Box 2 Immediate exercise test procedure and endpoints

Modified Bruce treadmill protocol® Symptom-limited Other end-points Ischemia (R1.0 mm ST segment shift for 80 msec after the J point) Y Blood pressure (R10 mm Hg systolic) Significant arrhythmia (sustained supraventricular tachyarrhythmia; high-grade ventricular ectopy [R2 consecutive beats, sustained bigeminy]) Positive result: R 1.0 mm horizontal ST

segment shift Nondiagnostic result: < 85% maximum predicted heart rate with no ST shift a Includes two initial 3-minute states (1.7 mph, 0% grade and 1.7 mph, 5% grade) before the standard Bruce protocol.

injury marker before exercise testing. Almost two-thirds of the patients had negative immediate exercise tests, approximately 13% were positive and less than 25% were nondiagnostic (Fig. 3). There was no mortality during the 30-day follow-up interval. The negative predictive value for a cardiac event was 99.7% at 30 days. In the nondiagnostic group, all events were accounted for by revascularization in 32% of the 79 patients who had further evaluation. The positive predictive value of the exercise test was 33% for a cardiac event (four non-Q MIs detected after admission, 12 myocardial revascularizations) or a confirmatory imaging test for CAD (two patients). These results extended the authors' previous findings to a large, heterogeneous population in that testing was uncomplicated, the bulk of patients had negative tests and could be released directly from the ED, negative predictive value was excellent, and the low positive predictive value involved a relatively small group with positive exercise tests. The safety and accuracy of this method has been confirmed in patients with known CAD by a specific study of immediate exercise testing of 100 consecutive patients with this disease [46]. Although exercise testing is considered to have limited value in women, the authors' experience has confirmed the reliability of a negative immediate exercise test in this group. The negative predictive value of the test was 99% in 661 women with a mean age of 54 years studied in the CPU [47].

Comparison of exercise testing and myocardial scintigraphy

The utility of myocardial scintigraphy has been well established in patients presenting with chest pain [48]. However, the cost and logistics of this

ra CL

Negative Non-Diagnostic

Positive

Fig. 3. Proportion of 1000 patients with negative, positive, and nondiagnostic immediate exercise tests. Numbers in bars indicate number of patients.

Negative Non-Diagnostic

Positive

Fig. 3. Proportion of 1000 patients with negative, positive, and nondiagnostic immediate exercise tests. Numbers in bars indicate number of patients.

method are prohibitive for many institutions. In this regard, the authors have shown that > 70% of low-risk patients presenting with chest pain qualify for immediate exercise testing and that more complex and expensive stress imaging techniques can be appropriately reserved for the remainder of patients [49]. Moreover, a comparative study of 239 low risk patients by Senaratne and colleagues [50] revealed that early treadmill testing was as informative and more cost-effective than scintigraphy in identifying low-risk patients who did not require hospitalization. In this study, in which the follow-up period was 20 months, exercise testing was applicable in all but 9.6% of patients. These investigators report that, compared with scintigraphy as the initial cardiac study, exercise testing yielded a savings of more than $86,000 in this group of patients. In contrast to our strategy in which noncardiologists assess patients and perform immediate exercise testing, with cardiology consultation available as required, Senaratne and colleagues [50] emphasize the essential role of cardiologists in these processes. In this regard, the expertise of the authors' noncardiology CPU physicians in performing exercise testing has been confirmed by their accuracy in test interpretation and the complete absence of complications [51]. Analysis of 645 immediate exercise ECGs revealed a concordance of greater than 98% between the interpretations of these physicians and the authors' staff cardiologists.

Immediate exercise testing in special groups

The authors have recently explored a number of other issues presented by early exercise testing in patients presenting with chest pain. The use of beta-blockers or rate-limiting calcium channel-blockers often precludes diagnostic exercise testing because of attenuation of exertional heart rate by these agents. These drugs are associated with reduction of peak exercise heart rate and rate-pressure product, resulting in an increased frequency of nondiagnostic tests compared with patients not receiving these agents [52]. However, a majority (>60%) of patients taking these medications did have a diagnostic test. Therefore, it is our experience that use of these drugs should not preclude early exercise testing.

Recent trials of non-STE ACS have demonstrated the prognostic importance of multiple clinical factors in patients presenting with this diagnosis, including elevated cardiac injury markers, ST-segment deviation, age R 65 years,

R three coronary risk factors, known CAD, R two anginal episodes in the previous 24 hours and aspirin use in the previous 7 days. These factors comprise the TIMI risk score for prediction of fatal and nonfatal coronary events, which increase directly with the number of these risk factors [53]. However, in patients presenting to their CPU, the authors have found that, with the exception of elevated cardiac injury markers and ST-segment deviation, both of which preclude exercise testing, the test can be safely performed for reliable risk stratification regardless of the presence of the other TIMI risk factors [54]. Because it has recently been reported that augmenting the standard exercise ECG with additional leads enhances its sensitivity for detecting ischemia [55], the authors evaluated this innovation in their CPU patients. In this setting, the addition of four leads (two posterior and two right-sided) to the standard 12-lead ECG enhanced the sensitivity of the test minimally without altering specificity [56]: sensitivity rose only minimally from 7.6% to 8.0% based on detection of two patients who were positive only in the additional leads compared with 37 patients with positive findings in the standard exercise ECG. These additional leads were also not useful in detecting ischemia or injury in the resting ECG in patients admitted to the CPU [57]. In a study of 2021 patients referred for elective outpatient treadmill testing, the authors also found that the 16-lead exercise ECG did not afford increased sensitivity in this setting [58], thereby failing to confirm the prior study of Michaelides and colleagues [55].

A notable aspect of the authors' CPU experience has been the high recidivism rate of patients discharged from the unit with a negative evaluation. During a 7.5-year period, 13% of 1960 patients had R two or more negative immediate exercise tests and accounted for 26% of the CPU visits [59]. Further, of the latter group, almost 10% had R four negative exercise tests during this period. The multi-exercise test patients were relatively young (mean age 52 years) and most of them were women. Beyond the traditional differential diagnosis of multiple somatic causes of chest pain [60], common and underdiagnosed conditions responsible for this symptom include anxiety syndromes and somatoform disorders [11,60-62].

Further issues

Several aspects of the authors' application of immediate exercise testing in CPU patients warrant comment. As previously noted, patients in whom this method is used are carefully screened to confirm their low-risk status, as outlined in Box 1. The test is terminated at the initial appearance of any abnormality (see Box 2). Although noncardiologists perform the clinical assessment and exercise tests in CPU patients, these specially trained physicians have ready availability of consultation by staff cardiologists. In regard to the relatively large proportion (>20%) of patients with nondiagnostic tests (negative but peak heart rate < 85% of predicted maximum), the authors have found that those with negative tests at R 80% of maximum predicted heart rate had uneventful outcomes on follow-up [45]. Therefore, use of this lower heart rate for a diagnostic test for the purpose of risk stratification appears prudent and would reduce the nondiagnostic group by 25% [45]. Although follow-up is only 30 days, the purpose of this approach is to determine short-term risk. This strategy is predicated on timely follow-up and further outpatient evaluation. Finally, although clinical assessment is basically reliable in identifying low-risk patients, it is imperfect and can result in inadvertent exercise testing in patients with ACS. This possibility is minimized by physician expertise and experience together with continued caution in the selection of patients for testing and in the indications for test termination.

A recurrent question concerns the necessity of performing exercise testing before discharge after a negative ADP rather than a short time after discharge. The former approach provides the most efficient completion of the evaluation and obviates concern regarding lack of return of patients for the outpatient test, which would contribute to the hazard of incomplete assessment and missed ACS [6]. However, where testing is not feasible and the system and patient characteristics are conducive to early return for testing (within 48 hours), it is reasonable to consider this approach. The authors have discharged selected very low-risk patients from their CPU without a predis-charge exercise test. They have specifically studied this approach in a group of very low-risk women presenting to the ED with chest pain who were les than 50 years old, nondiabetic, and nonsmokers [63]. Of the entire group of 346 women, 175 were discharged from the CPU without exercise testing. At 30 days follow-up, none of these patients had confirmatory evidence of CAD or ACS. The results suggest that the risk of ACS is very minimal in women with low-risk profiles who present with chest pain and that stress testing in the CPU may not be necessary to determine disposition in these patients. These findings have implications for optimal use of limited resources.

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