ECG Diagnosis of Coronary Artery Disease: A Comparison of 3-Lead Ambulatory ECG Registration and Exercise Testing Fredrik J.

Frogner, M.D. and Steen Juul-Moller, M.D., Ph.D., FESC Department of Cardiology, University Hospital, Malmo, Sweden Objective: In order to assess the diagnostic accuracy of ST depression in the diagnosis of coronary artery disease (CAD) in patients with suspected myocardial ischemia we compared ST depression in 3-lead ambulatory ECG (AECG) with that of exercise tolerance testing (ETT). Methods: Significant coronary artery stenosis in coronary angiography was used as a standard reference. ST analysis could be performed in 106 of the investigated 113 patients, all with suspected CAD. One person with left bundle branch block was excluded from the ST analysis, and six persons could not perform ETT. Results: Seventy-eight of the 106 patients had at least one significant stenosis (>70% narrowing) and 28 had no stenosis according to coronary angiography. The sensitivity for AECG was 62% and for ETT it was 63%, the specificity for AECG was 79% and for ETT the specificity was 57%. The accuracy for AECG was 66%, and for ETT it was 61%. We also evaluated late potentials (LPs) from the AECG tapes in order to correlate LP to left ventricular function (LVF), myocardial infarction (Ml), and/or CAD. We found that LP correlates better to advanced CAD than to Ml or LVF. Conclusion: The accuracy of ST diagnosis of CAD in patients with suspected myocardial ischemia using AECG was equal to that of a maximal ETT. LP finding from an AECG tape may support the argument for CAD in patients with ST depressions at AECG. A.N.E. 1997;2(2):141-145 myocardial ischemia; ambulatory ECG; exercise test Noninvasive diagnosis of coronary artery disease (CAD) is a controversial clinical topic. The routine method is ST segment analysis of ECG, and the most widespread ECG method for ST analysis is the maximal exercise tolerance test (ETT). In addition to the ST response, ETT also provides information about blood pressure reaction, chest pain, and exercise capacity, together forming a well-evaluated judgment of the patient.1 Lately, the ambulatory ECG (AECG) has been increasingly popular for diagnosing transient myocardial ischemia. Its clinical role, however, in diagnosing CAD has been second to that of ETT.2 The AECG method was first described in 1962,3 and since then it has been improved so that it now offers a wide selection of analyses including long-term arrhythmias, late potentials (LPs), and heart rate variability (HRV) in addition to the ST segment analysis. Since the number of leads in AECG has increased from 1 or 2 to 3, it may be time to redefine the use of this method in diagnosing CAD. The purpose of this study was to compare the AECG ST analysis from 3 leads (Franks orthogonal leads or X, Y, Z leads) to that of a conventional 12-lead maximal ETT, using the results from a coronary angiography as golden standard. We also wished to correlate LP from AECG to CAD, left ventricular function (LVF), and/or myocardial infarction (MI). METHODS Patients Ninety-one consecutive patients of both sexes were referred to coronary angiography for preoper-

The source of funding was a grant from the Swedish Heart and Lung Foundation. Address for reprints: Steen Juul-Moller, M.D., Department of Cardiology, University Hospital, S-205

02 Malmo, Sweden. Fax: 46-4033-6209. 141

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ative evaluation of angina pectoris. These patients were subsequently investigated with 24-hour AECG and maximal ETT in connection to the angi-ography. Furthermore, 22 consecutive patients with typical angina pectoris and normal coronary angiography were included after similar investigations with 24-hour AECG and maximal ETT. All patients including 53 patients with previous MI, were investigated due to symptomatic CAD. Two patients were treated with digitalis, 63 were on calcium antagonists, 69 had long-acting nitroglycerin, and 66 patients were treated with /3-blockade at the time of the investigation. The patients included 79 males (mean age 60.6) and 34 females (mean age 58.1). Patients with ST depression (STD) (i.e., at least 0.1-mV plateau or downsloping depression in at least 2 leads) on 12-lead resting ECG were not enrolled in this study. Also, patients with echocar-diographic diagnosed left ventricular hypertrophy were not enrolled. Seven of the 113 patients who underwent coronary angiography could not be evaluated with both of the ECG methods. One had left bundle branch block (LBBB), and was thus excluded from ST segment analysis. The remaining six patients could not perform ETT due to unstable angina pectoris. Thus, 106 patients were investigated with both ETT and AECG for ST segment analysis. All patients performed physical activities during the AECG monitoring. Twenty-eight patients had no CAD (0 vessel disease [vd]) according to the coronary angiography, 25 had one vessel disease (1 VD), 23 had two vessel disease (2 VD), and 30 had either three vessel disease or main stem lesion (3 VD/MS). Patients with 3 VD and MS lesion are regarded as one group, since the risk of cardiac events is especially high among these patients. LPs could be analyzed in 103 of the 113 patients. In nine patients the total noise vector exceeded 1.00 [AV and one person was not analyzed due to LBBB; all others were analyzed irrespective of QRS duration. Patients with at least two abnormal of the following were considered to have LPs 4,5: (1) Total QRS duration >120 ms; (2) RMS40 <25 //V; and (3) LAS40 >40 ms. A 4-polar Butterworth filter, 40 -250 Hz, was used in the

micropotential analysis. Cardiac Catheterization Significant CAD was defined as a stenosis of the coronary area of >70% in at least one major vessel. The lesions were measured by a digital method

from two-dimensional (2-D) digitized x-ray pictures selected by the radiologists. LVF was eyeballed during the cardiac catheterization and was classified as normal, slightly decreased (hypokinesis in at least one left ventricular segment), or severely decreased (akinesis or inverse movement in at least two segments of the left ventricle). For the purpose of this study, a main stem stenosis was grouped equal to 3 VD. All investigations were judged independently by two experienced radiologists. Ambulatory ECG Recording A 3-lead Model 423 Dynacord AM ECG tape recorder and a Del-Mar Strata Scan (Del Mar Avionics, Irvine, CA, USA) 563 ECG computer system was used for obtaining and evaluating all tapes. The recordings were semiautomatically analyzed without knowledge of the outcome in the other tests. All tapes were autocalibrated, 10 mm equal to 1 mV. An ischemic episode (STD) was defined as a transient horizontal or downsloping ST segment depression of a0.1 mV comparing a measure point between p and Q to a measure point at the J point. The slope (horizontal or

downsloping) was measured 0.64 seconds after the J point. The shortest acceptable duration was 1 minute. For each episode a 25 mm/s ECG print-out was made. In case of baseline deviations, the actual deviation at the second measurement point was calculated in order to correctly estimate the depression. The AECG tests were analyzed without knowledge of the outcome of the other diagnostic tests. ETT All patients underwent a maximal ETT, using a bicycle ergometer and Marquette Case 12 equipment (Marquette Electronics, Inc., Milwaukee, WI, USA). The patients were asked to refrain from smoking for at least 6 hours before the test, which was performed between 9 and 11 A.M. The patients were exercised in the sitting position starting with a workload of 60 watts, which was increased by 10 watts every minute until a Borg-scale score of 15 or until symptoms. Leads CH 1-6 were observed during the test and a print-out of the standard 12-lead ECG during the test was analyzed and repeated after 3, 6, and 10 minutes, or until the ECG had returned to normal. All ST readings were performed at 0.80 seconds after the J point. The exercise tests were

A.N.E. April 1997 Vol. 2, No. 2 Frogner and Juul-Moller ECG in CAD 143

Evaluation of ST Diagnosis of CAD Comparing 24 Hour Ambulatory ECG (AECG) and Maximal Exercise Tolerance Test (ETT) with the Findings from Coronary Angiography as Standard Pred. Pred. Sensitivity Accurac Value/ Value/ Specificity y Positive Negative 62% 89 AE 42 66 79% 63% % CG % % 57% 80 ET 36 61 % The number of true positive tests were 48 for AECG and 49 for ETT. The number of true negative tests were 22 for AECG and 16 for ETT. There were 6 false positive tests for AECG and 12 for ETT. The number of false negative tests were 30 for AECG and 29 for ETT. Tabl e1 analyzed without knowledge of the outcome of the other two diagnostic tests. Statistical Analysis Sensitivity, specificity, predictive values, and accuracy were determined using standard techniques. Odds ratio (OR) was used to describe the LP data. Fisher's exact test was used to calculate P values. A P value <0.05 was considered statistically significant. RESULTS AECG Versus ETT Compared to angiography verified CAD, the accuracy for AECG was 66% and for ETT 61% (Table AECG ETT 1). Seventy-eight patients had at least one significant coronary artery stenosis. AECG identified 48 and ETT 49 of these patients correctly. Combining AECG and ETT, the ST segment analysis was pathological in 62 of these patients (Fig. 1). Three VD or main stem stenosis was demonstrated in 30 patients, and STD was found in 20 (AECG) and in 20 (ETT). Six of these patients had STD in neither of the methods. For this group the diagnostic sensitivity combining AECG and ETT was 80%. In 28 patients no significant CAD was found. AECG identified 22 and ETT 16 of these correctly. The distribution of ST segment depressions according to the number of diseased vessels demonstrates an increasing rate of true abnormal STD with increasing number of diseased vessels (Fig. 2). Micropotential Analysis Among the 103 patients that could be evaluated for LP 49 had had an MI, and 15 of those had LP. Fifty-four had had no MI, and 14 of those had LP, OR = 1.26 (0.53-2.99). Thirtyfour of the 103 patients had 3 VD/MS of whom 16 had LP. Of the \aAECQ PETT ;

ANGIOGRAPHY

4J % 2 1 Min

56% 44 %

6 1 %

7 6 6

i'" 1 Negative in all methods: 13 No sten n= I vessel disease n-25 2 disease n-23 $ dise n=3

Figure 1. Relationship between the three diagnostic methods used. Positive findings are represented within the respective circles. Negative findings are represented outside of respective circle.

Figure 2. Distribution of ST segment depression according to the number of vessels with stenosis among 106 patients who have undergone coronary angiography.

144 A.N.E. April 1997 Vol. 2, No. 2 Frogner and Juul-Moller ECG in CAD

Table 2. Relationship Between Different Subsets of Patients with Respect to LP Analyzed from Ambulatory ECG Tapes Ml vs. no Ml Normal LVF vs. Decreased LVF 0 VD vs. 3 VD/MS 1.03(0.46-2.34) NS NS 1 -2 VD vs. 3 VD/MS 0-2 VD vs. 3 VD/MS

Odds ratio 1.26(0.53-2.99) 3.83(3.83-9.26) P-Value NS

3.20(0.98-10.45) 4.22(1.57-11.39) <0.01 <0.005

LVF = left ventricular function; Ml = myocardial infarction; MS = main stem lesion; VD = vessel disease. remaining 69 patients 13 had LP, OR = 3.83 (1.58-9.26). Forty-four of the patients had abnormal LVF, and 16 had LP. Fifty-nine had normal LVF of whom 21 had LP; OR = 1.03 (0.46-2.34). The statistical relationship between different subsets of patients with respect to LP can be viewed in Table 2. Figure 3 shows the distribution of LP in relationship to number of stenosed vessels. DISCUSSION ST segment analysis is a basic tool for identifying CAD. Until now ETT has been the overall dominating test. However, in special situations where ETT is not feasible, AECG has been used. The rejection of AECG as a general routine method for ST analysis is a consequence of the very few studies comparing ETT and AECG in an unbiased manner. One of these studies demonstrated a better diagnostic precision for ETT,6 while four others showed that the methods identify somewhat different patient populations, and that they are complementary.7"10 In contrast, in several investigations AECG ST analysis have had greater prognostic value than that of ETT,11 especially after MI,1213 and it has been suggested that those with AECG ST depression have a greater amount of myocardium at risk than those without ST depression.14 It has been shown that the amplitude of ST segSO 40 < 7 30-% wtt hLP 2010. 0< . 22 17 --3 VD/MS n>34

Figure 3. LP related to number of stenosed vessels. LP = late potential.

ment depression on AECG is related to the extent of reversible scintigraphic perfusion abnormalities.15 In the present study, we used a 3-lead AECG monitor instead of the conventional 2-lead AECG monitors used in the previous studies. We found that a 3-lead AECG had a diagnostic accuracy comparable to that of a standard ETT in relationship to angiographic findings. Both methods had a relatively low sensitivity in patients with 3 VD/MS. However, the sensitivity could be substantially improved combining AECG and ETT. Gianrossi et al.16 reported a sensitivity of 68% and a specificity of 77% when applying a metaanalysis to 147 consecutively published reports comparing exercise-induced ST depression with coronary angiogra-phy.16 In the present study the specificity of ETT was 57%. This difference may be explained by the difference in diagnostic criteria between Gianrossi et al.16 and the present study (50% narrowing vs 70% as a minimum for significant stenosis at coronary angiography) in combination with different selection criteria

in the metaanalysis. All patients in the present study performed physical activities during the AECG monitoring, which may have improved the accuracy of the AECG ST analysis. In the present study, 13 patients with significant coronary artery stenosis had only STD at AECG, not during ETT. The majority of these patients had stenosis at the right coronary artery, and the greater specificity using AECG compared to ETT may reflect our use of the orthogonal Frank leads during AECG, covering even the inferior and posterior part of the heart. The exercise tolerance test is covering the anterior wall better than the inferior using only chest leads during the exercise. This difference in lead placement may explain the better specificity for AECG than for ETT. LPs are thought to reflect damaged tissue that serves as substrate for ventricular arrhythmias. It has previously been shown that LPs are related to ventricular tachycardia (VT) following MI.1718 It has also been shown that guided surgery may extin-

A.N.E. April 1997 Vol. 2, No. 2 Frogner and Juul-Moller ECG in CAD 145

guish both LP and VT.19 Occlusion of a major coronary artery in dogs has been shown to produce a zone with decreased amplitude in the high frequency components within the QRS complex,20 similar to that found in patients with LP. Abboud et al.21 have also demonstrated that those zones are more frequently found in patients with CAD (78%) than among those without CAD (15%). Vatterott et al.22 have shown that reperfusion of an infarct related artery following MI leads to a diminished frequency of LP as compared with patients with an occluded artery. In our study, we found no relationship between decreased LVF or MI and LP, while we found that LPs are more frequently found among patients with advanced CAD (3 VD/MS ) than among others. These findings may indicate that a concomitant diagnosis of LP can be utilized as an extra argument for CAD in patients with ST depression. In conclusion, 3-lead AECG can reliably be utilized for routine diagnosis of CAD. Also, LP correlates better to advanced CAD than to LVF or MI. Limitations of the Present Study The reproducibility of the ST results from the two ECG methods is dependent of the composition of diseases in the investigated patient group. We have only investigated patients with a clinical diagnosis of angina pectoris. However, we have not only investigated consecutive patients referred for coronary angiography, but also a selected group of angina patients with normal findings at coronary angiography. This improves the analysis for specificity of the ECG methods, but impairs the reproducibility of the results. REFERENCES 1. Bruce RA, Hornsten TR. Exercise stress testing in evaluation of patients with ischemic heart disease. Prog CardiovascDis 1969;11:371-390. 2. ACC/AHA Task Force Report Guidelines for Ambulatory Electrocardiography. J Am Coll Cardiol 1989; 13:249-258. 3. Holter N J. New method for heart studies with continuous electrocardiography of active subjects. Science 1962j: 138: 12141220 4. Kelen G. Ambulatory electrocardiography

signal averaging. Cardiol Clin 1992;3:539549. 5. Fetsch T, Pietersen AH, Shenasa M. Holter system for late potentialscomparison between Holter based and real-

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19.Marcus NH, Falcone RA, Dresden C A, et al. Body surface late potentials: Effects of endocardial resection in patients with ventricular tachycardia. Circulation 1984;70:632-637. 20.Mor-Avi V, Shargorodsky B, Abboud S, et al. Effects of coronary occlusion on highfrequency content of the epicar-dial electrogram and body surface electrocardiogram. Circulation 1987;76:237-243. 21.Abboud S, Belhassen B, Miller HI, et al. High frequency electrocardiography using an advanced method of signal averaging for noninvasive detection of coronary artery disease in patients with normal conventional electrocardiogram. J Electrocardiol 1986;19:371-380. 22.Vatterott PJ, Hammill SC, Bailey KR, et al. Late potentials on signal-averaged electrocardiograms and patency of the infarct-related artery in survivors of acute myocardial infarction. J Am Coll Cardiol 1991;17:330-337.