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26. Borer JS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnston GS. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronaryartery disease. N Engl J Med 1977;296:839-44. 27. Borer JS, Kent KM, Bacharach SL, et al. Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with coronary artery disease; comparison with exercise electrocardiography. Circulation 1979; 60:572-80.
28. Berger HJ, Reduto LA, Johnstone DE, Borkowski H, Sands JM, Cohen LS, Langou RA, Gottschalk A, Zaret BL, Pytlic L. Global and regional left ventricular response to bicycle exercise in coronary artery disease; assessment by quantitative radionuclide angiocardiography. Am J Med 1979;66:13-21. 29. Iskandrian AS, Hakki AH, Segal BL, Kane SA, Amenta A. Assessment of myocardial perfusion pattern in patients with multivessel coronary artery disease. AM HEART J 1983; 106:1089-96.
Prognostic value of a normal exercise echocardiogram Follow-up information was obtained from 148 patients who had normal resting and post-treadmill exercise echocardiograms to determine the prognostic value of a normal exercise echocardiogram in patients evaluated for suspected coronary artery disease. There were 77 men and 71 women with a mean age of 52.5 years and a pretest likelihood of coronary artery disease of 39%. Patients were followed for a mean duration of 28.4 + 8.5 months. The exercise ECG was abnormal in 69 patients (47%) including 28 who had ischemic responses. Cardiac events occurred in six patients, three with normal and three with abnormal exercise ECGs. Events occurred only in those patients (6 of 68) who exercised to work loads less than 6 METS or who achieved less than 85% of the age-predicted maximal heart rate. Three patients had coronary artery bypass grafting for angina from 10.5 to 22.5 months after echocardiography. A fourth patient had bypass grafting for mild single-vessel disease at the time of mitral valve replacement. Two patients had myocardial infarctions (0.85% per year) at 7.5 and 41 months after echocardiography. There were no deaths. Coronary revascularization is infrequently required in the 28 months after a normal exercise echocardiogram. A normal exercise echocardiogram in a patient with good exercise capacity was predictive of an excellent prognosis, even in those who had abnormal exercise ECGs. Myocardial infarction and death were rare events, even in patients with decreased exercise capacity. (AM HEART J 1990;120:49.)
Stephen G. Sawada, MD, Thomas Ryan, MD, Mary Jo Conley, Betty C. Corya, MD, Harvey Feigenbaum, MD, and William F. Armstrong, MD.* IrzdianapoZis, Ind.
Accurate assessment of prognosis in patients with known or suspected coronary artery disease is a major goal of noninvasive exercise testing. Cardiac events may occur in some patients who have ST seg-
From the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine. Supported in part by the Herman C. Krannert Fund, Indianapolis, Ind.; grants HL-06308 and HL-07182 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.; and the American Heart Association, Indiana Affiliate, Indianapolis, Ind. Received Reprint N562, *Current Medicine, 4/I/20442
for publication
Jan.
12, 1990;
requests: Stephen G. Sawada, 926 W. Michigan St., Indianapolis, address: Division of Cardiology, Ann Arbor, Mich.
accepted
Feb.
26, 1990.
MD, Indiana University IN 46202-5250. University
of Michigan
Hospital, School
of
ment depression during exercise, but many others are not at increased risk.1-5 Both thallium scintigraphy and radionuclide ventriculography have been used in combination with exercise ECGs to improve risk stratification of patients with suspected coronary artery disease.6-g. Two-dimensional echocardiography, performed at rest and immediately after treadmill exercise, is a completely noninvasive, relatively low-cost technique that has proven accuracy for the diagnosis of coronary artery disease. lo-l5 Exercise-induced regional wall motion abnormalities are sensitive indicators of significant coronary artery disease. The absence of these abnormalities may identify those without physiologically significant coronary artery disease and thus those who are at low risk for future cardiac 49
50
Sawada et al.
events. This follow-up study was performed to determine whether normal exercise echocardiographic findings can identify a low-risk population. METHODS Patient selection.
Between December1984and December 1986, normal resting and post-treadmill exercise echocardiogramswere obtained from 184 patients evaluated at Indiana University Hospital and the Krannert Institute of Cardiology. Ten patients were excluded from the follow-up study after undergoing exercise echocardiography for the following reasons:evaluation of left ventricular function before aortic valve replacement (onepatient), evaluation of left ventricular function before or after renal or bone marrow transplantation (six patients), performanceof limited exercisetesting after myocardial infarction (one patient) or immediately before coronary artery bypass grafting (one patient), and coronary angioplasty (one patient). One other patient was excluded becauseof a technically inadequateexerciseechocardiogram.The remaining 173 patients who were included in the follow-up study underwent resting and immediate post-treadmill exercise echocardiography for the diagnosisof coronary artery diease. Exercise ECG. All patients underwent treadmill exercisetesting by meansof a modified Balke protocol.16Continuous ECG monitoring wasperformed with three bipolar leads.Exercise test endpoints were:development of fatigue or chest pain preventing further exercise, 23 consecutive premature ventricular contractions, >lO mm Hg decline in systolic blood pressureduring exercise,and attainment of ~85% of the age-predicted maximal heart rate. The exercise ECG response was graded as normal, ischemic,or nondiagnostic by a cardiologist who had no knowledge of the results of exercise echocardiography or other diagnosticprocedures.The exerciseECG wasdefined asshowingischemiawith the development of 1 mm or more of horizontal to downsloping ST segment depression80 msecafter the J point in a lead with a normal baseline.The ECG responsewas considerednondiagnostic in the presence of an abnormal baseline ST segment, left bundle branch block, treatment with digitalis glycosides,or position- or hyperventilation-induced ST segmentchanges. Exercise echocardiography. Two-dimensionalechocardiogramswererecordedwith commercially availableequipment (Advanced Technology Laboratories Mark 300 or Ultramark 4, Advanced Technology Laboratories, Inc., Bothell, Wash.) usinga 2.25or 3.0 MHz mechanicalsector scanner.The resting echocardiogramswere recorded with the patient in the left lateral decubitus position in four views (parasternallong- and short-axis and apicalfour- and two-chamber views). Immediately after termination of exercise,echocardiogramswere again recorded with patients in the left lateral position. Digital acquisition of all echocardiogramswasperformed by meansof an on-line analysissystem (Nova Microsonics Pre-Vue, Nova Microsonics, Mahwah, N.J.). The proce-
American
July 1990 Heart Journal
dure for preparation of the echocardiogramsfor analysis has been described previously.13 The echocardiographic imageswere arranged in a quad-screenformat with the appropriate resting and postexercise views placed side by side. The resting and exercise echocardiographic data were interpreted by an investigator who had no knowledgeof the results of exercise ECGs, additional diagnostic tests, and clinical outcome. Resting and exercise echocardiograms were considered normal if all left ventricular segments contracted normally at rest and remained normal or becamehyperdynamic with exercise.The development of regional hypokinesia, akinesia, or dyskinesiawasconsidered an abnormal response.Patients who had abnormal resting or exerciseechocardiogramswere excluded from the study. A normal exercise echocardiogramis shown in Fig. 1. Coronary angiography. Coronary angiography wasperformed during the follow-up period according to the judgment of the referring physician. Angiograms were interpreted by a cardiologistwho visually estimatedpercentages of diameter stenosis.Significant coronary artery disease wasdefined as 50% or more stenosisof a major epicardial coronary artery or major branch vessel. Pretest likelihood of coronary artery disease. The pretest likelihood of coronary artery diseasewas determined on the basisof age,sex, symptom status, and results of previous exerciseECG testing with tables published by Diamond and Forrester.l7 Patients who had substernal chestpain that wasinduced by exerciseand relieved by rest or nitroglycerin were considered to have typical angina. Patients wereconsideredto have atypical chestpain if their discomfort wasnot predictably precipitated by exertion or if it was not rapidly relieved by rest or nitroglycerin. Patient follow-up. Referring physicians and patients were contacted by mail and asked to complete questionnaires with the patients’ clinical data. The physician, patient, or both individuals were contacted by telephone if the questionnairewasnot returned. For patients who were followed at Indiana University Medical Center, information was also obtained by review of medical records. Significant cardiac events were defined ascoronary angioplasty, coronary artery bypassgrafting, myocardial infarction, sudden cardiac death, or death resulting from an ischemic event. The diagnosisof myocardial infarction was made on the basisof typical symptoms and ECG changes coupled with an increase in creatine kinase >180 IU/ml with more than 6 % MB fraction. Diagnosisof clinically silent infarction wasmade on the basisof new pathologic Q waves (240 msecin duration) or new regional akinesia or dyskinesia determined by resting echocardiography. Statistical analysis. The values for clinical variables were expressed as the mean ? the standard deviation. Fisher’s exact test was used to compare proportions between patient groups. The t test was usedto compare the meansof continuousvariables betweenpatient groups.The Mann-Whitney U test was used to compare the pretest likelihood of coronary artery diseaseof the study group with that of patients who did not have adequatefollow-up.
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51
1. Parasternal long-axis echocardiogramsrecorded at rest and immediately after exercise showing normal resting wall motion and hyperdynemic wall motion after exercise.DIAS, diastole; SYS, systole;LA, left atrium; LV, left ventricle; RV, right ventricle.
Fig.
RESULTS
Exercise echocardiography was performed in 3 of 173 patients as part of a diagnostic evaluation that included coronary angiography. These three patients
who had normal exercise echocardiograms underwent coronary angioplasty at the time of angiography (Table I). All of these patients had stable, atypical chest pain at the time of evaluation and good exercise capacity. The decision to perform angioplasty was influenced by favorable coronary anatomy. The remaining 170 patients were included in the study and complete follow-up data was obtained from 148 (87%). Follow-up information was inadequate or could not be obtained from 22. Six patients could not be contacted after moving out of state because of a change in occupation or retirement. Two others had normal coronary angiographic findings
and did not return for medical follow-up. The remaining patients could not be contacted directly or
through their referring physicians. The mean age of patients who had inadequate follow-up was 49.4 years (range 18 to 70 years); 10 were women. In these patients the estimated pretest likelihood of coronary artery disease was 32.4% (36% in men and 28% in women). Eighteen of the 22 patients (82 % > achieved 285 % of the age-predicted maximal heart rate during exercise, and the mean work load achieved was 7.2 ? 2.6 METS. The mean double product (peak heart rate - systolic blood pressure product) was 29.7 * 6.2 X lo3 mm/min. Follow-up was successful in 148 patients (77 men and 71 women) who were followed for a mean of 28.4 +- 8.5 months (range 1 to 46.5 months). The mean age was 52.5 + 10.6 years (range 28 to 81 years). The pretest probability of coronary artery disease for the study group was 39.3% (40.5% in women and 38.0 % in men) (Fig. 2). Fifty-seven patients were receiving antianginal medication: beta blockers (20 pa-
52
Sawada et al.
Table
American
July 1990 Heart Journal
I. Results of exercisetesting and coronary angiography in patients undergoing early intervention Age Sex
(Yr)
Subject
~85% Maximal heart rate*
58 F 57 M 35 M
1
2 3
1185 % Maximal heart rate 26 METS Atypical pain Angina ECG response Normal Nondiagnostic Ischemic Abbreviations
No. of patients
35 33 33
METS
6 6 8
Exercise
ECG
Nondiagnostic Ischemic Normal
Angiographicf disease
1 vessel 2 vessel 1 vessel
maximum. stenosis.
test results in patients
Test results
product
(Xl03 mmlmin)
Yes Yes Yes
METS, Metabolic equivalents. *Achieved heart rate 285% of the age-predicted tone or more coronary arteries ~50% diameter
Table II. Exercise follow-up
Double
with
successful % of
Patients
102
69
92 16 10
62 11 7
79 41 28
53 28 19
as in Table I.
tients), coronary vasodilators (21 patients), and beta blockers plus coronary vasodilators (16 patients). Results of exercise testing are shown in Table II. Sixty-eight patients achieved less than 85% of the age-predicted maximal heart rate or exercised to work loads less than 6 METS. Sixteen patients (11% ) had atypical chest pain during exercise, and 10 patients (7 % ) had angina, The mean double product was 25.3 t- 7.7 X lo3 mm/min and the mean work load achieved was 7.1 +- 2.9 METS. The exercise ECG response was abnormal in 69 (47 % ), including 24 who achieved less than 85% of the age-predicted maximal heart rate or less than 6 METS. Twentyeight patients had ischemic exercise ECGs, including 16 who had 2 mm or more of ST segment depression. Cardiac events. Six of the 148 patients (4.1%) had cardiac events. Four patients had coronary artery bypass grafting (1.7% per year), and two had nonfatal myocardial infarction (0.85% per year) (Table III). Three patients had coronary angiography and coronary artery bypass grafting for worsening angina. One other patient had coronary artery bypass grafting for 50% diameter stenosis of a single vessel at the time of mitral valve replacement for severe mitral insufficiency. In those with worsening angina, coronary angiography and coronary artery bypass surgery were performed from 10.5 to 22.5 months after a normal exercise echocardiogram. A second exercise
echocardiogram was abnormal in one patient who was reevaluated before undergoing coronary artery bypass grafting. The diagnosis of myocardial infarction was made in two patients based on the echocardiographic finding of new resting wall motion abnormalities. An 81-year-old man had a prolonged episode of chest pain 7.5 months after a normal exercise echocardiogram but did not immediately seek medical attention. Results of resting echocardiography performed 6 months later showed inferior wall akinesia. The patient has had no recurrent events in 24 months of additional follow-up after the diagnosis of myocardial infarction. A second patient developed increasing angina 41 months after undergoing exercise echocardiography for stable angina. There was no cardiac enzyme or ECG evidence of infarction, but results of resting echocardiography showed a new area of inferior wall akinesia. More extensive inferior wall motion abnormalities occurred during repeat exercise echocardiography, and coronary angiographic findings showed right coronary occlusion with collateral supply. Five of six patients who had cardiac events achieved less than 85% of the age-predicted maximal heart rate during exercise (Table III). Five of six also achieved work loads of less than 6 METS. Cardiac events were more frequent in patients who did not achieve at least 85% of the age-predicted maximal heart rate (10.9% versus 1.0%) p = 0.011) or who did not achieve work loads of at least 6 METS (8.9 % versus 1.1% , p = 0.029). Cardiac events occurred in 2 of 27 (7.5% ) who presented for exercise echocardiography with angina. Cardiac events occurred in three patients with normal exercise ECGs and three with abnormal exercise ECGs. None of the 26 women with abnormal exercise ECGs had an event. Only 1 of 28 patients (3.5 % ) with significant ST segment depression had a cardiac event. The event (coronary artery bypass grafting) occurred in 1 of 16 (6.3%) with 2 mm or more of ST segment depression. Fifty-three patients had persistent or recurrent
Volume
120
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Prognosis of normal
Men (ilen
exercise 2DE
53
Women h=71)
90
80 70 60 50 40 30 20 10 0 0
10
20
30
40
Number
Fig. 2. Pretest
Table
111.Clinical
Subject 1 2 3 4 5 6
81 M 59 M 51 F 57 M
78 M
60
70
20
likelihood
HR
of coronary
METS
No No No Yes No No
MI, Myocardial infarction; CABG, coronary *After echocardiographic evaluation.
4 5 12 5 4 3 artery
30
40
50
70
Number of Patients
28570
Maximal
10
of Patients
and exercise test data of patients
Age Sex fyr) 52 F
50
artery
disease in patients
with
successful follow-up.
with events Exercise ECG
Event type, time *
Angiographic disease
Symptoms on follow-up
Nondiagnostic Normal Ischemic Normal Normal Nondiagnostic
MI 7.5 mo MI 41 mo CABG 22.5 mo CABG 10.5 mo CABG 12.5 mo CABG, MVR 1 mo
No angiography I vessel 3 vessel
Atypical pain New angina New angina Worsening angina Worsening angina Dyspnea
bypass grafting;
MVR,
chest pain after echocardiographic evaluation, Cardiac events occurred in 4 of 13 who had new or recurrent angina. All four also achieved less than 6 METS or less than 85% of the age-predicted maximal heart rate. Forty patients had persistent or recurrent atypical chest pain, 25 of whom achieved less than 6 METS or less than 85 % of the age-predicted maximal heart rate. However, cardiac events occurred in only one with atypical pain after echocardiographic evaluation. There were no events in women with persistent or recurrent atypical chest pain. Twenty-one patients underwent coronary angiography during the follow-up period including five who had cardiac events. Four of the 16 patients without events had significant coronary artery disease, two
mitral
valve replacement;
3 vessel 2 vessel
1 vessel
other abbreviations
as in Table I.
had single-vessel disease, one had double-vessel disease, and one had stenoses of several branch vessels. DISCUSSION
Accurate assessment of prognosis in patients evaluated with known or suspected coronary artery disease is a major goal of noninvasive exercise testing. Exercise echocardiography is a newer completely noninvasive imaging technique relatively low in cost compared with competing technologies. Results of previous studies have demonstrated the accuracy of the technique for the diagnosis of coronary artery disease. lo-l5 In this study the prognostic value of a normal exercise echocardiogram was assessed in patients evaluated for suspected coronary artery disease.
54
Sawada et al.
Normal exercise echocardiography identified a population at low risk for cardiac events. Only 4.1% of patients had cardiac events. Coronary artery bypass grafting was performed at a rate of 1.7% per year, and serious ischemic events were even less frequent (myocardial infarction rate = 0.85% per year, death rate = 0% per year). In this study population, with an intermediate probability of coronary artery disease, a low cardiac event rate may not be unexpected. However, nonfatal infarction and death were unusual even in those who initially had angina and who had the highest pretest likelihood of disease. High-risk patients frequently have exercise-induced ST segment depression, but many others who have ST segment depression do not have significantly increased risk. ‘a 3, 4 In this study cardiac events were infrequent even though the proportion of patients with abnormal exercise ECGs exceeded 40 % . We have previously shown that exercise echocardiography has considerable diagnostic value in the setting of an abnormal but nondiagnostic ECG.l” Of the 28 patients who had significant ST segment depression in this study population, 16 had 2 mm or more of ST segment depression and only one had a cardiac event (coronary artery bypass grafting). Results of previous exercise ECG studies have also shown that profound ST segment depression may not indicate a poor prognosis except in those with decreased exercise capacity.4g 18,lg The prognostic value of exercise ECGs may be enhanced by assessment of hemodynamic parameters and achieved work loads.5 The prognosis of symptomatic patients improves with increasing exercise capacity.2y l8 In this study all patients who had cardiac events could be identified by failure to achieve a work load of 6 or more METS (approximating the end of stage II of the Bruce protocol) or failure to achieve a heart rate of at least 85 % of the agepredicted maximal heart rate. However, patients with cardiac events comprised only 8.9 % (6 of 68) of the patients who were exercised to low work loads or achieved less than 85 % of the age-predicted maximal heart rate. Nonfatal myocardial infarction occurred in only 2.9% (2 of 68) suggesting that a normal exercise echocardiogram is indicative of a favorable prognosis in the vast majority of those who have reduced exercise capacity. Patients with reduced exercise capacity at the time of the initial exercise echocardiographic evaluation and who subsequently have recurrent angina appear to be at greatest risk. In contrast, those who had recurrent atypical chest pain and reduced exercise capacity are at very low risk for future cardiac events. In five of six patients who had cardiac events, at
American
July 1990 Heart Journal
least 7 months elapsed between the time of exercise echocardiography and the cardiac event. In the remaining patient, coronary artery bypass grafting for mild single-vessel disease was performed during mitral valve replacement 1 month after exercise echocardiography. The prognostic value of a normal exercise echocardiogram may diminish with the passage of time and progression of coronary artery disease. In addition, unpredictable events such as plaque fissure or intraplaque hemorrhage may result in abrupt progression of disease in a patient who previously had no obstructive coronary artery disease.20 In this study progression of coronary artery disease probably accounted for the events in two patients (Table III) who had events 2 or more years after exercise echocardiography. A second exercise echocardiogram may provide useful information in a patient who has a change in symtoms or new symptoms. Four patients who had events had angina of new onset or worsening of previouslystableanginaafter exerciseechocardiography. Results of repeat exercise echocardiography showed exercise-induced abnormalities in two, including one who also had a severe but limited resting wall motion abnormality and was presumed to have had a small myocardial infarction. The diagnosis of coronary artery disease in women is complicated by the frequency of abnormal exercise ECGs in the absence of significant coronary artery disease. In a previous report from this laboratory, results of exercise echocardiography showed diagnostic accuracy in women. 21 Findings in the present study indicate that exercise echocardiography also has prognostic value in women. Cardiac events occurred in only 2 of 71 women (2.8 % ), both of whom had had no symptoms or signs of ischemia during exercise testing. No events occurred in women with abnormal exercise ECGs or recurrent atypical chest pain. Limitations of the study. Three patients who underwent coronary angiography and angioplasty shortly after echocardiographic evaluation were excluded from the follow-up study. Follow-up was incomplete or could not be obtained in 22 patients. Unknown cardiac events may have occurred in these patients, but their cardiac event rate probably would not be any higher than the event rate in the study group. Two patients who were lost to follow-up had normal coronary angiograms. The mean age of the patients lost to follow-up was 3 years less than the mean age of the study group (49.4 years versus 52.5 years, p = 0.2). The pretest likelihood of coronary artery disease of the group lost to follow-up was less than that of the study group (32.4% versus 39.3%) p = NS). In patients lost to follow-up the mean dou-
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ble product was 29.7 f 6.2 X lo3 mm/min compared to 25.4 1 7.7 x lo3 mm/min in the study group
(p = 0.006). In this study echocardiography was performed at rest and immediately after treadmill exercise in all patients. Recent data from this and other laboratories suggest that bicycle exercise echocardiography, which permits imaging during exercise, may have slightly higher sensitivity for the detection of coronary artery disease compared to echocardiography performed after treadmill exercise.22* 23 It is possible that a normal bicycle exercise echocardiogram may be even more predictive of a good prognosis. The study group was a referral-based population, which may not be representative of the population encountered in a primary care setting. A normal exercise echocardiogram may be most helpful to the clinician who is evaluating a patient with an abnormal exercise ECG or persistent chest pain. Even in these patients serious ischemic events are rare, and thus more costly invasive procedures may be avoided. In this study a normal exercise echocardiogram identified patients who were unlikely to have coronary artery bypass grafting or serious ischemic events in the 28 months after evaluation. A normal exercise echocardiogram in a patient with good exercise capacity was predictive of an excellent prognosis, even in those with abnormal exercise ECGs. Patients who had persistent or recurrent atypical chest pain after echocardiographic evaluation were also at low risk for cardiac events. Serious ischemic events, myocardial infarction, and death were unusual even in those who had reduced exercise capacity. We thank Barbara Wolfe and Naomi Fineberg, PhD, for assistance in the preparation of this manuscript. REFERENCES
1. Giagnoni E, Secchi MB, Wu SC, et al. Prognostic value of exercise EKG testing in asymptomatic normotensive subjects. N Engl J Med 1983;309:1085-9. 2. Weiner DA, Ryan TJ, McCabe CH, et al. Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am Co11 Cardiol 1984;3:772-9. 3. Ryan TJ, Weiner DA, McCabe CH, et al. Exercise testing in the Coronary Artery Surgery Study randomized population. Circulation 1985;72(suppl V):V31-8. 4. Podrid PJ, Graboys TB, Lown B. Prognosis of medically treated patients with coronary-artery disease with profound ST-segment depression during exercise testing. N Engl J Med 1981;305:1111-6. 5. Chaitman BR. The changing role of the exercise electrocardiogram as a diagnostic and prognostic test for chronic ischemic heart disease. J Am Co11 Cardiol 1986;8:1195-10. 6. Brown KA, Boucher CA, Okada RD, et al. Prognostic value of
Prognosisof normal exerciseZDE
7.
8.
9. 10.
11.
12.
13.
14.
15.
16.
17. 18. 19. 20.
21. 22.
23.
55
thallium-201 imaging in patients presenting for evaluation of chest pain. J Am Co11 Cardiol 1983;4:994-01. Pamelia FX, Gibson RS, Watson DD, Craddock GB, Sirowatka J, Beller GA. Prognosis with chest pain and normal thallium-201 exercise scintigrams. Am J Cardiol 1985;55: 9206. Wackers FJT, Russo DJ, Russo D, Clements JP. Prognostic significance of normal quantitative planar thallium-201 stress scintigraphy in patients with chest pain. J Am Co11 Cardiol 1985;6:27-30. Pryor DB, Harrell FE, Lee KL, et al. Prognostic indicators from radionuclide angiography in medically treated patients with coronary artery disease. Am J Cardiol 1984;53:18-22. Robertson WS, Feigenbaum H, Armstrong WF, Dillon JC, O’Donnell J, McHenry PL. Exercise echocardiography: a clinically practical addition in the evaluation of coronary artery disease. J Am Co11 Cardiol 1983;2:1085-91. Limacher MC, Quinones MA, Poliner LR, Nelson JG, Winters Jr WL, Waggoner AD. Detection of coronary artery disease with exercise two-dimensional echocardiography: description of a clinically applicable method and comparison with radionuclide ventriculography. Circulation 1983;67:1211-8. Visser CA, van der Wieken RL, Kan G, et al. Comparison of two-dimensional echocardiography with radionuclide angiography during dynamic exercise for the detection of coronary artery disease. AM HEART J 1983;106:528-34. Armstrong WF, O’Donnell J, Dillon JC, McHenry PL, Morris S, Feigenbaum H. Complementary value of two-dimensional exercise echocardiography to routine treadmill exercise testing. Ann Intern Med 1986;105:829-35. Ryan T, Vasey CG, Presti CF, O’Donnell JA, Feigenbaum H, Armstrong WF. Exercise echocardiography: detection of coronary artery disease in patients with normal left ventricular wall motion at rest. J Am Co11 Cardiol 1988;11:993-9. Crawford MH, Amon KW, Vance WS. Exercise 2-dimensional echocardiography: quantitation of left ventricular performance in patients with severe angina pectoris. Am J Cardiol 1983;51:1-6. McHenry PL, Phillips JF, Knoebel SB. Correlation of computer quantitated treadmill exercise electrocardiogram with arteriographic location of coronary artery disease. Am J Cardiol 1972;30:747-52. Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med 1979;300:1350-8. Dagenais GR, Rouleau JR, Christen A, Fabia J. Survival of patients with a strongly positive exercise electrocardiogram. Circulation 1982;3:452-6. Dagenais GR, Rouleau JR, Hochart P, Magrina J, Cantin B, Dumesnil JG. Survival with painless strongly positive exercise electrocardiogram. Am J Cardiol 1988;62:892-5. Waller BF. Atherosclerotic and nonatherosclerotic coronary artery factors in acute myocardial infarction. In: Pepine CJ, ed. Acute myocardial infarction. Vol. 20 of Cardiovascular Clinics; Brest AN, ed. Philadelphia: FA Davis Company, 1989:29-104. Sawada S, McHenry PL, Armstrong WF, Ryan T, Feigenbaum H. Exercise echocardiographic detection of coronary artery disease in women. J Am Co11 Cardiol 1989;14:1440-7. Presti CF, Armstrong WF, Feigenbaum H. Comparison of echocardiography at peak exercise and after bicycle exercise in evaluation of patients with known or suspected coronary artery disease. J Am Sot Echocardiogr 1988;1:119-26. Applegate RJ, Dell’Italia LJ, Crawford MH. Usefulness of two-dimensional echocardiography during low-level exercise testing early after uncomplicated myocardial infarction. Am J Cardiol 1987;60:10-4.
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26. Borer JS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnston GS. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronaryartery disease. N Engl J Med 1977;296:839-44. 27. Borer JS, Kent KM, Bacharach SL, et al. Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with coronary artery disease; comparison with exercise electrocardiography. Circulation 1979; 60:572-80.
28. Berger HJ, Reduto LA, Johnstone DE, Borkowski H, Sands JM, Cohen LS, Langou RA, Gottschalk A, Zaret BL, Pytlic L. Global and regional left ventricular response to bicycle exercise in coronary artery disease; assessment by quantitative radionuclide angiocardiography. Am J Med 1979;66:13-21. 29. Iskandrian AS, Hakki AH, Segal BL, Kane SA, Amenta A. Assessment of myocardial perfusion pattern in patients with multivessel coronary artery disease. AM HEART J 1983; 106:1089-96.
Prognostic value of a normal exercise echocardiogram Follow-up information was obtained from 148 patients who had normal resting and post-treadmill exercise echocardiograms to determine the prognostic value of a normal exercise echocardiogram in patients evaluated for suspected coronary artery disease. There were 77 men and 71 women with a mean age of 52.5 years and a pretest likelihood of coronary artery disease of 39%. Patients were followed for a mean duration of 28.4 + 8.5 months. The exercise ECG was abnormal in 69 patients (47%) including 28 who had ischemic responses. Cardiac events occurred in six patients, three with normal and three with abnormal exercise ECGs. Events occurred only in those patients (6 of 68) who exercised to work loads less than 6 METS or who achieved less than 85% of the age-predicted maximal heart rate. Three patients had coronary artery bypass grafting for angina from 10.5 to 22.5 months after echocardiography. A fourth patient had bypass grafting for mild single-vessel disease at the time of mitral valve replacement. Two patients had myocardial infarctions (0.85% per year) at 7.5 and 41 months after echocardiography. There were no deaths. Coronary revascularization is infrequently required in the 28 months after a normal exercise echocardiogram. A normal exercise echocardiogram in a patient with good exercise capacity was predictive of an excellent prognosis, even in those who had abnormal exercise ECGs. Myocardial infarction and death were rare events, even in patients with decreased exercise capacity. (AM HEART J 1990;120:49.)
Stephen G. Sawada, MD, Thomas Ryan, MD, Mary Jo Conley, Betty C. Corya, MD, Harvey Feigenbaum, MD, and William F. Armstrong, MD.* IrzdianapoZis, Ind.
Accurate assessment of prognosis in patients with known or suspected coronary artery disease is a major goal of noninvasive exercise testing. Cardiac events may occur in some patients who have ST seg-
From the Krannert Institute of Cardiology, Department of Medicine, Indiana University School of Medicine. Supported in part by the Herman C. Krannert Fund, Indianapolis, Ind.; grants HL-06308 and HL-07182 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.; and the American Heart Association, Indiana Affiliate, Indianapolis, Ind. Received Reprint N562, *Current Medicine, 4/I/20442
for publication
Jan.
12, 1990;
requests: Stephen G. Sawada, 926 W. Michigan St., Indianapolis, address: Division of Cardiology, Ann Arbor, Mich.
accepted
Feb.
26, 1990.
MD, Indiana University IN 46202-5250. University
of Michigan
Hospital, School
of
ment depression during exercise, but many others are not at increased risk.1-5 Both thallium scintigraphy and radionuclide ventriculography have been used in combination with exercise ECGs to improve risk stratification of patients with suspected coronary artery disease.6-g. Two-dimensional echocardiography, performed at rest and immediately after treadmill exercise, is a completely noninvasive, relatively low-cost technique that has proven accuracy for the diagnosis of coronary artery disease. lo-l5 Exercise-induced regional wall motion abnormalities are sensitive indicators of significant coronary artery disease. The absence of these abnormalities may identify those without physiologically significant coronary artery disease and thus those who are at low risk for future cardiac 49
50
Sawada et al.
events. This follow-up study was performed to determine whether normal exercise echocardiographic findings can identify a low-risk population. METHODS Patient selection.
Between December1984and December 1986, normal resting and post-treadmill exercise echocardiogramswere obtained from 184 patients evaluated at Indiana University Hospital and the Krannert Institute of Cardiology. Ten patients were excluded from the follow-up study after undergoing exercise echocardiography for the following reasons:evaluation of left ventricular function before aortic valve replacement (onepatient), evaluation of left ventricular function before or after renal or bone marrow transplantation (six patients), performanceof limited exercisetesting after myocardial infarction (one patient) or immediately before coronary artery bypass grafting (one patient), and coronary angioplasty (one patient). One other patient was excluded becauseof a technically inadequateexerciseechocardiogram.The remaining 173 patients who were included in the follow-up study underwent resting and immediate post-treadmill exercise echocardiography for the diagnosisof coronary artery diease. Exercise ECG. All patients underwent treadmill exercisetesting by meansof a modified Balke protocol.16Continuous ECG monitoring wasperformed with three bipolar leads.Exercise test endpoints were:development of fatigue or chest pain preventing further exercise, 23 consecutive premature ventricular contractions, >lO mm Hg decline in systolic blood pressureduring exercise,and attainment of ~85% of the age-predicted maximal heart rate. The exercise ECG response was graded as normal, ischemic,or nondiagnostic by a cardiologist who had no knowledge of the results of exercise echocardiography or other diagnosticprocedures.The exerciseECG wasdefined asshowingischemiawith the development of 1 mm or more of horizontal to downsloping ST segment depression80 msecafter the J point in a lead with a normal baseline.The ECG responsewas considerednondiagnostic in the presence of an abnormal baseline ST segment, left bundle branch block, treatment with digitalis glycosides,or position- or hyperventilation-induced ST segmentchanges. Exercise echocardiography. Two-dimensionalechocardiogramswererecordedwith commercially availableequipment (Advanced Technology Laboratories Mark 300 or Ultramark 4, Advanced Technology Laboratories, Inc., Bothell, Wash.) usinga 2.25or 3.0 MHz mechanicalsector scanner.The resting echocardiogramswere recorded with the patient in the left lateral decubitus position in four views (parasternallong- and short-axis and apicalfour- and two-chamber views). Immediately after termination of exercise,echocardiogramswere again recorded with patients in the left lateral position. Digital acquisition of all echocardiogramswasperformed by meansof an on-line analysissystem (Nova Microsonics Pre-Vue, Nova Microsonics, Mahwah, N.J.). The proce-
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July 1990 Heart Journal
dure for preparation of the echocardiogramsfor analysis has been described previously.13 The echocardiographic imageswere arranged in a quad-screenformat with the appropriate resting and postexercise views placed side by side. The resting and exercise echocardiographic data were interpreted by an investigator who had no knowledgeof the results of exercise ECGs, additional diagnostic tests, and clinical outcome. Resting and exercise echocardiograms were considered normal if all left ventricular segments contracted normally at rest and remained normal or becamehyperdynamic with exercise.The development of regional hypokinesia, akinesia, or dyskinesiawasconsidered an abnormal response.Patients who had abnormal resting or exerciseechocardiogramswere excluded from the study. A normal exercise echocardiogramis shown in Fig. 1. Coronary angiography. Coronary angiography wasperformed during the follow-up period according to the judgment of the referring physician. Angiograms were interpreted by a cardiologistwho visually estimatedpercentages of diameter stenosis.Significant coronary artery disease wasdefined as 50% or more stenosisof a major epicardial coronary artery or major branch vessel. Pretest likelihood of coronary artery disease. The pretest likelihood of coronary artery diseasewas determined on the basisof age,sex, symptom status, and results of previous exerciseECG testing with tables published by Diamond and Forrester.l7 Patients who had substernal chestpain that wasinduced by exerciseand relieved by rest or nitroglycerin were considered to have typical angina. Patients wereconsideredto have atypical chestpain if their discomfort wasnot predictably precipitated by exertion or if it was not rapidly relieved by rest or nitroglycerin. Patient follow-up. Referring physicians and patients were contacted by mail and asked to complete questionnaires with the patients’ clinical data. The physician, patient, or both individuals were contacted by telephone if the questionnairewasnot returned. For patients who were followed at Indiana University Medical Center, information was also obtained by review of medical records. Significant cardiac events were defined ascoronary angioplasty, coronary artery bypassgrafting, myocardial infarction, sudden cardiac death, or death resulting from an ischemic event. The diagnosisof myocardial infarction was made on the basisof typical symptoms and ECG changes coupled with an increase in creatine kinase >180 IU/ml with more than 6 % MB fraction. Diagnosisof clinically silent infarction wasmade on the basisof new pathologic Q waves (240 msecin duration) or new regional akinesia or dyskinesia determined by resting echocardiography. Statistical analysis. The values for clinical variables were expressed as the mean ? the standard deviation. Fisher’s exact test was used to compare proportions between patient groups. The t test was usedto compare the meansof continuousvariables betweenpatient groups.The Mann-Whitney U test was used to compare the pretest likelihood of coronary artery diseaseof the study group with that of patients who did not have adequatefollow-up.
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1. Parasternal long-axis echocardiogramsrecorded at rest and immediately after exercise showing normal resting wall motion and hyperdynemic wall motion after exercise.DIAS, diastole; SYS, systole;LA, left atrium; LV, left ventricle; RV, right ventricle.
Fig.
RESULTS
Exercise echocardiography was performed in 3 of 173 patients as part of a diagnostic evaluation that included coronary angiography. These three patients
who had normal exercise echocardiograms underwent coronary angioplasty at the time of angiography (Table I). All of these patients had stable, atypical chest pain at the time of evaluation and good exercise capacity. The decision to perform angioplasty was influenced by favorable coronary anatomy. The remaining 170 patients were included in the study and complete follow-up data was obtained from 148 (87%). Follow-up information was inadequate or could not be obtained from 22. Six patients could not be contacted after moving out of state because of a change in occupation or retirement. Two others had normal coronary angiographic findings
and did not return for medical follow-up. The remaining patients could not be contacted directly or
through their referring physicians. The mean age of patients who had inadequate follow-up was 49.4 years (range 18 to 70 years); 10 were women. In these patients the estimated pretest likelihood of coronary artery disease was 32.4% (36% in men and 28% in women). Eighteen of the 22 patients (82 % > achieved 285 % of the age-predicted maximal heart rate during exercise, and the mean work load achieved was 7.2 ? 2.6 METS. The mean double product (peak heart rate - systolic blood pressure product) was 29.7 * 6.2 X lo3 mm/min. Follow-up was successful in 148 patients (77 men and 71 women) who were followed for a mean of 28.4 +- 8.5 months (range 1 to 46.5 months). The mean age was 52.5 + 10.6 years (range 28 to 81 years). The pretest probability of coronary artery disease for the study group was 39.3% (40.5% in women and 38.0 % in men) (Fig. 2). Fifty-seven patients were receiving antianginal medication: beta blockers (20 pa-
52
Sawada et al.
Table
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July 1990 Heart Journal
I. Results of exercisetesting and coronary angiography in patients undergoing early intervention Age Sex
(Yr)
Subject
~85% Maximal heart rate*
58 F 57 M 35 M
1
2 3
1185 % Maximal heart rate 26 METS Atypical pain Angina ECG response Normal Nondiagnostic Ischemic Abbreviations
No. of patients
35 33 33
METS
6 6 8
Exercise
ECG
Nondiagnostic Ischemic Normal
Angiographicf disease
1 vessel 2 vessel 1 vessel
maximum. stenosis.
test results in patients
Test results
product
(Xl03 mmlmin)
Yes Yes Yes
METS, Metabolic equivalents. *Achieved heart rate 285% of the age-predicted tone or more coronary arteries ~50% diameter
Table II. Exercise follow-up
Double
with
successful % of
Patients
102
69
92 16 10
62 11 7
79 41 28
53 28 19
as in Table I.
tients), coronary vasodilators (21 patients), and beta blockers plus coronary vasodilators (16 patients). Results of exercise testing are shown in Table II. Sixty-eight patients achieved less than 85% of the age-predicted maximal heart rate or exercised to work loads less than 6 METS. Sixteen patients (11% ) had atypical chest pain during exercise, and 10 patients (7 % ) had angina, The mean double product was 25.3 t- 7.7 X lo3 mm/min and the mean work load achieved was 7.1 +- 2.9 METS. The exercise ECG response was abnormal in 69 (47 % ), including 24 who achieved less than 85% of the age-predicted maximal heart rate or less than 6 METS. Twentyeight patients had ischemic exercise ECGs, including 16 who had 2 mm or more of ST segment depression. Cardiac events. Six of the 148 patients (4.1%) had cardiac events. Four patients had coronary artery bypass grafting (1.7% per year), and two had nonfatal myocardial infarction (0.85% per year) (Table III). Three patients had coronary angiography and coronary artery bypass grafting for worsening angina. One other patient had coronary artery bypass grafting for 50% diameter stenosis of a single vessel at the time of mitral valve replacement for severe mitral insufficiency. In those with worsening angina, coronary angiography and coronary artery bypass surgery were performed from 10.5 to 22.5 months after a normal exercise echocardiogram. A second exercise
echocardiogram was abnormal in one patient who was reevaluated before undergoing coronary artery bypass grafting. The diagnosis of myocardial infarction was made in two patients based on the echocardiographic finding of new resting wall motion abnormalities. An 81-year-old man had a prolonged episode of chest pain 7.5 months after a normal exercise echocardiogram but did not immediately seek medical attention. Results of resting echocardiography performed 6 months later showed inferior wall akinesia. The patient has had no recurrent events in 24 months of additional follow-up after the diagnosis of myocardial infarction. A second patient developed increasing angina 41 months after undergoing exercise echocardiography for stable angina. There was no cardiac enzyme or ECG evidence of infarction, but results of resting echocardiography showed a new area of inferior wall akinesia. More extensive inferior wall motion abnormalities occurred during repeat exercise echocardiography, and coronary angiographic findings showed right coronary occlusion with collateral supply. Five of six patients who had cardiac events achieved less than 85% of the age-predicted maximal heart rate during exercise (Table III). Five of six also achieved work loads of less than 6 METS. Cardiac events were more frequent in patients who did not achieve at least 85% of the age-predicted maximal heart rate (10.9% versus 1.0%) p = 0.011) or who did not achieve work loads of at least 6 METS (8.9 % versus 1.1% , p = 0.029). Cardiac events occurred in 2 of 27 (7.5% ) who presented for exercise echocardiography with angina. Cardiac events occurred in three patients with normal exercise ECGs and three with abnormal exercise ECGs. None of the 26 women with abnormal exercise ECGs had an event. Only 1 of 28 patients (3.5 % ) with significant ST segment depression had a cardiac event. The event (coronary artery bypass grafting) occurred in 1 of 16 (6.3%) with 2 mm or more of ST segment depression. Fifty-three patients had persistent or recurrent
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Number
1
Prognosis of normal
Men (ilen
exercise 2DE
53
Women h=71)
90
80 70 60 50 40 30 20 10 0 0
10
20
30
40
Number
Fig. 2. Pretest
Table
111.Clinical
Subject 1 2 3 4 5 6
81 M 59 M 51 F 57 M
78 M
60
70
20
likelihood
HR
of coronary
METS
No No No Yes No No
MI, Myocardial infarction; CABG, coronary *After echocardiographic evaluation.
4 5 12 5 4 3 artery
30
40
50
70
Number of Patients
28570
Maximal
10
of Patients
and exercise test data of patients
Age Sex fyr) 52 F
50
artery
disease in patients
with
successful follow-up.
with events Exercise ECG
Event type, time *
Angiographic disease
Symptoms on follow-up
Nondiagnostic Normal Ischemic Normal Normal Nondiagnostic
MI 7.5 mo MI 41 mo CABG 22.5 mo CABG 10.5 mo CABG 12.5 mo CABG, MVR 1 mo
No angiography I vessel 3 vessel
Atypical pain New angina New angina Worsening angina Worsening angina Dyspnea
bypass grafting;
MVR,
chest pain after echocardiographic evaluation, Cardiac events occurred in 4 of 13 who had new or recurrent angina. All four also achieved less than 6 METS or less than 85% of the age-predicted maximal heart rate. Forty patients had persistent or recurrent atypical chest pain, 25 of whom achieved less than 6 METS or less than 85 % of the age-predicted maximal heart rate. However, cardiac events occurred in only one with atypical pain after echocardiographic evaluation. There were no events in women with persistent or recurrent atypical chest pain. Twenty-one patients underwent coronary angiography during the follow-up period including five who had cardiac events. Four of the 16 patients without events had significant coronary artery disease, two
mitral
valve replacement;
3 vessel 2 vessel
1 vessel
other abbreviations
as in Table I.
had single-vessel disease, one had double-vessel disease, and one had stenoses of several branch vessels. DISCUSSION
Accurate assessment of prognosis in patients evaluated with known or suspected coronary artery disease is a major goal of noninvasive exercise testing. Exercise echocardiography is a newer completely noninvasive imaging technique relatively low in cost compared with competing technologies. Results of previous studies have demonstrated the accuracy of the technique for the diagnosis of coronary artery disease. lo-l5 In this study the prognostic value of a normal exercise echocardiogram was assessed in patients evaluated for suspected coronary artery disease.
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Sawada et al.
Normal exercise echocardiography identified a population at low risk for cardiac events. Only 4.1% of patients had cardiac events. Coronary artery bypass grafting was performed at a rate of 1.7% per year, and serious ischemic events were even less frequent (myocardial infarction rate = 0.85% per year, death rate = 0% per year). In this study population, with an intermediate probability of coronary artery disease, a low cardiac event rate may not be unexpected. However, nonfatal infarction and death were unusual even in those who initially had angina and who had the highest pretest likelihood of disease. High-risk patients frequently have exercise-induced ST segment depression, but many others who have ST segment depression do not have significantly increased risk. ‘a 3, 4 In this study cardiac events were infrequent even though the proportion of patients with abnormal exercise ECGs exceeded 40 % . We have previously shown that exercise echocardiography has considerable diagnostic value in the setting of an abnormal but nondiagnostic ECG.l” Of the 28 patients who had significant ST segment depression in this study population, 16 had 2 mm or more of ST segment depression and only one had a cardiac event (coronary artery bypass grafting). Results of previous exercise ECG studies have also shown that profound ST segment depression may not indicate a poor prognosis except in those with decreased exercise capacity.4g 18,lg The prognostic value of exercise ECGs may be enhanced by assessment of hemodynamic parameters and achieved work loads.5 The prognosis of symptomatic patients improves with increasing exercise capacity.2y l8 In this study all patients who had cardiac events could be identified by failure to achieve a work load of 6 or more METS (approximating the end of stage II of the Bruce protocol) or failure to achieve a heart rate of at least 85 % of the agepredicted maximal heart rate. However, patients with cardiac events comprised only 8.9 % (6 of 68) of the patients who were exercised to low work loads or achieved less than 85 % of the age-predicted maximal heart rate. Nonfatal myocardial infarction occurred in only 2.9% (2 of 68) suggesting that a normal exercise echocardiogram is indicative of a favorable prognosis in the vast majority of those who have reduced exercise capacity. Patients with reduced exercise capacity at the time of the initial exercise echocardiographic evaluation and who subsequently have recurrent angina appear to be at greatest risk. In contrast, those who had recurrent atypical chest pain and reduced exercise capacity are at very low risk for future cardiac events. In five of six patients who had cardiac events, at
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least 7 months elapsed between the time of exercise echocardiography and the cardiac event. In the remaining patient, coronary artery bypass grafting for mild single-vessel disease was performed during mitral valve replacement 1 month after exercise echocardiography. The prognostic value of a normal exercise echocardiogram may diminish with the passage of time and progression of coronary artery disease. In addition, unpredictable events such as plaque fissure or intraplaque hemorrhage may result in abrupt progression of disease in a patient who previously had no obstructive coronary artery disease.20 In this study progression of coronary artery disease probably accounted for the events in two patients (Table III) who had events 2 or more years after exercise echocardiography. A second exercise echocardiogram may provide useful information in a patient who has a change in symtoms or new symptoms. Four patients who had events had angina of new onset or worsening of previouslystableanginaafter exerciseechocardiography. Results of repeat exercise echocardiography showed exercise-induced abnormalities in two, including one who also had a severe but limited resting wall motion abnormality and was presumed to have had a small myocardial infarction. The diagnosis of coronary artery disease in women is complicated by the frequency of abnormal exercise ECGs in the absence of significant coronary artery disease. In a previous report from this laboratory, results of exercise echocardiography showed diagnostic accuracy in women. 21 Findings in the present study indicate that exercise echocardiography also has prognostic value in women. Cardiac events occurred in only 2 of 71 women (2.8 % ), both of whom had had no symptoms or signs of ischemia during exercise testing. No events occurred in women with abnormal exercise ECGs or recurrent atypical chest pain. Limitations of the study. Three patients who underwent coronary angiography and angioplasty shortly after echocardiographic evaluation were excluded from the follow-up study. Follow-up was incomplete or could not be obtained in 22 patients. Unknown cardiac events may have occurred in these patients, but their cardiac event rate probably would not be any higher than the event rate in the study group. Two patients who were lost to follow-up had normal coronary angiograms. The mean age of the patients lost to follow-up was 3 years less than the mean age of the study group (49.4 years versus 52.5 years, p = 0.2). The pretest likelihood of coronary artery disease of the group lost to follow-up was less than that of the study group (32.4% versus 39.3%) p = NS). In patients lost to follow-up the mean dou-
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ble product was 29.7 f 6.2 X lo3 mm/min compared to 25.4 1 7.7 x lo3 mm/min in the study group
(p = 0.006). In this study echocardiography was performed at rest and immediately after treadmill exercise in all patients. Recent data from this and other laboratories suggest that bicycle exercise echocardiography, which permits imaging during exercise, may have slightly higher sensitivity for the detection of coronary artery disease compared to echocardiography performed after treadmill exercise.22* 23 It is possible that a normal bicycle exercise echocardiogram may be even more predictive of a good prognosis. The study group was a referral-based population, which may not be representative of the population encountered in a primary care setting. A normal exercise echocardiogram may be most helpful to the clinician who is evaluating a patient with an abnormal exercise ECG or persistent chest pain. Even in these patients serious ischemic events are rare, and thus more costly invasive procedures may be avoided. In this study a normal exercise echocardiogram identified patients who were unlikely to have coronary artery bypass grafting or serious ischemic events in the 28 months after evaluation. A normal exercise echocardiogram in a patient with good exercise capacity was predictive of an excellent prognosis, even in those with abnormal exercise ECGs. Patients who had persistent or recurrent atypical chest pain after echocardiographic evaluation were also at low risk for cardiac events. Serious ischemic events, myocardial infarction, and death were unusual even in those who had reduced exercise capacity. We thank Barbara Wolfe and Naomi Fineberg, PhD, for assistance in the preparation of this manuscript. REFERENCES
1. Giagnoni E, Secchi MB, Wu SC, et al. Prognostic value of exercise EKG testing in asymptomatic normotensive subjects. N Engl J Med 1983;309:1085-9. 2. Weiner DA, Ryan TJ, McCabe CH, et al. Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am Co11 Cardiol 1984;3:772-9. 3. Ryan TJ, Weiner DA, McCabe CH, et al. Exercise testing in the Coronary Artery Surgery Study randomized population. Circulation 1985;72(suppl V):V31-8. 4. Podrid PJ, Graboys TB, Lown B. Prognosis of medically treated patients with coronary-artery disease with profound ST-segment depression during exercise testing. N Engl J Med 1981;305:1111-6. 5. Chaitman BR. The changing role of the exercise electrocardiogram as a diagnostic and prognostic test for chronic ischemic heart disease. J Am Co11 Cardiol 1986;8:1195-10. 6. Brown KA, Boucher CA, Okada RD, et al. Prognostic value of
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