topeesp.gif (5672 bytes)

[ Scientific Activities - Actividades Científicas ]

Noninvasive Predischarge Risk Assessment in Patients With Uncomplicated Myocardial Infarction

George A. Beller, M.D.

Chief Cardiovascular Division Department of Medicine
University of Virginia Health System
Charlottesville, Virginia, U.S.A.


Invasive versus conservative strategies

Noninvasive risk assessment
Vasodilator stress imaging


There has been a great deal of interest in determining the most cost-effective approach to risk stratification after acute myocardial infarction (1-7). The major determinants of prognosis after acute myocardial infarction relate to the degree of left ventricular dysfunction as evidenced by a depressed ejection fraction and extent of wall motion abnormalities, extent of residual jeopardized myocardium both in the distribution of the infarct-related artery or in remote myocardium, and the arrhythmogenicity potential of the left ventricle. The extent of jeopardized myocardium can best be evaluated by determination of extent and severity of inducible ischemia by noninvasive techniques and/or extent of angiographic coronary artery disease. Certain high-risk clinical variables have been identified that are associated with an increased risk of subsequent cardiac death or reinfarction. These variables are summarized in Slide #1.

fig1.jpg (35009 bytes)


Invasive Versus Conservative Strategies

Controversy exists concerning the most cost-effective approach to risk stratification in the thrombolytic era and the age of coronary intervention. Many patients who are successfully reperfused and have uncomplicated courses are candidates for early hospital discharge. The issue is whether or not "routine" coronary angiography performed early in the course of hospitalization yields superior information with respect to prognostication than exercise testing or exercise pharmacologic stress imaging. Results of certain large randomized clinical trials have indicated that either immediate or delayed elective angioplasty of the infarct-related vessel in patients without recurrent angina did not improve outcome or enhance left ventricular function (8-11). Michels and Yusuf (12) combined data from five trials that examined angioplasty performed more than 12 hours after myocardial infarction to patients who received only thrombolytic therapy and reported no difference in mortality rate or nonfatal infarction at either 6 weeks or 1 year of follow-up. In the TOPS study, Ellis et al (13) showed no functional or clinical benefit from routine late angioplasty in postinfarction patients receiving thrombolytic therapy who had negative functional test results for ischemia prior to randomization to medical therapy or elective revascularization.

The TIMI–III-B study specifically compared an early invasive strategy with a more conservative strategy in patients with unstable angina or non–Q-wave myocardial infarction (14). At 1 year, no difference in death or nonfatal infarction rate was seen between groups, although a substantial number of patients in the conservative group crossed over for subsequent revascularization (64%) (15).

The VANQWISH trial examined outcomes following acute non–Q-wave myocardial infarction comparing a conservative versus an invasive approach using a randomized protocol (16). In the conservative arm, patients underwent stress 201Tl planar imaging with symptom-limited treadmill exercise or dipyridamole vasodilator stress imaging. Coronary angiography was only performed in this group for those patients developing spontaneous postinfarction angina associated with ischemic ST-segment changes or exercise-induced ST-segment depression, evidence of myocardial ischemia in two or more vascular territories, or increased lung thallium uptake on 201Tl scintigraphy. Of interest was that the death or recurrent myocardial infarction rate was higher in the invasive group at discharge, 1 month and 1 year, although the mortality curves tended to converge at the end of follow-up at 44 months (Slide #2). Thus, the results of the randomized trials cited above, which compared a routine invasive approach to a "selective" angiographic approach showed no difference in outcomes.

fig2.jpg (27270 bytes)

In contrast to these prior studies, the FRISC-II study showed a decrease in the composite endpoint of death or myocardial infarction at 6 months in patients with non–Q-wave myocardial infarction randomized to an invasive strategy (17). Symptoms of angina and re-admission were halved by the invasive strategy.

Outcome studies comparing more invasive versus more conservative strategies showed no relation between use of invasive cardiac procedures and subsequent mortality rates in patients with acute myocardial infarction (18-24). Rouleau and coworkers (18) reported that although coronary angiography was more commonly performed in the United States than in Canada (68% vs. 35%), as were revascularization procedures after infarction (31% vs. 12%), no difference in mortality (22% in Canada and 23% in the U.S.), or rate of reinfarction (14% in Canada and 13% in the U.S.) was observed at a mean follow-up of 42 months. Angina, however, was more prevalent in Canada (33% vs. 27%).

Krumholz et al (25) found no significant difference in short- or long-term mortality rates or hospital costs in patients admitted to hospitals with on-site cardiac catheterization facilities compared to those admitted to hospitals without such facilities. The cardiac catheterization rate was higher in the hospitals with facilities (38.6% vs. 26.9%; p<0.001), but the revascularization rate was similar (20.5% vs. 19.5%) during the initial episode of care and at 3 years (29.7% vs. 29.7%).

In the GUSTO-II trial, the incidence of coronary angiography after acute myocardial infarction was 81% in U.S. centers compared to 26% in Canadian centers (26). The incidence of revascularization after myocardial infarction in U.S. centers was 59%, compared to 15% in Canadian centers. Despite these large differences in postinfarction angiography and revascularization, mortality rates were comparable at 5.6% for U.S. centers and 5.7% for Canadian centers.

Taken together, most of the randomized studies and virtually all of the epidemiologic studies examining variation in practice patterns have shown no significant advantage of an early invasive strategy compared to a more early conservative strategy in patients undergoing selective angiography for spontaneous ischemia, clinical high-risk variables (e.g. prior infarction, congestive heart failure), or inducible myocardial ischemia. FRISC-II was the only randomized study showing a statistically significant advantage for an invasive strategy (17). However, that study employed only exercise electrocardiographic (ECG) treadmill testing for identification of patients with inducible ischemia following an uncomplicated non–Q-wave infarction.


Noninvasive Risk Assessment

Slide 3 lists the various noninvasive tests presently available for risk assessment after acute myocardial infarction. Studies in the literature published in the 1980s indicated that submaximal or symptom-limited exercise testing or pharmacologic stress testing with vasodilator stress, performed in conjunction with 201Tl perfusion imaging, could separate high- and low-risk subsets of patients who experienced an uncomplicated myocardial infarction (27). Gibson and colleagues (28) reported that approximately 50% of patients 65 years of age or younger with an uncomplicated myocardial infarction who showed either multiple 201Tl perfusion defects in more than one coronary vascular supply region, a reversible thallium defect within or outside the infarct zone or abnormal lung thallium uptake on predischarge submaximal exercise perfusion imaging subsequently experienced either cardiac death, recurrent infarction or hospitalization for Class III-IV angina. The cardiac event rate was only 6% for patients who had either a normal stress perfusion scan after infarction or solely persistent defects in the supply region of the infarct-related artery.

fig3.jpg (27918 bytes)

Other studies published in the prethrombolytic and pre-interventional era also reported a high sensitivity in perfusion imaging for detecting multivessel CAD after infarction. In a pooled analysis of 508 patients, there was a 72% sensitivity for multiple thallium defects in more than one coronary vascular supply region for identifying multivessel disease, with an 86% specificity. In these studies, the sensitivity of exercise ECG testing alone for detecting multivessel disease was only 59% (29).

Gibson and Beller (30) performed a pooled analysis of 17 studies in the literature comprising 1,426 patients who underwent both exercise ECG testing and exercise 201Tl perfusion imaging after uncomplicated myocardial infarction. The prevalence of ischemic ST-segment depression was 24% in that patient population, compared to 55% who manifested 201Tl redistribution (Slide #4). Thus, the sensitivity of myocardial perfusion imaging is significantly greater than the sensitivity of exercise ECG testing for identifying residual ischemia after uncomplicated infarction.

fig4.jpg (38962 bytes)


Shaw et al (27) performed a pooled analysis of test results from studies reported in the literature from 1980 to 1995. The death or myocardial infarction rate was 15.7% in patients with exercise-induced ST-segment depression on predischarge risk stratification using exercise electrocardiography, compared to a 9.9% subsequent combined event rate in patients without ST-segment depression (Slide #5). In contrast, the cardiac death or myocardial infarction rate was 16.7% in patients exhibiting multiple perfusion defects in more than one coronary supply region, compared to a 2% combined event rate in patients with exercise perfusion scans showing defects confined to one vascular region (Slide #6). Thus, this pooled analysis of data published in the literature also shows the superiority of exercise perfusion imaging in identifying patients at high risk for subsequent cardiac events.

fig5.jpg (24081 bytes)

fig6.jpg (27323 bytes)


The value of stress perfusion imaging can still be demonstrated in the thrombolytic era. DeCock and coworkers found that reversible defects on 201Tl scintigraphy were superior than exercise ECG variables for identifying high-risk patients after a Q-wave myocardial infarction (31). Basu and colleagues (32), employing exercise 201Tl imaging after thrombolytic therapy, reported that reversible ischemia on stress scintigrams predicted death, reinfarction, or subsequent unstable angina in 33 of 37 patients. The predictive value of the perfusion imaging procedure was superior to that of exercise ECG test variables alone.

Dakik et al (33) reported that quantitative exercise single-photon emission computed tomographic (SPECT) 201Tl perfusion imaging performed in postinfarction patients who had received thrombolytic therapy provided significant incremental prognostic information to clinical data. In that study, coronary angiographic variables did not further improve the prognostic model, which comprised clinical, resting ejection fraction, and 201Tl SPECT variables (Slide #7). Basu et al (34) used "nitrate-enhanced" 201Tl perfusion imaging in conjunction with exercise testing and found that 68% of post-myocardial infarction patients who received thrombolysis had evidence of viable but jeopardized myocardium. Of these, 49% had subsequent death or reinfarction. Only 13% of patients with no evidence of viable myocardium at jeopardy experienced subsequent cardiac events (p<0.001).

fig7.jpg (30886 bytes)

More recently, 99mTc-labeled perfusion agents have emerged as alternatives to 201Tl for both diagnostic and prognostic assessment of patients with coronary artery disease. With respect to risk stratification after acute myocardial infarction, Travin and coworkers (35) found that the number of ischemic defects on 99mTc-sestamibi SPECT was the only significant correlate of a future event when clinical, stress test, and imaging variables were assessed by Cox regression analysis. Patients with ³ 3 reversible 99mTc-sestamibi defects had an event rate of 38% (Slide #8).

fig8.jpg (21199 bytes)


Vasodilator Stress Imaging

Pharmacologic stress imaging is a useful alternative to exercise stress for risk stratification after acute myocardial infarction. Brown et al (36) performed dipyridamole 201Tl scintigraphy at a mean of 62 hours after hospitalization for acute myocardial infarction. By stepwise multivariate logistic regression analysis, the best predictor of subsequent cardiac events was the presence of dipyridamole-induced 201Tl redistribution within the infarct zone. Bosch et al (37) found that the presence of thallium redistribution on dipyridamole scintigraphy was the only independent predictor of subsequent events when imaging was performed 3 days after admission. Mahmarian et al (38) reported on the utility of adenosine 201Tl SPECT perfusion imaging performed in uncomplicated postinfarction patients. Univariate predictors of cardiac events in that study were quantified perfusion defect size, absolute extent of left ventricular ischemia, and the resting ejection fraction. Mahmarian et al (39) also reported that with adenosine 201Tl SPECT imaging, 82% of all noninfarct coronary stenosis of ³ 70% narrowing could be identified. In that study, 42% of noninfarct stenoses of 51-69% were detected (Slide #9). All infarct-related vessel stenoses were identified on scintigraphy.

fig9.jpg (32296 bytes)

Dipyridamole 99mTc-sestamibi myocardial perfusion imaging performed in 451 patients with their first acute infarction predicted early and late cardiac events (40). The extent and severity of the stress defect and reversibility of the defect were the most important predictors of cardiac death and recurrent infarction. Early dipyridamole imaging has been found to be safe without events attributed to the dipyridamole stress (41).

Based on data described above, as well as other reports in the literature, a decision-making algorithm is proposed that could be applied to the prognostic evaluation of uncomplicated postinfarction patients. Certainly, patients who manifest symptoms of congestive heart failure or hemodynamic compromise are candidates for early invasive evaluation. Similarly, patients with postinfarction angina are at high risk for recurrent ischemic events and should be evaluated early employing invasive strategies. However, a significant number of patients could be adequately risk stratified by an early noninvasive strategy using exercise or pharmacologic gated SPECT imaging. This permits the simultaneous assessment of resting ejection fraction, infarct size, regional systolic thickening abnormalities, and myocardial perfusion defects at rest and during stress. Vasodilator imaging can be performed as early as the third hospital day, whereas exercise perfusion imaging will often not be performed until the fourth or fifth hospital day. High-risk patients demonstrating residual ischemia or a multivessel disease scan pattern would then be referred for selective angiography where an invasive strategy aimed at revascularization would be undertaken. Patients with low-risk noninvasive stress perfusion imaging findings (e.g. lack of inducible ischemia, lack of a multivessel disease scan pattern, and lack of evidence for hibernating myocardium) would be eligible for aggressive medical therapy with subsequent follow-up imaging performed as indicated.



1. Verani MS. Risk assessment after myocardial infarction: have the rules changed with thrombolytic therapy? J Nucl Cardiol 1996;3:S50-S59.
2. Berman DS. Use of 201Tl for risk stratification after myocardial infarction and thrombolysis. Circulation 1997;96:2758-2761.
3. Beller GA. Risk stratification after acute myocardial infarction in the thrombolytic era. Eur Heart J 1997;18:886-888.
4. Beller GA. Determining prognosis after acute myocardial infarction in the thrombolytic era. Non-invasive investigations still have a place. Br Med J 1997;315:761-762.
5. Verani MS. Diagnosis and management of acute myocardial infarction. J Nucl Cardiol 1997;4:S158-S163.
6. Quiñones MA. Risk stratification after myocardial infarction. Clinical science versus practice behavior. Circulation 1997;95:1352-1354.
7. Verani MS. Risk stratifying patients who survive an acute myocardial infarction. J Nucl Cardiol 1998;5:96-108.
8. Rogers WJ, Baim DS, Gore JM, Brown BG, Roberts R, Williams DO, Chesebro JH, Babb JD, Sheehan FH, Wackers FJ, et al. Comparison of immediate invasive, delayed invasive, and conservative strategies after tissue-type plasminogen activator. Results of the Thrombolysis in Myocardial Infarction (TIMI) Phase II-A trial. Circulation 1990;81:1457-1476.
9. Baim DS, Braunwald E, Feit F, Knatterud GL, Passamani ER, Robertson TL, Rogers WJ, Solomon RE, Williams DO. The Thrombolysis in Myocardial Infarction (TIMI) Trial phase II: additional information and perspectives. J Am Coll Cardiol 1990;15:1188-1192.
10. SWIFT (Should We Intervene Following Thrombolysis?) Trial Study Group. SWIFT trial of delayed elective intervention v conservative treatment after thrombolysis with anistreplase in acute myocardial infarction. Br Med J 1991;302:555-560.
11. The TIMI Study Group. Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI) phase II trial. N Engl J Med 1989;320:618-627.
12. Michels KB, Yusuf S. Does PTCA in acute myocardial infarction affect mortality and reinfarction rates? A quantitative overview (meta-analysis) of the randomized clinical trials. Circulation 1995;91:476-485.
13. Ellis SG, Mooney MR, George BS, da Silva EE, Talley JD, Flanagan WH, Topol EJ. Randomized trial of late elective angioplasty versus conservative management for patients with residual stenoses after thrombolytic treatment of myocardial infarction. Treatment of Post-Thrombolytic Stenoses (TOPS) Study Group. Circulation 1992;86:1400-1406.
14. The TIMI IIIB Investigators. Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-Q-wave myocardial infarction. Results of the TIMI IIIB trial. Circulation 1994;89:1545-1556.
15. Anderson HV, Cannon CP, Stone PH, Williams DO, McCabe CH, Knatterud GL, Thompson B, Willerson JT, Braunwald E. One-year results of the Thrombolysis In Myocardial Infarction (TIMI) IIIB clinical trial. A randomized comparison of tissue-type plasminogen activator versus placebo and early invasive versus early conservative strategies in unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol 1995;26:1643-1650.
16. Boden WE, O’Rourke RA, Crawford MH, Blaustein AS, Deedwania PC, Zoble RG, Wexler LF, Kleiger RE, Pepine CJ, Ferry DR, Chow BK, Lavori PW. Outcomes in patients with acute non-Q-wave myocardial infarction randomly assigned to an invasive as compared with a conservative management strategy. Veterans Affairs Non-Q-Wave Infarction Strategies in Hospital (VANQWISH) Trial Investigators. N Engl J Med 1998;338:1785-1792.
17. FRISC II Investigators. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease. Lancet 1999;354:708-715.
18. Rouleau JL, Moye LA, Pfeffer MA, Arnold JM, Bernstein V, Cuddy TE, Dagenais GR, Geltman EM, Goldman S, Gordon D, Hamm P, Klein M, Lamas GA, McCans J, McEwan P, Menapace FJ, Parker JO, Sestier F, Sussex B, Braunwald E. A comparison of management patterns aftrer acute myocardial infarction in Canada and the United States. The SAVE investigators. Survival and Ventricular Enlargement study. N Engl J Med 1993;328:779-784.
19. Van de Werf F, Topol EJ, Lee KL, Woodlief LH, Granger CB, Armstrong PW, Barbash GI, Hampton JR, Guerci A, Simes RJ, Ross AM, Califf RM. Variations in patient management and outcomes for acute myocardial infarction in the United States and other countries. Results from the GUSTO trial. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. JAMA 1995;273:1586-1591.
20. Pilote L, Califf RM, Sapp S, Miller DP, Mark DB, Weaver WD, Gore JM, Armstrong PW, Ohman EM, Topol EJ. Regional variation across the United States in the management of acute myocardial infarction. GUSTO-1 Investigators. Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries. N Engl J Med 1995;333:565-572.
21. Guadagnoli E, Hauptman PJ, Ayanian JZ, Pashos CL, McNeil BJ, Cleary PD. Variation in the use of cardiac procedures after acute myocardial infarction. N Engl J Med 1995;333:573-578.
22. Every NR, Parsons LS, Fihn SD, Larson EB, Maynard C, Hallstrom AP, et al. Long-term outcome in acute myocardial infarction patients admitted to hospitals with and without on-site cardiac catheterization facilities. MITI Investigators. Myocardial Infarction Triage and Intervention. Circulation 1997;96:1770-1775.
23. Marrugat J, Sanz G, Masia R, Valle V, Molina L, Cardona M, Sala J, Seres L, Szescielinski L, Albert X, Lupon J, Alonso J. Six-month outcome in patients with myocardial infarction initially admitted to tertiary and nontertiary hospitals. RESCATE Investigators. Recursos Empleados en el Sindrome Coronario Agudo y Tiempos de Espera. J Am Coll Cardiol 1997;30;1187-1192.
24. Yusuf S, Flather M, Pogue J, Hunt D, Varigos J, Piegas L, Avezum A, Anderson J, Keltai M, Budaj A, Fox K, Ceremuzynski L. Variations between countries in invasive cardiac procedures and outcomes in patients with suspected unstable angina or myocardial infarction without initial ST elevation. OASIS Regulatory Investigators. Organisation to Assess Strategies for Ischaemic Syndrome. Lancet 1998;352:507-514.
25. Krumholz HM, Chen J, Murillo JE, Cohen DJ, Radford MJ. Admission to hospitals with on-site cardiac catheterization facilities. Impact on long-term costs and outcomes. Circulation 1998;98:2010-2016.
26. Armstrong PW, Granger CB, Knight D, Sutherland W, Clapp-Channing N, Hlatky M, Mark D. Temporal trends in the process of myocardial infarction management; Canadian/US GUSTO experience. Circulation 1996;94(suppl):I-28. Abstract.
27. Shaw LJ, Peterson ED, Kesler K, Hasselblad V, Califf RM. A metaanalysis of predischarge risk stratification after acute myocardial infarction with stress electrocardiographic, myocardial perfusion, and ventricular function imaging. Am J Cardiol 1996;78:1327-1337.
28. Gibson RS, Watson DD, Craddock GB, Crampton RS, Kaiser DL, Denny MJ, Beller GA. Prediction of cardiac events after uncomplicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigraphy and coronary angiography. Circulation 1983;68:321-336.
29. Gimple LW, Beller GA. Assessing prognosis after acute myocardial infarction in the thrombolytic era. J Nucl Cardiol 1994;1:198-209.
30. Gibson RS, Beller GA. Value of predischarge myocardial perfusion scintigraphy, in: Fuster V, Ross R, Topol EJ, eds. Atherosclerosis and Coronary Artery Disease, vol. 2. Philadelphia: Lippincott-Raven, 1996:1167-1191.
31. de Cock, Visser FC, Van Eenige MJ, Bezemer PD, Roos JC, Roos JP. Prognostic value of thallium-201 exercise scintigraphy in low-risk patients after Q-wave myocardial infarction: comparison with exercise testing and catheterization. Cardiology 1992;81:342-350.
32. Basu S, Senior R, Dore C, Lahiri A. Value of thallium-201 imaging in detecting adverse cardiac events after myocardial infarction and thrombolysis: a follow-up of 100 consecutive patients. Br Med J 1996;313:844-888.
33. Dakik HA, Mahmarian JJ, Kimball KT, Koutelou MG, Medrano R, Verani MS. Prognostic value of exercise 20Tl tomography in patients treated with thrombolytic therapy during acute myocardial infarction. Circulation 1996;94:2735-2742.
34. Basu S, Senior R, Raval U, Lahiri A. Superiority of nitrate-enhanced 201Tl over conventional redistribution 201Tl imaging for prognostic evaluation after myocardial infarction and thrombolysis. Circulation 1997;96:2932-2937.
35. Travin MI, Dessouki A, Cameron T, Heller GV. Use of exercise technetium-99m sestamibi SPECT imaging to detect residual ischemia and for risk stratification after acute myocardial infarction. Am J Cardiol 1995;75:665-669.
36. Brown KA, O’Meara J, Chambers CE, Plante DA. Ability of dipyridamole-thallium-201 imaging 1 to 4 hours after acute myocardial infarction to predict in-hospital and later recurrent myocardial ischemic events. Am J Cardiol 1990;65:160-167.
37. Bosch X, Magriñá J, March R, Sanz G, Garcia A, Betriu A, Navarro-Lopez F. Prediction of in-hospital cardiac events using dipyridamole-thallium scintigraphy performed very early after acute myocardial infarction. Clin Cardiol 1996;19:189-196.
38. Mahmarian JJ, Mahmarian AC, Marks FG, Pratt CM, Verani MS. Role of adenosine thallium-201 tomography for defining long-term risk in patients after acute myocardial infarction. J Am Coll Cardiol 1995;25:1333-1340.
39. Mahmarian JJ, Pratt CM, Nishimura S, Abreu A, Verani MS. Quantitative adenosine 201Tl single-photon emission computed tomography for the early assessment of patients surviving acute myocardial infarction. Circulation 1993;87:1197-1210.
40. Brown KA, Heller GV, Landin RS, Shaw LJ, Beller GA, Pasquale MJ, Haber SB. Early dipyridamole 99mTc-sestamibi single photon emission computed tomographic imaging 2-4 days after acute myocardial infarction predicts in-hospital and postdischarge cardiac events. Comparison with submaximal exercise imaging. Circulation 1999;100:(in press).
41. Heller GV, Brown KA, Landin RJ, Haber SB. Safety of early IV dipyridamole Tc99m sestamibi SPECT myocardial perfusion imaging after first myocardial infarction. Am Heart J 1996;15:1488-1492.



This company contributed to the Congress:

agilent.gif (2552 bytes)