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Regional Coronary Anatomy in Rest Angina
Regional Coronary Anatomy in Rest Angina· Comparison of Patients wlth Rest and Exertional Angina using Quantitative Coronary Angiography John R. Wilson, M.D.; Jack L. Martin, M.D.;f William 1. Untereker, M.D.;t and 10hn W. Hirshfeld, /r., M.D.
To determine If padeDti with rest ........ bave more _vere feIIoIuII ischemia than patieDts with esertlo.... ........, we eompued the severity of left com...." IIItery (LeA) In 29 padeDb witla tnlDsieDt mterlol" lldaemle ST-T e at reIt, _d 30 patIe... with _terlor ST e es oDly d....... esedioD. The peraat. .e diameter ateDOlls • • measured with Vernier callpen • (2 X lesion diameter X 100 perceDt)/(prelienotle + postiteDOtic diameter). There W8I DO dIrf..-ace betweeD tile two are-.. ID the ..... diameter _DOlls of _ocduded LeA vessels either wheD ... ftIIeII were eompued (rest: 6' ± 12 pereeDt; esertIoIud: 70 ± 13 pereent [p=NSD or wheD oDly the _um-. stenosis In each patleDt was com.... (rest:
ste.....
T heduction role of coronary anatomic factors in the proof rest angina is uncertain. Previous
studies have demonstrated that the distribution of coronary angiographic lesions in patients with rest and exertional angina are similar,'? suggesting that anatomic factors are not responsible for rest angina. However, these studies have not specifically compared the degree of coronary stenosis and collateralization in the region of ischemia. Therefore, it remains possible that rest angina is due to more severe regional ischemia than in exertional angina. Moreover, with only one exception, previous studies have used qualitative methods to evaluate coronary angiograms. This approach has a high intra- and interobserver variability and therefore does not permit accurate quantitative comparisons of lesion severity.8-10 In the presence of coronary stenoses greater than 60 percent, minor increases in stenosis severity can have major effects on coronary reserve.11 Therefore, studies in which qualitative techniques were used to compare angiographic lesions in rest -From the CardJac Hemodynamic Laboratories, Hospital of the University'of ~Iy&nia, and the Cardiovascular See-
tion, DeparbDent of Medicine, University of PeDDSYlvania School ol Medicine, PbiladeJ~~ f$upported by a research fellowship from the American Heart Association, Southeastern Pe~lvania Chapter. ~Supported by a SPecial InvestigatorsbiP from the American Heart Aaociation, Southeuteni PeDD8)'lvania Chapter. Manuscript received January 21; revision ~~ April 21. Reprint requatl: Dr. Wa.on, Ht}lJ?ittJL Unbmtv of PBM8fIlotJnUJ, 3400 Spruce Street, PhlladelphltJ 19096
411
74 ± 10 percent; uertiomII: 75 ± 12 peraDt [p=NS)). To... oc:eIuIioD of at last _e major v.... of the LeA .... oeconed with IimUar freq8eney In pade.. with nit ('/29) _d esertlo.... (12/30) (p=NS). However, coIIatend developllleDt to 76-100 perceDt LeA I_OBI slpUlcBDtIy I. . frecpaeDt In rest ...... (4/21 v ' " [I' percentD tIuua ID esertlo.... ....... (21/30 v-els [70 perceDtD, ( p < .03). We eoDdll4e tIIat patient. wItIa rest ........ do DOt have more severe COIOII8I)' IteDOIes tIuua ..tIe.ts _ uerdonal ......., bid fnqaeDtIy may have IDOn seven regIo.... .hemla due to reduced eoIIaterizadoD of Jeopardized myocardium.
w.
and exertional angina may have overlooked small but important differences in severity of stenosis. The present study was therefore undertaken to determine if patients with angina at rest have more severe coronary obstruction and/or less collateralizanon in the region of ischemia than patients with exertional angina. Anterior ST-T changes have been shown to correspond anatomically to ischemia in the distribution of the left coronary artery.11 Accordingly, the degree of left coronary artery stenosis and collateralization was compared in patients with reversible ST-T changes in the anterior precordial leads at rest and patients with similar ECG changes during exertion. Coronary angiograms were analyzed using a quantitative technique. METHODS
Patient Selection Patients with rest angina were selected by reviewing aD
cardiac catheterization reports on patients studied between January, 1974 and January, 1981 at the Hospital of the University of PeDD8)'lvania. Patients were identiSed who had ODe or more episodes of tmplOvoked resting chest pain ac-
>1
companied by transient mm ST-seJPDent elevation or depression or marked T -wave changes in the electrocardiographic leads Vt, V 2 , Va and/or V" within two weeks prior to cardiac catheterization. Patients with Q waves in the anteriol' leads, enzymatic evidence of myocardial necrosis and <50 percent left coronary artery stenosis were excluded. Thirty-three patients fuIfllled these criteria, 29 of whom Regional Coronary Anatomy In Reel Angina (WI/.on .t al)
had high quality angiographic studies available for analysis. None of the patients underwent ergonovine testing due to the presence of significant fixed coronary artery lesions. For comparison, a second group of patients with exertional angina and no history of rest or noctuma1 angina were identified as follows. All exercise stress test reports on patients studied between August, 1978 and January, 1981 were reviewed to identify patients with exertional angina who developed chest pain accompanied by 1 mm horizontal or down-sloping ST-segment depression or > 1 mm STsegment elevation in Vt, V2 , Va and/or V.. Cardiac catheterization reports were then reviewed to identify those patients who also underwent cardiac catheterization within two weeks of exercise testing. From this group, patients with Q waves in the anterior ECG leads, conduction disturbances, and/or insignificant coronary artery stenosis were excluded. Thirty patients fuI8lled these criteria for inclusion in the exertional angina group.
>
Angiographic AntJIy8f8
Selective coronary arteriography was performed using either the Sones or Judkins technique. Nitrates were withheld for at least six hours prior to catheterization. Angiography was performed with a Philips 6-inch image intensi6er and recorded on 35 mm film. Studies .mcluded left ventriculography in the right anterior oblique projection and selective left and right coronary arteriography. Coronary arteriography was routinely performed in right and left anterior oblique projections, as well as in various other views to maximally visualize coronary occlusions. Films were analyzed independently by two reviewers according to the technique of RafIIenbuel and co-workers.s Reviewers were blinded to the patient's clinical history. Each fllm was projected on a Vanguard XR-35 projector (8 x 10 inch screen). The extent of coronary obstruction was measured with a Vernier caliper (LS Starrett Company) (accuracy = 0.04 mm.) Measurements were performed near the center of the x-ray beam and only at end-diastole. Because of the eccentric lumen of many obstructions, lesions were measured in as many projections as possible. Three segments were measured: the pre-stenotic vessel diameter, the narrowest diameter of the obstructed area, and the poststenotic diameter. The percentage of obstruction was calculated as:
=
percent diameter stenosis 2 X lesion diameter X 100 percent pre-stenotic + post-stenotic diameter To establish the precision of measurements, the degree of stenosis of 29 obstructed lesions in 17 angiograms were analyzed at two different times by the same observer. Differences in severity of stenosis averaged 4 ± 4 percent (range: 0-12 percent). Variability between measurements made by the two observers averaged 5 ± 5 percent (range: ().,16 percent). Reported stenosis diameter represents the average of the measurements made by the two observers. Vessels with obstructions too severe to measure were designated as 90 percent stenosis for purposes of statistical analysis. Collateral flow was considered absent if none was visualized on angiography. Collaterals were considered present if observed to fill either, part or an of the arterial system distal to a lesion. No attempt was made to grade the degree of collateralization since physiologic and technical variables (amount of contrast: agent injected) may substantially iDfluence coUateral visualization.1 8
Table l-C8Jdea1 C~1ia in PIIIierW _ala Read,.. and Eserdonal .4....... Rest (N-29)
±9
Exertional (N-30)
± 8·
Age (years)
54
Sex
24M/SF
29M/IF
Exertional Angina
14/29 (48%)
30/30 (100%)
Resting ECG NSST IMI Normal
16/29 (55%) 2/29 (7%) 11/29 (38%)
13/30 (43%) 5/30 (17%) 12/30 (40%)
EKG with Angina ST ! ST Twave
8/29 (28%) 16/29 (55%) 5/29 (17%)
28/30 (93%)· 2/30 (7%)·
r
58
*p <.05 compared with rest angina group Nonspecific ST and T wave change (NSST); inferior myocardial infarction (IMI) Sta&ffcal AntJlyril
The significance of differences in the distribution and relative severity of disease in each coronary artery wu evaluated with the chi square method. Differences in absolute degree of left coronary artery occlusion was evaluated both with the Student's t-test and with the rank sum test. 1 • Differences in the degree of collateralization was evaluated with the chi square method. A p value < .05 was considered significant.
REsuLTS CUnical Characteristics (Table 1) The patients with rest angina were slightly younger (54 ± 9 years) (mean ± standard deviation) than the patients with exertional angina (58 ± 8 Table 2--ltIasimal De.,._ 01 SIelUMU in Eaela Major Coronary .4rtery in alae PadenU .aIa Read,.. and Eserdo,",' .4r&«ina * <50%
50-75%
76-95%
100%
LAD Rest Exertional
0 3 (iO%)
14 (48%) 12 (40%)
10 (34%) 6 (20%)
5 (18%) 9 (30%)
CxC Rest Exertional
14 (48%) 8 (27%)
8 (28%) 7 (23%)
4 (14%) 5 (17%)
3 (10%) 10 (33%)
LC System Rest Exertional t
14 (24%) 11 (18%)
22 (38%) 19 (32%)
14 (24%) 11 (18%)
8 (14%) 19 (32%)
RCA Rest Exertional
13 (45%) 9 (30%)
8 (28%) 6 (20%)
0(0%) 6 (20%)
8 (27%) 9 (30%)
*No significant difterence was noted between the two groupe using chi square analysis Circumflex coronary artery (CxC); left anterior descending coronary artery (LAD); right coronary artery (RCA) tp-O.ll compared with rest angina CHEST I 82 I 4 I OCTOBER, 1812
417
LEFT CORONARY SYSTEM ANATOMY 100
100
......
...
.. ..•
.....••••
...
..•• •• •• ..•••
• •
o
en
"~
70
.. o e
CD
V)
....Q)CD 60 E
e
o
p=NS
•• •
•• • •• • •• • •
• •• •• •
....'
• •• ••
•• ••• •• •• • 50....-.--....&-...-----=-----.......
....-.~ ....c 90 CD "Z-
cf
.s: u 0
w .5
80
en
..
"~
0
c
CD
70
V)
"0 E
";C 0
~
60
...... • • •• •• •
..••• • • • •
p=NS
•••
•• • •• • •• •• • • •• •
... • •• •
• 50.......---..:.--------~•
Exertional
Rest
Exertional
Rest
Angina
Angina
Angina
Angina
(N=38)
(N=45)
(N=23)
(N=28)
FmUBE 1. Comparison of the degree of steDOIis of UIlOOCluded left corolW)' artery vessels in the patients with restiDI and aertional augiDa. Oil the left, diameter stenosis of aD unoccluded vessels is compared. On the right, diameter IteDosIs of the most severe lesion identdled in each patient is compared.
years) (p <.04). The majority of patients in both groups were men. A history of exertional angina was reported by half of the patients with rest angina.
In the patients with rest angina, ST segmentelevation was observed during angina in 55 percent of the patients, ST segment depression in 28 percent and T wave inversion in 17 percent. Seven of the 16 ~tients with rest angina and ST segment elevation had a history of exertional angina. In the patients with exertional angina and no rest angina, ST-segment depression was noted in 28 patients and ST segment elevation in two.
DUtribution of Coronary Lesions The distribution of coronary lesions was not significantly different in the two patient groups. In the patients with rest angina, ,single vessel disease was noted in 24 percent, double vessel disease in 28 percent, biple vessel disease in 28 percent and left main coronary artery disease in 20 percent The distribution of coronary disease in the patients with exertional angina was 10 percent, 27 percent, 53 percent and 10 percent, respectively. 411
Degree of Stenoaia (Table 2) Total occlusion of at least one major vessel of the left coronary system was observed in six of 29 patients with rest angina versus 12 of 30 patients with exertional angina (p == NS). There was no difference in the mean diameter stenosis of unocc1uded left coronary vessels either when all vessels were compared (rest: 69 ± 12 percent, exertion: 70 ± 13 percent (p == NS» or when the maximal stenosis in each patient was compared (rest: 74 ± 10 percent, exertion: 75 ± 12 percent (p == NS» (Fig 1). Sequential coronary lesions of the left coronary artery were noted in six of the patients with rest angina and four of the patients with exercise angina. Comparisons of coronary lesion severity following exclusion of these patients did not influence the overall results.
Collateral Vessels(Table 3) The incidence of coDateralization to severely stenotic (76-90 percent diameter stenosis) vessels of the left coronary system was significantly less in the patients with rest angina (1/14 [7 percent]) than in Regional Coronary Anatomy In Rnt Angina (Wllaon ., aI)
Table 3--Compari... of I6e lneiffenee of Colltderali"";on for _ Gille. Dep-ee of ConJrlllr7 Saenoai. in PfId.... . .1& Ra' ",.., Eserlional A"';... Percent Stenosis
Rest (N-29)
Exertional (N - 30)
P
LAD 76-00 100
1/10 (10%) 3/4 (75%)
4/6 (67%) 8/9 (89%)
0.10 0.79
CxC 76-90 100
0/4 (0%) 0/3 (0%)
3/6 (50%) 6/9 (67%)
0.19 0.18
LC System 76-00 100 76-100
1/14 (7%) 3/7 (43%) 4/21 (19%)
7/12 (58%) 14/18 (78%) 21/30 (70%)
<.04 0.44 <.03
RCA 76-90 100
8/8 (100%)
1/5 (20%) 9/9 (100%)
Circumflex coronary artery (CxC); left anterior descending coronary artery (LAD); left coronary system (LC system); right coronary artery (RCA)
the patients with exertional angina (7/12 [58 percent] ), (p <.04). Similarly, the incidence of collateraIization to either severely stenotic or totally occluded vessels of the left coronary system was signiflcantly less in the patients with rest angina (4/21 [19 percent]) than in patients with exertional angina (21/30 [70 percent]) (p <.05). In contrast, both groups demonstrate collateralization to all totally occluded right coronary arteries.
Coronary Anatomy and ST-Segment Directional Changes Angiographic findings were similar in patients with rest angina and ST-segment elevation (N = 16) and in patients with ST depression or T wave changes (n = 13). The most severe coronary stenosis of the left coronary system in patients with ST-segment elevation averaged 72 ± 11 percent versus 74 ± 9 percent in the other patients (p = NS ). The distribution of single, double, triple vessel and left main disease were comparable. CollateraIization to the left coronary system distal to areas of 76-100 percent obstruction was observed in 2/13 patients with ST-segment elevation versus 2/10 patients with ST-segment depression or T wave changes (p= NS). DISCUSSION
This study differs in two major ways £rom previous comparative studies of rest and exertional angina. First, coronary angiograms were analyzed using a quantitative rather than qualitative technique. The utility of quantitative techniques and their advantage over qualitative techniques has already been established.I " Second, an attempt was
made to compare angiographic features in the region of ischemia rather than comparing the severity of disease throughout the coronary circulation, as has been done by others. To identify the region of ischemia, the presence of reversible ST-T changes in the anterior precordial leads was considered to correspond anatomically to ischemia in the distribution of the left coronary artery. In support of this approach, Papapietro and co-workers'P have observed that transient ST changes in the anterior pre-· cordial leads in patients with single vessel disease is almost always associated with stenosis of the left anterior descending coronary artery.
Severity of Coronary Lesions in Rest Angina The results of this study indicate that both the overall distribution of coronary lesions and the severity of coronary lesions within the ischemic region are similar in patients with rest and exertional angina. The majority of patients in both groups had double or triple vessel disease, as noted by others.!" In addition, the average diameter stenosis of unoceluded left coronary vessels in the patients with rest angina was comparable to that observed in the patients with exertional angina. The only noteworthy diHerence between lesion severity in the two groups was a higher incidence of 100 percent occlusions of the left coronary vessels in patients with exertional angina. However, this difference was not statistically significant. Neill and co-workers! have recently noted a higher incidence of total left anterior descending occlusion in patients with rest angina.
Reduced Collaterals in Rest Angina The only major anatomic diHerence between the patients with rest and exertional angina was a strikingly lower incidence of collateralization in the patients with rest angina. Collateralization was noted distal to 76-100 percent left coronary artery lesions in only 19 percent of vessels in rest angina coinpared with 70 percent of vessels in exertional angina. In an extensive analysis of collaterals in 200 patients with coronary disease, Levin us noted a 50-60 percent incidence of eollateralization to severely narrowed or completely occluded vessels of the left coronary artery. Thus, the incidence of collateraIization to the left coronary artery in our patients with exertional angina is comparable to that in other populations. Collateralization to the right coronary artery, a vessel presumably Dot involved in the ischemic process in our patients, was also comparable to previous studies both in the patients with rest and the patients with exertional angina. Our finding of reduced collateralization in rest angina is consistent with several previous reports. CHEST I 82 I .. I OCTOBER, 1982
411
In a study of 20 patients with rest angina, Fischl and co-workers- noted a 27 percent incidence of collateralization to the left coronary artery in the presence of severe stenoses and suggested that this incidence was abnormally low. RafIlenbeu1 and coinvestigators' recently noted a 21 percent incidence of collateralization to severely stenotic vessels in 25 patients with rest angina. They also remarked on this finding as abnormal. Finally, intraoperative measurements of retrograde flow in stenosed coronary arteries has detected less retrograde How in patients with rest or prolonged angina than in patients with chronic exertional angina.f Retrograde flow is inHuenced primarily by the extent of collateral flow. In contrast to our findings, Neill and co-workers 1 recently reported no evidence of impaired collateralization in 70 patients with rest angina when compared to 49 patients with exertional angina. This finding may be due to their inclusion of patients with rest angina, but without reversible ST-T changes and of patients with inferior ischemia. It is conceivable that collateralization to the right coronary artery is not impaired in rest angina. Moreover, in the study by Neill and co-workers 1 the incidence of collateralization to severely stenotic coronary arteries was less than 20 percent with exertional angina, an incidence considerably lower than that observed by others. II Potential Limitatiom It would have been of interest to perform ergonovine maleate testing in our patients with rest angina to define the incidence of coronary spasm. However, during the time period that catheterization was performed in these patients, ergonovine testing was considered relatively contraindicated in patients with significant fixed coronary lesions. Our assumption that anterior precordial ST-T changes reflect ischemia in the left coronary artery distribution is consistent with previous studies. I,ll However, it is possible that ischemia in other areas was responsible for the ECG changes in some of the patients. This potential error should occur with similar frequency in both rest and exertional angina and therefore should not significantly Influence our results.
Clinical Implications Our findings suggest that patients with coronary disease and reversible ST-T changes at rest are composed of two anatomic subgroups which are indistinguishable based on ECG criteria. In one subgroup, rest angina is associated with severe fixed 420
coronary stenosis usually without collateralization. This finding suggests that regional ischemia may be more severe in these patients than in patients with exertional angina. In addition, the absence of 001lateralization suggests either abnormally rapid progression in the rate of coronary obstruction or an inability to develop eollaterals." Pathologic studies of coronary arteries obtained from patients with unstable angina have demonstrated an abnormally high incidence of multiple plaque hemorrhages," a finding consistent with rapid progression of coronary lesions. Our data, therefore, suggest that severe flow limitation may play an important role in initiating rest angina in these patients. H this is the case, aggressive early treatment of the underlying coronary obstructive disease might be the optimal approach to therapy in such patients. In a second subgroup, resting ischemia develops in the presence of only moderate coronary stenoses. Transient reductions in coronary flow rather than severe fixed coronary flow limitation is a likely etiology for this type of rest angina. 17, 18 Ergonovine testing in this subgroup probably should be performed. ACKNOWLEDGMENT: The authors thank John Kastor, M.D. for his support and review of the manuscript, Nancy Ferraro. R.N., for technical assistance, and Mrs. Brenda Barnard and Mrs. Pabicia Wyatt for their preparation of the manuscript.
REFERENCES 1 Neill WA, Wharton TP Jr, F1uri-Lundeen J, Cohn IS. Acute coronary insufBciency-coronary occlusion after intermittent ischemic attaclcs. N Engl J Moo 1980; 302:1157-62 . S McMahon MM, Brown G, Culdngnan R, Rolett EL, Bolson E, Frimer M, et ale Quantitative coronary angiography: Measurement of the "critical" stenosis in patients with unstable angina and single-vessel disease without collaterals. Circulation 1979; 60: 106-13 3 Parker FB Jr, Neville JF Jr, Hanson EL, Webb WR. Retrograde and antegrade pressures and flows in preinfarction syndrome. Circulation (supplement II) 1974; 11-122-11-126 4 Fischl SJ, Herman MV, Corlin R. The intennediate coronary syndrome: Clinical, angiographic and therapeutic aspects. N Eng! J Med 1973; 288:1193-98 5 Raftlenbeul W, Smith LR, Rogers WJ, Mantle JA, Raclcley CE, Russell RO Jr. Quantitative coronary angiography: Coronary anatomy of patients with unstable angina pectoris reexamined one year after optimal medical therapy. Am J Cardiol 1979; 43:699-707 6 Fuster V, Frye RL, Connolly DC, Danielson MA, Elveback LR, Kurland LT. Arteriograpbic patterns early in the onset of the coronary syndromes. Br Heart J 1975; 37:1200-55 7 Day LJ, Thibault GE, Sowton E. Acute coronary insuf6c~ency: Review of 46 patients. Br Heart J 1977; 39: 363-70
8 Bjork L, Spindola-Franco H, van Houten FX, Cohn PF, Regional Coronary Anatomy In Reat Angina (Wllaon .t .,)
Adams DF. Comparison of observer performance with 16 mm cinefluorography and 70 mm camera fluorography in coronary arteriography. Am J Cardioll975; 36:474-78 9 Detre ICM, Wright E, Murphy ML, Takaro J. Observer agreement in evaluating coronary angiop"ams. Circula-
10
11 12
13
tion 1975; 52:979-86 Zir LM, Miner SW, Dinsmore BE, Cilbett JP, Harthorne }W. Interobserver variability in coronary angiography. Circulation 1976; 53:627-32 Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Qudiol 1974; 34:48-55 Papapietro SE, Niess CS, Paine TO, Mantle JA, Racldey CE, Russell RO, et ale Transient electrocardiographic changes in patients with unstable angina: Relation to coronary arterial anatomy. Am J Cardiol 1980; 46:28-33 Gregg DE, Patterson RE. Functional importance of coro-
nary coDaterals. N Eng} J Med 1980; 303: 1404-06 14 Colton T. Statistics in medicine. Boston: Little, Brown, 1974 15 Levin DC. Pathways and functional significance of the coronary coDateral circulation. Circulation 1974; 50: 831-37 16 Caulfield JB, Gold HI{, Leinbach RC. Coronary artery lesions associated with unstable angina. Am J Cardiol 1975; 35: 126( abstract) 17 Maseri A, L'Abbate A, Baroldi C, Chierchia S, Marzilli M, Ballestra AM, et ale Coronary vasospasm as a possible cause of myocardial infarction. N Eng! J Med 1978; 299:1271-77 18 Maseri A, Severi S, DeNes M, L-Abbate A, Chierchia S~ Marzilli M, et aI. ·'Variant" angina: One aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 1978; 42: 1019-35
Second National Congress on Respiratory Diseases The Second National Congress on Respiratory Diseases, sponsored by the Indian Chest Society, will be held in Bombay, India, December 2-4, 1982. The opening of the Congress will be preceded by an intensive one-day postgraduate seminar in respiratory diseases. For information, contact Dr. A. A. Mahashur, Secretary-General, c/o Department of Chest Medicine CVTC, K.E.M. Hospital, Parel, Bombay 400 012, India.
CHE8I' I •
I 4 I
OCTOIIER. 1 .
411
To determine If padeDti with rest ........ bave more _vere feIIoIuII ischemia than patieDts with esertlo.... ........, we eompued the severity of left com...." IIItery (LeA) In 29 padeDb witla tnlDsieDt mterlol" lldaemle ST-T e at reIt, _d 30 patIe... with _terlor ST e es oDly d....... esedioD. The peraat. .e diameter ateDOlls • • measured with Vernier callpen • (2 X lesion diameter X 100 perceDt)/(prelienotle + postiteDOtic diameter). There W8I DO dIrf..-ace betweeD tile two are-.. ID the ..... diameter _DOlls of _ocduded LeA vessels either wheD ... ftIIeII were eompued (rest: 6' ± 12 pereeDt; esertIoIud: 70 ± 13 pereent [p=NSD or wheD oDly the _um-. stenosis In each patleDt was com.... (rest:
ste.....
T heduction role of coronary anatomic factors in the proof rest angina is uncertain. Previous
studies have demonstrated that the distribution of coronary angiographic lesions in patients with rest and exertional angina are similar,'? suggesting that anatomic factors are not responsible for rest angina. However, these studies have not specifically compared the degree of coronary stenosis and collateralization in the region of ischemia. Therefore, it remains possible that rest angina is due to more severe regional ischemia than in exertional angina. Moreover, with only one exception, previous studies have used qualitative methods to evaluate coronary angiograms. This approach has a high intra- and interobserver variability and therefore does not permit accurate quantitative comparisons of lesion severity.8-10 In the presence of coronary stenoses greater than 60 percent, minor increases in stenosis severity can have major effects on coronary reserve.11 Therefore, studies in which qualitative techniques were used to compare angiographic lesions in rest -From the CardJac Hemodynamic Laboratories, Hospital of the University'of ~Iy&nia, and the Cardiovascular See-
tion, DeparbDent of Medicine, University of PeDDSYlvania School ol Medicine, PbiladeJ~~ f$upported by a research fellowship from the American Heart Association, Southeastern Pe~lvania Chapter. ~Supported by a SPecial InvestigatorsbiP from the American Heart Aaociation, Southeuteni PeDD8)'lvania Chapter. Manuscript received January 21; revision ~~ April 21. Reprint requatl: Dr. Wa.on, Ht}lJ?ittJL Unbmtv of PBM8fIlotJnUJ, 3400 Spruce Street, PhlladelphltJ 19096
411
74 ± 10 percent; uertiomII: 75 ± 12 peraDt [p=NS)). To... oc:eIuIioD of at last _e major v.... of the LeA .... oeconed with IimUar freq8eney In pade.. with nit ('/29) _d esertlo.... (12/30) (p=NS). However, coIIatend developllleDt to 76-100 perceDt LeA I_OBI slpUlcBDtIy I. . frecpaeDt In rest ...... (4/21 v ' " [I' percentD tIuua ID esertlo.... ....... (21/30 v-els [70 perceDtD, ( p < .03). We eoDdll4e tIIat patient. wItIa rest ........ do DOt have more severe COIOII8I)' IteDOIes tIuua ..tIe.ts _ uerdonal ......., bid fnqaeDtIy may have IDOn seven regIo.... .hemla due to reduced eoIIaterizadoD of Jeopardized myocardium.
w.
and exertional angina may have overlooked small but important differences in severity of stenosis. The present study was therefore undertaken to determine if patients with angina at rest have more severe coronary obstruction and/or less collateralizanon in the region of ischemia than patients with exertional angina. Anterior ST-T changes have been shown to correspond anatomically to ischemia in the distribution of the left coronary artery.11 Accordingly, the degree of left coronary artery stenosis and collateralization was compared in patients with reversible ST-T changes in the anterior precordial leads at rest and patients with similar ECG changes during exertion. Coronary angiograms were analyzed using a quantitative technique. METHODS
Patient Selection Patients with rest angina were selected by reviewing aD
cardiac catheterization reports on patients studied between January, 1974 and January, 1981 at the Hospital of the University of PeDD8)'lvania. Patients were identiSed who had ODe or more episodes of tmplOvoked resting chest pain ac-
>1
companied by transient mm ST-seJPDent elevation or depression or marked T -wave changes in the electrocardiographic leads Vt, V 2 , Va and/or V" within two weeks prior to cardiac catheterization. Patients with Q waves in the anteriol' leads, enzymatic evidence of myocardial necrosis and <50 percent left coronary artery stenosis were excluded. Thirty-three patients fuIfllled these criteria, 29 of whom Regional Coronary Anatomy In Reel Angina (WI/.on .t al)
had high quality angiographic studies available for analysis. None of the patients underwent ergonovine testing due to the presence of significant fixed coronary artery lesions. For comparison, a second group of patients with exertional angina and no history of rest or noctuma1 angina were identified as follows. All exercise stress test reports on patients studied between August, 1978 and January, 1981 were reviewed to identify patients with exertional angina who developed chest pain accompanied by 1 mm horizontal or down-sloping ST-segment depression or > 1 mm STsegment elevation in Vt, V2 , Va and/or V.. Cardiac catheterization reports were then reviewed to identify those patients who also underwent cardiac catheterization within two weeks of exercise testing. From this group, patients with Q waves in the anterior ECG leads, conduction disturbances, and/or insignificant coronary artery stenosis were excluded. Thirty patients fuI8lled these criteria for inclusion in the exertional angina group.
>
Angiographic AntJIy8f8
Selective coronary arteriography was performed using either the Sones or Judkins technique. Nitrates were withheld for at least six hours prior to catheterization. Angiography was performed with a Philips 6-inch image intensi6er and recorded on 35 mm film. Studies .mcluded left ventriculography in the right anterior oblique projection and selective left and right coronary arteriography. Coronary arteriography was routinely performed in right and left anterior oblique projections, as well as in various other views to maximally visualize coronary occlusions. Films were analyzed independently by two reviewers according to the technique of RafIIenbuel and co-workers.s Reviewers were blinded to the patient's clinical history. Each fllm was projected on a Vanguard XR-35 projector (8 x 10 inch screen). The extent of coronary obstruction was measured with a Vernier caliper (LS Starrett Company) (accuracy = 0.04 mm.) Measurements were performed near the center of the x-ray beam and only at end-diastole. Because of the eccentric lumen of many obstructions, lesions were measured in as many projections as possible. Three segments were measured: the pre-stenotic vessel diameter, the narrowest diameter of the obstructed area, and the poststenotic diameter. The percentage of obstruction was calculated as:
=
percent diameter stenosis 2 X lesion diameter X 100 percent pre-stenotic + post-stenotic diameter To establish the precision of measurements, the degree of stenosis of 29 obstructed lesions in 17 angiograms were analyzed at two different times by the same observer. Differences in severity of stenosis averaged 4 ± 4 percent (range: 0-12 percent). Variability between measurements made by the two observers averaged 5 ± 5 percent (range: ().,16 percent). Reported stenosis diameter represents the average of the measurements made by the two observers. Vessels with obstructions too severe to measure were designated as 90 percent stenosis for purposes of statistical analysis. Collateral flow was considered absent if none was visualized on angiography. Collaterals were considered present if observed to fill either, part or an of the arterial system distal to a lesion. No attempt was made to grade the degree of collateralization since physiologic and technical variables (amount of contrast: agent injected) may substantially iDfluence coUateral visualization.1 8
Table l-C8Jdea1 C~1ia in PIIIierW _ala Read,.. and Eserdonal .4....... Rest (N-29)
±9
Exertional (N-30)
± 8·
Age (years)
54
Sex
24M/SF
29M/IF
Exertional Angina
14/29 (48%)
30/30 (100%)
Resting ECG NSST IMI Normal
16/29 (55%) 2/29 (7%) 11/29 (38%)
13/30 (43%) 5/30 (17%) 12/30 (40%)
EKG with Angina ST ! ST Twave
8/29 (28%) 16/29 (55%) 5/29 (17%)
28/30 (93%)· 2/30 (7%)·
r
58
*p <.05 compared with rest angina group Nonspecific ST and T wave change (NSST); inferior myocardial infarction (IMI) Sta&ffcal AntJlyril
The significance of differences in the distribution and relative severity of disease in each coronary artery wu evaluated with the chi square method. Differences in absolute degree of left coronary artery occlusion was evaluated both with the Student's t-test and with the rank sum test. 1 • Differences in the degree of collateralization was evaluated with the chi square method. A p value < .05 was considered significant.
REsuLTS CUnical Characteristics (Table 1) The patients with rest angina were slightly younger (54 ± 9 years) (mean ± standard deviation) than the patients with exertional angina (58 ± 8 Table 2--ltIasimal De.,._ 01 SIelUMU in Eaela Major Coronary .4rtery in alae PadenU .aIa Read,.. and Eserdo,",' .4r&«ina * <50%
50-75%
76-95%
100%
LAD Rest Exertional
0 3 (iO%)
14 (48%) 12 (40%)
10 (34%) 6 (20%)
5 (18%) 9 (30%)
CxC Rest Exertional
14 (48%) 8 (27%)
8 (28%) 7 (23%)
4 (14%) 5 (17%)
3 (10%) 10 (33%)
LC System Rest Exertional t
14 (24%) 11 (18%)
22 (38%) 19 (32%)
14 (24%) 11 (18%)
8 (14%) 19 (32%)
RCA Rest Exertional
13 (45%) 9 (30%)
8 (28%) 6 (20%)
0(0%) 6 (20%)
8 (27%) 9 (30%)
*No significant difterence was noted between the two groupe using chi square analysis Circumflex coronary artery (CxC); left anterior descending coronary artery (LAD); right coronary artery (RCA) tp-O.ll compared with rest angina CHEST I 82 I 4 I OCTOBER, 1812
417
LEFT CORONARY SYSTEM ANATOMY 100
100
......
...
.. ..•
.....••••
...
..•• •• •• ..•••
• •
o
en
"~
70
.. o e
CD
V)
....Q)CD 60 E
e
o
p=NS
•• •
•• • •• • •• • •
• •• •• •
....'
• •• ••
•• ••• •• •• • 50....-.--....&-...-----=-----.......
....-.~ ....c 90 CD "Z-
cf
.s: u 0
w .5
80
en
..
"~
0
c
CD
70
V)
"0 E
";C 0
~
60
...... • • •• •• •
..••• • • • •
p=NS
•••
•• • •• • •• •• • • •• •
... • •• •
• 50.......---..:.--------~•
Exertional
Rest
Exertional
Rest
Angina
Angina
Angina
Angina
(N=38)
(N=45)
(N=23)
(N=28)
FmUBE 1. Comparison of the degree of steDOIis of UIlOOCluded left corolW)' artery vessels in the patients with restiDI and aertional augiDa. Oil the left, diameter stenosis of aD unoccluded vessels is compared. On the right, diameter IteDosIs of the most severe lesion identdled in each patient is compared.
years) (p <.04). The majority of patients in both groups were men. A history of exertional angina was reported by half of the patients with rest angina.
In the patients with rest angina, ST segmentelevation was observed during angina in 55 percent of the patients, ST segment depression in 28 percent and T wave inversion in 17 percent. Seven of the 16 ~tients with rest angina and ST segment elevation had a history of exertional angina. In the patients with exertional angina and no rest angina, ST-segment depression was noted in 28 patients and ST segment elevation in two.
DUtribution of Coronary Lesions The distribution of coronary lesions was not significantly different in the two patient groups. In the patients with rest angina, ,single vessel disease was noted in 24 percent, double vessel disease in 28 percent, biple vessel disease in 28 percent and left main coronary artery disease in 20 percent The distribution of coronary disease in the patients with exertional angina was 10 percent, 27 percent, 53 percent and 10 percent, respectively. 411
Degree of Stenoaia (Table 2) Total occlusion of at least one major vessel of the left coronary system was observed in six of 29 patients with rest angina versus 12 of 30 patients with exertional angina (p == NS). There was no difference in the mean diameter stenosis of unocc1uded left coronary vessels either when all vessels were compared (rest: 69 ± 12 percent, exertion: 70 ± 13 percent (p == NS» or when the maximal stenosis in each patient was compared (rest: 74 ± 10 percent, exertion: 75 ± 12 percent (p == NS» (Fig 1). Sequential coronary lesions of the left coronary artery were noted in six of the patients with rest angina and four of the patients with exercise angina. Comparisons of coronary lesion severity following exclusion of these patients did not influence the overall results.
Collateral Vessels(Table 3) The incidence of coDateralization to severely stenotic (76-90 percent diameter stenosis) vessels of the left coronary system was significantly less in the patients with rest angina (1/14 [7 percent]) than in Regional Coronary Anatomy In Rnt Angina (Wllaon ., aI)
Table 3--Compari... of I6e lneiffenee of Colltderali"";on for _ Gille. Dep-ee of ConJrlllr7 Saenoai. in PfId.... . .1& Ra' ",.., Eserlional A"';... Percent Stenosis
Rest (N-29)
Exertional (N - 30)
P
LAD 76-00 100
1/10 (10%) 3/4 (75%)
4/6 (67%) 8/9 (89%)
0.10 0.79
CxC 76-90 100
0/4 (0%) 0/3 (0%)
3/6 (50%) 6/9 (67%)
0.19 0.18
LC System 76-00 100 76-100
1/14 (7%) 3/7 (43%) 4/21 (19%)
7/12 (58%) 14/18 (78%) 21/30 (70%)
<.04 0.44 <.03
RCA 76-90 100
8/8 (100%)
1/5 (20%) 9/9 (100%)
Circumflex coronary artery (CxC); left anterior descending coronary artery (LAD); left coronary system (LC system); right coronary artery (RCA)
the patients with exertional angina (7/12 [58 percent] ), (p <.04). Similarly, the incidence of collateraIization to either severely stenotic or totally occluded vessels of the left coronary system was signiflcantly less in the patients with rest angina (4/21 [19 percent]) than in patients with exertional angina (21/30 [70 percent]) (p <.05). In contrast, both groups demonstrate collateralization to all totally occluded right coronary arteries.
Coronary Anatomy and ST-Segment Directional Changes Angiographic findings were similar in patients with rest angina and ST-segment elevation (N = 16) and in patients with ST depression or T wave changes (n = 13). The most severe coronary stenosis of the left coronary system in patients with ST-segment elevation averaged 72 ± 11 percent versus 74 ± 9 percent in the other patients (p = NS ). The distribution of single, double, triple vessel and left main disease were comparable. CollateraIization to the left coronary system distal to areas of 76-100 percent obstruction was observed in 2/13 patients with ST-segment elevation versus 2/10 patients with ST-segment depression or T wave changes (p= NS). DISCUSSION
This study differs in two major ways £rom previous comparative studies of rest and exertional angina. First, coronary angiograms were analyzed using a quantitative rather than qualitative technique. The utility of quantitative techniques and their advantage over qualitative techniques has already been established.I " Second, an attempt was
made to compare angiographic features in the region of ischemia rather than comparing the severity of disease throughout the coronary circulation, as has been done by others. To identify the region of ischemia, the presence of reversible ST-T changes in the anterior precordial leads was considered to correspond anatomically to ischemia in the distribution of the left coronary artery. In support of this approach, Papapietro and co-workers'P have observed that transient ST changes in the anterior pre-· cordial leads in patients with single vessel disease is almost always associated with stenosis of the left anterior descending coronary artery.
Severity of Coronary Lesions in Rest Angina The results of this study indicate that both the overall distribution of coronary lesions and the severity of coronary lesions within the ischemic region are similar in patients with rest and exertional angina. The majority of patients in both groups had double or triple vessel disease, as noted by others.!" In addition, the average diameter stenosis of unoceluded left coronary vessels in the patients with rest angina was comparable to that observed in the patients with exertional angina. The only noteworthy diHerence between lesion severity in the two groups was a higher incidence of 100 percent occlusions of the left coronary vessels in patients with exertional angina. However, this difference was not statistically significant. Neill and co-workers! have recently noted a higher incidence of total left anterior descending occlusion in patients with rest angina.
Reduced Collaterals in Rest Angina The only major anatomic diHerence between the patients with rest and exertional angina was a strikingly lower incidence of collateralization in the patients with rest angina. Collateralization was noted distal to 76-100 percent left coronary artery lesions in only 19 percent of vessels in rest angina coinpared with 70 percent of vessels in exertional angina. In an extensive analysis of collaterals in 200 patients with coronary disease, Levin us noted a 50-60 percent incidence of eollateralization to severely narrowed or completely occluded vessels of the left coronary artery. Thus, the incidence of collateraIization to the left coronary artery in our patients with exertional angina is comparable to that in other populations. Collateralization to the right coronary artery, a vessel presumably Dot involved in the ischemic process in our patients, was also comparable to previous studies both in the patients with rest and the patients with exertional angina. Our finding of reduced collateralization in rest angina is consistent with several previous reports. CHEST I 82 I .. I OCTOBER, 1982
411
In a study of 20 patients with rest angina, Fischl and co-workers- noted a 27 percent incidence of collateralization to the left coronary artery in the presence of severe stenoses and suggested that this incidence was abnormally low. RafIlenbeu1 and coinvestigators' recently noted a 21 percent incidence of collateralization to severely stenotic vessels in 25 patients with rest angina. They also remarked on this finding as abnormal. Finally, intraoperative measurements of retrograde flow in stenosed coronary arteries has detected less retrograde How in patients with rest or prolonged angina than in patients with chronic exertional angina.f Retrograde flow is inHuenced primarily by the extent of collateral flow. In contrast to our findings, Neill and co-workers 1 recently reported no evidence of impaired collateralization in 70 patients with rest angina when compared to 49 patients with exertional angina. This finding may be due to their inclusion of patients with rest angina, but without reversible ST-T changes and of patients with inferior ischemia. It is conceivable that collateralization to the right coronary artery is not impaired in rest angina. Moreover, in the study by Neill and co-workers 1 the incidence of collateralization to severely stenotic coronary arteries was less than 20 percent with exertional angina, an incidence considerably lower than that observed by others. II Potential Limitatiom It would have been of interest to perform ergonovine maleate testing in our patients with rest angina to define the incidence of coronary spasm. However, during the time period that catheterization was performed in these patients, ergonovine testing was considered relatively contraindicated in patients with significant fixed coronary lesions. Our assumption that anterior precordial ST-T changes reflect ischemia in the left coronary artery distribution is consistent with previous studies. I,ll However, it is possible that ischemia in other areas was responsible for the ECG changes in some of the patients. This potential error should occur with similar frequency in both rest and exertional angina and therefore should not significantly Influence our results.
Clinical Implications Our findings suggest that patients with coronary disease and reversible ST-T changes at rest are composed of two anatomic subgroups which are indistinguishable based on ECG criteria. In one subgroup, rest angina is associated with severe fixed 420
coronary stenosis usually without collateralization. This finding suggests that regional ischemia may be more severe in these patients than in patients with exertional angina. In addition, the absence of 001lateralization suggests either abnormally rapid progression in the rate of coronary obstruction or an inability to develop eollaterals." Pathologic studies of coronary arteries obtained from patients with unstable angina have demonstrated an abnormally high incidence of multiple plaque hemorrhages," a finding consistent with rapid progression of coronary lesions. Our data, therefore, suggest that severe flow limitation may play an important role in initiating rest angina in these patients. H this is the case, aggressive early treatment of the underlying coronary obstructive disease might be the optimal approach to therapy in such patients. In a second subgroup, resting ischemia develops in the presence of only moderate coronary stenoses. Transient reductions in coronary flow rather than severe fixed coronary flow limitation is a likely etiology for this type of rest angina. 17, 18 Ergonovine testing in this subgroup probably should be performed. ACKNOWLEDGMENT: The authors thank John Kastor, M.D. for his support and review of the manuscript, Nancy Ferraro. R.N., for technical assistance, and Mrs. Brenda Barnard and Mrs. Pabicia Wyatt for their preparation of the manuscript.
REFERENCES 1 Neill WA, Wharton TP Jr, F1uri-Lundeen J, Cohn IS. Acute coronary insufBciency-coronary occlusion after intermittent ischemic attaclcs. N Engl J Moo 1980; 302:1157-62 . S McMahon MM, Brown G, Culdngnan R, Rolett EL, Bolson E, Frimer M, et ale Quantitative coronary angiography: Measurement of the "critical" stenosis in patients with unstable angina and single-vessel disease without collaterals. Circulation 1979; 60: 106-13 3 Parker FB Jr, Neville JF Jr, Hanson EL, Webb WR. Retrograde and antegrade pressures and flows in preinfarction syndrome. Circulation (supplement II) 1974; 11-122-11-126 4 Fischl SJ, Herman MV, Corlin R. The intennediate coronary syndrome: Clinical, angiographic and therapeutic aspects. N Eng! J Med 1973; 288:1193-98 5 Raftlenbeul W, Smith LR, Rogers WJ, Mantle JA, Raclcley CE, Russell RO Jr. Quantitative coronary angiography: Coronary anatomy of patients with unstable angina pectoris reexamined one year after optimal medical therapy. Am J Cardiol 1979; 43:699-707 6 Fuster V, Frye RL, Connolly DC, Danielson MA, Elveback LR, Kurland LT. Arteriograpbic patterns early in the onset of the coronary syndromes. Br Heart J 1975; 37:1200-55 7 Day LJ, Thibault GE, Sowton E. Acute coronary insuf6c~ency: Review of 46 patients. Br Heart J 1977; 39: 363-70
8 Bjork L, Spindola-Franco H, van Houten FX, Cohn PF, Regional Coronary Anatomy In Reat Angina (Wllaon .t .,)
Adams DF. Comparison of observer performance with 16 mm cinefluorography and 70 mm camera fluorography in coronary arteriography. Am J Cardioll975; 36:474-78 9 Detre ICM, Wright E, Murphy ML, Takaro J. Observer agreement in evaluating coronary angiop"ams. Circula-
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11 12
13
tion 1975; 52:979-86 Zir LM, Miner SW, Dinsmore BE, Cilbett JP, Harthorne }W. Interobserver variability in coronary angiography. Circulation 1976; 53:627-32 Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Qudiol 1974; 34:48-55 Papapietro SE, Niess CS, Paine TO, Mantle JA, Racldey CE, Russell RO, et ale Transient electrocardiographic changes in patients with unstable angina: Relation to coronary arterial anatomy. Am J Cardiol 1980; 46:28-33 Gregg DE, Patterson RE. Functional importance of coro-
nary coDaterals. N Eng} J Med 1980; 303: 1404-06 14 Colton T. Statistics in medicine. Boston: Little, Brown, 1974 15 Levin DC. Pathways and functional significance of the coronary coDateral circulation. Circulation 1974; 50: 831-37 16 Caulfield JB, Gold HI{, Leinbach RC. Coronary artery lesions associated with unstable angina. Am J Cardiol 1975; 35: 126( abstract) 17 Maseri A, L'Abbate A, Baroldi C, Chierchia S, Marzilli M, Ballestra AM, et ale Coronary vasospasm as a possible cause of myocardial infarction. N Eng! J Med 1978; 299:1271-77 18 Maseri A, Severi S, DeNes M, L-Abbate A, Chierchia S~ Marzilli M, et aI. ·'Variant" angina: One aspect of a continuous spectrum of vasospastic myocardial ischemia. Am J Cardiol 1978; 42: 1019-35
Second National Congress on Respiratory Diseases The Second National Congress on Respiratory Diseases, sponsored by the Indian Chest Society, will be held in Bombay, India, December 2-4, 1982. The opening of the Congress will be preceded by an intensive one-day postgraduate seminar in respiratory diseases. For information, contact Dr. A. A. Mahashur, Secretary-General, c/o Department of Chest Medicine CVTC, K.E.M. Hospital, Parel, Bombay 400 012, India.
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OCTOIIER. 1 .
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