The Magnitude of Exercise-Induced ST Segment Depression and the Predictive Value of Exercise Testing

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1 Clin. Cardiol. 2, (1979) 0 G. Witzstrock Publishing House Inc. The Magnitude of Exercise-Induced ST Segment Depression and the Predictive Value of Exercise Testing P. A. NAHORMEK, M.D., R. A. CHAHINE, A. MONTERO, M.D., R. J. LUCHI, M.D. M.D., A. E. RAIZNER, M.D., J. I. THORNBY, PH. D., T. ISHIMORI, M.D., From the Cardiology Section, Department of Medicine, Baylor College of Medicine and VA Medical Center and the Biostatics Section at the VA Medical Center, Houston, Texas, USA Summary: To assess whether the magnitude of exercise induced ST segment depression improves the predictive value of symptom limited exercise tests, and helps in the recognition of patients with more severe coronary heart disease, 90 consecutive patients with positive treadmill tests who also underwent selective coronary arteriography were reviewed. The predictive value. improved progressively with the increasing ST depression and was most reliable in a select group of patients with normal electrocardiographic baseline who were not receiving digitalis (73% with ST depression 3 1 mm to 100% with ST depression 3 4 mm). The incidence of 2 and 3 vessel disease increased from with ST depression 1 mm in the overall population to 100% with STdepression 3 4 mm in the select group, and the incidence of left main trunk lesions increased, respectively from 6 to 30%. The prediction of 2 and 3 vessel disease was found to be significantly greater when patients were dichotomized into those with ST depression 3 4 mm compared to < 4 mm. It is concluded that the magnitude of ST segment depression definitely improves the predictive value of exercise tests as well as the ability to recognize the patients with more severe disease. However, the markedly positive exercise tests cannot be utilized to accurately predict the presence of 2 or 3 vessel disease in individual cases unless ST depression Address for reprints: Robert A. Chahine, M.D. Chief, Cardiology Section VA Medical Center Houston, Texas Received: January 22, 1979 Accepted with revision: April 9, 1979 attains 4 mm or more in patients with normal electrocardiographic baselines who are not taking digitalis. In this group, the ability to predict left main trunk lesion is approximately 30 /0. Keywords: exercise testing, predictive value of exercise tests, magnitude of ST depression, coronary heart disease, left main trunk lesions, false positive tests Introduction After several decades of experience with exercise testing in the evaluation of ischemic heart disease and extensive correlations with coronary arteriograms (6, 10, 16, 17) and subsequent coronary events (8, 13,21), it would seem inappropriate to merely interpret test results as positive or negative. Although 1 mm or more of horizontal or downsloping ST segment depression remains the most popular criterion utilized in the interpretation of these tests (9, 18, 20), various studies have shown that thorough analysis of the morphology of the STsegment (3,12,15), magnitude of the depression (1 1, 14, 25), level of exercise at which the ST abnormalities appeared (1 1, 12) the presence or absence of associated chest pain (5, 24), arrhythmias (1, 23), or hypotension (19, 22) could significantly improve the predictive value of symptom limited exercise tests and help in the assessment of the severity and prognosis of the underlying disease. The markedly positive exercise test, with STdepression of more than 2 or 3 mm, has generally been found to correlate with more severe coronary disease (1 1, 14, 25). However, in one study, subjects with ST segment depression of 4 mm or more showed no greater incidence of subsequent coronary events than other positive responders (8), thus raising a question about the predictive value of the strongly positive tests. In addition, markedly positive exercise tests were found to be frequently associated with left main trunk

2 P. A. Nahormek et al: Magnitude of Exercise-Induced ST Depression 287 involvement (4). Further studiesshowed that such STdepression was highly sensitive in the diagnosisof left main coronary disease but was rather nonspecific, and the latter diagnosis accounted for only 20% of the patients with this exerciseinduced ST segment change (14). Some of the discrepancies were ascribed to the selection of patients and the methodology utilized during the exercise tests (7). Most studies were performed on a selective group of patients with known coronary heart disease and normal resting ST segments (1 1,25). The purpose of this study is to evaluate the predictive value of the magnitude of ST segment depression in an unselected patient population presenting to the exercise diagnostic laboratory for routine clinical cardiovascular work-up. Materials and Methods Ninety consecutive patients who had 1 mm or more of horizontal or downsloping ST segment depression on treadmill testing and who also underwent selective coronary arteriography within a week from the exercise test, constituted the subjects for this study. The treadmill tests were performed according to the Bruce protocol (2). A 12-lead electrocardiogram (ECG) was obtained in the sitting and standing positions, within an hour before starting the exercise test, in all patients. Three electrocardiographic leads consisting of V3, V5 and avf were monitored continuously during exercise and recordings were obtained at 1 min. intervals. A repeat 12-lead ECG was obtained immediately upon stopping, and then the three lead recordings of V3, V5 and avf were repeated at 1 min intervals post-exercise for at least 10 min, or until complete return to baseline. The blood pressure was also determined before starting, at the end of each stage, and at peak exercise using a standard clinical sphygmomanometer. The patients were exercised to symptomatic end points: moderately severe angina, dyspnea or exhaustion. The treadmill results were stratified according to the magnitude of the ST segment depression. Exercise tests with 2 1 mm, 2 2 mm, 2 3 mm, 2 4 mm and 2 5 mm ST depression were analyzed with regard to predictive value for coronary disease, as well as the incidence of 2 and 3 vessel coronary heart disease and left main trunk involvement, in order to assess the severity of disease. It should be kept in mind that the group of patients with ST depression 2 1 mm would include all those with 5 2 mm, 5 3 mm, 5 4 mm, and 5 5 mm. The group of patients with ST depression 5 2 mm would include all those with 3 3 mm, 5 4 mm, and 5 5 mm, etc. The coronary angiograms were performed according to standard techniques. Significant coronary heart disease was considered to be present when at least one or more major coronary arteries had a critical lesion which was defined as 75% or more decrease in lumen diameter. A patient was considered to have 1,2 or 3 vessel disease depending on how many of his major vessels had critical lesions. The left main coronary artery was considered to be critically narrowed if there was 50% or more decrease in its lumen diameter, and was considered equivalent to 2 vessel disease. The treadmill test was considered to be true positive when the exercise ECG showed 1 mm or more of horizontal or downsloping ST depression and the corresponding coronary angiogram showed at least one major vessel with a critical lesion. The predictive value (PV) was determined according to the following formula: PV = TP+FP (TP = True Positive and FP = False Positive). The predictive value for significant coronary heart disease was calculated for each of the groups stratified according to the magnitude of ST depression. In order to assess the effect of magnitude of ST depression on the ability to predict severity of disease, the incidence of 2 and 3 vessel disease and left main coronary artery involvement was also determined in each group. A select group of patients was identified on the basis of normal or near normal ST segments in the monitored electrocardiographic leads (Fig. 1) and no digitalis intake prior to the exercise test. These will be referred to as Group A in contradistinction to Group B which comprised the patients with abnormal baseline ECG (Fig. 2) and those receiving digitalis. The effect of ST depression on predictive value was tested using the Wilcoxon Rank Sum Test. One-tailed tests were utilized, addressing the question whether predictive value improves significantly with increasing ST depression. Effects of dichotomizing the ST depression data at 4 mm, and comparisons between patient groups, were tested using statistics which have approximately a X2 distribution under the null hypotheses. These latter tests were all two-tailed. Table I summarizes the predictive value of these treadmill tests for coronary heart disease in the overall population studied as well as in Groups A and B separately. The predictive value progressively improved from 73% with ST depression 3 1 mm to 89% with ST depression 2 5 mm in the overall population (p. < 0.01). Similarly the predictive value increased from 88% to 100% in Group A and from 57% to 67% in Group B. The predictive value was significantly greater in Group A than in Group B (p < 0.02). Table I Magnitude of exercise induced ST depression and predictive value of TMT overall Group A Group B STD 3 1 mm 65/90 (73%) 38/43 (88%) 27/47 (57%) STD 3 2 mm 52/66 (79%) 25/28 (90%) 27/38 (71%) STD 3 3 mm 43/53 (81%) 19/20 (95%) 24/33 (73%) STD 2 4 mm 16/18 (89%) 10/10 (loo%) 6/8 (75%) STD 3 5 mm 8/9 (89%) 6/6 (100%) 2/3 (67%)

3 288 P. A. Nahormek et al: Magnitude of Exercise-Induced ST Depression v3 v5 AVF Fig. 1 Marked exercise-induced ST segment depression in a patient with normal baseline electrocardiogram V3 V5 AVF Fig. 2 Marked exercise-induced ST segment depression in a patient with abnormal baseline electrocardiogram Table I1 summarizes the predictive value for two aspects of seventy of disease in the overall population studied. The prevalence of 2 and 3 vessel coronary heart disease increased from 61 % in patients with ST depression 3 1 mm to 89% in those with ST depression 5 5 mm (p. < 0.05), Table I1 Magnitude of exercise induced ST depression and the severity Of heart disease n 2 & 3 vessel CHD LMT STDslmm (61%) 5 ( 6%) STD mm (64%) 4( 6%) and the prevalence of left main trunk lesions increased from STD 3 3 mm (66%) 4( 8%) 6% to 22% (p. > 0.05). STD 3 4 mm (89%) 3 (17%) STD 5 mm 9 8 (89%) 2 (22%)

4 P. A. Nahormek et al: Magnitude of Exercise-Induced ST Depression 289 Tables 111 and IV represent a similar analysis of the treadmill results in Groups A and B. The prevalence of 2 and 3 vessel coronary heart disease in Group A increased from 69% to 100% (p > 0.05) and left main trunk involvement from 12% to 30% (p > 0.05), as ST depression increased from 2 1 mm to 2 5 mm. Failure to attain statistical significance in the subgroups of Table I11 is most probably due to the smaller number of patients involved in the analysis since the directional pattern of effects is even more pronounced than in Table 11. The trend in Group B was essentially similar to that of Group A, but to a lesser degree. Table I11 Magnitude of exercise induced ST depression and the serverity of coronary heart disease in group A n 2 & 3 vessel CHD LMT STDalmm 43 30( 69%) 5 (12%) STDa2mm 28 20( 71%) 4 (14%) STDa3mm 20 15( 75%) 4 (20%) STDa4mm (100%) 3 (30%) STDa5mm 6 6 (l0oyo) 2 (30%) Table IV Magnitude of exercise induced ST depression and the seventy of coronary heart disease in group B n 2 & 3 vessel CHD STDalmm (53%) STDa2mm (58%) STDa3mm (61%) STDa4mm 8 6 (75%) STD a 5 mm 3 2 (67%) If we dichotomize the ST depression values at 4 mm in Tables 11, I11 and IV we find a distinct increase in predictive value for 2 and 3 vessel disease in the overall population (Table II), the prevalence of 2 and 3 vessel disease increased from 54% for patients with ST depression < 4 mm to 89% for those with ST depression 3 4 mm (p < 0.02). Similarly in Group A (Table 111) the prevalence of 2 and 3 vessel disease increased from 6 1% for patients with ST depression < 4 mm to 100% for patients with STdepression b 4 mm (p < 0.05). However, in Group B (Table IV) dichotomization at 4 mm ST depression failed to show a statistically significant difference (p > 0.05). Discussion This study clearly reinforces previous observations that the magnitude of the exercise-induced ST depression improves the predictive value of treadmill tests and helps in the recognition of patients with more severe disease (1 1, 14, 25). In addition, it helps explain the discrepancies in previous studies (7) by analyzing the magnitude of ST depression in an unselected patient population presenting to the exercise laboratory for routine clinical cardiovascular work-up and by taking into consideration the effect of abnormal electrocardiographic baseline in such patients. As shown in Table I, analysis of the magnitude of exercise induced ST segment depression will help improve the predictive value of exercise tests no matter at what point the cut-off is selected, and regardless of whether the baseline ST segment is normal or abnormal. The predictive value of treadmill tests improved progressively from 73% with ST depression 3 1 mm to 89% with ST depression 3 5 mm in the overall population studied. Similar trends were noted in both the patients with normal or near normal baseline ST segment (Group A) and those with abnormal baseline and digitalis intake (Group B) with the predictive value significantly better in the former and virtually attaining 100% when such patients with ST b 4 mm are selected. Similar observations can be made with regard to the recognition of the patients with more severe disease, namely those with two and three vessel coronary artery involvement and those with left main trunk lesions as shown in Tables 11, I11 and IV. It should be noted that in patients with normal baseline and no digitalis intake, when ST depression is B 4 mm the recognition of patients with 2 and 3 vessel disease is virtually loo%, but the recognition of patients with left main trunk involvement is at best 30%. Nevertheless, this represents a sizeable percentage and exercise testing remains an important non-invasive technique to alert us to this high risk group of patients. While the predictive value for the presence of coronary heart disease improved progressively and significantly with any degree of ST segment depression, the ability to recognize the patients with more severe disease is best improved significantly when the ST depression is 3 4 mm. When patients are dichotomized into those with ST depression 3 4 mm and those with < 4 mm the difference in recognizing patients with a 2 and 3 vessel disease is statistically significant in the overall population studied (p < 0.02) as well as in Group A (p < 0.05), but not in Group B (p > 0.05). The possibility that baseline ST segments were not analyzed in this manner may account for some of the discrepancies in earlier studies (8, 11). It is therefore concluded that the magnitude of exerciseinduced ST segment depression definitely improves the predictive value of treadmill tests and helps in the recognition of patients with more severe coronary heart disease. The predictive value of the magnitude of ST depression is accentuated by the exclusion of patients with abnormal baseline and those who are receiving digitalis. However, the markedly positive exercise test cannot be utilized to predict the presence of 2 or 3 vessel disease in individual cases unless the ST depression attains 4 mm or more. Of perhaps greater importance, ST depression of 3 4 mm in patients with normal electrocardiographic baseline predicts left main trunk involvement in almost one-third of the patients.

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