Importance of coronary collateral circulation in interpreting exercise test results

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<ul><li><p>lnt&amp;reting </p><p>of Coronary Collateral </p><p>Exercise Test Results </p><p>JULIO F. TUBAU, MD BERNARD R. CHAITMAN, MD, FACC MARTIAL G. BOURASSA, MD, FACC JACQUES LESPliRANCE, MD GEORGES DUPRAS, MD </p><p>Montreal. Quebec, Canada </p><p>From the Montreal Heart Institute and the Uni- versity 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, ac- cepted July 29, 1980. </p><p>AWess for reprints: Bernard Ft. Chaitman. MD. Montreal Heart Institute, 5000 East, Belarger Street, Montreal, HlT lC8, Quebec, Canada. </p><p>Circulation in </p><p>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. </p><p>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 </p></li><li><p>COLLATERAL VESSELS AND EXERCISE TESTING-TUBAU ET AL. </p><p>Electrocardiographic exercise test: Each patient un- derwent 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 age- predicted maximal heart rate. </p><p>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 be- fore 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. </p><p>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 ex- tent of myocardial ischemia. </p><p>Assessment of collateral circulation: Coronary angiog- raphy was performed using the transfemoral approach.19 A coronary arterial stenosis of 90 percent or greater of the lu- minal diameter was considered a significant lesion for the purpose of this study; this degree of narrowing is usually re- quired to demonstrate collateral vessels at angiography. The presence of collateral circulation was assessed by an experi- enced 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). </p><p>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. </p><p>Results </p><p>Coronary angiography: Obstructive coronary ar- tery disease (90 percent or greater stenosis of the lu- minal diameter) was present in the left anterior de- </p><p>scending coronary artery in 22 patients, in the left cir- cumflex coronary artery in 5 patients and in the domi- nant 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 opac- ified 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). </p><p>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 elec- trocardiographic responses than did those with right or left circumflex coronary arterial stenosis (95 percent [21 of 221 versus 60 percent [9 of 151; p </p></li><li><p>COLLATERAL VESSELS AND EXERCISE TESTING-TUBAU ET AL. </p><p>TABLE I </p><p>Correlation of Exercise Electrocardiographic and Scintigraphic Results With Coronary Angiography </p><p>Exercise Test Thallium Perfusion Angiography Age (yr) Defect </p><p>&amp; Leads Max S-T An- Max HR Final % Collateral Case Sex Positive Depression gina (per min) TT (s) Rest/Ex Location Stenosis Vessels </p><p>Group A: Patients With Collateral Vessels </p><p>1 46M CMs 1.5 + 156 210 +/++ Septal 100% LAD RCA - LAD </p><p>2 51M v3-vs, CM?5 cc5 </p><p>165 645 --/+ Septal-apical 95% LAD RCA </p><p>LCX - LAD </p><p>3 48M Vs-Vs, II, aVF, 2 + 114 405 -/+ Septal CM5, CCs, CL </p><p>4 40M v3-vs, CM5. 4 - 170 660 -I- - cc5 </p><p>100% LAD RCA </p><p>LCX - LAD </p><p>100% LAD Diag </p><p>LCX - LAD </p><p>5 32M V4-Vs. Ill, aVF, 5 + 153 690 -I- - 90% LAD RCA - LAD CCs, CMs, CL </p><p>6 57F vs. CM5 3 F 123 360 -1-k Septal </p><p>7 5atd Vs. CCC,, CM5 2.5 + 158 240 -l- </p><p>95% LAD RCA </p><p>LCX - LAD </p><p>100% LAD I </p><p>RCA </p><p>LCX - LAD </p><p>! 56M V4, CM5, CC5 1 - 167 690 -I- - 100% LCX Diag - LCx 5aM 1V4-Vs, CM5 1.5 - 172 735 -/- - 95% RCA LCx - RCA </p><p>10 26F - 0 - 167 600 -/- - 100% RCA LCx - RCA </p><p>Group B: Patients With Minimal or No Collateral Vessels </p><p>1 .48M - 0 + 153 720 +/++ Septal-apical 100% LAD - </p><p>3 40M CMs </p><p>: </p><p>+ 165 645 -/+ Septal-inf 95% LAD - 62M vcv,. CM57 + 117 la0 --/+ Ant-lat, 90%LAD - </p><p>4 45M Vcc:M V:: CM: : z </p><p>147 360 -/+ apical </p><p>90% LAD - </p><p>: 58F 144 270 f/++ </p><p>Septel Ant-lat 90% LAD - </p><p>57F :* $ : :: </p><p>147 525 -/+ 90% LAD - 7 53F 5. 5 167 480 -1-F </p><p>Septal S&amp;p&amp;-;pi- 90% LAD - </p><p>t 35F 1 </p><p>+ la3 580 -J-F </p><p>-/+ Sepia1 100% LAD - </p><p>40F 115 500 Septal 95% LAD - 10 49M </p><p>~$CgMr 4 6. 5s t + 136 630 +/++ Inf-apical 100% LCX - </p><p>:: 43M V-; CM </p><p>v;, cb,, CE, + </p><p>: - 145 600 --/+ </p><p>-1-F Inf-posterior 90% RCA - </p><p>33F 177 660 Ant-lat 95% RCA, - Diag </p><p>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. </p><p>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 </p></li><li><p>COLLATERAL VESSELS AND EXERCISE TESTING-TUBAU ET AL. </p><p>TABLE II </p><p>Extent of Thallium-201 Perfusion Defect </p><p>No Two Defect Seaments </p><p>&gt;Two Seaments </p><p>Group A (n = 10) </p><p>6 (60%) 3 (30%) l(iO%) </p><p>Group B (n = 12) </p><p>0 (0%) 5 (42%) </p><p>p &lt; 0.005 </p><p>7 (58%) </p><p>p = probability. </p><p>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 electrocardio- gram 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. </p><p>exercise protocols and lead systems, the inclusion of patients with previous myocardial infarction, the lo- cation 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 electrocar- diogram and left ventricular contraction pattern at rest. </p><p>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 re- sults of other investigators.4*6 The difference may rep- resent (1) the amount of myocardium that can be ren- dered 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 suf- ficient to show significant differences in the location of the stenosed vessel. Our results suggest that once suf- ficient 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 </p><p>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 collateral- ization 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. </p><p>Myocardial scintigraphy: The sensitivity of myo- cardial 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 </p></li><li><p>COLLATERAL VESSELS AND EXERCISE TESTING-TUBAU ET AL. </p><p>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. </p><p>degree of collateralization with wall motion abnor- malities and angina but there are few data that correlate the physiologic effects of large collateral vessels visu- alized on angiography with exercise test results.20922-25 Collateral vessels usually become visible when the de- gree 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 in- creased 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 labo- ratories. 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 </p><p>TABLE IV </p><p>Reported Sensitivity of Exercise Myocardial Scintigraphy for Single Vessel Dlsease </p><p>First Author </p><p>h4assie7 LenaerG Bodenheimers Bloodi McCarthy 1 Botvinick12 Ritchie13 Bailey14 Present </p><p>study </p><p>n </p><p>15 13 16 </p><p>ii 8 </p><p>46 </p><p>f t </p><p>Sensitivity </p><p>(%) </p><p>9: 56 </p><p>2 t </p><p>:s 71 73t </p><p>Minimal Degree </p><p>of Luminal Stenosis </p><p>(%) </p><p>70 </p><p>z: 70 70 </p><p>;; </p><p>z </p><p>l Sensitivity of 100 percent (7 of 7) for stenosis of left anterior de- scending artery (LAD), of 86 percent (6 of 7) for stenosis of right cor- onary 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. </p><p>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 ap- proach selected to detect myocardial ischemia. </p><p>One possible explanation of this discrepancy is that the coronary collateral circulation can result in non- transmural 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 collat- eral vessels may affect the pattern and distribution of myocardial ischemia and both exercise electrocardiog- raphy and thallium-201 scintigraphy may reveal dif- ferent aspects of ischemia. </p><p>TABLE III </p><p>Reported Sensitivity of the Exercise Electrocardiogram for Single Vessel Disease </p><p>First Author </p><p>Minimal Stenotic Vessel (%) Degree of </p><p>Lead Luminal LAD RCA LCX Total System Stenosis (%) </p><p>Kassebaum 33 50 - Martin2 </p><p>4/E (50%) 12 </p><p>r;;F4rys 92 8123 </p><p>Go&amp;$lager5 5358 </p><p>sa 44 29 42 19/31(61%) (35%) &amp; </p><p>z: s 50 31167 20/51(39%) 18139 (46%) Present stud...</p></li></ul>