Rainer Zerback

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

Abstract 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 μg/l for CARDIAC T Quantitative and 30 to 700 μg/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 CARDIACT Quantitative and of 0 to 11% for CARDIACM. 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 CARDIACM. 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 μg/l), hemoglobin (up to 0.125 mmol/l), hematocrit (26 to 52%), bilirubin (up to 340 μmol/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.

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.

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 determination of NT-proBNP in whole blood

Abstract Background: The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. Methods: A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. Results: The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was ≤5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between −5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3mmol/L), icteric blood (bilirubin concentrations up to 582μmol/L), haemolytic blood (haemoglobin concentrations up to 62mg/L), biotin (up to 10mg/L), rheumatoid factor (up to 42IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140–165μL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. Conclusions: The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting. Clin Chem Lab Med 2006;44:1269–77.

Sensitivity and specificity of a quantitative point of care D-dimer assay using heparinized whole blood, in patients with clinically suspected deep vein thrombosis

D-dimer assays are efficient in the exclusion diagnostics of deep vein thrombosis (DVT) in patients without severe concomitant diseases. We have determined diagnostic sensitivity and specificity of a new point-of-care rapid assay for quantitative determination of D-dimer in heparinized whole blood in outpatients with suspected DVT. In 19 participating centers, 637 patients were included in the study, of which 77 were excluded, the majority because of inadequate documentation of analytical quality control measures. DVT was diagnosed in 223 of the remaining 560 patients by duplex ultrasound examination. The POC D-dimer assay showed a high sensitivity of 96.9% for the diagnosis of DVT and a high specificity of 60.8% at a pre-specified cutoff of 0.5 microg/ml. For Tina-quant D-dimer, sensitivity was slightly lower at 94.9%, with a specificity of 64.8%. The VIDAS D-dimer assay showed a sensitivity of 98.2%, but specificity was 40.7%. The area under the curve (AUC +/- standard error, 95% confidence interval) was 0.879 +/- 0.019 (0.845-0.909) for POC D-dimer, 0.908 +/- 0.016 (0.877-0.934) for Tina-quant D-dimer, and 0.895 +/- 0.018 (0.862-0.922) forVIDAS D-dimer. Differences were not statistically significant. The new whole blood POC D-dimer assay is a reliable tool for exclusion of DVT in symptomatic outpatients, displaying a comparable diagnostic performance as VIDAS D-dimer and Tina-quant D-dimer assays.

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 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.

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.

Equal performance of novel N-terminal proBNP (Cardiac proBNP®) and established BNP (Triage BNP®) point-of-care tests

BACKGROUND Recently, a novel point-of-care test (POCT) for N-terminal proBNP (NTproBNP) has been introduced (Cardiac proBNP®, Roche). AIM The aim was to compare the novel POCT for NTproBNP with the established POCT for BNP. METHODS NTproBNP and BNP were assessed in 222 individuals with chronic heart failure (n = 151) or controls (n = 71) with both POCTs. RESULTS NTproBNP and BNP were closely correlated upon regression analysis (r = 0.93; p < 0.01). NTproBNP and BNP were both correlated with ejection fraction and New York Heart Association stage. Receiver operating characteristic analysis yielded satisfying and equivalent predictive values for the detection of left ventricular dysfunction (ejection fraction <40%; NTproBNP: area under the curve 0.97; BNP: area under the curve 0.96; p > 0.05) and presence of New York Heart Association stage >2 (area under the curve 0.92 vs 0.91 for NT-proBNP and BNP, respectively; p > 0.05). CONCLUSION The NTproBNP POCT allows biochemical detection of heart failure with satisfactory predictive values, is equivalent to the BNP POCT and will improve near-patient testing.

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 mg/L) was compared with the quantitative cardiac-speci® c troponin T assay (cTnT ELISA; cutoff 0.1 mg/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 strati® cation. 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 classi® ed 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 mg/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 ® rst 6 h after admission. The admission Trop T and cTnT ELISA were the only signi® cant 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 con® rm acute or subacute myocardial infarction. Trop T is an excellent marker in detecting minor myocardial damage in UAP patients and is suitable for shortterm risk strati® cation. Scand J Clin Lab Invest 2000; 60: 665 ± 676