CURRICULUM
IN CARDIOLOGY
Assessment of reperfusion after thrombolytic therapy for myocardial infarction Anita Zeiler Arnold,
DO, and Eric J. Topol,
MD Cleveland,
Since 1980 when DeWood et a1.l established that 90% of acute myocardial infarctions are associated with int,racoronary thrombosis, the treatment of myocardial infarction has expanded rapidly, especially in the area of thrombolytic therapy. Numerous randomized, placebo-controlled trials have convincingly demonstrated the benefits of thrombolytic therapy in reducing mortality associated with acute myocardial infarction.2-4 Improvement in left ventricular function associated with thrombolytic therapy is presumably on the basis of a patent infarct-related artery (IRA), but there may be other mechanisms involved such as limiting infarct expansion that improve survival, also related to a patent IRA, independent of salvage of myocardium. Coronary artery patency has been shown to be the most important and independent factor to decrease the occurrence of late potentials after myocardial infarction, late potentials being a marker of spontaneous and inducible ventricular tachycardia as well as sudden death.5 It is therefore crucial to document reperfusion of the IRA as soon as possible. Unfortunately, there is a 25 ‘% to 30 % failure rate for thrombolytic therapy that is associated with a significantly worse prognosis; there is at least two to three times the death rate in those patients compared with patients with a patent IRA. If thrombolysis has failed to restore patency, the patient could be considered a candidate for fallback (secondary) mechanical intervention (coronary angioplasty or surgical revascularization). It is therefore highly desirable to find a means of documenting the success of thrombolytic therapy in a timely fashion. Coronary angiography was established as the “gold standard” for assessing IRA patency in the early studies of intracoronary streptokinase.6, 7 However, the standard of care was changed with the develop-
From
the Department
Received Reprint Cleveland 411/38403
for publication requests: Clinic
of Cardiology, Jan.
14, 1992;
The Cleveland accepted
Clinic March
Foundation. 2, 1992.
Eric J. Topol, MD, The Department of Cardiology, The Foundation, 9500 Euclid Ave., Cleveland, OH 44106.
Ohio
ment of intravenous thrombolytic agents with patency rates equivalent to those of intracoronary streptokinase.8, g Thrombolytic therapy could now be given without the necessity of coronary angiography, and indeed routine angiography may be undesirable in the setting of acute myocardial infarction, as demonstrated by the Thrombolysis In Myocardial Infarction (TIMI) study group.” Since angiography is no longer routinely performed, noninvasive markers have been sought to document reperfusion. There are a number of noninvasive methods that have been proposed to verify the patency of the IRA. The purpose of this review is to discuss the methods available, and the advantages and limitations of each method. BEDSIDE/CLINICAL
DETERMINANTS
Several noninvasive markers can indicate reperfusion after thrombolytic therapy with a reasonable degree of accuracy. As long as 50 years ago, noninvasive markers such as resolution of ST segment shifts on electrocardiography or the development of an accelerated idioventricular rhythm, were observed in experimental animals. l1 These markers are observed in humans as well, and are still reported in the current literature as signs of reperfusion. Saran et a1.12 used the percent reduction in ST segment elevation to predict IRA patency. When the ST segment elevation fell by less than 25 % of the baseline value, persistent coronary occlusion was likely, with a predictive accuracy of 86%. Califf et all3 found that complete resolution of ST-T wave changes was associated with a 96% patency rate on go-minute angiograms after thrombolytic therapy, but that this occurred in only 6 % of patients. Recent reports focus on electrocardiographic signs of reperfusion, either by frequently recorded 12-lead-electrocardiograms (ECGs), or by continuous ST segment shift monitoring and analysis (Figs. 1 and 2). The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 7 trial14 recently reported that when compared with other clinical variables, ST segment digital trend recovery has provided the vast majority of information concerning IRA patency. Continuous vectorcar441
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Arnold and Top01
American
August 1992 Heart Journal
Fig. 1. Continuous ST segmentmonitoring in a patient with successfulreperfusion. Resolution of ST segment elevation in the anterior leads is documented over time.
ABBB
B
Fig. 2. Continuous ST segmentmonitoring in a patient with initially successfulreperfusion (A) and intermittent occlusion of the infarct-related artery (B).
diography using a computerized monitoring system (MIDA 1000, Ortivus Medical, Taby, Sweden) for on-line dynamic analysis of QRS complex and ST segment changes has been used successfully by Dellborg et a1.15 to accurately predict reperfusion. Of 21 patients analyzed who had thrombolytic therapy or angioplasty for acute myocardial infarction, 16 had a patent IRA and five had persistent occlusion at the time of emergency angiography. Using vectorcardiography analysis (Fig. 3), the authors correctly identified 15 of 16 patients with a patent IRA and five of six with persistent occlusion (sensitivity, 94%; specificity, 80 5%). Some authors have found reperfusion arrhythmias to be a marker for IRA patency,16 while other investigators have not found it to be as reliable.17q l8 In 386 patients treated with tissue plasminogen activator (TPA) for acute myocardial infarction in the TAMItrial, ventricular tachycardia, ventricular fibrillation,
second- and third-degree heart block, and severe sinus bradycardia were all documented with similar frequencies following thrombolytic administration. None of the arrhythmias recorded, however, were associated with rates of reperfusion any higher than 77% (range: 64% for second-degree heart block to 77% for ventricular fibrillation).13 It therefore appears that bedside or clinical parameters are severely lacking in accuracy to detect patients who have failed reperfusion, or even to identify patients at high risk for recurrent spontaneous ischemia after thrombolysis.ig LABORATORY
DETERMINANTS
Early peaking of the total creatine kinase (CK) level and the CK-MB isoenzyme have identified patients with successful reperfusion after streptokinase therapy,6, 2o but the delay in laboratory determination and the number of patients not accurately iden-
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0.200 mV. 40.
4
8 hours
Fig. 3. Pharmacologic reperfusion. Print-out directly from the computer screenof a trend analysis of a trend curve showingchangesin the ST vector magnitude and in the QRS vector difference over time. This patient has an acute inferior myocardial infarction. Acute coronary angiography after 25 minutes of vectorcardiographic monitoring showedTIMI grade 3 flow in the right coronary artery. Arrow indicates first injection of contrast material. (Reprinted with permissionof the American Heart Association).
tidied by this method make it a less desirable marker of IRA patency. Recent reports have focused on the use of peak serum myoglobin to detect coronary reperfusion. Dillon et al.“’ analyzed plasma myoglobin (Mb) concentration-time curves and the results of immediate angiography in 20 patients with acute myocardial infarction undergoing attempted reperfusion. They concluded that their mathematical model allowed the prediction of successful reperfusion with an overall predictive accuracy of 95% and was reliably estimated from two samples drawn within 60 minutes of therapy.21 OthersZ2 have reported similar results monitoring peak serum Mb concent,ration as a marker for reperfusion. Although the Mb concentration is a useful marker and can be assayed quickly (10 minutes by latex agglutination turbidmetry) in certain laboratories, there are still patients who will not be diagnosed as thrombolytic failures by these methods.2” NUCLEAR IMAGING Thallium-201 imaging. While thallium-201 imaging has been used as a marker for early reperfusion as well asto quantify myocardial salvage,24it has several important limitations. The most significant is the delay in administering thrombolytic therapy to obtain initial images. Also, the hyperemic phase of reperfusion affects the distribution of the tracer,
which tends to concentrate thallium in the infarct area if given too soon after reperfusion. Delayed redistribution also makes it difficult to distinguish persistently ischemic myocardium from scar tissue,2” which has important implications for treatment. Thallium-201 combined with intracoronary technetium 99m (Tc-99m) pyrophosphate can predict myocardial salvage after intracoronary thrombolysis, but this requires an invasive approach and is not preferred over angiography to determine IRA patency.26 Technetium-99m stannous pyrophosphate imaging. Wheelan et a1.27used early and late Tc-99m stannous pyrophosphate (PPi) as a marker of reperfusion after thrombolytic therapy. They reported that strongly positive early Tc-99m-PPi images were as reliable as early peaking CK-MB fractions in predicting reperfusion. In the 78% of their patients with early peaking CK-MB fractions, the majority (91 ?C.) also had strongly positive scans suggesting reperfusion. None of the control patients had early CK-MB peaks, and none had positive PPi scans. These results were confirmed by Hashimoto et a1.,‘8 who accurately detected 89 7;’ of patent IRAs as confirmed by angiograms performed several weeks after acute myocardial infarction. None of their patients with unsuccessful reperfusion by angiography had positive scans. This degree of accuracy was achieved with
Augusl
444
Table
Arnold
and
Top01
American
I. Characteristics
of noninvasive
markers
of reperfusion
Method
after thrombolytic
Advantages
therapy
1992
Heart Journal
_____ Limitations
Electrocardiography
ST segment resolution Reperfusion arrhythmia Continuous ST segment monitoring
Readily available, inexpensive Readily available, inexpensive Highly accurate
Limited accuracy Low specificity Not readily available, special equipment
Easily obtained Estimates reperfusion in 60 minutes
Time delay Needs further validation
Available in most hospitals
Time delay for initial images Reperfusion hyperemia affects distribution Delayed redistribution affects interpretation Inferior wall imaging limited
Chemical
Creatine kinase-MB Peak serum myoglobin Nuclear
imaging
Thallium-201
Technetium Magnetic
99-isonitrile
resonance
imaging
No time delay for images No redistribution (MRZ)
Tissue characterization
Conventional
Gadolinium Cine-MRI
enhanced
Altered T2 images, long imaging times, metallic prostheses, arrhythmia interference with gating Similar to conventional MRI Similar to conventional MRI
Better tissue characterization High spatial resolution, low acquisition time, superior temporal resolution
Echocardiography
Regional wall motion
Readily available, bedside imaging
Transmitral Doppler Sonicated albumin
Readily available, bedside imaging Perfusion study, enhanced images
From Dellborg
M, Top01 EJ, Swedberg
K. AM HEART
Abnormality may persist several days after reperfusion Accurate in 256 of patients Not widely applied
J 1991;122:943-8
emission computed tomography (CT) imaging, which corrects for adjacent osseous activity to obtain better quality images when compared with conventional planar scanning. Technetium-99m hexakis-2-methoxy-2-isobutyl-isonitrile imaging. A radiopharmaceutical recently
used in reperfusion imaging is technetium-99m-hexakis2-methoxy-2-isobutyl-isonitrile (Tc-99-isonitrile), which is distributed in proportion to myocardial blood flow. Advantages include the virtual lack of redistribution, so it can be given immediately before thrombolytic therapy without the delay of obtaining initial images, as with conventional thallium-201 imaging. Scans done several hours later will still reflect the prethrombolytic anatomy. Also, because it has a higher energy peak (140 keV), its image is superior to that of thallium-201 (except when the inferior left ventricular wall overlaps the liver, which limits interpretation). 2g IRA patency can be indirectly as-
sessed several hours after thrombolytic therapy with the administration of a second dose of isotope. Several studies30-32 have documented the effectiveness of this radiopharmaceutical to assess the extent of jeopardized myocardium and subsequent myocardial salvage after thrombolytic therapy. NUCLEAR
MAGNETIC
RESONANCE
IMAGING
Magnetic resonance imaging (MRI), with its unique ability to characterize tissue, has the potential to delineate normal from ischemic myocardium after reperfusion. The edema associated with myocardial infarction and necrosis, prolongs relaxation times Tl and T2, therefore altering the intensity of the myocardial signal. With the prolonged relaxation times, the T2 weighted images result in a loss of signal with decreased delineation of normal myocardium. This loss results in longer imaging times and lower specificity for conventional MRI.
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Gadolinium-DTPA (diethylene triamine pentaacetic acid) enhances differences between normal and infarcted tissue and makes MRI a more useful technique. Although this enhanced difference with gadolinium was more evident ex vivo, gadolinium-DTPA images may play a role in post-thrombolytic assessment of IRA patency.33 Van Rossum et a1.34studied 19 patients with gated MRI using gadolinium-DTPA 47 to 72 hours after the onset of myocardial infarction. The results were compared with coronary angiograms taken just before the MRI scan. Contrast ratios of the signal intensity of infarcted tissue to normal tissue were constructed. Although the maximum contrast ratios (infarct tissue/normal) were not different between patients with a patent IRA compared with those with persistent occlusion, the contrast ratio as a function of time did identify patent IRAs. The authors admit, however, that the number of patients studied was small and that clinical use was limited by overlap between contrast ratios. In contrast, Van der Wall et a1.35reported that gadolinium-DTPA-enhanced MRI could not accurately identify patients in whom thrombolytic therapy was successful. While this technique may prove useful in the future, MRI imaging is less accurate than other available methods and poses logistic problems that prohibit its widespread application. Cine-MRI has been studied to detect left ventricular functional characteristics after successful reperfusion. The technique has a high spatial resolution, a shorter acquisition t,ime, and superior temporal resolution when compared with spin-echo MRI. As of yet, however, it has not been widely used to predict IRA patency. Several limitations of tine-MRI, such as metallic hardware in the patient that precludes examination, the inaccuracy of imaging with cardiac dysrhythmias, and the length of time required for examination in critically ill patients36 currently make this technique less than optimal. ECHOCARDIOGRAPHY
Echocardiography is useful in evaluating regional wall motion abnormalities after myocardial infarct,ion, and in evaluating myocardial salvage after t.hrombolytic treatment. Broderick et a1.37noted wall motion abnormalities in all patients before the administration of thrombolytic therapy, and found that 80”;. showed improvement in the IRA subserved segments at the time of late study (3 days later). In the patients whose regional wall motion scores did not improve, most required additional intervention with angioplasty or coronary artery bypass surgery.
Assessing reperfusion
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445
Because of the postischemic improvement in left ventricular contractile function that occurs over several days, conventional echocardiography may not be an adequate method to assess the initial success of reperfusion with thrombolytic agents. Touchstone et a1.38 found that 75% of their patients treated with intravenous streptokinase had a patent IRA several hours later, but only 45 % had echocardiographic evidence of improvement in regional wall motion. In the remainder, improvement occurred up to 10 days later. Oh et a1.3g at the Mayo Clinic reported echocardiographic improvement in wall motion abnormalities in 29% of patients who had successful reperfusion, but also in 11% of patients who did not reperfuse after lytic therapy. While in some patients who reperfuse improvement in wall motion can be detected as early as 24 hours after thrombolytic therapy,40 this does not appear to be a sufficiently sensitive marker of reperfusion. Feigenbaum41 has advocated the use of digital recording of the echocardiogram, with a storage system in the intensive care unit that allows for easy retrieval and the creation of a continuous-loop display of several images. These can be compared with baseline studies to observe subtle changes after thrombolytic therapy.41 Myocardial perfusion imaging with the use of sonicated albumin may increase the diagnostic accuracy of establishing reperfusion with echocardiography, but this technique is not widely applied.42, 43 Left ventricular diastolic filling, as measured by transmitral Doppler flows, has also been studied as a method to assess reperfusion. If reperfusion occurs, there should be improvement in left ventricular diastolic filling, detected by echo-Doppler measurements of transmitral flows. Masuyama et a1.,44 however, were able to show improvement in left ventricular diastolic filling via pulsed Doppler echocardiography in only 25% of patients in whom the IRA was patent. Ultrasonic tissue characterization with conventional two-dimensional echocardiography can define ventricular wall motion abnormalities. The hypothesis is that pathologic changes of the myocardium, such as those produced by acute myocardial infarction, alter the physical properties of the tissue. These alterations can then be quantified by frequency-dependent ultrasonic attenuation and backscatter. Milunski et a1.45 used this technique to determine if ultrasonic tissue characterization could identify acute myocardial infarction, and if the early effects of reperfusion were reflected accordingly. They found that patients with documented IRA patency had a characteristic increase in the cyclic variation in sig-
446
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and Topol
nals over time, whereas there was no such recovery in patients with an occluded IRA. While this technique requires some modification of the conventional echocardiographic equipment, it may be a useful modality in detecting reperfusion. CONCLUSIONS
Thrombolytic therapy conclusively decreases the mortality associated with acute myocardial infarction. Still, between 25 ‘% and 30 6%of patients are not successfully reperfused. Interventions that can restore IRA patency can be implemented if patients can be identified who did not reperfuse with thrombolytic treatment. Several noninvasive techniques can assist in this determination (Table I), but as of now the “gold standard” remains coronary angiography. We need to continue to evaluate and refine noninvasive modalities to identify patients who are candidates for further intervention. SUMMARY
The benefits of thrombolytic therapy in reducing the mortality associated with acute myocardial infarction are well documented. Presumably, this is on the basis of a patent IRA, although other mechanisms may be involved. Because there is a 25 % to 30 ‘% failure rate for thrombolytic therapy that is associated with a significantly worse prognosis, it is crucial to document reperfusion in a timely fashion. In cases of failure to reperfuse, the patient could be considered a candidate for secondary mechanical intervention. While coronary arteriography is presently the “gold standard” to document reperfusion, this is an invasive procedure associated with small but defined risks for the patient. A noninvasive marker that is readily available and highly accurate is most desirable. There are a number of methods currently used to document coronary reperfusion noninvasively. This review discusses the advantages and disadvantages of each method, and the need for continued evaluation and refinement in noninvasive modalities to identify patients who are candidates for further intervention.
Amemzan
5.
6.
7.
8.
9.
10.
Il. 12.
13.
14.
15.
16.
17.
18.
19. REFERENCES
1. DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980;303:897-902. 2. Second International Study of Infarct Survival (ISIS-2) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction. ISIS-2. Lancet 1988;2:349-60. 3. Kennedy JW, Martin GV, Davis. KB, et al. The Western Washington intravenous streptokinase in acute myocardial infarction trial. Circulation 1988:77:345-52. 4. GruppoItalianoperloStudiodellaStreptochinasinell’Infarcto
20.
21.
22.
August 1992 Heart Journal
myocardio (GISSI). Effectiveness of intravenous thrombolyt 1: treatment in acute myocardial infarction. I,ancet 1986;1:3% 401. De Chillou C. Sadoul N. Briancon S, Aliot E. Factors determining the occurrence of late potentials on the signal averaged electrocardiogram after a first myocardial infarction: a multi variate analysis. J Am Co11 Cardiol 1991;18:7638-42. Ganz W, Buchbinder N, Marcus H, et, al. Intracoronary thrombolysis in evolving myocardial infarction. A.M HEART J 1981;101:4-13. Rentrop R, Blank H, Karsch JR, et al. Selective intracoronary thrombolvsis in acute mvocardial infarction and unstable angina pectoris. Circulation 1981;63:307-17. Verstraete M, Bory M, Collen D. et al. Randomized trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Lancet 1985;1:842-7. Chesebro JH, Knatteud G, Roberts R, et al. Thrombolysis In Myocardial Infarction (TIMI) trial. Phase I. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142-54. TIM1 Research Group. Immediate versus delayed catheterization and angioplasty following thrombolytic therapy for acute mvocardial infarction. JAMA 1988;260:2849-58. Tennet R, Wiggers CJ. The effect of coronary occlusion on myocardial contraction. Am J Physiol 1935;112:351-61. Saran RK, Been M, Furniss SS, et al. Reduction in ST segment evaluation after thrombolysis predicts either coronary reperfusion, or preservation of left ventricular function. Br Heart .J 1990;64:113-7. Califf RM. O’Neill WW, Stack RS, Aronson L, Mark DB. Mantel1 S, George BS, Candela RJ, Kereiakes DJ, Abbottsmith CH, Top01 EJ. Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988;108:658-62. Krucoff MW, Wagner BL, Sigmon KN, O’Connor CM, Granger CB, Kereiakes DJ, George BS, Wall TC, Samaha JK, and the TAM1 7 Study Group. The relative roles of clinical variables and continuous ST segment monitoring for “real time” noninvasive detection of reoerfusion in the TAM1 7 Trial IAbstract]. Circulation 199i;84:11-117. Dellborg M, Top01 EJ, Swedberg K: Dynamic QRS complex and ST segment vectorcardiographic monitoring can identify vessel patency in patients with acute myocardial infarction treated with reperfusion therapy. AM HEART ,J 1991$X: 943-8. Goldberger S, Greenspon AJ, Urban PL, Muza B, Berger B: Reperfusion Arrhythmia: a marker for restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction. AM HEART J 1983;105:26-32. Miller FC, Krucoff MW. Satler LF, Green CE, Fletcher RD, DelNegro AA, Pearle DL, Kent KM, Rackley CE. Ventricular arrhythmia during reperfusion. AM HEART J 1986;112:928-32. Kircher BJ, Top01 EJ, O’Neill WW, Pitt B. Prediction of infarct artery recanalization after intravenous thrombolytic therapy. Am J Cardiol 1987;59:513-5. Muller DW, Top01 EJ, Ellis SG, Woodlief LH. Sigmon KW, Kereiakes DJ, George BS, Worley SJ, Samaha JK, Phillips H, Califf RM. Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. J Am Co11 Cardiol 1991;18:1594-601. Schwartz F, Schuler G, Katus M, et al. Intracoronary thrombolysis in acute myocardial infarction: correlations among serum enzyme, scintigraphic, and hemodynamic findings. Am J Cardiol 1982;50:32-8. Dillon GA, Ellis AK, Klocke FJ. Rapid determination of coronary reperfusion in acute myocardial infarction patients using myoglobin kinetics [Abstract]. Circulation 1991;(suppl 18):11-115. Clemmensen P, Jurlander B, Grande P, Ohman EM, Wagner GS. Monitoring peak serum-myoglobin for noninvasive pre-
Volume Number
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24.
25.
26.
27.
28.
29.
30.
31.
32.
33
34.
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diction of coronary reperfusion in patients [Abstract]. Circulation 1991;(suppl 18):11-117. Ishii J, Nomura M, Ando T, Hasegawa H, Kimura M, Tateishi H, Kurokawa H, Kondo T, Hishida H. Early detection of coronary reperfusion based on serum myoglobin concentration [Abstract]. Circulation 1991;(suppl 18):R-117. Beller GA. Role of mvocardial nerfusion imazine in evaluatinz thrombolytic therapy for acut’e myocardial-infarction. J Am Co11 Cardiol 1987;9:661-8. Beller GA. Noninvasive assessment of myocardial salvage after coronary reperfusion: a perpetual quest of nuclear cardiology. J Am Co11 Cardiol 1989;14:874-6. Schafer .J, Mathey DG, Montz R, et al. Use of dual intracoronary scintigraphy with thallium-201 and technetium-99m pyrophosphate to predict improvement in left ventricular wall motion immediately after intracoronary thrombolysis in acute myocardial infarction. J Am Co11 Cardiol 1983;2:737-44. Wheelan K, Wolfe C, Corbett J, et al. Early positive technetium-99m stannous pyrophosphate images as a marker of reperfusion after thrombolytic therapy for acu: e myocardial infarct ion. Am J Cardiol 1985,56:252-6. Hashimoto T, Kamhara H, Fudo .T,- et. al; Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate. Am 3 Cardiol 1987;60:952-7. Pfisterer M, Muller-Brand J, Spring P, et al. Assessment of the extent of jeopardized myocardium during acute coronary occlusion followed by reperfusion in man using techetium99m isonitrile imaging. AM HEAK~ J 1991;122:7-12. Pellikka PA, Behrenbeck T, Verani MS, et al. Serial changes in myocardial perfusion using tomographic technetium-99mhexakis-2-methoxy-2-methylpropyl-isonitrile imaging following reperfusion therapy of myocardial infarction. J Nucl Med 1990::0:1269-75. Christ.ian TF, Gibbons RJ, Gersh BJ. Effect of infarct location on myocardial salvage assessed by technetium-99m-isonitrile. .J Am Call Cardiol 1991;17:1303-8. Behrenbeck T, Pellikka PA, Huber KC, et al. Primary ar,gioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99rh iionitrile. d Am Co11 Cardiol 1991;17:365-72. DeRoos A, Van Rossum AC, Van der Wall E, et al. Reperfused and nonreperfused myocardial infarction: diagnostic potential of Gd-DTPA enhanced MR imaging. Radiology 1989;172:71720. Van Rossum AC, Visser FC, Van Eenige MJ, et al. Value of gadolinium-diethylene-triamine-pentaacetic acid dynamics in
Assessing reperfusion
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36.
37.
38.
39.
40.
41. 42.
43.
44.
45.
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magnetic resonance imaging of acute myocardial infarction with occluded and reperfused coronary arteries after thrombolysis. Am J Cardiol 1990;65:845-51. Van der Wall EE, Van-Dijkman PRM, DeRoos A, et al. Diagnostic significance of gadolinium-DTPA (diethylene-triaminepen&acetic acid) enhanced magnetic resonance imaging in thromholytic treatment for acute myocardial infarction: its potential in assessing reperfusion. Br Heart J 1990;63:12-7. Meese RB, Sprinter CE, Negro-Vilar R, et al. Detection, characterization and functional assessment of reperfused Q-wave acute myocardial infarction by tine magnetic resonance imaging. Am J Cardiol 1990;66:1-9. Broderick TM, Bourdillon PDV, Ryan T, et al. Comparison of regional and global left ventricular function by serial echocardiograms after reperfusion in acute myocardial infarction. J Am Sot Echocardiogr 1989;2:315-23. Touchstone DA, Beller GA, Nygaard TW, et al. Effects of successful intravenous reperfusion therapy on regional myocardial function and geometry in humans: a tomographic assessment using 2-D echocardiography. J Am Co11 Cardiol 1989;13: 1506-13. Oh JK, Gersh BJ, Nassef LA. et al. Effects of acute reperfusion on regional myocardial function: serial two-dimensional echocardiography assessment. Int J Cardiol 1989;22:161-8. Bourdillon PDV, Broderick TM, Williams ES, et al. Early recovery of regional left ventricular function after reperfusion in acute myocardial infarction assessed by 2-dimensional echocardiography. Am J Cardiol 1989;63:641-6. Feigenbaum H. Role of echocardiography in acute myocardial infarction. Am J Cardiol 1990;66:17H-22H. Reisner SA, Ong LS, Lichtenberg GS, et al. Myocardial perfusion imaging by contrast echocardiography with use of intracoronary sonicated albumin in humans. .J Am Co11 Cardiol 1989;14:660-5. Meerbaum S. Promise and status of myocardial contrast enhanced 2-dimensional echocardiography: delineation of ischemic risk zone and quantitation of myocardial perfusion defects. J Am Co11 Cardiol 1986;7:395-6. Masuyama T, Kudama K, Lee JM, Nanto S, Kitabatake A, Kamada T. Effects of coronary angioplasty on left ventricular diastolic filling in patients with old myocardial infarction: a study of pulsed Doppler echocardiography. Eur Heart J 1991;12:34-8. Milunski MR, Mohr GA, Perez JE, et al. Ultrasonic tissue characterization with integrated backscatter: acute myocardial ischemia, reperfusion, and stunned myocardium in patients. Circulation 1989;80:491-503.
IN CARDIOLOGY
Assessment of reperfusion after thrombolytic therapy for myocardial infarction Anita Zeiler Arnold,
DO, and Eric J. Topol,
MD Cleveland,
Since 1980 when DeWood et a1.l established that 90% of acute myocardial infarctions are associated with int,racoronary thrombosis, the treatment of myocardial infarction has expanded rapidly, especially in the area of thrombolytic therapy. Numerous randomized, placebo-controlled trials have convincingly demonstrated the benefits of thrombolytic therapy in reducing mortality associated with acute myocardial infarction.2-4 Improvement in left ventricular function associated with thrombolytic therapy is presumably on the basis of a patent infarct-related artery (IRA), but there may be other mechanisms involved such as limiting infarct expansion that improve survival, also related to a patent IRA, independent of salvage of myocardium. Coronary artery patency has been shown to be the most important and independent factor to decrease the occurrence of late potentials after myocardial infarction, late potentials being a marker of spontaneous and inducible ventricular tachycardia as well as sudden death.5 It is therefore crucial to document reperfusion of the IRA as soon as possible. Unfortunately, there is a 25 ‘% to 30 % failure rate for thrombolytic therapy that is associated with a significantly worse prognosis; there is at least two to three times the death rate in those patients compared with patients with a patent IRA. If thrombolysis has failed to restore patency, the patient could be considered a candidate for fallback (secondary) mechanical intervention (coronary angioplasty or surgical revascularization). It is therefore highly desirable to find a means of documenting the success of thrombolytic therapy in a timely fashion. Coronary angiography was established as the “gold standard” for assessing IRA patency in the early studies of intracoronary streptokinase.6, 7 However, the standard of care was changed with the develop-
From
the Department
Received Reprint Cleveland 411/38403
for publication requests: Clinic
of Cardiology, Jan.
14, 1992;
The Cleveland accepted
Clinic March
Foundation. 2, 1992.
Eric J. Topol, MD, The Department of Cardiology, The Foundation, 9500 Euclid Ave., Cleveland, OH 44106.
Ohio
ment of intravenous thrombolytic agents with patency rates equivalent to those of intracoronary streptokinase.8, g Thrombolytic therapy could now be given without the necessity of coronary angiography, and indeed routine angiography may be undesirable in the setting of acute myocardial infarction, as demonstrated by the Thrombolysis In Myocardial Infarction (TIMI) study group.” Since angiography is no longer routinely performed, noninvasive markers have been sought to document reperfusion. There are a number of noninvasive methods that have been proposed to verify the patency of the IRA. The purpose of this review is to discuss the methods available, and the advantages and limitations of each method. BEDSIDE/CLINICAL
DETERMINANTS
Several noninvasive markers can indicate reperfusion after thrombolytic therapy with a reasonable degree of accuracy. As long as 50 years ago, noninvasive markers such as resolution of ST segment shifts on electrocardiography or the development of an accelerated idioventricular rhythm, were observed in experimental animals. l1 These markers are observed in humans as well, and are still reported in the current literature as signs of reperfusion. Saran et a1.12 used the percent reduction in ST segment elevation to predict IRA patency. When the ST segment elevation fell by less than 25 % of the baseline value, persistent coronary occlusion was likely, with a predictive accuracy of 86%. Califf et all3 found that complete resolution of ST-T wave changes was associated with a 96% patency rate on go-minute angiograms after thrombolytic therapy, but that this occurred in only 6 % of patients. Recent reports focus on electrocardiographic signs of reperfusion, either by frequently recorded 12-lead-electrocardiograms (ECGs), or by continuous ST segment shift monitoring and analysis (Figs. 1 and 2). The Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) 7 trial14 recently reported that when compared with other clinical variables, ST segment digital trend recovery has provided the vast majority of information concerning IRA patency. Continuous vectorcar441
442
Arnold and Top01
American
August 1992 Heart Journal
Fig. 1. Continuous ST segmentmonitoring in a patient with successfulreperfusion. Resolution of ST segment elevation in the anterior leads is documented over time.
ABBB
B
Fig. 2. Continuous ST segmentmonitoring in a patient with initially successfulreperfusion (A) and intermittent occlusion of the infarct-related artery (B).
diography using a computerized monitoring system (MIDA 1000, Ortivus Medical, Taby, Sweden) for on-line dynamic analysis of QRS complex and ST segment changes has been used successfully by Dellborg et a1.15 to accurately predict reperfusion. Of 21 patients analyzed who had thrombolytic therapy or angioplasty for acute myocardial infarction, 16 had a patent IRA and five had persistent occlusion at the time of emergency angiography. Using vectorcardiography analysis (Fig. 3), the authors correctly identified 15 of 16 patients with a patent IRA and five of six with persistent occlusion (sensitivity, 94%; specificity, 80 5%). Some authors have found reperfusion arrhythmias to be a marker for IRA patency,16 while other investigators have not found it to be as reliable.17q l8 In 386 patients treated with tissue plasminogen activator (TPA) for acute myocardial infarction in the TAMItrial, ventricular tachycardia, ventricular fibrillation,
second- and third-degree heart block, and severe sinus bradycardia were all documented with similar frequencies following thrombolytic administration. None of the arrhythmias recorded, however, were associated with rates of reperfusion any higher than 77% (range: 64% for second-degree heart block to 77% for ventricular fibrillation).13 It therefore appears that bedside or clinical parameters are severely lacking in accuracy to detect patients who have failed reperfusion, or even to identify patients at high risk for recurrent spontaneous ischemia after thrombolysis.ig LABORATORY
DETERMINANTS
Early peaking of the total creatine kinase (CK) level and the CK-MB isoenzyme have identified patients with successful reperfusion after streptokinase therapy,6, 2o but the delay in laboratory determination and the number of patients not accurately iden-
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0.200 mV. 40.
4
8 hours
Fig. 3. Pharmacologic reperfusion. Print-out directly from the computer screenof a trend analysis of a trend curve showingchangesin the ST vector magnitude and in the QRS vector difference over time. This patient has an acute inferior myocardial infarction. Acute coronary angiography after 25 minutes of vectorcardiographic monitoring showedTIMI grade 3 flow in the right coronary artery. Arrow indicates first injection of contrast material. (Reprinted with permissionof the American Heart Association).
tidied by this method make it a less desirable marker of IRA patency. Recent reports have focused on the use of peak serum myoglobin to detect coronary reperfusion. Dillon et al.“’ analyzed plasma myoglobin (Mb) concentration-time curves and the results of immediate angiography in 20 patients with acute myocardial infarction undergoing attempted reperfusion. They concluded that their mathematical model allowed the prediction of successful reperfusion with an overall predictive accuracy of 95% and was reliably estimated from two samples drawn within 60 minutes of therapy.21 OthersZ2 have reported similar results monitoring peak serum Mb concent,ration as a marker for reperfusion. Although the Mb concentration is a useful marker and can be assayed quickly (10 minutes by latex agglutination turbidmetry) in certain laboratories, there are still patients who will not be diagnosed as thrombolytic failures by these methods.2” NUCLEAR IMAGING Thallium-201 imaging. While thallium-201 imaging has been used as a marker for early reperfusion as well asto quantify myocardial salvage,24it has several important limitations. The most significant is the delay in administering thrombolytic therapy to obtain initial images. Also, the hyperemic phase of reperfusion affects the distribution of the tracer,
which tends to concentrate thallium in the infarct area if given too soon after reperfusion. Delayed redistribution also makes it difficult to distinguish persistently ischemic myocardium from scar tissue,2” which has important implications for treatment. Thallium-201 combined with intracoronary technetium 99m (Tc-99m) pyrophosphate can predict myocardial salvage after intracoronary thrombolysis, but this requires an invasive approach and is not preferred over angiography to determine IRA patency.26 Technetium-99m stannous pyrophosphate imaging. Wheelan et a1.27used early and late Tc-99m stannous pyrophosphate (PPi) as a marker of reperfusion after thrombolytic therapy. They reported that strongly positive early Tc-99m-PPi images were as reliable as early peaking CK-MB fractions in predicting reperfusion. In the 78% of their patients with early peaking CK-MB fractions, the majority (91 ?C.) also had strongly positive scans suggesting reperfusion. None of the control patients had early CK-MB peaks, and none had positive PPi scans. These results were confirmed by Hashimoto et a1.,‘8 who accurately detected 89 7;’ of patent IRAs as confirmed by angiograms performed several weeks after acute myocardial infarction. None of their patients with unsuccessful reperfusion by angiography had positive scans. This degree of accuracy was achieved with
Augusl
444
Table
Arnold
and
Top01
American
I. Characteristics
of noninvasive
markers
of reperfusion
Method
after thrombolytic
Advantages
therapy
1992
Heart Journal
_____ Limitations
Electrocardiography
ST segment resolution Reperfusion arrhythmia Continuous ST segment monitoring
Readily available, inexpensive Readily available, inexpensive Highly accurate
Limited accuracy Low specificity Not readily available, special equipment
Easily obtained Estimates reperfusion in 60 minutes
Time delay Needs further validation
Available in most hospitals
Time delay for initial images Reperfusion hyperemia affects distribution Delayed redistribution affects interpretation Inferior wall imaging limited
Chemical
Creatine kinase-MB Peak serum myoglobin Nuclear
imaging
Thallium-201
Technetium Magnetic
99-isonitrile
resonance
imaging
No time delay for images No redistribution (MRZ)
Tissue characterization
Conventional
Gadolinium Cine-MRI
enhanced
Altered T2 images, long imaging times, metallic prostheses, arrhythmia interference with gating Similar to conventional MRI Similar to conventional MRI
Better tissue characterization High spatial resolution, low acquisition time, superior temporal resolution
Echocardiography
Regional wall motion
Readily available, bedside imaging
Transmitral Doppler Sonicated albumin
Readily available, bedside imaging Perfusion study, enhanced images
From Dellborg
M, Top01 EJ, Swedberg
K. AM HEART
Abnormality may persist several days after reperfusion Accurate in 256 of patients Not widely applied
J 1991;122:943-8
emission computed tomography (CT) imaging, which corrects for adjacent osseous activity to obtain better quality images when compared with conventional planar scanning. Technetium-99m hexakis-2-methoxy-2-isobutyl-isonitrile imaging. A radiopharmaceutical recently
used in reperfusion imaging is technetium-99m-hexakis2-methoxy-2-isobutyl-isonitrile (Tc-99-isonitrile), which is distributed in proportion to myocardial blood flow. Advantages include the virtual lack of redistribution, so it can be given immediately before thrombolytic therapy without the delay of obtaining initial images, as with conventional thallium-201 imaging. Scans done several hours later will still reflect the prethrombolytic anatomy. Also, because it has a higher energy peak (140 keV), its image is superior to that of thallium-201 (except when the inferior left ventricular wall overlaps the liver, which limits interpretation). 2g IRA patency can be indirectly as-
sessed several hours after thrombolytic therapy with the administration of a second dose of isotope. Several studies30-32 have documented the effectiveness of this radiopharmaceutical to assess the extent of jeopardized myocardium and subsequent myocardial salvage after thrombolytic therapy. NUCLEAR
MAGNETIC
RESONANCE
IMAGING
Magnetic resonance imaging (MRI), with its unique ability to characterize tissue, has the potential to delineate normal from ischemic myocardium after reperfusion. The edema associated with myocardial infarction and necrosis, prolongs relaxation times Tl and T2, therefore altering the intensity of the myocardial signal. With the prolonged relaxation times, the T2 weighted images result in a loss of signal with decreased delineation of normal myocardium. This loss results in longer imaging times and lower specificity for conventional MRI.
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Gadolinium-DTPA (diethylene triamine pentaacetic acid) enhances differences between normal and infarcted tissue and makes MRI a more useful technique. Although this enhanced difference with gadolinium was more evident ex vivo, gadolinium-DTPA images may play a role in post-thrombolytic assessment of IRA patency.33 Van Rossum et a1.34studied 19 patients with gated MRI using gadolinium-DTPA 47 to 72 hours after the onset of myocardial infarction. The results were compared with coronary angiograms taken just before the MRI scan. Contrast ratios of the signal intensity of infarcted tissue to normal tissue were constructed. Although the maximum contrast ratios (infarct tissue/normal) were not different between patients with a patent IRA compared with those with persistent occlusion, the contrast ratio as a function of time did identify patent IRAs. The authors admit, however, that the number of patients studied was small and that clinical use was limited by overlap between contrast ratios. In contrast, Van der Wall et a1.35reported that gadolinium-DTPA-enhanced MRI could not accurately identify patients in whom thrombolytic therapy was successful. While this technique may prove useful in the future, MRI imaging is less accurate than other available methods and poses logistic problems that prohibit its widespread application. Cine-MRI has been studied to detect left ventricular functional characteristics after successful reperfusion. The technique has a high spatial resolution, a shorter acquisition t,ime, and superior temporal resolution when compared with spin-echo MRI. As of yet, however, it has not been widely used to predict IRA patency. Several limitations of tine-MRI, such as metallic hardware in the patient that precludes examination, the inaccuracy of imaging with cardiac dysrhythmias, and the length of time required for examination in critically ill patients36 currently make this technique less than optimal. ECHOCARDIOGRAPHY
Echocardiography is useful in evaluating regional wall motion abnormalities after myocardial infarct,ion, and in evaluating myocardial salvage after t.hrombolytic treatment. Broderick et a1.37noted wall motion abnormalities in all patients before the administration of thrombolytic therapy, and found that 80”;. showed improvement in the IRA subserved segments at the time of late study (3 days later). In the patients whose regional wall motion scores did not improve, most required additional intervention with angioplasty or coronary artery bypass surgery.
Assessing reperfusion
after thrombolysis
445
Because of the postischemic improvement in left ventricular contractile function that occurs over several days, conventional echocardiography may not be an adequate method to assess the initial success of reperfusion with thrombolytic agents. Touchstone et a1.38 found that 75% of their patients treated with intravenous streptokinase had a patent IRA several hours later, but only 45 % had echocardiographic evidence of improvement in regional wall motion. In the remainder, improvement occurred up to 10 days later. Oh et a1.3g at the Mayo Clinic reported echocardiographic improvement in wall motion abnormalities in 29% of patients who had successful reperfusion, but also in 11% of patients who did not reperfuse after lytic therapy. While in some patients who reperfuse improvement in wall motion can be detected as early as 24 hours after thrombolytic therapy,40 this does not appear to be a sufficiently sensitive marker of reperfusion. Feigenbaum41 has advocated the use of digital recording of the echocardiogram, with a storage system in the intensive care unit that allows for easy retrieval and the creation of a continuous-loop display of several images. These can be compared with baseline studies to observe subtle changes after thrombolytic therapy.41 Myocardial perfusion imaging with the use of sonicated albumin may increase the diagnostic accuracy of establishing reperfusion with echocardiography, but this technique is not widely applied.42, 43 Left ventricular diastolic filling, as measured by transmitral Doppler flows, has also been studied as a method to assess reperfusion. If reperfusion occurs, there should be improvement in left ventricular diastolic filling, detected by echo-Doppler measurements of transmitral flows. Masuyama et a1.,44 however, were able to show improvement in left ventricular diastolic filling via pulsed Doppler echocardiography in only 25% of patients in whom the IRA was patent. Ultrasonic tissue characterization with conventional two-dimensional echocardiography can define ventricular wall motion abnormalities. The hypothesis is that pathologic changes of the myocardium, such as those produced by acute myocardial infarction, alter the physical properties of the tissue. These alterations can then be quantified by frequency-dependent ultrasonic attenuation and backscatter. Milunski et a1.45 used this technique to determine if ultrasonic tissue characterization could identify acute myocardial infarction, and if the early effects of reperfusion were reflected accordingly. They found that patients with documented IRA patency had a characteristic increase in the cyclic variation in sig-
446
Arnold
and Topol
nals over time, whereas there was no such recovery in patients with an occluded IRA. While this technique requires some modification of the conventional echocardiographic equipment, it may be a useful modality in detecting reperfusion. CONCLUSIONS
Thrombolytic therapy conclusively decreases the mortality associated with acute myocardial infarction. Still, between 25 ‘% and 30 6%of patients are not successfully reperfused. Interventions that can restore IRA patency can be implemented if patients can be identified who did not reperfuse with thrombolytic treatment. Several noninvasive techniques can assist in this determination (Table I), but as of now the “gold standard” remains coronary angiography. We need to continue to evaluate and refine noninvasive modalities to identify patients who are candidates for further intervention. SUMMARY
The benefits of thrombolytic therapy in reducing the mortality associated with acute myocardial infarction are well documented. Presumably, this is on the basis of a patent IRA, although other mechanisms may be involved. Because there is a 25 % to 30 ‘% failure rate for thrombolytic therapy that is associated with a significantly worse prognosis, it is crucial to document reperfusion in a timely fashion. In cases of failure to reperfuse, the patient could be considered a candidate for secondary mechanical intervention. While coronary arteriography is presently the “gold standard” to document reperfusion, this is an invasive procedure associated with small but defined risks for the patient. A noninvasive marker that is readily available and highly accurate is most desirable. There are a number of methods currently used to document coronary reperfusion noninvasively. This review discusses the advantages and disadvantages of each method, and the need for continued evaluation and refinement in noninvasive modalities to identify patients who are candidates for further intervention.
Amemzan
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6.
7.
8.
9.
10.
Il. 12.
13.
14.
15.
16.
17.
18.
19. REFERENCES
1. DeWood MA, Spores J, Notske R, et al. Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction. N Engl J Med 1980;303:897-902. 2. Second International Study of Infarct Survival (ISIS-2) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both or neither among 17,187 cases of suspected acute myocardial infarction. ISIS-2. Lancet 1988;2:349-60. 3. Kennedy JW, Martin GV, Davis. KB, et al. The Western Washington intravenous streptokinase in acute myocardial infarction trial. Circulation 1988:77:345-52. 4. GruppoItalianoperloStudiodellaStreptochinasinell’Infarcto
20.
21.
22.
August 1992 Heart Journal
myocardio (GISSI). Effectiveness of intravenous thrombolyt 1: treatment in acute myocardial infarction. I,ancet 1986;1:3% 401. De Chillou C. Sadoul N. Briancon S, Aliot E. Factors determining the occurrence of late potentials on the signal averaged electrocardiogram after a first myocardial infarction: a multi variate analysis. J Am Co11 Cardiol 1991;18:7638-42. Ganz W, Buchbinder N, Marcus H, et, al. Intracoronary thrombolysis in evolving myocardial infarction. A.M HEART J 1981;101:4-13. Rentrop R, Blank H, Karsch JR, et al. Selective intracoronary thrombolvsis in acute mvocardial infarction and unstable angina pectoris. Circulation 1981;63:307-17. Verstraete M, Bory M, Collen D. et al. Randomized trial of intravenous recombinant tissue-type plasminogen activator versus intravenous streptokinase in acute myocardial infarction. Lancet 1985;1:842-7. Chesebro JH, Knatteud G, Roberts R, et al. Thrombolysis In Myocardial Infarction (TIMI) trial. Phase I. A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142-54. TIM1 Research Group. Immediate versus delayed catheterization and angioplasty following thrombolytic therapy for acute mvocardial infarction. JAMA 1988;260:2849-58. Tennet R, Wiggers CJ. The effect of coronary occlusion on myocardial contraction. Am J Physiol 1935;112:351-61. Saran RK, Been M, Furniss SS, et al. Reduction in ST segment evaluation after thrombolysis predicts either coronary reperfusion, or preservation of left ventricular function. Br Heart .J 1990;64:113-7. Califf RM. O’Neill WW, Stack RS, Aronson L, Mark DB. Mantel1 S, George BS, Candela RJ, Kereiakes DJ, Abbottsmith CH, Top01 EJ. Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988;108:658-62. Krucoff MW, Wagner BL, Sigmon KN, O’Connor CM, Granger CB, Kereiakes DJ, George BS, Wall TC, Samaha JK, and the TAM1 7 Study Group. The relative roles of clinical variables and continuous ST segment monitoring for “real time” noninvasive detection of reoerfusion in the TAM1 7 Trial IAbstract]. Circulation 199i;84:11-117. Dellborg M, Top01 EJ, Swedberg K: Dynamic QRS complex and ST segment vectorcardiographic monitoring can identify vessel patency in patients with acute myocardial infarction treated with reperfusion therapy. AM HEART ,J 1991$X: 943-8. Goldberger S, Greenspon AJ, Urban PL, Muza B, Berger B: Reperfusion Arrhythmia: a marker for restoration of antegrade flow during intracoronary thrombolysis for acute myocardial infarction. AM HEART J 1983;105:26-32. Miller FC, Krucoff MW. Satler LF, Green CE, Fletcher RD, DelNegro AA, Pearle DL, Kent KM, Rackley CE. Ventricular arrhythmia during reperfusion. AM HEART J 1986;112:928-32. Kircher BJ, Top01 EJ, O’Neill WW, Pitt B. Prediction of infarct artery recanalization after intravenous thrombolytic therapy. Am J Cardiol 1987;59:513-5. Muller DW, Top01 EJ, Ellis SG, Woodlief LH. Sigmon KW, Kereiakes DJ, George BS, Worley SJ, Samaha JK, Phillips H, Califf RM. Determinants of the need for early acute intervention in patients treated conservatively after thrombolytic therapy for acute myocardial infarction. J Am Co11 Cardiol 1991;18:1594-601. Schwartz F, Schuler G, Katus M, et al. Intracoronary thrombolysis in acute myocardial infarction: correlations among serum enzyme, scintigraphic, and hemodynamic findings. Am J Cardiol 1982;50:32-8. Dillon GA, Ellis AK, Klocke FJ. Rapid determination of coronary reperfusion in acute myocardial infarction patients using myoglobin kinetics [Abstract]. Circulation 1991;(suppl 18):11-115. Clemmensen P, Jurlander B, Grande P, Ohman EM, Wagner GS. Monitoring peak serum-myoglobin for noninvasive pre-
Volume Number
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33
34.
124 2
diction of coronary reperfusion in patients [Abstract]. Circulation 1991;(suppl 18):11-117. Ishii J, Nomura M, Ando T, Hasegawa H, Kimura M, Tateishi H, Kurokawa H, Kondo T, Hishida H. Early detection of coronary reperfusion based on serum myoglobin concentration [Abstract]. Circulation 1991;(suppl 18):R-117. Beller GA. Role of mvocardial nerfusion imazine in evaluatinz thrombolytic therapy for acut’e myocardial-infarction. J Am Co11 Cardiol 1987;9:661-8. Beller GA. Noninvasive assessment of myocardial salvage after coronary reperfusion: a perpetual quest of nuclear cardiology. J Am Co11 Cardiol 1989;14:874-6. Schafer .J, Mathey DG, Montz R, et al. Use of dual intracoronary scintigraphy with thallium-201 and technetium-99m pyrophosphate to predict improvement in left ventricular wall motion immediately after intracoronary thrombolysis in acute myocardial infarction. J Am Co11 Cardiol 1983;2:737-44. Wheelan K, Wolfe C, Corbett J, et al. Early positive technetium-99m stannous pyrophosphate images as a marker of reperfusion after thrombolytic therapy for acu: e myocardial infarct ion. Am J Cardiol 1985,56:252-6. Hashimoto T, Kamhara H, Fudo .T,- et. al; Early estimation of acute myocardial infarct size soon after coronary reperfusion using emission computed tomography with technetium-99m pyrophosphate. Am 3 Cardiol 1987;60:952-7. Pfisterer M, Muller-Brand J, Spring P, et al. Assessment of the extent of jeopardized myocardium during acute coronary occlusion followed by reperfusion in man using techetium99m isonitrile imaging. AM HEAK~ J 1991;122:7-12. Pellikka PA, Behrenbeck T, Verani MS, et al. Serial changes in myocardial perfusion using tomographic technetium-99mhexakis-2-methoxy-2-methylpropyl-isonitrile imaging following reperfusion therapy of myocardial infarction. J Nucl Med 1990::0:1269-75. Christ.ian TF, Gibbons RJ, Gersh BJ. Effect of infarct location on myocardial salvage assessed by technetium-99m-isonitrile. .J Am Call Cardiol 1991;17:1303-8. Behrenbeck T, Pellikka PA, Huber KC, et al. Primary ar,gioplasty in myocardial infarction: assessment of improved myocardial perfusion with technetium-99rh iionitrile. d Am Co11 Cardiol 1991;17:365-72. DeRoos A, Van Rossum AC, Van der Wall E, et al. Reperfused and nonreperfused myocardial infarction: diagnostic potential of Gd-DTPA enhanced MR imaging. Radiology 1989;172:71720. Van Rossum AC, Visser FC, Van Eenige MJ, et al. Value of gadolinium-diethylene-triamine-pentaacetic acid dynamics in
Assessing reperfusion
35.
36.
37.
38.
39.
40.
41. 42.
43.
44.
45.
after thrombolysis
447
magnetic resonance imaging of acute myocardial infarction with occluded and reperfused coronary arteries after thrombolysis. Am J Cardiol 1990;65:845-51. Van der Wall EE, Van-Dijkman PRM, DeRoos A, et al. Diagnostic significance of gadolinium-DTPA (diethylene-triaminepen&acetic acid) enhanced magnetic resonance imaging in thromholytic treatment for acute myocardial infarction: its potential in assessing reperfusion. Br Heart J 1990;63:12-7. Meese RB, Sprinter CE, Negro-Vilar R, et al. Detection, characterization and functional assessment of reperfused Q-wave acute myocardial infarction by tine magnetic resonance imaging. Am J Cardiol 1990;66:1-9. Broderick TM, Bourdillon PDV, Ryan T, et al. Comparison of regional and global left ventricular function by serial echocardiograms after reperfusion in acute myocardial infarction. J Am Sot Echocardiogr 1989;2:315-23. Touchstone DA, Beller GA, Nygaard TW, et al. Effects of successful intravenous reperfusion therapy on regional myocardial function and geometry in humans: a tomographic assessment using 2-D echocardiography. J Am Co11 Cardiol 1989;13: 1506-13. Oh JK, Gersh BJ, Nassef LA. et al. Effects of acute reperfusion on regional myocardial function: serial two-dimensional echocardiography assessment. Int J Cardiol 1989;22:161-8. Bourdillon PDV, Broderick TM, Williams ES, et al. Early recovery of regional left ventricular function after reperfusion in acute myocardial infarction assessed by 2-dimensional echocardiography. Am J Cardiol 1989;63:641-6. Feigenbaum H. Role of echocardiography in acute myocardial infarction. Am J Cardiol 1990;66:17H-22H. Reisner SA, Ong LS, Lichtenberg GS, et al. Myocardial perfusion imaging by contrast echocardiography with use of intracoronary sonicated albumin in humans. .J Am Co11 Cardiol 1989;14:660-5. Meerbaum S. Promise and status of myocardial contrast enhanced 2-dimensional echocardiography: delineation of ischemic risk zone and quantitation of myocardial perfusion defects. J Am Co11 Cardiol 1986;7:395-6. Masuyama T, Kudama K, Lee JM, Nanto S, Kitabatake A, Kamada T. Effects of coronary angioplasty on left ventricular diastolic filling in patients with old myocardial infarction: a study of pulsed Doppler echocardiography. Eur Heart J 1991;12:34-8. Milunski MR, Mohr GA, Perez JE, et al. Ultrasonic tissue characterization with integrated backscatter: acute myocardial ischemia, reperfusion, and stunned myocardium in patients. Circulation 1989;80:491-503.
