Accelerated dignostic protocols (ADPs) have been increasingly utilized in low-risk patients with the final step comprising one of the cardiac stress tests methods if the ACS is excluded. The most commonly used ADPs usually entail 6 to 12 hours of clinical observation, serial 12-lead ECGs, continuous ECG monitoring, and measurement of serial serum cardiac injury markers (10,12,14,20,24). Positive findings indicate ACS (usually non-ST elevation [non-STE] ACS, rarely ST elevation MI) and mandate admission for further management. Negative findings are consistent with the absence of MI and ischemia at rest. In these cases, a stress test is performed to detect inducible ischemia. Patients with a positive test are admitted, and those with a negative result are discharged to outpatient follow-up. Multiple methods are currently available to detect stress-induced ischemia, the most widely available and readily applicable of which is treadmill exercise testing. The utility of this test in conjunction with ADPs has been has been well demonstrated, as indicated by its safety and predictive accuracy in this setting.

Until it was validated by recent studies, there were strong admonitions against early exercise testing even in low-risk patients presenting with symptoms suggestive of ACS (9,25). The evolution of this approach is reflected in the statement of The 31st Bethesda Conference on Emergency Cardiac Care (1999) that “ADPs, including exercise testing as a key element, have been associated with reduced hospital stay and lower costs” (10). The absence of adverse effects and the accurate identification of low clinical risk were also recognized. A subsequent Science Advisory of the AHA concluded that contemporary studies “confirmed the safety of symptom-limited treadmill exercise ECG testing after 8 to 12 hours of evaluation in patients who have been identified as being at low to intermediate risk by a clinical algorithm that uses serum markers of myocardial necrosis and resting ECGs” (26). This strategy is incorporated in the 2002 guidelines of the ACC/AHA for management of patients with non-ST-elevation ACS in which it is recommended that exercise testing can be performed in stable, low-risk patients if “a follow-up 12-lead ECG and cardiac marker measurements after 6 to 8 hours of observation are normal” (23). Recent exercise testing guidelines are in accord with these recommendations (27,28). It is noteworthy that these recent recommendations reflect evolution from earlier versions, which advised exercise testing only after patients had been symptom free for a “minimum of 48 hours” (29).

All studies of early exercise testing in patients presenting with chest pain have required that patients are clinically stable with no ECG evidence of ischemia/injury. The criteria for a
positive test for myocardial ischemia are the standard indicators: ≥1.0 mm horizontal or downsloping ST segment shift 60 to 80 msec after the J point. Other exercise-induced alterations that indicate an abnormal test and the need for further evaluation include angina, arrhythmias, and exercise-induced fall in blood pressure. The first two investigations of this method included only small numbers of patients, but they demonstrated its safety in low-risk patients in the ED setting (30,31), and its utility was confirmed in multiple subsequent publications (Table 10-1). Of note, there have been no reports of adverse events in any study of early exercise testing of low-risk patients.

The first study of exercise testing in patients with the clinical profile of those currently included in ADPs was published from our institution in 1994. In this investigational protocol, selected patients presenting with chest pain who were designated for admission by ED physicians to rule out ACS underwent immediate treadmill testing (32) (Table 10-1). The study group comprised 93 patients in whom ED symptom-limited exercise testing was performed by a cardiologist using a modified Bruce protocol without prior measurement of any markers. The test was performed within a median time of less than 1 hour from the decision to admit. Positive tests occurred in 13% of patients, negative in 64%, and nondiagnostic (no ischemia but peak heart rate <85% of age-predicted maximum) in 13%. Ischemic ECG changes occurred at a significantly lower percentage of age-predicted maximal heart rate (70%) in patients with true-positive tests compared to those with false-positives (>90%) (Fig. 10-2). No complications were associated with exercise testing. Coronary angiography revealed significant coronary artery disease (CAD) in 6 of the 13 patients with positive tests, 5 of whom had multivessel involvement. A majority (54%) of the 81 patients with negative or nondiagnostic results was discharged immediately after the exercise test. At 6-month follow-up, there were no coronary events in patients with negative or nondiagnostic exercise tests. There are several unique aspects of this study, which demonstrated the utility of early exercise testing in low-risk patients and provided the basis for our current approach of “immediate” exercise testing in low-risk patients without excluding MI by a traditional series of negative cardiac serum markers. In contrast to the preceding studies, it included only patients who were assigned to admission for a traditional rule-out MI protocol. In these patients, exercise testing was performed prior to the latter process, there were no adverse effects of testing, true- and false-positive tests were related to the heart rate at ST-segment depression, the majority of patients were discharged immediately following a negative or nondiagnostic test, and there were no coronary events during the posthospital course. Of note, one patient with a positive test was found to have non-ST-elevation MI by subsequent serial serum enzymes. Coronary angiography revealed right coronary artery stenosis, coronary angioplasty was performed, and the clinical course was uncomplicated.

Gibler and associates demonstrated the utility of early exercise testing in 782 patients in whom low risk was indicated by an ADP (33) (Table 10-1). Their protocol included serial ECGs and serum CK-MB, 9 hours of continuous ST-segment monitoring, and a resting ECG followed by symptom-limited exercise testing in those with negative findings. There were no adverse effects and no mortality at 30-day follow-up in the patients with negative tests. The negative predictive value of the exercise test was 99%. Although the positive predictive value was less than 50%, only 9 of 782 patients (<2%) had positive exercise tests, which was lower than in our initial investigation (32).