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Role of coronary arteriography in the evaluation of patients with coronary artery disease
Role of Coronary Arteriography in the Evaluation of Patients with Coronary Artery Disease ARTHUR
alf a century
SELZER,
M.D. and RICHARD
ago the clinician was guided in his and therapeutic endeavors by morphologic criteria, mostly based on postmortem examination. During the past few decades the emphasis has shifted from purely morphologic approaches to physiologic and biochemical aspects of disease. In the field of cardiovascular diseases spectacular advances are related to better understanding of physiologic and functional alterations of the cardiovascular system, to the capability of clinical assessment of pathophysiologic disorders and to precise in vivo recognition of morphologic changes. Thus, the decision making process in cardiology is based on physiologic, functional and morphologic considerations. Yet, in coronary artery disease the enthusiasm generated by the development of coronary arteriography once again placed morphology in a preeminent position. Anatomic changes in the coronary artery, demonstrated by the injection of a contrast medium, became the principal-and in many cases the only-yardstick in the decision making process. Coronary arteriography is closely tied in with surgical revascularization of the myocardium, inasmuch as the principal indication for performing this test is to assess a patient for the aortocoronary bypass operation. There are two aspects of surgical treatment of coronary artery disease: the remedial aspect and the prophylactic aspect. In the former case, the typical patient suffers from disabling chest pain; the physician establishes the ischemic origin of the pain; coronary arteriography is performed to assess the morphologic abnormalities and the suitability of the obstructing lesions for a bypass operation. Prophylactic operations aim at preventing myocardial infarction or death: here morphologic considerations are paramount; functional and physiologic aspects are considered unimportant or even irrelevant. The remedial use of myocardial surgical revascularization is widely accepted as a major advance in cardiovascular diseases. Its prophylactic use is the subject of a controversy and is being hotly debated in medical
H diagnostic
C. PASTERNAK,
M.D.
journals. Opinions have been expressed as to wide overuse of coronary arteriography [l] and aortocoronary bypass operations [z] due to overemphasis on prophylactic aspects of the operation. The purpose of the following discussion is to review the question as to whether the present basis of our knowledge justifies morphologic consideration as the sole basis for clinical decisions. A review of this problem requires answers to the following questions. (1) How reliable is arteriographic estimation of coronary artery stenotic lesions? (2) How effective are adaptive and compensatory processes in the coronary circulation? (3) Are all lesions equally threatening, i.e., is their progression inevitable? (4) How reliable (or unreliable) are clinical manifestations of reduced myocardial blood supply? Reliabilityof Coronary Arteriography. Considerable technical advances have been made during the past decade that permit a clearer cineangiogram of the coronary circulation and facilitate correct interpretation of obstructive lesions. Nevertheless, the accuracy of evaluating the severity of lesions is overrated, and the custom of expressing the degree of narrowing in terms of percentages tends to mislead the clinician who may be inclined to take this literally. Coronary arteriography requires multiple injections of the contrast medium in various projections to visualize the coronary arteries adequately. The anatomic course of coronary arteries tends to be tortuous, hence coronary arterial segments can be seen perpendicular to the filming plane, parallel to it or at any angle to it. A stenotic lesion is shown in the segment parallel to the film in its true linear projection, whereas in the perpendicular projection, it may not be visible at all. In addition to problems related to the angle of the stenotic segment to the film, superimposition of other coronary branches or of the coronary catheter may interfere with the visibility of the stenotic area. The arteriographer is thus accustomed to seeing the stenotic segment in some projections but not in others. The projection showing the narrowest-almost always the best seen-segment is the
From the Division of Cardiology, Presbyterian Hospital of Pacific Medical Center, San Francisco, California. Requests for reprints should be addressed to Dr. Arthur Seizer. Division of Cardiology, Pacific Medical Center, P.O. Box 7999, San Francisco, CA 94120.
April 1981
The American Journal of Medicine
Volume 70
747
EDITORIALS-SELZER.
I 0
PASTERNAK
rI
c.
0) 8
igure 1. Diagrammatic presentation of arteriographic image of stenotic coronary arteries shown in the projection presenting the most severe narrowing (above) and crosssection of the artery across the stenotic portion (below). A, central lumen; B, eccentric slit-like stenotic lumen causing overestimation of the severity of stenosis; C, eccentric crescentic stenotic lumen causing underestimation of the severity of stenosis.
basis for calculating the severity of the stenosis. Calculations of the degree of stenosis are based on the assumption that the stenosed lumen is circular. The arteriographer estimates the linear diameter of the narrowest level and expresses it as a percentage of the “normal” diameter of that vessel and, on this basis, calculates luminal area stenosis. Occasionally, confusion may develop whether “percent stenosis” expresses linear or area stenosis if this point is not specifically indicated (e.g., a 50 percent linear stenosis indicates a 75 percent area stenosis of a circular orifice). The accuracy of evaluating the degree of stenosis involves several assumptions: that the “measurement” of the narrowest level of stenosis is correct: that the residual lumen of the stenotic segment is circular; and that the nonstenotic artery represents the true control level (i.e., is not diffusely narrowed). Of these assumptions, the most fallacious is the acceptance that a circular lumen is the rule, i.e., a circumferential plaque producing an hour-glass type lesion. On the contrary, plaques tend to be irregularly shaped, producing lumens that are elliptic, crescentic or slit-like [3]. Our review of 12 random coronary arteriograms, obtained to evaluate the location of the remaining lumen in stenotic vessels, showed that in the 20 severe localized coronary lesions found, 40 percent had a central lumen whereas in 60 percent it was eccentric. Figure 1 presents in a diagrammatic form three lesions of round, crescentic and slit-like shape, illustrating the gross overestimation or underestimation of the severity of the lesion when the shape is other than circular. The imprecise and subjective manner of interpretating coronary arteriograms is illustrated by studies
748
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comparing reports of multiple readers and showing frequent disagreement between them [4]. Comparison of angiographic evaluation of coronary stenosis with postmortem examination of the vessels emphasizes further the frequent discrepancy between the two [5]. Recently, attempts have been made to refine the accuracy of coronary arteriography by using computerized analysis of stenotic lesions [6]. Although this technique unquestionably enhances the capability of evaluating stenotic lesions more precisely than visual inspection, it assumes a circular or elyptic lumen. In the presence of irregularly shaped, crescentic or slit-like lumens, computer reading of arteriograms may be just as likely to underestimate or overestimate lesions as does the angiography [7]. It is evident from the foregoing discussion that there are serious reservations regarding the prevailing custom of expressing arteriographic images of coronary plaques in terms of percent stenosis of the lumen. In the first place, this implies a precision in measurement when none exists. Furthermore, it ignores the modifiers that can enhance or minimize the effect of stenosis upon myocardial perfusion, such as the effect of other stenotic lesions in the affected vessel, the length of the stenotic segment or the diffuse atherosclerotic changes reducing the caliber of the “nonstenosed” portion of the artery with which the luminal narrowing is compared. Clinical decisions are often based on these numerical presentations of coronary arterial stenoses, accepting them as accurate. Perhaps a semiquantitative evaluation of coronary artery stenotic lesions, such as “mild,” “modFurthererate, ” “severe” would be more appropriate. more, even if the degree of the narrowing could be evaluated more accurately,, the physiologic consequences of the stenosis and its role in the production of ischemia cannot be deduced from the anatomy alone, considering the many physiologic factors affecting coronary flow through stenotic arteries. Effects and Consequences of Coronary Artery Stenosis. When an atherosclerotic plaque develops in a coronqry artery, it does not affect myocardial blood flow until it severely obstructs the lumen of the artery. Best available experimental evidence [8-lo] indicates that in order to interfere with the maximum coronary flow (i.e., myocardial oxygen supply for its highest requirement, e.g., strenuous exercise] the lumen has to be reduced to 15 percent of its original area, which in a coronary arteriogram would be shown as a 60 to 65 percent linear lesion, provided the stenotic lumen is circular. The lumen has to be reduced to 5 percent (85 percent to 90 percent of linear stenosis) to affect resting myocardial oxygen supply. In physiologic terms, a plaque protuding into the lumen of a coronary artery has to obstruct most of the lumen in order to generate resistance to flow and generate a pressure gradient (decrease in arterial pressure in the artery distal to the obstruction]. The pressure gradient is related to the magnitude of flow, hence different degrees of obstruction are necessary to produce
Volume 70
EDITORIALS-SELZER,
&hernia at the maximal and at the minimal (or resting) flow through a given artery. It follows that the effect of coronary stenosis upon myocardial oxygen supply can be expressed as an exponential relationship, namely, there is no effect up to the critical zone of narrowing; once this zone is entered, minute increments 13 stenosis will produce large increases in pressure gradient, i.e., decrease in coronary flow. Experimental studies by Gould et al. [&lo] demonstrated the importance of factors other than the degree of narrowing which can act as modifiers. Given two identical degrees of stenosis, one of greater length will restrict myocardial flow more than the shorter one. In the presence of multiple areas of stenosis, reduction in coronary flow is not determined by the most severe degree of stenosis: milder stenoses provide additive effects like resistors in a series, further restricting coronary flow. Even the presence or absence of poststenotic dilatation of a coronary artery may influence myocardial perfusion. However, the most important modifier affecting coronary flow is the magnitude of available collateral flow. The development of physiologically significant coronary artery stenosis induces an immediate compensatory reaction. There are physiologic collateral vessels connecting coronary branches, which are no larger than ZOO p and which are incapable of supplying more than a fraction of the deficient blood supply [ll]. However, myocardial ischemia stimulates growth of larger collateral vessels which may eventually carry enough volume to compensate fully obstructing lesions. It is not unusual to find complete occlusion of the right coronary artery without having produced myocardial infarction. There are even a number of cases on record of complete occlusion of the main left coronary artery with survival and with relatively little evidence of myocardial ischemia [l&13]. It should be pointed out that coronary arteriography is capable of visualizing only some types of collateral vessels. Contrast visualization will show retrograde filling of a completely occluded artery, and of a nonvisualized artery belonging to the other coronary system (e.g., left anterior descending branch visualized with injection of the right coronary artery system). However, collateral vessels forming within one coronary artery system and conpensating a partially occluded vessel may not be seen in the coronary arteriogram. Furthermore, the volume of collateral circulation and its effectiveness cannot be evaluated by contrast visualization. It is a widely Progressiw of Coronary Atherosclkrosis. held assumption that obstructjve coronary artery lesions inevitably progress. Many clmlcal and s,urgical decisions are based on the premise that a partially obstructing plaque will, in time, completely occlude the vessel. This view grossly oversimplifies the natural history of coronary artery disease because plaques differ morphologically and progression is a highly variable process. Pathologists recognize active plaques, rich in lipid deposits,
PASTERNAK
which tend to grow, but also fibrous plaques, which are considered “burned out” [3]. Occlusion of an artery is not necessarily caused by a gradual growth of plaque, but it is frequently produced by other mechanisms individually or in combination: rupture of a plaque, development of a subintimal hemorrhage or thrombus formation. A superimposition of coronary artery spasm has also recently been suggested [l4]. These mechanisms involve an abrupt increase in the degree of stenosis or a sudden occlusion, which may occur in previously severely stenosed arteries, although they are not limited to them. Thus, myocardial infarction may be caused by a gradual completion of a chronic occlusive process or by any one of these accelerated events. The former may be anticipated, the latter are often unexpected. It is clear that the separation of progressive lesions from nonprogressive lesions and the knowledge of the rate of progression are among the most critical issues in the natural history or coronary artery disease. Nonprogressive lesions produce a stable status; slowly progressive lesions permit the formation of collateral circulation which may, in part or entirely, compensate the effects of stenosis. Rapidly progressive lesions are presumably responsible for angina pectoris, particularly its unstable form, and for myocardial infarction. Relatively little is known regarding the ratio of progressive versus nonprogressive lesions and the rate of progression. Reports have documented different rates. Bennis et al. [15]found progressive lesions in 52 percent of the patients studied serially over an average two year period. Marchandise et al. [16]found no evidence of progression in normal and mildly diseased coronary arteries over an average 42 month period; however, in moderately stenosed arteries progression occured in 20 percent of the cases. Bourassa [17] reported progression of moderately severe lesions in one-third of the cases in his series over an average six year period; they developed mostly in patients who showed a corresponding increase in symptoms. Clinical Implications. The clinical manifestations of coronary artery disease are caused by myocardial ischemia and its various consequences. It follows that stenotic lesions, which have not yet reached the point of critical narrowing for the production of myocardial ischemia, may or may not be of potential clinical significance, depending on whether the lesion is a progressive one and whether there is time for compensatory development of collateral circulation. As pointed out, the critical severity of stenosis at which the coronary reserve first begins to be impaired involves a reduction of the lumen to about 15 percent of its control level (i.e., 85 percent luminal area stenosis); considering that in most studies “significant” lesions are diagnosed at a lesser degree of stenosis, many lesions demonstrated by coronary arteriography are clinically silent. In view of the margin of error in estimating the severity of stenotic lesions, the abrupt, exponential
April 1981
The American Journal of Medicine
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EDITORIALS-SELZER.
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change in resistance occurring in the critical zone, and the modifying factors already discussed, it becomes apparent that coronary artery disease as demonstrated by coronary arteriography is of limited clinical and prognostic significance, unless physiologic consequences can be evaluated and taken into consideration. The reliable physiologic method of evaluating stenotic lesions is not available in the clinical setting at present, namely, measurement of the pressure gradient and flow in the stenotic artery. One can now only estimate the consequence of coronary stenosis indirectly by symptoms, electrocardiographic changes, perfusion isotope scanning and hemodynamic abnormalities. The clinical manifestation of reduced flow producing myocardial ischemia is angina pectoris. Effort angina implies reduction of reserve coronary flow: angina at rest suggests that the myocardial flow is jeopardized at a point close to the resting level or implies coronary spasm: progression of angina may be related to an increase in stenosis without the simultaneous development of collateral circulation. Reversible changes in the S-T segment of the electrocardiogram, developing during attacks of chest pain-be it a spontaneous angina1 attack or produced by exercise tests-confirms reliably the presence of myocardial ischemia, especially when the observed changes are of considerable magnitude. Thallium-201 perfusion studies performed during ischemia (postexercise) may also provide confirmation of myocardial ischemia. Furthermore, the location and magnitude of ischemia change can often be evaluated by these studies, Hemodynamic consequences of ischemia, namely, reversible wall-motion abnormalities of the left ventricle, development of high left atria1 pressure or of mitral regurgitation, are significant diagnostic observations. Gated blood pool scanning permits noninvasive evaluation of wall motion abnormalities as well as changes in ejection fraction with exercise. There are inherent limitations in some of these tests for ischemia: painless ischemia does occur: electrocardiographic and nuclide changes are semiquantitative and involve both false-positive and false-negative results. Nevertheless, clinical observations and tests, especially when used in combination with each other, provide evidence for the physiologic consequences of coronary artery stenosis that arteriography is incapable of supplying. The prognostic evaluation of patients with coronary artery disease as well as the decision making regarding possible surgical revascularization are customarily based on the number of vessels showing significant coronary artery stenosis. This is based on several epidemiologic studies showing differences in survival of patients depending upon the number of vessels showing atherosclerotic changes. This appraisal of patients with coronary disease has serious drawbacks when applied to individual cases. It encourages reliance upon morphologic changes as the sole criterion. The fact that epidemiologic studies were performed entirely on
750
April 1981
The American Journal of Medicine
symptomatic patients is often ignored, and prognostic data are extrapolated to asymptomatic patients with arteriographic evidence of coronary disease-with decisions being based on criteria for which there is no clinical basis in fact. Furthermore, a group of patients with a certain morphologic pattern contain a mixture of those who become severely ischemic and others who have lesions well compensated by collaterals. Finally, even the pure morphologic criteria are indefinite with wide variation of the severity of involvement of each vessel to be counted as “diseased.” It should be pointed out that even from the epidemiologic standpoint, data are now available to show that functional myocardial indices (e.g., ejection fraction) are independent prognostic indicators that outweigh the importance of the number of affected vessels [l&20]. Thus, in individual decison making regarding prognosis and management of a patient, symptoms, hemodynamic performance, electrocardiographic changes and dynamic evaluation (stress testing and radionuclide studies] are of infinitely greater importance than simply the number of arteries showing atherosclerotic changes. In conclusion, arguments are presented that the morphologic image of the coronary circulation as seen in the coronary arteriogram is of limited value as a sole determinant of the patient’s prognosis or as a sole basis for therapeutic decision making. Morphologic abnormalities should be interpreted in the light of their physiologic effects upon the myocardium, and judged on the basis of clinical manifestations of disease and various functional indices. ‘Only when the triad of morphologic changes, physiologic consequences and clinical manifestations are given equal weight can evaluation of coronary artery disease be considered complete. REFERENCES 1. Phibbs B: The abuse of coronary arteriography. N Engl J Med 1979; 301: 1394-1396. 2. Varnauskas E: Need for coronary bypass surgery in Europe. In: Roskamm H, Schmuziger M. eds. Coronary heart surgery. Berlin Heidelberg, New York: Springer Verlag, 1979; 385-388. 3. Vlodaver Z, Edwards JE: Pathology of coronary artherosclerosis. Prog Cardiovasc Dis 1971: 14: 256274. 4. Zir LM, Miller SW, Dinsmore RE. Gilbert JP. Hawthorne JW: Interobserver variability in coronary arteriography. Circulation 1976; 53: 627-632. 5. Arnett EN, Isner JM, Redwood DR. et al.: Coronary artery narrowing in coronary heart disease. Comparison of cineangiographic and necropsy findings. Ann Intern Med 1979.91: 330-356. 6. McMahon MM, Brown BG. Cukingnan R, et al.: Quantitative coronarv anaioaraohv: measurements of the “critical” stenosis”in p&e&swiih unstable angina and single vessel disease without collaterals. Circulation 1979; 60: 106113. 7. Seizer A: Computer assisted measurements of coronary artery stenosis: letter to the editor. Circulation 1979; 60: 1196. 8. Gould KL. Lioscomb K. Hamilton GW: Pathologic basis for assessing &tical coronary stenosis. Am J Car&o1 1974; 3: 87-94. 9. Gould KL, Lipscomb K: Effect of coronary stenosis on coro-
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10. 11. 12.
13. 14. 15.
nary flow reserve and resistance. Am J Cardiol1974; 34: 48-55. Gould KL: Pressure flow characteristics of coronary stenosis in unsedated dogs at rest and during coronary vasodilatation. Circ Res 1978; 43: 242-253. Baroldi G. Scomazzoni G: Coronary circulation in the normal and pathological heart. Washington, D.C., Office of the Sureeon General. Denartment of the Armv. 1967. Goldbgrg S, Grossman W, Markis JE, Cohen MV, Baltaxe HA, Levin DC: Total occlusion of the left main coronary artery. A clinical, hemodynamic and angiographic profile. Am-J Med 1978; 64: 3-8. Greenspan M, Iskandrian AS, Segal BL, Kimbris D, Bemia CE: Complete occhrsion of the left main coronary artery. Am Heart 1 1979: 98: 83-86. Maseri A, L’Abbate A, Baroldi G, et al.: Coronary vasospasm as a uossible cause of mvocardial infarction. N EngIl _ I Med 1978’ 299: 1271. Bennis CE, Gorlin R, Kemp HG, Herman MV: Progression of coronary artery disease. A clinical arteriographic study.
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Circulation 1973; 47: 455-464. 16. Marchandise B, Bourassa MG, Chaitman BR, Lesperance J: Angiographic evaluation of the natural history of normal coronary arteries and mild coronary atherosclerosis. Am J Cardioll978; 41: 216-220. 17. Bourassa MG: Presentation of the 28 Annual Scientific Session. American Colleee of Cardiolosvv. _” Miami Beach. March 11%15,1979. U 18. Vliekstra RE. Assad-Morel] IL. Frve RL, et al.: Survival predictors in coronary artery disease; medical and surgical comoarison. Mavo Chn Proc 1977: 52: 85-90. 19. Gross 8. Vaid AK, Cohen MV: Prognosis of patients rejected for coronary revascularisation surgery. Am J Med 1978; 64: 9-20. 20. Hammermeister KE. DeRouen TA, Dodge HT: Variables predictive of survival in patients with coronary artery disease. Selection bv univariate and multivariate analyses from the clinical, electrocardiographic, exercise, arteriographic and quantitative angiographic evaluations. Circulation 1979; 59: 421-430.
April 1981
The American Journal of Medicine
Volume 70
751
alf a century
SELZER,
M.D. and RICHARD
ago the clinician was guided in his and therapeutic endeavors by morphologic criteria, mostly based on postmortem examination. During the past few decades the emphasis has shifted from purely morphologic approaches to physiologic and biochemical aspects of disease. In the field of cardiovascular diseases spectacular advances are related to better understanding of physiologic and functional alterations of the cardiovascular system, to the capability of clinical assessment of pathophysiologic disorders and to precise in vivo recognition of morphologic changes. Thus, the decision making process in cardiology is based on physiologic, functional and morphologic considerations. Yet, in coronary artery disease the enthusiasm generated by the development of coronary arteriography once again placed morphology in a preeminent position. Anatomic changes in the coronary artery, demonstrated by the injection of a contrast medium, became the principal-and in many cases the only-yardstick in the decision making process. Coronary arteriography is closely tied in with surgical revascularization of the myocardium, inasmuch as the principal indication for performing this test is to assess a patient for the aortocoronary bypass operation. There are two aspects of surgical treatment of coronary artery disease: the remedial aspect and the prophylactic aspect. In the former case, the typical patient suffers from disabling chest pain; the physician establishes the ischemic origin of the pain; coronary arteriography is performed to assess the morphologic abnormalities and the suitability of the obstructing lesions for a bypass operation. Prophylactic operations aim at preventing myocardial infarction or death: here morphologic considerations are paramount; functional and physiologic aspects are considered unimportant or even irrelevant. The remedial use of myocardial surgical revascularization is widely accepted as a major advance in cardiovascular diseases. Its prophylactic use is the subject of a controversy and is being hotly debated in medical
H diagnostic
C. PASTERNAK,
M.D.
journals. Opinions have been expressed as to wide overuse of coronary arteriography [l] and aortocoronary bypass operations [z] due to overemphasis on prophylactic aspects of the operation. The purpose of the following discussion is to review the question as to whether the present basis of our knowledge justifies morphologic consideration as the sole basis for clinical decisions. A review of this problem requires answers to the following questions. (1) How reliable is arteriographic estimation of coronary artery stenotic lesions? (2) How effective are adaptive and compensatory processes in the coronary circulation? (3) Are all lesions equally threatening, i.e., is their progression inevitable? (4) How reliable (or unreliable) are clinical manifestations of reduced myocardial blood supply? Reliabilityof Coronary Arteriography. Considerable technical advances have been made during the past decade that permit a clearer cineangiogram of the coronary circulation and facilitate correct interpretation of obstructive lesions. Nevertheless, the accuracy of evaluating the severity of lesions is overrated, and the custom of expressing the degree of narrowing in terms of percentages tends to mislead the clinician who may be inclined to take this literally. Coronary arteriography requires multiple injections of the contrast medium in various projections to visualize the coronary arteries adequately. The anatomic course of coronary arteries tends to be tortuous, hence coronary arterial segments can be seen perpendicular to the filming plane, parallel to it or at any angle to it. A stenotic lesion is shown in the segment parallel to the film in its true linear projection, whereas in the perpendicular projection, it may not be visible at all. In addition to problems related to the angle of the stenotic segment to the film, superimposition of other coronary branches or of the coronary catheter may interfere with the visibility of the stenotic area. The arteriographer is thus accustomed to seeing the stenotic segment in some projections but not in others. The projection showing the narrowest-almost always the best seen-segment is the
From the Division of Cardiology, Presbyterian Hospital of Pacific Medical Center, San Francisco, California. Requests for reprints should be addressed to Dr. Arthur Seizer. Division of Cardiology, Pacific Medical Center, P.O. Box 7999, San Francisco, CA 94120.
April 1981
The American Journal of Medicine
Volume 70
747
EDITORIALS-SELZER.
I 0
PASTERNAK
rI
c.
0) 8
igure 1. Diagrammatic presentation of arteriographic image of stenotic coronary arteries shown in the projection presenting the most severe narrowing (above) and crosssection of the artery across the stenotic portion (below). A, central lumen; B, eccentric slit-like stenotic lumen causing overestimation of the severity of stenosis; C, eccentric crescentic stenotic lumen causing underestimation of the severity of stenosis.
basis for calculating the severity of the stenosis. Calculations of the degree of stenosis are based on the assumption that the stenosed lumen is circular. The arteriographer estimates the linear diameter of the narrowest level and expresses it as a percentage of the “normal” diameter of that vessel and, on this basis, calculates luminal area stenosis. Occasionally, confusion may develop whether “percent stenosis” expresses linear or area stenosis if this point is not specifically indicated (e.g., a 50 percent linear stenosis indicates a 75 percent area stenosis of a circular orifice). The accuracy of evaluating the degree of stenosis involves several assumptions: that the “measurement” of the narrowest level of stenosis is correct: that the residual lumen of the stenotic segment is circular; and that the nonstenotic artery represents the true control level (i.e., is not diffusely narrowed). Of these assumptions, the most fallacious is the acceptance that a circular lumen is the rule, i.e., a circumferential plaque producing an hour-glass type lesion. On the contrary, plaques tend to be irregularly shaped, producing lumens that are elliptic, crescentic or slit-like [3]. Our review of 12 random coronary arteriograms, obtained to evaluate the location of the remaining lumen in stenotic vessels, showed that in the 20 severe localized coronary lesions found, 40 percent had a central lumen whereas in 60 percent it was eccentric. Figure 1 presents in a diagrammatic form three lesions of round, crescentic and slit-like shape, illustrating the gross overestimation or underestimation of the severity of the lesion when the shape is other than circular. The imprecise and subjective manner of interpretating coronary arteriograms is illustrated by studies
748
April 1981
The American Journal of Medicine
comparing reports of multiple readers and showing frequent disagreement between them [4]. Comparison of angiographic evaluation of coronary stenosis with postmortem examination of the vessels emphasizes further the frequent discrepancy between the two [5]. Recently, attempts have been made to refine the accuracy of coronary arteriography by using computerized analysis of stenotic lesions [6]. Although this technique unquestionably enhances the capability of evaluating stenotic lesions more precisely than visual inspection, it assumes a circular or elyptic lumen. In the presence of irregularly shaped, crescentic or slit-like lumens, computer reading of arteriograms may be just as likely to underestimate or overestimate lesions as does the angiography [7]. It is evident from the foregoing discussion that there are serious reservations regarding the prevailing custom of expressing arteriographic images of coronary plaques in terms of percent stenosis of the lumen. In the first place, this implies a precision in measurement when none exists. Furthermore, it ignores the modifiers that can enhance or minimize the effect of stenosis upon myocardial perfusion, such as the effect of other stenotic lesions in the affected vessel, the length of the stenotic segment or the diffuse atherosclerotic changes reducing the caliber of the “nonstenosed” portion of the artery with which the luminal narrowing is compared. Clinical decisions are often based on these numerical presentations of coronary arterial stenoses, accepting them as accurate. Perhaps a semiquantitative evaluation of coronary artery stenotic lesions, such as “mild,” “modFurthererate, ” “severe” would be more appropriate. more, even if the degree of the narrowing could be evaluated more accurately,, the physiologic consequences of the stenosis and its role in the production of ischemia cannot be deduced from the anatomy alone, considering the many physiologic factors affecting coronary flow through stenotic arteries. Effects and Consequences of Coronary Artery Stenosis. When an atherosclerotic plaque develops in a coronqry artery, it does not affect myocardial blood flow until it severely obstructs the lumen of the artery. Best available experimental evidence [8-lo] indicates that in order to interfere with the maximum coronary flow (i.e., myocardial oxygen supply for its highest requirement, e.g., strenuous exercise] the lumen has to be reduced to 15 percent of its original area, which in a coronary arteriogram would be shown as a 60 to 65 percent linear lesion, provided the stenotic lumen is circular. The lumen has to be reduced to 5 percent (85 percent to 90 percent of linear stenosis) to affect resting myocardial oxygen supply. In physiologic terms, a plaque protuding into the lumen of a coronary artery has to obstruct most of the lumen in order to generate resistance to flow and generate a pressure gradient (decrease in arterial pressure in the artery distal to the obstruction]. The pressure gradient is related to the magnitude of flow, hence different degrees of obstruction are necessary to produce
Volume 70
EDITORIALS-SELZER,
&hernia at the maximal and at the minimal (or resting) flow through a given artery. It follows that the effect of coronary stenosis upon myocardial oxygen supply can be expressed as an exponential relationship, namely, there is no effect up to the critical zone of narrowing; once this zone is entered, minute increments 13 stenosis will produce large increases in pressure gradient, i.e., decrease in coronary flow. Experimental studies by Gould et al. [&lo] demonstrated the importance of factors other than the degree of narrowing which can act as modifiers. Given two identical degrees of stenosis, one of greater length will restrict myocardial flow more than the shorter one. In the presence of multiple areas of stenosis, reduction in coronary flow is not determined by the most severe degree of stenosis: milder stenoses provide additive effects like resistors in a series, further restricting coronary flow. Even the presence or absence of poststenotic dilatation of a coronary artery may influence myocardial perfusion. However, the most important modifier affecting coronary flow is the magnitude of available collateral flow. The development of physiologically significant coronary artery stenosis induces an immediate compensatory reaction. There are physiologic collateral vessels connecting coronary branches, which are no larger than ZOO p and which are incapable of supplying more than a fraction of the deficient blood supply [ll]. However, myocardial ischemia stimulates growth of larger collateral vessels which may eventually carry enough volume to compensate fully obstructing lesions. It is not unusual to find complete occlusion of the right coronary artery without having produced myocardial infarction. There are even a number of cases on record of complete occlusion of the main left coronary artery with survival and with relatively little evidence of myocardial ischemia [l&13]. It should be pointed out that coronary arteriography is capable of visualizing only some types of collateral vessels. Contrast visualization will show retrograde filling of a completely occluded artery, and of a nonvisualized artery belonging to the other coronary system (e.g., left anterior descending branch visualized with injection of the right coronary artery system). However, collateral vessels forming within one coronary artery system and conpensating a partially occluded vessel may not be seen in the coronary arteriogram. Furthermore, the volume of collateral circulation and its effectiveness cannot be evaluated by contrast visualization. It is a widely Progressiw of Coronary Atherosclkrosis. held assumption that obstructjve coronary artery lesions inevitably progress. Many clmlcal and s,urgical decisions are based on the premise that a partially obstructing plaque will, in time, completely occlude the vessel. This view grossly oversimplifies the natural history of coronary artery disease because plaques differ morphologically and progression is a highly variable process. Pathologists recognize active plaques, rich in lipid deposits,
PASTERNAK
which tend to grow, but also fibrous plaques, which are considered “burned out” [3]. Occlusion of an artery is not necessarily caused by a gradual growth of plaque, but it is frequently produced by other mechanisms individually or in combination: rupture of a plaque, development of a subintimal hemorrhage or thrombus formation. A superimposition of coronary artery spasm has also recently been suggested [l4]. These mechanisms involve an abrupt increase in the degree of stenosis or a sudden occlusion, which may occur in previously severely stenosed arteries, although they are not limited to them. Thus, myocardial infarction may be caused by a gradual completion of a chronic occlusive process or by any one of these accelerated events. The former may be anticipated, the latter are often unexpected. It is clear that the separation of progressive lesions from nonprogressive lesions and the knowledge of the rate of progression are among the most critical issues in the natural history or coronary artery disease. Nonprogressive lesions produce a stable status; slowly progressive lesions permit the formation of collateral circulation which may, in part or entirely, compensate the effects of stenosis. Rapidly progressive lesions are presumably responsible for angina pectoris, particularly its unstable form, and for myocardial infarction. Relatively little is known regarding the ratio of progressive versus nonprogressive lesions and the rate of progression. Reports have documented different rates. Bennis et al. [15]found progressive lesions in 52 percent of the patients studied serially over an average two year period. Marchandise et al. [16]found no evidence of progression in normal and mildly diseased coronary arteries over an average 42 month period; however, in moderately stenosed arteries progression occured in 20 percent of the cases. Bourassa [17] reported progression of moderately severe lesions in one-third of the cases in his series over an average six year period; they developed mostly in patients who showed a corresponding increase in symptoms. Clinical Implications. The clinical manifestations of coronary artery disease are caused by myocardial ischemia and its various consequences. It follows that stenotic lesions, which have not yet reached the point of critical narrowing for the production of myocardial ischemia, may or may not be of potential clinical significance, depending on whether the lesion is a progressive one and whether there is time for compensatory development of collateral circulation. As pointed out, the critical severity of stenosis at which the coronary reserve first begins to be impaired involves a reduction of the lumen to about 15 percent of its control level (i.e., 85 percent luminal area stenosis); considering that in most studies “significant” lesions are diagnosed at a lesser degree of stenosis, many lesions demonstrated by coronary arteriography are clinically silent. In view of the margin of error in estimating the severity of stenotic lesions, the abrupt, exponential
April 1981
The American Journal of Medicine
Volume 70
749
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change in resistance occurring in the critical zone, and the modifying factors already discussed, it becomes apparent that coronary artery disease as demonstrated by coronary arteriography is of limited clinical and prognostic significance, unless physiologic consequences can be evaluated and taken into consideration. The reliable physiologic method of evaluating stenotic lesions is not available in the clinical setting at present, namely, measurement of the pressure gradient and flow in the stenotic artery. One can now only estimate the consequence of coronary stenosis indirectly by symptoms, electrocardiographic changes, perfusion isotope scanning and hemodynamic abnormalities. The clinical manifestation of reduced flow producing myocardial ischemia is angina pectoris. Effort angina implies reduction of reserve coronary flow: angina at rest suggests that the myocardial flow is jeopardized at a point close to the resting level or implies coronary spasm: progression of angina may be related to an increase in stenosis without the simultaneous development of collateral circulation. Reversible changes in the S-T segment of the electrocardiogram, developing during attacks of chest pain-be it a spontaneous angina1 attack or produced by exercise tests-confirms reliably the presence of myocardial ischemia, especially when the observed changes are of considerable magnitude. Thallium-201 perfusion studies performed during ischemia (postexercise) may also provide confirmation of myocardial ischemia. Furthermore, the location and magnitude of ischemia change can often be evaluated by these studies, Hemodynamic consequences of ischemia, namely, reversible wall-motion abnormalities of the left ventricle, development of high left atria1 pressure or of mitral regurgitation, are significant diagnostic observations. Gated blood pool scanning permits noninvasive evaluation of wall motion abnormalities as well as changes in ejection fraction with exercise. There are inherent limitations in some of these tests for ischemia: painless ischemia does occur: electrocardiographic and nuclide changes are semiquantitative and involve both false-positive and false-negative results. Nevertheless, clinical observations and tests, especially when used in combination with each other, provide evidence for the physiologic consequences of coronary artery stenosis that arteriography is incapable of supplying. The prognostic evaluation of patients with coronary artery disease as well as the decision making regarding possible surgical revascularization are customarily based on the number of vessels showing significant coronary artery stenosis. This is based on several epidemiologic studies showing differences in survival of patients depending upon the number of vessels showing atherosclerotic changes. This appraisal of patients with coronary disease has serious drawbacks when applied to individual cases. It encourages reliance upon morphologic changes as the sole criterion. The fact that epidemiologic studies were performed entirely on
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symptomatic patients is often ignored, and prognostic data are extrapolated to asymptomatic patients with arteriographic evidence of coronary disease-with decisions being based on criteria for which there is no clinical basis in fact. Furthermore, a group of patients with a certain morphologic pattern contain a mixture of those who become severely ischemic and others who have lesions well compensated by collaterals. Finally, even the pure morphologic criteria are indefinite with wide variation of the severity of involvement of each vessel to be counted as “diseased.” It should be pointed out that even from the epidemiologic standpoint, data are now available to show that functional myocardial indices (e.g., ejection fraction) are independent prognostic indicators that outweigh the importance of the number of affected vessels [l&20]. Thus, in individual decison making regarding prognosis and management of a patient, symptoms, hemodynamic performance, electrocardiographic changes and dynamic evaluation (stress testing and radionuclide studies] are of infinitely greater importance than simply the number of arteries showing atherosclerotic changes. In conclusion, arguments are presented that the morphologic image of the coronary circulation as seen in the coronary arteriogram is of limited value as a sole determinant of the patient’s prognosis or as a sole basis for therapeutic decision making. Morphologic abnormalities should be interpreted in the light of their physiologic effects upon the myocardium, and judged on the basis of clinical manifestations of disease and various functional indices. ‘Only when the triad of morphologic changes, physiologic consequences and clinical manifestations are given equal weight can evaluation of coronary artery disease be considered complete. REFERENCES 1. Phibbs B: The abuse of coronary arteriography. N Engl J Med 1979; 301: 1394-1396. 2. Varnauskas E: Need for coronary bypass surgery in Europe. In: Roskamm H, Schmuziger M. eds. Coronary heart surgery. Berlin Heidelberg, New York: Springer Verlag, 1979; 385-388. 3. Vlodaver Z, Edwards JE: Pathology of coronary artherosclerosis. Prog Cardiovasc Dis 1971: 14: 256274. 4. Zir LM, Miller SW, Dinsmore RE. Gilbert JP. Hawthorne JW: Interobserver variability in coronary arteriography. Circulation 1976; 53: 627-632. 5. Arnett EN, Isner JM, Redwood DR. et al.: Coronary artery narrowing in coronary heart disease. Comparison of cineangiographic and necropsy findings. Ann Intern Med 1979.91: 330-356. 6. McMahon MM, Brown BG. Cukingnan R, et al.: Quantitative coronarv anaioaraohv: measurements of the “critical” stenosis”in p&e&swiih unstable angina and single vessel disease without collaterals. Circulation 1979; 60: 106113. 7. Seizer A: Computer assisted measurements of coronary artery stenosis: letter to the editor. Circulation 1979; 60: 1196. 8. Gould KL. Lioscomb K. Hamilton GW: Pathologic basis for assessing &tical coronary stenosis. Am J Car&o1 1974; 3: 87-94. 9. Gould KL, Lipscomb K: Effect of coronary stenosis on coro-
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10. 11. 12.
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nary flow reserve and resistance. Am J Cardiol1974; 34: 48-55. Gould KL: Pressure flow characteristics of coronary stenosis in unsedated dogs at rest and during coronary vasodilatation. Circ Res 1978; 43: 242-253. Baroldi G. Scomazzoni G: Coronary circulation in the normal and pathological heart. Washington, D.C., Office of the Sureeon General. Denartment of the Armv. 1967. Goldbgrg S, Grossman W, Markis JE, Cohen MV, Baltaxe HA, Levin DC: Total occlusion of the left main coronary artery. A clinical, hemodynamic and angiographic profile. Am-J Med 1978; 64: 3-8. Greenspan M, Iskandrian AS, Segal BL, Kimbris D, Bemia CE: Complete occhrsion of the left main coronary artery. Am Heart 1 1979: 98: 83-86. Maseri A, L’Abbate A, Baroldi G, et al.: Coronary vasospasm as a uossible cause of mvocardial infarction. N EngIl _ I Med 1978’ 299: 1271. Bennis CE, Gorlin R, Kemp HG, Herman MV: Progression of coronary artery disease. A clinical arteriographic study.
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Circulation 1973; 47: 455-464. 16. Marchandise B, Bourassa MG, Chaitman BR, Lesperance J: Angiographic evaluation of the natural history of normal coronary arteries and mild coronary atherosclerosis. Am J Cardioll978; 41: 216-220. 17. Bourassa MG: Presentation of the 28 Annual Scientific Session. American Colleee of Cardiolosvv. _” Miami Beach. March 11%15,1979. U 18. Vliekstra RE. Assad-Morel] IL. Frve RL, et al.: Survival predictors in coronary artery disease; medical and surgical comoarison. Mavo Chn Proc 1977: 52: 85-90. 19. Gross 8. Vaid AK, Cohen MV: Prognosis of patients rejected for coronary revascularisation surgery. Am J Med 1978; 64: 9-20. 20. Hammermeister KE. DeRouen TA, Dodge HT: Variables predictive of survival in patients with coronary artery disease. Selection bv univariate and multivariate analyses from the clinical, electrocardiographic, exercise, arteriographic and quantitative angiographic evaluations. Circulation 1979; 59: 421-430.
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