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Evaluation of R Wave Amplitude Changes versus ST-Segment Depression in Stress Testing PETER E. BONORIS, M.D., PAUL S. GREENBERG, M.D., GEORGE W. CHRISTISON, MARK J. CASTELLANET, M.D., AND M. H. ELLESTAD, M.D. Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 SUMMARY Exercise ECGs and coronary angiograms were reviewed in 266 patients (81 normals and 185 with significant coronary artery disease). Thirty-three false positive and 96 false negative ST responses to stress testing were purposely chosen to determine if the R wave could reduce the number of false ST responses. R wave amplitude changes were measured in the control and in the immediate postexercise period. An increase or no change in R wave was taken as evidence of an abnormal response, while a decrease in the R wave was a normal response. The sensitivity by ST segment was 48% and the specificity was 59%. These values were low because of the large number of false positive and negative ST responses in the study. It was our purpose to determine if these lowered values could be significantly improved by the R wave. Using R wave criteria, the sensitivity was 63% (P < 0.01) while the specificity was 79% (P < 0.01). The sensitivity and specificity of stress testing can be significantly improved using R wave changes. EXERCISE STRESS TESTING is undoubtedly one of the most common noninvasive methods for detecting coronary artery disease. However, it is known that stress testing fails to accurately distinguish all cases and because of this some criticism has been directed at the test.' Sensitivity and specificity is dependent on the prevalence of disease in most studies. It has been shown that as the specificity increases the sensitivity decreases, the values also being dependent on the degree of ST depression used to denote disease. McConahay,' using the double Master's test for ST depression of . 0.75 mm, reported a sensitivity of 42% and specificity of 91%, but when he used ST . 1 mm, the sensitivity was 35% and the specificity 100%. Mason et al.,3 using a near-maximal exercise test for ST depression > 0.75 mm, reported a sensitivity of 84% and a specificity of 83%, and when they used ST depression of > 1 mm found the sensitivity to be 78% and the specificity 89%. This study was undertaken to test two new criteria for exercise ECG evaluation. to 69 (mean 49.2). In the CAD group were 63 males with ages ranging from 37 to 72 (mean 55.8) and 15 females whose ages ranged from 40 to 70 (mean 56.6). The DMI group constituted 53 males with ages from 29 to 66 (mean 51.3), and eight females with ages from 40 to 74 (mean 53.6). The AMI group consisted of 39 males 39 to 74 years of age (mean 53.4) and seven females whose ages ranged from 27 to 64 with a mean of 53.2. Another group of 53 apparently healthy subjects, 39 males and 14 females, underwent maximal treadmill stress testing for screening evaluation. Their ages ranged from 19 to 38 with a mean of 30. Their history and physical examination revealed no evidence or symptoms of heart disease. These patients were volunteers, with no known risk factors for coronary artery disease, in a Long Beach Heart Association study of risk factors and had not undergone angiography.4 Patients with hypertension, cardiomyopathy, conduction defects, valvular diseases or who had been taking digitalis in the last two weeks, or beta-blockers, diuretics or nitrates within 48 hours were excluded. The interval between the treadmill stress test and coronary angiography ranged from the same day to 4 months with an average of one week. Materials and Methods A retrospective study was done reviewing the records of 266 nonconsecutive patients with a treadmill stress test (TST) and a coronary angiogram in a two-year period from 1974 to 1976. Thirty-three false positive and ninety-six false negative ST responses to treadmill stress testing were purposely chosen sequentially from a computer printout of patients in our files who satisfied the restrictions cited. The 266 patients were analyzed in four groups as follows: normal patients, patients with coronary artery disease (CAD) without previous myocardial infarction, patients with previous transmural diaphragmatic infarction (DMI), and patients with previous transmural anterior infarction (AMI). Criteria for previous infarction were Q waves of 0.04 sec or more in leads III, aVF, or in V2-V6. In the normal group were 51 males whose ages ranged from 25 to 72 (mean 48.6) and 30 females with ages from 31 Treadmill Stress Test Patients underwent a progressive maximal treadmill stress test (TST) according to the Ellestad protocol5 I using the maximal predicted heart rate as a target end point. Three leads (CM,, a vertical bipolar lead, and a unipolar V1 lead) were monitored continuously and recorded in the sitting position (control) and in the standing position immediately after exercise. The mean difference between the R-wave sitting and standing was 0.5 mm. The R wave control measurement was taken in the sitting position for comparison with ST changes which we routinely measure sitting for the control value. The CM, lead was used for all measurements. ST depression > 1 mm below the resting level 60 msec from the J point if horizontal or downsloping and > 1.5 mm of depression at 80 msec if upsloping, in the immediate postexercise period, was defined as positive (ischemic). R wave amplitude was measured from the isoelectric line to the peak of the R wave in mm for an average of 12 consecutive beats. The average value was used in the study so the respiratory variation, if any, was From the Division of Clinical Physiology, Section of Cardiology and the Memorial Hospital Medical Center, Long Beach, California. Supported in part by funds from the Long Beach Heart Association and Memorial and Children's Medical Center Foundation. Address for reprints: M. H. Ellestad, M.D., Department of Clinical Physiology, Memorial Hospital Medical Center, 2801 Atlantic Avenue, Long Beach, California 90801. Received September 12, 1977; revision accepted December 23, 1977. 904 EXERCISE STRESS TESTING/Bonoris et al. Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 minimized. An increase in R wave amplitude or no change immediately after exercise was defined as evidence of abnormality, while a decrease in the amplitude was defined as evidence of a normal response. In a previous study,7 we noted that R wave increase correlated with coronary disease while a decrease correlated with no or minimal disease. As the normal patient exercises, tachycardia and catecholamine release result in a reduced left ventricular volume and by the Brody effect a decrease in R wave, while the patient with coronary disease, as exercise progresses and ischemia develops, increases his left ventricular volume and R wave increases. An index (ARST) was formed from the algebraic summation of the R wave and ST-segment changes. ST depression was taken as a positive value. The R wave was taken as positive if there was an increase and negative if a decrease (fig. 1). An index of 0 or a positive value was taken to represent abnormality, while a negative index was taken as evidence of a normal response. Treadmill stress tests were evaluated in each group using three criteria: ST depression, change in R wave amplitude, and the index (,ARST). Specificity and sensitivity for each criteria were determined and compared each with the other criteria. Specificity and sensitivity in each criteria were compared to determine if the index or the R wave changes could significantly reduce the number of false positive and negative responses by ST criteria. The numbers of false positive and negative responses were purposely large numbers and therefore resulted in a low sensitivity and specificity. However, it was our purpose to see if these lowered values could be improved by the R wave or index. 905 Heart Catheterization Left and right heart catheterization and coronary angiography were performed using the Sones or Judkins technique. Coronary angiography was performed on 35 mm film with multiple views. Left ventricular angiography was performed in the RAO position. Occlusion of 70% or more of luminal diameter in one or more coronary arteries was defined as significant, while normal coronary angiograms were defined as no occlusion or less than 30% cross sectional narrowing. Patients with obstruction of 31% to 69% were arbitrarily excluded from the study. Coronary arteries were divided into branches according to the reporting system of the American Heart Association.8 The coronary anatomy was examined by two independent observers without knowledge of the treadmill stress test and any discrepancies were resolved by a third observer. Results Angiographically Normal Group Treadmill Stress Test The ST segments were normal in 48 (59%) and positive in 33 (4 1 %) of the 81 patients with normal coronary anatomy. The high incidence of false positives was due to patient selection as noted previously. The R wave increased in 14 (17%) by 3.6 mm ± 0.9 SEM. Three (4%) showed no change and 64 (79%) showed a decrease of 3.45 + 0.25 mm (fig. 2). These differences in the R wave amplitude were significant lo0 * * R INCREASE R DECREASE R NO CHANGE 64 80, 70L 46 60[ I~- z 'a 50* I 40 30 20 1C 0/I ,'0 _ _ f _ __ AR -1 _ _ ~~ST =+2_ - -_ARST FIGURE 1. = _ 1 I _ 1 1 Ir +1 Schematic representation of calculation of the index (ARST), in two cases with STdepression and R wave increased and decreased. 25 14 II NORMAL I CAD DMI AMI FIGURE 2. R wave amplitude changes in the normal and in the disease groups. Decrease in R wave amplitude is seen primarily in normal patients. In the A MI group the percentage of the patients with a decrease in R wave amplitude is higher than that with increase. Numbers on the top of the bars represent the number of patients. 906 CIRCULATION (P < 0.01). The index (ARST) was negative in 57 (70%) and in 24 (30%) of the patients was 0 or positive. Thus, of the 81 patients with normal coronary anatomy, 59% had a negative test and 41% were false positives by ST criteria. Evaluation by changes in R wave amplitude revealed 64 (79%) had a true negative test and 17 (21%) had a false positive one. By using ARST as a criterion, 57 (70%) had a negative index (true negative test) and 24 (30%) had an index of 0 or a positive value (false positive test) (fig. 3 and 4). The R wave was more specific than the ST segment (P < 0.01) or index (P < 0.05) in detecting normal subjects. The index, although not significantly different from the ST, still gave better results. Ventricular Function Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 Although all patients had normal coronary arteries, it is very interesting that eleven (65%) of the seventeen with increased or no change in R wave amplitude had segmental abnormalities in the left ventriculogram and five of them had significant ST-segment depression. CAD Group Treadmill Stress Test There were 78 patients in this group. Of these, 44 (57%) were true positives by ST criteria and the remaining 34 (43%) were negatives. The R wave increased in 46 (59%) by + 2.98 ± 0.41 mm, remained the same in 7 (9%), and decreased in 25 (32%) by - 2.83 ± 0.33 mm (fig. 2). All these differences were significant (P < 0.01). The index was 0 or positive in 59 (76%) patients and negative in 19 (24%). Thus, the sensitivity by ST-was 57%, by R 68%, and by ZXRST 76% (fig. 3). Severity of Disease Of the 46 patients with an increase in R wave amplitude, 10 (22%) had single vessel disease, 17 (37%) had two vessel disease and 19 (41%) had three vessel disease. Of the 25 patients with a decrease in R wave amplitude, 10 (40%) had single vessel disease, 10 (40%) had two vessel disease and five (20%) had three vessel disease. Out of seven patients with no change in the R wave, five (71%) had two vessel disease, and two (29%) had three vessels with significant cross-sectional narrowing (table 1). Diaphragmatic Myocardial Infarction Group Treadmill Stress Test Of the 61 patients with previous diaphragmatic infarction, 29 (48%) were classified as having a positive exercise ECG and 32 (52%) as having a negative test using STsegment depression as the criterion. The R wave increased in 32 (53%) patients by + 4.58 ± 0.65 mm and decreased in 22 E ST I.- ER 90, n ST 90 8 7 VOL 57, No 5, MAY 1978 ER O ARST Li ARST 80 70 50 60 C,, I.- + LU I-- 20 1{ 0 1 2Z 3 4 I~- C* 50 LU E 40 24 30 20 10 I- 7 0 TN 70/^ - CAD NORMAL AMI DMI FIGURE 3. Sensitivity and specificity by the three criteria in normal and diseased groups. The ability of R wave changes or the Index (ARST) to detect disease is significantly higher than that of ST alone. FP TP FN OVERALL DISEASED FIGURE 4. True negative (TN), false positive (FP), true positive NORMAL (TP), and false negative (FN) by three criteria in the normal and in the overall diseased group. The sensitivity was higher by R and increased more by ARST. The R wave was more specific than the ARST, which was more sensitive. The ST was significantly less sensitive and specific when compared to the other two criteria. EXERCISE STRESS TESTING/Bonoris et al. 907 TABLE 1. Correlation Between R Wave Amplitude Changes and Diseased Vessels Vessels CAD N = 78 DMI Patients 1 2 3 1 2 3 4 or more T 46 (59) 25 (32) 7 (9) 32 (53) 22 (36) 7 (11) 15 (33) 22 (48) 9 (19) 93 (50) 69 (37) 23 (13) 10 (22) 10 (40) 17 (37) 10 (40) 5 (71) 19 (41) 5 (20) 2 (29) 9 (19) 7 (28) 6 (13) 4 (16) 1 (14) 20 (44) 6 (24) 3 (43) 3 (9) 7 (32) 5 (16) 5 (23) 3 (43) 2 (13) 5 (23) 1 (11) 15 (16) 24 (35) 2 (8) 36 (39) 27 (39) 13 (57) 16 (50) 5 (23) 4 (57) 7 (47) 8 (36) 2 (22) 42 (45) 18 (26) 8 (35) 3 (9) 5 (23) 2 (13) 7 (32) 2 (22) 13 (40) 10 (45) 3 (43) 6 (40) 7 (32) 5 (56) 11 (24) 8 (32) 3 (43) 8 (25) 8 (36) 1 (14) 2 (13) 3 (14) 4 (45) 21 (23) 19 (28) 8 (35) 16 (50) 4 (18) 3 (43) 9 (60) 10 (45) 2 (22) 45 (48) 20 (29) 8 (35) l T N = 61 l AMI N = 46 l Overall disease l N = 185 Branches R wave changes T T 2 (13) 4 (18) 2 (22) 14 (15) 16 (23) 2 (8) 13 (14) 14 (290) 5 (22) Numbers in parentheses represent percentages. Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 (36%) by - 2.28 ± 0.31 mm (P < 0.01). In seven patients (I %) the R wave did not change (fig. 2). The index (ARST) was 0 or positive in 41 (67%) patients and negative in the remaining 20 (33%) of the 61 patients. Thus, the sensitivity in patients with diaphragmatic infarction was 48% by ST criteria, 64% by R, and 67% by ARST. The false negative responders were 52% using the ST, and 36% using the R wave amplitude. The index in this group was again more sensitive with a false negative incidence of 33% (fig. 3). Severity of Disease Of the 32 patients with an increase in R wave amplitude, three (9%) had single vessel disease, 13 (40%) had two diseased vessels, and 16 (50%) had three vessel disease. Of the 22 with a decrease in R wave amplitude, seven (32%) had single vessel disease, 10 (45%) had two vessel disease and five (23%) had three diseased vessels. Out of seven with no change in R wave, three (43%) had two and four (57%) had three vessel disease (table 1). Anterior Myocardial Infarction Group Treadmill Stress Test In this group, 46 patients with a previous anterior myocardial infarction were studied. Of these, 16 (35%) were found to have a positive exercise ECG, and 30 (65%) were false negative using ST criteria. The R wave increased in 15 (33%) by + 2.73 ± 0.49 mm, showed no change in nine (19%), and decreased by - 2.59 ± 0.31 mm in 22 (48%) (P < 0.01), (fig. 2). Thus, with R wave changes as the criteria, 24 patients (52%) were found to have a positive exercise ECG and 22 (48%) were false negative. The index was 0 or positive in 27 (59%) and negative in 19 (4 1%) of the 46 patients (fig. 3). Severity of Disease The distribution of the diseased vessels in this group was as follows: Of the 15 with increase in R wave, two (13%) had single vessel disease, six (40%) had two and seven (47%) had three vessels with significant disease. Of the 22 with decrease in R wave, seven (32%) had single vessel disease, seven (32%) had two, and eight (36%) had three vessel disease. Finally, of the nine patients with no changes in the R wave, two (22%) had single, five (56%) had two, and two (22%) had three vessels with significant obstruction (table 1). All Patients with Coronary Artery Disease This group included all 185 patients with coronary artery disease with or without a previous infarction. Of these, 89 (48%) had a true positive and 96 (52%) a false negative exercise ECG according to the ST pattern. Using the R wave amplitude changes, 116 (63%) were true positives (P < 0.01) and 69 (37%) were false negatives. The sensitivity increased when the index (AvRST) was used for the interpretation. Thus, 127 (69%) of the 185 patients were classified correctly (P < 0.01) and only 58 (31%) patients were found to have a false negative exercise ECG (fig. 4). The index was more sensitive than ST and R (P < 0.01). Severity of Disease Of the 93 patients with increase in R wave, 15 (16%) had single vessel disease, 32 (34%) had two, and 42 (45%) had three diseased vessels. Of the 69 with a decrease in R wave, 24 (35%) had single vessel disease, 27 (39%) had two, and 18 (26%) had three significantly occluded vessels. Out of 23 with no change in R wave, two (9%) had one, 13 (56%) had two, and eight (35%) had three vessel disease (table 1). False Positive and False Negative Group In order to test our data, the 33 false positives and the 96 false negative patients by ST-segment criteria were analyzed separately. All of these patients had been interpreted 100% incorrectly by ST alone. Using the R wave amplitude changes, there were a total of 17 false positive responses. Of the 33 false positive ST responses, 23 (70%) were correctly identified by the R wave. The R wave reduced the 96 false negative ST responses by 47 (51%). The index (ARST) was more sensitive but somewhat less specific. There were 24 false positive responses and 58 false negative responses by using the index (fig. 5). The breakdown in males and females, and the sensitivity VOL 57, No 5, MAY 1978 CIRCULATION 908 RST RST 33 100 90 70 (3%) had 60 z versus no change. Correlation Between ST and R Wave Amplitude In the normal group, 70% of the 33 patients with ST depression (false positives) had a decrease in R wave amplitude immediately after exercise, while the percentage of R wave decrease in the true negatives was 86%. In the overall diseased group, the correlation was as follows: 75% of the 89 patients with ST depression had increased R wave amplitude and in 25% it was decreased (table 3). 501 40 30 Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 20 Discussion The most extensively studied parameter of exercise ECG is ST depression, which has been found to be fairly well correlated with the presence of coronary artery disease on angiography as well as with coronary events in a long term follow-up study.9"- McConahay,' Mason,3 Kassebaum," Bailey," and Lewis et al.14 report sensitivities from 78 to 50% and specificities in the range of 80 to 90%, all higher than in our series. Our reported sensitivity of 48% and specificity of 59% were low because of the large numbers of false positive and negative responses which we purposely included to determine if the R wave changes or index could reduce these false responses by ST criteria and therefore enhance the sensitivity and specificity of the treadmill stress 10 ~o FP FN FIGURE 5. The percentage of false negative (FN) and false positive (FP) tests by the three criteria. All the patients in this group were classified incorrectly by ST segment changes. The R wave and the index were more sensitive and specific, so the number of false responders was minimized. and specificity for all groups and all three criteria, in table 2. are shown test. Statistical Analysis The fact that CM, may explore primarily the anterior wall be a cause for a false negative exercise ECG in patients with previous anterior infarction and disease in the vessels nourishing the anterior wall only. Had we used ischemic changes in the other leads recorded, we would expect a 5 to 10% increase in sensitivity. The sensitivity, measured by ST-segment depression and the presence of false negative responders, depends on the severity of the disease" 1", 15 patients with single vessel disease are commonly false negatives. Our data support this The three criteria were analyzed in patients with and without coronary artery disease, using the McNemar test. The results are as follows: Normal patients: R versus ST X2 = 9.4 (P < 0.01) R versus RST X' = 5.1 (P < 0.05) RST versus ST X2 = 2.1 N.S. Overall diseased group: R versus ST X2 = 11.3 (P < 0.01) can so TABLE 2. Specificity and Sensitivity in Males and Females by ST, R, and ARST Normal (N = 81) CAD (N = 78) DM1 (N = 61) Males Females Males Females Males Females (N 51) (N = 30) (N = 63) (N = 15) (N = 53) (N = 8) = ST R ARST ST X2 = 22.9 (P < 0.01) R X2 = 8.1 (P < 0.01) Young Healthy Group Of the 53 young asymptomatic healthy subjects who did not have angiograms and were evaluated for screening only, 48 (90%) had a decrease in the R wave amplitude immediately after exercise, four (7%) had an increase, and one 80 EU versus FP TN FP TN FN TP FN TP FN TP FN TP 23 28 10 20 26 37 8 7 25 28 7 1 AMI (N 46) Overall disease (N = 185) Males Females Males Females (N = 39) (N = 7) (N = 155) (N = 30) FN TP FN TP FN TP FN TP = 26 13 4 3 77 78 19 11 (45) (55) (33) (67) (41) (59) (53) (47) (45) (55) (88) (12) (67) (33) (57) (43) (50) (50) (63) (37) 12 39 5 25 18 45 7 8 18 35 4 4 18 21 4 3 54 101 15 15 (23) (77) (17) (83) (29) (71) (47) (53) (34) (66) (50) (50) (46) (54) (57) (43) (35) (65) (50) (50) 16 35 8 22 15 48 4 11 17 36 3 5 17 22 2 5 49 106 9 21 (31) (69) (27) (73) (24) (76) (27) (73) (32) (68) (37) (63) (44) (56) (28) (72) (32) (68) (30) (70) Numbers in parentheses represent percentages. EXERCISE STRESS TESTING/Bonoris et al. 909 TABLE 3. Correlation Between ST and R Normal Overall dis. AMI DMI CAD * ** STp STn N = 48 N = 44 N = 34 N = 29 N = 32 N = 16 N = 30 N = 89 N = 96 N 10 7 34 19 25 14 8 16 67 49 or-% 30 N 23 14 41 77 10 56 15 86 4 44 18 50 8 53 14 75 22 51 %70 86 23 44 14 56 50 47 25 49 RWA T l N = 33 ST, ST. STp STn STp ST. STp STn 47 *Significant (ischemic) ST depression. **ST with no depression. Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 concept, but the changes in the R wave consistently correlate better with the angiograms than does the ST-segment depression. The number of false positive patients, based on ST segments, in this study was 33 (41%) of 81 with normal coronary arteries. We believe the inclusion of a large group of known false positives provides the opportunity to rigorously test the R wave criteria. Analysis of changes in the R wave amplitude make it possible to increase the specificity from 59% to 79%, and the sensitivity as follows: in the CAD group from 57% to 68%, in the DMI group from 48% to 64%, and in the AMI group from 35% to 52%, and finally in all patients with coronary artery disease from 48% to 63%. Using the index (ARST), the specificity was 70%, which is somewhat lower than by R wave but higher than found using the ST segment. The sensitivity was 76%, 67%, and 59% for CAD, DMI, and AMI, respectively, and 69% for the overall diseased group. As table 3 shows, 25% of the patients with ST depression had a decreased R wave amplitude, which according to our criteria should represent a negative stress test. On the other hand, 51% of the patients with no ST depression but with disease (false negatives) had an increase in R wave amplitude, a finding which would suggest disease. Fourteen percent of the normals without ST depression had an increase in R wave, while 25% of the patients with coronary disease and ST depression had a decrease in R wave. These discrepancies can be reduced by the index (ARST), but eventually the combination of these findings with other coexisting signs and symptoms will play the most important role.4 Prospective studies are needed to resolve these differences before R wave criteria can be clinically im- plemented. Mechanism of R Wave Change Brody"6 postulated that the intracavitary blood mass influences the QRS complex. This has been documented by others in experiments with animals, by mathematical calculations, and by experimental models.'7-22 It would appear that under the sympathetic drive of exercise both systolic and diastolic volume progressively decrease even though stroke volume is maintained. The failure of the ischemic ventricle to decrease its volume during strenuous exercise"-" seems to be responsible for the absence of the usual reduction of the R wave amplitude. In a previous study, an increase in R wave correlated with more severe disease and more severe segmental abnormalities in the left ventriculogram.7 Consequently, in this study an increase or no change in R wave was taken to indicate coronary disease while a decrease in R wave was taken as a normal response to exercise stress testing. This tends to be supported in our young normal subjects in whom 90% had the expected reduction in the R wave. Although current evaluation of an exercise ECG is usually primarily based upon the ST-segment changes, other factors can affect the interpretation. These include angina during the test, presence of angina in the history, premature ventricular contractions or other arrhythmias during the test, duration of the test, hypotensive response to exercise, maximal systolic blood pressure, resting ECG, time of onset of the ST depression, heart rate response to exercise,26-3 and others. Ellestad4 showed that using multivariate analysis, these findings and symptoms increase the percentage of correct interpretation. The addition of these two new criteria may also be useful in the above method. The ability to identify 79% of those with normal coronary arteries is especially encouraging in view of the large group of false positives included in this patient sample. By using R wave amplitude changes and the index (ARST), the specificity increased by 20% and 1 1%, respectively. The sensitivity increased in the overall diseased group by 15% and 21%. The preliminary studies are encouraging, but it remains to be demonstrated how much these criteria will improve the predictive power of the exercise stress test when they are applied to other patient cohorts. Although statistically significantly better than STsegment depression alone, the R wave and index criteria still leave a considerable number of false positive and false negative responders. Acknowledgments The authors thank Larry J. Leamy, Ph.D. for the statistical analysis, and Mrs. Fritzie Cohn for secretarial assistance. References 1. Borer JS, Brensike JF, Redwood DR, Itscoitz SB, Passamani ER, Stone NJ, Richardson JM, Levy RI, Epstein SE: Limitations of the electrocardiographic response to exercise in predicting coronary artery disease. N Engl J Med 293: 367, 1975 2. McConahay DR, McCallister BD, Smith RE: Postexercise electrocardiography: Correlations with coronary arteriography and left ventricular hemodynamics. Am J Cardiol 28: 1, 1971 3. Mason RE, Likar I, Biern RO, Ross RS: Multiple-lead exercise electrocardiography. Experience in 107 normal subjects and 67 patients with angina pectoris, and comparison with coronary cinearteriography in 84 patients. Circulation 36: 517, 1967 4. Ellestad MH, Savitz S, Bergdall D, Teske J: The false positive stress test. Multivariate analysis of 215 subjects with hemodynamic, angiographic and clinical data. Am J Cardiol 40: 681, 1977 910 CIRCULATION 5. Ellestad MH: Stress Testing, Principles and Practice. Philadelphia, F. A. Davis Company, 1975, pp 67-100 6. Ellestad MH, Allen W, Wan MCK, Kemp GL: Maximal treadmill stress testing for cardiovascular evaluation. Circulation 39: 517, 1969 7. Bonoris P, Greenberg P, Castellanet M, Ellestad MH: Predictive value of R wave amplitude changes in treadmill stress testing. (abstr) Circulation Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 56 (suppl III): 111-197, 1977 8. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee on grading of coronary artery disease, Council on cardiovascular surgery, American Heart Association. Circulation 51 (suppl): 5-40, 1975 9. Mattingly TW: The postexercise electrocardiogram: Its value in the diagnosis and prognosis of coronary arterial disease. Am J Cardiol 9: 395, 1962 10. Robb GP, Marks HH: Latent coronary artery disease. Determination of its presence and severity by the exercise electrocardiogram. Am J Cardiol 13: 603, 1964 11. Doyle JT, Kinch SH: The prognosis of an abnormal electrocardiographic stress test. Circulation 41: 545, 1970 12. Kassebaum DG, Sutherland KI, Judkins MP: A comparison of hypoxemia and exercise electrocardiography in coronary artery disease. Diagnostic precision of the methods correlated with coronary angiography. Am Heart J 75: 759, 1968 13. Bailey IK, Griffith LSC, Rouleau J, Strauss HW, Pitt B: Thallium-201 myocardial perfusion imaging at rest and during exercise. Comparative sensitivity to electrocardiography in coronary artery disease. Circulation 55: 79, 1977 14. Lewis RP, Marsh DG, Sherman JA, Forester WF, Schaal SF: Enhanced diagnostic power of exercise testing for myocardial ischemia by addition of postexercise left ventricular ejection time. Am J Cardiol 39: 767, 1977 15. Cohn PF, Vokonas PS, Herman MV, Gorlin R: Postexercise electrocardiogram in patients with abnormal resting electrocardiograms. Circulation 43: 648, 1971 16. Brody DA: A theoretical analysis of intracavitary blood mass influence on the heart-lead relationship. Circ Res 4: 731, 1956 17. Manoach M, Grossman E, Varon D, Gitter S: QRS amplitude changes during heart filling and digitalization. Am Heart J 83: 292, 1972 VOL 57, No 5, MAY 1978 18. Nelson CV, Lange RL, Hecht HH, Carlisle FP, Ruby AS: Effect of intracardiac blood, and of fluids of different conductivities on the magnitude of surface vectors. (abstr) Circulation 14: 977, 1956 19. Manoach M, Gitter S, Grossman E, Varon D, Cassner S: Influence of hemorrhage on the QRS complex of the electrocardiogram. Am Heart J 82: 55, 1971 20. Nelson CV, Chatterjee M, Angelakos ET, Hecht HH: Model studies on the effect of the intracardiac blood on the electrocardiogram. Am Heart J 62: 83, 1961 21. Horan LG, Flowers NC, Brody DA: Body surface potential distribution: Comparison of naturally and artificially produced signals as analyzed by digital computer. Circ Res 13: 373, 1963 22. Bayley RH, Kalbfleisch JM, Berry PM: Changes in the body's QRS surface potentials produced by alterations in certain compartments of the nonhomogeneous conducting model. Am Heart J 77: 517, 1969 23. Mann T, Brodie BR, Grossman W, McLaurin LP: Effect of angina on the left ventricular diastolic pressure-volume relationship. Circulation 55: 761, 1977 24. Sharma B, Raphael MJ, Thadani V, Taylor SH, Steiner RE, Goodwin JF: Left ventricular pressure-volume changes during exercise-induced pain in patients with angina pectoris. (abstr) Br Heart J 36: 1038, 1974 25. McCans JF, Parker JO: Left ventricular pressure-volume relationships during myocardial ischemia in man. Circulation 48: 775, 1973 26. Bruce RA, Hornsten TR: Exercise stress testing in evaluation of patients with ischemic heart disease. Progr Cardiovasc Dis 2: 371, 1969 27. Cole J, Ellestad MH: Significance of chest pain during treadmill exercise. Am J Cardiol, in press 28. Lichtlen P: The hemodynamics of clinical ischemic heart disease, Ann Clin Res 3: 333, 1971 29. Thomson PD, Kelemen MH: Hypotension accompanying the onset of exertional angina. A sign of severe compromise of left ventricular blood supply. Circulation 52: 28, 1975 30. Hinkle LE Jr, Carver ST, Plakun A: Slow heart rates and increased risk of cardiac death in middle-aged men. Arch Intern Med 129: 732, 1972 31. Ellestad MH, Wan MKC: Predictive implications of stress testing. Follow-up of 2700 subjects after maximum treadmill stress testing. Circulation 51: 363, 1975 Vectorcardiographic Quantification of Infarct Size in Baboons SAMUEL A. WICKLINE, AND J. JUDSON MCNAMARA, M.D. SUMMARY A vectorcardiographic method has been developed for determining the absolute size of myocardial infarcts in baboons resulting from coronary artery ligation. Spatial area (mvolt * msec) and voltage (mvolt) difference-vectors were obtained for 8 animals by measuring the voltage loss and temporal deviation from pre- to postligation McFee scalar leads. The difference vectors were then correlated with the absolute infarct volumes, which were derived by histological assessment 10 days after ligation. Absolute lesion sizes ranged from approximately 2 cc to 14 cc, involving 10-30% of ventricular muscle mass. The correlation coefficient, r, for the area deviation index was 0.98 (SEE = ± 0.24 cc); and for the voltage deviation index, r was 0.92 (SEE = 0.51 cc). These results demonstrate that the severity of infarction can be accurately determined if prepathological vectorcardiograms are available. NONINVASIVE QUANTIFICATION of absolute infarct size using electrophysiological data would be of considerable benefit in the management of patients with acute infarctions and in the assessment of experimental therapeutic interventions. Although epicardial QRS and ST-complex changes during infarction have been correlated with subjacent myocardial necrosis,'-' the invasiveness of the recording technique precludes its eventual clinical implementation. Recent investigations of infarcts using extensive body surface maps indicate that surface potential recordings also contain a sub- stantial amount of potentially quantifiable information.4 These studies suggest that necrosis in specific ventricular wall segments will produce characteristic alterations in maps of body surface potential. By subtracting postinfarction and control thoracic potentials point-for-point, a voltage difference map that represents the original electrical contribution of the necrotic segment to the control map can be derived.4 This method of "difference mapping" appears promising, but body surface recording in general is too cumbersome and extenuating to be clinically practicable at present. From the Department of Surgery and Physiology, John A. Burns School of Medicine, University of Hawaii, Queen's Medical Center, Honolulu, Hawaii. Supported by NIH Grant HL1457-03A1. Address for reprints: J. Judson McNamara, M.D., Department of Surgery, Queen's Medical Center, 1301 Punchbowl Street, Honolulu, Hawaii 96813. Received August 3, 1977; revision accepted December 7, 1977. The simple vectorcardiogram offers an alternative source of noninvasive electrical data for examining acute and chronic infarctions. The vectorcardiographic representation of myocardial electrical activity as an equivalent dipole has proven its utility in diagnosis8512 and theoretical Evaluation of R wave amplitude changes versus ST-segment depression in stress testing. P E Bonoris, P S Greenberg, G W Christison, M J Castellanet and M H Ellestad Downloaded from http://circ.ahajournals.org/ by guest on August 13, 2017 Circulation. 1978;57:904-910 doi: 10.1161/01.CIR.57.5.904 Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231 Copyright © 1978 American Heart Association, Inc. All rights reserved. Print ISSN: 0009-7322. 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