Assessing cardiac risk--how low (risk) should you go?

Stress testing has many uses in cardiology, including evaluating patients with chest pain (1), assessing risk after myocardial infarction (2), and optimizing the timing of return to work after myocardial infarction (3). The addition of cardiac imaging to the electrocardiographic stress test, whether by nuclear scintigraphy or echocardiography, is of particular value for women (4) and for patients whose electrocardiogram (ECG) is difficult to interpret, such as those with left bundle branch block or those receiving digoxin. In addition, the use of pharmacologic agents to mimic the stress of exercise has broadened the application of these tests to patients unable to exercise, such as patients with peripheral vascular disease, stroke, or deconditioning. Pharmacologic stress testing is also used to risk-stratify patients scheduled to undergo noncardiac surgery (5). Stress testing with cardiac imaging can identify subtle exercise-induced perfusion abnormalities by nuclear scintigraphy, or regional wall motion abnormalities by echocardiography (6,7). These tests have a greater sensitivity for detecting coronary artery disease than does electrocardiographic stress testing alone, as perfusion abnormalities and regional wall motion abnormalities occur earlier (at a lower workload) than symptoms or ECG changes. Most patients who undergo one of these tests for screening purposes have at least an intermediate pretest probability of coronary artery disease, based on cardiac risk factors. In this issue of The American Journal of Medicine, Elhendy and colleagues (8) report the prognostic value of exercise echocardiography in patients with a low pretest probability of coronary artery disease. Cardiac events were defined as nonfatal myocardial infarction or death. The 5-year event-free survival of more than 98% shows that their algorithm performed well in identifying low-risk patients who had undergone a stress echocardiogram. The authors reported that exercise echocardiographic variables were significant predictors of cardiac events during long-term follow-up. While on the surface this may be taken to support the use of exercise testing with cardiac imaging for screening low-risk patients, these findings should be viewed from a practical clinical perspective. First, how should cardiac events be defined for low-risk patients? In relatively young persons with few risk factors, the most common first cardiac presentation would be new cardiac symptoms or an acute coronary syndrome (the spectrum encompassing unstable angina to myocardial infarction without ST-segment elevation). In the “pretroponin” era covered by this study, many of the cases of acute coronary syndrome may have been labeled as unstable angina rather than nonfatal myocardial infarction because biomarkers were less sensitive for myocardial necrosis. In current practice, most of these patients would undergo either medical or interventional treatment and might avoid the events (myocardial infarction, death) that were used as endpoints. Perhaps a looser definition of cardiac event may be required when studying low-risk patients. Indeed, twice as many patients were excluded from the analysis as had events, and the patients who were excluded all underwent coronary intervention. Many of the physicians may have acted upon a positive exercise echocardiogram by proceeding to a coronary angiogram and revascularization; these patients would have been censored from the analysis. Thus, the true value of the test will be difficult to assess. Second, only 9 of the 19 cardiac events were identified by exercise echocardiography. This finding is not surprising, as the value of the test is in detecting inducible ischemia from coronary lesions that limit flow at rest or that limit flow reserve so that the increased myocardial demands during exercise are not met. In studies that have examined angiographic features of lesions that subsequently progressed to cause infarction, more than 50% of the lesions were mild prior to plaque rupture and thrombosis (9). Yet, these mild lesions may not be identified by stress echocardiography. Third, and most important, when applying any diagnostic test to a group with a low risk for a disease, one must be cognizant of the risk of false-positive results and a low positive predictive value. A positive test in a very low-risk group may not necessarily put a patient at a high risk for a disease, as is nicely illustrated in Table 2 of the report by Elhendy and colleagues (8). Of the 346 abnormal stress echocardiograms, only 9 were from patients who had a subsequent event. Hence, fewer than 3% of the abnormal stress tests were associated with events. If an abnormal stress echocardiogram led the patient to another diagnostic test such as coronary angiography, 97% of the patients would have an invasive test with little or no likelihood of an event. The exercise echocardiogram variAm J Med. 2001:111:73–74. From the Division of Cardiology and the Department of Medicine (MHP), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, and the Department of Cardiology (CAD), Deborah Heart and Lung Center, Browns Mills, New Jersey. Requests for reprints should be addressed to Michael H. Picard, MD, Cardiac Ultrasound Lab, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114.