Variant angina pectoris: Clinical and anatomic spectrum and results of coronary bypass surgery

Variant Angina Pectoris: Clinical and Anatomic Spectrum and Results of Coronary Bypass Surgery

SAMUEL J. SHUBROOKS, Jr., MD’ JOHN M. BETE, MD ADOLPH M. HUTTER, Jr., MD, FACC PETER C. BLOCK, MD MORTIMER J. BUCKLEY, MD, FACC WILLARD M. DAGGETT, MD, FACC+ ELDRED D. MUNDTH, MD, FACC Boston, Massachusetts

From the Cardiac Unit, Department of Medicine, and Cardiac Surgical Service of the Massachusetts General Hospital, Boston, Mass., and the Departments of Medicine and Surgery, Harvard Medical School, Boston, Mass. This study was supported in part by Grants HL 5196, HEPP 06664 and Contract NOI HV 71443 from the U. S. Public Health Service, Bethesda, Md. Manuscript accepted December 11. 1974. Present address: Cardiology Unit, New England Deaconess Hospital, Boston, Mass. + Established Investigator of the American Heart Association. Address for reprints: Adolph M. Hutter, Jr., MD, Cardiology Unit, Massachusetts General Hospital, Fruit St., Boston, Mass. 02114. l

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Twenty patients are described with the variant anglna syndrome (recurrent angina at rest with S-T segment elevations occurring only during pain and no evolution of infarction). In contrast to patients previously reported on, all but one had progressive unstable angina before hospitalization. Angina was frequently associated with arrhythmias, including ventricular fibrillation (2 instances), ventricular tachycardia (4), frequent ventricular premature beats (5), atrioventrlcular block (4), sinus bradycardia (2), sinoatrial exit block (1) and supraventricular tachycardia (1). Seventeen patients had significant proximal stenosis of one or more coronary artertes with good distal vessels. Bypass surgery in 15 of these patients resulted in one noncardiac postoperative death, one perloperative infarction and relief of pain in all 14 survivors. After a 17 month mean follow-up period (range 4 to 38 months), all survivors are pain-free. Three patients had no signfflcant coronary disease; one of these became asymptomatic with medical therapy, one continues to have angina and one died suddenly. Patients with normal coronary arteries could not be distinguished clinically or by electrocardiogram from those with severe obstructive lesions. This experience suggests that all patients with the variant angina syndrome should be studied by coronary angiography, and that most patients with significant fixed coronary lesions will do well after coronary bypass surgery.

In 1959, Prinzmetal et al.’ described a form of variant angina pectoris characterized by pain occurring at rest or during ordinary activity rather than with exertion. The electrocardiogram during this variant angina showed S-T segment elevations with prompt return to control levels upon remission of pain. Since there was no evolution of myocardial infarction and since the course was believed to be stable or to improve with time, this type of angina was differentiated from “preinfarctional angina.” However, many studies have indicatedzg that subsequent infarction in areas in which S-T-segment elevations were observed frequently occurs and that mortality in the follow-up period is significant. Since Prinzmetal’s original description, coronary angiography and coronary artery bypass surgery have come into general use. However, the roles of medical and surgical therapy in this syndrome are controversial, and it has recently been suggested that the latter is not appropriate for the majority of these patients.‘O This paper therefore describes the clinical spectrum, angiographic features and results of medical and surgical therapy in 20 patients admitted to the Massachusetts General Hospital with the variant angina syndrome, 15 of whom had coronary bypass surgery.

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TABLE I Clinical Data on 20 Patients with Variant Angina Pectoris

Case no.

Age (yr) & Sex

Duration of Accelerated Angina

Duration of Angina

Anterior 1 2 3 4 5 6 7 8 9 10 11 12

54M 54M 5EM 64.F 58F 50F 53M 58M 49M 52F 56F 59F

1 8 1 1 1 10 3 4 2 8 1 12

1 1 5 1 1 3 2 1 2 8 1 12

month months year week hour years weeks years days days hour hours

55M

14 15 16 17 18” 19* 20*

45F 44M 53F 39F 42F 45F 58F

2 years 2 3 4 18 6 2 4

or lnferoapical

1 1 1 3

month hour hour weeks

*Patients without significant coronary artery disease. AF = atrial flutter; AVB = atrioventricular block; NTG bradycardia; 2” = second degree; SVT = supraventricular ventricular premature beats; VT = ventricular tachycardia.

VI-V, V,-V,, aVL I, aVL, V,-V, V monitor

VF VT VPBs

..

VI--V, aVL, V,--V, I, aVL, V,-V, I, aVL, V,--V, V,--V, VI--V,

SB, VPBs VT SAB . . .

... ... ... VPBs,

SVT,

AF

S-T Elevations 2’AVB,

No Yes Yes Yes No No No

No Partial

ll,lll, ll,lll, II,IIl, II,III, ll,lll, ll,lll, ll,lll,

aVF aVF aVF aVF aVF aVF aVF,

SB, SA VPBs SA, SB, 3” AVB VPBs 2” AVB SB, 2” AVB, VT

Yes Yes Yes Yes Yes

V,-V, --___-

VT, VF

...

= nitroglycerin; SA = sinus arrest; SAB = sinoatrial block; SB = sinus fibrillation; VPBs = tachycardia; 3” = third degree; VF = ventricular

The clinical characteristics of these patients are shown in Table I. The total duration of angina ranged from 1 hour to 10 years. All patients had angina at rest, frequently at a predictable time of day. In contrast to the stable course depicted in Prinzmetal’s original description,l all but one of the patients in this series (Patient 16, who had stable angina over a 4 angina

VI--V,

aVF

History and Physical Examination

unstable

VI--V, I, aVL,

II,IIl,

Results with Comment

had progressive,

Yes Yes Yes Yes No Yes Yes Yes Yes Yes Partial Partial

Yes

Twenty patients admitted to the Massachusetts General Hospital from January 1971 to January 1974 fulfilled the criteria for variant angina pectoris: recurrent angina at rest associated with S-T segment elevations, not in the area of an old infarction, with return of the S-T segments to control levels after relief of pain, and without evolution of myocardial infarction by serial electrocardiograms or by cardiac enzymes. These patients were 8 men averaging 53 years of age and 12 women averaging 52 years of age. All patients had selective coronary angiography. Seventeen patients had significant obstructive coronary lesions, that is, greater than 70 percent luminal narrowing. Three patients had no significant coronary artery disease by angiogram.

period)

Arrhythmias During Pain

Yes

Patient Selection

month

S-T Elevations

S-T Elevations

Yes Yes No No No Yes Yes Yes Yes Yes Yes No

Few hours 2 weeks 1 week . . .

weeks years months months months weeks years

Pain Relief with NTG

or Anterolateral

hour week days week hour weeks days month days days hour hours

Inferior 13

Exertional Angina

for 1

hour to 1 month, leading to hospitalization for increasing frequency and duration of severe pain. Although previous reports have described exertional pain only rarely in variant angina,4T8J0J-14 12 of our patients had angina on exertion as well as during rest; in 7, the pain began with exertion only and progressed to pain during rest. All 12 of these patients had significant obstructive coronary lesions. The three patients with angiographically normal arteries (Patients 18 to 20) had pain only during rest. Pain was completely relieved by nitroglycerin in 15 patients; 2 had no response and 3 had only partial relief. Physical examination of the cardiovascular system was normal except for the presence of an apical fourth heart sound gallop in 10 patients. All three patients with variant angina and no significant coronary artery disease were female. Electrocardiographic Findings Figure 1 shows the course of S-T segment changes during and after pain in Patient 19, who had angiographically normal coronary arteries. Similar S-T elevations during pain occurred inferiorly or inferoapitally in 8 patients and anteriorly or anterolaterally in 12 patients (Table I). Concurrent S-T depressions appeared in reciprocal leads in all. The three patients

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I

II,

II


‘.I

.A\ I

5i

!

i’i

FIGURE 1. Case 19. Electrocardiograms showing representative changes in S-T segments during pain. A, in the absence of pain. 6, during pain, showing marked S-T elevations in the inferior leads with reciprocal depressions anterolaterally. C, 30 minutes later, after relief of pain, showing persistent slight anterolateral S-T depressions. D, return to normal 3 hours later.

TABLE II Cardiac Catheterization Case no.

Data and Course of 20 Patients with Variant

Location of Significant Coronary Lesions

8 9 10 11 12

Proximal LAD Proximal LAD, onal, LCxM Proximal LAD Proximal LAD Proximal LAD Proximal LAD, Proximal LAD;

Left Ventricle ~.~ or Anterolateral

RCA

Proximal LAD, LCx Proximal LAD, LAD diagonal; occluded RCA Proximal LAD; occluded RCA Proximal LAD, LCxM; occluded RCA Proximal LAD, LCxM

~_~~

Follow-Up Data

-_ ____

LAD LAD, LAD diagonal LAD LAD

diag-

RCA occluded

~~_____

S-T Elevations

Normal LAD

Pectoris

Coronary Vessels Bypassed

.~ Anterior

1 2

Angina

~__

lnferoaplcal aneurysm Normal lnferoapical akinesis; slight anterolateral hypokinesls Normal Slightly enlarged; inferior akinesls; anterolateral hypokinesls Anterolateral hypokinesls; apical dyskinesis Slight enlargement; inferior akinesis; anterolateral and apical hypokinesis Apical akinesis; inferior hypokinesis

No angina, 25 mo. No angina, 19 mo.

LAD LAD LAD,

RCA

No No No No No

None LAD,

RCA

No angina, 7 mo. No angina, 6 mo.

LAD

angina, angina, angina, angina, angina,

22 mo. 14 mo. 22 mo. 38 mo. 9 mo.

No angina, 4 mo.

LAD,

LCxM,

LAD,

LCxM

RCA

Died postop No angina,

11 mo.

_ lnferlor 13 14 15 16 17 18 19 20

LCA ostium, distal RCA Proximal LAD, LCx and RCA, Proximal LAD, mid RCA Proximal LAD, LAD diagonal, mid RCA Proximal LCx, LCxM None None None

or lnferoapical

S-T Elevations

lnferoapical hypoktnesis Normal lnferoapical akinesis Inferior hypokinesis

LAD, LAD, LAD, LAD.

Normal Normal Normal Normal

None None None None

RCA LCx, RCA RCA

RCA

LAD = left anterior descending coronary artery; LCA = left coronary artery; LCx = left circumflex cumflex marginal artery; Ml = myocardial infarction; postop = postoperatively; preop = preoperatively; artery.

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No Ml No No

angina, 20 mo. with anesthesia preop angina, 10 mo. angina, 5 mo.

No angina, 5 mo. Recurrent angina, 17 mo. No angina, 40 mo. Died suddenly, 8 mo. artery; RCA

LCxM

= left cir-

=

coronary

rjght

VARIANT

without significant coronary disease angiographically (Patients 18 to 20) had S-T elevations inferiorly, a finding reported in the majority of patients with variant angina and insignificant coronary disease.2AJoi3~rs-18 Nevertheless, four such patients had anterior S-T elevations.2J1J8Jg Thus, the location of S-T elevation does not predict presence or absence of fixed obstructive coronary lesions. In the other 17 cases, the location of S-T elevation correctly predicted a cardiac area supplied by a significantly obstructed coronary artery. However, several patients (Cases 6,7,9 to 11, 13 to 16) had additional significant coronary disease that was not predicted by the leads showing S-T elevations (Table II). The electrocardiogram in the absence of pain returned to normal in 6 patients, including the 3 without significant coronary disease, and showed persistent nonspecific S-T segment and T wave abnormalities in the other 14. In no cases did new Q waves develop, nor was there serial evolution of nontransmural infarction. Four patients (Cases 2,7,9 and 11) had electrocardiographic evidence of an old inferior wall infarction; all four had S-T elevations in the anterior leads during variant angina. Serious arrhythmias during episodes of pain were common (Table I). With pain, ventricular fibrillation occurred in two patients and ventricular tachycardia in four, including one patient without significant coronary disease angiographically (Case 19). Five additional patients had frequent ventricular premature beats during pain. Whether ischemia involved the anterior or inferior wall did not appear to affect the incidence of ventricular irritability. Second degree atrioventricular (A-V) block of the Wenckebach type occurred in three patients, including two with angiographically normal coronary arteries. Intermittent complete A-V block occurred in one patient. All four patients with A-V block had evidence of inferior wall ischemia. Marked sinus bradycardia during pain occurred in two patients with inferior and in one patient with anterior ischemia. Sinoatrial (S-A) exit block of the Wenckebach type was seen in one patient with anterior ischemia. One patient had periods of supraventricular tachycardia during pain. The frequency of arrhythmias in our patients is in accord with data from previous studies in which venirritability,3>4p7,8JoJ5J6Jg atria1 fibrillatricular tion 4pg~14supraventricular tachycardia,lOJl second and ‘third degree A-V block,3,4,10-12.16,‘7,20-22extreme sinus slowing18 and S-A block22 have been reported. Angiography Coronary angiographic data are summarized in Table II. Seventeen patients had greater than 70 percent fixed obstruction of a major coronary artery. Five patients had significant disease of one major coronary vessel only (Cases 1,3 to 5 and 17). Nine patients had significant disease of two major arteries with the left anterior descending artery being involved in all (Cases 2, 6 to 10, 12, 15 and 16). Three patients (Cases 11, 13 and 14) had the equivalent of significant three vessel disease. All patients had ade-

ANGINA PECTORS-6HUSROOKS ET AL.

quate distal vessels and none had diffuse inoperable disease. Three patients (Cases 18 to 20) had no angiographically significant coronary disease. The occurrence of multiple vessel obstructive disease is in contrast to Prinzmetal’s suggestion that variant angina is associated with severe disease of a single coronary artery on1y.l Indeed, the distribution of coronary lesions in these patients does not appear to differ from that in patients with typical exertional angina, except for the absence of diffuse distal disease. Left ventricular angiograms were performed for all but three patients and were normal in eight. Four patients with old inferior infarction had evidence of inferior wall akinesis or dyskinesis. Eight patients had evidence of hypokinesis in the left ventricular areas supplied by stenotic vessels (Table II). Coronary spasm is often postulated to be an etiologic factor in initiation of pain in patients with variant angina. This was not observed in any of our patients; however, none of our patients experienced angina during angiography. Prinzmetal et al.’ originally proposed that pain was due to “temporarily increased tonus of a single large narrowed coronary artery.” More recently, spasm has been demonstrated to occur during coronary angiography of patients with variant angina, either in an essentially normal vesse116,22 or in the area of a plaque that did not cause significant obstruction in the absence of spasm.‘O Thus, spasm may be an important factor, at least in patients with the syndrome of variant angina and normal coronary arteries. The role of spasm in patients with significant fixed obstructive lesions is not known. Experimental studies of coronary occlusion in dogs have indicated that S-T elevations are indicative of more severe myocardial ischemia than are S-T depressions. 23 Possibly, the combination of spasm and fixed obstruction might result in greater ischemia. Hospital Course Medical treatment: After admission to the hospital, despite absolute bed rest, angina associated with S-T elevations continued to occur in all patients but one (Case 6). Four patients (Cases 8, 13, 14 and 19) had no further pain on treatment with long-acting nitrates and propranolol in doses of 80 to 160 mg/day. One patient (Case 17) continued to have angina with propranolol in a dose of 320 mglday but not when the dose was increased to 560 mglday. Two patients (Cases 7 and 20) had a marked decrease in frequency and severity of pain with long-acting nitrates alone. The other patients continued to experience angina with propranolol (40 to 320 mg/day) and, in most cases, long-acting nitrates. Because of continued pain at rest in spite of intensive medical therapy, 10 patients underwent intraaortic balloon pumping before angiography. This procedure resulted in cessation of pain in all but two patients, one with continued significant pain (Case 4) and one with persistent mild pain (Case 2). Bypass surgery: Because of the unstable progressive severity of their angina and the frequently asso-

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ciated arrhythmias despite intensive medical therapy in most cases, 15 of the 17 patients with significant coronary lesions underwent coronary arterial bypass grafting. Two patients (Cases 8 and 17) received only medical therapy in spite of anatomic features suitable for bypass grafting. Six patients had single vein grafts, all to the left anterior descending coronary artery. Seven patients had double grafts, to the left anterior descending and right coronary arteries in five, to the left anterior descending artery and its diagonal branch in one and to the left anterior descending and circumflex arteries in one. Two patients had triple grafts to the left anterior descending, left circumflex and right coronary arteries. There was one in-hospital death (due to severe pulmonary infection and renal failure). One patient (Case 14) had an intraoperative myocardial infarction related to failure of a temporary pacemaker to function when complete A-V block occurred during induction of anesthesia. All others tolerated the bypass procedure well. Follow-Up All 14 patients surviving bypass surgery are living after an average follow-up period of 17 months (range 4 to 38 months) and all are pain-free (Table II). No patient has had further difficulties with arrhythmias, and no myocardial infarctions have occurred postoperatively. The favorable postoperative course of these patients differs from previously reported experiences. Five of the six patients with bypass surgery described by McAlpin et al. lo had pain at rest within 4 weeks, associated with occlusion of the graft in three and occlusion of the vessel just distal to the graft in another. Recently, Bodenheimer et a1.12 reported that two of three patients with bypass grafting had continued pain postoperatively, one with a perioperative infarction and one with an occluded graft. Betriu et al.” described a patient with bypass grafting who had a postoperative infarction and continued angina with an occluded graft. The two patients in our series with significant obstructive lesions treated medically are asymptomatic, one (Case 8) 7 months after admission on a regimen of isosorbide dinitrate and propranolol, 160 mg/day, and one (Case 17) 5 months after admission on a regimen of isosorbide dinitrate, quinidine and propranol01, 560 mg/day. Prinzmetal et al.’ and, more recently. McAlpin et al.1° suggested that the clinical course in these patients is rather stable and that their symptoms tend to decrease with time. The latter investigators therefore recommended that surgery be reserved only for patients with incapacitating symptoms refractory to medical therapy. In contrast, review of other reported cases indicates a high incidence of infarction and death for patients given medical therapy alone.2-g We hope that successful bypass surgery will alter this unfavorable prognosis. Patients without significant coronary artery disease: Of the three patients in this group, one (Case 19), who had multiple episodes of ventricular tachycardia during pain, has had gradual disappearance of symptoms and is doing well 40 months after 146

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admission on therapy with isosorbide dinitrate, propranolol, quinidine and diphenylhydantoin. Another (Case 18), after several months without pain, again experienced frequent angina1 episodes relieved by nitroglycerin; long-acting nitrates could not be employed because of severe headaches associated with their use. The third patient (Case 20) died suddenly during an episode of pain 8 months after hospitalization while receiving long-acting nitrates. Patients having angina pectoris in association with evidence of myocardial ischemia but with normal coronary angiograms have been reported to follow a benign course. 24,25 Whether the occurrence of S-T elevations during pain is associated with a more unfavorable course in such patients with normal coronary arteries is unknown. The association of A-V block or serious ventricular arrhythmias, or both, with pain in two of our three patients without significant coronary disease, and in most of the similar isolated cases previously reported,3*4J5-17Jg appears to indicate a severe degree of ischemia in these patients, perhaps related to occlusive spasm. Although the condition of two of our patients improved with time after medical therapy, as has that of some other similar patients 11,12,17~18 one of our patients and four described by others4J5J8Jg di e d suddenly during angina1 episodes. Surgery does not appear to be indicated for these patients. Dhurandhar et a1.15 described such a patient with documented proximal right coronary arterial spasm only who had bypass grafting to the distal right coronary artery. Ten days postoperatively recurrent variant angina developed, and he died with the graft remaining patent. Recently, Betriu et al.” reported on three patients with nonsignificant obstructive lesions who underwent bypass grafting; one died postoperatively, one had recurrence of pain and one had a postoperative infarction with an unknown subsequent course. The demonstration by Oliva et al.,” in a patient having the variant angina syndrome with normal coronary arteries in the absence of pain, that the site of spasm during pain varied and at times involved a long segment of the right coronary artery extending as far distally as the posterior descending artery, may explain the ineffectiveness of bypass grafting in these patients. Conclusions Our experience suggests that all patients with the variant angina syndrome should be studied by coronary angiography since no clinical or electrocardiographic manifestations could distinguish those patients with angiographically normal coronary arteries from those with severe proximal obstructive lesions. In contrast to findings in most previous reports, all but one of our patients had an unstable and progressive course. Although our patients were inevitably a selected group, since their angina was severe enough to result in hospitalization, the same is true of other series. Patients with severe proximal obstructive lesions can undergo coronary artery bypass surgery with a low risk and excellent postoperative course over a prolonged follow-up period.

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References 1. Prlnzmetal M, Kennamer R, Yerllss R, et al: Angina pectoris. I. A variant form of angina pectoris. Am J f&d 27:375-388, 1959 2. Bobba P, Dlguglellmo L, Vecchlo C, et al: Coronarographic patterns in Prinzmetal’s variant angina. Acta Cardiol (Brux) 26: 568-580, 1971 3. Co&y RS, Gkldlngs TA, See JR, et al: Variant angina: case reports and critique. Am J Med 53:739-742, 1972 4. Glanelly R, Mugler F, Harrison DC: Prinzmetal’s variant of angina pectoris with only slight coronary atherosclerosis. Calif Med 108:129-132, 1968 5. Guazzi M, Florentlnl C, Polese A, et al.: Continuous electrocardiographic recording in Prinzmetal’s variant angina pectoris. Br Heart J 32:611-616, 1970 6. Peretz DI: Variant angina pectoris of Prinzmetal. Can Med Assoc J 85:1101-1103, 1961 7. Robinson JS: Prinzmetal’s variant angina pectoris: report of a case. Am Heart J 70:797-800, 1965 8. Sllverman ME, Flamm MD: Variant angina pectoris: anatomical findings and prognostic implications. Ann Intern Med 75:339343,197l 9. Yeh BK, Rogers CM: Prinzmetal’s angina. Chest 58:396-398, 1970 10. McAlpln RN, Kattus AA, Alvaro AB: Angina pectoris at rest with preservation of exercise capacity: Prinzmetal’s variant angina. Circulation 47:946-958, 1973 11. Betrlu A, Sollgnac A, Bourassa MG: The variant form of angina: diagnostic and therapeutic implications. Am Heart J 87:272278, 1974 12. Bodenhelmer M, Llpskl J, Donoso E, et al: Prinzmetal’s variant angina: a clinical and electrocardiographic study. Am Heart J 871304-313, 1974 13. Krlstlan-Kerln N, Davies B, MacLeod C: Nonocclusive coronary disease associated with Prinzmetal’s angina pectoris. Chest 64~352-355, 1973

14. Kwoczynskl J, Boguckl R: The variant form of angina pectoris: sequence of ST-T afterations. MS Chest 52:399-401, 1967 15. Dhurandhar RW, Waft DL, Sliver MD, et al: Prinzmetal’s variant forms of angina with arteriographic evidence of coronary artery spasm. Am J Cardiol30:902-905, 1972 16. Whlflng RB, Klein MD, Vandeneer J, et al; Variant angina pectoris. N Engl J Med 282:709-719, 1970 17. Dflva PB, Potts DE, Pfuse RO: Coronary arterial spasm in Prinzmetal’s angina: documentation by coronary arteriography. N Engl J Med 288:745-751, 1973 18. Cheng TO, Bashctur 1, Kelser GA, et al: Variant angina of Prinzmetal with normal coronary arteriograms-a variant of the variant. Circulation 47:476-485, 1973 19. ChrIstIan N, Bottl RE: Prinzmetal’s variant angina pectoris with prolonged electrocardiographic changes in the absence of obstructive coronary disease. Am J Med Sci 263:225-232, 1972 20. Bottl RE: A variant form of angina pectoris with recurrent transient complete heart block. Am J Cardiol 17:443-446, 1966 21. Glllllan RE, Hawley RR, Warbasse JR: Second degree heart block occurring in a patient with Prinzmetal’s variant angina. Am Heart J 771380-383.1969 22. Lasser RP, DeLapar NS: Repetitive transient myocardiil ischemia, Prinzmetal type, without angina pectoris, presenting with Stokes-Adams attacks. Chest 64:350-352, 1973 23. Ekmekcl A, Toyoshlma H, Kwoczynskl J, et al: Angina pectoris. IV. Clinical and experimental difference between is&tern& with S-T elevation and ischemia with 3-T depression. Am J Cardiol 71412-426, 1961 24. Bemlller CR, Peplne CJ, Rogers AK: Long-term observations in patients with angina and normal coronary arteriograms. Circulation 47136-43, 1973 25. Kemp HG Jr, Vokonas PS, Cohn PF, et al.: The angina syndrome associated with normal coronary arteriograms-report of a six year experience. Am J Med 54:735-742. 1973

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