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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
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JACC Vol. 4, No.3September 1984:635-9
(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,
aVF aVF and V6 · There is reciprocal ST~ "'I segment depression in leads VI to
V4' Compari son with the controlelectrocardiogram (A) indicates development of acute inferior wallmyocardial infarction.
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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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ReferencesI. Schroeder JS, Bolen JL, Quint RA, et al. Provocation of coronary
spasm with ergonovine maleate. Am J Cardiol 1977;40:487-91.
2. Curry RC, Pepine CJ, Sabom MB, Feldman RL, Christie LG, ContiCR. Effects of ergonovine in patients with and without coronary arterydisease. Circulation 1977;58:803-9.
3. Heupler F, Proudfit W, Rajavi M, Shirey EK, Greenstreet R, SheldonWe. Ergonovine maleate provocative test for coronary arterial spasm.Am J Cardiol 1978;41:631-40.
4. Curry RC, Pepine CJ, Sabom MB, Conti CR. Similarities of ergonovine-induced and spontaneous attacks of variant angina. Circulation1979;59:307-12.
5. Cipriano PR, Guthaner DF, Orlick AE, Ricci DR, Wexler L, Silverman JF. The effects of ergonovine maleate on coronary arterialsize. Circulation 1979;59:82-9.
6. Crevey BJ, Owen SF, Pitt B. Irreversible coronary occlusion relatedto administration of ergonovine. Circulation 1981;64:853-6.
7. Buxton A, Goldberg S, Hirshfeld JW, et al. Refractory ergonovineinduced coronary vasospasm: importance of intracoronary nitroglycenn, Am J Cardiol 1980;46:329-34.
8. Waters DD, Chaitman BR, Dupras G, Theroux P, Mizgala HF. Coronary artery spasm during exercise in patients with variant angina.Circulation 1979;59:580-5.
9. Orlick AE, Ricci DR, Cipriano PR, Guthaner DF, Harrison De.Coronary hemodynamic effects of ergonovine maleate in human subjects. Am J Cardiol 1980;45:48-52.
10. Cannon RO, Watson RM, Rosing DR, Epstein SE. Angina causedby abnormal coronary arteriolar vasoconstriction in patients with insignificant fixed coronary artery disease (abstr). Circulation1982;66(suppl 11):11-44.
II. Cannon RO, Watson RM, Rosing DR, Epstein SE. Small vessel coronary constriction as a cause of atypical angina: pitfalls of ergonovinetesting (abstr). Circulation 1982;66(suppl 11):11-248.
12. Abrams J. Nitroglycerin and long acting nitrates. N Engl J Med1980;302:1234-7.
13. Kern MJ, Ganz P, Horowitz JD, et al. Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronaryartery disease. Circulation 1983;67:1178-85.
14. Yasue H, Touyama M, Kato H, Tanaka S, Akiyama F. Prinzmetal'svariant form of angina as a manifestation of alpha-adrenergic receptormediated coronary artery spasm: documentation by coronary arteriography. Am Heart J 1976;91:148-55.
15. Robertson D, Robertson RM, Nies AS, Oates JA, Friesinger GC.Variant angina pectoris: investigation of indexes of sympathetic nervous system function. Am J Cardiol 1979;43:1080-5.
16. Robertson RM, Wood AJJ, Vaughn WK, Robertson D. Exacerbationof vasotonic angina pectoris by propranolol. Circulation 1982;65:281-5.
17. Yasue H, Omote S, Takizawa A, et al. Pathogenesis and treatmentof angina pectoris at rest as seen from its response to various drugs.Jpn Circ J 1978;42:1-10.
18. Cannon RO, Watson RM, Rosing DR, Epstein SE. Detrimental effectof propranolol on anginal threshold of patients with angina and insignificant epicardial coronary artery disease (abstr). J Am CoIl Cardiol1983;1:595.
19. Madias JE. The syndrome of variant angina culminating in acutemyocardial infarction. Circulation 1979;59:297-306.
20. Heupler FA Jr. Provocative testing for coronary arterial spasm: risk,method and rationale. Am J Cardiol 1980;46:335-7.
21. Moran TJ, French WJ, Abrams HF, Criley JM. Postmyocardial infarction angina and coronary spasm. Am J CardioI1982;50:197-202.
22. Koiwaya Y, Torii S, Takeshita A, Nakagaki 0, Nakamura M. Postinfarction angina caused by coronary arterial spasm. Circulation1982;65:275-80.