Importance of coronary collateral circulation in interpreting exercise test results

of Coronary Collateral Circulation in lnt&reting

Exercise Test Results

JULIO F. TUBAU, MD BERNARD R. CHAITMAN, MD, FACC MARTIAL G. BOURASSA, MD, FACC JACQUES LESPliRANCE, MD GEORGES DUPRAS, MD Montreal. Quebec, Canada

From the Montreal Heart Institute and the University of Montreal Medical School, Montreal. Quabec,Cawh.Thiistudywassupportedinpart by Medical Research Council of Canada Grant MA-7290 and Canadian Heart Foundation Grant 799-536. Manuscript received June 16, 1980; revised manuscript received July 22, 1980, accepted July 29, 1980. AWess for reprints: Bernard Ft. Chaitman. MD. Montreal Heart Institute, 5000 East, Belarger Street, Montreal, HlT lC8, Quebec, Canada.

The importance of the coronary collateral clrculatlon as a cause of false negatlve exercise tests was studled In 37 patients who had a 90 percent or greater Isolated stenosk of the lumlnal dlameter In one major coronary artery. Slxteen patlents had large collateral vessels and 21 patlents had elther mlnlmal or no collateral clrculatlon. Myocardlal sclntlgraphy was performed In 22 of the 37 patlents. The flnal treadmlll tlme was slmllar In both groups (521 f 192 versus 554 f 144 seconds [mean f standard error of the mean]). The presence and depth of S-T segment depresslon was not Influenced by the degree of collaterallzatlon. The sensttlvlty of the exercise electrocardiogram was greater for patients wlth dlsease In the left anterior descending than In the rlght or left circumflex coronary arteries (95 versus 60 percent, p <0.03). Among the 22 pattents wlth thallium-201 scktlgrams, myocardtal perfusion defects were more common In patlents wlthout collateral clrculatlon (100 versus 40 percent, p
Single vessel coronary artery disease is a common cause of false negative results in diagnostic stress testing. l4 The addition of thallium-201 scintigraphy to such testing has increased the detection of patients with single vessel disease but false negative results are still common in patients with isolated right or left circumflex coronary artery disease.T-l4 There are few data that evaluate the role of the coronary collateral circulation as a possible cause of false negative tests. Clearly, if large well developed collateral vessels distal to a high grade coronary arterial stenosis could prevent or rapidly reverse transient myocardial ischemia, no significant electrocardiographic changes or perfusion defects would be observed. This study examines the hypothesis that coronary collateral circulation can cause false negative exercise electrocardiograms and myocardial scintigrams. Methods Study patients: The study group consisted of 37 patients with single coronary arterial stenosis equal to or greater than 90 percent of the luminal diameter in one of the three major coronary arteries and no other arterial stenosis of 50 percent or greater. All patients had chest pain for at least 6 months before cardiac catheterization. There were 26 men and 11 women whose mean age was 47 years (range 26 to 62). Patients with a previous myocardial infarction, cardiomyopathy or valvular heart disease were excluded.

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Electrocardiographic exercise test: Each patient underwent a maximal symptom-limited stress test performed with use of 14 electrocardiographic leads according to a modified Bruce protocol.15*‘s A test was considered positive if horizontal or downsloping S-T segment depression of 1 mm or more or a slow upsloping S-T segment depressed 2 mm or more at 0.08 second after the J point occurred.l+l’ All patients with a negative test achieved at least 85 percent of their agepredicted maximal heart rate. Myocardial scintigraphy: Myocardial scintigraphy was performed in 22 of the 37 patients after 2 millicuries (mCi) of thallium-201 was injected intravenously 45 to 60 seconds before terminating exercise. Anteroposterior, 30° left anterior oblique and left lateral views were obtained using standard techniques. The total of 150,000 counts/view over the left ventricle were registered with a Picker-Dyna 4/5 gamma camera equipped with a high resolution collimator and a 20 percent window. Counts originating from the spleen or liver were avoided using a 12 cm leaded mask. The scintigrams were photographed in black and white on 70 mm film after 30 percent background subtraction and a 9 point matrix smoothing. The scintigram at rest was obtained 4 to 10 days after exercise. The scintigrams were interpreted qualitatively by three observers unaware of the clinical status, exercise test results or location of the diseased vessel. The test was considered positive if a localized reversible perfusion defect was present. The extent of the defect was analyzed semiquantitatively by dividing each scintigram into five segments as described by Rigo et al.ls The myocardial segments corresponding to each coronary artery were considered in order to quantify the extent of myocardial ischemia. Assessment of collateral circulation: Coronary angiography was performed using the transfemoral approach.19 A coronary arterial stenosis of 90 percent or greater of the luminal diameter was considered a significant lesion for the purpose of this study; this degree of narrowing is usually required to demonstrate collateral vessels at angiography. The presence of collateral circulation was assessed by an experienced cardiovascular radiologist unaware of the results of noninvasive testing.2o The average ejection fraction calculated by the area-length method2r was 0.62 f 0.08 (mean f standard error of the mean). Statistical analysis: The differences between groups were analyzed using the chi-square test for nonparametric variables and the unpaired t test and analysis of variance for parametric variables.

scending coronary artery in 22 patients, in the left circumflex coronary artery in 5 patients and in the dominant right coronary artery in 10 patients. The patients were classified into two groups on the basis of the degree of collateralization. In group A (n = 16 patients), the distal segment of the stenosed vessel was clearly opacified and large intercoronary collateral vessels were visible. Group B (n = 21 patients) was characterized by minimal or absent collateral blood flow (involving only the interseptal-intermarginal branches). Exercise electrocardiography: The physiologic limitation to exercise was greatest in patients with left anterior descending arterial stenosis. These patients had a final treadmill exercise time of 481 f 177 (mean f standard deviation) seconds versus 626 f 98 seconds in patients with either right or left circumflex coronary artery disease (p KO.05). Exercise was terminated by angina in 91 percent of patients (20 of 22) with but in only 20 percent of patients (3 of 15) without left anterior descending arterial stenosis (p cO.005). The patients with left anterior descending stenosis of the left anterior descending common artery had more ischemic electrocardiographic responses than did those with right or left circumflex coronary arterial stenosis (95 percent [21 of 221 versus 60 percent [9 of 151; p <0.03). However, among the 30 patients with a positive electrocardiographic test the number and location of positive leads, depth of S-T segment depression and duration of ischemia after exercise did not correlate with the location of the diseased vessel. Leads VA to Ve, CC5 or CM5 recorded significant S-T segment depression in the patients with right or left circumflex coronary artery disease. The presence and depth of S-T segment depression was not influenced by the degree of coronary collateralization (Fig. 1). Of 16 patients in group A (with collateral vessels), 94 percent had a positive electrocardiographic test compared with 71 percent of the 21 patients in group B (without collateral vessels) (difference not significant [NS]). The maximal treadmill time was 521 f 192 seconds for patients in group A compared with 554 f 144 seconds in patients in Group B. The maximal pressure-rate product was also similar in both groups. The frequency of angina during exercise was 56 percent (9 of 16) patients in Group A and 67 percent (14 of 21) in patients in group B (difference not significant). Myocardial scintigraphy: Exercise thallium-201

Results Coronary angiography: Obstructive coronary artery disease (90 percent or greater stenosis of the luminal diameter) was present in the left anterior de-

x6 50 28 fan Ez ;g 25

,E 50 .$ E DO Ez gal 25pm& aes

&P aeu)

< 1mm Depth

28

t?9mm of ST Segment

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0 Number

1-3 of Positive

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FIGURE 1. The depth of S-T segment depression (lefl) and the number of positive ekctrocardiographic laads (right) was similar in patients with (group A) and without (group 9) collateral vesSdS.

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TABLE I Correlation of Exercise Electrocardiographic and Scintigraphic Results With Coronary Angiography Exercise Test

Case

Age (yr) & Sex

Max S-T Depression

Leads Positive

Angina

Thallium Perfusion Defect Max HR (per min)

Final TT (s)

Rest/Ex

Angiography % Stenosis

Location

Collateral Vessels

Group A: Patients With Collateral Vessels 1

46M

CMs

2

51M

v3-vs,

1.5

+

CM?5

156

210

+/++

100% LAD

165

645

--/+

Septal-apical

Septal

95% LAD

cc5

3

48M

Vs-Vs, II, aVF, CM5, CCs, CL

2

+

114

405

-/+

Septal

100% LAD

4

40M

v3-vs,

4

-

170

660

-I-

-

100% LAD

5

+

153

690

-I-

-

90% LAD

3

•F

123

360

-1-k

Septal

95% LAD

CM5.

cc5

5

32M

V4-Vs. Ill, aVF, CCs, CMs, CL

6

57F

vs.

7

5atd

Vs. CCC,,CM5

2.5

+

158

240

-l-

56M 5aM 26F

V4,

1

-

! 10

1.5 0

-

167 172 167

690 735 600

-I-/-/-

CM5

CM5,

CC5

1V4-Vs, CM5 -

100% LAD

100% LCX 95% RCA 100% RCA

-

RCA -

LAD

RCA LCX RCA LCX

Diag LCX

-

LAD

-

LAD

RCA -

RCA LCX RCA I LCX

LAD

LAD

-

LAD

-

LAD

Diag - LCx LCx - RCA LCx - RCA

Group B: Patients With Minimal or No Collateral Vessels 1 3 4

.48M 40M 62M

-

0

+ +

:

+

:

z

:

::

CMs vcv,.

CM57

: 7

45M 58F 57F 53F

Vcc:M V:: CM: :* $

t 10

35F 40F 49M

~$CgMr

::

43M 33F

V”-“; CM v;, cb,, CE,

5.

5

1 4

6.

5s

153 165 117

720 645 la0

+/++ -/+ --/+

147 144 147 167

360 270 525 480

t

+

la3 115 136

:

+ -

145 177

+’

100% LAD 95% LAD 90%LAD

-/+ f/++ -/+ -1-F

Septal-apical Septal-inf Ant-lat, apical Septel Ant-lat Septal S&p&-;pi-

LAD LAD LAD LAD

-

580 500 630

-J-F -/+ +/++

Sepia1 Septal Inf-apical

100% LAD 95% LAD 100% LCX

-

600 660

--/+ -1-F

Inf-posterior Ant-lat

90% 90% 90% 90%

90% RCA 95% RCA, Diag

-

-

Ant = anterior; Diag = diagonal branch of left anterior descending artery; ex = exercise; HR = heart rate; inf = infero; LAD = left anterior descending coronary artery; lat = lateral; LCx = left circumflex coronary artery: Max = maximal: RCA = right coronary artery; S-T3 = depression; TT = treadmill time.

scintigrams were performed in 22 patients (Table I). Among the 16 patients with left anterior descending arterial stenosis, 81 percent had a positive scintigram compared with 50 percent of the 6 patients with right or left circumflex coronary artery disease (difference not significant). Myocardial perfusion defects were more common in patients without collateral vessels. All 12 patients in group B had perfusion defects compared with only 40 percent (4 of 10) of patients in group A (p
in patients with occluded coronary arteries and well developed collateral vessels (Fig. 2). The perfusion defect corresponded to the site of coronary artery disease in 94 percent of the 16 patients with a positive scan (Fig. 3). Discussion Exercise electrocardiography: The sensitivity of exercise electrocardiography in the detection of coronary artery disease is decreased in patients with single vessel disease (Table III) .ldJ6 The sensitivity ranges from 33 to 95 percent, reflecting the use of different

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TABLE II Extent of Thallium-201 Perfusion Defect No Defect

Two Seaments

>Two Seaments

Group A (n = 10)

6 (60%)

3 (30%)

l(iO%)

Group B (n = 12)

0 (0%)

5 (42%)

7 (58%)

p < 0.005 p = probability.

FIGURE 2. Patient 7 (group A). Top, contrast injection into the right coronary artery and posterior descending coronary artery (PDA) opacifies the left anterior descending coronary artery (LAD) through large epicardial vessels (arrow). Bottom,tha exercise electrocardiogram shows horizontal S-T segment depression in leads Vs, CC5 and CM5; the myocardial scintigrams at rest and during exercise are normal. AP = anteroposterior; LAO = left anterior oblique.

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exercise protocols and lead systems, the inclusion of patients with previous myocardial infarction, the location of the diseased vessel and the degree of coronary arterial narrowing required for detection. The higher sensitivity observed in this study results from the presence in all patients of a stenosis of 90 percent or greater of luminal diameter and a normal electrocardiogram and left ventricular contraction pattern at rest. The sensitivity of exercise electrocardiography was increased in our patients with left anterior descending coronary disease this finding is similar to the results obtained by McHenry et al3 but in contrast to the results of other investigators.4*6 The difference may represent (1) the amount of myocardium that can be rendered potentially ischemic during exercise or (2) the exercise electrocardiographic lead system recorded during and after exercise, or both. A luminal narrowing or less than 75 percent at angiography may not reduce coronary blood flow during exercise by an amount sufficient to show significant differences in the location of the stenosed vessel. Our results suggest that once sufficient muscle has been rendered ischemic to produce an S-T segment shift, the location of the diseased vessel cannot be predicted from the number or location of positive electrocardiographic leads or from the depth of S-T segment depression. Kaplan et al.6 were also unable to predict the location of single vessel coronary disease in 18 patients who underwent submaximal treadmill tests using leads I, aVF and Vg or CMS.s The presence of extensive collateral vessels to the stenosed vessel was not associated with a decreased likelihood of S-T segment depression or an increased work capacity. Similar results have been reported by Martin and McConahay.2 Thus, extensive collateralization in patients with single vessel disease is not a cause of false negative electrocardiographic results. Decreased sensitivity of the test is related mainly to the degree of coronary arterial narrowing and to the location of the diseased vessel. Myocardial scintigraphy: The sensitivity of myocardial scintigraphy in detecting single vessel disease (range 43 to 92 percent, Table IV) is greater than that reported for exercise electrocardiography.7-14 In studies that reported sensitivity according to location of the diseased vessel,lO perfusion defects were more common when the left anterior descending coronary artery was obstructed. False negative scans were more common in patients with well developed collateral vessels (p
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TABLE IV Reported Sensitivity of Exercise Myocardial Scintigraphy for Single Vessel Dlsease

First Author

FIGURE 3. Patient 9 (group B). A septal perfusion defect (arrow) during exercise is seen in this patient, who had a 95 percent stenosis in the left anterior descending artery and no collateral vessels. The exercise electrocardiogram shows horizontal S-T segment depression in leads Vg, CMs and CCs.

degree of collateralization with wall motion abnormalities and angina but there are few data that correlate the physiologic effects of large collateral vessels visualized on angiography with exercise test results.20922-25 Collateral vessels usually become visible when the degree of luminal stenosis exceeds 75 to 90 percent and the collateral channels measure 100 mm or more.22 Smaller collateral vessels are not visualized with conventional angiographic techniques and consequently could not be assessed in our study. The sensitivity of myocardial scintigraphy for small perfusion defects may be increased with use of the seven pinhole collimator.26 The radionuclide technique we used in this study is the standard method used in most nuclear medicine laboratories. Collateral blood vessels are more common in patients with multivessel diseasez5; our study group was highly selected. We chose patients with isolated single vessel stenosis of 90 percent or greater to avoid the variable of proximal luminal obstruction that might jeopardize collateral flow and we included no patients with a prior myocardial infarction in order to have a

h4assie7 LenaerG Bodenheimers Bloodi McCarthy’ 1 Botvinick12 Ritchie13 Bailey14 Present study

Minimal Degree of Luminal Stenosis

n

Sensitivity (%)

15 13 16

9’: 56

ii

2

z: 70 70

8 46

:s

;;

(%) 70

t

71

ft

z

73t

Sensitivity of 100 percent (7 of 7) for stenosis of left anterior descending artery (LAD), of 86 percent (6 of 7) for stenosis of right coronary artery (RCA), of 25 percent (1 of 4) for stenosis of left circumflex coronary artery (LCx). t Sensitivity of 81 percent (13 of 16) for stenosis of LAD, of 50 percent (2 of 4) for stenosis of RCA and of 50 percent (1 of 2) for stenosis of LCx. l

more homogeneous study group. Our results show that collateral vessels can cause false negative thallium scans but do not influence the exercise electrocardiogram. The apparent discrepancy between these two noninvasive tests indicates the importance of the diagnostic approach selected to detect myocardial ischemia. One possible explanation of this discrepancy is that the coronary collateral circulation can result in nontransmural or subendocardial rather than transmural ischemia. Exercise electrocardiography readily detects subendocardial ischemia, whereas exercise thallium-201 scintigraphy may be more easily defined in the presence of transmural myocardial ischemia. Thus, large collateral vessels may affect the pattern and distribution of myocardial ischemia and both exercise electrocardiography and thallium-201 scintigraphy may reveal different aspects of ischemia.

TABLE III Reported Sensitivity of the Exercise Electrocardiogram for Single Vessel Disease Stenotic Vessel (%) First Author

LAD

RCA

LCX

Kassebaum’ Martin2 r;;F4rys

33

50

-

92

sa 44

29 42

Go&$lager5 Present study

5358 z:

s60

60 50

Lead System

Total 4/E (50%) 8123 19/31(61%) (35%)

&

31167 20/51(39%) 18139 (46%) 30137 (81%)

;:1, &F, Vs/CMs 12, CCs, CM5, CL

Minimal Degree of Luminal Stenosis (%)

12

50 50 75 sx

LAD = left anterior descending coronary artery; LCx = left circumflex

-

9”:

coronary artery; RCA = right coronary artery.

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References 1. Kassebaum OG, Sutherland KI, Judkins MP. A comparison of hypoxemia and exercise electrocardiography in coronary artery disease. Am Heart J 1988;75:759-78. 2. Martin CM, McConahay OR. Maximal treadmill exercise electrocardiography. Circulation 1972;48:958-82. 3. MeHenry PL, Phlllps JF, Knoebel SS. Correlation of computer quantitated treadmill exercise electrocardiogram with arteriographic location of coronary artery disease. Am J Cardiol 1972; 30:747-52. 4. Bartel AJ, Behar VS, Peter RH, Orgaln ES, Kong Y. Graded exercise stress tests in angiographically documented coronary artery disease. Circulation 1974;49:348-58. 5. Goldschlager N, Seizer A, Cohn K. Treadmill stress tests as indications of presence and severity of coronary artery disease. Ann Intern Med 1978;85:277-88. 8. Kaplan MA, Harrls CN, Aronow WS, Parker OP. Ellestad MH. Inability of the submaximal treadmill stress test to predict the location of coronary disease. Circulation 1973;47:250-5. 7. Massle 6. Botvlnlck EH. Brundaae B. Correlation of thallium-201 scintigram with coronary anatomy: factors affecting region by region sensitivity. Am J Cardiol 1979;44:818-22. 8. Lenaers A, Block P, Van Thlel E, et al. Segmental analysis of thallium-201 stress myocardial scintigraphy. J Nucl Med 1977; 18:509-18. 9. Bodenhelmer MB, Banka VS, Fooshee CM, Helfant RH. Extent and severity of coronary heart disease. Determinations by thallous chloride 201 myocardial perfusion scanning and comparison with stress electrocardiography. Arch Intern Med 1979;139:830-4. 10. Blood OK, McCarthy OM, Sclacca RR, Cannon PJ. Comparison of single-dose and double-dose thallium-201 myocardial perfusion scintigraphy for the detection of coronary artery disease and prior myocardial infarction. Circulation 1978;58:777-88. 11. McCarthy OM, Blood OK, Sclacca RR, Cannon PJ. Single dose myocardial perfusion imaging with thallium-201: application in patients with nondiagnostic electrocardiographic stress tests. Am J Cardiol 1979;43:899-908. 12. Botvlnfck EH, Taradash MR, Shames OM, Parmley WW. Thallium-201 myocardial perfusion scintigraphy for the clinical clarification of normal, abnormal and equivocal electrocardiographic stress tests. Am J Cardiol 1978;41:43-51. 13. Rltchle JL, Zaret BL, Strauss HW, at al. Myocardial imaging with thallium-201: a multicenter study in patients with angina pectoris

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or acute myocardial infarction. Am J Cardiol 1978;42:345-50. 14. Bailey IK, Grlfflth LSC, Rouleau J, Strauss HW, Pltt 6. Thallium201 myocardial perfusion imaging at rest and during exercise. Comparative sensitivity to electrocardiography in coronary artery disease. Circulation 1977;55:79-87. 15. Bruce RA. Exercise testing of patients with coronary heart disease. Ann Clin Res 1971;3:323-32. 18. Chaltman BR, Bourassa MO, Wagnlarl P, Corbara F, Ferguson RJ. Improved efficiency of treadmill exercise testing using a multiple lead ECG system and basic hemodynamic exercise response. Circulation 1978$7:71-g. 17. Kurlta A, Chaltman BR, Bourassa MG. Significance of exerciseinduced junctional S-T depression in evaluation of coronary artery disease. Am J Cardiol 1977;40:492-7. 18. Rlgo P, Becker LC, Grlfflth LSC, et al. Influence of coronary collateral vessels on the results of thallium-201 myocardial stress imaging. Am J Cardiol 1979;44:452-8. 19. Bourassa MO, Lesp&ance J, Campeau L. Selective coronary angiography using a percutaneous femoral technique. Can Med Assoc J 1970;102:170-3. 20. Bourassa MG, Lesperance J, Oavld P. Considerations sur le r6le de la circulation collaterale dans la maladie coronarienne. Ann Cardiol Angeiol (Paris) 1974;23:473-8. 21. Sandler H, Dodge HT. The use of single plane angiograms for the calculation of left ventricular volumes in man. Am Heart J 1988; 751325-34. 22. Bourassa MG, Sollgnac A, Goulet C, Lesperance J. Regression and appearance of coronary collaterals in humans during life (abstr). Circulation 1974;5O:Suppl ll:ll-127-35. 23. Hamby RI, Antabllan A, Schwertz A. Reappraisal of the functional significance of the coronary collateral circulation. Am J Cardiol 1978;38:305-9. 24. Harrls CN, Kaplan MA, Parker OP. Aronow WS, Ellestad MH. Anatomic and functional correlates of intercoronary collateral vessels. Am J Cardiol 1972;30:81 l-4. 25. Levln DC. Pathways and functional significance of the coronary collateral circulation. Circulation 1974;50:831-8. 28. Vogel RA, Klrch DL, LeFree MT, Ralnwaks JO, Jensen OP, Steele PP. Thallium-201 myocardial perfusion scintigraphy: results of standard and multi-pinhole tomographic techniques. Am J Cardiol 1979;43:787-93.

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