CORRELATION OF CORONARY ARTERIOGRAM, ELECTROCARDIOGRAM AND EXERCISE TEST IN SPONTANEOUS ANGINA A POSSIBLE CAUSE OF ANGINAL ATTACK

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1 THE KURUME MEDICAL JOURNAL Vol.27, P , 1980 CORRELATION OF CORONARY ARTERIOGRAM, ELECTROCARDIOGRAM AND EXERCISE TEST IN SPONTANEOUS ANGINA A POSSIBLE CAUSE OF ANGINAL ATTACK YASUO OHKITA The Third Department o f Internal Medicine, Kurume University School of Medicine, Kurume, 830, Japan Received for publication May 24, 1980 Combination of coronary spasm and organic coronary stenosis has been postulated as a possible cause of spontaneous angina. The present study was performed to clarify the role of organic stenosis and spasm of coronary in spontaneous angina according to the coronary arteriography and the shifts of ST-segment in the 12-lead ECG during anginal attack in 53 patients with spontaneous angina. In 33 cases of ST elevation during attack, only 14 cases (42 %) had organic stenosis. Three cases had multivessel disease (MVD), and 3 cases had collateral vessels. The incidence of organic stenosis in the corresponding to the electrocardiogram was higher in the anteroseptal area than in the inferior area. In 20 cases of ST depression during attack, 19 cases (95 %) had organic stenosis. Fourteen cases had MVD and 10 cases had collateral vessels. The incidence of organic stenosis, including MVD, and collateral vessels was higher in cases of ST depression than in cases of ST elevation. And also the incidence of positive response to the exercise test is higher in cases of ST depression than in cases of ST elevation. The results suggest that coronary spasm is the main cause of spontaneous angina in cases of ST elevation, and organic stenosis of coronary in addition to coronary spasm is the main cause of the anginal attack in cases of ST depression. INTRODUCTION In general, angina pectoris is identified by transient episodes of chest pain, caused by imbalance between coronary blood flow and myocardial requirement for oxygen due to changes in coronary circulation. However, spontaneous angina, one subcategory of angina pectoris (ISFC and WHO, 1979), is characterized by episodes of chest pain, occurring without apparent increased oxygen demand of the myocardium. Some cases of spontaneous angina associated with the transient elevation of ST-segment during anginal attacks have been well-known as variant angina (Prinzmetal et al., 1959). As to the mechanism of variant angina, an increasing number of evidences have brought forward that spasm of a large coronary is responsible for the attack (Kimura et al., 1978; Maseri et al., 1978). However, various degrees of organic stenosis of coronary arteries have been reported in conjunction of variant angina (MacAlpin et al., 1973; Kimura 1980). Arteriographically, the patient with normal or near normal 119

2 120 OHKITA coronary could have a better prognosis than the patient with organic stenosis of coronary ies (Selzer et al., 1976; Conti et al., 1979). Other cases of spontaneous angina show the depression of ST-segment during anginal attacks. The mechanism of this type of angina is not yet clear (Conti et al., 1979). A few reports have been presented concerning the difference of STsegment shifts, elevation or depression, from the arteriographical viewpoints (Plotnic et al., 1975 ; Maseri et al., 1975; Maseri et al., 1978). Moreover, some experimental and clinical evidence suggests that epicardial ST depression is related to milder ischemia of the myocardial layers than ST elevation is (Ekmekci et al., 1961 ; Maseri et al., 1978). Accordingly, it is clinically important to elucidate the significance of ST-segment shifts in spontaneous angina. The aim of the present study is to clarify the clinical characteristics of spontaneous angina, using selective coronary arteriography, electrocardiography and the exercise test. SUBJECTS AND METHODS The subjects were fifty-three patients with spontaneous angina, 45 males and 8 females, admitted to Kurume University Hospital from August 1974 to September The patients satisfied the following criteria : 1) recurrent episodes of chest pain which occur without apparent relation to exercise, 2) effective response to nitroglycerin or isosorbide nitrate, 3) transient shifts of ST-segment (elevation or depression) in the 12-lead electrocardiogram (ECG) during the anginal attack, 4) no electrocardiographic changes which suggest myocardial infarction after episodes of chest pain, and 5) the two-step exercise test (Master, 1968) and selective coronary arteriograms were performed. Patients with severe spontaneous angina such as impending myocardial infarction were excluded from this study. The definition of chest pain included chest discomfort when it was associated with transiently significant elevation or depression of STsegment during attack. In this study, we used the one 12- lead ECG obtained during anginal attack showing the most remarkable shift of ST-segment. The shift of ST-segment was measured at the point of 0.06 sec from S wave (Bruce et al., 1974) and the corresponding PQ junction line. When abnormal ST depression was seen in the control ECG, the degree of ST depression was measured by the difference of the shift of ST-segment before and during the attack. The sensitivity in ECG was 1mV/1 cm. The two-step exercise test was performed in all patients during daytime in order to check the exercise capacity. The exercise test was immediately stopped when chest pain occurred. The number of steps in the test was gradually increased until a significant shift of ST-segment was observed immediately after the exercise. The patients who endured "double" load in the exercise test, took physical training according to the method of our laboratory (Hwang et al., 1973). Fifty-three patients were divided into three groups according to the electrocardiographic findings as shown in Table 1. Nineteen patients belonged to group l, showing transient ST elevation during spontaneous angina and negative response to the exercise test. Twelve patients who showed transient ST elevation during spontaneous attack and at the exercise test were designated as group Il a. Two patients who showed transient ST elevation dur-

3 A CAUSE OF SPONTANEOUS ANGINA 121 Characteristics TABLE 1 of subjects Fig. 1. Time of anginal attack associated with the most striking shift of ST-segment in each patient with spontaneous angina. Anginal attack usually occurred during the period from midnight to early morning in all three groups. ing spontaneous attack and transient ST depression at the exercise test belonged to group g b. Seventeen patients who showed transient ST depression during spontaneous attack and at the exercise test were designated as group IIia. Three patients who showed transient ST depression during spontaneous attack and negative response to the exercise test were designated as group fb. When elevation and depression of ST-segment appeared in opposite leads of the ECG, the elevation of ST-segment was considered as the primary change. Selective coronary cine arteriography was carried out by Sones' technique (Sones and Shirey, 1962). Many coronary injections with multiple projections were used, and each film was interpreted by at least two observers according to the criteria of the American Heart Association Committee (Austen et al., 1975). Determination of the degree of organic coronary stenosis was done by administration of nitro-

4 122 OHKITA glycerin or isosorbide nitrate. Stenosis of more than 75% (according to AHA's criteria) was considered significant. The extent of significant stenosis in the major three coronary arteries was estimated. Presence or absence of collateral vessels was also checked in each patient. RESULTS I. Time at the onset of spontaneous angina TABLE 2 Electrocardiographic and coronary arterio graphic findings in 19 patients of group I The asterisk shows developed collateral vessels. The circled number indicates the segment of coronary in GAG (according to AHA's criteria). The arrow marks show the elevation or depression of ST-segment. EGG=electrocardiogram, L=aVL lead, F=aVF lead. CAG=coronary arteriogram, RCA=right coronary, LMT=left main trunk, LAD=ieft anterior descending, CX=left circumflex

5 A CAUSE OF SPONTANEOUS ANGINA 123 Anginal attacks usually occurred during rest at night in all groups. Fig. 1 shows the relation of time of the anginal attack for each group. In 44 of 53 patients (83 %), the most striking shift of the ST-segment during spontaneous angina was observed from 8 : 00 p. m, to 8 : 00 a. m.. There were scarcely differences of time at the onset of spontaneous angina in three groups. I. Electrocardiographic findings 1) Resting electrocardiogram As shown in Tables 2, 3 and 4, ST depression, Q (more than 0.5 mv) or q (less than 0.5 mv) wave and conduction disturbances were revealed in the resting ECG without attack. Eleven patients (21 %) showed ST depression in the resting ECG. Sixteen patients (30%) showed either q or Q wave. Five patients had right bundle branch block (RBBB). There was no statistically significant difference in the incidence of q or Q wave and RBBB. The highest incidence of normal ECG's was found in group I. ST depression was frequently observed in group III. The statistical significance was seen among TABLE 3 Electrocardiographic and coronary arteriographic findings in 12 patients of group II a (No. 1-12) and 2 patients of group Jib (No. 13, 14) The abbreviations and symbols are the same as those in Table 2.

6 124 OHKITA the incidences of three groups (p< to 0.01 by t-test). 2) Electrocardiographic findings during anginal attack Thirteen of 19 patients (68 %) in group I showed ST elevation in lead II, III and avf, and the other patients (32%) showed it in lead V1-5. The degree of ST elevation was 5.2 } 4.8 mm (Mean } SD). Five of 14 patients (36%) in group II had ST elevation in lead II, III and avf, and the other 9 patients (64%) exhibited its change in lead V1-5, showing 4.1 } 4.2 mm high. Patients in group I with ST elevation in lead II, III and avf were encountered twice the incidence in group II. However, this was not significant statistically. The degree of ST elevation was almost the same between the two groups. The degrees of ST elevation with and without reciprocal ST depression TABLE 4 Electrocardiographic and coronary arteriographic findings in 17 patients of group IIIƒ (No. 1-17) and in 3 patients of group IIIb (No ). The abbreviations and symbols are the same as those in Table 2.

7 A CAUSE OF SPONTANEOUS ANGINA 125 were 6.9 }5. 4 mm and 2.5 } 1.2 mm, respectively. This was a statistically significant difference (p<0.025 by t-test). In group III, all 20 patients showed ST depression in precordial lead V1-5, having 2.0 } 0.8 mm in depth. The degree of ST-segment shift was less in group III than in group I and II (p< 0.01 by t-test). 3) Electrocardiographic findings at the exercise test All patients in group I received physical training because of a negative response to the exercise test. In all patients of group II a, the exercise test resulted in a transiently significant elevation of ST-segment in the leads in which ST elevation appeared during spontaneous angina. The degree of ST elevation induced by exercise was 6.5 } 6.7 mm, which was almost same degree as that during spontaneously anginal attack. Two patients of group II b showed transiently significant ST depression in the leads in which ST elevation was seen during spontaneous angina. All patients in group IIIa showed transiently significant ST depression at the exercise test in the leads in which ST depression was seen during spontaneous angina. ST depression was 1.9 } 0.8 mm deep. The degree of the shift was less than that in group II a (p<o.025 by t-test). Three patients in growp IIIb showed no significant shift of ST-segment after the exercise test. The incidence of positive response to the exercise test is higher in cases of ST depression than in cases of ST elevation (p<o.001 by t-test). III. Coronary cine-arteriographic findings 1) Number of diseased vessels and presence of collaterals Thirteen patients (68%) in group I showed no significant stenosis of coronary arteries. The other 9 patients had single vessel disease (SVD). Only one of them had collateral vessels. Five patients (42%) in group IIa had no significant stenosis of coronary arteries. Five patients (42%) showed SVD, one patient (8%) had double vessel disease (DVD), and one patient (8% ) had triple vessel disease (TVD). In group II b, one patient had no significant coronary stenosis, and the other one had DVD. Only 2 patients (14%) in group II had collaterals. There was no statistically significant difference between the number of diseased coronary arteries and the pres- Fig. 2. Comparison of ST elevation group (I, II) and ST depression group (III) concerning the number of coronary arteries with significant stenosis (A) and the incidence of collateral vessels (B). White bars show ST elevation group (group I, II) and black bars show ST depression group (group III). As shown in Fig. A, the incidence of normal or near normal coronary arteries in the group of ST elevation is higher than that in the group of ST depression. On the other hand, the incidence of multi-vessel disease (MVD) in the group of ST elevation is lower than that in the group of ST depression. The incidence of single vessel disease (SVD) is almost same in both groups. Collateral vessels are much developed in the group of ST depression (B).

8 OHKITA 126 ence of and II. collateral vessels in group I Only one patient (6 %) of group IIIa had no significant stenosis of coronary arteries. Four patients (24%) had SVD, 7 (41 %) had DVD, and 5 (29 %) had TVD. Two patients of group Mb had DVD and the other one had SVD. Three patients (15%) of group III had left main trunk disease. Ten of 20 patients (50%) had collateral vessels. Fig. 2 shows comparison of ST elevation (group I and II) and ST depression (group III). The incidence of normal or near normal coronary arteries was found to be higher in groups I and II than in group M (p<0.001). On the other hand, the incidence of multivessel disease in coronary arteries was high in group III (p < 0.001), and the presence of collateral vessels was also high in group M (p<0.005 by t-test) as Fig. 3. Comparison of the leads in ECG with most striking shift of ST-segment during spontaneous angina and the degree of stenosis of the corresponding coronary. The degree of stenosis in right coronary (RCA) was checked when patients had shifts of ST-segment in leads II, III and avf (referred to as F). The degree of stenosis in left anterior descending (LAD) was also estimated when patients had shifts of ST-segment in leads V1-5. In patients with ST elevation (group I and II), the incidence of significantly organic stenosis in the corresponding coronary is high in the anteroseptal area. In patients with ST depression (group III), all patients show ST depression mainly in the precordial leads, and 19 (95 %) of them had organic stenosis in left coronary (17 in LAD, 2 in CX).

9 A CAUSE compared with the other OF groups. 2) Correlation of the electrocardiographic leads with ST-segment shifts and coronary arteriographic findings Fig. 3 shows comparison of the most striking shifts of ST-segments and the stenosis of the corresponding coronary. In groups I and II, only 3 of 18 patients (17%) with ST elevation in lead II, III, avf during angina had significant stenosis in right coronary (RCA), and 10 of 15 patients (67 %) with ST elevation in lead V1-5 during angina had significant stenosis in left anterior descending (LAD). The incidence of significant stenosis in the corresponding to ST elevation was higher in the anteroseptal area than in the inferior area (p<0.005 by t-test). In comparing groups I and II, the incidence of significant stenosis of the corresponding to ST-segment shifts was twice in group II than in group I. However, this difference was not statistically significant. Eleven patients (92%) in group IIa had at least SPONTANEOUS ANGINA % stenosis in the corresponding. It suggests that this definite (but not significant) coronary stenosis plays an important role in ST-segment shifts at exercise test. In group III, all 20 patients had ST depression in lead V1-5 during attack. Seventeen patients (85%) had significant organic stenosis in LAD, and 2 patients (10%) had significant stenosis in circumflex (CX). Eight of 20 patients (40%) had ST depression not only in the precordial leads but also in the inferior leads. Seven of 8 patients (88%) had significant organic stenosis not only in the left coronary but also in the right coronary. CASE PRESENTATION Case (group cordial 1. A 47 year-old male patient IIa, No. 9) complained of prepain at night. Electrocardio- graphic revealed findings during anginal significant elevation Fig. 4. Left coronary arteriogram of the case (No. 9) of group IIa. In control arteriogram (A), the mild stenosis of LAD was observed (arrow mark). In figure of B, vasospasm occurred (arrow mark) subsequent to mild chest discomfort. Administration of nitroglycerin led to immediate disappearance of spasm (C), and organic stenosis was detected at the same area (arrow mark). attack of ST-

10 128 OHKITA Fig. 5. Coronary arteriogram of the case (No. 2) of the group la. Fig. A shows 90% stenosis of RCA (arrow mark 1). In Fig. B, we can see 50% stenosis of LMT (arrow mark 2), 75% stenosis of LAD (arrow mark 3) and 99% stenosis of CX (arrow mark 4). Namely, this patient has triple vessel disease associated with developed collateral vessels from RCA to CX (arrow mark 5). segment in lead V2-5 and avl associated with reciprocal ST depression in lead II, III and avf. He was examined by the exercise test. Two minutes after exercise, chest discomfort appeared and ST elevation was seen in lead V3-5. In the coronary arteriography, he complained of mild chest discomfort, and severe spasm appeared in the segment 7 of LAD (Fig. 4). Administration of nitroglycerin resulted in rapid disappearance of spasm. In the coronary arteriogram, 75 % (by the criteria of AHA) of organic stenosis was observed in the area where spontaneous spasm occurred during mild chest discomf ort. Case 2. A 47 year-old male patient (group IIIa. No. 2) complained of chest discomfort at night and in the morning. Electrocardiographic findings during angina showed significant depression of ST-segment in lead V3-6, II, III and avf. He had also chest discomfort associated with ST depression at the exercise test. Coronary arteriogra- phic findings revealed TVD including collateral vessels from RCA to CX (Fig. 5). DISCUSSION It has been well established that angina pectoris causes a shift of the STsegment in the electrocardiogram. Some experimental evidences support the thesis that epicardial ST elevation is produced by acute occlusion of a large coronary (Rikita et al., 1954) and ST depression in the epicardial leads is due to subendocardial ischemic injury (Guyton et al., 1977). Moreover, other experimental and clinical evidences suggest that epicardial ST depression is related to milder ischemia of the myocardial layers than ST elevation is (Ekmekci et al., 1961.; Maseri et al., 1978). In spontaneous angina, the type of ST elevation during attack is wellknown as variant angina (Prinzmetal

11 A CAUSE OF SPONTANEOUS ANGINA 129 et al., 1959). The mechanism of variant angina seems to be coronary spasm (Oliva et al., 1973 ; Kimura et al., 1978; Maseri et al, 1978). In our coronary arteriographic findings, however, organic stenosis of coronary is observed in 42 percent of variant angina. Especially, single vessel disease is seen with high incidence (Fig. 2). Some investigators described that more than 80 percent of patients with variant angina demonstrated significantly organic stenosis (MacAlpin et al., 1973 Shubrooks et al., 1975). Other investigators showed that organic stenosis of coronary was observed in a half of the patients (Endo et al., 1975 ; Kimura, 1980). The incidence of organic stenosis of the corresponding to electrocardiographic leads with ST elevation was lower in the inferior leads than in the anteroseptal leads. Normal electrocardiograms at rest, with ischemc STsegment elevation in the inferior leads, characterized normal or near normal coronaries in variant angina (Selzer et al., 1976). The coronary flow patterns are different in left and right coronary arteries (Berne and Levy, 1972) left coronary flow increases mainly in diastolic phase and right coronary flow enhances mainly in systolic phase. There may be some differences of coronary vasospasm in left and right coronary arteries. It is a relevant question whether anginal attacks in patients with variant angina is induced by stress testing. Some investigators reported that the attack of variant angina is rarely induced by exercise (Prinzmetal et al, 1959; MacAlpin et al., 1973). Recently, some reseachers have mentioned that the anginal attack is evoked by exercise, leading to ST elevation. This elevation is related to the coronary vasospasm (Yasue et al., 1979; Waters et al., 1980). In this study, 12 patients (36%) showed transient ST elevation at stress testing during daytime. The degree of coronary stenosis in these patients was not as severe as that in patients with ST depression. Consequently, anginal attacks associated with transient ST elevation seems to be more related to coronary vasospasm. The other type of spontaneous angina includes ST-segment depression during anginal attack. Its mechanism is not clear (Coati et al., 1979). According to the report of Maseri and his co-workers (1977), ST depression during attack was seen in patients with multi-vessel disease. Our observations are in accordance with their data. Namely, the present study showed that the incidence of normal or near normal coronary was higher in ST elevation group, and the incidence of multi-vessel disease with or without collateral was higher in ST depression group. The incidence of organic stenosis in ST depression was more than that in ST elevation (p<0.001). It is sometimes quite difficult to distinguish spontaneous angina of ST depression from severe effort angina. Angina of effort is based on an increase in consumption of myocardial oxygen due to various stress under the condition of fixed organic stenosis. In spontaneous angina with ST depression, on the other hand, no significant increases in heart rate and blood pressure were observed before the appearance of ST depression (G auzzi et al., 1975; Figueras et al., 1979). Our clinical observations on 5 out of 20 patients of group III revealed that heart rate and arterial pressure rose a little at the onset of chest pain (our unpublished data). In all the patients of group f, spontaneous angina occurred frequently at night and in the early morning. At daytime, however, spontaneous an-

12 130 OHKITA gina in most cases did not occur despite an increase in physical activity and myocardial oxygen demand. Namely, spontaneous angina associated with ST depression may occur before significant changes of hemodynamics. Accordingly, spontaneous angina with ST depression would be different from effort angina in the mechanism of attack Plotnick and his collaborators (1975) reported on the incidence of coronary organic stenosis and collateral vessels in unstable angina : In the incidence of collateral vessels, there was no statistically significant difference bet - ween the patients of ST elevation and of ST depression. However, the present study showed that the incidence of collateral vessels in the ST depression group was higher than that in the ST elevation group (p<o.005). It may be explained that the ST depression group has severe organic stenosis of coronary arteries, leading to ischemia in the myocardium (subendocardium). Therefore, collateral vessels would be highly developed in this group. The surrounding evidence for vasospasm is obtained clinically. Ca-antagonists are dramatically effective for patients who show ST elevation during spontaneous angina (Kimura et al., 1978; Yasue et al., 1978; Heupler and Proudf it, 1979). Thus, these results suggest that the anginal attack of ST elevation group is mainly induced by vasospasm, and in ST depression group the attack is elicited by vasospasm under the conditions of organic stenosis with or without collateral vessels of coronary. ACKNOWLEDGMENTS The auther wishes to express sincere gratitude to Prof. H. Toshima and Assist. Prof. T. Matoba for their persistent advice and encouragement, and also to Assist. Prof. F. Utsu and Dr. H. Bekki for their advice in coronary arteriography. The auther is grateful to Dr. G. W. Meyer for his help in English. REFERENCES AUSTEN, W. G., EDWARDS, J. E., FRYE, R. L., GENSINI, G. G., GOTT, V. L., GRIFFITH, L. S. C., MCGOON, D. C., MURPHY, M. L. and ROE, B. B. (1975). A reporting system on patients evaluated for coronary disease : Report of the Ad Hoc committee for grading of coronary disease. Council on cardiovascular surgery, American Heart Association. Circulation, 51 (6), Page BERNE, R. M. and LEVY, M. N. (1972). Cardiovascular physiology. ed. 2, St. Louis, Mosby, p BRUCE, R. A. (1974). Progress in exercise cardiology, in Progress in Cardiology, Vol. 3., ed. by Yu, P. N., Goodwin, J. F., Philadelphia, Lea and Febiger, p CONTI, C. R., PEPINE, C. J. and CURRY, R. C. (1979). Coronary spasm : An important mechanism in the pathophysiology of ischemic heart disease. Curr. Probl. Cardiol. 4(4), EKMECKI, A., TOYOSHIMA, H., KWOCZYNSKI, J. K., NAGAYA, T. and PRINZMETAL, M. (1961). Angina pectoris. IV. Clinical and experimental difference between ischemia with ST elevation and ischemia with ST depression. Am. J. Cardiol. 7, ENDO, M., KANDA, I., HOSODA, S., HAYASHI, H., HIROSAWA, K. and KONNO, S. (1975). Prinzmetal's variant form of angina pectoris : Re-evalution of mechanisms. Circulation, 52, FIGUERAS, J., SINGH, B. N., GANZ, P. W., CHARUZI, Y. and SWAN, H. J. C. (1979). Mechanism of rest and nocturnal angina : Observations during continuous hemodynamic and electrocardiographic monitoring. Circulation, 59, GUAZZI, M., POLESE, A., FIORENTINI, C., MAGRINI, F., OLIVARI, M. T. and BARTORELLI, C. (1975). Left and right heart hemodynamics during spontaneous angina pectoris. Brit. Heart J. 37,

13 A CAUSE OF SPONTANEOUS ANGINA 131 GUYTON, R. A., MCCLENATHAN, J. H., NEW MAN, G. E. and MICHAELIS, L. L. (1977). Significance of subendocardial ST segment elevation caused by coronary stenosis in the dog : Epicardial ST segment depression, local ischemia and subsequent necrosis. Am. J. Cardiol. 40, HEUPLER, F. A. and PROUDFIT, W. L. (1979). Nifedipine therapy for refractory coronary spasm. Am. J. Cardiol. 44, HWANG, Y. S., KIMURA, N. and TOSHIMA, H. (1973). Clinical study of variant form of angina pectoris. Kurume Med. J. 20, International Society and Federation of Cardiology/World Health Organization (1979). Nomenclature and criteria for diagnosis of ischemic heart disease. Circulation, 59, KIMURA, E., HOSODA, S., KATOH, K., ENDO, M., YASUE, S., ASADA, S. and KUROIWA, A. (1978). Panal discussion on the variant form of angina pectoris. Jap. Circulat. J. 42, KIMURA, E. (1980). Variant form of angina pectoris : It's clinical features and treatment. Jap. Heart J. 21, MACALPIN, R. N., KATTUS, A. A. and ALVARO, A. B. (1973). Angina pectoris at rest with preservation of exercise capacity. Prinzmetal's variant angina. Circulation, 47, MASERI, A., PESOLA, A., MARZILLI, M., SEV ERI, S., PARODI, O., LABBATE, A., BALLESTRA, A. M., MALTINTI, G., DE NES, M. and BIAGINI, A. (1977). Coronary vasospasm in angina pectoris. Lancet, 1, MASERI, A., SEVERI, S., DE NES, M., LABBATE, A., CHIERCHIA, S., MARZILLI, M., BALLESTRA, A. M., PARODI, O., BIAGINI, A. and DISTANTE, A. (1978). "Variant" angina : One aspect of a continuous spectrum of vasospastic myocardial ischemia. Am. J. Cardiol. 42, MASTER, A. M. (1968). The Master two-step test. Am. Heart J. 75, OLIVA, P. B., POTTS, D. E. and PLUSS, R. G. (1973). Coronary spasm in Prinzmetal angina. New Engl. J. Med PLOTNICK, G. D. and CONTI, C. R. (1975). Transient ST-segment elevation in unstable angina : Clinical and hemodynamic significance. Circulation, 51, PRINZMETAL, M., KENNAMER, R., MERLISS, R., WADA, T. and BOR, W. (1959). Angina pectoris I. A variant form of angina. Am. J. Med., 27, RAKITA, L., BORDUAS, J. L., ROTHMAN, S. and PRINZMETAL, M. (1954). Studies of the mechanism of ventricular activity XII. Early changes in the RS-T segment and QRS complex following acute coronary occulusion : Experimental study and clinical applications. Am. Heart J. 48, SELZER, A., LANGSTON, M., RUGGEROLI, C. and COHN, K. (1976). Clinical syndrome of variant angina with normal coronary arteriogram. New. Engl. J. Med. 295, SHUBROOKS, S. J., BETE, J. M., NUTTER, A. M., BLOCK, P. C., BUCKLEY, M. J., DAGGETT, W. M. and MUNDTH, E. D. (1975). Variant angina pectoris : Clinical and anatomic spectrum and results of coronary bypass surgery. Am. J. Cardiol. 36, SONES, F. M. and SHIREY, E. K. (1962). Cine coronary arteriography. Mod. Concepts. Cardiovasc. Dis. 31, WATERS, D. D., CHAITMAN, B. R., BOURASSA, M. G. and TUBAU, J. F. (1980). Clinical and angiographic correlates of exercise-induced ST-segment elevation : Increased detection with multiple ECG leads. Circulation, 61, YASUE, H., OMOTE, S., TAKIZAWA, A., NAGAO, M., MIWA, K., KATO, H., TANAKA, S. and AKIYAMA, F. (1978). Pathogenesis and treatment of angina pectoris at rest as seen from its response to various drugs. Jap. Circulat. J. 42, YASUE, H., OMOTO, S., TAKIZAWA, A., NAGAO, M., MIWA, K. and TANAKA, S. (1979). Circadian variation of exercise capacity in patients with Prinzmetal's variant angina : Role of exercise-induced coronary arterial spasm. Circulation, 59,