lACC Vol. 4, No.3September 1984:635-9

Refractory Coronary Artery Spasm

VIRINDERJIT S. BAMRAH, MD, FACC, GREGORY J. SCHUCHARD, MD

Milwaukee, Wisconsin

635

A patient with an episode of refractory myocardial isch­emia induced by ergonovine is described. The patientunderwent cardiac catheterization 2 weeks after an in­ferior wall myocardial infarction for evaluation of re­current rest angina. He developed severe spasm of theproximal right coronary artery in response to ergonovinewhich was partially relieved with nitrates and calciumchannel antagonists. However, myocardial ischemia per-

Coronary artery spasm has become a frequently recognizedcause of angina as awareness and knowledge of this inter­esting disease entity has expanded. It has been identified inpatients with and without obstructed coronary arteries andin vein grafts after coronary artery bypass surgery. Thecomplications of coronary spasm include severe cardiac ar­rhythmias, such as ventricular tachycardia and fibrillation,conduction disturbances, acute myocardial infarction andsudden death. The administration of ergonovine has beenused as a very sensitive and specific provocative test todocument coronary spasm.

Most patients with spontaneous or ergonovine-inducedcoronary artery spasm respond promptly, that is, within 3to 5 minutes, to sublingual nitroglycerin 0-5). However,in a few patients ergonovine resulted in serious cardiovas­cular complications due to intractable coronary artery spasm(6,7). We report a case of severe and intractable myocardialischemia that was induced by ergonovine and resulted inacute myocardial infarction.

Case ReportClinical history and findings. A 67 year old white man

with known hypertension, peptic ulcer disease and chronic

From the Cardiovascular Section, Medical Service, Veterans Admin­istration Medical Center, Wood (Milwaukee), Wisconsin and the Depart­ment of Medicine, The Medical College of Wisconsin, Milwaukee. Manu­script received January 18, 1984; revised manuscript received April 10,1984, accepted April 16, 1984.

Address for reprints: Virinderjit S. Barnrah, MD, Cardiovascular Sec­tion/I I 1M, Veterans Administration Medical Center, 5000 West NationalAvenue, Wood (Milwaukee), Wisconsin 53193.

©1984 by the American College of Cardiology

sisted, culminating in a new inferior wall infarction.The possible mechanism of continuing intense isch­

emia despite partial relief of the proximal right coronaryspasm is discussed. It is suggested that ergonovine testingshould perhaps be avoided during the early postinfarc­tion period. Furthermore, if an ergonovine test is anti­cipated, beta-adrenergic blocking agents should be with­held.

obstructive pulmonary disease was hospitalized because ofsevere retrosternal chest pain radiating to both arms and thejaw and lasting approximately 1 hour. The pain was onlyslightly relieved with 1.2 mg of sublingual nitroglycerin andrequired 10 mg of intravenous morphine sulfate for completecontrol. Blood pressure was 142/94 mm Hg, pulse 70/minand regular and an S4 gallop was audible at the apex. Theadmission electrocardiogram showed sinus rhythm, 2 mmST segment elevation in leads II, III and aVF and 1 mmST segment depression in leads VI and V2' On the secondhospital day, Q waves developed in leads II, III and aVF.The serial electrocardiograms and serum cardiac enzymeswere compatible with the development of acute inferior wallmyocardial infarction. The ST segments returned to baselinevalues by the third day. On the fourth hospital day, thepatient developed another episode of severe retrosternal chestpain with ST segment elevation in leads II, III and aVF.The patient was started on treatment with oral nifedipine(30 mg every 6 hours), oral metoprolol (50 mg twice daily)and nitroglycerin paste (2 inches [5.08 em] every 6 hourstopically). He had two additional similar episodes of chestpain that were controlled by morphine sulfate.

Cardiac catheterization and angiography. Cardiaccatheterization was performed on the 13th day after infarc­tion because of the recurrent rest angina. Left ventricularend-diastolic pressure at rest was elevated at 20 mm Hg.The left ventriculogram showed moderate hypokinesia ofthe diaphragmatic and posterolateral segments in the 30°right and 60° left anterior oblique views, respectively. Theright coronary artery was dominant and showed two areasof 20 and 40% narrowing, respectively, in its proximalsegment and another 20% narrowing in its middle segment

0735-1097/84/$3.00

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(Fig. lA). The left main trunk, anterior descending andproximal circumflex vessels were normal. The second mar­ginal branch of the left circumflex vessel was totally oc­cluded as its origin and opacified slowly by means of col­lateral vessels.

Ergonovine study. The recurrent postinfarction anginaappeared to be somewhat out of proportion to the extentand severity of atherosclerotic coronary artery disease. Theoccluded second marginal branch was considered to be re­sponsible for the inferior wall myocardial infarction, butcoronary artery spasm was considered as a possible expla­nation for the postinfarction angina.

To evaluate the possible role of coronary artery spasm,0.05 mg of ergonovine maleate was given intravenouslywhile pulmonary and systemic arterial pressures and cardiacrhythm were monitored continuously. The patient developedhis typical severe retrostemal chest pain with ST segmentelevation in leads II, III and aVF, and ST segment depres­sion in leads I, aVL and V4 to V6 within 5 minutes ofergonovine administration (Fig. 2). Repeat angiographyshowed further narrowing of the two proximal right coronaryartery lesions to 80 and 50% stenosis, respectively (Fig.18). Five minutes after 0.8 mg of sublingual nitroglycerin,the 80% proximal narrowing decreased to 60% (Fig. lC).Despite the partial relief of proximal right coronary arteryspasm, intense chest pain and ST segment changes persisted.

Sublingual nifedipine (20 mg), intracoronary nitroglyc­erin (up to 700 ug), intravenous nitroglycerin infusion (upto 100 ug/min), morphine sulfate (4 mg), meperidine hy­drochloride (Demerol) (25 mg) and atropine (2 mg) wereadministered without any relief of chest pain or electrocar­diographic changes. The intensity of chest pain and STsegment elevation actually became progressively worse. Inresponse to nitroglycerin, the systolic aortic pressure de­creased slightly from the pre-ergonovine level of 145 mmHg but remained above 90 mm Hg throughout the study.The pulmonary artery diastolic pressure also remainedbelow 15 mm Hg in response to nitroglycerin infusion. Theheart rate was unchanged during the first 12 minutes afterergonovine administration, and then it increased to a max­imal level of 120 beats/min. ST segment elevation pro­gressively increased to a maximum of 6 mm from the base­line value. The patient then developed three episodes ofventricular fibrillation which were successfully cardio­verted. Right and left coronary angiography was repeatedseveral times and showed no further reduction in the prox­imal right coronary artery narrowing. The left coronary ar­tery was unchanged from the pre-ergonovine angiogram.The patient continued to have chest pain, elevation of STsegments in the inferior leads and ST segment depressionin the anterolateral leads.

Subsequent hospital course. The patient was trans­ferred to the coronary care unit after placement of a Swan­Ganz catheter and a temporary pacemaker. After completion

Figure 1. Right coronary artery angiograms in left anterior obliqueview. A, Proximal segment of right coronary artery shows twoseparate lesions causing 20 and 40% narrowing, respectively. B,After ergonovine administration, the severity of narrowing in­creases in both lesions to 80 and 50%, respectively. C, Aftersublingual nitroglycerin (0.8 mg), the severity of the proximallesion decreases from 80 to 60%. The second lesion persists as50% stenosis.

of the catheterization procedure, two-dimensional echocar­diography showed reduced wall motion in the inferior andposterolateral segments. Over the next 48 hours, serum en­zyme measurements (creatine kinase of 1,853 IV/liter withMB fraction of 16%) were diagnostic of a new myocardialinfarction. The patient was free from further episodes of

lACC 'I ol. 4, No. 3September 1984:635- 9

BAMRAH AND SCHUCHARDCORONARY SPASM

637

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Figure 2. Serial 12 lead electrocar­diograms. A, Control electrocardio­gramshowingQwavein leads II andaVF and T wave inversion in leadsII, III, aVF, Vs and V6 , indicatingrecent inferior wall myocardial in­farction . B, Electrocard iogram 5minutes after the administration ofergonovine , showing marked STsegment elevation in leads II, III andaVF and reciprocal ST seg mentdepression in leads aVL and VI toV4 . C, Electrocardiogram 2 daysafter ergonovine study, showingdeepQ waves, ST segment elevationandT wave inversion in leads II, III,

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angina on a medical regimen of oral verapamil (120 mgfour times daily) and nitroglycerin paste (2 inche s [5.0 8 em]topically four times daily) . A repeat echocardiogram Imonth later demonstrated considerable impro vement in theleft ventricular segmental wall motion with residual hypo­kinesia present only in the apical segment.

A symptom-limited exercise stress test was performed21/2 month s later. The patient exercised for 660 seconds ,achie ving a maximal age-predicted heart rate of 128 beatslmin. Mild angina and premature ventricular complexes de­veloped; howe ver , there was no ST segment change . Theradionuclide angiogram at this time showed an ejection frac­tion of 0.54 at rest, decreasing to 0.49 during maximalexercise .

DiscussionThe primary purpose of this report is to illustrate that

some episodes of ergonovine-induced coronary artery spasmmay be unusually prolonged and relatively intractable tocommonly available vasod ilators.

Refractory coronary artery spasm. In view of only amode st degree of fixed coronary artery disease (total occlu­sion of second marg inal branch ) in our case, coro nary va­sospasm was considered as a mechanism underlying post-

infarction rest ang ina. We there fore felt justified in per­forming the ergonovine test.

The ergonovine-provoked coronary artery spasm and theresultant myocardial ischemia in our patient were totallyrefractory to sublingual , intravenous and intracoronary ni­troglycerin, sublingual nifedipine and atropine. This pro­longed ischemic epi sode resulted in acute inferior wall myo­cardi al infarction . Crevey et al. (6) reported on a patientwho also developed in response to ergonovine intract ableright coronary artery spasm that resulted in acute inferiorwall myocard ial infarction . The ir patient and several otherswho either developed myocardial infarction or died after anergonovine test were reported (6-8) to have severe two orthree vessel atherosclero tic coronary artery disease. Eventhough our patient also had athero sclerot ic coronary arterydisease , the significant obstruction was limited to only thesecond marginal branch of the left circumflex vessel.

In several patients recently reported (6-8) on , ergo­novine-provoked coronary artery spasm was resi stant tocommonly employed vasodilators. Multiple factor s, suchas specific vasodilator used , route of administration anddose of ergonovine used , should be discussed regardingergonovine testing. The right coronary artery spasm in thecase reported by Crevey et al. (6) was intrac table to sub­lingual nitroglycerin. These investigators did not admini ster

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intravenous or intracoronary nitroglycerin, calcium channelblocking drugs or alpha-adrenolytic agents to reverse thespasm. Buxton et al. (7) reported on five patients with se­rious ischemic complications (including three deaths) sec­ondary to ergonovine testing. In the two patients who sur­vived, the ergonovine-induced spasm was reversed only bylarge doses of intracoronary nitroglycerin; sublingual andintravenous nitroglycerin were ineffective. Of the three pa­tients who died of irreversible coronary spasm, all receivedsublingual nitroglycerin, one received intravenous nitro­glycerin, one received a small (100 I-Lg) dose of intraco­ronary nitroglycerin and two received phentolamine withoutany effect on the spasm. Our patient received 700 I-Lg ofintracoronary nitroglycerin that did not completely relievethe coronary artery spasm. Buxton et al. (7) also recom­mended that ergonovine be given in small and equal serialdoses (0.025 or 0.05 mg each) and that the total dose shouldnot exceed 0.2 mg. Our patient and that of Crevey et al.(6) received only 0.05 mg and developed drug-resistantspasm.

Mechanism of ergonovine-induced myocardial isch­emia. In our patient, the exact mechanism of the prolongedischemic episode is not clear. The spasm of the proximalright coronary artery probably was not responsible for per­sistent ischemia since the maximal obstruction in responseto ergonovine was 80%, which promptly decreased to 60%after sublingual nitroglycerin. This modest degree of ob­struction usually does not cause intense ischemia in theabsence of a markedly augmented myocardial oxygen de­mand. The oxygen demand in our patient was not signifi­cantly increased since the heart rate and blood pressure afterergonovine administration were unchanged. There was noevidence of air or blood clot embolism or dissection in­volving the right coronary artery. Collapse of this arterywas unlikely because the systolic blood pressure remainedabove 90 mm Hg despite substantial amounts of nitroglyc­erin.

Persistent spasm of the resistance vessels in the rightcoronary artery vascular bed, despite partial reversal offocal spasm of the proximal segment of the right coronaryartery, may have contributed to the continuation of an isch­emic event. A high arteriolar resistance would be anticipatedto curtail the nutrient flow, even if the spasm of the epi­cardial portion of the vessel was reversed. Orlick et al. (9)showed that ergonovine may provoke the syndrome of cor­onary spasm, not only by augmenting resistance in the epi­cardial segment of the coronary artery, but also by limitingthe capacity of coronary arterioles to dilate in response toincreased metabolic demands or ischemia. Recently,Cannon et al. (10,11) also demonstrated that abnormal ar­teriolar constriction in the coronary vascular bed (reducedarteriolar vasodilatory reserve) may result in myocardialischemia, either spontaneously or in response to ergonovine.Nitroglycerin is a potent dilator of large (epicardial) coro-

nary arteries, but it has a weak vasodilatory action on thearterioles (12). Thus, it is possible that, even if the proximalright coronary artery spasm was partially relieved, myo­cardial ischemia persisted because of ergonovine-inducedhigh resistance in the arterioles.

Metoprolol, a beta-adrenergic blocking agent that ourpatient was taking, could have also contributed to his pro­longed ischemic episode. Kern et al. (13) demonstrated thatbeta-adrenergic blockade can potentiate coronary artery va­soconstriction in some patients with coronary artery disease,probably on the basis of unopposed alpha-adrenergic va­somotor tone. Several other studies (14-18) have also shownprolongation of ischemic episodes of beta-adrenergicblockade in patients with documented vasospastic angina.Our patient was probably resistant to nifedipine since hehad experienced rest angina in the immediate post-myocar­dial infarction period while he was receiving oral nifedipinetherapy. Although nifedipine has a more generalized va­sodilatory effect on the coronary vascular bed, it was in­effective in this patient.

Ergonovine test after recent myocardial infarction.The safety of an ergonovine test during the early post-myo­cardial infarction period is not known. Several authors (19­22) have suggested that the test should be avoided duringthis period. The augmented myocardial oxygen demand oc­curring secondary to ergonovine-induced elevation of bloodpressure and the reduction of myocardial blood flow sec­ondary to ergonovine-induced spasm would be potentiallydetrimental to recently necrotic myocardium and might evenenlarge the infarct size (19,20). Moreover, the ergonovine­induced coronary spasm may be unresponsive to nitrogly­cerin, as was seen in our patient. Recently, however, Moranet al. (21) and Koiwaya et al. (22) reported that ergonovine­induced spasm was promptly relieved with sublingual ni­troglycerin in some patients while others required intracor­onary nitroglycerin. There were no ergonovine-related com­plications in their patients.

Clinical implications. Whereas most episodes of er­gonovine-provoked vasospastic angina promptly respond tosublingual nitroglycerin, occasional episodes may be un­usually prolonged or totally refractory to sublingual nitro­glycerin. In these patients, alternate routes for nitroglycerinadministration, that is intravenous or preferably intraco­ronary, and other agents such as calcium channel blockingdrugs should be employed without undue delay. In somepatients, these episodes may be totally refractory. Ergo­novine testing should probably be avoided in patients duringthe early post-myocardial infarction period. Moreover, if anergonovine test is anticipated, beta-adrenergic blockingagents should be discontinued beforehand.

We gratefully acknowledge the secretarial assistance of Donna Shaugh­nessy and the editorial assistance of Catherine Walther in the preparationof this manuscript.

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