THE WESTERN Journal of Medicine Refer to: Allaire BI, Schroeder JS: Prinzmetal's angina-Clinical and anatomic aspects. West J Med 122:187-193, Mar 1975 Prinzmetal's Angina Clinical and Anatomic Aspects BASIL 1. ALLAIRE, MD, and JOHN S. SCHROEDER, MD, Stanford A review of 120 patients who had a discharge diagnosis of intermediate coro- nary syndrome showed 12 patients with documented transient ST elevation dur- ing spontaneous rest pain consistent with Prinzmetal's angina. Coronary arteri- ography showed severe proximal occlusive coronary atherosclerosis in nine of the patients, and normal or minimal disease in the other three patients. In two of these three, there was documented coronary arterial spasm with reproduction of symptoms during arteriography. Although a shorter history of chest pain, pres- ence of an old myocardial infarction and a positive finding on electrocardio- gram treadmill test tended to predict the patients with severe occlusive coro- nary artery disease, these methods were inadequate to select candidates for arteriography. All patients responded well to nitroglycerine while in the hos- pital. Five of the nine patients with coronary artery disease had coronary by- pass operations, with two excellent, two fair and one poor result. One of the three patients with normal findings on coronary arteriograms died with refrac- tory ventricular arrhythmia six months after study. The other two have had good-to-moderate relief of symptoms on long-acting vasodilators and propran- olol. Current concepts of the syndrome of Prinzmetal's angina and ST elevation are reviewed. It appears that this syndrome has a wide spectrum of clinical presentations and coronary arteriographic anatomies. IN 1959, PRINZMETAL and co-workers first de- duration and cyclical in nature. Postmortem exami- scribed a variant form of angina, characterized by nation in several of their patients showed severe recurrent spontaneous episodes of chest pain asso- proximal occlusive coronary artery disease. The ciated with transient ST segment elevation during authors postulated that the pain syndrome oc- these episodes.1 The pain frequently was of long curred during major vessel occlusion due to transient spasm. This theory was supported by From the Cardiology Division, Stanford University School of eriental work shown s elevatio ec Medicine, Stanford. experimental work showmg ST elevation m elec- Submitted, revised, October 7, 1974. trocardiograms of dogs on occlusion near the This work was supported in part by NIH Grant No. HL-5866 and Program Project Grant No. NIH-PO1-HL-15833-01. origin of the coronary artery, with rapid resolution Reprint requests to: J. S. Schroeder, MD, Cardiology Division, 2 Stanford University School of Medicine, Stanford, CA 94305. on release of the ligature.2 These observations THE WESTERN JOURNAL OF MEDICINE 187
Transcript
THE WESTERNJournal of Medicine
Refer to: Allaire BI, Schroeder JS: Prinzmetal's angina-Clinicaland anatomic aspects. West J Med 122:187-193, Mar 1975
Prinzmetal's AnginaClinical and Anatomic Aspects
BASIL 1. ALLAIRE, MD, and JOHN S. SCHROEDER, MD, Stanford
A review of 120 patients who had a discharge diagnosis of intermediate coro-nary syndrome showed 12 patients with documented transient ST elevation dur-ing spontaneous rest pain consistent with Prinzmetal's angina. Coronary arteri-ography showed severe proximal occlusive coronary atherosclerosis in nine ofthe patients, and normal or minimal disease in the other three patients. In two ofthese three, there was documented coronary arterial spasm with reproduction ofsymptoms during arteriography. Although a shorter history of chest pain, pres-ence of an old myocardial infarction and a positive finding on electrocardio-gram treadmill test tended to predict the patients with severe occlusive coro-nary artery disease, these methods were inadequate to select candidates forarteriography. All patients responded well to nitroglycerine while in the hos-pital. Five of the nine patients with coronary artery disease had coronary by-pass operations, with two excellent, two fair and one poor result. One of thethree patients with normal findings on coronary arteriograms died with refrac-tory ventricular arrhythmia six months after study. The other two have hadgood-to-moderate relief of symptoms on long-acting vasodilators and propran-olol. Current concepts of the syndrome of Prinzmetal's angina and ST elevationare reviewed. It appears that this syndrome has a wide spectrum of clinicalpresentations and coronary arteriographic anatomies.
IN 1959, PRINZMETAL and co-workers first de- duration and cyclical in nature. Postmortem exami-scribed a variant form of angina, characterized by nation in several of their patients showed severerecurrent spontaneous episodes of chest pain asso- proximal occlusive coronary artery disease. Theciated with transient ST segment elevation during authors postulated that the pain syndrome oc-these episodes.1 The pain frequently was of long curred during major vessel occlusion due to
transient spasm. This theory was supported byFrom the Cardiology Division, Stanford University School of eriental work shown selevatio ec
Medicine, Stanford. experimental work showmg ST elevation m elec-Submitted, revised, October 7, 1974. trocardiograms of dogs on occlusion near theThis work was supported in part by NIH Grant No. HL-5866
and Program Project Grant No. NIH-PO1-HL-15833-01. origin of the coronary artery, with rapid resolutionReprint requests to: J. S. Schroeder, MD, Cardiology Division, 2Stanford University School of Medicine, Stanford, CA 94305. on release of the ligature.2 These observations
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have been confirmed by other reports of severeproximal occlusive coronary artery disease oncoronary arteriography in these patients.2-4 Re-cently, reports from this institution and othershave described normal or near-normal findings oncoronary arteriograms in patients with a well-documented clinical syndrome of variant angina.5'6These reports have docunmented coronary spasmduring the arteriogram and suggest that spasmcausing near-occlusion of a normal or minimallydiseased coronary artery may also be responsiblefor the syndrome of variant angina in some pa-tients. This wide disparity of coronary arterio-graphic anatomy, with its significant implicationsfor flexibility in the diagnosis and treatment, pre-cipitated a retrospective review of patients withvariant angina studied at Stanford University Hos-pital. The purpose of this report is to present ourexperience with the spectrum of clinical presenta-tions, differing coronary arteriographic anatomiesand the implications of these results regarding the
pathophysiology of the rest angina and ST segmentelevation and its treatment.
MethodsWe reviewed the medical records of Stanford
University Hospital from 1965 to 1973 and foundthat 120 patients had been discharged with diag-noses which included preinfarction angina, anginadecubitus, coronary insufficiency, variant anginaand Prinzmetal's angina. All these medical recordswere reviewed in detail. Twelve patients fulfilledthe electrocardiographic criteria; that is, docu-mented ST segment elevation recorded duringchest pain in the hospital, with return to isoelectricline after subsidence of the pain. These episodeswere not associated with significant serum glu-tamic-oxaloacetic transaminase (SGOT), lactic de-hydrogenase (LDH) or creatine phosphokinase(CPK) enzyme rises and were not associated withthe development of Q waves on serial electro-cardiograms. In three patients, the ST elevation
TABLE 1.-Patient Characteristics and FindingsDuration Results on Electrocardiography
Age (yrs)I of CAD RiskPatient Sex Symptoms Factors Pain* Pain-free
1...48/ a 2 years FHx ST elev. -V,-3 Normal
2 . 61/ 3 years tlipids, obesity, smoking, HBP ST elev. II, III, AVF, 10 NormalA-V block
3 .. ..47/ 1 week FHx ST elev. II, Ill, AVF, Inferior MIarrhythmias
4 47/9 5 years tlipids, smoking, HBP ST elev. II, III, AVF Normal
5 .. 71/9 1 month tlipids ST elev. AVL, V,4 Deep inversion, T,VI-V4
6 .. ..49/ 1 year FHx, Tlipids, smoking, HBP ST elev. V,4 Normal
7 .. 58/9 10 years Tlipids, FHx ST elev., II, III, AVF Abnormal ST-T wavesII, III, AVF
8 .4/ 40/ 1 month Tlipids ST elev., II, III, AVF Inferior MI
9 .4/ 48/ 3 weeks Obesity ST elev. II, III, AVF, Abnormal T,sinus bradycardia arrhythmia
Without coronary occlusive disease
10.43/s 6 years Smoking ST elev. II, III, AVF,arrhythmias
3 weeks FHx, Tlipids, obesity, HBP ST elev, I, II, Ill, AVF12' 44/9 11 years
Abbreviations:CAD = coronary artery diseaseFHx = positive family history forHBP = high blood pressure
coronary artery disease
ST elev., II, III, AVF, 30A-V block, cardiac arrest
ST elev. = ST segment elevationf = elevated
*All changes seen on electrocardiograms occurred during spontaneous pain and were not related to arteriography.
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11 .44/9
Normal
Normal
Normal
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occurred in the precordial leads without evidenceof true posterior ischemia. In the other nine, theST elevation occurred in the inferior leads (Table1). All twelve patients had rest pain only. It waswithout obvious precipitating cause and usuallyoccurred at night.
All patients were routinely admitted to hospitaland treated medically for 24 to 72 hours, at whichtime coronary arteriography by the Judkins tech-nique was carried out. There were no complica-tions from the procedure. Spontaneous spasm ofone coronary artery occurred in two patients dur-ing the study. In both patients, there was spasmin an area distal to the catheter tip with associatedchest pain and ST elevation similar to other docu-mented episodes. Follow-up of these patients wasobtained through the patient's private physicianor from medical records.
Results (Figures 1 and 2)On the basis of coronary arteriography, the pa-
tients can be divided into two anatomic groups.Group I consists of nine patients in whom therewas severe proximal occlusive coronary artery dis-ease of at least one major coronary artery, withor without atherosclerosis in the other arteries.
Group II consists of three patients in whom therewas minimal or no coronary atherosclerosis oncoronary arteriography. In two of these patients(patients 10 and 11), spasm of the right coronaryartery was documented during coronary arteriog-raphy. The spasm was associated with reproduc-tion of the patient's chest pain and ST elevationon lead II of the electrocardiograph (ECG) moni-tor. Repeated right coronary injections docu-mented relief of the spasm over three to five min-utes with relief of the chest pain and return of theST segments to normal. The other patient is sus-pected of having coronary spasm, although thiswas not documented during arteriography.
In the patients in Group I, the duration ofsymptoms ranged from three weeks to five years,with a wide variety of coronary atherosclerosisrisk factors. The patients with severe occlusivecoronary disease were more likely to have had aprevious myocardial infarction or abnormal ST-Twaves during pain-free episodes or both. TheGroup II patients were more likely to have had alonger history of symptoms, ranging from threeweeks to eleven years, and to have a normal elec-trocardiogram during pain-free periods.
Figure 1.-Serial rhythm monitoringstrips from patient 10, who had docu-mented right coronary artery spasmduring arteriography. All rhythm stripsobtained during spontaneous painepisodes. A-normal sinus rhythm,pain-free; B-varying A-V block andventricular premature contractions pre-ceding the onset of angina and STelevation; C-ventricular prematurecontractions and ventricular tachy-cardia, pain-free.
VI V2
Figure 2.-Electrocardi-ographic leads V,, V2and V3 showing STsegment elevation andreversal of T waveinversion during painepisodes in patient 5.
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A
V3
7/16/ 7210:30 a.m.
PAIN FREE
7/16/7210:45 a.m.
DURING PAIN
7/18/72PAIN FREE
7/19/72DURING PAIN
7/26/72PAIN FREE
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long-acting vasodilators for chest pain while inthe hospital. All 12 patients had moderate-to-dramatic response to vasodilators, with thegreatest response noted in the patients who hadonly rest angina. Patients 4 and 9, who had severeocclusive coronary artery disease and positive re-sults from exercise tests, continued to have exer-tionally-induced angina as well as repeated boutsof rest angina and ST elevation while in the hos-pital. Of the nine patients with proximal occlusivecoronary disease, five have had coronary arterybypass operations without complications. Of thissurgical group, three patients are free from pain,one patient has exertionally-induced angina onmoderate activity and one has angina on severeactivity.The two patients with insignificant occlusive
disease, but with demonstrated right coronaryartery spasm, have had dramatic decrease in theirchest pain following the long-term use of long-acting vasodilators and beta-blockade. In one ofthese patients, the addition of thorazine to thedrug regimen in an effort to produce alpha-block-ade resulted in little additional improvement.There was spontaneous subsidence of pain asso-ciated with enzyme elevation in one (patient 6)after a suspected acute myocardial infarction. Oneof the three patients without occlusive coronarydisease died seven months after study, with unre-mitting chest pain and cardiogenic shock.7
DiscussionReports in the recent medical literature have
described at least 41 patients with Prinzmetal'svariant angina who have been studied bycoronary arteriography or postmortem examina-tion.2-4'6'8-13 Of the 41 patients reported, 19 hadsignificant proximal occlusive coronary disease.One of the 19 patients had associated spasm dur-ing arteriography. There were eight of the 41patients who had normal vessels, or less than 25percent occlusion of the coronary arteries. Threeof the eight patients had angiographically demon-strated spasm during coronary arteriography, withassociated ST elevation and chest pain. This coro-nary arteriographic spectrum of anatomic findingsis generally in accord with ours, indicating thatapproximately 75 percent of patients with Prinz-metal's variant angina will have severe occlusivecoronary artery disease. A smaller, but importantnumber of patients will have normal or near-nor-mal coronary arteries. Spasm during coronaryarteriography has occasionally been documented
in this group. Although patients with severe proxi-mal occlusive disease tended to have shorter dura-tion of chest pain symptoms and were more likelyto have positive findings on a treadmill exercisetest, the high incidence of severe occlusive proxi-mal disease would indicate that all patients withthis syndrome should have coronary arteriography.
Our experience with treadmill exercise testingin variant angina is limited and has not been ofhelp in differentiating the patients with coronaryspasm from those with occlusive coronary arterydisease. In the two patients with documented coro-nary spasm only, both had normal response toexercise testing at maximal heart rates of 150 and160. Only three patients with severe proximalocclusive disease were given exercise tests; oneshowed a positive stress test consisting of 1 mmof ST segment depression, the second stopped thetest because of fatigue with only minimal ST de-pression and the third had resting ST abnormal-ities, which precluded a definite diagnostic re-sponse during exercise. Cheng et al reported fourpatients with variant angina without significantcoronary artery disease.6 In one of their patients,there was ST segment elevation and chest painduring a Masters two-step exercise test. Kemp etal described a patient with ST segment elevationduring exercise testing who had a severe occlusionof the left anterior descending and circumflexarteries.9 Care must be taken in using stress test-ing for this patient group, however, because ofthe possibility of severe proximal occlusive diseaseand the precarious balance between myocardialoxygen demands and delivery. Stress testingshould not be carried out if there is residual STelevation on electrocardiogram or other evidenceof a recent myocardial infarction, such as enzymeelevation.
In general, it is our impression that the ST ele-vation during exercise testing at the onset of chestpain may be indicative of severe proximal occlu-sive disease.
Three of our 12 patients reported had seriousarrhythmias during the spontaneous episodes ofchest pain (Figure 1). All three of these patientshad ST elevation in the inferior leads. Two of thepatients had accompanying transient atrioventric-ular (A-V) block. One patient had repeated boutsof ventricular tachycardia during episodes of pain,and one patient had ventricular tachycardia pro-gressing to ventricular fibrillation. MacAlpin et al,in a study of 20 patients with variant angina, re-ported a 25 percent incidence of arrhythmias dur-
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ing the pain period.4 Two of their patients alsohad documented ventricular tachycardia or fibril-lation, and two had varying degrees of atrioven-tricular block. In view of the high incidence ofarrhythmias during chest pain, these patients re-quire careful monitoring and may be candidatesfor sudden death.
The cause of the coronary artery spasm, whichwas initially suggested as the cause of variantangina by Prinzmetal,l and now documented in anumber of medical reports' 6 8 is unclear. Guazziet al found no hemodynamic changes duringchronic monitoring in patients with Prinzmetal'sangina to account for a change in myocardial oxy-gen demands.14 These data would suggest thatchanges in cardiac work are not the primarycauses in the precipitation of the rest pain in thispatient group. MacAlpin et al suggested that dur-ing rest and sleep the tone of the larger vessels ishighest and the diameter smallest, which may pre-dispose to coronary spasm.'1 The frequent com-plaint of rest or nocturnal angina in patients withPrinzmetal's variant angina is consistent with thishypothesis. These observations would suggest thatpatients with Prinzmetal's angina who have nor-mal or only minimally diseased coronary arteriesmost likely have myocardial ischemia on thebasis of changes in coronary blood flow due tocoronary spasm occurring at rest.
In contrast, in patients with unprovoked or restchest pain due to severe occlusive coronary arterydisease, also called preinfarction angina, the restangina frequently is caused by changes in myo-cardial work and oxygen demands. Cannom et alhave documented rises in heart rate and bloodpressure preceding the onset of chest pain duringcontinuous hemodynamic monitoring in certainpatients with unstable or preinfarction angina.'5These patients with severe proximal occlusive dis-ease may have either ST depression or elevationduring their rest pain episodes. These changesnoted on electrocardiograms may be the only dis-tinguishing feature between variant angina andtypical angina pectoris in this patient group.
Medical treatment is frequently rewarding inpatients with Prinzmetal's angina whether theyhave occlusive coronary disease or normal coro-nary arteries. The acute episodes of chest painwith ST elevation almost invariably respond tonitroglycerin, although two of our 12 patients re-quired narcotics for complete relief of the pain onseveral occasions. Of our 12 patients, seven hadan excellent response to long-acting vasodilators,
either prophylactically or in causing a decrease inthe frequency and severity of their rest anginaattacks. Guazzi et al found that chronic use ofpropranolol was effective in his four patients,using doses as high as 480 mg per day.'6 Theseauthors postulated direct or secondary effects inarterial tone as a result of the propranolol admin-istration.14 In the two long-term patients withnormal coronaries whom we have followed atStanford University Hospital, therapy with pro-pranolol and vasodilators has been satisfactory inrelieving approximately 75 percent of disabilitycaused by pain. In view of this excellent responseto medical therapy, we do not believe that coro-nary bypass operation is indicated in patients withnormal or minimal coronary artery disease.
MacAlpin et al suggested that denervation byadventitial stripping, coupled with coronary arterybypass operation in instances of severe occlusivedisease, may alleviate the problem of recurrentspasm at or beyond the site of bypass.4 Of thosein our patient group in whom coronary artery by-pass surgical procedures were carried out, onepatient has had recurrent angina following triplebypass operation, but not of Prinzmetal's type andnot associated with ST elevation; three patientshave been pain-free for three months, six months,and one and a half years, following operation, andthe remaining patient has had pronounced im-provement.
Conclusions* Prinzmetal's variant angina is a spectrum of
clinical presentations with pronounced variationin coronary arteriographic anatomic findings,rather than a specific anatomic disease entity. Itis characterized by symptoms of spontaneouschest pain with or without radiation to the neck,shoulders, jaws or arms, which occurs at rest andis associated with ST segment elevation duringchest pain, but without progression to frank myo-cardial infarction upon resolution of the pain.
* Patients with normal findings on resting elec-trocardiograms, a negative response to a tread-mill exercise test and a long history of restangina are more likely to have normal or mini-mally diseased coronary arteries. Despite this, thehigh incidence of severe proximal occlusive coro-nary disease indicates that all patients should havecoronary arteriographic study.
* Short- and long-term medical treatment in-cludes short-acting vasodilators, to which thereis usually an excellent response. Patients fre-
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quently respond to long-acting vasodilators suchas isosorbide dinitrate, given both prophylacticallyand to decrease the frequency and severity ofattacks. Propranolol has occasionally been help-ful in these patients and can be tried in thosepatients with minimal coronary artery disease.
0 Coronary artery bypass operation should beconsidered only for the patient with high-gradeproximal occlusive coronary lesions.
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