- Email: [email protected]
Exercise thallium-201 scintigraphy after thrombolytic therapy with or without angioplasty for acute myocardial infarction
The
CORONARY AR7ERY DISEASE
American Journal of Cardiology
JUNE 1, 1993, VOL. 71, NO. 15
Exercise Thallium-201 Scintigraphy After Thrombolytic Therapy With or Without Angioplasty for Acute Myocardial Infarction Howard L. Haber, MD, George A. Belier, MD, Denny D. Watson, PhD, and Lawrence W. Gimple, MD Scant data are available concerning the appliczk tion and results of exercise thalliu~201 (R-201) scitiigraphy after acute myocardial infarction (AMI) treated with thrombolytic therapy. The goals of this study were to determine the ability of exercise R-201 scintigraphy to detect inducible ib chemia and to identify multivessel coronary artery disease (CAD) in 66 consecutive postinfarction m tients who received thrombolytic therapy and u11derwent both predischarge noninvasive testing and coronary angiography. Exerciseinduced R-201 redistribution on quantitative scitiigraphy was significantly more prevalent than exercise Sl-segment depression (46 vs 14%, p ~0.001). Sensitivity and specificity of exercise ST depression alone for identification of multivessel disease was 29 and 96%, respectively. Sensitivity of a r* mote R-201 defect for multivessel CAD detection was 25 and 67%, respectively - not significantly diierent from values for ST depression alone. When considered as a single variable, the presence of either ST depression or a remote lb201 defect was associated with a 56% sensitivity (p eO.05, compared with either ST depression or TI201 redistribution alone), but a somewhat dimiu ished speciticity of 76%. There was no difference in extent or severity of angiographic CAD in p tients with multivessel CAD with or without iu ducible ischemia. In conclusion, this study shows that exercise TM01 imaging is more sensitive than exercise ST depression for detection of residual ischemia duri* submaximal exercise in patients who received thrombolytic therapy for From the Division of Cardiology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia. This study was supported in part by Grant ROl-HL-26205 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Dr. Haber is a Research Fellow of the American Heart Association, Virginia Affiliate (1991-92). Manuscript received September 24, 1992; revised manuscript received January 4, 1993, and accepted January 5. Address for reprints: George A. Beller, MD, Box 158, Division of Cardiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.
AMI. The combination of the presence of either TC 201 redistribution or ischemic ST depression was better than either variable alone for identifying patients with multivessel CAD. (AmJCardiol1993;71:1257-1261)
here is a large amount of published data in the prethrombolytic era demonstrating the clinical use of predischarge exercise electrocardiographic stresstesting and myocardial perfusion imaging after uncomplicated acute myocardial infarction (AMI) for detecting stress-induced ischemia for purposes of risk stratification.’ We and others reported that patients with inducible ischemic ST-segmentdepression or thallium201 (Tl-201) redistribution defects, either within or remote from the infarct zone, have a higher probability of experiencing a subsequent cardiac event than patients without these noninvasive markers of ischemia.lb7Perfusion defects in myocardial beds observed outside or “remote” from the coronary supply region of the infarct-related artery identify patients with multivessel coronary artery disease(CAD) who are at increasedrisk for cardiac death or recurrent infarction during follow-up.2,3 Scant data are available comparing coronary arteriography and exercise Tl-201 scintigraphy in the thrombolytic era. Accordingly, this study comparesexercise Tl201 scintigraphic evidence of inducible ischemia with coronary arteriography and exerciseelectrocardiographic parameters and determines the prevalence of remote defects in patients with multivessel CAD.
T
METHODS Patient group: The study group consisted of 88
consecutive patients who underwent exercise Tl-201 scintigraphic stress testing and coronary angiography after intravenous thrombolytic therapy for AMI (either streptokinase 1.5 million units, or recombinant tissuetype plasminogen activator 100 mg) if they had 230 minutes of chest pain considered to bc causedby myocardial ischemia and ST-segmentelevation (0.1 mV) in 22 contiguous electrocardiographic leads. Patient demographicswere noted. A subsetof 21 patients underwent percutaneoustranshrminal coronary anTHALLIUM-201 SCINTIGRAPHYAFTERTHROMBOLYSIS 1257
TABLE I Clinical Postinfarction
and Angiographic Characteristics of Patients Receiving Thrombolytic Therapy
Age (year) Men/women Prior myocardial Infarction Location of myocardial infarctron Anterror Inferior Creatine kinase (IU) Q-wave myocardial Infarction Thrombolyhc agent Tissue-type plasmmogen activator complex Streptokmase Trme to thrombolysis (hours) No. of coronary arteries narrowed > 50% In drameter 1 2 3 Infarct artery patency Thrombolytic alone Thrombolytic & angioplasty
55* 11 71 (81%)/17 (19%) 6 (7%) 38 50 2,826 71
(43%) (57%) + 2,101 (81%)
32 (36%) 56 (64%) 3.5 2 1.3
57 (65%) 20 (22%) 11 (13%) 72 (82%) 6 (7%)
gioplasty of the infarct-related vessel before exercise TI201 scintigraphy. In these patients, the location of the infarct-related artery was recorded. Exetcise m ad quartitative exercisethallium2oi~ . The exercise treadmill test was performed 14 f 12 days after infarction in 78 patients (89%) using the Naughton protocol* and in 10 patients (11%) using a symptom-limited Bruce protocol.’ Significant ST-segment depression was defined as 21.0 mm of horizontal or downsloping depression below baseline 80 ms after the J point on 3 consecutive beats. The method used for quantitative planar Tl-201 exercise scintigraphy has previously been describcd.‘*3 Both analog and computer-processed images were interpreted by 2 independent observers unaware of subjects’ clinical history, and the quantitative data wcrc used for analysis. For intcrprctation, the images were analyzed using an 11-segment model in which the anterior and 70” left anterior oblique projections were each divided into 3 segments, whereas the 45” left anterior oblique projection was divided into 5 segments. Using this quantitative planar imaging technique, we have reported no difference between 2.5-hour redistribution images and images obtained after reinjection of a second dose of Tl-201 to
No PTCA
+ PTCA (n-21)
(k67)
ST Depression
14%1
Any TI-201 Redistribution
_I’ 48% , I
19% I I
p < 0.05
FIGlJREl.lheinddenceofanyischemic~in~67 pathts who did not undergo pwwtaneuus twmtsluminal comnary angioplasty (PICA) (left) and in the 21 who did (I&$&). Any thallium (Tl)-201 mdistrihth was *3 times as
I258
THE AMERICAN
JOURNAL
OF CARDIOLOGY VOLUME71
detect defect reversibility. ‘” A scintisaphic pattern of multivessel CAD was designated when a stress perfusion abnormality was noted in any myocardial segment remote from the infarct zone. Lung uptake was assessed qualitatively. l2amnay Md@aphy Coronary arteriography was performed 6 + 12 days after infarction and 90% of patients had arteriography before Tl-201 scintigraphy. The coronary arteries were examined in multiple projections according to a 15segment model recommended by the American Heart Association.’ I Coronary artery narrowing was considered significant if the stenosis was 250% in any projection as judged by a blinded observer using calipers. Patency was designated only if Thrombolysis in Myocardial Infarction trial grade 2 or 3 flow was demonstrated during selective coronary injection. I2 Patients with 250% stenosis in 21 noninfarct vessels were defined as having multivessel CAD. Data analysis: Data were compiled and analyzed on a minicomputer (VAX 8200, Digital Equipment Corporation) with RS/l software (Bolt, Berancck and Newman). Continuous variables were expressed as mean f SD, and differences between groups were cstimatcd by means of either Student’s I test with pooled variance or l-way analysis of variance. Categorical data were exprcsxd as proportions, and differences between groups were estimated using the Fisher exact test. Stepwise regression analysis was used to develop predictive models for certain variables with all significant univariate determinants entered into the model. These stepwisc analyses included both normal errors (for continuous variables) and logistic models (for dichotomous variables). Differences between groups were considered significant at a p value co.05 (2-tailed). RESULTS Patient characterist&~ Table 1 depicts the clinical and angiographic characteristics of our patient population. Only 6 patients had a history of AMI. Angiographically, most patients (65%) had l-vessel CAD, whereas only 13% had 3-vcsscl CAD. Thrombolytic therapy alone resulted in an 82% patency rate, and an additional 7% achieved patency after successful angioplasty of an occluded infarct-related artery before exercise testing. Detection of residual ischemia: Exercise-induced Tl-201 redistribution was significantly more prevalent than cxcrcisc ST-segment depression (48 vs 14%, p
from the infarct zone, and 4% had redistribution defects only remote from the infarct zone. Slightly more than one half of these patients had no inducible Tl-201 redistribution. Patients with infarct zone redistribution had similar exercisework loads (4.7 YE2.1 vs 4.1 + 2.0 METS), peak exercise heart rates (120 f 15 vs 122 -t 16 beats/min), prevalence of ischemic ST depression (19 vs 14%) and prevalence of angiographic multivessel CAD (48 vs 32%) than those without. As expected,there were a fewer number of persistent defects in those with (1.6 + 1.6) than those without (3.8 + 2.0) infarct zone redistribution.
(&i-square = 5.67, p = 0.02) were independent predictors of multivessel CAD.
DISCUSSION Data are just becoming available concerning the use of predischarge exercise Tl-201 stresstesting for detection of residual ischemia and underlying multivessel CAD in postinfarction patients receiving thrombolytic therapy.13-l7The direct extrapolation of results of noninvasive testing in patients with AMI reported before the thrombolytic era may not be valid. Patient populations may be quite different since patients receiving thrombolytic therapy are usually younger, have a lower prevalence of prior AMI, have more l-vessel CAD, evolve Noninvasive detection of multivessel coronary s tery dii The sensitivity and specificityof exerciseST mostly Q-wave AMIs, and have a higher prevalence depression alone f& identtication of multivessel CAD of infarct-vessel patency than the more heterogeneous was 29 and 96%, respectively (Figure 3). The sensitivity patient cohorts reported in the prethrombolytic era. Adand speci6city of a remote Tl-201 defect for multivessel ditionally, more postinfarction patients are currently unCAD detection was 35 and 87%, respectively - not sig- dergoing early angiography with interventional procenificantly different from values obtained for exercise ST dures before predischarge risk assessment,even in the depression alone (Figure 3). When considered as a sin- absenceof objective evidence of recurrent ischemia. gle variable, the presence of either ST depression or a Detecth of residual ischemia by exercise eledroremote Tl-201 defect was associatedwith an improved cardiography: There is a great deal of information resensitivity of 58% (p co.05 compared with either elec- garding the value of exercise electrocardiographic stress trocardiographic or Tl-201 criteria alone), but a diminished specificity of 78% (Figure 3). TABLE II Correlates of Multivessel Coronary Disease in The clinical, exercise and scintigraphic correlations Postinfarction Patients Receiving Thrombolytic Therapy of multivessel CAD in these postinfarction patients are listed in Table II. The only significant clinical correlate No. of Coronary Arteries 1 >1 Narrowed > 50% in Diameter (n = 57) (n = 31) p Value of multivessel CAD was advancedage. Among exercise and scintigraphic variables, exercise-induced ST-segClinical Age (year) ment depression,increasedlung Tl-201 uptake, the num52 k 10 59 2 10 0.004 Anterior myocardial infarction 20 (35%) 16 (52%) NS ber of segmentswith initial defects, the number of segQ-wave myocardial infarction a (15%) 8 (26%) NS ments with redistribution, the presence of a remote TlExercise testingiscintigraphic 201 abnormality as well as the combination of either METS achieved 4.5 f 2.1 4.5 + 2.0 NS exercise ST-segment depressionor a remote Tl-201 abPeak heart rate (beats/mln) 122 + 16 119 & 17 NS Exercise ST depression 2 (4%) 9 (29%) 0.002 normality when considered as a single variable correlatExercise ST elevation 22 (39%) 11 (37%) NS ed with multivessel CAD. By multivariate analysis, only Increased visual 11(19%) 28 (39%) NS the presence of either exercise ST-segment depression lung uptake or a remote Tl-201 abnormality considered as a single Initial defects/pt. 3.5 2 2.0 4.4 2 2.2 0.04 Redistribution segmentsipt. 0.8 + 1.3 1.5 i 2.0 0.03 variable (&i-square = 9.02, p = 0.003) and advancedage Pts. with remote defects Pts. with remote defects or ST depression
Remote
METS = metabolic
7 (13%) 12 (22%)
11 (35%) la (58%)
0.03 0.002
equivalents.
None 52%
n ST Depression 5 0
60
P$
40
q Remote
TI-201 Redistribution
0 ST Depression
Incidence and Location of Redistribution (n = 67 Patients)
FIGURE 2. Pie chart demonstrating the incidence and locz~ tion of thallium201 redistribution in the 67 patients who did not undergo percutaneous transluminal coronary angioplao ty. The imideace of thallium201 redistribution within the infarct zone was 43%.
or
Remote TI-201 Redistribution
20 0 Sensitivity
Specificity
FlGURE 3. Sensitivity and specificity of exercise ST-segment depression (so/id bars), the presence of remote thallium (TI)-201 redistribution (hatched bars), and either ST depression or remote thallium201 redistribution considered as a single variable for the detection of multivessel coronary artery disease.
THALLIUM-201 SCINTIGRAPHYAFTERTHROMBOLYSIS 1259
testing soon after recovery from an uncomplicated AMI not treated with thrombolytic agents. In one recent review of the published reports,1829% of 3,776 patients pooled from 17 series in the literature exhibited exercise-inducedST-segmentdepressionon predischargesubmaximal exercise testing. The incidence of exerciseinduced ST depression on predischarge stresstesting is less in patients treated with thrombolytic therapy. In the Thrombolysis in Myocardial Infarction-IIB Multicenter Trial, the incidence of exercise ST depression in the 1,626 patients in the conservativearm was 17.7%at discharge and 19.4% at 6 weeks.19 Tilkemeier et alI6 reported a 15% incidence of STsegment depression in postinfarction patients receiving thrombolytic therapy or angioplasty, or both, compared with those receiving no intervention during a comparable time period of survey. The postinfarction patients who were treated medically and did not undergo any intervention had a 35% incidence of predischargeexercise-induced ST depression. In the present study, only 14% of the 67 patients treated with a thrombolytic agent and managed without percutaneous transluminal coronary angioplasty before testing exhibited exercise-induced ST depression on submaximal treadmill exercise testing. This value is comparableto the incidence of ST depression reported from the Thrombolysis in Myocardial Infarction-JIB trial (17%)19and the study of Tilkemeier et all6 in comparablepatient cohorts. DetecWm
of residual
ischemia
by stress
thallium
201 scintigrqhyi In the prethrombolytic era, the sensitivity of exercise n-201 scintigraphy for detection of residual ischemia after an uncomplicated AMI was found to be superior to that of exerciseelectrocardiography alone.2 We reported that exercise-induced Tl-201 redistribution occurred in 51% of postinfarction patients not receiving thrombolytic therapy,compared with 33% for ST-segmentdepression2 As observed in the prethrombolytic era, data from this study show that the detection rate of residual ischemia with exerciseTl-201 scintigraphy (48%) was significantly higher than for ST-segment depression (14%). These data confirm the findings of Tilkemeier et all6 who reported a 42% incidence of exercise-inducedTl201 redistribution in postinfarction patients who received thrombolytic therapy, compared with the incidence of 15% for ischemic ST-segment depression cited previously. Sutton and Top01’~ evaluated postinfarction patients receiving thrombolytic therapy who had 270% residual stenosis of the infarct vessel by angiography. In these patients, 51% had inducible ischemia by Tl-201 criteria, which is similar to the 48% detection rate in patients treated with thrombolytic therapy in our study using quantitative planar scanning techniques. . Detedonofnnlltivessel Coronary~diseaSe: Multivessel CAD is an important prognostic variable in patients surviving uncomplicated AMT, and one of the goals of predischargenoninvasive risk stratification is to identify patients with functionally important multivessel CAD who might benefit from early coronary angiography and revascularization.2~20~21 In the present study, 35% had multivessel CAD by coronary angiography (22% with 2-vessel and 13% with 3-vessel disease).A 1260
Tl-201 defect remote from the infarct zone was observed in 35% of thesepatients. The sensitivity for detection of multivessel CAD by Tl-201 scintigraphy (35%) was slightly, but not significantly, higher than that of ‘exerciseinduced ST depression(29%). However, if a remote Tl201 defect or ischemic ST depression,or both, was considered as a single variable for multivessel CAD detection, then 58% of patients with signiticant angiographic multivessel CAD would have been identitied. Using either ST depression or a remote Tl-201 defect as a single variable only slightly decreasedthe specificity for multivessel CAD detection from 97% for a remote defect alone to 78%. The sensitivity of a remote Tl-201 defect for multivessel CAD detection in this study of patients receiving thrombolytic therapy was similar to that reported by Sutton14(35%) and Burns22(40%) and their co-workers. Previous publications suggesta higher sensitivity for Tl-201 scintigraphy for detecting multivessel CAD in the prethrombolytic era. In a series of studies comprising 508 patients, there was a 72% sensitivity of a remote Tl201 defect for detecting multivessel CAD associated with an 86% speciticity.34f23In these prior series, 59% of patients with multivessel CAD had ischemic ST-segment depression.The positive predictive value of a remote 71-201defect for identifying multivessel CAD was significantly higher than the positive predictive value of ST-segmentdepression. The prevalenceof a remote Tl-201 defect in the present cohort of patients receiving thrombolytic therapy (35%) is less than the prevalenceof remote defects seen in our laboratory in the prethrombolytic era. Gibson et al3 found that 65 of 154 patients with Q-wave infarction (42%) and 36 of 87 with non-Q-wave infarction (41%) had stress-induceddefects in >l vascular region with use of the same submaximal stresstest protocol as utilized in this current study. There are several possible explanations for a diminished sensitivity of a remote Tl-201 defect for multivesse1CAD identification in the thrombolytic era. First, the incidence of prior AMI is lower than the seriesreported before the thrombolytic era. In our study undertaken in the prethrombolytic era,’ 17% of patients had a prior AMI compared with 7% in the current study. A prior AMI remote from the zone of new myocardial necrosis would be associatedwith a high prevalenceof a remote defect. Second, patients with non-Q-wave AMI constituted a substantial percentage of postinfarction cohorts reported in the prethrombolytic era,’ whereasonly patients with ST-segment elevation generally received thrombolytic agents. Patients with non-Q-wave AMI have a comparable angiographic extent of CAD than patients with Q-wave AMI, but have a higher incidence of stress-inducedischemia.3 Third, in the prethrombolytic era, 30 to 50% of patients had 3-vessel disease.The overall prevalenceof 2or 3-vessel diseasewas 60 to 75%.24,25In contrast, approximately 10% of patients treated with thrombolytic therapy have 3-vessel disease.26Bayesian principles would predict diminished predictive value for noninvasive testing in the thrombolytic cohort. In the present
THE AMERICANJOURNALOF CARDIOLOGY VOLUME71 JUNE 1, 1993
studv, onlv 35% of uatients treated with thrombolvtic with left main or 3-vessel coronarv disease after a fmt mvocardial infarction? Am . the&by had multivessel CAD, with only 13% de&nJ6. card~~li9ss~s61-372. Dunn RF, Freedman B, Bailey IK, Ure” R, Kelly DT. Noninvasive prediction strating 3-vessel disease.In our prethrombolytic postin- of multivessel disease after myocardial infarction. Circulation 1980;62:72&734. farction cohort. 58% had multivessel CAD and 22% had 7. HLI”F: J, GOATSML, Nash E, ~raemer HC, Debusk RF, Bew WE III, LOW H. Comparative value of maximal treadmill testing, exercise thallium myocardial per3-vessel diseases Because a defect remote from the in- fusion scintigmphy and exercise radionuclide venhiculography for distinguishing farct zone is more likely to be induced by exercisestress high- and low-risk patients soon after acute myocardial infaction. Am J Cardiol in the presenceof 3-vessel than 2-vessel disease,27it is 1984;53:1221-1227. Naughton JP, Hader R. Exercise testing and exercise training in coronary artay not surprising that the detection rate of remote defects 8.disease. In: Naughton JP, Hellerstein HK, Mohler IC, eds. Methods of Exercise in patients with multivessel CAD in the thrombolvtic era Testing. New York: Academic Press, 1973:79-91. 9. B&e RA, Blackman JR, Jones JW, Strait G. Exercising testing in adult noris decreasing. mal subjects and cardiac patients. Pediatrics 1963;32:742-756. Study limitations: One limitation is that the study 10. Watson DD, Smith WH, Vinson E, Kaul S, Blackbum T, Beller GA. Quntipopulation comprised only 31 patients with multivessel the analysis of rest reinjection compared to redistribution (abstr). J Am Coil Car1992;19’129A. CAD. Despite this limited number of patients with mul- diOl 11. Austin WG, Edwards JE, Frye RC, Gensini GG, Gott VL, Griffith LSC, McGoon tivessel CAD, the percentagewith 2- and 3-vessel dis- DC, Murphy ML, Roe BB. A reporting system on patients evaluated for coronary easeis comparableto previously reported seriesof post- artery disease. Report of the Ad Hoc Committee for grading of coronary artery disCouncil on Caxliovascular Surgery, American Heart Association. Circu&ion infarction patients who received thrombolytic therapyF8 ease, 1975;51(suppl IV):IV-5-IV40. It is doubtful that inclusion of more patients with mul- 12. The TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial: phase I findings. N Engl J Med 1985;3123932-936. tivessel CAD would have altered the sensitivity or speci- 13. Touchstone DA, B&r GA, Nygaard TW, Watson DD, Tedesco C, Kaul S. ficity of exerciseTl-201 scintigraphy for the detection of Functional significance of pxedischarge exercise thallium-201 findings following “remote” ischemia. Of the 8 patients with multivessel intravenous sbreptokinase therapy during acute myocardial infarction. Am Heart J CAD who had ST-segment depression with exercise 14. 1988;116:15ao-1507. Sutton JM, Top01 El. Significance of a negative exercise thallium test in the testing, only 4 had scintigraphic evidence of multivessel presence of a critical residual stenosis after thrombolysis for acute myocardial infarcdisease.Because 2 of these patients had apical Tl-201 tion. Circulation 1991;83:1278-1286. Stewart RE, Kander N, J”ni JE, Ellis SG, O’Neill WW, Schork MA, Topol abnormalities, the scintigrams were not diagnostic of re- 15. EJ, Schwaiger M. Submaximal exercise thallium-201 SPECT for assessment of mote ischemia. This points out the difficulty of ‘correlat- interventional therapy in patients with acute myocardial infarction. Am Heart J 1991; 121:1033-1041. ing the apex to specilic vascular zones.A secondlimita- 16. Tilkemeier PL, Guiney TB, LaRaia PJ, Boucher CA. Prognostic value of pm tion is the absenceof follow-up prognostic data to deter- discharge low-level exercise thallium testing after thrombolytic treatment of acute mine if residual ischemia within the infarct zone or myocaxlial infaction. Am J Cardiol 1990;66:1203-1207. Candell-Riera J, Pe”“anyer-Miialda G, Caste11J, Rius-Davi A, Domingo E, remote defects in patients with multivessel CAD identi- 17. Alvarez-Auf%” E, Olona M, Ross&J, Ortega D, Dom&ech-Tom& FM, Soler-Soler fied patients with a higher event rate. Such follow-up is J. Uncomplicated first myocardial infarction: strategy for comprehensive prognosdifficult to obtain becausephysicians currently intervene tic srudies. J Am Coil Cardiol 1991;18:1207-1219. Fro&her VF, Perdue ST, Atwood JE, DesPois P, Sivarajan ES. Exercise testwith revascularization when ischemia is provoked by 18. ing of patients recovering from myowdial infarction. Eur Probl Cardiol 1986,ll: stress imaging. Finally, most patients in this study had 371~444. 19. The TIMI Study Group. Comparison of invasive and conservative strategies submaximal exercise testing. However, there ‘were no after mahnent with i”@ave”ous tissue plasmi”oge” activator i” acute myocaniial signiticant differences in any clinical, angiographic or infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) phase II scintigraphic parameteramong those who had symptom- trial. N Engl J Med 1989;320:618627. Roubii GS, Harris PJ, Bernstein L, Kelly DT. Coronary anatomy and proglimited versus submaximal testing. Furthermore, in a 20. nosis after myocadial infarction in patients 60 years of age and younger. Circulameta-analysis of 24 studies using exercise testing after lion 1983;67:743-749. AMI, Froelicher et al29 demonstratedthat submaximal 21. Muller DWM, Top01 EJ, Ellis SG, S&on KN, Lee K, Califf RM, and the Study Group. Multivessel coronary artery disease: a key predictor of shortor predischargetesting has greater predictive prognostic TAMI term prognosis after reperfwion therapy for acute myocadial infarction. Am Heart power than postdischargeor maximal testing. .I 1991;121:1042-1049. Acknowledgment: We are grateful to Jerry Curtis for his superb editorial assistancein preparing this manuscript.
1. Gibson RS, Taylor GJ, Watson DD, Stebbins PT, Martin RP, Crampton RS, Beller GA. Predicting the extent and location of coronary artery disease during the early postinfarction period by quantitative thallium-201 scintigmphy. Am J Cardiol 1981;47:101~1019. 2. Gibson RS, Watson DD, Craddock GB, Crampton RS, Kaiser DL, Denny MJ, B&r GA. Prediction of cardiac events after ““complicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigmphy and coronary angiography. Circulaion 1983;68:321-336. 3. Gibson RS, Belle1 GA, Gheorghiade M, Nygaard TW, Watson DD, Huey BL, Sayer SL, Kaiser DL. The prevalence and clinical significance of residual myoardial ischemia 2 weeks after ““complicated non-Q wave infarction: a prospective natural history study. Circulation 1986;73:118&1198. 4. Brown KA, Weiss RM, Clements JP, Wackers FJT. Usefulness of residual ischemia myocaxlium within prior infarct zone for identifying patients at high risk late after acute myocardial infarction. Am .I Cardiol 1987;60:15-19. 5. Patterson RE, Horowitz SF, Eng C, Meller J, Goldsmith SJ, Pichard A, Halgash DA, Hetman MV, Gorlin R. Can noninvasive exercise test criteria identify patients
22. Bums RI. Freeman MR. Li” P. Cox F. Morean CD. Armstrone RW. and the TPAT Study houp. Limit&” of e&&e thalli~ singld photon tomography early after myoadial infarction (abstr). .I Am Co// Cardiol 1989;13:125A. 23. Abraham RD, Freedman SB, Dunn RF, Newman H, Roubii GS, Harris PJ, Kelly DT. Prediction of multivessel coronary artery disease and prognosis early after acute myocardial infarction by exercise electrocardiography and thallium-201 myocardial perfusion scimigraphy. Am J Cardiol 1986;58:423-427. 24. Topol ET, Holmes DR, Rogers WJ. Coronary angiography after thrombalytic therapy for ac”tc myocardial infarction. Ann Intern Med 1991;114:877-885. 25. Nicod P, Gilpin EA, D&rich H, Henning H, Maisel A, Blacky R, Smith SC Jr, Rico” F, Ross J Jr. Trends in “se of coronary angiography in subacute. phase of myocaxliaJ infarction. Circulation 1991;84: 1004-1015. 26. Rogers WJ, Babb JD, Bairn DS, Chesbro JH, Gore JM, Roberts R, Williams DO, Frederich M, Passamani EF, Braunwald E, for the TIM1 ll Investigators. Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plastiogen activator, heparin and aspirin for acute myowdial infarction. J Am Coil Cardiol 1991;17:1007-1016. 27. Nygaard ‘IW, Gibson RS, Ryan JM, Gascho JA, Watson DD, Beller GA. Prevalence of high-risk thallium-201 scintigraphy fmdings in left main coroniuy artery stenosis: comparison with patients with m@tiple- and single-vessel coronary artery disease. Am J Cardiol 1984;53:462-469. 28. Top01 EJ, Holmes DR, Rogers WJ. Coronary angiography after thromb+tic therapy for acute myocardial infarction. Ann Intern Med 1991;114:877-885. 29. Froelicher VF, Perdue S, Pewen W, Risch M. Application of “x%-analysis using an electronic spread sheet to exercise testing in patients after myocardial infarction. Am J Med 1987;83:1045-1054.
THALLIUM-201 SCINTIGRAPHYAFTERTHROMBOLYSIS 1261
CORONARY AR7ERY DISEASE
American Journal of Cardiology
JUNE 1, 1993, VOL. 71, NO. 15
Exercise Thallium-201 Scintigraphy After Thrombolytic Therapy With or Without Angioplasty for Acute Myocardial Infarction Howard L. Haber, MD, George A. Belier, MD, Denny D. Watson, PhD, and Lawrence W. Gimple, MD Scant data are available concerning the appliczk tion and results of exercise thalliu~201 (R-201) scitiigraphy after acute myocardial infarction (AMI) treated with thrombolytic therapy. The goals of this study were to determine the ability of exercise R-201 scintigraphy to detect inducible ib chemia and to identify multivessel coronary artery disease (CAD) in 66 consecutive postinfarction m tients who received thrombolytic therapy and u11derwent both predischarge noninvasive testing and coronary angiography. Exerciseinduced R-201 redistribution on quantitative scitiigraphy was significantly more prevalent than exercise Sl-segment depression (46 vs 14%, p ~0.001). Sensitivity and specificity of exercise ST depression alone for identification of multivessel disease was 29 and 96%, respectively. Sensitivity of a r* mote R-201 defect for multivessel CAD detection was 25 and 67%, respectively - not significantly diierent from values for ST depression alone. When considered as a single variable, the presence of either ST depression or a remote lb201 defect was associated with a 56% sensitivity (p eO.05, compared with either ST depression or TI201 redistribution alone), but a somewhat dimiu ished speciticity of 76%. There was no difference in extent or severity of angiographic CAD in p tients with multivessel CAD with or without iu ducible ischemia. In conclusion, this study shows that exercise TM01 imaging is more sensitive than exercise ST depression for detection of residual ischemia duri* submaximal exercise in patients who received thrombolytic therapy for From the Division of Cardiology, Department of Internal Medicine, University of Virginia Health Sciences Center, Charlottesville, Virginia. This study was supported in part by Grant ROl-HL-26205 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Dr. Haber is a Research Fellow of the American Heart Association, Virginia Affiliate (1991-92). Manuscript received September 24, 1992; revised manuscript received January 4, 1993, and accepted January 5. Address for reprints: George A. Beller, MD, Box 158, Division of Cardiology, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908.
AMI. The combination of the presence of either TC 201 redistribution or ischemic ST depression was better than either variable alone for identifying patients with multivessel CAD. (AmJCardiol1993;71:1257-1261)
here is a large amount of published data in the prethrombolytic era demonstrating the clinical use of predischarge exercise electrocardiographic stresstesting and myocardial perfusion imaging after uncomplicated acute myocardial infarction (AMI) for detecting stress-induced ischemia for purposes of risk stratification.’ We and others reported that patients with inducible ischemic ST-segmentdepression or thallium201 (Tl-201) redistribution defects, either within or remote from the infarct zone, have a higher probability of experiencing a subsequent cardiac event than patients without these noninvasive markers of ischemia.lb7Perfusion defects in myocardial beds observed outside or “remote” from the coronary supply region of the infarct-related artery identify patients with multivessel coronary artery disease(CAD) who are at increasedrisk for cardiac death or recurrent infarction during follow-up.2,3 Scant data are available comparing coronary arteriography and exercise Tl-201 scintigraphy in the thrombolytic era. Accordingly, this study comparesexercise Tl201 scintigraphic evidence of inducible ischemia with coronary arteriography and exerciseelectrocardiographic parameters and determines the prevalence of remote defects in patients with multivessel CAD.
T
METHODS Patient group: The study group consisted of 88
consecutive patients who underwent exercise Tl-201 scintigraphic stress testing and coronary angiography after intravenous thrombolytic therapy for AMI (either streptokinase 1.5 million units, or recombinant tissuetype plasminogen activator 100 mg) if they had 230 minutes of chest pain considered to bc causedby myocardial ischemia and ST-segmentelevation (0.1 mV) in 22 contiguous electrocardiographic leads. Patient demographicswere noted. A subsetof 21 patients underwent percutaneoustranshrminal coronary anTHALLIUM-201 SCINTIGRAPHYAFTERTHROMBOLYSIS 1257
TABLE I Clinical Postinfarction
and Angiographic Characteristics of Patients Receiving Thrombolytic Therapy
Age (year) Men/women Prior myocardial Infarction Location of myocardial infarctron Anterror Inferior Creatine kinase (IU) Q-wave myocardial Infarction Thrombolyhc agent Tissue-type plasmmogen activator complex Streptokmase Trme to thrombolysis (hours) No. of coronary arteries narrowed > 50% In drameter 1 2 3 Infarct artery patency Thrombolytic alone Thrombolytic & angioplasty
55* 11 71 (81%)/17 (19%) 6 (7%) 38 50 2,826 71
(43%) (57%) + 2,101 (81%)
32 (36%) 56 (64%) 3.5 2 1.3
57 (65%) 20 (22%) 11 (13%) 72 (82%) 6 (7%)
gioplasty of the infarct-related vessel before exercise TI201 scintigraphy. In these patients, the location of the infarct-related artery was recorded. Exetcise m ad quartitative exercisethallium2oi~ . The exercise treadmill test was performed 14 f 12 days after infarction in 78 patients (89%) using the Naughton protocol* and in 10 patients (11%) using a symptom-limited Bruce protocol.’ Significant ST-segment depression was defined as 21.0 mm of horizontal or downsloping depression below baseline 80 ms after the J point on 3 consecutive beats. The method used for quantitative planar Tl-201 exercise scintigraphy has previously been describcd.‘*3 Both analog and computer-processed images were interpreted by 2 independent observers unaware of subjects’ clinical history, and the quantitative data wcrc used for analysis. For intcrprctation, the images were analyzed using an 11-segment model in which the anterior and 70” left anterior oblique projections were each divided into 3 segments, whereas the 45” left anterior oblique projection was divided into 5 segments. Using this quantitative planar imaging technique, we have reported no difference between 2.5-hour redistribution images and images obtained after reinjection of a second dose of Tl-201 to
No PTCA
+ PTCA (n-21)
(k67)
ST Depression
14%1
Any TI-201 Redistribution
_I’ 48% , I
19% I I
p < 0.05
FIGlJREl.lheinddenceofanyischemic~in~67 pathts who did not undergo pwwtaneuus twmtsluminal comnary angioplasty (PICA) (left) and in the 21 who did (I&$&). Any thallium (Tl)-201 mdistrihth was *3 times as
I258
THE AMERICAN
JOURNAL
OF CARDIOLOGY VOLUME71
detect defect reversibility. ‘” A scintisaphic pattern of multivessel CAD was designated when a stress perfusion abnormality was noted in any myocardial segment remote from the infarct zone. Lung uptake was assessed qualitatively. l2amnay Md@aphy Coronary arteriography was performed 6 + 12 days after infarction and 90% of patients had arteriography before Tl-201 scintigraphy. The coronary arteries were examined in multiple projections according to a 15segment model recommended by the American Heart Association.’ I Coronary artery narrowing was considered significant if the stenosis was 250% in any projection as judged by a blinded observer using calipers. Patency was designated only if Thrombolysis in Myocardial Infarction trial grade 2 or 3 flow was demonstrated during selective coronary injection. I2 Patients with 250% stenosis in 21 noninfarct vessels were defined as having multivessel CAD. Data analysis: Data were compiled and analyzed on a minicomputer (VAX 8200, Digital Equipment Corporation) with RS/l software (Bolt, Berancck and Newman). Continuous variables were expressed as mean f SD, and differences between groups were cstimatcd by means of either Student’s I test with pooled variance or l-way analysis of variance. Categorical data were exprcsxd as proportions, and differences between groups were estimated using the Fisher exact test. Stepwise regression analysis was used to develop predictive models for certain variables with all significant univariate determinants entered into the model. These stepwisc analyses included both normal errors (for continuous variables) and logistic models (for dichotomous variables). Differences between groups were considered significant at a p value co.05 (2-tailed). RESULTS Patient characterist&~ Table 1 depicts the clinical and angiographic characteristics of our patient population. Only 6 patients had a history of AMI. Angiographically, most patients (65%) had l-vessel CAD, whereas only 13% had 3-vcsscl CAD. Thrombolytic therapy alone resulted in an 82% patency rate, and an additional 7% achieved patency after successful angioplasty of an occluded infarct-related artery before exercise testing. Detection of residual ischemia: Exercise-induced Tl-201 redistribution was significantly more prevalent than cxcrcisc ST-segment depression (48 vs 14%, p
from the infarct zone, and 4% had redistribution defects only remote from the infarct zone. Slightly more than one half of these patients had no inducible Tl-201 redistribution. Patients with infarct zone redistribution had similar exercisework loads (4.7 YE2.1 vs 4.1 + 2.0 METS), peak exercise heart rates (120 f 15 vs 122 -t 16 beats/min), prevalence of ischemic ST depression (19 vs 14%) and prevalence of angiographic multivessel CAD (48 vs 32%) than those without. As expected,there were a fewer number of persistent defects in those with (1.6 + 1.6) than those without (3.8 + 2.0) infarct zone redistribution.
(&i-square = 5.67, p = 0.02) were independent predictors of multivessel CAD.
DISCUSSION Data are just becoming available concerning the use of predischarge exercise Tl-201 stresstesting for detection of residual ischemia and underlying multivessel CAD in postinfarction patients receiving thrombolytic therapy.13-l7The direct extrapolation of results of noninvasive testing in patients with AMI reported before the thrombolytic era may not be valid. Patient populations may be quite different since patients receiving thrombolytic therapy are usually younger, have a lower prevalence of prior AMI, have more l-vessel CAD, evolve Noninvasive detection of multivessel coronary s tery dii The sensitivity and specificityof exerciseST mostly Q-wave AMIs, and have a higher prevalence depression alone f& identtication of multivessel CAD of infarct-vessel patency than the more heterogeneous was 29 and 96%, respectively (Figure 3). The sensitivity patient cohorts reported in the prethrombolytic era. Adand speci6city of a remote Tl-201 defect for multivessel ditionally, more postinfarction patients are currently unCAD detection was 35 and 87%, respectively - not sig- dergoing early angiography with interventional procenificantly different from values obtained for exercise ST dures before predischarge risk assessment,even in the depression alone (Figure 3). When considered as a sin- absenceof objective evidence of recurrent ischemia. gle variable, the presence of either ST depression or a Detecth of residual ischemia by exercise eledroremote Tl-201 defect was associatedwith an improved cardiography: There is a great deal of information resensitivity of 58% (p co.05 compared with either elec- garding the value of exercise electrocardiographic stress trocardiographic or Tl-201 criteria alone), but a diminished specificity of 78% (Figure 3). TABLE II Correlates of Multivessel Coronary Disease in The clinical, exercise and scintigraphic correlations Postinfarction Patients Receiving Thrombolytic Therapy of multivessel CAD in these postinfarction patients are listed in Table II. The only significant clinical correlate No. of Coronary Arteries 1 >1 Narrowed > 50% in Diameter (n = 57) (n = 31) p Value of multivessel CAD was advancedage. Among exercise and scintigraphic variables, exercise-induced ST-segClinical Age (year) ment depression,increasedlung Tl-201 uptake, the num52 k 10 59 2 10 0.004 Anterior myocardial infarction 20 (35%) 16 (52%) NS ber of segmentswith initial defects, the number of segQ-wave myocardial infarction a (15%) 8 (26%) NS ments with redistribution, the presence of a remote TlExercise testingiscintigraphic 201 abnormality as well as the combination of either METS achieved 4.5 f 2.1 4.5 + 2.0 NS exercise ST-segment depressionor a remote Tl-201 abPeak heart rate (beats/mln) 122 + 16 119 & 17 NS Exercise ST depression 2 (4%) 9 (29%) 0.002 normality when considered as a single variable correlatExercise ST elevation 22 (39%) 11 (37%) NS ed with multivessel CAD. By multivariate analysis, only Increased visual 11(19%) 28 (39%) NS the presence of either exercise ST-segment depression lung uptake or a remote Tl-201 abnormality considered as a single Initial defects/pt. 3.5 2 2.0 4.4 2 2.2 0.04 Redistribution segmentsipt. 0.8 + 1.3 1.5 i 2.0 0.03 variable (&i-square = 9.02, p = 0.003) and advancedage Pts. with remote defects Pts. with remote defects or ST depression
Remote
METS = metabolic
7 (13%) 12 (22%)
11 (35%) la (58%)
0.03 0.002
equivalents.
None 52%
n ST Depression 5 0
60
P$
40
q Remote
TI-201 Redistribution
0 ST Depression
Incidence and Location of Redistribution (n = 67 Patients)
FIGURE 2. Pie chart demonstrating the incidence and locz~ tion of thallium201 redistribution in the 67 patients who did not undergo percutaneous transluminal coronary angioplao ty. The imideace of thallium201 redistribution within the infarct zone was 43%.
or
Remote TI-201 Redistribution
20 0 Sensitivity
Specificity
FlGURE 3. Sensitivity and specificity of exercise ST-segment depression (so/id bars), the presence of remote thallium (TI)-201 redistribution (hatched bars), and either ST depression or remote thallium201 redistribution considered as a single variable for the detection of multivessel coronary artery disease.
THALLIUM-201 SCINTIGRAPHYAFTERTHROMBOLYSIS 1259
testing soon after recovery from an uncomplicated AMI not treated with thrombolytic agents. In one recent review of the published reports,1829% of 3,776 patients pooled from 17 series in the literature exhibited exercise-inducedST-segmentdepressionon predischargesubmaximal exercise testing. The incidence of exerciseinduced ST depression on predischarge stresstesting is less in patients treated with thrombolytic therapy. In the Thrombolysis in Myocardial Infarction-IIB Multicenter Trial, the incidence of exercise ST depression in the 1,626 patients in the conservativearm was 17.7%at discharge and 19.4% at 6 weeks.19 Tilkemeier et alI6 reported a 15% incidence of STsegment depression in postinfarction patients receiving thrombolytic therapy or angioplasty, or both, compared with those receiving no intervention during a comparable time period of survey. The postinfarction patients who were treated medically and did not undergo any intervention had a 35% incidence of predischargeexercise-induced ST depression. In the present study, only 14% of the 67 patients treated with a thrombolytic agent and managed without percutaneous transluminal coronary angioplasty before testing exhibited exercise-induced ST depression on submaximal treadmill exercise testing. This value is comparableto the incidence of ST depression reported from the Thrombolysis in Myocardial Infarction-JIB trial (17%)19and the study of Tilkemeier et all6 in comparablepatient cohorts. DetecWm
of residual
ischemia
by stress
thallium
201 scintigrqhyi In the prethrombolytic era, the sensitivity of exercise n-201 scintigraphy for detection of residual ischemia after an uncomplicated AMI was found to be superior to that of exerciseelectrocardiography alone.2 We reported that exercise-induced Tl-201 redistribution occurred in 51% of postinfarction patients not receiving thrombolytic therapy,compared with 33% for ST-segmentdepression2 As observed in the prethrombolytic era, data from this study show that the detection rate of residual ischemia with exerciseTl-201 scintigraphy (48%) was significantly higher than for ST-segment depression (14%). These data confirm the findings of Tilkemeier et all6 who reported a 42% incidence of exercise-inducedTl201 redistribution in postinfarction patients who received thrombolytic therapy, compared with the incidence of 15% for ischemic ST-segment depression cited previously. Sutton and Top01’~ evaluated postinfarction patients receiving thrombolytic therapy who had 270% residual stenosis of the infarct vessel by angiography. In these patients, 51% had inducible ischemia by Tl-201 criteria, which is similar to the 48% detection rate in patients treated with thrombolytic therapy in our study using quantitative planar scanning techniques. . Detedonofnnlltivessel Coronary~diseaSe: Multivessel CAD is an important prognostic variable in patients surviving uncomplicated AMT, and one of the goals of predischargenoninvasive risk stratification is to identify patients with functionally important multivessel CAD who might benefit from early coronary angiography and revascularization.2~20~21 In the present study, 35% had multivessel CAD by coronary angiography (22% with 2-vessel and 13% with 3-vessel disease).A 1260
Tl-201 defect remote from the infarct zone was observed in 35% of thesepatients. The sensitivity for detection of multivessel CAD by Tl-201 scintigraphy (35%) was slightly, but not significantly, higher than that of ‘exerciseinduced ST depression(29%). However, if a remote Tl201 defect or ischemic ST depression,or both, was considered as a single variable for multivessel CAD detection, then 58% of patients with signiticant angiographic multivessel CAD would have been identitied. Using either ST depression or a remote Tl-201 defect as a single variable only slightly decreasedthe specificity for multivessel CAD detection from 97% for a remote defect alone to 78%. The sensitivity of a remote Tl-201 defect for multivessel CAD detection in this study of patients receiving thrombolytic therapy was similar to that reported by Sutton14(35%) and Burns22(40%) and their co-workers. Previous publications suggesta higher sensitivity for Tl-201 scintigraphy for detecting multivessel CAD in the prethrombolytic era. In a series of studies comprising 508 patients, there was a 72% sensitivity of a remote Tl201 defect for detecting multivessel CAD associated with an 86% speciticity.34f23In these prior series, 59% of patients with multivessel CAD had ischemic ST-segment depression.The positive predictive value of a remote 71-201defect for identifying multivessel CAD was significantly higher than the positive predictive value of ST-segmentdepression. The prevalenceof a remote Tl-201 defect in the present cohort of patients receiving thrombolytic therapy (35%) is less than the prevalenceof remote defects seen in our laboratory in the prethrombolytic era. Gibson et al3 found that 65 of 154 patients with Q-wave infarction (42%) and 36 of 87 with non-Q-wave infarction (41%) had stress-induceddefects in >l vascular region with use of the same submaximal stresstest protocol as utilized in this current study. There are several possible explanations for a diminished sensitivity of a remote Tl-201 defect for multivesse1CAD identification in the thrombolytic era. First, the incidence of prior AMI is lower than the seriesreported before the thrombolytic era. In our study undertaken in the prethrombolytic era,’ 17% of patients had a prior AMI compared with 7% in the current study. A prior AMI remote from the zone of new myocardial necrosis would be associatedwith a high prevalenceof a remote defect. Second, patients with non-Q-wave AMI constituted a substantial percentage of postinfarction cohorts reported in the prethrombolytic era,’ whereasonly patients with ST-segment elevation generally received thrombolytic agents. Patients with non-Q-wave AMI have a comparable angiographic extent of CAD than patients with Q-wave AMI, but have a higher incidence of stress-inducedischemia.3 Third, in the prethrombolytic era, 30 to 50% of patients had 3-vessel disease.The overall prevalenceof 2or 3-vessel diseasewas 60 to 75%.24,25In contrast, approximately 10% of patients treated with thrombolytic therapy have 3-vessel disease.26Bayesian principles would predict diminished predictive value for noninvasive testing in the thrombolytic cohort. In the present
THE AMERICANJOURNALOF CARDIOLOGY VOLUME71 JUNE 1, 1993
studv, onlv 35% of uatients treated with thrombolvtic with left main or 3-vessel coronarv disease after a fmt mvocardial infarction? Am . the&by had multivessel CAD, with only 13% de&nJ6. card~~li9ss~s61-372. Dunn RF, Freedman B, Bailey IK, Ure” R, Kelly DT. Noninvasive prediction strating 3-vessel disease.In our prethrombolytic postin- of multivessel disease after myocardial infarction. Circulation 1980;62:72&734. farction cohort. 58% had multivessel CAD and 22% had 7. HLI”F: J, GOATSML, Nash E, ~raemer HC, Debusk RF, Bew WE III, LOW H. Comparative value of maximal treadmill testing, exercise thallium myocardial per3-vessel diseases Because a defect remote from the in- fusion scintigmphy and exercise radionuclide venhiculography for distinguishing farct zone is more likely to be induced by exercisestress high- and low-risk patients soon after acute myocardial infaction. Am J Cardiol in the presenceof 3-vessel than 2-vessel disease,27it is 1984;53:1221-1227. Naughton JP, Hader R. Exercise testing and exercise training in coronary artay not surprising that the detection rate of remote defects 8.disease. In: Naughton JP, Hellerstein HK, Mohler IC, eds. Methods of Exercise in patients with multivessel CAD in the thrombolvtic era Testing. New York: Academic Press, 1973:79-91. 9. B&e RA, Blackman JR, Jones JW, Strait G. Exercising testing in adult noris decreasing. mal subjects and cardiac patients. Pediatrics 1963;32:742-756. Study limitations: One limitation is that the study 10. Watson DD, Smith WH, Vinson E, Kaul S, Blackbum T, Beller GA. Quntipopulation comprised only 31 patients with multivessel the analysis of rest reinjection compared to redistribution (abstr). J Am Coil Car1992;19’129A. CAD. Despite this limited number of patients with mul- diOl 11. Austin WG, Edwards JE, Frye RC, Gensini GG, Gott VL, Griffith LSC, McGoon tivessel CAD, the percentagewith 2- and 3-vessel dis- DC, Murphy ML, Roe BB. A reporting system on patients evaluated for coronary easeis comparableto previously reported seriesof post- artery disease. Report of the Ad Hoc Committee for grading of coronary artery disCouncil on Caxliovascular Surgery, American Heart Association. Circu&ion infarction patients who received thrombolytic therapyF8 ease, 1975;51(suppl IV):IV-5-IV40. It is doubtful that inclusion of more patients with mul- 12. The TIMI Study Group. The Thrombolysis in Myocardial Infarction (TIMI) trial: phase I findings. N Engl J Med 1985;3123932-936. tivessel CAD would have altered the sensitivity or speci- 13. Touchstone DA, B&r GA, Nygaard TW, Watson DD, Tedesco C, Kaul S. ficity of exerciseTl-201 scintigraphy for the detection of Functional significance of pxedischarge exercise thallium-201 findings following “remote” ischemia. Of the 8 patients with multivessel intravenous sbreptokinase therapy during acute myocardial infarction. Am Heart J CAD who had ST-segment depression with exercise 14. 1988;116:15ao-1507. Sutton JM, Top01 El. Significance of a negative exercise thallium test in the testing, only 4 had scintigraphic evidence of multivessel presence of a critical residual stenosis after thrombolysis for acute myocardial infarcdisease.Because 2 of these patients had apical Tl-201 tion. Circulation 1991;83:1278-1286. Stewart RE, Kander N, J”ni JE, Ellis SG, O’Neill WW, Schork MA, Topol abnormalities, the scintigrams were not diagnostic of re- 15. EJ, Schwaiger M. Submaximal exercise thallium-201 SPECT for assessment of mote ischemia. This points out the difficulty of ‘correlat- interventional therapy in patients with acute myocardial infarction. Am Heart J 1991; 121:1033-1041. ing the apex to specilic vascular zones.A secondlimita- 16. Tilkemeier PL, Guiney TB, LaRaia PJ, Boucher CA. Prognostic value of pm tion is the absenceof follow-up prognostic data to deter- discharge low-level exercise thallium testing after thrombolytic treatment of acute mine if residual ischemia within the infarct zone or myocaxlial infaction. Am J Cardiol 1990;66:1203-1207. Candell-Riera J, Pe”“anyer-Miialda G, Caste11J, Rius-Davi A, Domingo E, remote defects in patients with multivessel CAD identi- 17. Alvarez-Auf%” E, Olona M, Ross&J, Ortega D, Dom&ech-Tom& FM, Soler-Soler fied patients with a higher event rate. Such follow-up is J. Uncomplicated first myocardial infarction: strategy for comprehensive prognosdifficult to obtain becausephysicians currently intervene tic srudies. J Am Coil Cardiol 1991;18:1207-1219. Fro&her VF, Perdue ST, Atwood JE, DesPois P, Sivarajan ES. Exercise testwith revascularization when ischemia is provoked by 18. ing of patients recovering from myowdial infarction. Eur Probl Cardiol 1986,ll: stress imaging. Finally, most patients in this study had 371~444. 19. The TIMI Study Group. Comparison of invasive and conservative strategies submaximal exercise testing. However, there ‘were no after mahnent with i”@ave”ous tissue plasmi”oge” activator i” acute myocaniial signiticant differences in any clinical, angiographic or infarction: results of the Thrombolysis in Myocardial Infarction (TIMI) phase II scintigraphic parameteramong those who had symptom- trial. N Engl J Med 1989;320:618627. Roubii GS, Harris PJ, Bernstein L, Kelly DT. Coronary anatomy and proglimited versus submaximal testing. Furthermore, in a 20. nosis after myocadial infarction in patients 60 years of age and younger. Circulameta-analysis of 24 studies using exercise testing after lion 1983;67:743-749. AMI, Froelicher et al29 demonstratedthat submaximal 21. Muller DWM, Top01 EJ, Ellis SG, S&on KN, Lee K, Califf RM, and the Study Group. Multivessel coronary artery disease: a key predictor of shortor predischargetesting has greater predictive prognostic TAMI term prognosis after reperfwion therapy for acute myocadial infarction. Am Heart power than postdischargeor maximal testing. .I 1991;121:1042-1049. Acknowledgment: We are grateful to Jerry Curtis for his superb editorial assistancein preparing this manuscript.
1. Gibson RS, Taylor GJ, Watson DD, Stebbins PT, Martin RP, Crampton RS, Beller GA. Predicting the extent and location of coronary artery disease during the early postinfarction period by quantitative thallium-201 scintigmphy. Am J Cardiol 1981;47:101~1019. 2. Gibson RS, Watson DD, Craddock GB, Crampton RS, Kaiser DL, Denny MJ, B&r GA. Prediction of cardiac events after ““complicated myocardial infarction: a prospective study comparing predischarge exercise thallium-201 scintigmphy and coronary angiography. Circulaion 1983;68:321-336. 3. Gibson RS, Belle1 GA, Gheorghiade M, Nygaard TW, Watson DD, Huey BL, Sayer SL, Kaiser DL. The prevalence and clinical significance of residual myoardial ischemia 2 weeks after ““complicated non-Q wave infarction: a prospective natural history study. Circulation 1986;73:118&1198. 4. Brown KA, Weiss RM, Clements JP, Wackers FJT. Usefulness of residual ischemia myocaxlium within prior infarct zone for identifying patients at high risk late after acute myocardial infarction. Am .I Cardiol 1987;60:15-19. 5. Patterson RE, Horowitz SF, Eng C, Meller J, Goldsmith SJ, Pichard A, Halgash DA, Hetman MV, Gorlin R. Can noninvasive exercise test criteria identify patients
22. Bums RI. Freeman MR. Li” P. Cox F. Morean CD. Armstrone RW. and the TPAT Study houp. Limit&” of e&&e thalli~ singld photon tomography early after myoadial infarction (abstr). .I Am Co// Cardiol 1989;13:125A. 23. Abraham RD, Freedman SB, Dunn RF, Newman H, Roubii GS, Harris PJ, Kelly DT. Prediction of multivessel coronary artery disease and prognosis early after acute myocardial infarction by exercise electrocardiography and thallium-201 myocardial perfusion scimigraphy. Am J Cardiol 1986;58:423-427. 24. Topol ET, Holmes DR, Rogers WJ. Coronary angiography after thrombalytic therapy for ac”tc myocardial infarction. Ann Intern Med 1991;114:877-885. 25. Nicod P, Gilpin EA, D&rich H, Henning H, Maisel A, Blacky R, Smith SC Jr, Rico” F, Ross J Jr. Trends in “se of coronary angiography in subacute. phase of myocaxliaJ infarction. Circulation 1991;84: 1004-1015. 26. Rogers WJ, Babb JD, Bairn DS, Chesbro JH, Gore JM, Roberts R, Williams DO, Frederich M, Passamani EF, Braunwald E, for the TIM1 ll Investigators. Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plastiogen activator, heparin and aspirin for acute myowdial infarction. J Am Coil Cardiol 1991;17:1007-1016. 27. Nygaard ‘IW, Gibson RS, Ryan JM, Gascho JA, Watson DD, Beller GA. Prevalence of high-risk thallium-201 scintigraphy fmdings in left main coroniuy artery stenosis: comparison with patients with m@tiple- and single-vessel coronary artery disease. Am J Cardiol 1984;53:462-469. 28. Top01 EJ, Holmes DR, Rogers WJ. Coronary angiography after thromb+tic therapy for acute myocardial infarction. Ann Intern Med 1991;114:877-885. 29. Froelicher VF, Perdue S, Pewen W, Risch M. Application of “x%-analysis using an electronic spread sheet to exercise testing in patients after myocardial infarction. Am J Med 1987;83:1045-1054.
THALLIUM-201 SCINTIGRAPHYAFTERTHROMBOLYSIS 1261