Independent prognostic value of cardiac troponin T in patients with confirmed pulmonary embolism.

BACKGROUND: Cardiac troponin T (cTnT) is a sensitive and specific marker, allowing the detection of even minor myocardial cell injury. In patients with severe pulmonary embolism (PE), myocardial ischemia may lead to progressive right ventricular dysfunction. It was therefore the purpose of this study to test the presence of cTnT and its prognostic implications in patients with confirmed PE. METHODS AND RESULTS: Fifty-six consecutive patients with confirmed PE were enrolled in this prospective study. PE was confirmed by pulmonary angiography, lung scan, or echocardiography and subsidiary analyses. Severity of PE was assessed by a clinical scoring system, and cTnT was measured within 12 hours after admission. cTnT was elevated (>/=0.1 microg/L) in 18 (32%) patients with massive and moderate PE but not in patients with small PE. In-hospital death (odds ratio 29. 6, 95% CI 3.3 to 265.3), prolonged hypotension and cardiogenic shock (odds ratio 11.4, 95% CI 2.1 to 63.4), and need for resuscitation (odds ratio 18.0, 95% CI 2.6 to 124.3) were more prevalent in patients with elevated cTnT. cTnT-positive patients more often needed inotropic support (odds ratio 37.6, 95% CI 5.8 to 245.6) and mechanical ventilation (odds ratio 78.8, 95% CI 9.5 to 653.2). After adjustment, cTnT remained an independent predictor of 30-day mortality (odds ratio 15.2, 95% CI 1.22 to 190.4). CONCLUSIONS: cTnT may improve risk stratification in patients with PE and may aid in the identification of patients in whom a more aggressive therapy may be warranted.

Admission troponin T level predicts clinical outcomes, TIMI flow, and myocardial tissue perfusion after primary percutaneous intervention for acute ST-segment elevation myocardial infarction.

BACKGROUND: In ST-segment elevation myocardial infarction, a troponin T >/=0.1 microg/L on admission indicates poorer prognosis despite early reperfusion. To evaluate the underlying reason, we studied the value of cardiac troponin T (cTnT) for prediction of outcomes, epicardial blood flow, and myocardial reperfusion after primary percutaneous intervention. METHODS AND RESULTS: Patients (n=140) admitted within 12 hours after onset of symptoms were stratified by admission cTnT. Epicardial and myocardial reperfusion were graded by the TIMI score and by measurement of relative increases of myoglobin, cTnT, and creatine kinase (CK)-MB 60 minutes after recanalization, respectively. cTnT was positive in 64 patients (45.7%) and was associated with longer median time intervals to admission (5.5 versus 3.5 hours, P<0.001) and higher mortality rates after 30 days (12.5% versus 3.9%, P=0.06) and 9 months (14% versus 3.9%, P=0.005). cTnT independently predicted a 3.2-fold risk for incomplete epicardial reperfusion (P=0.03). In addition, cTnT >/=0.1 microg/L was associated with more severely impaired myocardial perfusion despite normal epicardial flow, as indicated by lower 60-minute ratios of myoglobin (2.6 versus 7.6, P=0.007), cTnT (6.6 versus 29.2, P<0.001), and CK-MB (3.5 versus 21.4, P=0.002) and a tendency for less resolution of ST-segment elevations (54% versus 60%, P=0.08). CONCLUSIONS: cTnT predicts poorer clinical outcomes, lower rates of postprocedural TIMI 3 flow, and more severely compromised myocardial perfusion despite normal epicardial flow. Thus, a cTnT-positive patient may require more aggressive adjunctive therapy when treated by percutaneous coronary intervention. The impact of preexisting or evolving microvascular dysfunction and the effect of therapies that target myocardial perfusion require further prospective evaluation.

Risk stratification in patients with inferior acute myocardial infarction treated by percutaneous coronary interventions: the role of admission troponin T.

BACKGROUND: Cardiac troponin T (cTnT) elevations on admission indicate a high-risk subgroup of patients with ST-segment elevation acute myocardial infarction (AMI). This finding has been attributed to less effective reperfusion after thrombolytic therapy. The aim of this study was to determine the role of admission cTnT on the efficacy of percutaneous coronary interventions (PCIs) in inferior AMI. METHODS AND RESULTS: One hundred fifty-nine consecutive patients with inferior ST-segment AMI were enrolled and followed up for a mean of 448 days. Patients were stratified by cTnT on admission. A cTnT >/=0.1 microg/L was found in 58% of patients. These patients had longer time intervals from onset of symptoms to therapy (P:<0. 001) and higher 30-day (10.8% versus 1.5%, P:=0.027) and long-term (17.2% versus 4.5%, P:=0.023) cardiac mortalities. Rates of the combined end point of death, nonfatal reinfarction, and need for repeated target vessel revascularization procedures were not different in cTnT groups (log rank, 0.69; P:=0.41). PCI was attempted in 93.3% of cTnT-positive and 98.5% cTnT-negative patients (P:=0.24) but was less frequently successful in patients with cTnT >/=0.1 microg/L (77.9% versus 96.9%, P:<0.001). Coronary stenting reduced 30-day and long-term cardiac mortality, particularly among cTnT-positive patients. In a multivariate analysis, cTnT indicated an approximately 5-fold-higher risk (adjusted OR, 4.6; 95% CI, 0.79 to 27.11; P:=0.089) and was a strong albeit not independent risk predictor. CONCLUSIONS: In inferior AMI, a positive admission cTnT is associated with lower success rates of direct PCI and higher rates of cardiac events over the short and long term. These patients benefit from coronary stenting.

Elevated serum concentrations of cardiac troponin T in acute allograft rejection after human heart transplantation.

OBJECTIVES: This study evaluates the concept and diagnostic efficacy of using serum troponin T for the detection of cardiac graft rejection. BACKGROUND: Cardiac troponin T is a cardiospecific myofibrillar protein, which is only detectable in the circulation after cardiac myocyte damage. It might be expected to be released during acute heart allograft rejection, allowing noninvasive rejection diagnosis. METHODS: In 35 control subjects and in 422 samples from 95 clinically unremarkable heart allograft recipients more than 3 months postoperatively, troponin T serum concentrations were compared to the histological grade of acute graft rejection in concurrent endomyocardial biopsies. RESULTS: Mean troponin T serum concentrations were identical in control subjects (23.2 +/- 1.4 ng/liter) and in heart transplant recipients without graft rejection (International Society for Heart and Lung Transplantation [ISHLT] grade 0; 22.4 +/- 1.7 ng/liter). Mean troponin T concentrations increased in parallel with the severity of graft rejection (ISHLT grade 1: 27.8 +/- 1.8 ng/liter; grade 2: 33.2 +/- 2.7 ng/liter; grade 3A: 54.6 +/- 6.5 ng/liter; grade 3B and 4: 105.4 +/- 53.7 ng/liter; p < 0.001 for grades 3 and 4 vs. grades 0 and 1). The proportion of positive samples also increased in parallel with rejection severity, reaching 100% in rejections of grade 3B and 4. Sensitivity and specificity for the detection of significant graft rejection (ISHLT grade 3/4) were 80.4% and 61.8%, respectively. The negative predictive value was most remarkable with 96.2%. Intraindividual longitudinal analysis of troponin T levels and biopsy results in 15 patients during long-term follow-up confirmed these findings. CONCLUSIONS: The present data demonstrate that acute allograft rejection after human heart transplantation is often associated with increased serum concentrations of troponin T. All cases of serious forms of graft rejection would have been detected before the development of clinical symptoms. Measurement of troponin T levels may become a useful ancillary parameter for noninvasive rejection diagnosis, being most valuable in the exclusion of severe cardiac graft rejection.

Measurement of free human leukocyte elastase and human leukocyte elastase/alpha 1 proteinase inhibitor complexes by an enzyme-linked immunosorbent assay.

We report on an ELISA procedure for the quantitative analysis of total human leukocyte (PMN)-elastase, i.e., the simultaneous determination of (i) free (non-complexed) PMN-elastase and of (ii) PMN-elastase that is complexed to alpha 1 proteinase inhibitor. Simultaneous detection of both forms of PMN-elastase was achieved using a monoclonal antibody that recognizes a PMN-elastase-specific epitope present on both the uncomplexed and the complexed form of the enzyme. The test system described is reliable, easy to perform and permits the determination of total PMN-elastase in complex biological fluids such as plasma or seminal fluid. It is to be expected that this test system will be useful for investigations of human PMN-elastase in biological specimens obtained from both normal and pathological conditions.

Diagnostic and prognostic role of myoglobin in patients with suspected acute coronary syndrome. North-Württemberg Infarction Study (NOWIS) Group.

In patients with suspected acute coronary syndrome, myoglobin is, according to IFCC and NACB guidelines, the marker of choice for early determination of acute infarction, in particular in combination with creatine kinase-MB, 4 hours after admission with a sensitivity of 96%, and correctly excludes Q-wave infarctions. In patients without acute myocardial infarction, a positive troponin T (relative risk 31.5%), but not an elevated myoglobin (relative risk 4.5%), is highly predictive for adverse in-hospital outcome.

Evaluation of CoaguChek Pro ACT in cardiac catheterization laboratory.

The objective of this study was to assess the analytical performance of CoaguChek Pro ACT assay versus Hemochron Celite ACT assay concerning activated clotting time (ACT) values and the correlations versus heparin. Enrolled were 158 patients and 101 normal subjects from five cardiac catheterization laboratories (cathlabs). Two different CoaguChek Pro ACT lots were compared to different lots of Hemochron Celite ACT. All sites used arterial blood and one site also used venous blood. Determinations were carried out before and directly after heparinization, and 1-4 h later. Besides the ACT values, hematocrit, platelet counts and factor Xa levels were also determined. The correlations between the Hemochron Celite lots and the two different CoaguChek Pro lots for arterial and venous blood for all sites were good (r=0.88 and 0.84). The agreement between both CoaguChek Pro ACT lots was excellent (r=0.99). The correlations between heparin and CoaguChek Pro ACT were similar to those for the Hemochron Celite lots. There was no influence of the hematocrit and the platelets. The imprecision of the method was very good (CV<6%). This demonstrates that the CoaguChek Pro ACT assay is especially useful for monitoring heparin in cathlabs.

Recalibration of the point-of-care test for CARDIAC T Quantitative with Elecsys Troponin T 3rd generation.

The rapid troponin T assay CARDIAC T Quantitative was recalibrated using Elecsys Troponin T 3rd Generation as a new reference method. This paper presents the method comparisons at six centres using the new reference method. Method comparison between CARDIAC T Quantitative versus Elecsys Troponin T 3rd Generation were performed using 319 samples from patients with acute coronary syndromes. The quality of the CARDIAC T Quantitative was controlled by a daily single determination of CARDIAC Control Troponin T, and for the Elecsys Troponin T 3rd Generation, the Elecsys controls were included in each run. The results for the control materials for the CARDIAC T Quantitative were between 93% and 107% of the target values. The CV ranged from 7% to 16%. From the regression analysis, according to Bablok and Passing (y=1.07x) and the Bland and Altman plot, the bias between CARDIAC T Quantitative and Elecsys Troponin T 3rd Generation is from +6% to +7%. The correlation coefficient is 0.93, and a 3x3 comparison of the clinical efficiency yielded 92% clinical concordance between CARDIAC T Quantitative and Elecsys Troponin T 3rd Generation. In conclusion, CARDIAC T Quantitative was in good agreement with the reference and calibration method Elecsys Troponin T 3rd Generation.

Analytical and clinical performance of an improved qualitative troponin T rapid test in laboratories and critical care units.

OBJECTIVE: To evaluate the performance of a visual troponin T rapid test in the hands of nontraditionally trained personnel of 2 critical care units in comparison to 3 laboratories. METHODS: Method comparisons of the troponin T rapid test versus cardiac troponin T enzyme-linked immunosorbent assay were performed with 804 samples from 510 patients with suspected acute coronary syndromes. Cross-reactivity with skeletal troponin T was studied up to 5000 microg/L. RESULTS: Laboratories and critical care units obtained comparable results in the analytical cutoff of the test (0.11 and 0. 10 microg/L) and in the diagnostic sensitivities in the detection of acute myocardial infarction (96% and 93% after 8 hours) and of high-risk patients with unstable angina pectoris (100% and 100%). Different percentages of false-positive results (0.2% and 3%) were found, which may reflect different objectives and strategies in these hospital units. The cross-reactivity with skeletal troponin T was less than 0.01%. CONCLUSIONS: The troponin T rapid test gives reliable results not only when used by laboratory personnel experienced in the execution of analytical methods, but also in the hands of nurses and physicians working in clinical units outside the laboratory.

Clinical performance of the new cardiac markers troponin T and CK-MB on the Elecsys 2010. A multicentre evaluation.

Elecsys assays for the cardiac markers Troponin T (cTnT) and CK-MB have been evaluated in an international multicenter study on the random access analyzer Elecsys 2010 to characterize their clinical performance and their comparability with respective established routine methods. In method comparison studies of Elecsys Troponin T (TnT) with Enzymun-Test TnT, good correlations (r > or = 0.95) and a high degree of correspondence (slopes in 4 laboratories between 0.95 and 1.05) were found. The method comparison studies of Elecsys CK-MB with various CK-MB routine methods lead to good correlations but some systematic deviation in the slopes due to varying standardization. In a reference population of 350 persons upper reference limits (97.5th percentile) of 0.03 milligrams/l for Elecsys TnT and 3.1 milligrams/l for Elecsys CK-MB were found. In cardiosensitivity studies the equivalent diagnostic information of the new Elecsys assays to routine methods was confirmed in the early diagnosis of acute myocardial infarction (AMI), the detection of minor myocardial damages in patients with unstable angina pectoris (UAP) and in time course data monitoring of AMI and bypass surgery patients. The superior sensitivity of cTnT versus CK-MB has been established in a screening situation where in 29 patients with cardiac diseases only cTnT, but not CK-MB, was found pathologically increased; this was due either to the larger diagnostic window of cTnT in AMI or to the more sensitive recognition of minor myocardial damage. In the same study, the cardiospecificity of Elecsys TnT was found to be at least 99.5%. This has also been demonstrated in an earlier study for Enzymun-Test TnT. Further cardiospecificity testing, e.g. in renal failure patients, showed results equivalent to those of Enzymun-Test TnT. An extended clinical study involving 294 patients with chest pain, of whom 58 had a final diagnosis of AMI, revealed highly comparable sensitivity and specificity for the Elecsys assays and routine methods. Thus, the already recommended clinical cut-off values of 0.1 milligrams/l for cTnT and 5 milligrams/l for CK-MB are also valid for the Elecsys assays. The slightly improved sensitivity of Elecsys TnT in the lower range even allows the recognition of pathological increase at cTnT concentrations below 0.1 milligrams/l in special situations with sufficient additional clinical information. Summarizing, provide the two cardiac markers on the Elecsys 2010 at least equivalent or even superior diagnostic information in various clinical situations of cardiac disease compared with routine methods. The short turn-around time and reliable performance qualify the Elecsys assays as new methods of choice for routine and emergency use.

[Value of laboratory parameters in risk assessment of patients with coronary heart disease and chronic myocardial ischemia]. / Wertigkeit von Laborparametern bei der Risikostratifizierung von Patienten mit koronarer Herzkrankheit und chronischer Myokardischämie.

The main purpose of laboratory tests in patients with acute coronary syndromes is the exclusion of an acute myocardial infarction and the detection of myocardial micronecrosis. Patients with minor myocardial cell damage can best be identified by measurement of cardiac troponin T and possibly also cardiac troponin I levels. Other serum markers of acute ischemia lack specificity and are, therefore, currently of little clinical significance.

[Monitoring ischemia with new markers]. / Ischämiemonitoring mit neuen Markern.

The measurement of cardiac enzymes is critical for the diagnosis of acute myocardial infarction. Cardiac enzymes, however, are by no means ideal marker molecules, primarily due to their non-specific tissue distribution and low concentration in cardiomyocytes. Many limitations of cardiac enzymes can be overcome by the measurement of cardiospecific troponin T or I with immunological techniques. In the evaluation of new diagnostic methods it is important to define the purpose of marker molecule measurement, i.e., monitoring of definite myocardial infarction or establishing the proper diagnosis in patients with suspected myocardial infarction. For monitoring of success of reperfusion therapy and for the detection of reocclusion short-lived perfusion markers with rapid appearance in circulation such as myoglobin, fatty acid binding protein or glycogenisophosphorylase BB are preferable. For proper diagnosis in patients with suspected acute myocardial infarction test systems with high sensitivity and specificity are needed due to the low prevalence of disease in the patients tested. Troponin T determinations are particularly useful in this group of patients. With troponin T determinations it could be shown that some patients so far classified as having unstable angina do in fact have microinfarction. These data indicate the need for re-definition of diagnostic criteria of acute myocardial infarction.

[Modification of re-stenosis with drugs]. / Medikamentöse Beeinflussung der Re-Stenosierung.

In the treatment of patients with symptomatic coronary artery disease using PTCA, success is limited due to restenosis rates ranging from 30-50% of the lesions treated. Medical approaches to reduce the rate of restenosis were therefore tested in a number of trials. However, in only a few randomized and controlled trials were positive effects reported. Inhibiting platelet aggregation through the use of anti-glycoprotein IIb/IIIa monoclonal antibody 7E3 and, in some studies, with 3 omega fatty acids, a significant reduction in the rate of restenosis was observed. Many trials testing less potent inhibitors of platelet aggregation, such as acetylsalicylic acid, prostacyclin, thromboxane A2 receptor antagonists, and ticlopidine as well as anticoagulants such as heparin or coumarin, calcium antagonists, ACE-inhibitors, antiproliferative agents such as colchicine, methylprednisolone, and angiopeptin were inconclusive or without a positive treatment effect. The results of a hirudin multicenter trial on the rate of restenosis (Helvetica Trial) will soon be reported. There are many possible reasons for these disappointing results, such as poor standardization of the invasive studies, in analyzing the degree of coronary artery stenoses, the inadequate sample size in many trials, and insufficient local drug concentrations as well as the lack of beneficial effects of the study medication. Thus, at present there is no effective treatment to reduce the restenosis rate following PTCA. However, it can be expected that potent antithrombins, or inhibitors of platelet aggregation, may be useful.

Development and characterization of a rapid assay for bedside determinations of cardiac troponin T.

BACKGROUND: The appearance of cardiac proteins in blood is the most specific and sensitive indicator of acute myocardial cell necrosis. The measurement of cardiac markers, however, is time consuming and requires sophisticated equipment. To facilitate the biochemical detection for acute myocardial cell necrosis, a whole-blood rapid assay device for cardiac troponin T detection was developed that provides a test result within 20 minutes. METHODS AND RESULTS: Monoclonal antibody M7 is labeled with gold particles, and antibody 1B10 is labeled with biotin. Both antibodies, as well as buffer substances and detergents, are adsorbed onto paper fleeces mounted below an application well. Heparinized blood (160 microL) applied to this well solubilizes the dry chemistry reagents. Blood cells are separated from plasma via a glass-fiber fleece. The immunocomplexes formed are concentrated within the reading zone by binding of the biotin-labeled antibody with streptavidine immobilized to the test device. Troponin T bound to the test device serves as a control. The detection limit of this assay is 0.18 microgram/L with a cross-reactivity with skeletal troponin T of 0.5%. In clinical analyses involving 25 healthy volunteers, 62 patients with chest pain but without myocardial ischemia, 35 patients with acute myocardial infarction, 24 patients with minor myocardial cell damage due to radiofrequency ablation, and 35 patients with unstable angina, the rapid assay was comparable to the troponin T enzyme immunoassay in regard to sensitivity and specificity. CONCLUSIONS: This newly developed assay allows accurate, rapid, and convenient diagnosis of acute myocardial cell necrosis.

Cardiac troponin T in patients with end-stage renal disease: absence of expression in truncal skeletal muscle.

In patients with end-stage renal disease (ESRD), the serum concentration of cardiac troponin T (cTnT) may be increased without cardiac ischemia. One reason for this unexplained increase could be the extracardiac expression of cTnT. However, truncal skeletal muscle biopsies of five patients with ESRD showed no evidence of the expression of either cTnT mRNA (reverse transcription-PCR) or protein (immunoblot, immunofluorescence). We also measured the serum concentration of cTnT in 97 patients with ESRD. The serum cTnT concentration determined in both first and second generation cTnT assays was significantly lower P <0.01 in patients with a low cardiac risk than in patients with positive indicators of coronary artery disease. The correlation between cTnT and indicators of coronary artery disease is consistent with the hypothesis that cTnT in the serum of patients with ESRD originates from the heart.

Biochemical markers in the diagnosis of coronary artery disease.

For many years cardiac markers have been used to classify whether chest pain is attributable to acute myocardial infarction or not. However massive, myocardial infarction is frequently preceded by plaque inflammation and local thrombus formation. Novel cardiac markers focus on detection of these more subtle manifestations of coronary artery disease. Detection of inflammation of coronary artery plaques is best achieved by measurement of C-reactive protein and fibrinogen, while thrombus formation may be assessed by testing for fibrin formation and platelet activation. When coronary flow is severely impaired minor myocardial injury will occur and cellular constituents may egress from damaged myocytes. Among the many cardiac markers for myocardial cell necrosis, troponin T revealed the highest sensitivity and cardio-specificity. The superior performance of troponin T has not only refined detection of myocardial cell necrosis but has also improved the risk stratification process and may even facilitate therapeutic decision making in patients with acute coronary syndrome. This review will summarize the characteristics and performance of diagnostic tools used for classification and risk stratification of patients with suspected myocardial injury.

Cardiac troponin T levels at 96 hours reflect myocardial infarct size: a pathoanatomical study.

We determined the utility of single-point measurements of circulating cardiac troponin T (cTnT) for the noninvasive estimation of infarct size in 16 beagle dogs after left anterior descending artery (LAD) ligation. Pathoanatomical infarct sizes were determined by the triphenyltetrazolium chloride method and correlated with serum concentration changes of cTnT. Peak cTnT levels (14.10 +/- 4.71 microg/l) were reached after 110 +/- 21 h. A significant correlation was found between peak cTnT levels (p = 0.0001, r = 0. 83) or cumulative cTnT levels and relative infarct size (p = 0.0010, r = 0.72). A single cTnT measurement 96 h after LAD ligation was equally predictive of infarct size (p = 0.0010, r = 0.74) as peak or cumulative cTnT levels derived from serial sampling. cTnT levels at 96 h may thus be useful for practical and cost-effective estimation of infarct size.

Troponin T: a diagnostic marker for myocardial infarction and minor cardiac cell damage.

The diagnosis of acute myocardial infarction is straightforward when anginal pain is accompanied by typical ECG changes and in these patients measurements of cardiac markers are unnecessary in deciding whether thrombolytic therapy is appropriate. Cardiac markers in patients with acute ischaemic coronary syndromes, however, may serve to identify a high risk subgroup of patients with small acute infarctions or minor myocardial damage. In many patients with chest pain a valid diagnosis of myocardial cell injury depends on the result of biochemical assays. In 30% of patients with unstable angina, troponin T is elevated although myocardial infarction was ruled out by cardiac enzymes and ECG recordings. The outcome of these patients at 4 weeks and 6 months follow-up is not different from that of patients with definite myocardial infarction. To guide therapeutic decisions on these patients a troponin T test result needs to be available rapidly. The rapid troponin T test strip assay, which allows the determination of troponin T levels in whole blood at the patient's bedside, can be performed conveniently in the emergency room or in laboratories with less sophisticated equipment and has the potential to aid in the triage of chest pain patients and the selection of therapeutic strategies.

[Suspected acute coronary syndrome in patients without ST-elevation. Exclusion of infarction, early clinical estimation and non-coronary diagnoses]. / Verdachtsdiagnose akutes Koronarsyndrom bei Patienten ohne ST-Hebung. Infarktausschluss, klinische Ersteinschätzung und nicht-koronare Diagnosen.

BACKGROUND AND OBJECTIVE: Patients admitted to the hospital with suspected acute coronary syndrome (ACS) represent a collective at high risk. The NOWIS substudy aimed at evaluating 3 points: (1) Safe exclusion of myocardial infarction by history, symptoms, biochemical markers and the ECG, (2) value of the first diagnosis by the physician in the emergency room, and (3) prevalence and distribution of non-coronary leading diagnoses. PATIENTS AND METHODS: In 164 patients admitted with suspected ACS without ST-segment elevation (73 % men, median age 66 years) the cardiac markers myoglobin, troponin T and CK/CK-MB were assessed on admission and 4 h later. In 2 of the NOWIS centers, the diagnosis on admission, derived from the ECG, history and clinical symptoms, was compared with the leading diagnosis at discharge, based on coronary angiography and, if negative, on additional esophago-gastroscopy. RESULTS: (1) Myoglobin was the biochemical marker with the highest sensitivity 4 h after admission for acute myocardial infarction (classic) definition by CK-MB elevation) with 90.4 %, followed by troponin T with 84.6 %. Four h after admission, in 15.4 % of the infarction patients (prevalence 31.7 %) troponin T was normal. (2) The admission diagnosis instable angina pectoris was confirmed in 46.7 % (57 of 122), suspected acute infarction in 76.2 % (32 of 42). On the other hand, 90.4 % (57 of 63) of the patients with instable angina as leading diagnosis at discharge were correctly diagnosed on admission, but only 61.5 % (32 of 42) of the patients with infarction. (3) At discharge, 29.9 % (49 of 164) of the patients had a non-coronary leading diagnosis. Here, the most common were gastro-intestinal (55.1 %), costo-vertebral (18.4 %) and broncho-pulmonary (16.3 %). CONCLUSIONS: (1) Troponin and myoglobin are helpful in patients without ST-segment elevation; yet, 4 h after admission, a safe exclusion of myocardial infarction is not possible. (2) The clinical diagnosis on admission is important. However, it corresponds with the leading diagnosis at discharge, based on coronary angiography, in only 50 to 75 %. Patients admitted with suspected ACS should be monitored for 24 h in the hospital (chest pain units or coronary care units). (3) Nearly one third of the patients initially admitted with suspected ACS show a non-coronary leading diagnosis, thus underlining the value of further investigations and of an interdisciplinary approach.

Improved troponin T ELISA specific for cardiac troponin T isoform: assay development and analytical and clinical validation.

The first generation of troponin T ELISA (TnT 1) can yield false-positive results in patients with severe skeletal muscle injury. Therefore, a cardiac-specific second-generation troponin T ELISA (TnT 2) was developed, in which the cross-reactive antibody 1B10 has been replaced by a high-affinity cardiac-specific antibody M11.7. No cross-reactivity of TnT 2 was observed with purified skeletal muscle troponin T (1000 micrograms/L) or in test samples from 43 marathon runners and 24 patients with rhabdomyolysis and highly increased creatine kinase. TnT 2 was increased > 0.2 microgram/L in 5 of 40 patients with renal failure and in 4 of 20 muscular dystrophy patients. The detection limit is 0.012 microgram/L. Day-to-day imprecision (CV) within the range 0.19-14.89 micrograms/L was < 5.8%. In 4955 patients without myocardial damage, 99.6% had TnT < 0.10 microgram/L. Assay comparison (TnT 1 vs TnT 2) over the whole concentration range (i.e., in 323 samples from AMI-suspected patients) showed a slope, intercept, and standard error of estimate (Sey) of 1.18, 0.01 micrograms/L, and 0.81 microgram/L, respectively.