The need for a cost-effective strategy to detect ambulatory silent ischemia

The Need for a Cost-Effective Strategy to Detect Ambulatory Silent lschemia Prakash C. Deedwania, MD The study by Paul et al provides valuable informailent myocardial &hernia occurring during normal tion based on evaluation of patients with stable coronary activities (i.e., during daily life) is the most common form of ischemia encountered by patients with artery disease undergoing treadmill exercise tests as well stable coronary artery disease.’ A large number of stud- as AEM recordings for a 48-hour period. The study was ies have clearly demonstrated that the presence of ische- designed to correlate exercise test results with the presmia during daily life, regardless of associated symptoms, ence or absence of ambulatory ischemia during Holter is a powerful predictor of adverse clinical outcome and monitoring. Although the overall prevalence of ambulaincreased risk of death in patients with coronary artery tory ischemia in this study was somewhat high (>50%), and therefore the findings described may be skewed disease.lA Because most (>90%) episodes of &hernia during daily life are not associated with typical angina1 owing to patient selection bias inherent in the study symptoms, silent ischemic episodes remain largely unde- design, the findings do provide clinically meaningful tected unless patients are specifically evaluated with one information that could be helpful in developing a costof the many available noninvasive techniques.’ Ambu- effective strategy for selecting patients at increased risk latory electrocardiographic monitoring (AEM) for 24 to for ambulatory ischemia. First, the study results empha48 hours, designed to detect ST-segment depression, is size the importance of evaluating simple parameters such the most practical and readily available diagnostic mo- as time to onset of ischemia (i.e., 1 mm ST-segment dedality suitable for evaluating myocardial ischemia dur- pression) during exercise testing for identifying patients ing daily activities. Previous studies have indicated that at risk for ambulatory ischemia. Most patients who deas many as 30% to 40% of patients with coronary artery velop exercise-induced ischemia at advanced stages of disease and stable angina have evidence of spontaneous the exercise test (e.g., after 6 minutes on the Bruce proischemia detectable on 24-hour AEM. These silent ische- tocol) appear to be at minimal risk for ischemia during mic episodes may be present despite control of angina1 daily life, indicating that evaluation of such patients by symptoms with antianginal drugs.lA AEM may not be essential. Further incorporation of the Although clinicians routinely perform exercise tests magnitude of ischemic changes (i.e., ST-segment defor evaluating patients with coronary artery disease, and pression in mm) with time to onset of 21 mm of STthe findings provide clinically meaningful prognostic in- segment depression provided a better predictive value. formation, results of some recent studies indicate that For example, a patient who had delayed onset of ischeambulatory ischemia detected by AEM provides addi- mia during exercise testing and failed to have >2 mm of tional prognostic information.3,4 Because of these find- ST-segment depression, had a significantly lower risk for ings, there has been increasing enthusiasm for performambulatory ischemia than one who developed ischemia ing AEM in patients with coronary artery disease. at a similar exercise time but had >2 mm of ST-segment Although recent technologic advances have led to the depression. availability of a number of reliable Halter monitoring The improved predictive value of combining the 2 systems that appear suitable for ST-segment monitoring, parameters of exercise-induced ischemia led the investhe routine use of Halter monitoring in evaluating pa- tigators to develop an interesting predictive model that tients with stable coronary artery disease is neither well could be used in calculating the postexercise test probjustified nor cost-effective. The article by Paul et al in ability of the risk of ambulatory ischemia. Utilizing the this issue (page 991) emphasizes the importance of using ordinal logistic model, they showed that for a known readily available information from exercise test findings degree of maximal ST-segment depression and time to to develop a cost-effective strategy for appropriate use onset of 21 mm ST-segment depression during exercise of AEM for detecting silent ischemia. The iindings of testing, the clinician can not only predict the likelihood their study are especially important in light of the fact of ambulatory ischemia, but can also estimate the durathat the forces driving the current health care reformtion of ambulatory ischemia in a given patient. Such a would essentially make it impossible for clinicians to predictive model appears quite attractive because, theorecommend all diagnostic procedures for every patient, retically, it has the potential to estimate the risk of the and would force them to choose the most appropriate total ischemic burden during daily life in a patient with and economical test suitable for a given patient. coronary artery disease. A major limitation, however, is that it is difficult to recommend such a model for wideFrom the Division of Cardiology, Department of Medicine, Veterans spread clinical use unless it has been validated in a Affairs Medical Center, Fresno, and University of CalifomiaSan Franprospective fashion in a large number of unselected and cisco, School of Medicine, San Francisco, California. Manuscript diversified patients with a varied spectrum of diseases. received October 3, 1994, and accepted October 4, There is a clear need for a simple, reliable, and practiAddress for reprints: Prakash C. Deedwania, MD, Division of Catdiology, Department of Medicine, UCSF Program/VAMC, 2615 East cal method to identify patients at risk for ambulatory Clinton Avenue, Fresno, California 93703. ischemia during daily life. The model proposed in the

S

EDITORIALS 1061

present study does provide an attractive concept for future research and development in this area. Several previous studies have also evaluated the predictive value of exercise test parameters in identifying the risk of ambulatory ischemia in patients with stable coronary artery disease.5-7 The results of these studies revealed that, in general, patients who failed to develop inducible ischemia during exercise testing rarely had evidence of ambulatory ischemia. Based on these results, it is generally believed that there is no need to perform Holter monitoring for evaluation of ambulatory ischemia in patients with a negative exercise test result. In patients who do demonstrate evidence of exercise-induced ischemia, the lindings of 2 previous studies, including our own data,6,7 are in agreement with the results described in the present study by Paul et al. Both these studies6,7 demonstrated that most (90%) patients who had evidence of ischemia during daily life had early onset of exerciseinduced ischemia during the treadmill exercise test. Thus, it appears evident that the time to onset of ischemia during exercise testing is the single most reliable predictor of the risk of ambulatory ischemia, and should be used to stratify patients at high or low likelihood of developing silent &hernia during daily life. In our study,7 we also determined the value of additional exercise test parameters to enhance the predictive accuracy of exercise test findings in calculating the risk of ambulatory ischemia in patients with stable coronary artery disease. We utilized 2 separate predictive models to develop simple formulas for identifying patients at risk for ambulatory ischemia. For the first method, we utilized a pattern classification system, and the following algebraic equation was developed: derived score (D) = (6t -t-37d/lO,OOO)- 92, where t = time to onset of exertional ischemia, and d = peak exercise double product (peak heart rate X peak systolic blood pressure). If D was ~0 it indicated risk of ambulatory ischemia, and if D was >O it indicated no risk. The sensitivity, specificity, and predictive accuracy of this method were 65%, 84%, and 76%, respectively. For the second method, we utilized the binary decision tree. Of the 82 patients with a positive exercise test result, 54 developed ischemia within 4.25 minutes of exercise testing and were initially classified as those at risk for ambulatory silent ischemia. These patients were further substratified based on a peak exercise double product of 120,000. Of the 54 patients, 28 (52%) had a peak exercise double product <20,000, and 23 of these 28 (82%) had ambulatory silent ischemia. In contrast, only 2 of the 18 patients (11%) with delayed onset of ischemia (>4.25 minutes) and a

1062

THE AMERICAN JOURNAL OF CARDIOLOGYm VOLUME 74

higher (>20,000) peak exercise double product had silent ischemia during ambulatory monitoring. The overall sensitivity, specificity, and predictive accuracy of this method were 62%, 89%, and 77%, respectively. Both of these mathematical models are currently being tested in a prospective manner, and, if validated, should provide simple and clinically useful methods to stratify patients at risk for ambulatory ischemia. The availability of one or more of these predictive models, if found reliable in forecasting the risk of ambulatory ischemia, would indeed be the most cost-effective strategy for deciding which coronary artery disease patients need AEM. Because of the high prevalence of silent ischemia and the related adverse prognosis, clinicians are increasingly using AEM for evaluating patients with coronary artery disease. Although recent technologic advances have made it feasible to obtain high-quality, reliable AEM studies in most medical centers, the costs of routinely performing such studies in all patients with coronary artery disease would be prohibitive. An estimated 6 million people in the United States have stable coronary artery disease, and, at an average cost of $200, an AEM study for all patients would cost in excess of $1 billion. It is therefore evident that we must develop a cost-effective strategy to identify patients who are at increased risk for ambulatory ischemia. Such a strategy would enable us to obtain AEM recordings in a select group of patients and subsequently stratify such patients into groups with high and low risk for future coronary events. The results of the study by Paul et al suggest that a cost-effective strategy for identifying patients at risk for ambulatory ischemia can be developed. Further studies are needed to prospectively examine the predictive value of various models including the one proposed by Paul and associates.

1. Deedwania P, Carbajal E. Silent myocardial ischemia: a clinical perspective. Arch Intern Med 1991;151:2373-2382. 2. Yeung AC, Orav J, Bonassin E, Raby KE, Selwyn AP. Effects of asymptomatic ischemia on long-term prognosis in chronic stable coronary disease. Circulafion 1991;83:1598-1604. 3. Deedwania P, Carbajal E. Silent ischemia during daily life is an independent predictor of mortality in stable angina. Circulation 1990,81:748-756. 4. Deedwania P, CatbajaJ E. Ambulatory electrocardiography evaluation of asymptomatic, unstable, and stable coronary artery disease patients for myocardial ischemia. Car&l C/in 1992; 10:417430. 5. Mulcahy D, Keegan J, Sparrow .I, Park A, Wright C, Fox K. Ischemia in the ambulatory setting-the total ischemic burden: relation to exercise testing and investigative and therapeutic implications. J Am Cob Cardiol 1989;14:11661172. 6. Campbell S, Barry J, Rocco MB, Nabel EG, Mead-Walters K, Rebecca GS, Selwyn AP. Features of the exercise test that reflect the activity of ischemic heart disease out of hospital. Circularion 19X&74:72-80. 7. Deedwania P, Carbajal E. Exercise test predictors of ambulatory silent &hernia during daily life in stable angina pectoris. Am J Cardiol 1990;66:1151-1156.

NOVEMBER 15, 1994