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Interpretation of the exercise-induced ST-segment elevation
EDITORIALS
Interpretation of the Exercise-Induced ST-Segment Elevation Robert A. Chahine, MD, Maureen H. Lowery,
MD,
E
and E. Joseph Bauerlein, MD
lectrocardiographic ST-segment elevation during tion, and if they reviewed the 216 patients excluded, furexercise testing has been recognized since the ther support would probably be added to the prevailing early days of the Master 2-step tes@-; it was concepts. Left ventricular aneurysm: Extensive data have acthought at the time that it representedanother manifestation of severe myocardial ischemia. Subsequentstud- cumulated over the past 20 years correlating the presies further characterized the exercise-induced ST-seg- ence of exercise-inducedST-segmentelevation with varment elevation as reflecting a more severe or unstable ious clinical subsets.In a study published in 1976, one form of ischemic heart disease? Prinzmetal’s variant of us noted that “exercise-induced ST-segmentelevation angina,4or marked abnormality of left ventricular f&c- seemedto reflect the presenceof severe coronary distion or left ventricular aneurysm, or both.5 The preva- easemost commonly with an associatedleft ventricular lence of this tinding has varied depending on the popu- aneurysmand may relate more to the abnormal wall molation being evaluated,the criteria used to define ST el- tion than to the myocardial ischemia per se.“5 That evation, and the number of leads monitored.5-13The study examined an unselected population undergoing average reported incidence is approximately 5% in a stresstesting predominantly for the evaluation of ischgeneral population undergoing stress testing predomi- emit heart disease.Exercise-induced ST-segmentelevanantly for ischemic heart disease,and ranges between tion was found in 3.5% of patients studied and correlat0.5 and 52.0% in selectedpopulations.12~13 ed with the presenceof marked abnormality of left venClinical correlations: Since the early 1970s the fo- tricular function or aneurysm in the overwhelming cus regarding exercise-induced ST-segment elevation majority (>85%) of cases.Some relative limitations of has vacillated between the abnormality of left ventricu- that study are that patients were mostly older male vetlar function and specific types of myocardial ische- erans, and only 2 electrocardiographic leads (modified mia.3-25In this issue, Gallik et al26focus once more on V5 and v6) were monitored. Subsequently,Waterset al6 the severity of ischemia secondary to fixed proximal used multiple electrocardiographiclead monitoring in a coronary artery disease.They also stressthe reversibili- broader population and found a greater incidence of exty of the exercise-inducedelectrocardiographic tindings ercise-induced ST-segmentelevation (6.5%). They also after correction of the underlying problem by an inter- contirmed that in most patients (>75%), the exercise-inventional procedure(percutaneoustransluminal coronary duced ST-segment elevation correlated with a marked angioplasty or coronary artery bypass surgery) or opti- segmentalleft ventricular wall motion abnormality commization of medical therapy. The most common charac- prising akinesia or dyskinesia. The segmental abnorteristic that separatespatients in whom the exercise-in- mality could be reliably predicted by the occurrence of duced ST-segmentelevation reflects severereversible is- the ST elevation in the corresponding electrocardiochemia from those with marked abnormality of left graphic lead system.De Feyter et al,13also using mulventricular function appearsto be the absenceof past tilead electrocardiographic monitoring in 680 patients, history or electrocardiographic pattern of transmural found exercise-induced ST-segment elevation in 22%. myocardial infarction.5-*5 Gaflik et al appropriately When they divided the patients into groups, the incistressthat their patient selection was based on the ab- dence of ST elevation with exercise was 1% in those sence of previous myocardial infarction. However, they without clinically significant coronary artery disease,and do not focus sufficiently in their discussion on the rela- 52% in those with sign&ant coronary artery disease tive rarity of the type of patients they describe in rela- and previous myocardial infarction. In the latter group, tion to the overall prevalence of exercise-induced ST- the sensitivity of the exercise-induced ST-segmentelesegmentelevation. The ST-segmentelevation secondary vation for the diagnosis of left ventricular aneurysmwas to markedly abnormal left ventricular function or 90% and its speciiicity for left ventricular wall motion aneurysm usually accounts for most patients with such abnormality was 100%.In another study focusing on setindings when unselectedstresstests are reviewed.5,6,gJ3 lected patients who had documentation of 1 myocardial The data of Gallik et al do not contradict this percep- infarction before the exercise test, Weiner et all4 concluded that analysis of the exercise-inducedST changes could reliably predict the presenceof a left ventricular From the Division of Cardiology, Department of Medicine, University aneurysm. Several other reports have also inferred or of Miami School of Medicine, Miami, Florida. Manuscript received supportedthe concept that the exercise-inducedST-segFebroary 2, 1993, and accepted February 3. ment elevation correlates well with the presence of Address for retxints: Robert A. Chahine, MD. Division of Cardiolmarked abnormality of left ventricular function or ogy (D-39), University of Miami School of Medicine, P.O. Box ~euTysm~9,10~15,*4*~ 016960, Miami, Florida 33101. 100 THE AMERICANJOURNALOF CARDIOLOGY VOLUME72 JULY 1,1993
f+-inrmetal’s variant angina: Exercise-induced STsegmentelevation was described in Prinzmetal’s variant angina approximately 20 years ago.4 The focus at that time was more on the preservation of exercise capacity in such patients in contradistinction to exertional angina. However, subsequentstudies focused on the electrocardiographic ST shifts during exercise in such patients.18-23One study involving a relatively large group of patients found that approximately one third (35%) had exercise-induced ST-segment elevation.20Correlative studies confirmed that such patients truly develop coronary artery spasm with exercise.‘* It was also recognized that when exercise-induced ST-segment elevation occurs in the absence of electrocardiographic Q waves or ventriculographic evidence of left ventricular aneurysm, it may representan important diagnostic feature of variant angina.6However, the prevalence of this Iinding in different studies varied widely, depending on the selection of patients, and possible referral bias.5-14 Nevertheless, when unselected stress tests were reviewed, the percentageof patients with exercise-induced ST-segment elevation probably due to coronary artery spasmwas relatively small.5-13The observationsreported by Gallik et al26do not contradict this perception. &hernia
due to proximal coronay artery disease:
One of the earliest characterizationsof the exercise-induced ST-segment elevation was its relation to the severity of Iixed coronary artery disease,or the instability of the related coronary syndrome.3Although subsequent studies of larger populations tended to focus on the marked abnormality of left ventricular function or presence of an aneurysm, several reports continued to stress the severity of myocardial ischemia and the presenceof important proximal lesions correlating with this iind~g.8,10,11,16,17,25 m ereasthe prevalenceof such patients in a general population is obviously small, it may become more impressive when selection of patients with exercise-induced ST-segment elevation is based on the absenceof myocardial infarction, as well as the absence of coronary artery spasm.In this issue, Gal& et al26focused on such a population with fixed proximal coronary artery diseaseunderlying the exercise-inducedSTsegmentelevation. They stressedthe reversibility of this linding after correction of the underlying problem. Their observationsare cogent and encouraging.However, they do not appropriately stress that their population represents only a very small segment (5%) of the patients who displayed the exercise-induced ST-segment elevation in their own population and only 0.1 to 0.2% of their overall population undergoing stresstesting. Therefore, the value of their observations should be kept in perspective in relation to the rarity of the type of patients represented. The mechanism of exercise-induced ST-segment elevation: The postulation that the exercise-inducedST-
duced ST-segment elevation in patients with previous anterior myocardial infarction using stress tests with thallium imaging. They concluded that “myocardial ischemia is not required for the production of the exerciseinduced ST-segment elevation and the stress-induced ST-segment elevation primarily reflects the extent of previous anterior wall damage.” Therefore, the following question arises: Is the mechanism different in patients With severe ischemia in the absenceof previous myocardial infarction? In patients with Prinzmetal’s variant angina in whom ST-segmentelevation is due to severeexercise-inducedspasmresulting in total or near total proximal obstruction of a coronary artery, marked segmentalleft ventricular wall abnormalities have been observed in relation to the spasm.21Thus, the transient akinesia or dyskinesia occurring during spasm in the subtended myocardial segment could be implicated in the production of the ST-segmentelevation. Therefore, the concept that the exercise-inducedST-segmentelevation may be due to the abnormal wall motion abnormality is supportedby the observationsin patients with variant angina.21In regard to the subgroup of patients described by Gallik et al,26it should be emphasizedthat many similar patients with proximal coronary disease are observedwithout the occurrenceof exercise-induced ST-segmentelevation. The distinguishing featuresin this small, select group may relate to additional factors other than the proximal fixed coronary artery disease.These factors may include the coronary steal phenomenon, or added coronary vasoconstriction or spasm during exercise that may further decreaseflow to the subtendedmyocardial segment.The combination of factors may produce transient akinesia or dyskinesia during exercise, which may account for the ST-segmentelevation. Conclusion: As our knowledge expands and more data accumulates,the interpretation of exercise-induced ST-segment elevation is actually becoming simpler. In large, unselected populations undergoing workup for possible ischemic heart disease, the exercise-induced ST-segment elevation usually reflects marked left ventricular dysfunction or aneurysm in >75% of patients. These patients tend to have history of myocardial infarction and/or presence of electrocardiographic Q waves in the lead correspondingto the ST elevation. In the smaller group of patients with ST-segmentelevation during exercise in the absence of previous myocardial infarction, the diagnosismay be divided equally between severe coronary artery spasm and proximal iixed coronary disease.A common underlying mechanism related to the resulting marked abnormality of left ventricular function may be postulated. Although this dysfunction is permanent in the case of left ventricular aneurysm,it is usually a transient phenomenonin the remaining population.
segment elevation “is associatedmost commonly with 1. Kroop ICi, Jaffee HL, Master AM. The significance of RS-T elevation in acute left ventricular aneurysm and may relate more to the ab- coronary insufficiency. BUN N Y Acad Med 1949:465. 2. Master AM, Rosenfeld I. Two step exercise test: current statlls after twenty five normal wall motion than to the myocardial ischemia, per years. Mod Concepts Cardiovasc Dis 1967;36:19-24. se“5 appearsto have withstood the test of time.6,13-15,243. Formin NJ, Friesinger GC. Exercise-iiduced ST-segment elevation. Clinical, elecSeveral differently designedstudies came to similar con- trocardiographic and ateriographic studies in twelve patients. Am J Med 1970;49: clusions. Gewirtz et all5 tested the hypothesis that my- 459-464. 4. MacAlpin RN, Kattus AA, Ahwo AG. Angina pectoris at rest with preservaocardial ischemia may be responsible for exercise-in- tion of exercise capacity. Prinzmetal’s variant angina. Circulation 1973;47:94&958. EDITORIALS 101
5. Chahine RA, Raivler AE, Ishimori T. The clinical significance of exercise-induced ST-segment elevation. Circularion 1976;54:209-218. 6. Waters DD, Chaitmao BR, Boorassa MG, Tubau JF. Clinical and angiogmphic correlates of exercise-induced ST-segment elevation. Increased detection with moltiple ECG leads. Circulation 1980;61:28&296. 7. Bruce RA, Fisher LD, Petiger M, Weiner DA, Chaitmao BR. ST segment elevation with exercise: a marker for poor ventricular function and poor prognosis. Coronary Artery Surgery Study (CASS) confirmation of Seattle Heart Watch results. Circubrion 1988;4:897-905. 6. Longhurst JC, Kraus WL. Exercise-induced ST elevation io patients without myocardial infarction. Circulation 1979;60:616-627. 6. Sriwattanakomen S, Ticzon AR, Zubritzky SA, Blobner CG, Rice M, Daffy FC, Lanna EF. ST segment elevation daring exercise: electmcardiograpbic and arteriographic correlation in 38 patients. Am 3 Cardiol 1980;45:762-768. 10. Stiles GL, Tosati RA, Wallace AG. Clinical relevance of exercise-induced STsegment elevation. Am .I Cavdiol 1980;46:931-936. 11. Dunn RF, Freedman B, Kelly DT, Bailey IK, McLaughlin A. Exercise-induced ST-segment elevation in leads Vl or a VL. A predictor of anterior myocardial ischemia and left anterior descending coronary artery disease. Circulation 1981;63: 1357-1369. 12. Brace RA, Gey GO Jr, Cooper MN, Fischer LD, Peterson DR. Seattle Heart Watch: initial clinical, circulatory and electrocardiographic response to maximal exercise. Am J Cardiol 1974;33:45w70. 13. De Feyter PJ, Majid PA, Van Eenige MJ, Wardeh R, Wempe FN, Roos JP. Clinical significance of exercise-induced ST-segment elevation. Correlative angiographic study io patients with ischaemic heart disease. Br Heart J 1981;46:84-92. 14. Weiner DA, McCabe C, Klein MD, Ryan TJ. ST segment changes post-infarction: predictive value for multivessel coronary disease and left ventricular aneurysm. Circulation 1978;58:887-891. 15. Gewirtz H, Sullivan M, O’Reilly G, Winter S, Most A. Role of myocaniial ischemia in the genesis of exercise-induced ST-segment elevation in previous aoterior myocardial infarction. Am J Cardiol 1983;51:1293-1305. 16. Dunn RF, Bailey lK, Roger U, Kelly DT. Exercised induced ST-segment el-
evation correlation of thallium 201 myocardial Perfusion scanning and coronary arteriography. Circulation 1980;61:989-995, 17. Hegge FN, Tuna N, Burchell HB. Coronary atwiographic fmdings io patients with axis shifts or ST segment elevations on exercise testing. Am Heart J 1973; 86603614. 16. Fuller CM, Raizner AE, Chahine RA, Nahormek P, Ishimori T, Verani M, Nitishin A, Mokotoff D, Lo&i RL. Exercise-induced coronary arterial spasm: angiographic demonstration, documentation of ischemia by myowdial sciotigraphy and results of pharmacologic intervention. Am J Cardiol 1980;46:500-506. 16. Lahiri A, Subramaoian B, Miller-Craig M, Crawley .I, Raftery E. Exercise-induced ST-segment elevation io variant aogioa. Am J Cardiol 1980;45:887-894. 20. DeServi S, Falcone C, Gavazzi A, Mussini A, Bramucci E, Curti MT, Veccio C, Specchia G, Bobba P. The exercise test in variant angina: results in 114 patients. Circulation 198 1;64:68r1688. 21. Chahine R, Verani M, Zacca N, Rainer A, Pircher F, Miller R, Luchi R. Reversible segmental contraction abnormalities during exercise induced coronary artery spasm and their effect on global left ventricular function. Am J Cardioll98 1;47:45 1. 22. Shimokawa H, Matsuguchi T, Koiwaya Y, Fukoyama T, Orita Y, Nakamora M. Variable exercise capacity in variant angina and greater exertional thallium-201 myocardial defect during vasospastic ischemic ST segment elevation than with ST depression. Am Heart J 1982;103:142-151. 23. Specchia G, DeServi S, Falcone C, Angoli L, Mussini A, Bramucci E, Marioni GP, Ardissino D, Salerno J, Bobba P. Significance of exercise-induced STsegment elevation in patients without myocardial infarction. Circulation 1981;63: 4653. 24. Nostration FJ, Froelicher VF. ST elevation during exercise testing. Am .I Cardial 1989;63:986-988. 25. Auora R, Ioachim L, Matza D, Horowitz SF. The role of ischemia and ventitular asynergy in the genesis of exercise-induced ST elevation. Clin Cardiol1988; 11:127-139. 26. Gallii DM, Mahmarian JJ, Verani MS. Exercise-induced ST-segment elevation in patients without previous myocardial infarction-an ominous predictor of extensive, myocardial hypoperfusion amenable to therapy. Am J Cardiol1993;72: l-7.
The Case of a Fascinating Dimple Paolo Angelini, MD come coronary ostia by connecting with the epicardial coronary network that develops in situ (“bimodal theory”). Recently, Conte and Pellegrini5 and Bogers et al6 suggested,on the basis of observationsin human and rat embryos, that the in situ coronary network could “induce” orifices in the aortic wall when they come into close proximity to it. Only additional, more sophisticated studies of descriptive and experimental embryology could clarify what are the original components and what are the mechanisms of normal morphogenesis.Similar studies are being conducted at the laboratory of Experimental Embryology at the National Institute of Pediatrics,Mexico City (Dr. Maria Victoria de la Cruz’s group). The anatomic casesof blind coronary dimples would seemto support Hackensellner’stheory of primaiy, multiple coronary buds. The fact that no coronary artery is in close proximity with such “dimples” does not exclude the possibility that at an early age of the embryologic development a coronary artery could have been in close contact. In fact, the only abnormality would be that the coronary bud did not regress once a permanentconnection with a coronary artery did not develop. Casesof congenital coronary ostial stenosisand even atresiacould be the expressionof an intermediate defect From St.Luke’s EpiscopalHospital,TexasHeartInstitute,Houston,Texas. ‘m which the connection between the in situ coronary ManuscriptreceivedFebruary10,1993,andacceptedFebruary11. Address for reprints: Paolo Angelini, MD, St. Lukes Episcopal network and the coronary bud resulted incomplete. It Hospital, Texas Heart Institute, P.O. Box 20206, Houston, Texas could be hypothesized that if atresia at this level should 772250206. develop early in embryologic life, only a blind dimple e case of a coronary ostial dimple in the posterior aortic sinus, presentedin this issue by Shirani and Roberts’ is clinically irrelevant, but possibly quite revealing. The reported fmding of a “coronary dimple” is well documentedand, although quite rare, it has already been described in published reports as reviewed.’ The most surprising (and previously unreported) related tinding is that the dimple occurred in a patient with otherwise normal coronary arteries (2 ostia in their respective sinuses) and that it was located in the “non-coronary” cusp. The latter cusp quite exceptionally gives origin to a coronary artery in an otherwise normal heart2 Many more casesof coronary dimples have been seen but not reported as such, most frequently in the context of coronary ostial atresia.2 Observed anatomic anomalies again refer back to embryogenetic theories, as natural experiments can do. Current theories on the developmentof the coronary arteries are basically referrable to 2 schools of thought: (1) AbrikosotF proposed that there are areas of the aortic and pulmonary adjacent sinuses, programmed to give rise to the coronary arteries, that sprout toward the myocardium (“unimodal theory”). (2) Hackensellneti suggestedthat the early embryo transiently develops several coronary buds (normally 6 from both the aortic and pulmonary sinuses),and then only a few (usually 2) be-
T
102
THE AMERICANJOURNALOF CARDIOLOGY VOLUME72
JULY I,1993
Interpretation of the Exercise-Induced ST-Segment Elevation Robert A. Chahine, MD, Maureen H. Lowery,
MD,
E
and E. Joseph Bauerlein, MD
lectrocardiographic ST-segment elevation during tion, and if they reviewed the 216 patients excluded, furexercise testing has been recognized since the ther support would probably be added to the prevailing early days of the Master 2-step tes@-; it was concepts. Left ventricular aneurysm: Extensive data have acthought at the time that it representedanother manifestation of severe myocardial ischemia. Subsequentstud- cumulated over the past 20 years correlating the presies further characterized the exercise-induced ST-seg- ence of exercise-inducedST-segmentelevation with varment elevation as reflecting a more severe or unstable ious clinical subsets.In a study published in 1976, one form of ischemic heart disease? Prinzmetal’s variant of us noted that “exercise-induced ST-segmentelevation angina,4or marked abnormality of left ventricular f&c- seemedto reflect the presenceof severe coronary distion or left ventricular aneurysm, or both.5 The preva- easemost commonly with an associatedleft ventricular lence of this tinding has varied depending on the popu- aneurysmand may relate more to the abnormal wall molation being evaluated,the criteria used to define ST el- tion than to the myocardial ischemia per se.“5 That evation, and the number of leads monitored.5-13The study examined an unselected population undergoing average reported incidence is approximately 5% in a stresstesting predominantly for the evaluation of ischgeneral population undergoing stress testing predomi- emit heart disease.Exercise-induced ST-segmentelevanantly for ischemic heart disease,and ranges between tion was found in 3.5% of patients studied and correlat0.5 and 52.0% in selectedpopulations.12~13 ed with the presenceof marked abnormality of left venClinical correlations: Since the early 1970s the fo- tricular function or aneurysm in the overwhelming cus regarding exercise-induced ST-segment elevation majority (>85%) of cases.Some relative limitations of has vacillated between the abnormality of left ventricu- that study are that patients were mostly older male vetlar function and specific types of myocardial ische- erans, and only 2 electrocardiographic leads (modified mia.3-25In this issue, Gallik et al26focus once more on V5 and v6) were monitored. Subsequently,Waterset al6 the severity of ischemia secondary to fixed proximal used multiple electrocardiographiclead monitoring in a coronary artery disease.They also stressthe reversibili- broader population and found a greater incidence of exty of the exercise-inducedelectrocardiographic tindings ercise-induced ST-segmentelevation (6.5%). They also after correction of the underlying problem by an inter- contirmed that in most patients (>75%), the exercise-inventional procedure(percutaneoustransluminal coronary duced ST-segment elevation correlated with a marked angioplasty or coronary artery bypass surgery) or opti- segmentalleft ventricular wall motion abnormality commization of medical therapy. The most common charac- prising akinesia or dyskinesia. The segmental abnorteristic that separatespatients in whom the exercise-in- mality could be reliably predicted by the occurrence of duced ST-segmentelevation reflects severereversible is- the ST elevation in the corresponding electrocardiochemia from those with marked abnormality of left graphic lead system.De Feyter et al,13also using mulventricular function appearsto be the absenceof past tilead electrocardiographic monitoring in 680 patients, history or electrocardiographic pattern of transmural found exercise-induced ST-segment elevation in 22%. myocardial infarction.5-*5 Gaflik et al appropriately When they divided the patients into groups, the incistressthat their patient selection was based on the ab- dence of ST elevation with exercise was 1% in those sence of previous myocardial infarction. However, they without clinically significant coronary artery disease,and do not focus sufficiently in their discussion on the rela- 52% in those with sign&ant coronary artery disease tive rarity of the type of patients they describe in rela- and previous myocardial infarction. In the latter group, tion to the overall prevalence of exercise-induced ST- the sensitivity of the exercise-induced ST-segmentelesegmentelevation. The ST-segmentelevation secondary vation for the diagnosis of left ventricular aneurysmwas to markedly abnormal left ventricular function or 90% and its speciiicity for left ventricular wall motion aneurysm usually accounts for most patients with such abnormality was 100%.In another study focusing on setindings when unselectedstresstests are reviewed.5,6,gJ3 lected patients who had documentation of 1 myocardial The data of Gallik et al do not contradict this percep- infarction before the exercise test, Weiner et all4 concluded that analysis of the exercise-inducedST changes could reliably predict the presenceof a left ventricular From the Division of Cardiology, Department of Medicine, University aneurysm. Several other reports have also inferred or of Miami School of Medicine, Miami, Florida. Manuscript received supportedthe concept that the exercise-inducedST-segFebroary 2, 1993, and accepted February 3. ment elevation correlates well with the presence of Address for retxints: Robert A. Chahine, MD. Division of Cardiolmarked abnormality of left ventricular function or ogy (D-39), University of Miami School of Medicine, P.O. Box ~euTysm~9,10~15,*4*~ 016960, Miami, Florida 33101. 100 THE AMERICANJOURNALOF CARDIOLOGY VOLUME72 JULY 1,1993
f+-inrmetal’s variant angina: Exercise-induced STsegmentelevation was described in Prinzmetal’s variant angina approximately 20 years ago.4 The focus at that time was more on the preservation of exercise capacity in such patients in contradistinction to exertional angina. However, subsequentstudies focused on the electrocardiographic ST shifts during exercise in such patients.18-23One study involving a relatively large group of patients found that approximately one third (35%) had exercise-induced ST-segment elevation.20Correlative studies confirmed that such patients truly develop coronary artery spasm with exercise.‘* It was also recognized that when exercise-induced ST-segment elevation occurs in the absence of electrocardiographic Q waves or ventriculographic evidence of left ventricular aneurysm, it may representan important diagnostic feature of variant angina.6However, the prevalence of this Iinding in different studies varied widely, depending on the selection of patients, and possible referral bias.5-14 Nevertheless, when unselected stress tests were reviewed, the percentageof patients with exercise-induced ST-segment elevation probably due to coronary artery spasmwas relatively small.5-13The observationsreported by Gallik et al26do not contradict this perception. &hernia
due to proximal coronay artery disease:
One of the earliest characterizationsof the exercise-induced ST-segment elevation was its relation to the severity of Iixed coronary artery disease,or the instability of the related coronary syndrome.3Although subsequent studies of larger populations tended to focus on the marked abnormality of left ventricular function or presence of an aneurysm, several reports continued to stress the severity of myocardial ischemia and the presenceof important proximal lesions correlating with this iind~g.8,10,11,16,17,25 m ereasthe prevalenceof such patients in a general population is obviously small, it may become more impressive when selection of patients with exercise-induced ST-segment elevation is based on the absenceof myocardial infarction, as well as the absence of coronary artery spasm.In this issue, Gal& et al26focused on such a population with fixed proximal coronary artery diseaseunderlying the exercise-inducedSTsegmentelevation. They stressedthe reversibility of this linding after correction of the underlying problem. Their observationsare cogent and encouraging.However, they do not appropriately stress that their population represents only a very small segment (5%) of the patients who displayed the exercise-induced ST-segment elevation in their own population and only 0.1 to 0.2% of their overall population undergoing stresstesting. Therefore, the value of their observations should be kept in perspective in relation to the rarity of the type of patients represented. The mechanism of exercise-induced ST-segment elevation: The postulation that the exercise-inducedST-
duced ST-segment elevation in patients with previous anterior myocardial infarction using stress tests with thallium imaging. They concluded that “myocardial ischemia is not required for the production of the exerciseinduced ST-segment elevation and the stress-induced ST-segment elevation primarily reflects the extent of previous anterior wall damage.” Therefore, the following question arises: Is the mechanism different in patients With severe ischemia in the absenceof previous myocardial infarction? In patients with Prinzmetal’s variant angina in whom ST-segmentelevation is due to severeexercise-inducedspasmresulting in total or near total proximal obstruction of a coronary artery, marked segmentalleft ventricular wall abnormalities have been observed in relation to the spasm.21Thus, the transient akinesia or dyskinesia occurring during spasm in the subtended myocardial segment could be implicated in the production of the ST-segmentelevation. Therefore, the concept that the exercise-inducedST-segmentelevation may be due to the abnormal wall motion abnormality is supportedby the observationsin patients with variant angina.21In regard to the subgroup of patients described by Gallik et al,26it should be emphasizedthat many similar patients with proximal coronary disease are observedwithout the occurrenceof exercise-induced ST-segmentelevation. The distinguishing featuresin this small, select group may relate to additional factors other than the proximal fixed coronary artery disease.These factors may include the coronary steal phenomenon, or added coronary vasoconstriction or spasm during exercise that may further decreaseflow to the subtendedmyocardial segment.The combination of factors may produce transient akinesia or dyskinesia during exercise, which may account for the ST-segmentelevation. Conclusion: As our knowledge expands and more data accumulates,the interpretation of exercise-induced ST-segment elevation is actually becoming simpler. In large, unselected populations undergoing workup for possible ischemic heart disease, the exercise-induced ST-segment elevation usually reflects marked left ventricular dysfunction or aneurysm in >75% of patients. These patients tend to have history of myocardial infarction and/or presence of electrocardiographic Q waves in the lead correspondingto the ST elevation. In the smaller group of patients with ST-segmentelevation during exercise in the absence of previous myocardial infarction, the diagnosismay be divided equally between severe coronary artery spasm and proximal iixed coronary disease.A common underlying mechanism related to the resulting marked abnormality of left ventricular function may be postulated. Although this dysfunction is permanent in the case of left ventricular aneurysm,it is usually a transient phenomenonin the remaining population.
segment elevation “is associatedmost commonly with 1. Kroop ICi, Jaffee HL, Master AM. The significance of RS-T elevation in acute left ventricular aneurysm and may relate more to the ab- coronary insufficiency. BUN N Y Acad Med 1949:465. 2. Master AM, Rosenfeld I. Two step exercise test: current statlls after twenty five normal wall motion than to the myocardial ischemia, per years. Mod Concepts Cardiovasc Dis 1967;36:19-24. se“5 appearsto have withstood the test of time.6,13-15,243. Formin NJ, Friesinger GC. Exercise-iiduced ST-segment elevation. Clinical, elecSeveral differently designedstudies came to similar con- trocardiographic and ateriographic studies in twelve patients. Am J Med 1970;49: clusions. Gewirtz et all5 tested the hypothesis that my- 459-464. 4. MacAlpin RN, Kattus AA, Ahwo AG. Angina pectoris at rest with preservaocardial ischemia may be responsible for exercise-in- tion of exercise capacity. Prinzmetal’s variant angina. Circulation 1973;47:94&958. EDITORIALS 101
5. Chahine RA, Raivler AE, Ishimori T. The clinical significance of exercise-induced ST-segment elevation. Circularion 1976;54:209-218. 6. Waters DD, Chaitmao BR, Boorassa MG, Tubau JF. Clinical and angiogmphic correlates of exercise-induced ST-segment elevation. Increased detection with moltiple ECG leads. Circulation 1980;61:28&296. 7. Bruce RA, Fisher LD, Petiger M, Weiner DA, Chaitmao BR. ST segment elevation with exercise: a marker for poor ventricular function and poor prognosis. Coronary Artery Surgery Study (CASS) confirmation of Seattle Heart Watch results. Circubrion 1988;4:897-905. 6. Longhurst JC, Kraus WL. Exercise-induced ST elevation io patients without myocardial infarction. Circulation 1979;60:616-627. 6. Sriwattanakomen S, Ticzon AR, Zubritzky SA, Blobner CG, Rice M, Daffy FC, Lanna EF. ST segment elevation daring exercise: electmcardiograpbic and arteriographic correlation in 38 patients. Am 3 Cardiol 1980;45:762-768. 10. Stiles GL, Tosati RA, Wallace AG. Clinical relevance of exercise-induced STsegment elevation. Am .I Cavdiol 1980;46:931-936. 11. Dunn RF, Freedman B, Kelly DT, Bailey IK, McLaughlin A. Exercise-induced ST-segment elevation in leads Vl or a VL. A predictor of anterior myocardial ischemia and left anterior descending coronary artery disease. Circulation 1981;63: 1357-1369. 12. Brace RA, Gey GO Jr, Cooper MN, Fischer LD, Peterson DR. Seattle Heart Watch: initial clinical, circulatory and electrocardiographic response to maximal exercise. Am J Cardiol 1974;33:45w70. 13. De Feyter PJ, Majid PA, Van Eenige MJ, Wardeh R, Wempe FN, Roos JP. Clinical significance of exercise-induced ST-segment elevation. Correlative angiographic study io patients with ischaemic heart disease. Br Heart J 1981;46:84-92. 14. Weiner DA, McCabe C, Klein MD, Ryan TJ. ST segment changes post-infarction: predictive value for multivessel coronary disease and left ventricular aneurysm. Circulation 1978;58:887-891. 15. Gewirtz H, Sullivan M, O’Reilly G, Winter S, Most A. Role of myocaniial ischemia in the genesis of exercise-induced ST-segment elevation in previous aoterior myocardial infarction. Am J Cardiol 1983;51:1293-1305. 16. Dunn RF, Bailey lK, Roger U, Kelly DT. Exercised induced ST-segment el-
evation correlation of thallium 201 myocardial Perfusion scanning and coronary arteriography. Circulation 1980;61:989-995, 17. Hegge FN, Tuna N, Burchell HB. Coronary atwiographic fmdings io patients with axis shifts or ST segment elevations on exercise testing. Am Heart J 1973; 86603614. 16. Fuller CM, Raizner AE, Chahine RA, Nahormek P, Ishimori T, Verani M, Nitishin A, Mokotoff D, Lo&i RL. Exercise-induced coronary arterial spasm: angiographic demonstration, documentation of ischemia by myowdial sciotigraphy and results of pharmacologic intervention. Am J Cardiol 1980;46:500-506. 16. Lahiri A, Subramaoian B, Miller-Craig M, Crawley .I, Raftery E. Exercise-induced ST-segment elevation io variant aogioa. Am J Cardiol 1980;45:887-894. 20. DeServi S, Falcone C, Gavazzi A, Mussini A, Bramucci E, Curti MT, Veccio C, Specchia G, Bobba P. The exercise test in variant angina: results in 114 patients. Circulation 198 1;64:68r1688. 21. Chahine R, Verani M, Zacca N, Rainer A, Pircher F, Miller R, Luchi R. Reversible segmental contraction abnormalities during exercise induced coronary artery spasm and their effect on global left ventricular function. Am J Cardioll98 1;47:45 1. 22. Shimokawa H, Matsuguchi T, Koiwaya Y, Fukoyama T, Orita Y, Nakamora M. Variable exercise capacity in variant angina and greater exertional thallium-201 myocardial defect during vasospastic ischemic ST segment elevation than with ST depression. Am Heart J 1982;103:142-151. 23. Specchia G, DeServi S, Falcone C, Angoli L, Mussini A, Bramucci E, Marioni GP, Ardissino D, Salerno J, Bobba P. Significance of exercise-induced STsegment elevation in patients without myocardial infarction. Circulation 1981;63: 4653. 24. Nostration FJ, Froelicher VF. ST elevation during exercise testing. Am .I Cardial 1989;63:986-988. 25. Auora R, Ioachim L, Matza D, Horowitz SF. The role of ischemia and ventitular asynergy in the genesis of exercise-induced ST elevation. Clin Cardiol1988; 11:127-139. 26. Gallii DM, Mahmarian JJ, Verani MS. Exercise-induced ST-segment elevation in patients without previous myocardial infarction-an ominous predictor of extensive, myocardial hypoperfusion amenable to therapy. Am J Cardiol1993;72: l-7.
The Case of a Fascinating Dimple Paolo Angelini, MD come coronary ostia by connecting with the epicardial coronary network that develops in situ (“bimodal theory”). Recently, Conte and Pellegrini5 and Bogers et al6 suggested,on the basis of observationsin human and rat embryos, that the in situ coronary network could “induce” orifices in the aortic wall when they come into close proximity to it. Only additional, more sophisticated studies of descriptive and experimental embryology could clarify what are the original components and what are the mechanisms of normal morphogenesis.Similar studies are being conducted at the laboratory of Experimental Embryology at the National Institute of Pediatrics,Mexico City (Dr. Maria Victoria de la Cruz’s group). The anatomic casesof blind coronary dimples would seemto support Hackensellner’stheory of primaiy, multiple coronary buds. The fact that no coronary artery is in close proximity with such “dimples” does not exclude the possibility that at an early age of the embryologic development a coronary artery could have been in close contact. In fact, the only abnormality would be that the coronary bud did not regress once a permanentconnection with a coronary artery did not develop. Casesof congenital coronary ostial stenosisand even atresiacould be the expressionof an intermediate defect From St.Luke’s EpiscopalHospital,TexasHeartInstitute,Houston,Texas. ‘m which the connection between the in situ coronary ManuscriptreceivedFebruary10,1993,andacceptedFebruary11. Address for reprints: Paolo Angelini, MD, St. Lukes Episcopal network and the coronary bud resulted incomplete. It Hospital, Texas Heart Institute, P.O. Box 20206, Houston, Texas could be hypothesized that if atresia at this level should 772250206. develop early in embryologic life, only a blind dimple e case of a coronary ostial dimple in the posterior aortic sinus, presentedin this issue by Shirani and Roberts’ is clinically irrelevant, but possibly quite revealing. The reported fmding of a “coronary dimple” is well documentedand, although quite rare, it has already been described in published reports as reviewed.’ The most surprising (and previously unreported) related tinding is that the dimple occurred in a patient with otherwise normal coronary arteries (2 ostia in their respective sinuses) and that it was located in the “non-coronary” cusp. The latter cusp quite exceptionally gives origin to a coronary artery in an otherwise normal heart2 Many more casesof coronary dimples have been seen but not reported as such, most frequently in the context of coronary ostial atresia.2 Observed anatomic anomalies again refer back to embryogenetic theories, as natural experiments can do. Current theories on the developmentof the coronary arteries are basically referrable to 2 schools of thought: (1) AbrikosotF proposed that there are areas of the aortic and pulmonary adjacent sinuses, programmed to give rise to the coronary arteries, that sprout toward the myocardium (“unimodal theory”). (2) Hackensellneti suggestedthat the early embryo transiently develops several coronary buds (normally 6 from both the aortic and pulmonary sinuses),and then only a few (usually 2) be-
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THE AMERICANJOURNALOF CARDIOLOGY VOLUME72
JULY I,1993