(Circulation. 2000;101:101.)
© 2000 American Heart Association, Inc.
Current Perspective |
Infarct Size Measured by Single Photon Emission Computed Tomographic Imaging With 99mTc-Sestamibi
A Measure of the Efficacy of Therapy in Acute Myocardial Infarction
From the Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minn.
Correspondence to Raymond J. Gibbons, MD, E16A, Mayo Clinic, 200 1st St SW, Rochester, MN 55905.
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Abstract |
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 Top Abstract IntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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Background—Use of mortality as an end point in randomized trials of reperfusion therapy requires increasingly large sample sizes to test advances compared with existing therapy, which is already highly effective. There has been a growing interest in infarct size measurements by 99mTc-sestamibi SPECT (single photon emission computed tomographic) imaging as a surrogate end point.
Methods and Results—We reviewed the reports published in English regarding infarct size measurements by 99mTc-sestamibi. Four separate lines of published evidence support the validity of SPECT imaging with 99mTc-sestamibi for determination of infarct size. This end point has been used in a total of 7 randomized trials—1 single center and 6 multicenter. The end point compares favorably with left ventricular function and infarct size measurements with the use of other radiopharmaceuticals. The most important limitation of this approach is the absence thus far of a randomized trial that has shown a corresponding decrease in mortality in association with a therapy that reduces infarct size.
Conclusions—SPECT imaging with 99mTc-sestamibi is the best available measurement tool for infarct size. It has already served as an end point in early pilot studies to evaluate potential efficacy and in dose-ranging studies. It has the potential to serve as a surrogate end point to uncover advantages of new therapies that may be equivalent to existing therapies with respect to early mortality.
Key Words: infarction • radioisotopes • tomography
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Introduction |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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Multiple end points, including global left ventricular function,1 regional left ventricular function,2 early arterial patency,3 and clinical outcomes,4 have been used in various randomized trials as measures of the efficacy of reperfusion therapy in acute myocardial infarction. Clearly, the most important clinical outcome is that of patient mortality, which has formed the basis for multiple megatrials comparing thrombolytic agents with placebo and with each other. However, use of mortality as an end point requires increasingly large sample sizes (Figure 1
) to test advances compared with
existing therapy, which is already highly effective. Such very large
sample sizes limit the number of new therapies that can be tested and
impose prohibitive financial barriers on the early testing of
potentially promising therapies. End points that are potential
"surrogates" for both early and late patient mortality are
therefore attractive for several purposes: (1) to conduct very early
pilot studies to demonstrate potential efficacy of a new agent, (2) to
serve as end points for dose-ranging studies to select the "best
dose" of a new agent, and (3) to indicate a possible late mortality
benefit for a new therapy that may be "equivalent" to existing
therapy with respect to early mortality.
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As existing therapy improves, the third possibility may become more likely. It will be increasingly difficult to demonstrate an advantage in early mortality, even if one really exists, because of the decreasing mortality with existing therapy and the distinct possibility that the deaths that still occur in acute myocardial infarction may be related to phenomena that cannot be altered by reperfusion therapy. For example, some patients may die of embolic complications (cerebral or pulmonary) that are unrelated to therapy. Thus, at least a portion of the existing low mortality with reperfusion therapy may reflect an "irreducible foundation" of early mortality that is unlikely to be prevented with any new therapy.
In contrast, a new therapy might still reduce left ventricular damage and infarct size. Such a reduction might have favorable consequences for mortality over a much longer term (perhaps 5 to 10 years) than the short term (30 days) that has been used to date for megatrials of acute reperfusion therapy. Maintenance of a scientifically meaningful protocol over the long term to assess 5-year mortality in a megatrial (of 30 000 patients) would be extremely difficult. However, early measurements showing a reduction in infarct size are much more feasible and may indicate a potential benefit in late mortality.
There has been a growing interest in infarct size by 99mTc-sestamibi single photon emission computed tomographic (SPECT) imaging as a surrogate end point for all 3 purposes listed earlier. Multiple animal studies have supported the premise that measurement of the acute myocardial perfusion defect by injection of sestamibi during coronary occlusion provides an indication of myocardium at risk.5 Similarly, animal studies have consistently demonstrated that injection of sestamibi after coronary reperfusion permits measurement of infarct size.6 Treatment efficacy can be assessed either by measuring both the acute and final perfusion defect to estimate myocardial salvage or more simply by measuring the final perfusion defect to assess infarct size.7 The earliest clinical study using sequential imaging8 demonstrated a treatment effect from thrombolytic therapy in a very small, uncontrolled series of only 12 patients, demonstrating its potential statistical power. Sample size estimates are available7 with either myocardial salvage or infarct size used to assess treatment efficacy.
This review is intended to summarize the evidence to date supporting the validity of sestamibi infarct size as a measure of the efficacy of reperfusion therapy in human myocardial infarction.
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Evidence Supporting the Validity of SPECT Infarct Sizing |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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Multiple lines of evidence now support the validity of SPECT imaging with 99mTc sestamibi for determination of infarct size:
1. There is close association between this measurement and other
parameters that have traditionally been used clinically to
estimate infarct size. Table 1
summarizes the published comparisons of SPECT sestamibi infarct size
and multiple other parameters, including global left
ventricular function (ejection fraction),8 9 10
end systolic volume,11 regional left
ventricular function (regional wall
motion),8 9 creatine kinase release,12 and
201Tl infarct size.13 Figure 2 shows the relationship between
sestamibi infarct size measured at discharge and end-systolic
volume of the left ventricle measured 1 year later by electron-beam CT
imaging.11 Despite the potential confounders of
cardiomyopathic processes, ventricular
loading conditions, and intervening silent reinfarction, the
association between these 2 measures is quite strong.
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2. There is close association between SPECT sestamibi infarct size and
actual fibrosis in human hearts. Medrano et al14 have
reported a close correlation between the actual amount of pathological
fibrosis in human hearts explanted at the time of cardiac
transplantation from patients with ischemic heart disease and
the perfusion defect measured by ex vivo SPECT imaging after
intravenous in vivo injection of
99mTc sestamibi (Figure 3). They reported excellent correlation
(r=0.94) between their polar map technique (used in Figure 3) and a fixed threshold of 60% of peak counts (used by our
laboratory). The regression line in Figure 3 is shifted upward
from the line of identity, indicating that sestamibi imaging slightly
overestimated the amount of fibrosis, presumably because some
hibernating myocardium was misclassified as infarcted.
However, in this highly selected series of patients with severe left
ventricular dysfunction, hibernating myocardium
should be more prevalent than in less selected patients. Because the
mean overestimate by sestamibi in these highly selected patients was
only 8% of the left ventricle, the error in less selected patients
should be even smaller. These published data on fibrosis have been
confirmed by 2 studies that used myocardial biopsies at the time of
CABG.15 16
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The relationship between the sestamibi SPECT perfusion defect and
fibrosis demonstrated in these studies is superior to that previously
reported for regional wall motion (Table 2). The data in these 4 studies are
voluminous and beyond the scope of this article. Contrast left
ventriculography, radionuclide angiography, and 2-dimensional
echocardiography have all been shown to have a
significant major error rate; at least 15% of segments judged to be
akinetic or dyskinetic have proved not to have major fibrosis on
pathological examination. Two-dimensional
echocardiography, which should be the optimal
modality because of its tomographic properties, has a reported
correlation coefficient of only 0.53 between regional wall motion
assessment and fibrosis.20
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3. Sestamibi uptake predicts the response of myocardial regions with
abnormal function to subsequent revascularization.
201Tl has commonly been used to assess myocardial
viability. As shown by Medrano et al,14
99mTc-sestamibi might be expected to misclassify
viable myocardial segments with decreased resting blood flow as
infarcted. In a series of 31 patients with left ventricular
dysfunction, Udelson et al21 compared regional sestamibi
activity (as a percent of peak counts) with 201Tl
activity (as a percent of peak counts) determined on a redistribution
image after a resting 201Tl injection (Figure 4). The overall correlation between the 2
radiopharmaceuticals with respect to regional activity was highly
significant (r=0.78). More importantly, the regional
ventricular function of these segments was assessed by
2-dimensional echocardiography both before and
after subsequent coronary revascularization
with either PTCA or CABG. Segments that were abnormal at baseline and
improved after revascularization had higher initial
values of both sestamibi and thallium. Segments that were abnormal at
baseline and did not improve after
revascularization had lower initial uptake of both
radiopharmaceuticals. A value of 60% of peak counts on resting
sestamibi imaging separated those segments with reversible dysfunction
(which were presumably viable at baseline) from those segments with
irreversible dysfunction (which were presumably fibrotic at baseline).
This 60% threshold is the same threshold developed independently by
our laboratory to separate infarct from viable tissue.
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These findings were confirmed by Maes et al.15 Although the optimal sestamibi threshold for predicting functional improvement was 50% in their study, a 60% threshold did nearly as well.
4. Sestamibi infarct size is associated with subsequent patient
mortality. Miller et al22 reported a 2-year follow-up of
274 patients at the Mayo Clinic (86% with reperfusion therapy) who
underwent predischarge imaging with sestamibi to measure infarct size
(Figure 5). The measured infarct size in
this series was quite small, with a median of 12% of the left
ventricle. Approximately 25% of the patients had no measurable infarct
by this technique, which is valid down to about 3% to 4% of the left
ventricle.23 Despite the low 2-year mortality rate of 3%,
sestamibi infarct size was highly associated with both overall
mortality (
2=8.66, P=0.003) and
cardiac mortality (2=11.89,
P<0.001). Miller et al24 have also shown
a significant association between sestamibi infarct size at discharge
and 1-year mortality in a separate multicenter study of 249 patients.
These published data from relatively small patient series have been
confirmed by preliminary data from Burns et al,25 who have
demonstrated a similar association between discharge sestamibi infarct
size and 6-month mortality in a much larger series of 1184
patients.
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Experience With SPECT Sestamibi Imaging in Clinical Trials |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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Measurement of myocardial salvage and infarct size by 99mTc-sestamibi has now been used as end points in several randomized trials, discussed below.
1. A randomized trial comparing tissue plasminogen activator and PTCA.26 In this single-center trial, there was no detectable difference in myocardial salvage assessed by sestamibi between the 2 therapies. After adjustment for baseline inequalities, the difference in myocardial salvage was 0% of the left ventricle, with 95% confidence limits of ±6% of the left ventricle. There was also no difference between the 2 therapies with respect to ejection fraction at discharge or 6 weeks.
2. A pilot study assessing the potential efficacy of poloxamer-188 as
adjunctive therapy in patients receiving thrombolytic
therapy.27 In this randomized, multicenter trial of 114
patients, poloxamer-188–treated patients demonstrated a 38% reduction
in median myocardial infarct size compared with placebo (Figure 6) and a 13% improvement in median
ejection fraction.
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3. A pilot study of poloxamer-188 used as adjunctive therapy with PTCA.28 In this randomized, multicenter trial of 150 patients, there was no significant difference in final infarct size or ejection fraction between the poloxamer-188– and placebo-treated groups.
4. CORE (Collaborative Organization for RheothRX Evaluation) trial. This was a large (n=2948) international, multicenter, dose-ranging study29 that tested the hypothesis that poloxamer-188 plus standard therapy would improve patient outcome. Infarct size was measured with 99mTc-sestamibi as part of a substudy (n=1184). The dose of poloxamer-188 was adjusted downward during the course of the trial because of unacceptable renal toxicity. The subsequent lower doses were not associated with any significant reduction in infarct size or improvement in ejection fraction, despite a persistent increase in measured renal toxicity. Thus, the drug unintentionally targeted the kidney.
5. Pilot study comparing CY-1503 (P-selectin blocker) with placebo as an adjunct to PTCA. This multicenter, randomized trial (CALYPSO: Cylexin as an Adjunct to LYtic therapy to Prevent SuperOxide reflow injury) enrolled 150 patients with sestamibi imaging as a primary end point before termination by the data and safety monitoring committee because of lack of efficacy.
6. Single-center pilot study of 45 patients examining the efficacy of adenosine used as ancillary therapy with PTCA.30 Early predischarge images in this study did not show an increase in myocardial salvage compared with historical controls, but later (6 weeks after discharge) images did demonstrate greater myocardial salvage. Ejection fraction data were not reported.
7. Phase 2 study of the efficacy of adenosine used as ancillary therapy with thrombolysis.31 In this randomized, multicenter trial of 236 patients, the patients treated with adenosine demonstrated a significant reduction in infarct size. The benefit was striking in the prespecified subgroup of anterior infarcts; median infarct size was 45.5% of the left ventricle in the placebo group compared with 15% of the left ventricle in the adenosine group (P=0.014). Ejection fraction was not measured.
Sestamibi infarct size measurements have therefore been used to assess potential efficacy in these randomized trials and to assess the potential "best dose" in a larger dose-ranging trial (the CORE trial). In all the multicenter studies, images were acquired by each individual center but processed by a single central laboratory (Mayo Clinic). The results have generally been confirmed by similar findings with respect to ejection fraction.
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Comparison With Left Ventricular Function |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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Compared with left ventricular function measurements, perfusion imaging provides a number of advantages. Perfusion images are not influenced by the presence of arrhythmias, cardiomyopathies, valvular heart disease, or ventricular loading, which have a substantial effect on left ventricular function. Infarct sizing by perfusion imaging is less affected by the presence of myocardial stunning or hibernation.9 32 Finally, perfusion imaging permits detection of treatment benefit with much smaller sample sizes. Although a detailed discussion of this issue is beyond the scope of this article, the main advantage of infarct sizing by perfusion imaging is the absence of any variability when there is no measurable infarct, ie, when infarct size is 0%, which occurs in about 25% of the patients who have received reperfusion therapy.22 In contrast, ejection fraction measurements have a considerable variability in such patients, in whom the normal ejection fraction ranges from 50% to 75%.
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Comparison With Other Radiopharmaceuticals |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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Infarct size has been measured in experimental models with a variety of other radiopharmaceuticals, including 201Tl, 99mTc-pyrophosphate, and indium-111 antimyosin antibody.33 Clinical studies have shown an association between these measurements and left ventricular function, cardiac enzymes, cardiac pathology, and subsequent outcome. The largest such clinical study demonstrated the prognostic value of infarct size assessed by SPECT 201Tl imaging. Cerqueira et al34 reported the 5-year survival of 618 patients enrolled in multiple studies performed by the Western Washington Trials Group. There was a highly significant association (P=0.002) between thallium infarct size and subsequent mortality.
Several studies have demonstrated that 201Tl and 99mTc-sestamibi provide similar results for determination of infarct size.21 However, 99mTc-sestamibi provides higher count images that are more accurately quantified35 and the option to do short-term imaging to assess myocardium at risk. Compared with sestamibi, infarct-avid agents (pyrophosphate and antimyosin) have the potential advantage of distinguishing new from old infarction. However, their uptake depends more on the timing of administration after the acute event, they do not allow the option of assessing myocardium of risk, and there is less experience with their use in the setting of acute reperfusion therapy. There are relatively few clinical data regarding the use of 99mTc-tetrofosmin in acute infarction. It has not been studied in experimental models. Thus, compared with other radiopharmaceuticals, sestamibi has technical advantages and has been much more extensively studied.
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Limitations of This Approach |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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This approach has 5 major limitations:
1. SPECT imaging of a beating heart has definite technical limitations for the purposes of quantification. The 2 major limitations are degradation of image quality resulting from the effects of scatter and attenuation and the partial volume effect related to severely abnormal wall motion. The threshold of 60% of peak counts used by our laboratory to identify infarction was established on the basis of cardiac phantom studies.23 It provided the highest correlation coefficient (r=0.98) and the slope of the regression line between true and measured infarct size that was closest to unity (slope=1.01). Both the correlation coefficient and slope were better with a 60% than with a 50% threshold, which theoretically should be optimal if scatter and attenuation did not exist. In a later cardiac phantom study34 that used a newer-generation gamma camera with enhanced energy resolution and hardware software to perform scatter correction, the optimal threshold proved to be 55%, closer to the theoretical ideal. The normal limits of activity distribution in the basal inferior wall may extend below the 60% threshold in some patients whose body habitus leads to greater attenuation. In a consecutive series22 of 100 overweight (89±19 kg) patients with a normal resting ECG and no history of infarction who were referred for sestamibi imaging, 81 had no measurable defect and 8 had trivial defects measuring between 1% and 3% of the left ventricle. Although the remaining 11 patients had inferior wall defects that measured between 4% and 21% of the left ventricle, 7 of these, including all 4 patients with defects of >10% of the left ventricle, had further cardiac evaluation that suggested that the measured inferior defects were real. Thus, tissue attenuation can certainly lead to "false-positive" infarctions, although these should be quantitatively small. Both of the aforementioned effects of attenuation—the nonoptimal threshold and false-positive infarctions—could theoretically be removed with attenuation correction, but this has not yet been widely applied in clinical imaging.
Regions of severely abnormal wall motion could possibly lead to partial volume effects that result in overestimation of infarct size, particularly if the infarction is large and associated with an extensive area of dyskinesia. However, a previous study36 examined the influence of gating in 29 patients 5 to 8 days after myocardial infarction. Gated images provided significantly greater estimates of infarct size (mean difference of 4%), opposite in direction to the difference expected if partial volume effects significantly influence perfusion defect size. Partial volume effects therefore appear to have minimal clinical impact.
2. Sestamibi infarct size measurements are less commonly available and more technically demanding than left ventricular function measurements. Although this is true, the availability of SPECT imaging is certainly improving. Medicare data from 1994 show that nearly 1 million SPECT myocardial perfusion imaging studies were performed nationally and that this procedure is increasing at a rate of >10%/y. Although the procedure is technically demanding, we have used a quality control study and a phantom experiment to assess the technical performance of laboratories.37 Most laboratories are capable of acquiring high-quality SPECT images of a phantom that when processed in a central laboratory, provide measured "infarct" sizes that are very closely correlated with the actual defect size, with an average absolute error of <3% of the left ventricle.37
3. There may be late recovery of myocardium which will alter the measurement of infarct size over time. Galli et al38 carefully studied 71 patients with anterior myocardial infarction by sestamibi SPECT imaging at 5 weeks and 7 months after acute infarction. Using a polar map "normal limits" technique, they reported a late decline in measured infarct size. Their study design incorporated a number of features—use of a polar map technique, restriction to anterior infarcts, and inclusion of patients who did not receive reperfusion therapy and had occluded arteries by angiography—that would be expected to produce a larger perfusion defect at 5 weeks and therefore greater potential for a late decrease. Nevertheless, the change in extent of the defect was relatively modest (6% of the left ventricle). Given the difference in measurement technique and image timing used by Galli et al, applicability of their findings to the approach we have developed is questionable. Although this late change might argue for performing perfusion imaging after a longer delay following myocardial infarction, it would probably be much more difficult from the standpoint of patient compliance and patient dropout because of deaths, recurrent infarction, or other intervening clinical events. All the data validating infarct size measurements by SPECT sestamibi described previously were based on measurements performed at the time of hospital discharge. Clearly, further data are needed on serial determinations of defect size with the use of this technique in an unselected population of postinfarction patients to determine the overall magnitude of late change.
4. No randomized trial has shown a corresponding decrease in mortality in association with a therapy that reduces infarct size. This requirement has assumed increasing importance because of the experiences with ventricular arrhythmias on ambulatory monitoring as a surrogate end point. Frequent premature ventricular contractions after myocardial infarction were known to be associated with increased subsequent mortality. Although it was hypothesized that their suppression with antiarrhythmic therapy could be used as a measure of efficacy, the CAST trial demonstrated that such therapy produced an increase rather than a decrease in mortality. The only published randomized trial to demonstrate a reduction in infarct size involved poloxamer-188, which was subsequently shown in the CORE trial29 to have unacceptable renal toxicity at the doses initially used in the pilot study.
However, randomized trial data are available that compare therapies
that did not have a demonstrable difference in infarct size (Table 3). The Mayo trial comparing tissue
plasminogen activator and PTCA mentioned
previously did not show a significant difference in infarct size
between these 2 therapies. The difference reported was 0% of the left
ventricle, with 95% confidence limits of ±6% of the left ventricle.
Although the randomized PAMI (Primary Angioplasty in Myocardial
Infarction) trial40 reported a significant, large
difference in reinfarction or death between these 2 therapies, the
larger GUSTO IIb trial (Global Use of Strategies To Open occluded
coronary arteries in acute coronary
syndromes)41 found that the differences in reinfarction
and death between these 2 therapies were significant but more modest.
The modest difference in clinical outcome data observed in GUSTO IIb
could not be excluded by the results of the Mayo trial.
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A number of observational studies using sestamibi have reported
treatment effects that are similar to those reported by a randomized
trial using mortality as an end point (Table 3
).
Myocardial salvage by sestamibi is greater with tissue
plasminogen activator than by conventional
therapy without thrombolysis (13% versus 4% of the
left ventricle, P<0.003).8 Randomized
clinical trials have clearly shown a reduction in mortality with tissue
plasminogen activator compared with
placebo.4
When patients with patent arteries after reperfusion therapy have been compared with patients with occluded arteries after reperfusion therapy, patients with patent arteries have greater myocardial salvage (17% versus 0% of the left ventricle, P<0.001) and smaller infarct size (9% versus 19% of the left ventricle, P<0.05).39 The angiographic substudy of the GUSTO trial demonstrated a reduction in mortality associated with arterial patency.42
Myocardial salvage by sestamibi is clearly greater in anterior infarcts than in inferior infarcts (24% versus 10% of the left ventricle, P<0.01).39 A meta-analysis of randomized clinical trials showed that absolute mortality reduction was greater in anterior infarcts (3.7%) than in inferior infarcts (0.9%).43 Thus, the treatment effects on salvage and infarct size demonstrated by sestamibi have generally been consistent with the effects on mortality.
5. Sestamibi infarct size is a measure of efficacy, not safety. The demonstration of efficacy by this approach requires modest sample sizes, which are clearly not large enough to detect possible increases in adverse events that occur infrequently with existing therapy. The CORE trial29 demonstrated this principle.
This limitation is most relevant to the third purpose described earlier. From a regulatory standpoint, demonstration that a new therapy is "equivalent" to existing therapy with respect to early mortality will require a reasonably sized trial of perhaps 5000 to 10 000 patients. Such a trial should have sufficient power to assess other important safety concerns (strokes, renal insufficiency) that cannot be addressed by infarct size measurements. The development of reteplase is a potential example of this approach; the RAPID (Recombinant plasminogen activator Angiographic Phase II International Dose finding study) trial3 demonstrated an advantage in patency compared with tissue plasminogen activator, and the INJECT (INternational Joint Efficacy Comparison of Thrombolytics) trial44 showed equivalence to streptokinase with respect to mortality.
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Conclusions |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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On the basis of the available scientific evidence, SPECT imaging with 99mTc-sestamibi is the best available measurement tool for infarct size in clinical medicine. It has already served as an end point in early pilot studies to demonstrate potential efficacy of new therapies. It will likely be increasingly used in dose-ranging studies. Does the available evidence justify the use of this end point as a true "surrogate" to potentially uncover advantages of new therapies that may be "equivalent" to existing therapies with respect to early mortality? When this regulatory issue was last addressed by the Food and Drug Administration in 1992, the answer was clearly "no."45 The large body of evidence that has emerged since would appear to justify a reexamination of this issue.
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Acknowledgments |
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This work was supported in part by the Dupont Merck Pharmaceutical Company, North Billerica, Mass.
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References |
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TopAbstractIntroductionEvidence Supporting the Validity...Experience With SPECT Sestamibi...Comparison With Left Ventricular...Comparison With Other...Limitations of This ApproachConclusionsReferences |
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M. T. Roe, E. M. Ohman, A. C. P. Maas, R. H. Christenson, K. W. Mahaffey, C. B. Granger, R. A. Harrington, R. M. Califf, and M. W. Krucoff Shifting the open-artery hypothesis downstream: the quest for optimal reperfusion J. Am. Coll. Cardiol., January 1, 2001; 37(1): 9 - 18. [Abstract] [Full Text] [PDF]
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A. Schomig, A. Kastrati, J. Dirschinger, J. Mehilli, U. Schricke, J. Pache, S. Martinoff, F.-J. Neumann, M. Schwaiger, and The Stent versus Thrombolysis for Occluded Coronar Coronary Stenting plus Platelet Glycoprotein IIb/IIIa Blockade Compared with Tissue Plasminogen Activator in Acute Myocardial Infarction N. Engl. J. Med., August 10, 2000; 343(6): 385 - 391. [Abstract] [Full Text] [PDF]
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