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(Circulation. 1997;96:2932-2937.)
© 1997 American Heart Association, Inc.

Articles

Superiority of Nitrate-Enhanced ²⁰¹Tl Over Conventional Redistribution ²⁰¹Tl Imaging for Prognostic Evaluation After Myocardial Infarction and Thrombolysis

Sumit Basu, MBBS; Roxy Senior, MBBS, MD; Usha Raval; ; Avijit Lahiri, MBBS, MSc

From the Department of Cardiac Research, Northwick Park Hospital, and Institute for Medical Research, Harrow, Middlesex.

Correspondence to Dr A. Lahiri, MBBS, MSc, MRCP, FACC, FESC, Department of Cardiology, Northwick Park Hospital, Institute of Medical Research, Watford Rd, Harrow, Middlesex HA1 3 UJ, UK.

	Abstract

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Background ²⁰¹Tl imaging has been widely used for postinfarction risk stratification. However, thrombolytic therapy and aspirin have significantly changed outcome, and there are few nuclear imaging studies that assess prognosis in such patients. Furthermore, newer techniques of ²⁰¹Tl imaging, such as reinjection and nitrate-enhanced rest ²⁰¹Tl imaging, have been shown to improve the detection of viable but jeopardized myocardium.

Methods and Results We studied 100 consecutive patients, who remained event free 6 weeks after myocardial infarction and thrombolysis. Patients underwent conventional exercise and 4-hour redistribution imaging, followed on a separate day by nitrate-enhanced rest ²⁰¹Tl study. Planar images were reported semiquantitatively by two experienced observers blinded to clinical data. Redistribution and rest injection images were classified as demonstrating reversible ischemia if they showed improvement in uptake by at least two grades in at least two segments in comparison with the initial exercise scintigram. Patients were followed up for 8 to 32 months (mean, 21 months); during this period, 37 patients had first cardiac events. Reversible ischemia was present in 29 patients on redistribution, of whom 14 (48%) had events; of 71 without reversible defects, 23 (32%) had events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS). Nitrate-enhanced rest ²⁰¹Tl imaging detected reversible defects in 68 patients, of whom 33 (49%) had events, whereas of 32 without reversible defects, only 4 (13%) had subsequent cardiac events (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001).

Conclusions Thus, after myocardial infarction and thrombolysis, even "stable" patients have a high (68%) incidence of viable but jeopardized myocardium, causing a high event rate. Those identified to be at high risk by perfusion imaging may benefit from early intervention.

Key Words: myocardial infarction • radioisotopes • prognosis

	Introduction

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Management of acute myocardial infarction has undergone considerable changes in the past decade. Routine use of thrombolysis and aspirin has reduced mortality,^{1 2} but reperfusion may produce myocardial salvage, and if a partially infarcted region supplied by a stenotic artery remains, this may present a greater risk of future ischemic events.^{2 3 4} Use of treadmill exercise ECG for risk stratification after thrombolysis for myocardial infarction has been shown to be poorly predictive of future cardiac risk.⁵

²⁰¹Tl imaging has been widely used for risk stratification after acute myocardial infarction. It has been demonstrated to be superior to either exercise ECG or coronary arteriography at predicting high- and low-risk groups.^{6 7 8}

However, these studies were performed before the thrombolytic era. Very few studies have addressed the problem of risk stratification by myocardial perfusion imaging after myocardial infarction treated with thrombolysis.

Since the initial descriptions of ²⁰¹Tl redistribution by Pohost et al,⁹ exercise and 4-hour redistribution ²⁰¹Tl imaging has been used for diagnostic and prognostic testing. However, subsequent investigators have demonstrated that conventional imaging may overestimate the extent of infarction and hence underestimate viable and potentially jeopardized myocardium.^{10 11 12} Recent studies that used delayed redistribution¹³ or reinjection of ²⁰¹Tl^{14 15} have demonstrated a greater extent of viable but ischemic myocardium than conventional exercise/redistribution imaging. In addition, nitrate treatment is known to enhance flow to peri-infarct regions¹⁶ and thus improve ²⁰¹Tl delivery. Previous work has demonstrated improved detection of ischemic myocardium after myocardial infarction by use of nitrate-enhanced rest ²⁰¹Tl imaging.¹⁷

The aim of this study was to evaluate the role of ²⁰¹Tl imaging for prognostic assessment of patients who had remained stable at 6 weeks after myocardial infarction and who were treated with thrombolytic therapy. Furthermore, we tested the value of nitrate-enhanced rest ²⁰¹Tl imaging compared with conventional stress/redistribution ²⁰¹Tl imaging.

	Methods

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Patient Selection
Patients admitted to our coronary care unit with typical signs and symptoms of acute myocardial infarction, ie, chest pain of >30 minutes' duration, typical ST-segment elevation, or appearance of pathological Q waves on the 12-lead ECG and creatine kinase elevation more than twice normal with 6% or more MB isoenzyme, who had received thrombolytic therapy and remained stable were investigated 5 to 7 weeks after acute myocardial infarction. All patients gave informed consent, and the study was approved by the hospital ethical committee. Patients with left bundle-branch block or other ECG abnormalities that interfered with the diagnosis, those in Killip class IV heart failure, those with severe or life-threatening other illnesses, patients who would not be able to perform maximal symptom-limited exercise, and those who did not remain stable or suffered an adverse cardiac event before investigation were excluded.

Study Design
All patients underwent symptom-limited treadmill exercise and stress ²⁰¹Tl imaging followed by 4-hour redistribution imaging 5 to 7 weeks after acute myocardial infarction. In addition, on a separate day, rest ²⁰¹Tl imaging was performed after pretreatment with sublingual nitroglycerin (0.5 mg). All patients were subsequently followed up until the last patient had undergone at least 6 months of follow-up. Cardiac events constituting study end points were death; reinfarction, diagnosed by standard clinical, ECG, and enzyme criteria; unstable angina requiring hospital treatment; and new congestive heart failure causing hospitalization.

²⁰¹Tl Scintigraphy
Exercise testing was performed on a motorized treadmill with continuous ECG monitoring (standard 12-lead+CM₅). The Bruce protocol and standard criteria for test termination were used.¹⁸ At peak exercise, 74 MBq of ²⁰¹Tl was injected intravenously, and patients were encouraged to continue exercising for another minute whenever possible. Images were acquired by a mobile camera (Elscint, 205M) attached to a low-energy all-purpose collimator. The energy window setting was 68 to 83 keV. Planar images were obtained at 10 minutes and 4 hours after the injection of ²⁰¹Tl. Imaging was performed in the anterior, 45° left anterior oblique, and left lateral views for 10 minutes per view. Patients' physical activities were restricted between recordings.

Rest ²⁰¹Tl study was performed on a separate day 4 to 5 days after the exercise study. ²⁰¹Tl was injected 10 minutes after sublingual nitroglycerin (0.5 mg), and imaging was performed 60 minutes later in the same three views by methods described previously.¹⁹ Correct angulation was obtained for each image, and patient positioning was strictly controlled.

Image Analysis
²⁰¹Tl images were analyzed semiquantitatively by two independent observers blinded to patient identity, clinical diagnosis, and image type, ie, whether the image displayed was 4-hour redistribution or nitrate-enhanced rest study. The scans were read soon after imaging on a weekly basis throughout the course of the study. Differences in interpretation were resolved by consensus. Five myocardial regions were defined from the three planar views, and this was converted to a polar map with four segments in each of the following regions: anterior, lateral, inferior, and septal, with two segments forming the apex, as has been described previously.^{20 21 22} Planar images were visually assessed with both unenhanced images on a computer gray scale and processed images with smoothing and color coding. Matching views of the exercise images, 4-hour redistribution, and separate-day nitrate-enhanced rest studies were displayed side by side for comparison. The ²⁰¹Tl activity in each segment was visually graded as normal, mildly reduced, moderately reduced, severely reduced, or absent. The initial scan was considered normal if all 18 segments of the polar map were reported as having normal ²⁰¹Tl uptake. Reversible perfusion defect in a segment was thought to be present when there was a shift toward normal of at least two grades or complete normalization of a resting image compared with the initial exercise image. Patients were categorized on the basis of presence or absence of at least two partially or fully reversible segments (of the polar map) from the initial stress to the subsequent redistribution or rest ²⁰¹Tl image. For the purpose of this study, either fully or partially reversible perfusion defects were thought to be indicative of the presence of ischemia.

Statistical Analysis
Cox's proportional-hazards survival model was used to identify independent predictors of adverse cardiac events. The variables considered were presence or absence of reversible ischemia by stress/redistribution or stress and nitroglycerin-enhanced rest ²⁰¹Tl imaging. The clinical variables were age, sex, race, site of myocardial infarction, past history of coronary artery disease, ß-blocker therapy, peak serum creatine kinase level, and left ventricular ejection fraction measured before hospital discharge. Univariate and multivariate Cox regression was performed with both forward and backward variable selection. A cutoff point of P<.05 was used to select significant variables. Kaplan-Meier survival curves were also plotted for the two categories of patients with and without evidence of ischemia on stress/redistribution imaging and stress/nitrate-enhanced ²⁰¹Tl imaging (the most significant variable).

	Results

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A total of 230 consecutive patients admitted to the coronary care unit for suspected myocardial infarction were screened. Despite fulfilling the ECG entry criteria, 83 patients were excluded for reasons shown in Table 1.

View this table: [in this window] [in a new window]   Table 1. Patients Excluded at Initial Screening

Thus, 147 patients were identified for the study. Subsequently, 28 patients were excluded because of events (Table 2) that occurred before study investigation at 5 to 7 weeks after myocardial infarction. Another 19 were not included in the study for reasons given in Table 2. Hence, this study was performed in the remaining 100 patients who were stable at 5 to 7 weeks after myocardial infarction.

View this table: [in this window] [in a new window]   Table 2. Reasons for Exclusion of Screened Patients Before Imaging

Demography
Patient characteristics of the 100 patients are shown in Table 3. Patients did not stop cardioactive medication except sublingual nitrates within 2 hours before exercise ²⁰¹Tl imaging.

View this table: [in this window] [in a new window]   Table 3. Patient Characteristics

Patients were followed up for a period of 8 to 32 months (mean, 21 months) after myocardial infarction. Of the 100 patients, 37 had adverse cardiac events during the follow-up period (Fig 1).

View larger version (26K): [in this window] [in a new window]   Figure 1. Distribution of cardiac events and their prediction by stress/nitroglycerin (NTG)-enhanced rest 201Tl and stress/redistribution 201Tl imaging.

Stress and Redistribution ²⁰¹Tl Imaging
Twenty-nine patients had evidence of reversible perfusion defects by exercise and 4-hour redistribution imaging. Of those, 14 (48%) had subsequent adverse cardiac events. However, of the 71 patients with no evidence of reversible perfusion defects on redistribution imaging, 23 (32%) subsequently had cardiac events (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS) (Table 4).

View this table: [in this window] [in a new window]   Table 4. Association Between Presence or Absence of Reversible Defects on 201Tl Imaging and Events in 100 Patients

Stress and Separate-Day Nitroglycerin-Enhanced Rest Imaging
Exercise and separate-day nitroglycerin-enhanced rest ²⁰¹Tl imaging revealed a higher incidence of reversible perfusion defects, ie, in 68 patients, of whom 33 (49%) had cardiac events. Of the total of 37 patients who had an adverse cardiac event, ²⁰¹Tl imaging revealed reversible perfusion defects in 33 (89%) (Fig 2). Thirty-two patients did not have evidence of reversible perfusion defects; of these, only 4 (12.5%) had adverse cardiac events. This was a highly significant result (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001) (Table 4).

View larger version (57K): [in this window] [in a new window]   Figure 2. Exercise (left), redistribution (center), and nitrate (NTG)-enhanced rest 201Tl images (right) in anterior projection of a 54-year-old male patient with inferior myocardial infarction. Inferior wall defect (arrows) shows no reversibility on redistribution imaging but almost complete normalization by nitrate-enhanced rest imaging. This patient subsequently had inferior reinfarction.

By multivariate analysis, only four variables were found to independently predict adverse cardiac effects: presence of reversible defects by stress/separate-day nitroglycerin-enhanced rest ²⁰¹Tl imaging (P<.001), history of previous angina or myocardial infarction (P<.01), anterior myocardial infarction (P=.012), and log-transformed peak creatine kinase (P=.036).

A separate multivariate analysis was also performed after echocardiographic ejection fraction data, obtained before hospital discharge, were added to the variables described earlier (see "Statistical Analysis"). These data were available for 91 of these 100 patients. There were 32 cardiac events in this group, and ejection fraction was found to be the most significant variable (P<.001), followed by presence of reversible defects on stress/nitroglycerin-enhanced rest thallium imaging (P<.01) and log-transformed peak creatine kinase (P<.01). History of ischemic heart disease and site of myocardial infarction no longer remained independently predictive in this model.

Kaplan-Meier survival curves were plotted for the ²⁰¹Tl data. The groups with and without reversible perfusion defects (ischemia) by stress/nitroglycerin-enhanced rest ²⁰¹Tl imaging showed a clear and significant separation beginning at about 2 to 3 weeks after imaging, and the two curves continued to diverge throughout the follow-up period (Fig 3). The survival curves for stress/redistribution ²⁰¹Tl imaging failed to demonstrate significant separation between the two groups (Fig 4).

View larger version (15K): [in this window] [in a new window]   Figure 3. Kaplan-Meier event-free survival curve of patients with and without reversible (Rev.) perfusion defects by stress/nitroglycerin-enhanced rest 201Tl imaging (hazard ratio, 8.1; 95% CI, 2.7 to 23.8; P<.001).

View larger version (14K): [in this window] [in a new window]   Figure 4. Kaplan-Meier event-free survival curve of patients with and without reversible (Rev.) perfusion defects by stress/redistribution 201Tl imaging (hazard ratio, 1.5; 95% CI, 0.8 to 3.0; P=NS).

	Discussion

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In the prethrombolytic era, investigators had adopted different strategies to differentiate high- and low-risk patients after myocardial infarction; eg, Norris et al²⁴ and Peel et al²⁵ used clinical variables. The most widely used investigation has been treadmill exercise ECG,^{26 27 28} and factors that identified high-risk groups were 1 mm ST-segment depression, low total exercise time, and occurrence of arrhythmias. Left ventricular ejection fraction is also well known to be a sensitive marker of prognosis in such patients.^{29 30 31} In the same period, Gibson et al⁶ demonstrated that presence of ²⁰¹Tl defects in more than one vascular zone, redistribution of ²⁰¹Tl, and increased lung ²⁰¹Tl uptake were better predictors of future cardiac events than either exercise ECG or coronary angiography. Leppo et al³² and Brown et al³³ showed by both late and early postinfarct dipyridamole ²⁰¹Tl imaging that myocardial perfusion imaging was of prognostic value. Conversely, Hung et al,³⁴ in a study of 117 male patients studied by exercise ECG, ²⁰¹Tl imaging, and radionuclide ventriculography at 3 weeks after infarction, found that a reduced treadmill workload and a fall in ejection fraction on exercise were the only significant predictors of hard cardiac events.

The use of thrombolysis has greatly reduced mortality after myocardial infarction.^{1 2} However, the presence of salvaged myocardium in the infarct-related territory is likely to place the patient at higher risk of future cardiac events, especially in the presence of residual critical stenosis of the infarct-related artery. An area of such viable but ischemic myocardium may be the cause of angina, myocardial infarction, arrhythmia, and sudden death.^{2 3 4} In this context, the need for an investigation able to identify those patients at high risk becomes even more urgent.

Unlike in the prethrombolytic era, exercise ECG has proved inadequate in the current setting. Stevenson et al⁵ showed that among 256 patients who received thrombolytic therapy for myocardial infarction, of whom 41 had events, ST-segment depression at low workload and low exercise capacity identified only 50% and 70%, respectively, of those having cardiac events, and the positive predictive accuracy of exercise ECG was poor.

Our hospital is a large District General Hospital, where angioplasty was unavailable at the time of the study (1992 to 1994). This is quite usual within the National Health Service, and only a small fraction of patients, in tertiary centers, will have access to facilities for immediate intervention. We studied a group of clinically stable patients who had received thrombolytic therapy at 6 weeks after infarction. This strategy tended to eliminate those who were most unstable after myocardial infarction, because they would already have had an adverse cardiac event or have undergone invasive studies. However, even in this apparently stable group of patients, reversible myocardial perfusion defect by stress and nitroglycerin-enhanced rest ²⁰¹Tl imaging was superior to conventional stress/redistribution imaging for the detection of adverse cardiac events (sensitivity, 89%). This was the first prospective study of two ²⁰¹Tl protocols used for risk stratification after acute myocardial infarction that demonstrates a clear advantage of nitroglycerin-enhanced ²⁰¹Tl imaging.

The failure of ²⁰¹Tl redistribution to successfully stratify patients at high and low risk is due to its inability to identify areas of reversible perfusion defects in more than half the patients in whom they were shown to be present by nitroglycerin-enhanced rest ²⁰¹Tl imaging. The lack of ²⁰¹Tl redistribution at 4 hours in the majority of these patients may be due to the severe flow limitations caused by the infarct-related artery and may also be related to the limited ²⁰¹Tl plasma concentration during the redistribution phase.³⁵ Using a stress and 4-hour redistribution protocol, Tilkemeier et al³⁶ failed to show any prognostic value of exercise ²⁰¹Tl testing after acute myocardial infarction and thrombolysis.

The superiority of rest-injection or reinjection of ²⁰¹Tl, compared with conventional redistribution imaging, for the detection of myocardial viability is well established.^{14 15} Furthermore, it is known that nitrates enhance the relative flow to severely ischemic segments because of vasodilatation of the stenotic artery.³⁷ In addition, nitrates may also increase flow to peri-infarct regions by enhancing collateral flow distal to an occluded coronary artery.¹⁶ Thus, injection of ²⁰¹Tl at rest after pretreatment with nitrates improves tracer delivery to severely ischemic areas, allowing greater uptake of the tracer by viable myocardium. He et al³⁸ demonstrated that nitrate therapy before reinjection of ²⁰¹Tl improves the detection of viable myocardium.

Retrospective analysis confirmed the predictive value of left ventricular ejection fraction, as has been described previously by other authors.^{29 30 31} However, the temporal difference between left ventricular function assessment and myocardial perfusion imaging does not allow a direct comparison between the two tests.

In postinfarction patients, there is often a combination of hibernating myocardium and scar tissue.^{19 39} We have recently demonstrated that in patients with chronic congestive heart failure after myocardial infarction, there is evidence of painless myocardial ischemia in segments with reversible left ventricular dysfunction.⁴⁰

It is evident from our results that a majority of apparently stable patients have such viable but jeopardized ischemic regions after thrombolytic therapy for acute myocardial infarction. The presence of these areas is a marker of increased risk of subsequent cardiac events. An equally significant finding was that the absence of reversible perfusion defect was an excellent marker of good prognosis. These data highlight the importance of functional stratification of patients into risk categories by use of nitroglycerin-enhanced ²⁰¹Tl myocardial perfusion imaging, with a view to early intervention in patients who demonstrate reversible perfusion abnormalities by this technique.

Limitations of the Study
The study was performed at 6 weeks after infarction; this resulted in the elimination of a subset of high-risk patients who had events in the period between hospital discharge and perfusion imaging. Our data do not allow us to determine whether such patients would have been identified by this protocol, but it is reasonable to hypothesize that the test might be useful if applied earlier. Additional studies would be needed to test this assumption.

We used planar ²⁰¹Tl imaging and qualitative image analysis because, at the time this study was initiated, we did not have single photon emission CT imaging and a quantitative database. However, it should be noted that the majority of prognostic studies using ²⁰¹Tl were performed with planar imaging.⁴¹ Furthermore, the prospective design and the prognostic (as opposed to diagnostic) outcome parameter minimize the effect of this particular methodological limitation.

Even though the imaging was performed sequentially in a nonrandomized fashion, it is unlikely to have introduced a bias. Images were all analyzed blinded, in a random sequence. Furthermore, previous myocardial imaging studies in which imaging was performed in a nonrandomized sequence at intervals varying from 1 to 2 weeks have shown good concordance between the results of the two consecutive studies.^{21 22}

Finally, although this technique demonstrates excellent sensitivity for cardiac events, the specificity is low (44%). However, a number of our patients were followed up for <1 year and may have had events after the study was closed. This would have resulted in a larger number of apparently false positives by nitrate-enhanced imaging. We consider the fact that these superficially stable patients have reversible defects to be a marker of increased risk. Invasive investigation in some patients who remain fully stable is likely to be a price that has to be paid to improve management in those at higher risk.

	Acknowledgments

 
This study was funded by the Northwick Park Hospital Cardiac research fund. We thank Rita Hamill and Christopher Kinsey for technical help and Minal Shah, Jenny Ralph, and Catherine Belling for secretarial assistance.

Received February 10, 1997; revision received May 12, 1997; accepted June 2, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Second International Study of Infarct Survival Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both or neither among 17187 cases of suspected acute myocardial infarction: ISIS 2. Lancet. 1988;2:349-360.[Medline] [Order article via Infotrieve]

2. Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico. Long term effects of intravenous thrombolysis in acute myocardial infarction: final report of the GISSI study. Lancet. 1987;2:871-875.[Medline] [Order article via Infotrieve]

3. Simoons ML, Vos J, Tijssen JGP, Vermeer F, Verheught FWA, Krauss XH, Manger Cats V. Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of the Netherlands. J Am Coll Cardiol. 1989;14:1609-1615.[Abstract]

4. Feit F, Mueller HS, Braunwald E, Ross R, Hodges M, Herman MV, Knatterud GL, and TIMI Research Group. Thrombolysis in myocardial infarction (TIMI) phase II trial: outcome comparison of a `conservative strategy' in community versus tertiary hospitals. J Am Coll Cardiol. 1990;16:1529-1534.[Abstract]

5. Stevenson R, Umachandran V, Ranjadayalan K, Wilkinson P, Marchant P, Timmis AD. Reassessment of treadmill stress testing for risk stratification in patients with acute myocardial infarction treated by thrombolysis. Br Heart J. 1993;70:415-420.[Abstract/Free Full Text]

6. Gibson RS, Watson DD, Craddock EB, Crampton RS, Donald LK, 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;2:321-336.

7. Turner TD, Schwartz KM, Logic JR, Sheffield L, Kansal S, Roitman DI, Mantle JA, Russel RO, Rackley C, Rogers WJ. Detection of residual jeopardised myocardium 3 weeks after myocardial infarction by exercise testing with thallium-201 myocardial scintigraphy. Circulation. 1980;61:729-736.[Free Full Text]

8. 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 post-infarction period by quantitative thallium-201 scintigraphy. Am J Cardiol. 1981;47:1010-1019.[Medline] [Order article via Infotrieve]

9. Pohost GM, Zir LM, Moore RH, McKusick KA, Guiney TE, Beller GA. Differentiation of transiently ischemic from infarcted myocardium by serial imaging after a single dose of thallium-201. Circulation. 1977;55:294-302.[Abstract/Free Full Text]

10. Gibson RS, Watson DD, Taylor GJ Crosby IK, Wellous HL, Holt ND, Beller GA. Prospective assessment of regional myocardial perfusion before and after coronary revascularization surgery by quantitative thallium-201 scintigraphy. J Am Coll Cardiol. 1983;1:804-815.[Abstract]

11. Liu P, Kiess MC, Okada RD, Block PC, Strauss HW, Pohost GM, Boucher CA. The persistent defect on exercise thallium imaging and its fate after myocardial revascularization: does it represent scar or ischemia? Am Heart J. 1985;110:991-1001.[Medline] [Order article via Infotrieve]

12. Tillish J, Brunken R, Marshall R, Schwaiger M, Mandelkern M, Phelps M, Schelbert H. Reversibility of cardiac wall motion abnormalities predicted by positron tomography. N Engl J Med. 1986;314:884-888.[Abstract]

13. Kiat H, Berman DS, Maddahi J, Yang LD, Train KV, Rozanski A, Friedman J. Late reversibility of tomographic myocardial thallium-201 defect: an accurate marker of myocardial viability. J Am Coll Cardiol. 1988;12:1456-1463.[Abstract]

14. Dilsizian V, Rocco TP, Freedman NMT, Leon MB, Bonow RO. Enhanced detection of ischemic but viable myocardium by the reinjection of thallium after stress-redistribution imaging. N Engl J Med. 1990;323:141-146.[Abstract]

15. Kuijper AFM, Vliegen HW, Van der Wall EE, Oosterhuis WP, Zwinderman AH, van Eck-Smit BLF, Niemeyer MG, Pauwels EKJ. The clinical impact of thallium-201 re-injection scintigraphy for detection of myocardial viability. Eur J Nucl Med. 1992;19:783-789.[Medline] [Order article via Infotrieve]

16. Aoki M, Sakai K, Koyanagi S, Takeshita A, Nakamura M. Effect on nitroglycerine on coronary collateral function during exercise evaluated by quantitative analysis of thallium-201 single-photon emission computed tomography. Am Heart J. 1991;121:1361-1366.[Medline] [Order article via Infotrieve]

17. Basu S, Sridhara B, Senior R, Duncker DM, Raval U, Handler CE, Raftery EB, Lahiri A. Role of thallium-201 reinjection in the assessment of myocardial viability following myocardial infarction. Br Heart J. 1993;69:61. Abstract.

18. Ellestead MH, Allen W, Wan MCK, Kemp GL. Maximal treadmill stress testing for cardiovascular evaluation. Circulation. 1969;39:517-524.[Abstract/Free Full Text]

19. Senior R, Glenville B, Basu S, Sridhara BS, Anagnostou E, Stanbridge R, Edmondson SJ, Handler CE, Raftery EB, Lahiri A. Dobutamine echocardiography and thallium-201 imaging predict functional improvement following revascularisation in severe ischaemic left ventricular dysfunction. Br Heart J. 1995;74:358-364.[Abstract/Free Full Text]

20. Jain D, Lahiri A, Raftery EB. Clinical and prognostic significance of lung thallium uptake in acute myocardial infarction. Am J Cardiol. 1990;65:154-159.[Medline] [Order article via Infotrieve]

21. Sridhara BS, Sochor H, Rigo P, Braat S, Marinez-Duncker D, Cload P, Lahiri A. Myocardial single-photon emission computed tomographic imaging with technetium-99 m tetrofosmin: stress rest imaging with same day and separate day rest imaging. J Nucl Cardiol. 1994;1:138-143.[Medline] [Order article via Infotrieve]

22. Zaret BL, Rigo P, Wackers FJT, Hendel RC, Braat SH, Iskandrian AS, Sridhara BS, Jain D, Itti R, Serafini AN, Goris ML, Lahiri A, and the Tetrofosmin International Trial Study Group. Myocardial perfusion imaging with ^99mTc tetrofosmin: comparison to ²⁰¹Tl imaging and coronary angiography in a phase III multicenter trial. Circulation. 1995;91:313-319.[Abstract/Free Full Text]

23. ISIS-3 (Third International Study of Infarct Survival) Collaborative Group. ISIS-3: a randomised comparison of streptokinase vs tissue plasminogen activator vs anistreplase and of aspirin plus heparin vs aspirin alone among 41299 cases of suspected acute myocardial infarction. Lancet. 1993;339:753-770.

24. Norris RM, Caughey DE, Demming LW, Mercer CJ, Scott PJ. Coronary prognostic index for predicting survival after recovery from acute myocardial infarction. Lancet. 1970;2:485-487.[Medline] [Order article via Infotrieve]

25. Peel AAF, Semple T, Wang I, Lancaster WM, Dall JLG. A new coronary prognostic index for grading the severity of infarction. Br Heart J. 1962;24:745-760.

26. Theroux P, Waters DD, Halphren C, Debaisieux JC, Mizgala HF. Prognostic value of exercise testing soon after myocardial infarction. N Engl J Med. 1979;301:341-345.[Abstract]

27. Davidson DM, DeBusk RF. Prognostic value of single exercise test 3 weeks after uncomplicated myocardial infarction. Circulation. 1980;61:236-242.[Free Full Text]

28. Weld FM, Chu LK, Biggers JT Jr, Rolnitzky LM. Risk stratification with low level exercise testing 2 weeks after acute myocardial infarction. Circulation. 1981;64:306-314.[Abstract/Free Full Text]

29. Schelbert HR, Henning H, Ashburn WL, Verba JW, Karkner JS, O'Rourke RA. Serial measurement of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction. Am J Cardiol. 1976;38:407-415.[Medline] [Order article via Infotrieve]

30. Shah PK, Pichler M, Berman DS, Singh BN, Swan HJC. Left ventricular ejection fraction determined by radionuclide ventriculography in early stages of first transmural myocardial infarction. Am J Cardiol. 1980;45:542-546.[Medline] [Order article via Infotrieve]

31. Sanford CF, Corbett J, Nicod P, Curry GL, Lewis SE, Dehmer GJ, Anderson A, Moses B, Willerson JT. Value of radionuclide ventriculography in the immediate characterization of patients with acute myocardial infarction. Am J Cardiol. 1982;49:637-644.[Medline] [Order article via Infotrieve]

32. Leppo JA, O'Brien J, Rothendler JA, Getchell JD, Lee VW. Dipyridamole-thallium-201 scintigraphy in the prediction of future cardiac events after acute myocardial infarction. N Engl J Med. 1984;310:1014-1018.[Abstract]

33. Brown KA, O'Meara J, Chambers CE, Plante DA. Ability of dipyridamole-thallium-201 imaging one to four days after acute myocardial infarction to predict in-hospital and late recurrent myocardial ischemia events. Am J Cardiol. 1990;65:160-167.[Medline] [Order article via Infotrieve]

34. Hung J, Goris M, Nash E, Kraemer H, DeBusk R, Berger WE, Lew H. Comparative value of maximal treadmill testing, exercise thallium myocardial perfusion scintigraphy and exercise radionuclide ventriculography for distinguishing high- and low-risk patients soon after acute myocardial infarction. Am J Cardiol. 1984;53:1221-1227.[Medline] [Order article via Infotrieve]

35. Rocco TP. Rest re-injection of thallium-201 after redistribution imaging: new question, old solution. J Nucl Med. 1990;31:1623-1626.[Free Full Text]

36. Tilkemeier PL, Giuney TE, LaRia PJ, Boucher CA. Prognostic value of predischarge low-level exercise thallium testing after thrombolytic treatment of acute myocardial infarction. Am J Cardiol. 1990;66:1203-1207.[Medline] [Order article via Infotrieve]

37. Brown BG, Bolson R, Petersen RB, Pierce CD, Dodge HT. The mechanisms of nitroglycerin action: stenosis vasodilatation as a major component of the drug response. Circulation. 1981;64:1089-1097.[Abstract/Free Full Text]

38. He Z, Darcourt J, Guignier A, Ferrari E, Bussière F, Baudouy M, Morand P. Nitrates improve detection of ischaemic but viable myocardium by thallium-201 reinjection SPECT. J Nucl Med. 1993;34:1472-1477.[Abstract/Free Full Text]

39. Bonow RD, Dilsizian V, Cucolo A, Bacharach SL. Identification of viable myocardium in patients with chronic coronary artery disease and left ventricular dysfunction: comparing thallium scintigraphy with reinjection and PET imaging with 18F-fluorodeoxyglucose. Circulation. 1991;83:26-37.[Abstract/Free Full Text]

40. Senior R, Kaul S, Raval U, Lahiri A. Painless myocardial ischaemia is frequently associated with hibernating myocardium in congestive heart failure. Eur Heart J. 1996;17:154. Abstract.

41. Brown D. Prognostic value of thallium-201 myocardial perfusion imaging: a diagnostic tool comes of age. Circulation. 1991;83:363-380.[Free Full Text]

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