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(Circulation. 1999;99:1671-1677.)
© 1999 American Heart Association, Inc.
Clinical Investigation and Reports |
Diagnostic Marker Cooperative Study for the Diagnosis of Myocardial Infarction
From General Medicine (J.Z.) and Section of Cardiology (R.F., D.M., G.H., R.R.), Baylor College of Medicine, Houston, Tex, and Section of Cardiology (A.B., R.S.) and School of Public Health (C.-C.C.W., B.D.), University of Texas Health Science Center, Houston, Tex.
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Abstract |
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Background—Millions of patients present annually with chest pain, but only 10% to 15% have myocardial infarction. Lack of diagnostic sensitivity and specificity of clinical and conventional markers prevents or delays treatment and leads to unnecessary costly admissions. Comparative data are lacking on the new markers, yet using all of them is inappropriate and expensive.
Methods and Results—The Diagnostic Marker Cooperative
Study was a prospective, multicenter, double-blind study with
consecutive enrollment of patients with chest pain presenting to
the emergency department. Diagnostic sensitivity and
specificity and frequency of increase in patients with unstable angina
were determined for creatine kinase-MB (CK-MB) subforms, myoglobin,
total CK-MB (activity and mass), and troponin T and I on the basis of
frequent serial sampling for 
24 hours. Of 955 patients with chest
pain, 119 (12.5%) had infarction identified by use of CK-MB mass, and
203 (21%) had unstable angina. CK-MB subforms were most sensitive and
specific (91% and 89%) within 6 hours of onset, followed by myoglobin
(78% and 89%). For late diagnosis, total CK-MB activity (derived from
subforms) was the most sensitive and specific (96% and 98%) at 10
hours from onset, followed by troponin I (96% and 93%), but not until
18 hours, and troponin T (87% and 93% at 10 hours). In unstable
angina, CK-MB subforms were increased in 29.5%, myoglobin in 23.7%,
troponin I in 19.7%, and troponin T in 14.8%. All markers were
increased in 99 patients. With each marker as the
diagnostic standard, CK-MB subforms and myoglobin remained
the most sensitive for early diagnosis.
Conclusions—The CK-MB subform assay alone or in combination with a troponin reliably triages patients with chest pain and should lead to improved therapy and reduced cost.
Key Words: creatine kinase • troponin T • tropinin I • myoglobin • myocardial infarction
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Introduction |
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New markers for the diagnosis of myocardial infarction, cardiac troponin T1 and cardiac troponin I,2 and easily and rapidly performed quantitative assays for myoglobin3 and creatine kinase-MB (CK-MB) subforms4 have been developed, motivated in part by fibrinolytic therapy and angioplasty, which require an earlier, more rapid, and specific diagnosis. Fibrinolysis, within the first hour of onset, results in a 90% reduction in mortality compared with little if any reduction in mortality at 10 to 12 hours.5 In contrast, fibrinolytic therapy in unstable angina increased death and infarction.6 Thus, exclusion of infarction would also allow early administration of more appropriate therapy for unstable angina, viz, antithrombin and antiplatelet therapy.7 Another motivating factor for rapid triaging of chest pain in the emergency department is the high cost of unnecessary hospital admission, estimated at $12 billion annually.8 Risk stratification in patients with unstable angina is also rapidly becoming important as specific therapies become available.
Although several million patients present annually with chest
pain,9 only 
10% will subsequently be proven to have
infarction. Symptoms and signs do not differentiate between myocardial
infarction and ischemia in most patients, and the ECG is
diagnostic in only 40%.10 11
Unfortunately, conventional total CK-MB is not reliable in excluding
infarction until 
10 to 12 hours after onset of chest
pain.4 Accordingly, a multicenter, prospective,
double-blind study was performed in patients presenting with chest
pain to serially compare the sensitivity and specificity of all the
markers (myoglobin, CK-MB subforms, total CK-MB activity and mass, and
troponin T and I) for early and late diagnoses of infarction and to
determine the frequency with which they are increased in patients with
a clinical diagnosis of unstable angina.
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Methods |
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Study Design
A multicenter, prospective, double-blind study was performed involving Baylor College of Medicine and the University of Texas Medical School. Enrollment was consecutive 24 hours a day, 7 days per week, at 4 affiliated teaching hospitals in Houston, Tex: Ben Taub General Hospital, Hermann Hospital, The Methodist Hospital, and Veterans Affairs Medical Center. Data and statistical analyses were performed by the independent biostatistics core in the Department of Public Health at the University of Texas Health Science Center in Houston. The protocol was approved by the Institutional Review boards of the medical schools and hospitals, and signed informed consent was required for participation. Eligible enrollees had to be 21 years of age with chest pain
15 minutes suspected to be myocardial in origin
and occurring within 24 hours of presentation. Blood samples were obtained on arrival, 1 hour after arrival, every 2 hours up to 6 hours from onset of chest pain, and then every 4 hours thereafter for 24 hours. Samples were placed on ice for transport to the core laboratory. A study coordinator collected the clinical data. Results were not available to laboratory personnel. Management and disposition of the patient were determined by the attending physician. Attending physicians and investigators did not have access to results of the cardiac markers of the core laboratory. ECGs were interpreted by 2 cardiologists unaware of any results.
Assays for Cardiac Markers
Blood for CK-MB subforms was collected in EDTA,4
and the plasma was recovered; for all other markers, blood was clotted
and serum was recovered and stored at 2°C to 8°C if assayed the
same day or frozen at -20°C and assayed later. Standard controls
were assayed routinely. Total CK activity was quantified by use of a
spectrophotometric enzymatic assay (Sigma Diagnostics) with
an upper normal limit of 120 IU/L. Total plasma CK-MB mass was measured
with the Stratus CK-MB Fluorometric Enzyme Immunoassay (Dade
Intentional Inc) with an upper normal limit of 7 ng/mL. CK-MB subforms
(MB1 and MB2) and total serum CK-MB activity were quantified with the
Cardio REP CK Isoforms Procedure (Helena Laboratories) with upper
limits for MB2 of 2.5 IU/L, ratio of MB2 to MB1 of 1.6, and total CK-MB
activity of 9 IU/L. Myoglobin was determined by the Stratus Myoglobin
Fluorometric Enzyme Immunoassay (Dade International Inc) with an upper
normal limit level of 85 ng/mL. Cardiac troponin T was assayed by use
of the Cardiac Troponin T Assay (Boehringer Mannheim Corp),
which has an upper normal limit of 0.1 ng/mL. Cardiac troponin I was
assayed by the Stratus Cardiac Troponin I Fluorometric Enzyme
Immunoassay (Dade International Inc), which has an upper normal limit
of 1.5 ng/mL.
Criteria for the Diagnosis of Infarction and Other End
Points
The upper limit for an early diagnosis was arbitrarily defined
as 6 hours from onset of chest pain; late diagnosis was defined as any
subsequent time. The diagnostic standard for myocardial
infarction was a CK-MB mass 7 ng/mL and CK-MB index (CK-MB mass/CK)
2.5% determined by the results of the core laboratory in 2 samples
obtained in the first 24 hours after hospital arrival or in 1 sample if
only 1 sample was available for analysis. Unstable angina was a
clinical diagnosis determined by the investigator as chest pain
occurring at rest or with increased frequency or severity within the
prior 24 hours. Myocardial infarction was classified as Q-wave or
non–Q-wave infarction on the basis of any ECG obtained in the first 48
hours as follows: new or presumably new pathological Q wave 40 ms in
2 contiguous ECG leads; R wave 40 ms in V1
and R/S ratio 1 in V2; or loss of 25% R-wave
amplitude in 2 contiguous leads compared with a previous ECG or
documented on 2 serial ECGs. Although the criteria established
prospectively to confirm the diagnosis of myocardial infarction were
based on CK-MB detected by the mass assay, analysis was also
performed in which each marker was used as the diagnostic
standard and the relative sensitivity and specificity of the remaining
markers were determined.
Statistical Analyses
Differences in age and the proportion of men in each group were
tested with 1-way ANOVA and the 
2 test,
respectively. Sensitivity and specificity were obtained
cross-sectionally (at time period displayed ±0.5 hours). Exact 95%
CIs for binomial proportions were calculated for sensitivity and
specificity. Differences in sensitivity between the MB subforms and
myoglobin performed on the same samples were analyzed by
McNemar's test. A value of P0.05 was considered
significant. Receiver-operator characteristic (ROC) curves were
constructed for each marker, and the area under the curve was
calculated.12
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Results |
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Of the 955 patients enrolled, myocardial infarction was confirmed by CK-MB mass criteria in 119 (12.5%). Clinical characteristics of the patients are shown in Table 1
. In
the 119 patients with acute myocardial infarction confirmed by elevated
plasma CK-MB mass, the ECG was diagnostic (ST-segment
elevation) in only 45%. There were 36 patients (30.3%) who had Q-wave
infarcts; the remaining 83 had non–Q-wave infarction. Although not
prospectively planned, it is of note that the attending physicians
(blinded to the core laboratory results) made a diagnosis of myocardial
infarction based on clinical features and ECG findings in 128 patients,
38 of whom were not confirmed by CK-MB mass criteria. In 6 of these 38
patients, CK-MB mass was increased but in only 1 sample, which did not
meet the prospective criteria for infarction (2 samples); all 6 also
had increased troponin T, troponin I, CK-MB subforms, and total CK-MB
activity. Of the remaining 32 patients, 25% had increased troponin T,
34.3% had increased troponin I, 40.6% had increased myoglobin, and
65.6% had increased CK-MB subform activity. On admission, ECG findings
in these 32 patients were T-wave inversion (65.7%), ST-segment
depression (7.8%), Q waves (32.1%), and ST-segment elevation
(47.3%). Of the 119 patients with confirmed myocardial infarction, the
attending physician diagnosed 29 as having unstable angina (34.5%),
angina (6.9%), or a noncardiac cause (58.5%). The ECG findings in
these patients were ST-segment depression (34.5%), T-wave inversion
(44.8%), and ST-segment elevation (17.2%). In the 119 patients with
infarction, reperfusion therapy was administered to 34.4%:
thrombolytic therapy to 30 patients (25.2%) and
primary PTCA to 11 (9.2%).
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In Table 2, the diagnostic
sensitivity and specificity of each marker are compared with CK-MB mass
as the diagnostic standard at selected intervals from onset
of chest pain. The markers for early diagnosis, CK-MB subforms and
myoglobin, exhibited sensitivities of 91% and 78%, respectively, at 6
hours from onset, with similar specificities of 89%. In contrast,
total CK-MB mass, total CK-MB activity, and troponin I and T had
sensitivities of only 66.0%, 74.5%, 57.5%, and 61.7%, respectively.
The sensitivity and specificity of CK-MB subforms from the first sample
were 48.7% and 87.6%, respectively, which were similar to those of
myoglobin, 48.7% and 87.7%. The sensitivity and specificity of CK-MB
subforms from the combined first and second samples were 81.6% and
84.4%, respectively; for myoglobin, they were 76.3% and 83.5%. The
overall sensitivity and specificity, together with the 95% confidence
limits for each marker at 6 hours from onset, are shown in Figure 1. The results of using CK-MB subforms,
myoglobin, troponin T or I, or total CK-MB activity as the
diagnostic standard in contrast to CK-MB mass are shown in
Table 3. The CK-MB subforms were the most
sensitive diagnostic markers within 6 hours of onset of
symptoms, followed by myoglobin, regardless of which marker was used as
the diagnostic standard. It is of interest that the
sensitivities of CK-MB subforms for early diagnosis with total CK-MB
activity or cardiac troponin T as the standard were virtually identical
(82% and 84%). The specificity for early diagnosis was very high for
all markers regardless of the marker used as the standard.
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The most reliable marker for late diagnosis with the
diagnostic standard of total CK-MB mass was total CK-MB
activity, exhibiting 96% sensitivity and 98% specificity at 10 hours
(Figure 2). Troponin I exhibited a
sensitivity and specificity of 96% and 93%, but not until 18 hours
from onset. At 10 hours, troponin T had a specificity of 96% and a
sensitivity of 87%, which remained the same throughout the subsequent
interval. The sensitivities of CK-MB subforms and myoglobin decreased
significantly after 10 hours from onset of symptoms. The sensitivity
and specificity of each marker for late diagnosis with CK-MB subforms,
myoglobin, troponin T or I, or total CK-MB activity as the
diagnostic standard are shown in Table 4. There were 99 patients in whom all
markers were increased. It is noteworthy that all patients
presenting with infarction and ST-segment elevation exhibited an
increased in all markers. With CK-MB mass as the diagnostic
standard, 119 patients were identified as having an infarction compared
with 260 identified with CK-MB subforms, 170 with CK-MB activity, 231
with troponin I, 166 with troponin T, and 276 with myoglobin. Most of
these patients had a clinical diagnosis of unstable angina in which
CK-MB mass was not increased but other markers were. In 512 patients,
none of the markers was increased, and none of these patients was
diagnosed as having an infarction by the study criteria. The
specificity for total CK-MB activity, troponin I, troponin T, or CK-MB
mass was virtually identical, varying from 95% to 99% with each of
the other markers used as the standard. The specificity of the CK-MB
subforms or myoglobin was slightly less at 93% and 90%, respectively.
The total area enclosed by each ROC curve for each marker is included
in Table 5.
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The diagnosis of unstable angina was made in 203 (21.3%) patients.
Pertinent clinical characteristics are given in Table 1
. A
proportion of the unstable angina population exhibited an increase in
1 marker: CK-MB subforms were increased in 29.5%, myoglobin in
23.7%, troponin I in 19.7%, and troponin T in 14.8% (Table 6). ECG was abnormal in 67%,
consisting of T-wave inversion (69.9%), ST-segment depression
(21.3%), ST-segment elevation (27.2%), and left bundle-branch block
(0.06%) (Table 1).
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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In this multicenter, double-blind, prospective study with consecutive enrollment of 955 patients, 12.5% (119) had myocardial infarction and 21% (203) had unstable angina. The most sensitive early marker for myocardial infarction (6 hours after onset) was CK-MB subforms (91%), followed by myoglobin (78%). CK-MB subform analysis of the first sample and a second sample obtained 1 hour later accurately detected 80% of the patients subsequently confirmed to have myocardial infarction. The negative predictive value of CK-MB subforms at 6 hours was 97%, which is very important given that the probability of infarction in this population is only
10%.
The prospective diagnostic standard for myocardial
infarction was CK-MB mass, but with each marker used as the gold
standard, CK-MB subforms remained the most sensitive marker for early
diagnosis. Thus, a normal CK-MB subform at 6 hours reliably excludes
infarction. Total CK-MB (activity or mass), troponin I, and troponin T
were reliable late markers, with CK-MB activity having a sensitivity
and specificity of 96% and 98%, respectively, at 10 hours from onset;
for troponin I, sensitivity and specificity were 96% and 93%, but not
until 18 hours. In unstable angina, the markers were increased in 15%
to 30% of patients, with CK-MB subforms increased most frequently. This is the first study to compare the diagnostic accuracy of all the markers. Because laboratory personnel were blinded to clinical data and the investigators were blinded to the results of the markers, the analysis provides an objective comparison. The patient population was enrolled consecutively and appears reflective of the population with chest pain observed nationally given the frequency of infarction (12.5%). CK-MB mass was selected as the diagnostic standard because it has been the diagnostic standard worldwide for >2 decades and because extensive clinical and experimental evidence indicate increased plasma CK-MB reflects infarction. The most recent study13 performed in the conscious dog indicates that irreversible myocardial injury induced by complete coronary occlusion (15 to 20 minutes) and confirmed histologically by electron microscopy 72 hours later is associated with increased serum CK, whereas severe myocardial ischemia (glycogen depletion and cell swelling) induced by 10 to 15 minutes of coronary occlusion was not associated with increased serum CK. Neither serum CK-MB activity nor CK-MB subforms are increased with exercise-induced reversible myocardial ischemia14 (detected by thallium). Despite claims15 16 that the cardiac troponins may be released with ischemia, experimental studies to determine whether their release reflects myocardial ischemia, necrosis, or both are lacking.
There are no published studies in which all the markers are compared in relation to onset of symptoms. Other studies have evaluated selected markers, but usually in select populations, in relation to time of presentation, and frequently with inadequate sample size. Our results showing that CK-MB subforms are a reliable marker for triaging patients in the first 6 hours after onset of symptoms are virtually identical to those of a previously reported large, prospective study.4 Other studies have consistently shown CK-MB subforms to be the most sensitive and specific marker within 6 hours of onset of symptoms.17 18 The addition of myoglobin to CK-MB subforms did not increase diagnostic sensitivity. In 309 patients, de Winter et al19 noted myoglobin to be a sensitive early marker of myocardial infarction, whereas troponin T was a late marker, similar to total CK-MB. Brogan et al20 showed that troponin I and CK-MB had similar sensitivities and specificities in 171 patients.
In the GUSTO IIA study of 801 patients with unstable angina,
troponin T was increased in 36%, and the 30-day mortality rate was
11.8% compared with 3.9% in patients with normal
levels.7 In TIMI IIIB, a study of 1404 patients with
unstable angina and non–Q-wave infarction, troponin I was increased in
41%, with a mortality rate of 3.7% compared with 1.0% in the group
with normal levels.21 A recent study of just unstable
angina showed that troponin T and I were increased in
24%.22 In TIMI IIA (622 patients with unstable
angina),23 troponin T was increased in 19.5%, similar to
our results. The sensitivity of CK-MB subforms was greater, being
increased in 29.5%. It remains a conundrum as to whether a minor
increase in 1 marker should be diagnosed as myocardial infarction.
There was a core of 99 patients in whom all markers other than CK-MB
mass were increased. Myoglobin was increased in 276, and troponin I was
increased in 166. Most additional patients had a clinical diagnosis of
unstable angina. Thus, the CK-MB mass assay is less sensitive than
CK-MB activity, CK-MB subforms, or the troponins. CK-MB activity and
troponin T were virtually identical as diagnostic
standards, with 170 patients with increased CK-MB activity and 166 with
increased troponin T having an infarction. CK-MB subforms and troponin
I were also similar, with 260 with elevated CK-MB subforms and 231 with
elevated troponin I having an infarction. These results indicate
that CK-MB enzymatic activity is a more appropriate assay than CK-MB
mass.
We propose the diagnosis of myocardial infarction rather than unstable angina when associated with an increased CK-MB because the data suggest that myocardial necrosis, while controversial, does have significant prognostic and therapeutic potential. Patients with increased total CK-MB,24 troponin T,7 or troponin I21 consistently exhibit an increased risk of clinical events, including death. Even after PTCA, those with minimal increased total CK-MB exhibited increased risk over those without increased CK-MB.25 Patients with circumflex coronary obstruction seldom present with ST-segment elevation26 27 and should benefit from fibrinolytic therapy; however, given that the ECG findings are nonspecific and the risk of stroke with fibrinolytics is substantial, infarction needs to be confirmed before therapy. In TIMI IIIB,6 patients with unstable angina receiving thrombolytic therapy had increased death and infarction, but patients with non–Q-wave infarction had similar outcomes whether they received thrombolytics or not. However, the mean time from onset of symptoms to therapy was 9 hours, which is probably too late to be effective. An early diagnosis (80% within 1 hour after admission) can now be made in these individuals, and an appropriate trial with fibrinolytic therapy should be performed to test the hypothesis that thrombolysis is beneficial in non–Q-wave myocardial infarction.
The importance of triaging patients with chest pain in the
emergency room, in addition to the diagnostic and
therapeutic implications, is cost-effectiveness. We4 have
shown that early triaging based on CK-MB subforms could potentially
save billions of dollars through the avoidance of unnecessary hospital
admissions. A pilot study recently performed in 1314 patients with
chest pain triaged on the basis of CK-MB subforms reduced the cost per
patient by 35%. These results applied nationally would
represent billions of dollars saved.28 The assays
for each marker are automated, have similar costs, and require 25
minutes. In the selection of a single assay, CK-MB subforms provide the
earliest diagnosis; total CK-MB activity, derived from it, is the most
sensitive for late diagnosis. If one prefers a combination of assays,
then CK-MB subforms, in combination with troponin I or T, are
recommended. Sampling for 24 hours provides a baseline for subsequent
procedures, detection of early reinfarction, and a rough estimate of
infarct size from the peak serum activity. Early reinfarction
(accounting for 40% of deaths after thrombolysis) is
best detected by the CK-MB subforms because total CK-MB mass or
activity remains increased for 48 hours and the troponins for 10
days, whereas CK-MB subforms return to normal in 18 to 24 hours.
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Acknowledgments |
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This work was supported in part by grants from the Boehringer Mannheim Corporation, Dade International, Helena Laboratories, Spectral Diagnostics, Inc, and the NHLBI (grant P50-HL-54313-01). Syed Jaffri, MD, is acknowledged for technical assistance, and Debora H. Weaver and Valorie J. Garza are acknowledged for secretarial assistance.
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Footnotes |
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Reprint requests to Robert Roberts, MD, Don W. Chapman Professor of Medicine, Professor of Medicine and Cell Biology, Department of Medicine, Section of Cardiology, 6550 Fannin, MS SM677, Baylor College of Medicine, Houston, TX 77030.
Guest Editor for this article was Prediman K. Shah, MD, Cedars-Sinai Medical Center, Los Angeles, Calif.
Received April 30, 1998; revision received December 18, 1998; accepted December 30, 1998.
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NACB WRITING GROUP MEMBERS, D. A. Morrow, C. P. Cannon, R. L. Jesse, L. K. Newby, J. Ravkilde, A. B. Storrow, A. H.B. Wu, R. H. Christenson, NACB COMMITTEE MEMBERS, et al. National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Characteristics and Utilization of Biochemical Markers in Acute Coronary Syndromes Clin. Chem., April 1, 2007; 53(4): 552 - 574. [Full Text] [PDF]
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F. S. Villanueva, E. Lu, S. Bowry, S. Kilic, E. Tom, J. Wang, J. Gretton, J. J. Pacella, and W. R. Wagner Myocardial Ischemic Memory Imaging With Molecular Echocardiography Circulation, January 23, 2007; 115(3): 345 - 352. [Abstract] [Full Text] [PDF]
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U. Hoffmann, J. T. Nagurney, F. Moselewski, A. Pena, M. Ferencik, C. U. Chae, R. C. Cury, J. Butler, S. Abbara, D. F. Brown, et al. Coronary Multidetector Computed Tomography in the Assessment of Patients With Acute Chest Pain Circulation, November 21, 2006; 114(21): 2251 - 2260. [Abstract] [Full Text] [PDF]
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Part 5: Acute Coronary Syndromes Circulation, November 29, 2005; 112(22_suppl): III-55 - III-72. [Full Text] [PDF]
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M. C. Kontos, R. Shah, L. M. Fritz, F. P. Anderson, J. L. Tatum, J. P. Ornato, and R. L. Jesse Implication of different cardiac troponin I levels for clinical outcomes and prognosis of acute chest pain patients J. Am. Coll. Cardiol., March 17, 2004; 43(6): 958 - 965. [Abstract] [Full Text] [PDF]
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G. Patti, A. D'Ambrosio, S. Mega, G. Giorgi, E. M. Zardi, D. M. Zardi, G. Dicuonzo, A. Dobrina, and G. Di Sciascio Early interleukin-1 receptor antagonist elevation in patients with acute myocardial infarction J. Am. Coll. Cardiol., January 7, 2004; 43(1): 35 - 38. [Abstract] [Full Text] [PDF]
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N. S. Kleiman, N. Lakkis, C. P. Cannon, S. A. Murphy, P. M. DiBattiste, L. A. Demopoulos, W. S. Weintraub, E. Braunwald, and TACTICS-TIMI 18 Investigators Prospective analysis of creatine kinase muscle-brain fraction and comparison with troponin T to predict cardiac risk and benefit of an invasive strategy in patients with non-ST-elevation acute coronary syndromes J. Am. Coll. Cardiol., September 18, 2002; 40(6): 1044 - 1050. [Abstract] [Full Text] [PDF]
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L. Erhardt, J. Herlitz, L. Bossaert, M. Halinen, M. Keltai, R. Koster, C. Marcassa, T. Quinn, and H. van Weert Task force on the management of chest pain Eur. Heart J., August 1, 2002; 23(15): 1153 - 1176. [Full Text] [PDF]
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J. A. de Lemos, D. A. Morrow, C. M. Gibson, S. A. Murphy, M. S. Sabatine, N. Rifai, C. H. McCabe, E. M. Antman, C. P. Cannon, and E. Braunwald The prognostic value of serum myoglobin in patients with non-ST-segment elevation acute coronary syndromes: Results from the TIMI 11B and TACTICS-TIMI 18 studies J. Am. Coll. Cardiol., July 17, 2002; 40(2): 238 - 244. [Abstract] [Full Text] [PDF]
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L. K. Newby, A. B. Storrow, W. B. Gibler, J. L. Garvey, J. F. Tucker, A. L. Kaplan, D. H. Schreiber, R. H. Tuttle, S. E. McNulty, and E. M. Ohman Bedside Multimarker Testing for Risk Stratification in Chest Pain Units : The Chest Pain Evaluation by Creatine Kinase-MB, Myoglobin, and Troponin I (CHECKMATE) Study Circulation, April 10, 2001; 103(14): 1832 - 1837. [Abstract] [Full Text] [PDF]
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R Bholasingh, R J de Winter, J C Fischer, R W Koster, R J G Peters, and G T Sanders Safe discharge from the cardiac emergency room with a rapid rule-out myocardial infarction protocol using serial CK-MBmass Heart, February 1, 2001; 85(2): 143 - 148. [Abstract] [Full Text]
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D. A. Katz Risk stratification in unstable angina: the role of clinical prediction models J. Am. Coll. Cardiol., November 15, 2000; 36(6): 1809 - 1811. [Full Text] [PDF]
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R. J. de Winter, J. Fischer, R. Bholasingh, J. P. van Straalen, T. de Jong, J. G.P. Tijssen, and G. T. Sanders C-Reactive Protein and Cardiac Troponin T in Risk Stratification: Differences in Optimal Timing of Tests Early after the Onset of Chest Pain Clin. Chem., October 1, 2000; 46(10): 1597 - 1603. [Abstract] [Full Text] [PDF]
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F. S. Apple, F. P. Anderson, P. Collinson, R. L. Jesse, M. C. Kontos, M. A. Levitt, E. A. Miller, and M. M. Murakami Clinical Evaluation of the First Medical Whole Blood, Point-of-Care Testing Device for Detection of Myocardial Infarction Clin. Chem., October 1, 2000; 46(10): 1604 - 1609. [Abstract] [Full Text] [PDF]
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A. S. Jaffe, J. Ravkilde, R. Roberts, U. Naslund, F. S. Apple, M. Galvani, and H. Katus It's Time for a Change to a Troponin Standard Circulation, September 12, 2000; 102(11): 1216 - 1220. [Full Text] [PDF]
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