Potential of mid-infrared spectroscopy to aid the triage of patients with acute chest pain.

A total of 1,429 serum samples from 389 consecutive patients with acute chest pain were analyzed with the goal to aid the rapid diagnosis of acute myocardial infarction. To the best of our knowledge this is the largest and most comprehensive study on mid-infrared spectroscopy in cardiology. We were able to identify those signatures in the mid-infrared spectra of the samples, which were specific to either acute myocardial infarction or chest pain of other origin (angina pectoris, oesophagitis, etc). These characteristic spectral differences were used to distinguish between the cause of the donor's acute chest pain using robust linear discriminant analysis. A sensitivity of 88.5% and a specificity of 85.1% were achieved in a blind validation. The area under the receiver operating characteristics curve amounts to 0.921, which is comparable to the performance of routine cardiac laboratory markers within the same study population. The biochemical interpretation of the spectral signatures points towards an important role of carbohydrates and potentially glycation. Our studies indicate that the "Diagnostic Pattern Recognition (DPR)" method presented here has the potential to aid the diagnostic procedure as early as within the first 6 hours after the onset of chest pain.

Analytical performance of a portable critical care blood gas analyzer.

The portable blood gas analyzer OPTI Critical Care Analyzer was evaluated in comparison to routine laboratory assays using heparinized blood samples of adults and newborns. Within-run imprecision studies were performed with native blood using tonometry to adjust blood gas concentrations. The results obtained show a very close agreement between the OPTI system and the comparison methods for all parameters tested: hemoglobin (y=1.00x-0.2 g/l, r=0.997, n=81), sodium (y=1.13x-18.7 mmol/l, r=0.951, n=79), potassium (y=1.03x-0.04 mmol/l, r=0.972, n=79), pH (y=1.03x-0.29, r=0.958, n=57), pCO2 (y=1.03x-1.14 mm Hg, r=0.988, n=57) and pO2 (y=1.07x-0.85 mm Hg, r=0.995, n=57). The coefficients of variation for the within-run imprecision were below 1.1% for sodium and hemoglobin, and below 2.6% for all other parameters, except for pCO(2) with coefficients of variation up to 3.6% at low calibration gas concentrations. Due to this analytical performance and its portability, the OPTI system is well suited for low to medium test frequencies and immediate use in emergency rooms, intensive care or surgery units.

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.

Multicentre evaluation of a new point-of-care test for the quantitative determination of D-dimer.

Imprecision studies, interference testing and multicentre method comparisons using patient samples were carried out with of a new point-of-care test for D-dimer (CARDIAC D-Dimer). The CV of the within-series and the day-to-day imprecision with blood samples and control materials were between 7% and 13%. Compared with Tina-quant D-Dimer, CARDIAC D-Dimer showed a good correlation and accuracy (n=353; r=0.91; y=1.06x-0.03), compared with STA LIATEST D-Dimer some poorer accuracy (n=304; r=0.91; y=1.12x-0.03). No interference was detected for different hematocrit values (16% to 51%) and in investigations with hemoglobin (up to 0.13 mmol/l), biotin (up to 30 microg/l), bilirubin (up to 340 micromol/l), intralipid (up to 31.1 mmol/l) and rheumatic factor (up to 79 IU/ml). Overdosing or underdosing by 10 microl did not affect the test result. The diagnostic sensitivity of CARDIAC D-Dimer for the detection of acute venous thromboembolic diseases was 100% in our study. With CARDIAC D-Dimer reliable quantitative D-dimer results can be easily obtained. Because of the good analytical and clinical agreement with Tina-quant D-Dimer, it should be suitable for ruling out venous thromboembolic diseases.

Detection limit, cut-off and specificity of an improved rapid assay for cardiac troponin T.

The performance of an improved version of the troponin T rapid test TROPT Sensitive was investigated in a multicentre evaluation at twelve centres. The detection limit and the cut-off were determined in a method comparison with Elecsys Troponin T using a total of 365 samples from patients with suspected acute coronary syndromes and 91 samples from healthy blood donors or non-cardiological patients. The analytical specificity was determined by measuring 1271 blood samples from blood donors without any myocardial injury. The test cut-off (90% of results positive) is 0.08 microg/L, and the detection limit is about 0.05 microg/L. The analytical specificity of the test is between 99.7 and 99.9%. With its small area of undefined significance between positive and negative results and its high sensitivity and specificity, TROPT Sensitive is very well suited to the reliable detection of troponin T positive patients with acute coronary syndromes.

Evaluation of a point-of-care system for quantitative determination of troponin T and myoglobin.

We present the results of a multicenter evaluation of a new point-of-care system (Cardiac Reader) for the quantitative determination of cardiac troponin T (CARDIAC T Quantitative test) and myoglobin (CARDIAC M test) in whole blood samples. The Cardiac Reader is a CCD camera that optically reads the immunochemical test strips. The measuring range is 0.1 to 3 microg/l for CARDIAC T Quantitative and 30 to 700 microg/l for CARDIAC M. Both tests are calibrated by the manufacturer. The reaction times of the tests are 12 or 8 minutes, respectively. Method comparisons were performed with 281 heparinized blood samples from patients with suspected acute coronary syndromes. The results obtained with CARDIAC T Quantitative showed a good agreement compared with cardiac troponin T ELISA (r = 0.89; y = 0.93x + 0.02). The method comparison between CARDIAC M and Tina-quant Myoglobin also showed a good agreement between both assays (r = 0.98; y = 0.92x + 1.6). Test lot-to-lot comparisons yielded differences of 2% and 6% for CARDIAC T Quantitative and of 0 to 11% for CARDIAC M. The within-run imprecision with blood samples and control materials was acceptable for CARDIAC T Quantitative (CV 10 to 15%) and good for CARDIAC M (CV 5 to 10%). The between-instrument CV was below 7% for CARDIACT Quantitative and below 5% for CARDIAC M. The cross-reactivity of CARDIAC T Quantitative with skeletal troponin T was approximately 0.003%. No significant analytical interference was detected for any of the assays in investigations with biotin (up to 100 microg/l), hemoglobin (up to 0.125 mmol/l), hematocrit (26 to 52%), bilirubin (up to 340 micromol/l), triglycerides (up to 5.0 mmol/l), and 18 standard drugs. With the Cardiac Reader reliable quantitative results can be easily obtained for both cardiac markers. The system is, therefore, particularly suitable for use in emergency rooms, coronary care units and small hospitals.

Long-term prognostic value of serial troponin T bedside tests in patients with acute coronary syndromes.

The early presence of troponin T in serum strongly predicts short-term mortality and myocardial infarction in patients with acute coronary syndromes. We investigated the long-term outcome of the prognostic significance of the troponin T rapid bedside assay (TROPT) and compared this with the quantitative troponin T assay (cTnT enzyme-linked immunosorbent assay), myoglobin and creatine kinase-MB (CK-MB) mass. One hundred sixty-three patients with chest pain and suspected acute coronary syndromes were studied and followed prospectively for 3 years. Serial blood specimens were obtained at admission and at 3, 6, 12, 24, 48, 72, and 96 hours after admission. Patients were classified as having acute myocardial infarction in 99 patients (61%), unstable angina in 34 patients (21%), and no evidence for acute cardiac ischemia in 30 patients (18%). At 3 years, 28 patients (17%) had died of which 25 deaths (15%) were for cardiac reasons. Twenty-one patients (13%) had a nonfatal (recurrent) myocardial infarction. At admission 29% of the patients were TROPT positive (> or = 0.2 microg/L), another 31% became positive within 12 hours, and 39% remained negative. When adjusted for baseline variables, a positive TROPT (any sample 0 to 12 hours) was independently associated with a higher risk of cardiac mortality (RR 4.3, 95% confidence interval [CI] 1.3 to 14.0). Because troponin T stays elevated up to 2 weeks, later TROPT results between 24 and 96 hours remained significantly predictive for mortality. The cTnT enzyme-linked immunosorbent assay (any sample 0 to 12 hours; cutoff > or = 0.2 microg/L) was similarly predictive (RR 2.9, 95% CI 1.0 to 8.6). Early myoglobin results were significantly prognostic for cardiac mortality up to 12 hours after admission (RR 3.7; 95% CI 1.0 to 12.0). In contrast, serial CK-MB mass measurements were not predictive of mortality. Thus, a combination of a baseline TROPT and an additional TROPT 12 hours or later identifies a subgroup of patients at high risk for subsequent mortality and reinfarction, both at short-term but also at long-term.

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.

Time-dependent diagnostic performance of a rapid troponin T version 2 bedside test in patients with acute coronary syndromes.

In a prospective trial, the diagnostic performance of the second version of the troponin T rapid assay (Trop T; cutoff 0.2 microg/L) was compared with the quantitative cardiac-specific troponin T assay (cTnT ELISA; cutoff 0.1 microg/L) and other established cardiac markers such as CK, CK-MB activity, CK-MB mass and myoglobin. Additionally, a 30-day follow-up was performed to determine the suitability of the Trop T assay and the reference markers for short-term risk stratification. Two-hundred-and-eighty-six consecutive patients with chest pain and suspected acute myocardial infarction (AMI) were enrolled in two CCU departments. Serial blood specimens were taken at admission and at 3, 6, 12, 24, 48, 72 and 96 h after admission. According to the biochemical criterion CK-MB mass, the patients were classified as having AMI in 154 patients (54%), unstable angina (UAP) in 72 patients (27%) and no evidence for acute cardiac ischemia in 55 patients (19%). Analytical method comparison of Trop T with cTnT ELISA (cutoff 0.1 microg/L) showed a good agreement, Trop T yielded only 4% false-negative and 3% false-positive results. The diagnostic performance of Trop T for the detection of AMI was only slightly inferior compared to cTnT ELISA. Beyond 12 h after admission, Trop T and cTnT ELISA maintained a sensitivity close to 100%, whereas the sensitivity of the other cardiac markers decreased sharply. The diagnostic sensitivity of Trop T for the detection of minor myocardial damage in UAP patients was the same as for cTnT ELISA. Death within 30 days' follow-up occurred only in AMI patients with a positive Trop T test result within the first 6 h after admission. The admission Trop T and cTnT ELISA were the only significant biochemical predictors of major cardiac events. In conclusion, these data show that Trop T has similar diagnostic sensitivity as cTnT ELISA and is a useful tool to confirm acute or subacute myocardial infarction. Trop T is an excellent marker in detecting minor myocardial damage in UAP patients and is suitable for short-term risk stratification.

Quantitative bedside assay for cardiac troponin T: a complementary method to centralized laboratory testing.

BACKGROUND: In the evaluation of chest pain patients, whole blood bedside assays of highly specific cardiac molecules may be an attractive alternative to centralized clinical chemistry testing. We now report on an optimized test strip device for cardiac troponin T (cTnT) that can be analyzed by a cardiac reader for quantitative assessment of the test result. METHODS AND RESULTS: The cTnT test strip reader measures, via a CCD camera, the reflectance of the signal line. For quantitative analysis, a calibration curve was constructed from 1030 samples of 252 consecutive patients with acute coronary syndromes. In a method comparison of 140 samples, the quantitative results of the cTnT test strip reader correlated closely with the results of the cTnT ELISA (r = 0.98; y = 0.85x + 0. 002). Within-run and day-to-day (n = 10) mean CVs were between 11% and 16%, respectively. The cross-reactivity with skeletal troponin T was <0.02%. In patients with myocardial infarction, 45% and 91% of all samples were positive on admission and at 4-8 h after the onset of symptoms, respectively. ROC curve analysis demonstrated a comparable efficiency of the cTnT test strip reader and the laboratory-based cTnT ELISA in patients with suspected myocardial infarction. CONCLUSIONS: It is now possible to quantitatively determine cTnT at the patient's bedside with a rapid and convenient test device. This will facilitate the diagnostic work up of patients with suspected myocardial cell necrosis.

[Patient self-monitoring in follow-up of long-term anticoagulant therapy]. / Patienten-Selbstkontrolle in der Uberwachung der Antikoagulantien-Dauertherapie.

The CoaguChek system is a new system for simple self-testing of prothrombin time from capillary blood. The instrument works with a measuring principle which is completely new in coagulation: the motion of magnetic micro-particles in an oscillating magnetic field is stopped by the fibrin clot and is detected by a photodetector. The existing data show the analytical and clinical reliability of the system. Determinations for within series imprecision yielded a mean CV of 4.9%. The system is comparable to the comparison method Hepato Quick (y = 1.07 x -0.9% Quick; r = 0.89). Patient self-testing increases the relative time within therapeutic range from 54% to 84%.

An improved rapid troponin T test with a decreased detection limit: a multicentre study of the analytical and clinical performance in suspected myocardial damage.

In a multicentre study, we evaluated the analytical and diagnostic performance of the second version of the TROPT rapid test (TROPT 2, CARDIACT in the US). We tested TROPT 2 on 796 blood samples from 487 patients admitted on suspicion of myocardial infarction between 1 and 72 h after onset of symptoms and determined cTnT ELISA and CK MB mass in the corresponding serum samples. Frequency distributions of the results with TROPT 2 showed a detection limit of 0.18 microgram/l (for 50% positive results) as determined by the quantitative cTnT ELISA method. In a total of 796 samples the sensitivities in the detection of myocardial infarction (WHO criteria) 8-12 h after onset of symptoms were highest for cTnT ELISA (98%), followed by the rapid assay and CK MB mass (92%). A subgroup of 87 patients was primarily classified by the WHO criteria for definite infarction. Based on the maximum values within each patient time-series, diagnostic sensitivities for infarction were 100% for TROPT2, cTnT ELISA and CK MB mass. The corresponding specificities were 90%, 82% and 100%, respectively. After reclassification summarizing all cases of myocardial damage (acute and subacute myocardial infarctions and minor myocardial damage) the sensitivities were 87% (TROPT2), 100% (cTnT ELISA) and 71% (CK MB mass). The specificities of all three markers were 100%. Over 50% of all cases of minor myocardial damage were detected by TROPT 2. The clinical evaluation showed that the diagnostic performance of TROPT 2 is only slightly lower than that of cTnT ELISA.

Multicentre evaluation of an immunological rapid test for the detection of troponin T in whole blood samples.

In a multicentre study we assessed the analytical and diagnostic performance of a rapid test (TROPT rapid test, Boehringer Mannheim; in the USA: CARDIACT) for cardiac troponin T compared to quantitative troponin T ELISA and creatine kinase-MB mass determinations. The rapid test requires 150 microliters of heparinized or EDTA whole blood; serum is not suitable. Interference testing with biotin, haemoglobin and 27 standard drugs yielded no significant influence in the physiological range. Skeletal muscle troponin T concentrations > or = 40 micrograms/l gave positive results with the rapid test. We used the rapid test for 369 samples from 203 patients with suspected acute coronary syndromes and compared the results to troponin T ELISA and creatine kinase-MB mass. 90 patients (44%) were primarily classified as having myocardial infarction by the WHO criteria. Twenty-two (20%) of the 113 non-myocardial infarction patients were unstable angina pectoris cases showing increased troponin T ELISA but not increased creatine kinase-MB mass values. Consequently, these were classified as minor myocardial damage cases. The rapid test was positive in 99% of all samples with a troponin T ELISA value > or = 0.30 micrograms/l and negative in 95 to 96% of all samples below this value. Diagnostic sensitivities for the detection of acute myocardial infarction within the first 12 hours after onset of pain were the same, 90%, for the rapid test, troponin T ELISA and creatine kinase-MB mass. After 48 hours, diagnostic sensitivity of creatine kinase-MB mass sharply decreased whereas that of the troponin T assays remained close to 100% beyond 72 hours after onset of symptoms. Diagnostic specificities for acute myocardial infarction (WHO) of all markers remained between 80 and 100% over this time. The diagnostic sensitivity of the rapid test for the detection of high risk unstable angina pectoris patients with minor myocardial damage was nearly the same as for troponin T ELISA. A major advantage of the rapid test is the ease of use and 20 minute turn around time. This facilitates the detection of increased troponin T at alternate sites.

Multicenter evaluation of a new capillary blood prothrombin time monitoring system.

The analytical performance of the new capillary blood prothrombin time monitoring system CoaguChek was examined in a multicenter evaluation at six hospitals. The coefficients of variation of the INR obtained in the CoaguChek imprecision study were approximately 7% in the control plasma provided (within-run and day-to-day) and 4% in blood (within-run). The prothrombin times were ascertained in capillary blood (CoaguChek PT Test) and citrated venous plasma (Hepato Quick, Thromborel S) from 359 patients under oral anticoagulation therapy with phenprocoumon, acenocoumarin or warfarin. The agreement with the test results obtained with the comparison methods was acceptable versus Hepato Quick assay (n = 359; y = 1.23 x -0.49, r = 0.888) and good versus Thromborel S method (n = 359; y = 1.09 x -0.28, r = 0.895). A simplified assessment of all test results (n = 795) in a nine-field comparison table showed a concordance with the comparison methods of more than 80 (Hepato Quick: 81%, Thromborel S: 83%). The concordance between Hepato-Quick and Thromborel S was slightly higher (88%). Its good analytical performance and convenient handling recommend the CoaguChek system as a suitable system for decentralized prothrombin time testing.