Several studies demonstrated that in addition to conventional

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1 Long-Term Prognostic Value of Exercise Echocardiography Compared With Exercise 201 Tl, ECG, and Clinical Variables in Patients Evaluated for Coronary Artery Disease Leopoldo I. Olmos, MD; Habib Dakik, MD; Richard Gordon, MD; J. Kay Dunn, PhD; Mario S. Verani, MD; Miguel A. Quiñones, MD; William A. Zoghbi, MD Background The accuracy of exercise echocardiography and 201 Tl single photon emission computed tomography (SPECT) is similar in the diagnosis of coronary artery disease (CAD). However, comparative data on long-term prognosis are lacking. Methods and Results Clinical variables and exercise, echocardiographic, and 201 Tl tomographic parameters were studied in 248 patients (age, years [mean SD]; 189 men) who underwent simultaneous treadmill exercise 201 Tl SPECT and echocardiography. Follow-up was obtained in 225 patients (91%) at a mean of years. A total of 64 cardiac events occurred. With the use of stepwise logistic regression, 4 models simulating clinical stress testing scenarios were evaluated in the prediction of all cardiac events, ischemic events, and/or cardiac death. The best clinical models were exercise echocardiography with exercise ECG and exercise 201 Tl SPECT with exercise ECG. Both models were comparable in the prediction of cardiac events. For the exercise echocardiography model, exercise wall motion score index and induction of ischemia were the strongest predictors of events with ORs of 2.63 per unit increment (95% CI, 1.34 to 5.17; P 0.005) and 4.1 (95% CI, 1.32 to 12.79; P 0.015), respectively. For the model with exercise 201 Tl SPECT, the strongest predictor was ischemic perfusion defect (OR, 4.93; 95% CI, 1.72 to 14.08; P 0.003). The absence of ST changes during exercise decreased the risk of events. For the prediction of ischemic events and/or cardiac death, echocardiographic and 201 Tl parameters were the only predictive variables. Conclusions In patients evaluated for CAD, exercise echocardiography and 201 Tl combined with ECG variables provide comparable prognostic information and can be used interchangeably for risk stratification. (Circulation. 1998;98: ) Key Words: echocardiography coronary disease imaging ischemia prognosis Several studies demonstrated that in addition to conventional cardiac risk factors, resting left ventricular function and the presence or absence of stress-induced ischemia are among the most powerful predictors of cardiac events. 1 3 Currently, exercise echocardiography and radionuclide perfusion imaging are the 2 best modalities for the detection of exercise-induced ischemia and are superior to conventional stress ECG. 4,5 Although exercise echocardiography evaluates global and regional function and the radionuclide technique assesses relative myocardial perfusion, studies comparing these techniques have shown comparable results in the detection of coronary artery disease (CAD). 4,6 Current literature suggests that exercise echocardiography and radionuclide perfusion imaging are both capable of detecting subgroups of patients at higher risk for future cardiac events. 4,7 9 However, to date there has been no comparison of the 2 techniques for risk stratification in the same patients. The purpose of this study, therefore, was to compare the relative prognostic value of exercise echocardiography and exercise 201 Tl single photon emission computed tomography (SPECT) in patients with suspected or known CAD. The incremental prognostic value of both techniques compared with clinical variables and exercise ECG was evaluated. Methods Patient Population The population consisted of 248 patients (189 men; mean age, years) evaluated between 1986 and 1993 during a single treadmill exercise session who underwent exercise echocardiography simultaneously with 201 Tl SPECT. Most of these patients (85%) participated in a prospective study comparing the diagnostic value of exercise echocardiography with SPECT 201 Tl. 6 Patients were ex- Received May 29, 1998; revision received August 19, 1998; accepted September 2, Guest editor for this article was Richard L. Popp, MD, Stanford University Medical Center, Stanford, Calif. From the Section of Cardiology, Baylor College of Medicine and the Echocardiography and Nuclear Cardiology Laboratories of the Methodist Hospital, Houston, Tex. Correspondence to William A. Zoghbi, MD, Director, Echocardiography Research, Baylor College of Medicine, 6550 Fannin, SM 677, Houston, TX wzoghbi@bcm.tmc.edu 1998 American Heart Association, Inc. Circulation is available at

2 2680 Prognostic Value of Exercise Echo Versus 201 Tl TABLE 1. Baseline Characteristics of the Initial Study Population n % Male Chest pain History of myocardial infarction Diabetes mellitus Hypertension Hypercholesterolemia Smoking Obesity Prior revascularization Age (mean SD) was y. n 248. cluded if they had a recent myocardial infarction ( 2 months), significant valvular heart disease, dilated or hypertrophic cardiomyopathy, or previous cardiac transplantation. This investigation was approved by the institutional review board of Baylor College of Medicine. Baseline characteristics are depicted in Table 1. One hundred ninety-four patients (78%) were receiving cardiac medications consisting of calcium channel blockers in 47%, -blockers in 37%, nitrates in 31%, and aspirin in 44%. Indications for the test were evaluation of chest pain in 35%, screening for CAD in 52%, evaluation of ischemia 2 to 3 months after acute myocardial infarction in 8%, palpitations in 3%, and heart failure in 2%. Historical data were retrieved from medical records. Pretest probability of CAD 10 was low ( 25%) in 58% of patients, intermediate (26% to 69%) in 18%, and high ( 70%) in 24%. Cardiac catheterization was performed within 3 months in 84 patients, of whom 27 had single-vessel and 43 had multivessel disease. Exercise ECG All patients underwent a multistage treadmill exercise with the standard Bruce protocol. Criteria for interrupting the test were severe chest pain, diagnostic ST-segment shift 2 mm, extreme fatigue or dyspnea, systolic blood pressure 240 mm Hg, diastolic pressure 120 mm Hg, or the reaching of maximal age-predicted heart rate. ECG was diagnostic for ischemia when there was 1-mm flat or downsloping ST-segment depression 0.08 seconds after the J point. ST-segment depression in the presence of left bundle-branch block, TABLE 2. Association Between Exercise ECG Variables, Exercise Echocardiography, 201 Tl Variables, and Cardiac Events No Events (n 161) All Cardiac Events (n 64) P * Ischemic Events and Cardiac Death (n 24) P Cardiac Death (n 7) P Exercise ECG Normal, n (%) 88 (55) 21 (33) (50) (14) 0.08 Positive, n (%) 39 (24) 23 (36) (29) (57) 0.12 Nondiagnostic, n (%) 34 (21) 20 (31) (17) (29) 0.64 Angina, n (%) 8 (5) 4 (6) (0) (14) 0.28 Basal HR, bpm Max exercise HR, bpm Exercise duration, min Exercise 201 Tl Normal, n (%) 99 (62) 16 (25) 9 (38) 1 (14) Abnormal, n (%) 62 (39) 48 (75) (63) (86) Ischemia 15 (9) 13 (20) (13) (0) Fixed defect 43 (27) 27 (42) (42) (71) Mixed defect 4 (3) 8 (13) (8) (14) Abnormal segments, % Perfusion defect size, % Exercise 2D echocardiography Normal, n (%) 101 (63) 16 (25) 9 (38) 2 (29) Abnormal, n (%) 60 (37) 48 (75) (63) (71) Ischemia 9 (6) 12 (19) (8) (14) Fixed WMA 35 (22) 24 (39) (33) (43) Mixed WMA 16 (10) 12 (19) (21) (14) WMSI Rest Exercise LVEF, % Rest Exercise HR indicates heart rate; Max, maximal; 2D, 2-dimensional; WMA, wall motion abnormality; LVEF, left ventricular ejection fraction. *All cardiac events vs no events. Ischemic events and cardiac death vs no events. Cardiac death vs no events.

3 Olmos et al December 15, Figure 1. Event-free survival curves for total cardiac events with use of exercise 201 Tl SPECT and exercise echocardiography (echo). WMA indicates wall motion abnormality. ventricular hypertrophy, or digoxin was considered to be nondiagnostic. Exercise Echocardiography Two-dimensional echocardiograms were performed at rest and immediately after exercise with digital technology as previously described. 6 The left ventricle was divided into 16 segments, 6 and wall motion was semiquantified as follows: 1 normal or hyperdynamic, 2 hypokinetic, 3 akinetic, and 4 dyskinetic. Images were interpreted by one of 2 experienced investigators without knowledge of ECG, additional diagnostic tests, or clinical outcome. Overall interpretation was as follows: normal normal or hyperdynamic function with exercise, ischemia new wall motion abnormality with exercise, fixed abnormality resting wall motion abnormality without evidence of ischemia, and mixed abnormality resting wall motion abnormality with worsening function or contiguous or distant ischemia during exercise. A wall motion score index (WMSI) was derived as the sum of the individual scores divided by the total number of segments, and ejection fraction was determined by subjective estimation or with the multiple diameter method. 11 Exercise 201 Tl SPECT At peak exercise, 3 mci 201 Tl as thallous chloride was injected intravenously, and the patient was asked to exercise for an additional minute. After acquisition of the echocardiographic images, SPECT was performed by use of a large field-of-view, single-crystal, rotating gamma camera (ADAC, ARC ). 5 Redistribution images were obtained 4 hours later. Reconstructed tomographic slices were oriented in the short, horizontal long, and vertical long axes and displayed sequentially to assess regional perfusion. 5 Experienced observers unaware of the results of the echocardiography, additional tests, or clinical outcome performed the analyses. 201 Tl uptake was scored as follows: 1 normal, 2 mildly reduced, 3 moderately reduced, and 4 severely reduced. Perfusion defects were analyzed for the presence of complete redistribution (ischemia), no redistribution (fixed defect), or partial redistribution (mixed defect). Computerized polar maps were generated and compared with a normal data bank Tl defect size (percent) was obtained by computer in most patients (n 228). 5 In 20 patients studied in 1986 whose images could not be adequately processed, defect size was calculated as the number of exercise abnormal segments divided by the total number of segments (n 16) and expressed in percent. This semiquantitative analysis (percent abnormal segments) was also performed for all patients. Clinical Outcome Follow-up data were obtained by review of patient records, personal communication with the patients physicians, and telephone interviews and were available in 225 patients (91%). The remaining 23 patients could not be contacted but had similar baseline characteristics as the 225 patients. The following outcome events were recorded: myocardial infarction, revascularization procedures (angioplasty or coronary artery bypass), congestive heart failure or unstable angina requiring hospitalization, and death (cardiac and noncardiac). Analysis was censored at the onset of the first event. Statistical Analysis Comparison of the prognostic power of exercise echocardiography and exercise 201 Tl was accomplished in 3 steps. Step 1 involved univariate testing to determine which variables distinguished patients with from those without cardiac events. These analyses used the 2 test for association or Fisher s exact test for categorical variables and Student s t test or the Kruskal-Wallis test for continuous variables. 12 Figure 2. Event-free survival curves for ischemic events and cardiac death with use of exercise (Ex) 201 Tl SPECT and exercise echocardiography (echo). 2D indicates 2-dimensional.

4 2682 Prognostic Value of Exercise Echo Versus 201 Tl TABLE 3. Rate of Cardiac Events in Patients With Normal Results of Exercise Echocardiography or 201 Tl SPECT Normal Ex 2D Echo Normal Ex 201 Tl Events n Rate* n Rate* MI Hospitalization for unstable angina Hospitalization for heart failure Revascularization Cardiac death MI unstable angina MI cardiac death All cardiac events Ex indicates exercise; 2D, 2-dimensional; Echo, echocardiography; and MI, myocardial infarction. *Rate is percent per person-year of exposure calculated by use of a maximum of 5.5 years of follow-up in 225 patients. Step 2 involved using stepwise logistic regression to develop models capable of predicting events. 13 Three definitions for cardiac events were used (1) all cardiac events, (2) ischemic events (myocardial infarction, hospitalization owing to unstable angina) and cardiac death, and (3) cardiac death alone. The reason for this approach was to analyze the group of hard events separately from events such as revascularization procedures and congestive heart failure, which may be viewed as soft events but are also important in terms of morbidity and healthcare costs. For each of the 3 definitions of events, 4 logistic models were developed. The first had as its starting point the clinical and exercise ECG variables important in univariate analyses. The second model included resting echocardiographic variables in addition to the first model. The third model included exercise echocardiographic variables in addition to clinical and exercise ECG variables. The fourth model comprised 201 Tl SPECT variables in addition to clinical and exercise ECG variables. Variables that are highly correlated (eg, WMSI and ejection fraction) should not be included in the same model. In this situation, separate models with each of these variables were constructed, and the 1 with the best fit was reported. Pearson s 2 test was used to assess the fit of each of the models. 13 Step 3 consisted of comparing the predictive ability of the models using area under the receiver-operating characteristics curve (AUC). The AUC was determined by use of the trapezoidal rule. 14 AUCs were compared by the method of Hanley and McNeil. 14,15 A secondary aim was to compare event-free survival of patients on the basis of the results of exercise ECG, echocardiography, or 201 Tl SPECT. The Kaplan-Meier curves are shown and were compared by use of the log-rank test. 12 Significance was set at P Results During follow-up (up to 8 years; mean, years), 64 cardiac events occurred: 7 cardiovascular deaths, 8 nonfatal myocardial infarctions, 9 hospitalizations for unstable angina, 11 hospitalizations for heart failure, 28 revascularizations (16 coronary bypass surgery and 12 angioplasty), and 1 cardiac transplantation because of ischemic heart disease and severe heart failure. One patient suffered a noncardiovascular death but was not considered an event for the purposes of this study. Most events (59%) occurred after 90 days. Most of the early events ( 90 days) were revascularizations with either angioplasty (n 7) or bypass surgery (n 10). In contrast, ischemic events and cardiac death accounted for most of the late events (71%). Of the 17 patients with early revascularization, 15 had abnormal studies by both stress echocardiography and 201 Tl, and 2 were normal by both. Of the 11 patients hospitalized with heart failure, 5 (45%) had normal ejection fractions ( 50%) at the time of study, and only 2 had ejection fractions 35%. Of the 11 patients, 9 had abnormal exercise echocardiography, and 8 had abnormal exercise 201 Tl studies. Univariate Analysis Clinical Parameters and Treadmill Exercise ECG Among the clinical variables tested (Table 1), smoking was the only variable associated with all cardiac events (P 0.02), with a trend observed for chest pain (P 0.06) and hypertension (P 0.08). No clinical variables were associated with ischemic events and cardiac death. Diabetes mellitus was associated with cardiac death (P 0.05), whereas old age was of borderline significance (P 0.09). Exercise duration in the 225 patients was minutes. Peak exercise heart rate was bpm with maximal systolic and diastolic blood pressures of and mm Hg, respectively. Sixty-eight percent of patients reached 85% of their maximal age-predicted heart rate. A normal stress ECG and a higher maximal exercise heart rate characterized a group of patients with a lower risk for all cardiac events (Table 2). On the other hand, an ischemic response on exercise ECG was a weak predictor of Figure 3. Event-free survival curves for total cardiac events with use of quantitative parameters of exercise (Ex) 201 Tl and echocardiography (echo). PDS indicates perfusion defect size; ExWMS, exercise wall motion score.

5 Olmos et al December 15, Figure 4. Event-free survival for ischemic events and cardiac death with use of quantitative parameters of exercise (Ex) 201 Tl and echocardiography (echo). PDS indicates perfusion defect size; ExWMS, exercise wall motion score. risk. There was no association between exercise ECG variables and ischemic events or cardiac death. Exercise 201 Tl SPECT The presence of a normal or an abnormal 201 Tl study discriminated patients without events from those with any cardiac event, ischemic events and cardiac death combined, and cardiac death alone (Table 2). An abnormal exercise 201 Tl was a predictor of all cardiac events whether the study was classified as ischemia, fixed defect, or mixed defect. Quantitative analysis of the perfusion defect size or semiquantitative analysis with percent of abnormal segments also differentiated patients with and without events in each of the 3 cardiac events groups (Table 2). Exercise Echocardiography Concordance between exercise echocardiography and 201 Tl for normal and abnormal studies was 86% and for exact category of interpretation was 72%. The incidence of abnormal exercise echocardiography was higher in patients with any cardiac event (75%) compared with those without events (37%; P ; Table 2). This incidence was also higher in patients with combined ischemic events and cardiac death (63%; P 0.018) and in those with cardiac death alone (71%; P 0.069). An abnormal exercise echocardiogram was a predictor of all cardiac events whether the study was classified as ischemia or fixed wall motion abnormality (Table 2). Parameters of resting function, WMSI, and ejection fraction were predictors of all cardiac events. On the other hand, exercise WMSI and ejection fraction were significantly different in all subgroups of cardiac events, including death alone. Survival Analysis Patients with positive exercise ECGs for ischemia and nondiagnostic ECGs had worse survival than those with normal ECGs. These results reached statistical significance for the end points of all cardiac events and for cardiac death (P 0.02 to 0.001). For patients with normal stress ECGs, survival free from any event at 5.5 years was 75%. Figures 1 and 2 depict the survival analysis of the qualitative results of exercise echocardiography and 201 Tl SPECT for the outcomes of all cardiac events and ischemic events or cardiac death, respectively. A significant difference was seen between patients with normal and abnormal studies for all end points, including death alone (P 0.04), for both modalities. The rates for various cardiac events in patients with normal 201 Tl SPECT or normal exercise echocardiography are shown in Table 3 and were comparable. Figures 3 through 5 depict the results with quantitative parameters. Event-free survival in patients with perfusion defect size 15% (n 62) was significantly lower than in those with smaller defects (n 163). Similarly, the 67 patients with exercise WMSI 1.4, corresponding to 3 akinetic segments during stress out of the 16 segments or 18%, had Figure 5. Event-free survival curves for cardiac death with use of quantitative exercise (Ex) 201 Tl and echocardiography (echo). PDS indicates perfusion defect size; ExWMS indicates exercise wall motion score.

6 2684 Prognostic Value of Exercise Echo Versus 201 Tl higher cardiac event rates compared with the 158 patients with less extensive abnormality, regardless of the type of cardiac event analyzed (Figures 3 through 5). Multivariate Analysis Results of the multivariate analysis of the 4 models tested and their incremental value in predicting cardiac events are shown in Tables 4 through 6. All Cardiac Events The multivariate predictors for all the models are shown in Table 4. In the model of exercise 201 Tl SPECT, the most significant predictor was ischemia by 201 Tl SPECT; normal exercise ECG was still a negative predictor. The addition of perfusion defect size did not improve the power of the model for all events (OR, 1.00; P 0.36). For the exercise echocardiography model, exercise WMSI was the strongest predictor, followed by ischemia by echocardiography and exercise ECG. The incremental value for the 4 models tested, expressed as AUC and global X 2, is shown in Table 5 and Figure 6. The addition of resting echocardiography to clinical and exercise ECG improved the predictive power of the model but did not reach significance (P 0.2). However, the AUCs for the models including imaging during exercise were significantly greater (P 0.05 to 0.017), confirming a true incremental power for prediction of cardiac events for exercise echocardiography and 201 Tl SPECT (Figure 6). The power of the TABLE 4. Clinical Models and Multivariate Predictors of All Cardiac Events Significant Models and Predictors OR P 95% CI Clinical Ex ECG* Normal Ex ECG Smoking Max Ex HR, bpm Clinical Ex ECG rest 2D echo Rest WMSI Normal Ex ECG Max Ex HR, bpm Clinical Ex ECG Ex 201 Tl SPECT Ischemia by Ex 201 Tl Normal Ex ECG Clinical Ex ECG Ex 2D echo Ex WMSI Ischemia by Ex 2D echo Normal Ex ECG Ex indicates exercise; other abbreviations as in Table 2. *Variables at the starting point: normal Ex ECG, smoking, and maximal Ex HR. Calculated for every 10-unit increment. OR for WMSI is per unit increment. Variables at the starting point: rest WMSI in addition to those of clinical Ex ECG. Variables at the starting point: ischemia, fixed defect, mixed defect, and perfusion defect size (%) in addition to those of clinical Ex ECG. Variables at the starting point: ischemia, fixed WMA, mixed WMA, and Ex WMSI by Ex 2D echo in addition to those of Clinical Ex ECG rest 2D echo. exercise echocardiography and exercise 201 Tl models was comparable (P 0.4). Ischemic Events and Cardiac Death The first 2 models tested were not significant predictors of ischemic events and cardiac death. For the model including 201 Tl SPECT, the best multivariate predictor was an abnormal 201 Tl SPECT (Table 6). For the model comprising stress echocardiography, an abnormal exercise echocardiography was the only predictor (Table 6). The power of these 2 models was comparable (Table 5). Cardiac Death Models including cardiac imaging during stress were the only predictors of cardiac death (Table 6). In the model of 201 Tl SPECT, perfusion defect size was the strongest predictor, whereas for exercise echocardiography, exercise WMSI was the only significant predictor. The power of these 2 models was also similar (Table 5). Discussion The present study is the first to evaluate the comparative long-term prognostic power of exercise echocardiography and 201 Tl tomography in patients undergoing both imaging modalities during the same exercise test. Parameters of cardiac function and perfusion by the respective modalities were equally powerful in separating patients with low or high risk for cardiac events, including hard cardiac events. Although exercise ECG discriminated between patients with and without events, the addition of cardiac imaging with either echocardiography or 201 Tl during exercise improved the prognostic power and was similar for both imaging modalities. Exercise Echocardiography Versus Exercise 201 Tl SPECT Improvements in ultrasound technology and digital image capture have propelled the use of stress echocardiography in the evaluation of patients with CAD. Although exercise echocardiography evaluates ventricular function and 201 Tl scintigraphy reveals relative myocardial perfusion, studies TABLE 5. Incremental Value of Multivariate Models for Prediction of Cardiac Events Clinical Models AUC SE 2 With 2 P Associated All cardiac events Clinical Ex ECG Clinical Ex ECG rest 2D echo Clinical Ex ECG Ex 201 Tl SPECT Clinical Ex ECG Ex 2D echo Ischemic events and cardiac death Clinical Ex ECG Ex 201 Tl SPECT Clinical Ex ECG Ex 2D echo Cardiac death Clinical Ex ECG Ex 201 Tl SPECT Clinical Ex ECG Ex 2D echo SE indicates standard error of the AUC; other abbreviations as in Table 3.

7 Olmos et al December 15, TABLE 6. Clinical Models and Multivariate Predictors of Ischemic Events and/or Cardiac Death Ischemic Events and Cardiac Death Cardiac Death Significant Models and Predictors OR P 95% CI OR P 95% CI Clinical Ex ECG Ex 201 Tl SPECT Abnormal Ex 201 Tl Perfusion defect size by Ex 201 Tl Clinical Ex ECG Ex 2D echo Abnormal Ex 2D echo Ex WMSI Abbreviations as in Table 3. OR for perfusion defect is per 10-unit increment and for WMSI is per unit increment. comparing both techniques showed a similar accuracy in the diagnosis of CAD. 4,6 A paucity of data exists, however, on the prognostic power of exercise echocardiography. The prognostic impact of exercise echocardiography in patients with chronic CAD followed for 1 year was initially reported by Krivokapich et al. 8 More recently, longer-term follow-up was reported and demonstrated that a positive stress echocardiography is a strong independent predictor of outcome. 9 The present investigation extends these observations and demonstrates that the long-term prognostic power of exercise echocardiography is similar to that of exercise 201 Tl SPECT. The addition of imaging by either technique provided significant incremental value over that available solely from clinical and exercise parameters for all events and particularly for spontaneous cardiac events. The impact of systolic ventricular function on prognosis is well established. Exercise WMSI, a parameter that incorporates resting function and extent of myocardium at risk during stress, was the main predictor of events and the sole echocardiographic predictor of cardiac death by multivariate analysis. Patients with an exercise ejection fraction of 60% had a worse prognosis. It is worth noting, however, that the impact of exercise ejection fraction on prognosis was not better than that of exercise WMSI, the latter being easier to determine during stress. The present study extends earlier Figure 6. Comparison of AUCs of 4 models tested in predicting all cardiac events. Clin indicates clinical parameters; Ex, exercise; and Echo, echocardiography. observations with exercise radionuclide angiography 3 to exercise echocardiography, further emphasizing the importance of evaluating the extent of ventricular dysfunction during stress, in addition to detection of ischemia. Since the initial report by Brown et al 2 in 1983, several studies have demonstrated the prognostic significance of exercise 201 Tl scintigraphy. 7,16 18 In recent studies in which 201 Tl SPECT was performed, the size of the perfusion defect was shown to be a powerful predictor of ischemic events and cardiac death Iskandrian et al 16 have shown that a perfusion defect size of 15% identified patients with a high likelihood of cardiac events. In the present investigation, similar findings were observed. Ischemia was the main multivariate predictor of all cardiac events. However, perfusion defect size successfully separated the study population into low and high risk and was the sole multivariate predictor of cardiac death. These findings further demonstrate that exercise 201 Tl SPECT provides excellent risk stratification of patients with suspected CAD. The association between exercise echocardiography and cardiac events was remarkably similar to that of 201 Tl SPECT. Exercise WMSI (the counterpart of perfusion defect by 201 Tl SPECT) separated the study population into low and high risk and was the best multivariate echocardiographic predictor of cardiac death. An important goal of any stress modality is the ability to identify patients with a low cardiac event rate in addition to those at high risk. The cardiac event rate in patients with normal exercise 201 Tl SPECT was similar to that for exercise echocardiography, regardless of the type of outcome analyzed (Table 3), and further support that the 2 modalities are comparable in risk stratification. Study Limitations Most patients did not have angiography to evaluate the prognostic power of coronary anatomy. This stems from the design of the present investigation, which was to compare stress echocardiography and 201 Tl SPECT in a clinical setting. However, the addition of coronary angiography to stress perfusion imaging was shown not to improve risk stratification. 7 Availability of the stress test information to the clinician undoubtedly influences patient management. This may have triggered a revascularization procedure or alteration in medical management. For this reason, results were analyzed

8 2686 Prognostic Value of Exercise Echo Versus 201 Tl with all cardiac events and spontaneous events included. Furthermore, because this investigation is a comparative study, the influence on outcome affects the risk stratification of both modalities. Conclusions In patients evaluated for CAD, both exercise echocardiography and 201 Tl SPECT significantly improve the prognostic power of exercise ECG in assessing subsequent cardiac events and provide comparable prognostic information. The choice of imaging modality in a particular institution, however, depends on several factors, including availability, feasibility, expertise, and cost considerations. Acknowledgment We thank Eula Landry for her assistance in preparing the manuscript. References 1. McNeer JF, Margolis JR, Lee KL, Kisslo JA, Peter RH, Kong Y, Behar VS, Wallace AG, McCants CB, Rosati RA. The role of the exercise test in the evaluation of patients for ischemic heart disease. Circulation. 1978; 57: Brown KA, Boucher CA, Okada RD, Guiney TE, Newell JB, Strauss HW, Pohost GM. Prognostic value of exercise thallium-201 imaging in patients presenting for evaluation of chest pain. J Am Coll Cardiol. 1983;1: Jones RH, Johnson SH, Bigelow C, Pieper KS, Coleman E, Cobb FR, Pryor DB, Lee KL. Exercise radionuclide angiocardiography predicts cardiac deaths in patients with coronary artery disease. Circulation. 1991; 84(suppl I):I-52 I Nagueh SF, Zoghbi WA. Stress echocardiography for the assessment of myocardial ischemia and viability. Curr Probl Cardiol. 1996;21: Mahmarian JJ, Boyce TM, Goldberg RK, Cocanougher MK, Roberts R, Verani MS. Quantitative exercise thallium-201 single photon emission computed tomography for the enhanced diagnosis of ischemic heart disease. J Am Coll Cardiol. 1990;15: Quiñones MA, Verani MS, Haichin RN, Mahmarian JJ, Suarez J, Zoghbi WA. Exercise echocardiography versus thallium-201 single photon emission computed tomography in the evaluation of coronary artery disease: analysis of 292 patients. Circulation. 1992;85: Iskandrian AS, Verani MS. Risk assessment. In: Nuclear Cardiac Imaging: Principles and Applications. Philadelphia, Pa: FA Davis Publishers; 1996: Krivokapich J, Child JS, Gerber R, Lem V, Muser D. Prognostic usefulness of positive or negative exercise stress echocardiography for predicting coronary events in ensuing twelve months. Am J Cardiol. 1993; 71: Marwick TH, Mehta R, Arheart K, Lauer MS. Use of exercise echocardiography for prognostic evaluation of patients with known or suspected coronary artery disease. J Am Coll Cardiol. 1997;30: McCully RB, Roger VL, Mahoney DW, Karon BL, Oh JK, Miller FA Jr, Seward JB, Pellikka PA. Outcome after normal exercise echocardiography and predictors of subsequent cardiac events: follow-up of 1,325 patients. J Am Coll Cardiol. 1998;31: Quiñones MA, Waggoner AD, Reduto LA, Nelson JG, Young JB, Winters WL Jr, Ribeiro LG, Miller RR. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation. 1981;64: Rosner B. Fundamentals of Biostatistics. Belmont, Calif: Duxbury Press; Hosmer DW, Lemeshow S. Applied Logistic Regression. New York, NY: John Wiley & Sons; Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology. 1982;143: Hanley JA, McNeil BJ. A method of comparing the areas under receiver operating characteristic curves derived from the same cases. Radiology. 1983;148: Iskandrian AS, Chae SC, Heo J, Stanberry CD, Wasserleben V, Cave V. Independent and incremental prognostic value of exercise single photon emission computed tomographic (SPECT) thallium in coronary artery disease. J Am Coll Cardiol. 1993;22: Machecourt J, Longere P, Fagret D, Vanzetto G, Wolf JE, Polidori C, Comet M, Denis B. Prognostic value of thallium-201 single-photon emission computed tomographic myocardial perfusion imaging according to extent of myocardial defect: study in 1,926 patients with follow-up at 33 months. J Am Coll Cardiol. 1994;23: Marie P, Danchin N, Durand JF, Feldmann L, Grentzinger A, Olivier P, Karcher G, Juilliere Y, Virion JM, Beurrier D, Cherrier F, Bertrand A. Long-term prediction of major ischemic events by exercise thallium-201 single-photon emission computed tomography: incremental prognostic value compared with clinical, exercise testing, catheterization and radionuclide angiographic data. J Am Coll Cardiol. 1995;26: