Diagnostic performance of four point of care cardiac troponin I assays to rule in and rule out acute myocardial infarction

ObjectiveThis study evaluated the diagnostic performance of four point-of-care (POC) cardiac troponin I (cTnI) assays compared to a central laboratory cTnI assay for detecting myocardial injury and diagnosing acute myocardial infarction (AMI).Design and methodsPlasma obtained at admission, 3 h, and 6 h post-admission in 169 patients presenting with symptoms suggestive of acute coronary syndrome (ACS) was studied. cTnI concentrations were measured on the Instrumentation Laboratory prototype GEM Immuno, Radiometer AQT90, Mitsubishi PATHFAST, Abbott i-STAT and the Ortho-Clinical Diagnostic Vitros assays. MI was determined based on 99th percentiles according to Universal MI guidelines.ResultsFor ruling in MI at presentation (0 h), the GEM Immuno (sensitivity 63%, specificity 85%) and PATHFAST (sensitivity 53%, specificity 86%) were comparable to the OCD (sensitivity 68%, specificity 81%), and significantly better (p < 0.05) than the AQT90 (sensitivity 26%, specificity 93%) and i-STAT (sensitivity 32%, specificity 92%). cTnI concentrations and serial rising patterns after MI differed by each assay. Negative predictive values were > 90% and ROC AUCs were > 0.90 after 6 h for all assays. Detection of myocardial injury in non-ischemic pathologies accounted for lower than 100% specificity for MI.ConclusioncTnI is a sensitive biomarker for detection of myocardial injury. The analytical variability that exists between POC cTnI assays demonstrates substantial diagnostic differences for ruling in and ruling out MI in patients presenting with symptoms suggestive of ACS.     

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers

Objective. Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. Material and methods. We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H‐FABP) in 23 patients admitted with acute ST‐segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24?h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2?h after admission. Results. From 30?min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H‐FABP (p<0.05). Conclusions. The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.     

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers

OBJECTIVE: Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. MATERIAL AND METHODS: We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H-FABP) in 23 patients admitted with acute ST-segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24 h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2 h after admission. RESULTS: From 30 min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H-FABP (p<0.05). CONCLUSIONS: The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.     

Evaluation of the analytical performance of the advanced method for cardiac troponin I for the AxSYM platform: comparison with the old method and the Access system.

BACKGROUND: The determination of cardiac troponins is routinely used for rule in/out, risk stratification, and follow-up of patients with acute coronary artery syndrome. We evaluated the analytical and clinical performance of the advanced immunoassay for troponin I (cTnI) carried out on an AxSYM platform (Abbott Diagnostic Division) and compared these characteristics to those of the previous version of this assay and to cTnI on the Access 2 immunoassay system (Beckman Coulter, Inc.). METHODS: We assayed plasma samples from healthy subjects (n=66) and cardiac patients (n=132) using AxSYM Plus system assays called the old (OLD AxSYM) and advanced TnI (ADV AxSYM) methods and using an Access system. RESULTS: An improvement in analytical sensitivity (detection limit) was observed for the advanced cTnI AxSYM compared to the previous method (0.014 vs. 0.31 microg/L), while the cTnI value for the 10% CV (i.e., functional sensitivity) was 0.41 microg/L for the ADV and 1.9 microg/L for the OLD method. The kinetics of cTnI release was similar, as evaluated in 25 patients with typical acute myocardial infarction (AMI). A close linear relationship was found between the two methods on the AxSYM system (OLD cTnI=7.436+6.858 ADV cTnI; R=0.968, n=214) and with the Access system (OLD AxSYM=7.154+7.9 Access, R=0.876, n=158; ADV AxSYM=0.23+1.209 Access, R=0.927, n=160). However, wide bias was found between the OLD and ADV AxSYM methods (mean difference 118.4 microg/L, p<0.0001), while more similar results were found between the ADV AxSYM and Access methods (mean difference 2.6 microg/L, corresponding to a mean percentage difference of 17%, p<0.0001). In 106 patients with symptomatic rheumatoid arthritis with high rheumatoid factor (RF) concentration, the mean cTnI measured by the ADV AxSYM method was 0.009+/-0.031 mug/L (range 0-0.23 microg/L) with a significant correlation (R=0.316, p=0.001) between cTnI and RF values. Furthermore, in 60 of these serum samples the cTnI concentration was also measured using the Access method; significant correlation with the values found by the ADV AxSYM method was observed (R=0.468, p=0.0002). CONCLUSIONS: The present study indicates that the AxSYM Troponin-I ADV immunoassay shows improved analytical sensitivity compared to the OLD AxSYM method, as well as very similar clinical results to those determined using the Access method.     

Multicenter analytical evaluation of a high-sensitivity troponin T assay

BackgroundHigh-sensitivity cardiac troponin assays are being introduced clinically for earlier diagnosis of acute myocardial infarction (AMI). We evaluated the analytical performance of a high-sensitivity cardiac troponin T assay (hscTnT, Roche Diagnostics) in a multicenter, international trial.MethodsThree US and 5 European sites evaluated hscTnT on the Modular® Analytics E170, cobas® 6000, Elecsys 2010, and cobas® e 411. Precision, accuracy, reportable range, an inter-laboratory comparison trial, and the 99th percentile of a reference population were assessed.ResultsTotal imprecision (CVs) were 4.6–36.8% between 3.4 and 10.3 ng/L hscTnT. Assay linearity was up to 10,000 ng/L and the limit of blank and detection were 3 and 5 ng/L, respectively. The 99th percentile reference limit was 14.2 ng/L (n = 533). No significant differences between specimen types, assay incubation time, or reagent lots existed. A substantial positive bias (76%) exists between the 4th generation and hscTnT assays at the low end of the measuring range (< 50 ng/L). hscTnT serum pool concentrations were within 2SD limits of the mean of means in the comparison trial, indicating comparable results across multiple platforms and laboratories.ConclusionThe Roche hscTnT assay conforms to guideline precision requirements and will likely identify additional patients with myocardial injury suspicious for AMI.     

Short-term (90 min) diagnostic performance for acute non-ST segment elevation myocardial infarction and 30-day prognostic evaluation of a novel third-generation high sensitivity troponin I assay

ObjectivesWe evaluated a third-generation high sensitivity “guidelines acceptable” troponin I assay (hs-cTnI) against a contemporary “clinically usable” troponin assay (cTnI).Design and methodsRemnant samples of undifferentiated emergency department (ED) patients with suspected acute coronary syndrome were enrolled. Baseline and 90-minute samples were analyzed for cTnI and hs-cTnI. Sensitivity, specificity, positive and negative predictive values for AMI and 30-day adverse cardiac events (ACE) were compared.ResultsOf 486 ED patients, there were 465 patients who had blood remaining at the presentation for the hs-cTnI assays, with 12 AMIs. At presentation, the clinical sensitivity and specificity for AMI was 75% and 97% for cTnI and 83.3 and 82.1% for hs-cTnI. There were 407 patients who had paired baseline and 90-minute blood samples for cTnI and hs-cTnI including 9 of the 12 AMI patients. The sensitivity and specificity was 77.7% and 96.5% for cTnI and 100% and 81.9% for hs-cTnI at 90 min. A Δ change of 30% increase from baseline to 90 min improved the specificity to 94.5% (95% CI 92%–96%) without lowering the sensitivity. When AMI was defined as a Δ30% change of hs-cTnI at t = 0 and 90 min and one hs-cTnI result > 99th percentile cutoff, more than 3 times as many patients met the diagnostic criteria for AMI compared to results from the normal sensitive troponin assay; 28 (6.9%) for hs-cTnI vs. 9 (2.2%) with cTnI. There were 37 in-hospital or 30-day events, producing an OR of 3.03, 95% CI: 0.86–9.59 for cTnI, and 2.54, 95% CI: 1.27–5.10 for hs-cTnI, which detected 11 more cases.ConclusionsThe hs-cTnI assay achieved a 90-minute rule out for AMI and detected more 3 times as many AMI cases. The specificity increased with the Δ30% criteria. The hs-cTnI assay also detected more cases of patient at risk for adverse cardiac events at 30 days.     

The antibody configurations of cardiac troponin I assays may determine their clinical performance

BACKGROUND: Previous studies have shown superior clinical performance of the cardiac troponin I (cTnI) assay from Beckman-Coulter Diagnostics. This assay had a unique combination of monoclonal antibodies with 2 monoclonal antibodies directed against epitopes near the NH(2) terminus of the heart-specific region of troponin I. The approach has been adopted by the new cTnI assay from Abbott Diagnostics. The aim of our study was to investigate whether this approach affects the clinical performance of cTnI assays. METHODS: Cardiac troponin concentrations were measured in a random sample of patients with unstable coronary artery disease included in the GUSTO IV trial (n = 696) by the AccuTnI (Beckman-Coulter Diagnostics), Architect cTnI (Abbott Diagnostics), Immulite 2500 cTnI (Diagnostics Products Corporation), and Elecsys 2010 cTnT (Roche Diagnostics) assays and related to the 1-year mortality. The primary cutoff concentrations were based on the 99th percentile upper reference limits and an imprecision (CV) < or =10%. RESULTS: The sensitivities of the AccuTnI and Architect cTnI assays in identifying patients who died within 1 year were equal and were significantly higher (P <0.05) than those of the Immulite 2500 cTnI and the Elecsys cTnT assays. The concordance between the AccuTnI and Architect cTnI assays was 97%, but concordances between the Architect cTnI and the Elecsys cTnT assays were 89%-92% with more at-risk patients (P <0.01 to P <0.001) identified by the Architect cTnI assay. CONCLUSIONS: The Architect cTnI assay has clinical performance similar to that of the AccuTnI, probably as a result of the inclusion of a monoclonal antibody against troponin I epitope 41-49 in the assay.     

Delta changes for optimizing clinical specificity and 60-day risk of adverse events in patients presenting with symptoms suggestive of acute coronary syndrome utilizing the ADVIA Centaur TnI-Ultra assay

ObjectivesWe determined diagnostic accuracy and risk stratification using delta changes for the cardiac troponin I (cTnI) Centaur Ultra assay for ruling out acute myocardial infarction (AMI) and for risk prediction of adverse events in patients with symptoms of acute coronary syndrome.Design and methodscTnI was measured on admission and 6–24 h in 371 patients. Optimal deltas (percent change, absolute value of percent change, change, absolute value of change) were determined from ROC curve analysis. Risk stratification was performed for cardiac events and death within 60 days.ResultsAMI during hospitalization occurred in 49 patients and endpoints in 11 patients. Diagnostic accuracy by ROC curve was optimal (0.96) using the absolute value of change delta. Diagnostic specificities utilizing the 99th percentile (40 ng/L) for admission and follow-up samples were 84% and 81%, compared to: [90% percent change delta] 89.7%; [66.7% absolute value of percent change delta] 85.5%, [217 ng/L change delta] 99.0% and [55 ng/L absolute value of change delta] 93.7%. All four delta values showed substantially greater risk when the initial cTn value was normal.ConclusionsUtilizing delta cTnI values improves clinical specificity, diagnostic accuracy and risk assessment in patients presenting with symptoms of ACS.     

Performance evaluation of the new ADVIA® Centaur system cyclosporine assay (single-step extraction)

BackgroundCyclosporine (CsA) monitoring is essential for transplant success. We report a performance study of the recently released, fully automated Siemens ADVIA Centaur^® CsA assay.MethodsWhole blood samples from 248 transplant patients were prepared using a new 1-step extraction method. Performance evaluations vs. HPLC–tandem MS (LC-MS/MS), Abbott TDx and AxSYM assays were conducted according to CLSI EP5-A2 and EP9-A2 guidelines.ResultsThe correlation coefficient for LC-MS/MS and ADVIA Centaur was ≥ 0.97 at each site, and for each transplant type. Regression analysis yielded y = 0.94x + 19 for all sites: 95% CI = 0.91–0.96 (slope) and 10–28 (intercept). Absolute and relative bias was minimal for C0 and C2 sampling. Centaur vs. Abbott TDx and AxSYM assays: y = 0.72x + 6, r = 0.98, 95% CI = 0.70–0.73 (slope), 3–9 (intercept); and y = 0.69x + 18, r = 0.97, 95% CI = 0.67–0.71 (slope), 8–27(intercept). Within run CVs were 4.5%–7.1%, total CVs were 5.3%–7.7%.ConclusionsThe ADVIA Centaur assay compared favorably with LC-MS/MS and Abbott assays, displaying good correlation for all transplant types and methods.     

Performance evaluation and subsequent clinical experience with the Abbott Automated Architect STAT Troponin-I assay

BACKGROUND: Cardiac troponins are specific biochemical markers of myocardial injury used in the diagnosis of acute myocardial disease and cardiac risk stratification. To avoid misclassification of patients, troponin assays must demonstrate precision at the low end of the measuring range. We report our evaluation of the Architect STAT Troponin-I assay (Abbott Diagnostics), comparison of low-positive results with 2 other assays, and occurrence of heterophile antibody interference in the assay. METHODS: We assessed analytical performance on the ci8200 according to CLSI protocols, using quality-control and patient samples. Our healthy reference population included 480 blood donors. For correlation studies against the AxSYM first-generation cTnI (Abbott Diagnostics) and Access second-generation AccuTnI (Beckman Coulter) assays, we used 339 samples from hospital patients. RESULTS: The CV of the Architect STAT Troponin-I assay was 10% near the 99th percentile for the reference population (0.03 microg/L). Comparison with the AxSYM first-generation cTnI assay showed good correlation at higher concentrations, but better sensitivity of the Architect cTnI assay at low concentrations, which were clinically relevant as shown by review of patient histories. Correlation was good at the low end of the measuring range with the Access second-generation AccuTnI. Over the last 12 months we have identified 6 patients with heterophile antibodies causing positive interference. CONCLUSIONS: The Architect STAT Troponin-I assay provides highly sensitive measurement of cTnI with a CV of 10% near the upper limit of a reference population; however, heterophile antibodies can interfere with this assay.     

Total hCG tests

IntroductionThere are 12 types of automated total hCG tests sold today, the Abbott Architect, Abbott AxSym, the Beckman Access 2. Beckman DxI 800, the Ortho Vitros EciQ, Roche Elecsys hCG + β, Siemens ACS180, Siemens Centaur, Siemens Dimension, Siemens Immulite and Siemens Stratus, and the Tosoh A1A. All tests claim to be total hCG tests but do not define what total means. Total hCG test needs to detect all hCG variants in order to be used for all hCG test clinical applications. Here we assess this ability.MethodsCoded samples of pure hCG, nicked hCG, hyperglycosylated hCG, nicked hCG missing C-terminal peptide, nicked hyperglycosylated hCG, asialo hCG, hCGβ, nicked hCGβ and β-core fragment were tested blindly in serum and urine at 10 independent laboratories.ResultsWhile the Siemens Immulite total hCG test detected 8 of 9 hCG variant standards, other assays poorly detected important determinants such as nicked hCG missing the C-terminal peptide, β-core fragment, hyperglycosylated hCG, nicked hCG, asialo hCG, and hCGβ. Four assay appropriately detected 4 of 9 variants, 2 assays detected 3 of 9, 4 assays detected 2 of 9 and 1 assay only appropriately detected 1 of 7 hCG variants.DiscussionCare is needed in selecting a total hCG test. The Siemens Immulite tests performed best at detecting all the hCG variants making it appropriate for all applications. Nine assays had limited applications, 3 of the assays were appropriate for advanced pregnancy testing only.     

Clinical implications of the change of cardiac troponin I levels in patients with acute chest pain — An evaluation with respect to the Universal Definition of Myocardial Infarction

BackgroundThe Universal Definition of Myocardial Infarction incorporates elevated cardiac troponin levels (> 99th percentile) together with a significant rise/fall of troponins as biochemical criterion. We sought to evaluate the clinical implications of the relative change of cardiac troponin I (cTnI) levels with respect to the Universal Definition in patients with acute chest pain.MethodscTnI (Stratus CS) was measured serially in 454 patients within 24 h from admission. Acute myocardial infarction (AMI) was defined using the criteria adapted to the ESC/ACC consensus document, or corresponding to the Universal Definition together with prespecified cTnI changes of ≥ 20%, ≥ 50% and ≥ 100%. Follow-up was completed after 5.8 years.ResultsA peak cTnI level above the 99th percentile together with a cTnI change of ≥ 20% was found in 160 patients of whom 25 did not have AMI according to the ESC/ACC criteria. These 160 patients had a significantly raised mortality (HR 2.5 [95% CI 1.7–3.8]). Higher cTnI deltas were not associated with higher mortalities but identified smaller patient cohorts at risk.ConclusionsThe Universal Definition of AMI together with a ≥ 20% cTnI change appears to improve the discrimination of acute from chronic causes of cTnI release, and allows a reliable identification of patients at risk.     

Autoantibodies to cardiac troponin in acute coronary syndromes

BackgroundsIn a recent small study, patients with autoantibodies to cardiac troponin (cTnaAb) had higher cardiac troponin I (cTnI) release during an episode of acute coronary syndrome (ACS) than patients without cTnaAb and continued to have higher long-term levels of cTnI. However, the prognostic importance of the occurrence of cTnaAb is unknown.MethodsIn 957 nonST-elevation ACS patients cTnaAb and cTnI were analyzed at randomization and after 6 months. Outcomes were assessed through 5 years.ResultsSeven and 11% of the patients were cTnaAb positive at inclusion and 6 months, respectively. The cardiac troponin I (cTnI) concentration at inclusion was independently associated with the development of cTnaAb (OR 1.53, 95% CI 1.25–1.88). The presence of cTnaAb was associated with an increased cTnI level at 6 months (OR 2.39, 95% CI 1.50–3.81). cTnaAb was not independently associated with death and AMI during follow-up (HR 0.97, 95% CI 0.61–1.54).ConclusionDevelopment of cTnaAb after an episode of nonST-elevation ACS is associated with the acute myocardial damage, but occurs only in a minority of patients. Furthermore, the presence of cTnaAb is associated with chronically elevated cTnI concentrations. However, the occurrence of cTnaAb is not associated with an adverse long-term prognosis.     

Serum free L-carnitine in association with myoglobin as a diagnostic marker of acute myocardial infarction

BackgroundEarly diagnosis of acute myocardial infarction (AMI) in patients with chest pain is necessary to initiate appropriate treatment. Elevation of ST-segment in ECG is the only marker that cardiologists depend on in diagnosis. The aim of this study was to monitor the level of serum free L-carnitine in combination with myoglobin (Myo) and creatine kinase (total activity and CK-MB level) for usefulness as a predictor of AMI in ICU patients.Design and methodsIn the present study serum total CK activity and CK-MB, Myo, and free L-carnitine levels were determined in 90 patients admitted to the ICU at Ain Shams University Hospital and correlated the sensitivity and specificity of each parameter.ResultsObtained data revealed that, 47/90 who were diagnosed as AMI showed a highly significant reduction in serum free L-carnitine level in all cases as compared to normal control (P < 0.001), 24/90 diagnosed as unstable angina showed a non significant reduction of serum carnitine and 19/90 who were diagnosed as noncardiac showed non significant changes in the level of serum free carnitine as compared to normal control. In addition, serum free L-carnitine level was negatively correlated to CK-MB and Myo (r = ? 0.61 and ? 0.52) respectively. The sensitivity of carnitine assay was considerably higher (95.5%) compared to CK-MB (87%) and Myo (89.5%) even considering patients with a short delay until admission.ConclusionComparing the changes in serum total CK, levels of CK-MB, Myo and carnitine, the sensitivity and specificity were significantly higher for serum free L-carnitine. For this reason, serum free L-carnitine can be used as a good predictor for AMI diagnosis from other diseases.     

Fit-for-purpose evaluation of architect i1000SR immunoassay analyzer

BackgroundLast year Abbott Laboratories introduced the Architect i1000SR modular chemiluminescent immunoassay analyzer for laboratories performing <200 test/day. The analyzer has a diverse menu of most routinely tested assays for the low to mid volume hospital laboratory. We evaluated the analytical performance, productivity and efficiency of this system for a 1-y period.MethodThe analytical performance was ascertained by i) determining functional sensitivity in serum matrix for cTnI and measuring precision for other assays. ii) Accuracy was determined by performing patient correlations for TSH, cTnI and FT4 assays. iii) Analyzer productivity and efficiency were evaluated by determining the expected annual throughput and impact of routine workload on STAT TATs, respectively.ResultsCoefficient of variation ranging from 3.6 to 8.2% was achieved for all assays evaluated. Functional sensitivity for cTnI was found to be 0.05 ng/ml. Patient correlation gave regression coefficients ranging from 0.875–0.998. An average hourly throughput ranged from 41–48 tests per hour (tph).ConclusionsWe find the Architect i1000SR random access immunoassay analyzer met all of the requirements desired in a low to mid volume instrument. Stat turn around times (TAT) are maintained to < 20 min.     

Revaluation of biological variation of glycated hemoglobin (HbA(1c)) using an accurately designed protocol and an assay traceable to the IFCC reference system

BackgroundGlycated hemoglobin (HbA_1c) has a key role for diagnosing diabetes and monitoring glycemic state. As recently reviewed, available data on HbA_1c biological variation show marked heterogeneity. Here we experimentally revaluated these data using a well designed protocol.MethodsWe took five EDTA whole blood specimens from 18 apparently healthy subjects on the same day, every two weeks for two months. Samples were stored at ? 80 °C until analysis and assayed in duplicate in a single run by Roche Tina-quant® Gen.2 immunoassay. Data were analyzed by the ANOVA. To assess the assay traceability to the IFCC reference method, we preliminarily carried out a correlation experiment.ResultsThe bias (mean ± SD) of the Roche immunoassay was 0.3% ± 0.7%, confirming the traceability of the employed assay. No difference was found in HbA_1c values between men and women. Within- and between-subject CV were 2.5% and 7.1%, respectively. Derived desirable analytical goals for imprecision, bias, and total error resulted 1.3%, 1.9%, and 3.9%, respectively. HbA_1c had marked individuality, limiting the use of population-based reference limits for test interpretation. The estimated critical difference was ~ 10%.ConclusionsFor the first time we defined biological variation and derived indices for the clinical application of HbA_1c measurements using an accurately designed protocol and an assay standardized according to the IFCC.     

PAPP-A as a marker of increased long-term risk in patients with chest pain

ObjectivesLong-term risk stratification in patients presenting with acute coronary syndromes (ACS) is possible by measuring cardiac troponin (cTn). The present study examined whether PAPP-A measured in an emergency department (ED) chest pain population in association with conventional and novel high sensitivity cTn (hs-cTnI) assays can predict long-term mortality.MethodsIn 320 patients with cTn measurements the earliest heparinized plasma PAPP-A concentration after presentation was used for risk stratification for death by Kaplan–Meier and Cox analyses. Subgroup analyses using the earliest PAPP-A concentrations were also performed in a cohort of subjects with presentation cTnI ≤ 99th percentile but with significantly changing cardiac troponin concentrations as measured by the AccuTnI assay and the hs-cTnI assay (n = 45 and 120 subjects, respectively).ResultsSubjects with PAPP-A concentrations in the highest tertile were at higher risk for death (HR > 2.00; p ≤ 0.05 at 2 years) even after adjusting for cTnI at presentation. In the cohort with cTnI ≤ 99th percentile but with changing hs-cTnI concentrations, subjects in the top PAPP-A tertile had a higher probability for death (p = 0.02).ConclusionEarly measurement of PAPP-A may identify chest pain patients at higher risk for long-term death. Additional prospective ACS studies are required to fully elucidate PAPP-A's role.     

Evaluation of five immunoturbidimetric assays for urinary albumin quantification and their impact on albuminuria categorization

ObjectivesThe study was designed to evaluate the performance of five automated immunoturbidimetric assays to quantify urinary albumin, each corresponding to a combination of a reagent and an analyzer (Olympus on AU640®, Roche on Cobas Integra, Abbott on Architect, Ortho-Clinical Diagnostics Vitros on Fusion and Siemens on Dimension).Design and methodsTo assess imprecision, albumin was measured in three urinary pools with a mean value of 25, 66 and 131 mg/L. One hundred and eight patient urine samples were then used to compare each turbidimetric method using the Passing–Bablok regression and Bland–Altman analyses. Concordance of the albumin/creatinine ratio (ACR), according to the albuminuria classifications proposed by the KDIGO, was calculated to test the agreement between the different assays.ResultsAll immunoturbidimetric methods evaluated in this study exhibited acceptable imprecision (CV < 6%). Mean values for 108 urine samples varied from 0.5 to 762.2 mg/L. Significant differences were found (p < 0.05) between all methods except between Olympus and Ortho (p = 1.0) and between Abbott and Roche (p = 0.12). Regarding the albuminuria categories based on the ACR proposed by the KDIGO, only the classification obtained with the Roche method was significantly different from the four other methods (p < 0.001).ConclusionsWe demonstrated that all assays were not strictly equivalent which could affect ACR categories in clinical practice, suggesting the need for harmonization of commercial methods.     

Comparison of cardiac troponin I immunoassays variably affected by circulating autoantibodies

BACKGROUND: We recently provided evidence that circulating autoantibodies against cardiac troponin I (cTnI) or the troponin complex cause negative interference in cTnI immunoassays. By comparing three cTnI immunoassays, we further explored the phenomenon of circulating autoantibodies and their consequences in patient samples. METHODS: We developed a cTnI immunoassay with a novel assay design using three antibodies, two of which bind epitopes outside the stable, central part of cTnI. Samples from 541 chest pain patients were measured with the new cTnI assay and with a first-generation cTnI assay (Innotrac Aio cTnI) using a conventional midfragment assay design. Using another sample cohort, we also compared the new assay with a second-generation cTnI assay (Access AccuTnI). RESULTS: The analytical detection limit of the new cTnI assay was 0.012 microg/L, and the lowest concentration giving a total imprecision (CV) of 10% was 0.060 microg/L. The mean difference (95% limits of agreement) between the new cTnI and Aio cTnI assays was larger in admission samples (21.0%; -107.8% to 149.7%) than in samples taken 6-12 h (12.8%; -61.5% to 87.2%) and 24 h after admission (3.0%; -71.3% to 77.4%; P <0.001). With the lowest concentrations giving 10% CV (0.22 microg/L for Aio cTnI) used as cutoffs, 14.3% (n = 76) of admission samples were positive only with the new assay, whereas 13.5% (n = 72) were positive with both assays. Of samples taken at 6-12 and 24 h, 10.2% (n = 31) and 8.3% (n = 29) were positive only with the new assay. ROC curve analysis of admission samples showed a significantly higher area under the curve for the new cTnI assay (0.940) than for the Aio cTnI assay (0.846; P <0.001). The new cTnI assay gave generally lower results than the AccuTnI assay; the mean (95% limits of agreement) differences were -58.9% (-151.8% to 34.0%) in admission samples. In samples with severe interference from autoantibodies, median ratios between the new assay and AccuTnI were higher than in samples with no apparent troponin autoantibodies (0.875 vs 0.481; P<0.001). CONCLUSIONS: The new cTnI assay, which is based on a novel antibody combination different from the conventional midfragment antibody approach, offers improved detection of cTnI in samples containing troponin autoantibodies.     

Interference of gadolinium-based contrast agents on colorimetric calcium assays

ObjectiveThe aim of this study was to evaluate the potential interference of five gadolinium-based contrast agents (GBCAs), gadodiamide (Omniscan®), gadobenate dimeglumine (Multihance®), gadoxetate disodium (Primovist®), gadobutrol (Gadovist®), and gadoteridol (Prohance®), on three clinical laboratory widely used colorimetric calcium assays including the newly developed 5-nitro-5′methyl-l,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (NM-BAPTA) method.MethodsPlasma was collected from healthy volunteers aged 23–52, and spiked with varying concentrations of the five GBCAs. Calcium determinations were performed in duplicates using the o-cresolphthalein complexone (OCP), arsenazo-III dye, and NM-BAPTA methods on the Roche Integra 400, Abbott Architect 16000, and Roche Modular P automated analyzers respectively.ResultsGadobenate dimeglumine, gadobutrol, and gadoteridol did not interfere with any of the assays. There was a small positive bias (8%, p < 0.01) at a very high concentration (25 mmol/L) of gadoxetate disodium when calcium was assayed using the arsenazo-III method. Gadodiamide at a very high concentration (50 mmol/L) induced a significant positive bias (16%, p < 0.01) on calcium when measured using the NM-BAPTA method; however a much larger bias (90%, p ≪ 0.01) was observed when calcium was measured using the arsenazo-III method. Significant interferences in calcium measurements using the OCP method began at gadodiamide concentrations as low as 0.5 mmol/L (− 9%, p < 0.01). This negative bias was more pronounced at higher gadodiamide concentrations.ConclusionsOf all 5 GBCAs tested, only gadodiamide showed significant interference on the OCP calcium assay at clinically relevant concentrations. The NM-BAPTA assay showed minimum interference with the five GBCAs and demonstrated equal or better performance than the OCP and the arsenazo-III methods in terms of interference with GBCAs.