a calcium antagonist at a high dose (e.g mg day )1 verapamil, mg day )1 diltiazem, mg day )1 nifedipine) is started [2, 3]. f symptomatic relief is not obtained, a second calcium antagonist from another class or a longacting nitrate should be added [2, 3, 6, 18]. t is preferred to combining diltiazem or verapamil with dihydropyridines (nifedipine, amlodipine or nicardipine). Diltiazem and verapamil are more potent negative inotropes than dihydropyridines, which in return are more potent peripheral vasodilators [6]. The most dangerous complication in patients with Prinzmetal s angina is cardiac arrest. According to MacAlpin et al. [19], it occurs in 27% of patients. n this study, during 25 years of follow-up, in a group of 81 patients, 27 patients had at least one episode of cardiac arrest. Thirteen patients (16%) were successfully resuscitated and nine patients (11%) died suddenly. According to the literature, the incidence of sudden death is lower in patients treated with calcium channel blockers (up to 5%), compared with groups without routine use of Ca-blockers (up to 11%) [19]. Most authors believe that this treatment can reduce the risk of sudden death if it prevents angina attacks [18, 22, 23]. Our observations are in agreement with this opinion. n our patients cardiac arrest occurred despite the treatment with calcium antagonists, but all of them suffered from severe chest pain before the event. Therefore, we think that doses of calcium antagonists in the first and second patient were not high enough. When the doses of diltiazem were increased and amlodipine was added to the therapy, we did not observe any pain or arrhythmias. n the third patient, because of the episodes of ventricular fibrillation, which occurred despite high dose of diltiazem (360 mg day )1 ), we implanted an automatic cardioverter-defibrillator. t is still an open question whether automatic cardioverter-defibrillators should be implanted in all patients with Prinzmetal s angina after cardiac arrest. n our opinion, it is necessary in patients with variant angina after cardiac arrest who remain symptomatic, despite the treatment with maximally tolerated doses of calcium antagonists. t is in agreement with the opinion of Meisel et al. [24]. Results of electrophysiological studies are usually normal in patients with variant angina and cardiac arrest [25 28]. So electrophysiological examination seems not to be useful in qualifying patients for automatic cardioverter-defibrillator implantation. The treatment with antiarrhythmic drugs, according to many authors, is not effective and does not protect patients with Prinzmetal s angina against cardiac arrest [18, 29]. Antiarrhythmic drugs should be used only during attacks. n one of our patients, xylocaine was administrated during paroxysmal ventricular tachycardia and it did not prevent him from ventricular fibrillation. An exception is made for amiodarone because of its vasodilatory effects [18]. We administrated amiodarone in both our patients after ventricular fibrillation. n the first patient before ventricular fibrillation we observed complete atrioventricular block. n this patient during arteriography, spasm of the right coronary artery occurred. According to Mayer et al. [5], the high-degree atrioventricular block may occur during vasospasm of the coronary artery supplying blood to the atrioventricular node. n 90% of patients it is the right coronary artery and in the remaining 10%, the left circumflex artery. n this patient a DDD pacemaker was implanted to avoid recurrent syncope due to atrioventricular blocks. t is believed that permanent pacemaker insertion is indicated in most patients with pure coronary artery spasm who develop complete heart block or asystole during angina [30]. Many studies show that patients with variant angina are at the highest risk of cardiac death or acute myocardial infarction during the early phase of the follow-up period, when disease activity is high [5, 19, 30 33]. So during the first year of observation the patient must be followed very closely [19]. Although, in the great majority of patients there is a tendency for symptoms to decrease. Some patients may have periods of remission and exacerbation of disease activity [5]. Therefore, we believe that careful follow-up and medical therapy should not be discontinued.

8 CASE REPORT: CARDAC ARREST RELATED TO CORONARY SPASM 375 Conclusions Coronary spasm is an underestimated cause of sudden cardiac arrest in patients without significant coronary or other structural heart diseases. These patients need to be intensively treated with calcium antagonists and nitrates. n patients who remain symptomatic despite such a treatment, the implantation of an automatic cardioverter-defibrillator seems to be an adequate solution. References 1 Prinzmetal M, Kennamer R, Merliss R, Wada W, Bor N. A variant form of angina pectoris. Am J Med 1959; 27: Braunwald E, Antman EM, Beasley JW et al. ACC/AHA guidelines for the management of patients with unstable angina and non-st-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2000; 36: Braunwald E, Antman EM, Beasley JW et al. 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9 376 W. SENUK et al. of ischaemic sudden death by medical treatment. Eur Heart J 1986; 7 (Suppl. A): Bott-Silverman C, Heupler FA Jr. Natural history of pure coronary artery spasm in patients treated medically. J Am Coll Cardiol 1983; 2: Bott-Silverman C, Heupler FA Jr. What is the long-term prognosis of patients with coronary spasm and normal coronary arteries? nt J Cardiol 1984; 6: Yasue H, Takizawa A, Nagao M et al. Long-term prognosis for patients with variant angina and influential factors. Circulation 1988; 78: Walling A, Waters DD, Miller DD, Roy D, Pelletier GB, Theroux P. Long-term prognosis of patients with variant angina. Circulation 1987; 76: Received 18 April 2002; revision received 5 August 2002; accepted 15 August Correspondence: Wojciech Seniuk, ul.starowiejska 1g/3, Poznań, Poland (fax: ; wseniuk@ poczta.onet.pl).