Case reports Coronary artery spasm as the cause of myocardial infarction during coronary arteriography H. Jurgen Engel, M.D. H a r r y L. P a g e , J r . , M . D . W. Barton Campbell, M.D.
Nashville, Tenn.
Mechanisms of angina pectoris and myocardial infarction in the absence of angiographically demonstrable coronary artery disease have been the subject of numerous recent publications. Metabolic changes, abnormal enzyme activities, 1 abnormal hemoglobin-oxygen dissociation curves, 2 impairment of oxygen diffusion, altered myocardiatcell properties, 3 disease of small vessels, 9 the mitral valve prolapse syndrome, ~ and misinterpretation of the arteriogram, 6 have all been suggested as possible causes of this enigma. Coronary artery spasm has been the central theme of many discussions either occurring spontaneously (as suggested in Prinzmetal's variant angina) or being catheter-induced. Although coronary artery spasm has been shown to result in transient myocardial ischemia and various potentially lethal arrhythmias, myocardial necrosis d u e t o a r t e r i a l s p a s m i n a n o n o b s t r u c t e d coronary artery to our knowledge has been demonstrated only once before. 7 An understanding of this possibility and the conditions of its occurrence can be valuable in the analysis of coronary arteriograms as will be shown in the instance we report.
Case history A 43-year-o!d white woman was admitted to St. Thomas Hospital in May, 1970, because of severe substernal chest pain with variable radiation into the left jaw. left shoulder, left arm. the upper posterior chest, or the right arm. These symptoms had begun three months prior to admission and
From the St. Thomas Hospital, Department of Cardiology, Nashville. Received for publication Jan. 14. 1974. Reprint requests to: Dr H. J. Engel, Department of Cardiology, St. Thomas Hospital. Nashville. Tenn. 37203.
April, 1976, Vol. 91, No. 4, pp. 501-506
were not always related to exertion. The pain was associated with weakness, nausea, and at times sweating and shortness of breath. The distress was temporarily relieved by nitroglycerin, but after about 10 minutes the anginal symptoms would frequently recur and last as long as 30 minutes. The patient observed t h a t during these episodes her hands would " t u r n blue" and her feet would become quite cold. The electrocardiogram at t h a t time showed intermittent nonspecific T-wave changes (Fig. 1). After a cholecystectomy in April. 1970. marked T-wave inversion in the precordial leads was observed following severe substernal pain. Serial electrocardiograms, serum enzymes, and white cell counts failed co show evidence of a myocardial infarction. Cervical spine series showed no significant abnormalities. A hiatal hernia and other abnormalities of the esophagus and stomach were excluded. On chest xray the heart was of normal configuration. Serum cholesterol was repeatedly elevated in the range of 270 to 365 rag. per cent and triglycerides were elevated co 228 mg. per cent. Glucose metabolism was found to be normal. The blood pressure had never been elevated and the patient denied smoking cigarettes. Physical examination was normal. Because of persistence of angina-like symptoms in spite of medication with isosorbide dinitrate, intermittent meperidine, and nitroglycerin, selective coronary arteriography was carried out iasing the Judkins technique, s Prior to intubation of the right coronary artery, 0.4 mg. of nitroglycerin was administered sublingually and. following each injection of contrast into the right coronary artery, the catheter was withdrawn from the ostium. On each injection, the proximal right coronary artery was noted to have a 10ng, symmetrical. segmental occlusion thought to represent more ~han 90 per cent loss of the internal cross-section area of the artery (Fig. 2). No collateral vessels were seen into the distal right coronary artery. The entire left coronary system appeared to be without disease. Following the third injection of the right coronary artery the ST segments in Leads II. IIL and aV F became markedly elevated with T-wave inversions in these leads and the patient complained of severe chest pain. Serial electrocardiograms over the next days (Fig. 3) continued co show evidence of an injury pattern and permanent Q-waves developed in Leads II, III. a n d a V F. The serum glutamic oxaloacetic transaminase (SGOT) rose from 57 to 78 to 147 and the creatine phosphokinase (CPK) from 4 co 70 to 90 over three successive days. The patient had episodes of nodal
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Fig. 1. Electrocardiogram on May 15, 1970. before the first coronary cineangiography demonstrating mild, nonspecific T-wave changes.
tachycardia and continued to have intermittent chest pain. Therefore, five weeks after the coronary cineangiography, a venous bypass graft from the aorta to the right coronary artery was performed. At the time of surgery, the proximal and distal right coronary artery were noted to be very soft and pliable. The lumen appeared to be uncompromised and there was no evidence of atheromatous disease. Her postoperative course was free of complications but she continued to have intermittent chest pain. Seven weeks after surgery the ST segments in the precordial leads were again noted to be markedly inverted and repeat coronary cineangiography was performed in August, 1970. The repeat study revealed a normal left ventriculogram and a patent venous graft to the distal right coronary artery. The proximal right coronary artery was noted to be without evidence of occlusive disease or luminal irregularity. The left coronary arterial system continued to be free of visible atherosclerotic changes. Various medications failed to relieve the patient's chest pain. Because of recurrent severe, and at times incapacitating pain, a third angiographic study was performed tlu'ee years later in August, 1973. At this time the venous graft was found to be obstructed. Again the proximal right coronary artery was free of stenotic lesions or atherosclerotic changes {Fig. 4). At the region of the graft anastomosis the lumen of the right coronary artery appeared to be somewhat irregular and narrowed. 502
Discussion T h e i n c i d e n c e o f m y o c a r d i a l i n f a r c t i o n as a complication of coronary arteriography varies f r o m 0.1 t o 2.5 p e r c e n t in t h e l i t e r a t u r e . 9 Coronary occlusions during cardiac catheterizat i o n u s u a l l y r e s u l t f r o m e m b o l i z a t i o n of f o r e i g n m a t e r i a l f r o m t h e t i p of t h e c a t h e t e r or d i s l o d g m e n t o f a t h e r o m a t o u s m a t e r i a l . 1~ S u b i n t i m a l d i s s e c t i o n of a c o r o n a r y a r t e r y a n d p r o l o n g e d c a t h e t e r o b s t r u c t i o n o f a s t e n o t i c v e s s e l ar e o t h e r r e a s o n s for c r i t i c a l d e c r e a s e o f c o r o n a r y b l o o d flow t h a t m a y b e p a r t i c u l a r l y i n h e r e n t t o t h e p e r c u t a n e o u s t r a n s f e m o r a l a p p r o a c h . 11 M e t i c u lous observation of certain procedural precaut i o n s p u b l i s h e d b y o n e o f t h e a u t h o r s 1~ h a s b e e n s u c c e s s f u l in c o m p l e t e l y a v o i d i n g e m b o l i c accid e n t s in 1,130 c o r o n a r y a r t e r i o g r a m s t h a t w e r e c a r r i e d o u t in o u r c a r d i o v a s c u l a r l a b o r a t o r y d u r i n g t h e p a s t 12 m o n t h s . T h e a n g i o g r a p h i c d e m o n s t r a t i o n o f a l o n g segm e n t a l s u b t o t a l occlusion of the right c o r o n a r y a r t e r y t h a t w a s d o c u m e n t e d d u r i n g t h e first
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Fig. 2. First coronary arteriography on May 20, 1970, demonstrating a long segmental proximal stenosis of the right coronary artery in the right anterior oblique projection.
Fi9. 3. Electrocardiogram on May 22, 1970, two days after the first coronary arteriography demonstrating an evolving inferior-lateral myocardial infarction.
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Fig. 4. Third coronaryarteriographyon Aug. 22, 1973,demonstrating a normal proximalright coronaryartery and luminal irregularity and narrowing at the level of the graft anastomosis. procedure {Fig. 2) precludes an embolic etiology in this instance. Subintimal dissection of coronary arteries is recognized by a peculiar linear stain close to the orifice of the respective artery. This was not present in our case. We are, therefore, led to conclude that severe coronary artery spasm occurred resulting in myocardial necrosis in the inferior left ventricular wall. There is evidence to suggest that segmental arterial contractions are independent from the physiologic regulation of arteriolar coronary blood flow in which local hypoxia, vasoactive metabolites such as adenosine, and catecholamines play an important role. ~3-~ The tone of vascular smooth muscle is known to be a function of the intracellular Ca +§ ion concentration which triggers the action of actomyosin ATPase." Epinephrine and norepinephrine influence the calcium ion concentration within the smooth muscle cell ~ but the effect of catecholamines on coronary circulation is still somewhat controversial in the literature TM 19 and their role in the production of coronary spasm is unknown. While the exact mechanism of arterial spasm has not been established on the molecular level,
504
angiographic experiences offer some clues concerning the circumstances contributing to its existence. The problem of functional arterial stenosis during arteriography of various organs has been Well recognized for many years and has been the subject of many publications. 2~ 21 Recently, coronary artery spasm has been repeatedly documented during catheterization. 22-2~ Considerations a b o u t the etiology of arterial spasm during angiography have included sudden stretching of the muscle layer of the artery by catheter or guide wire, sudden sharp rise of intra-arterial pressure by forceful angiography, and mechanical stimulation of the arterial smooth muscle by the presence of a catheter in the vessel. TM 24 This explanation is analogous to the hypothesis that mechanical stimulation of the vessel wall is responsible for sustained arterial contraction in perforating gunshot wounds of medium-sized arteries34 In order to recognize local contractions in the region of selective intubation, a scout injection into the parent vessel is generally performed in angiographies other than coronary arteriography, and aortic root injections have been recommended in cases of suspected coronary artery spasm. ~3
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Coronary artery spasm
Reports have documented arterial spasm without intubation of the vessel. These cases may be due to chemical irritation by the contrast material or to increased sensitivity to catecholamines. 2~ Spontaneous coronary artery spasm has been seen in cases of Prinzmetal's variant angina. ~5 Local contractions usually occur adjacent to the inserted catheter, but also have been observed more distally. 21 Since, in elderly patients the function of arterial smooth muscle tissue is commonly impaired by fibrosis, coronary artery spasm is encountered predominantly in younger patients. The right coronary artery appears to be more prone to local contractions both secondary to mechanical stimulation by catheter and spontaneously, as seen in Prinzmetal's angina. ~, ~3 Demany, Tambe, and Zimmermann ~ report seven cases of coronary artery spasm representing almost 1 per cent of their coronary arteriograms. The arterial contractions were associated with chest pain in only three cases, and electrocardiographic changes such as patterns of ischemia or injury and an instance of second degree A-V block were all readily reversible by administration of nitroglycerin. Demany, Tambe, and Zimmermann 2: defined arterial spasmas disappearance of the luminal narrowing within two minutes after sublingual administration of nitroglycerin. In none of their cases did enzyme rises indicate permanent myocardial damage. Our observation of sustained arterial contraction in spite of the administration of nitroglycerin and the occurrence of myocardial necrosis secondary to functional narrowing of a coronary artery necessitates a reconsideration of the nature of coronary artery spasm. Experiments in dogs have shown that enzyme rises occur after coronary artery occlusion of about 20 minutes' duration and t h a t irreversible tissue injury will have taken place after 40 to 60 minutes. 2~, 27These findings may not necessarily correspond to the situation in the human, but suggest t h a t coronary blood flow must certainly have been critically diminished for more than 20 minutes to produce a transmural infarction. The recommendation of Demany, Tambe, and Zimmermann :2 to perform an aortic root injection after 20 to 30 minutes in cases of suspected coronary artery spasm is, therefore, somewhat questionable. Another unusual aspect in the patient is the length of the tightly narrowed segment in the proximal right coronary artery. The evaluation of
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stenotic areas within the proximal 2 cm. of the right coronary artery can often be difficult.23 In our case, the region of spastic contraction extended distally for an unusually long distance. Although the morphology of the tightly stenosed segment appeared to be somewhat smooth and lacked the usual ragged appearance of coronary artery disease, the findings were misinterpreted because myocardial necrosis due to catheterinduced spasm had never been described and subsequent clinical findings provided additional evidence for the diagnosis of organic occlusive coronary artery disease. Since repeated coronary arteriograms failed to demonstrate atheromatous coronary artery disease in the patient, the question arises as to the nature of her persistent chest pain. Prinzmetal's variant angina must be considered in this setting. This syndrome has been shown to result from spasm of atherosclerotic as well as normal coronary arteries. It is not provoked by increased cardiac work and is accompanied by certain electrocardiographic features such as transient ST segment elevations and arrhythmias. 2~ Although it is tempting to ascribe our patient's chest pain to spontaneous spastic activity of her coronary arteries, the diagnosis of Prinzmetal's angina cannot be made without the characteristic electrocardiographic criteria. Observations in this patient confirm coronary artery spasm as a cause of myocardial infarction during coronary arteriography. However, the etiology of her persistent intractable angina pectoris remains undefined and calls for a broader concept in the understanding of ischemic heart disease, a concept that may uncomfortably complicate the task of evaluating coronary arteriograms.
Summary Catheter-induced coronary artery spasm has been observed frequently. It is usually transient, reacts to the administration of nitroglycerin, and its distribution is generally confined to an area in proximity to the intubated catheter. A 43-yearold woman with recurrent chest pain was found to have a rather long segment of tight proximal obstruction of the right coronary artery and experienced a myocardial infarction during coronary catheterization. Because of recurrent attacks of severe chest pain, coronary artery bypass surgery was performed which failed to result in significant improvement of her symptoms. Two repeat
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coronary cineangiograms seven weeks and three years after surgery revealed the proximal right c o r o n a r y a r t e r y to be free of stenotic lesions or of luminal irregularities. After considering possible m e c h a n i s m s o f m y o c a r d i a l n e c r o s i s in t h e prese n c e o f n o r m a l c o r o n a r y a r t e r i e s it is c o n c l u d e d that myocardial necrosis can result from cathet e r - i n d u c e d c o r o n a r y a r t e r y s p a s m in s p i t e o f administration of nitroglycerin.
13. 14. 15. 16.
REFERENCES
1. Arbogast, R., and Bourassa, M. G.: Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms, Am. J. Cardiol. 32:257, 1973. 2. Elliot, R. S., and Bratt, G.: The paradox of myocardial ischemia and necrosis in young women with normal coronary arteriograms, Am. J. Cardiol. 23:633, 1969. 3. Likoff, W., Segal, B. L., and KasPerian, H.: Paradox of normal selective coronary arteriograms in patients considered to have unmistakable coronary artery disease, N. Engl. J. Med. 276:1063, 1967. 4. James, T. N.: Disease of small coronary arteries, Circulation 40:13, 1969. 5. Jeresaty, R. M.: Mitral valve prolapse-click syndrome, Progr. Cardiovasc. Dis. 15:623, 1973. 6. Vlodaver, Z., French, R., Van Tassel, R. A., et al:: Correlation of the antemortem coronary arteriogram and the postmortem specimen, Circulation 47:162, 1973. 7. Cheng, T. 0., Bashour, T., Singh, B. K., et al.: Myocardial infarction in the absence of coronary arteriosclerosis. Result of coronary spasm? Am. J. Cardiol. 30:680, 1972. 8. Judkins, M. D.: Percutaneous transfemoral selective coronary arteriography, Rad. Clin. North Am. 6:467, 1968. 9. Adams, D. F., Fraser, D. B., and Abrams, H. L.: The complications of coronary arteriography, Circulation 48:609, 1973. 10. Takaro, T., Piffare, R., Wuerflein, R. D., et al.: Acute coronary occlusion following arteriography: mechanisms and surgical relief, Surgery 72:1018, 1972. 11. Haas, J. M., Peterson, C. R., and Jones, R. Co: Subintimal dissection of the coronary arteries, Circulation 38:678, 1968. 12. Page, H. L., Jr., and Campbell, W. B.: Prevention of
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17. 18. 19.
20. 21. 22. 23. 24. 25. 26. 27. 28.
morbid complications during percutaneous transfemoral coronary arteriography, Chest. (In press) Gellai, M., Norton, J. M., and Detar, D.: Evidence for direct control of coronary vascular tone by oxygen, Circ. Res. 32:279, 1973. Berne, R. M.: Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow, Am. J. Physiol. 204:317, 1963. Yurchak, P. M., Rolett, P. M., and Cohen, L. S., et al.: Effects of norepinephrine on the coronary circulation in man, Circulation 30:180, 1964. Peiper, U., and Schmidt, E.: Relaxation of coronary arteries by electromechanical decoupling or adrenergic stimulation, Pfluegers Arch. 337:107, 1972. Murphy, R. A., Bohr, D. F., and Newman, D. L.: Arterial actomyosin: Mg, Ca, and ATP ion dependencies for ATPase activity, Am. J. Physiol. 217:666, 1969. Moran, N. C.: Adrenergic drugs and the cardiovascular system, Mod. Concepts Cardiovasc. Dis. 7:99, 1966. Schmidt, E., and Peiper, U.: Tonus~inderungen von isolierten Coronararterien durch Depolarisation und oder Noradrenalin vor und nach Blockierung adrenerger Rezeptoren, Arch. Pharmacol. 275:383, 1972. Meaney, T. F., and Buonocore, E.: Contractions in the renal arteries during arteriography, Radiology 86:41, 1966. Wickbprn, J., and Bartley, O. O.: Arterial "spasm" in peripheral arteriography using the catheter method, Acta Radiol. 47:433, 1957. Demany, M. A., Tambe, A., and Zimmerman, H. A.: Coronary artery spasm, Dis. Chest 53:714, 1968. O'Reilly, R. J., Spellberg, R. D., and King, T. W.: Recognition of proximal right coronary artery spasm during coronary arteriography, Radiology 95:305, 1970. Lindbohm, A.: Arterial spasm caused by puncture and catheterization, Acta Radiol. 47:449, 1957. Cheng, T. 0., Bashour, T., and Kelser, G. A., et al.: Variant angina of Prinzmetal with normal coronary arteriograms, Circulation 47:476, 1973. Savranoglu, N., Boucek, R. J., and Casten, G.: The extent of reversibility of myocardial ischemia in dogs, AM. HEART J. 58:726, 1959. Jennings, R. B., Sommers, H. M., and Smyth, G. A.: Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog, Arch. Pathol. 70:68, 1960. Prinzmetal, M., Kennamer, R., and Merliss, R., et al.: Angina pectoris. I. A variant form of angina pectoris: preliminary report, Am. J. Med. 27:375, 1959.
April, 1976, Vol. 91, No. 4
Nashville, Tenn.
Mechanisms of angina pectoris and myocardial infarction in the absence of angiographically demonstrable coronary artery disease have been the subject of numerous recent publications. Metabolic changes, abnormal enzyme activities, 1 abnormal hemoglobin-oxygen dissociation curves, 2 impairment of oxygen diffusion, altered myocardiatcell properties, 3 disease of small vessels, 9 the mitral valve prolapse syndrome, ~ and misinterpretation of the arteriogram, 6 have all been suggested as possible causes of this enigma. Coronary artery spasm has been the central theme of many discussions either occurring spontaneously (as suggested in Prinzmetal's variant angina) or being catheter-induced. Although coronary artery spasm has been shown to result in transient myocardial ischemia and various potentially lethal arrhythmias, myocardial necrosis d u e t o a r t e r i a l s p a s m i n a n o n o b s t r u c t e d coronary artery to our knowledge has been demonstrated only once before. 7 An understanding of this possibility and the conditions of its occurrence can be valuable in the analysis of coronary arteriograms as will be shown in the instance we report.
Case history A 43-year-o!d white woman was admitted to St. Thomas Hospital in May, 1970, because of severe substernal chest pain with variable radiation into the left jaw. left shoulder, left arm. the upper posterior chest, or the right arm. These symptoms had begun three months prior to admission and
From the St. Thomas Hospital, Department of Cardiology, Nashville. Received for publication Jan. 14. 1974. Reprint requests to: Dr H. J. Engel, Department of Cardiology, St. Thomas Hospital. Nashville. Tenn. 37203.
April, 1976, Vol. 91, No. 4, pp. 501-506
were not always related to exertion. The pain was associated with weakness, nausea, and at times sweating and shortness of breath. The distress was temporarily relieved by nitroglycerin, but after about 10 minutes the anginal symptoms would frequently recur and last as long as 30 minutes. The patient observed t h a t during these episodes her hands would " t u r n blue" and her feet would become quite cold. The electrocardiogram at t h a t time showed intermittent nonspecific T-wave changes (Fig. 1). After a cholecystectomy in April. 1970. marked T-wave inversion in the precordial leads was observed following severe substernal pain. Serial electrocardiograms, serum enzymes, and white cell counts failed co show evidence of a myocardial infarction. Cervical spine series showed no significant abnormalities. A hiatal hernia and other abnormalities of the esophagus and stomach were excluded. On chest xray the heart was of normal configuration. Serum cholesterol was repeatedly elevated in the range of 270 to 365 rag. per cent and triglycerides were elevated co 228 mg. per cent. Glucose metabolism was found to be normal. The blood pressure had never been elevated and the patient denied smoking cigarettes. Physical examination was normal. Because of persistence of angina-like symptoms in spite of medication with isosorbide dinitrate, intermittent meperidine, and nitroglycerin, selective coronary arteriography was carried out iasing the Judkins technique, s Prior to intubation of the right coronary artery, 0.4 mg. of nitroglycerin was administered sublingually and. following each injection of contrast into the right coronary artery, the catheter was withdrawn from the ostium. On each injection, the proximal right coronary artery was noted to have a 10ng, symmetrical. segmental occlusion thought to represent more ~han 90 per cent loss of the internal cross-section area of the artery (Fig. 2). No collateral vessels were seen into the distal right coronary artery. The entire left coronary system appeared to be without disease. Following the third injection of the right coronary artery the ST segments in Leads II. IIL and aV F became markedly elevated with T-wave inversions in these leads and the patient complained of severe chest pain. Serial electrocardiograms over the next days (Fig. 3) continued co show evidence of an injury pattern and permanent Q-waves developed in Leads II, III. a n d a V F. The serum glutamic oxaloacetic transaminase (SGOT) rose from 57 to 78 to 147 and the creatine phosphokinase (CPK) from 4 co 70 to 90 over three successive days. The patient had episodes of nodal
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Fig. 1. Electrocardiogram on May 15, 1970. before the first coronary cineangiography demonstrating mild, nonspecific T-wave changes.
tachycardia and continued to have intermittent chest pain. Therefore, five weeks after the coronary cineangiography, a venous bypass graft from the aorta to the right coronary artery was performed. At the time of surgery, the proximal and distal right coronary artery were noted to be very soft and pliable. The lumen appeared to be uncompromised and there was no evidence of atheromatous disease. Her postoperative course was free of complications but she continued to have intermittent chest pain. Seven weeks after surgery the ST segments in the precordial leads were again noted to be markedly inverted and repeat coronary cineangiography was performed in August, 1970. The repeat study revealed a normal left ventriculogram and a patent venous graft to the distal right coronary artery. The proximal right coronary artery was noted to be without evidence of occlusive disease or luminal irregularity. The left coronary arterial system continued to be free of visible atherosclerotic changes. Various medications failed to relieve the patient's chest pain. Because of recurrent severe, and at times incapacitating pain, a third angiographic study was performed tlu'ee years later in August, 1973. At this time the venous graft was found to be obstructed. Again the proximal right coronary artery was free of stenotic lesions or atherosclerotic changes {Fig. 4). At the region of the graft anastomosis the lumen of the right coronary artery appeared to be somewhat irregular and narrowed. 502
Discussion T h e i n c i d e n c e o f m y o c a r d i a l i n f a r c t i o n as a complication of coronary arteriography varies f r o m 0.1 t o 2.5 p e r c e n t in t h e l i t e r a t u r e . 9 Coronary occlusions during cardiac catheterizat i o n u s u a l l y r e s u l t f r o m e m b o l i z a t i o n of f o r e i g n m a t e r i a l f r o m t h e t i p of t h e c a t h e t e r or d i s l o d g m e n t o f a t h e r o m a t o u s m a t e r i a l . 1~ S u b i n t i m a l d i s s e c t i o n of a c o r o n a r y a r t e r y a n d p r o l o n g e d c a t h e t e r o b s t r u c t i o n o f a s t e n o t i c v e s s e l ar e o t h e r r e a s o n s for c r i t i c a l d e c r e a s e o f c o r o n a r y b l o o d flow t h a t m a y b e p a r t i c u l a r l y i n h e r e n t t o t h e p e r c u t a n e o u s t r a n s f e m o r a l a p p r o a c h . 11 M e t i c u lous observation of certain procedural precaut i o n s p u b l i s h e d b y o n e o f t h e a u t h o r s 1~ h a s b e e n s u c c e s s f u l in c o m p l e t e l y a v o i d i n g e m b o l i c accid e n t s in 1,130 c o r o n a r y a r t e r i o g r a m s t h a t w e r e c a r r i e d o u t in o u r c a r d i o v a s c u l a r l a b o r a t o r y d u r i n g t h e p a s t 12 m o n t h s . T h e a n g i o g r a p h i c d e m o n s t r a t i o n o f a l o n g segm e n t a l s u b t o t a l occlusion of the right c o r o n a r y a r t e r y t h a t w a s d o c u m e n t e d d u r i n g t h e first
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Fig. 2. First coronary arteriography on May 20, 1970, demonstrating a long segmental proximal stenosis of the right coronary artery in the right anterior oblique projection.
Fi9. 3. Electrocardiogram on May 22, 1970, two days after the first coronary arteriography demonstrating an evolving inferior-lateral myocardial infarction.
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Fig. 4. Third coronaryarteriographyon Aug. 22, 1973,demonstrating a normal proximalright coronaryartery and luminal irregularity and narrowing at the level of the graft anastomosis. procedure {Fig. 2) precludes an embolic etiology in this instance. Subintimal dissection of coronary arteries is recognized by a peculiar linear stain close to the orifice of the respective artery. This was not present in our case. We are, therefore, led to conclude that severe coronary artery spasm occurred resulting in myocardial necrosis in the inferior left ventricular wall. There is evidence to suggest that segmental arterial contractions are independent from the physiologic regulation of arteriolar coronary blood flow in which local hypoxia, vasoactive metabolites such as adenosine, and catecholamines play an important role. ~3-~ The tone of vascular smooth muscle is known to be a function of the intracellular Ca +§ ion concentration which triggers the action of actomyosin ATPase." Epinephrine and norepinephrine influence the calcium ion concentration within the smooth muscle cell ~ but the effect of catecholamines on coronary circulation is still somewhat controversial in the literature TM 19 and their role in the production of coronary spasm is unknown. While the exact mechanism of arterial spasm has not been established on the molecular level,
504
angiographic experiences offer some clues concerning the circumstances contributing to its existence. The problem of functional arterial stenosis during arteriography of various organs has been Well recognized for many years and has been the subject of many publications. 2~ 21 Recently, coronary artery spasm has been repeatedly documented during catheterization. 22-2~ Considerations a b o u t the etiology of arterial spasm during angiography have included sudden stretching of the muscle layer of the artery by catheter or guide wire, sudden sharp rise of intra-arterial pressure by forceful angiography, and mechanical stimulation of the arterial smooth muscle by the presence of a catheter in the vessel. TM 24 This explanation is analogous to the hypothesis that mechanical stimulation of the vessel wall is responsible for sustained arterial contraction in perforating gunshot wounds of medium-sized arteries34 In order to recognize local contractions in the region of selective intubation, a scout injection into the parent vessel is generally performed in angiographies other than coronary arteriography, and aortic root injections have been recommended in cases of suspected coronary artery spasm. ~3
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Coronary artery spasm
Reports have documented arterial spasm without intubation of the vessel. These cases may be due to chemical irritation by the contrast material or to increased sensitivity to catecholamines. 2~ Spontaneous coronary artery spasm has been seen in cases of Prinzmetal's variant angina. ~5 Local contractions usually occur adjacent to the inserted catheter, but also have been observed more distally. 21 Since, in elderly patients the function of arterial smooth muscle tissue is commonly impaired by fibrosis, coronary artery spasm is encountered predominantly in younger patients. The right coronary artery appears to be more prone to local contractions both secondary to mechanical stimulation by catheter and spontaneously, as seen in Prinzmetal's angina. ~, ~3 Demany, Tambe, and Zimmermann ~ report seven cases of coronary artery spasm representing almost 1 per cent of their coronary arteriograms. The arterial contractions were associated with chest pain in only three cases, and electrocardiographic changes such as patterns of ischemia or injury and an instance of second degree A-V block were all readily reversible by administration of nitroglycerin. Demany, Tambe, and Zimmermann 2: defined arterial spasmas disappearance of the luminal narrowing within two minutes after sublingual administration of nitroglycerin. In none of their cases did enzyme rises indicate permanent myocardial damage. Our observation of sustained arterial contraction in spite of the administration of nitroglycerin and the occurrence of myocardial necrosis secondary to functional narrowing of a coronary artery necessitates a reconsideration of the nature of coronary artery spasm. Experiments in dogs have shown that enzyme rises occur after coronary artery occlusion of about 20 minutes' duration and t h a t irreversible tissue injury will have taken place after 40 to 60 minutes. 2~, 27These findings may not necessarily correspond to the situation in the human, but suggest t h a t coronary blood flow must certainly have been critically diminished for more than 20 minutes to produce a transmural infarction. The recommendation of Demany, Tambe, and Zimmermann :2 to perform an aortic root injection after 20 to 30 minutes in cases of suspected coronary artery spasm is, therefore, somewhat questionable. Another unusual aspect in the patient is the length of the tightly narrowed segment in the proximal right coronary artery. The evaluation of
American Heart Journal
stenotic areas within the proximal 2 cm. of the right coronary artery can often be difficult.23 In our case, the region of spastic contraction extended distally for an unusually long distance. Although the morphology of the tightly stenosed segment appeared to be somewhat smooth and lacked the usual ragged appearance of coronary artery disease, the findings were misinterpreted because myocardial necrosis due to catheterinduced spasm had never been described and subsequent clinical findings provided additional evidence for the diagnosis of organic occlusive coronary artery disease. Since repeated coronary arteriograms failed to demonstrate atheromatous coronary artery disease in the patient, the question arises as to the nature of her persistent chest pain. Prinzmetal's variant angina must be considered in this setting. This syndrome has been shown to result from spasm of atherosclerotic as well as normal coronary arteries. It is not provoked by increased cardiac work and is accompanied by certain electrocardiographic features such as transient ST segment elevations and arrhythmias. 2~ Although it is tempting to ascribe our patient's chest pain to spontaneous spastic activity of her coronary arteries, the diagnosis of Prinzmetal's angina cannot be made without the characteristic electrocardiographic criteria. Observations in this patient confirm coronary artery spasm as a cause of myocardial infarction during coronary arteriography. However, the etiology of her persistent intractable angina pectoris remains undefined and calls for a broader concept in the understanding of ischemic heart disease, a concept that may uncomfortably complicate the task of evaluating coronary arteriograms.
Summary Catheter-induced coronary artery spasm has been observed frequently. It is usually transient, reacts to the administration of nitroglycerin, and its distribution is generally confined to an area in proximity to the intubated catheter. A 43-yearold woman with recurrent chest pain was found to have a rather long segment of tight proximal obstruction of the right coronary artery and experienced a myocardial infarction during coronary catheterization. Because of recurrent attacks of severe chest pain, coronary artery bypass surgery was performed which failed to result in significant improvement of her symptoms. Two repeat
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coronary cineangiograms seven weeks and three years after surgery revealed the proximal right c o r o n a r y a r t e r y to be free of stenotic lesions or of luminal irregularities. After considering possible m e c h a n i s m s o f m y o c a r d i a l n e c r o s i s in t h e prese n c e o f n o r m a l c o r o n a r y a r t e r i e s it is c o n c l u d e d that myocardial necrosis can result from cathet e r - i n d u c e d c o r o n a r y a r t e r y s p a s m in s p i t e o f administration of nitroglycerin.
13. 14. 15. 16.
REFERENCES
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morbid complications during percutaneous transfemoral coronary arteriography, Chest. (In press) Gellai, M., Norton, J. M., and Detar, D.: Evidence for direct control of coronary vascular tone by oxygen, Circ. Res. 32:279, 1973. Berne, R. M.: Cardiac nucleotides in hypoxia: possible role in regulation of coronary blood flow, Am. J. Physiol. 204:317, 1963. Yurchak, P. M., Rolett, P. M., and Cohen, L. S., et al.: Effects of norepinephrine on the coronary circulation in man, Circulation 30:180, 1964. Peiper, U., and Schmidt, E.: Relaxation of coronary arteries by electromechanical decoupling or adrenergic stimulation, Pfluegers Arch. 337:107, 1972. Murphy, R. A., Bohr, D. F., and Newman, D. L.: Arterial actomyosin: Mg, Ca, and ATP ion dependencies for ATPase activity, Am. J. Physiol. 217:666, 1969. Moran, N. C.: Adrenergic drugs and the cardiovascular system, Mod. Concepts Cardiovasc. Dis. 7:99, 1966. Schmidt, E., and Peiper, U.: Tonus~inderungen von isolierten Coronararterien durch Depolarisation und oder Noradrenalin vor und nach Blockierung adrenerger Rezeptoren, Arch. Pharmacol. 275:383, 1972. Meaney, T. F., and Buonocore, E.: Contractions in the renal arteries during arteriography, Radiology 86:41, 1966. Wickbprn, J., and Bartley, O. O.: Arterial "spasm" in peripheral arteriography using the catheter method, Acta Radiol. 47:433, 1957. Demany, M. A., Tambe, A., and Zimmerman, H. A.: Coronary artery spasm, Dis. Chest 53:714, 1968. O'Reilly, R. J., Spellberg, R. D., and King, T. W.: Recognition of proximal right coronary artery spasm during coronary arteriography, Radiology 95:305, 1970. Lindbohm, A.: Arterial spasm caused by puncture and catheterization, Acta Radiol. 47:449, 1957. Cheng, T. 0., Bashour, T., and Kelser, G. A., et al.: Variant angina of Prinzmetal with normal coronary arteriograms, Circulation 47:476, 1973. Savranoglu, N., Boucek, R. J., and Casten, G.: The extent of reversibility of myocardial ischemia in dogs, AM. HEART J. 58:726, 1959. Jennings, R. B., Sommers, H. M., and Smyth, G. A.: Myocardial necrosis induced by temporary occlusion of a coronary artery in the dog, Arch. Pathol. 70:68, 1960. Prinzmetal, M., Kennamer, R., and Merliss, R., et al.: Angina pectoris. I. A variant form of angina pectoris: preliminary report, Am. J. Med. 27:375, 1959.
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