AccuTnI Assay Research Articles

100 Two Thirds of Patients With Acute Coronary Syndrome in High Risk Chest Pain Have a Negative First Conventional Troponin

Current guidelines recommend serial troponin measurements in patients presenting to the emergency department (ED) with suspected acute coronary syndrome (ACS). In clinical practice, a large proportion of patients with suspected ACS are discharged following a single negative troponin, yet the safety of such practice remains unclear. In this study, we aimed to characterize and compare the clinical outcomes of high-risk chest pain patients who receive single versus serial conventional troponin measurements. This was a prospective cohort study that enrolled consecutive chest pain patients transported via ambulance to University of Pittsburgh Medical Center-affiliated hospitals. We determined the onset of symptoms by reviewing the medical charts (ie, history of present illness). Troponin was measured using conventional Troponin I assay (Access AccuTnI assay, Beckman Coulter Inc.; 99th percentile cut-off at 0.04 ng/mL). The two study outcomes were 1) major adverse cardiac events (MACE) within 30 days of indexed ED admission, defined as a composite outcome of: any death, ACS, coronary revascularization, pulmonary embolus, cardiac arrest, ventricular dysrhythmia, cardiogenic shock, and acute heart failure; and 2) Post-discharge cardiovascular (CV) death within 30 days defined as reinfarction, death, and coronary revascularization occurring after discharge. Two independent reviewers retrospectively adjudicated the study outcomes from the charts. All disagreements were resolved by a third reviewer. We enrolled 2400 patients including 378 (15%) patients with ACS, of which 238 (63%) had a negative first troponin. In total, the study included 2188 (92%) patients with a negative first troponin result (age 58 ± 17; 47% females, 41% Black). In those with a negative first troponin, a single troponin was tested in 777 (36%) patients, while 1411 (64%) had serial troponin measurements, with 342 (24%) of the latter group having a marked troponin elevation on repeat testing. Patients who underwent serial troponin measurements were older (62 ± 15 vs 53 ± 18, p<0.001), had more comorbidities, and more often presented with symptoms highly suggestive of ACS. Patients with serial troponin testing more often presented within <6 hours of symptom onset (70% vs 60%, p<0.001). Only 17 (2%) patients had ACS in the single troponin group, while 221 (16%) had ACS among the serial troponin group. When controlling for HEART score, the groups had similar rate of 30-day readmission (OR, 0.89 [95% CI, 0.72-1.11], p = 0.304) and post-discharge CV death (single troponin, 12 [1.5%] vs serial troponin, 43 [3.0%]; OR, 1.08 [95% CI, 0.59-1.96], p = 0.806), however, the serial troponin patients were more likely to have 30-day MACE (OR, 2.1, [95% CI, 1.44-3.07], p<0.001). Approximately two-thirds of patients with ACS had a negative first troponin. Over 60% of chest pain patients with a negative initial troponin were deemed to require serial troponin testing, with one-fourth of these having a subsequent elevation on serial testing. The rate of post-discharge CV death and readmission did not differ between the groups, indicating appropriate patient selection by physicians. A universal strategy of discharging patients following a single negative conventional troponin remains unsafe and should only be implemented based on physician discretion.

503 Implementation of a High Sensitivity Troponin Assay and Overnight Rapid Emergency Department (ED) Discharge of Intermediate Risk Patients: Impact on the ED Length of Stay

Rapid evaluation and discharge of patients presenting with chest pain is a key goal of emergency care. We evaluated the length of stay before and after the implementation of a high-sensitivity troponin assay and a new protocol for overnight rapid ED discharge of intermediate risk patients at The Prince Charles Hospital. Patients aged >18years referred with low and intermediate-risk chest pain between 2018 and 2019 presenting to the Chest Pain Assessment Unit were examined using a before and after study design. Pre-intervention group were assessed using the Beckman-Coulter second generation AccuTnI assay (June-October 2018). Post-intervention (September-November 2019), patients were assessed using the High-Sensitive STAT Troponin-I assay (Abbott Laboratories). Post-intervention, intermediate risk patients presenting to ED overnight were also discharged from ED with outpatient functional testing if they had 2 negative serial troponins (3hours apart) and normal serial ECGs, routine blood tests and a chest x-ray. The primary outcome was the ED length of stay. The study consisted of 634 patients (mean age 59.7y±5.1y, 51% females, 35% low-risk and 65% intermediate-risk chest pain). The pre-intervention group (n=308 patients, mean age 61.3y±13.6, 48% female, 33% low and 67% intermediate risk) were comparable with the post-intervention group (n=326 patients, mean age 58.7y±12, 53% female, 36% low and 64% intermediate risk). The ED length of stay was significantly shorter post-intervention (mean LOS 8.6 v 5.2 hrs, p<0.001). Implementing a high-sensitivity troponin assay and protocol driven discharge of chest pain patients overnight is associated with a significantly lower ED length of stay.

A critical evaluation of the Beckman Coulter Access hsTnI: Analytical performance, reference interval and concordance

IntroductionWe investigated the analytical performance, outlier rate, carryover and reference interval of the Beckman Coulter Access hsTnI in detail and compared it with historical and other commercial assays. Materials and methodsWe compared the imprecision, detection capability, analytical sensitivity, outlier rate and carryover against two previous Access AccuTnI assay versions. We established the reference interval with stored samples from a previous study and compared the concordances and variances with the Access AccuTnI+3 as well as with two commercial assays. ResultsThe Access hsTnI had excellent analytical sensitivity with the calibration slope 5.6 times steeper than the Access AccuTnI+3. The detection capability was markedly improved with the SD of the blank 0.18–0.20 ng/L, LoB 0.29–0.33 ng/L and LoD 0.58–0.69 ng/L. All the reference interval samples had a result above the LoB value. At a mean concentration of 2.83 ng/L the SD was 0.28 ng/L (CV 9.8%). Carryover (0.005%) and outlier (0.046%) rates were similar to the Access AccuTnI+3. The combined male and female 99th percentile reference interval was 18.2 ng/L (90% CI 13.2–21.1 ng/L). Concordance amongst the assays was poor with only 16.7%, 19.6% and 15.2% of samples identified by all 4 assays as above the 99th, 97.5th and 95th percentiles. Analytical imprecision was a minor contributor to the observed variances between assays. ConclusionThe Beckman Coulter Access hsTnI assay has excellent analytical sensitivity and precision characteristics close to zero. This allows cTnI measurement in all healthy individuals and the capability to identify numerically small differences between serial samples as statistically significant. Concordance in healthy individuals remains poor amongst assays.

Cardiac Troponin I carryover by very high patient samples still causes false-positive results on the Beckman Coulter AccuTnI + 3.

False-positive cardiac troponin I results as a result of carryover have previously been reported on the Beckman Coulter AccuTnI assay. We sought to determine if the carryover problem had been resolved with the new AccuTnI + 3 assay. Carryover experiments were performed in parallel on the Beckman Coulter Access2 analyser using the legacy AccuTnI and new AccuTnI + 3 assays. The same negative patient pool sample was analysed before and after a single analysis of an extremely elevated patient sample. Analysis of a single extremely high sample caused elevations above the 99th percentile cut-off, and thus false-positive cardiac troponin I results on both assays. Both assays demonstrated carryover and subsequent further elevations in negative pool results the following day. Our study replicates our previously published findings of carryover and reagent pack contamination on the AccuTnI assay. Despite improvements on the new AccuTnI + 3 assay, carryover and reagent pack contamination are still present.

Falsely Increased hCG in Patients with High Leukocyte Counts

To the Editor: Falsely increased plasma troponin (Tn) I and T results have been reported for several Tn methods, including the Beckman Coulter UniCel DxI AccuTnI assay (Beckman Coulter, Chaska, MN) (1–3). We and others have also observed falsely increased human chorionic gonadotropin (hCG) using the Beckman Coulter Access Total βhCG on the UniCel DxI (1). These false increases were identified by the finding of substantially lower results following high-speed recentrifugation and reanalysis, suggesting a particulate interference. However, the sources of these false increases were not previously determined. In reviewing clinical data for patients from whom plasma samples were found to generate falsely high hCG results on the UniCel DxI in our laboratories, we found these patients had high blood leukocyte counts. Based on this finding, we investigated the interference of leukocytes in the Beckman Coulter Access Total βhCG assay. This study was approved by the Emory Institutional Review Board. First, we measured hCG in leftover plasma samples from patients with known high blood leukocyte content of >25 × 103/μL. The thirteen randomly selected samples (10 male, 3 female) were inverted several times in the original lithium heparin plasma separator tubes (PSTs) (Becton Dickinson) to disturb any particulates settled during storage (up to 24 h refrigerated) and then measured …

The hitchhiker’s guide to the troponin universe

Pathology Queensland consists of a network of 34 laboratories spread throughout Queensland. In 2007, biochemistry testing was standardised state-wide with the introduction of Beckman Coulter analysers. Their accuTnI assay was used for measuring cardiac troponin I. Simultaneously, the Universal Definition of Myocardial Infarction, as defined in 2000, was introduced with a new cardiac troponin I cut-off level according to the 99^th percentile. A number of issues ensued. The diagnosis of myocardial infarction increased dramatically straining emergency and cardiology resources. Unexpectedly, randomly occurring false positive results (flyers) were identified that had a significant impact on clinical intervention. ‘Highly sensitive' cardiac troponin assays were introduced into the market adding to the conundrum. We report more than 300 000 cardiac troponin I tests annually. Our experience with cardiac troponin testing will be presented as well as our research findings into the performance of troponin assays. Unlike our fictional Hitchhiker's Guide we have pursued analytical performance relentlessly. We have characterised assay robustness and between-assay variance, and presented guidance on how to universally define significant changes in serial cardiac troponin results. I will entertain our perspective regarding the value of ‘highly sensitive' cardiac troponin.

Biomarkers for Predicting Serious Cardiac Outcomes at 72 Hours in Patients Presenting Early after Chest Pain Onset with Symptoms of Acute Coronary Syndromes

Most outcome studies of patients presenting early to the emergency department with potential acute coronary syndromes have focused on either the index diagnosis of myocardial infarction (MI) or a composite end point at a later time frame (30 days or 1 year). We investigated the performance of 9 biomarkers for an early serious outcome. Patients (n=186) who presented to the emergency department within 6 h of chest pain onset had their presentation serum sample measured for the following analytes: creatine kinase, creatine kinase isoenzyme MB, enhanced AccuTnI troponin I (Beckman Coulter), high-sensitivity cardiac troponin T (hs-cTnT), ischemia-modified albumin, interleukin-6, investigation use only hs-cTnI (Beckman Coulter), N-terminal pro-B-type natriuretic peptide, and cardiac troponin I (Abbott AxSym). We followed patients until 72 h after presentation and determined whether they experienced the following serious cardiac outcomes: MI, heart failure, serious arrhythmia, refractory ischemic cardiac pain, or death. ROC curves were analyzed to determine the area under the ROC curve (AUC) and optimal cutoffs for the biomarkers. The AUCs for the hs-cTnI assay (0.86; 95% CI, 0.76-0.96), the AccuTnI assay (0.86; 95% CI, 0.78-0.95), and the hs-cTnT assay (0.82; 95% CI, 0.71-0.94) assays were significantly higher than those for the other 6 assays (AUC values≤0.71 for the rest of the biomarkers, P<0.05). The ROC curve-derived optimal cutoffs were ≥19 ng/L (diagnostic sensitivity, 80%; specificity, 88%), ≥0.018 μg/L (diagnostic sensitivity, 75%; specificity, 86%), and ≥32 ng/L (diagnostic sensitivity, 68%; specificity, 92%) for the hs-cTnI, AccuTnI, and hs-cTnT assays, respectively. The optimal cutoffs for predicting serious cardiac outcomes in this low-risk population are different from the published 99th percentiles. Larger studies are required to verify these findings.

Carryover can be a cause of false-positive results with the Beckman AccuTnI assay

Carryover can be a cause of false-positive results with the Beckman AccuTnI assay

High-Sensitive Troponin Testing and the “Runner's Syndrome”

Despite improved clinical care, heightened public awareness, and widespread health innovations, myocardial infarction (MI) is still responsible for nearly 12 million deaths worldwide each year, causing half of all deaths in several developed countries and representing one of the main causes of death in many developing countries. Nearly 2400 Americans die of MI each day, an average of 1 death every 37 s. It is estimated that in 2009, 785,000 Americans will have a new coronary attack, and about 470,000 will have a recurrent attack ( 1 American Heart AssociationHeart disease and stroke statistics—2009 update. http://www.americanheart.org/presenter.jhtml?identifier=3037327 Google Scholar ). Therefore, further efforts should be placed on early, accurate diagnosis and appropriate triage to prevent mortality and related morbidity ( 1 American Heart AssociationHeart disease and stroke statistics—2009 update. http://www.americanheart.org/presenter.jhtml?identifier=3037327 Google Scholar ). According to the new universal definition of MI, troponin testing is of paramount importance (if not the mainstay) in the diagnosis, because MI is diagnosed in the presence of clinical evidence of ischemia when blood levels of this most sensitive and specific biomarker are increased above the 99th percentile of a normal reference population ( 2 Thygesen K. Alpert J.S. White H.D. Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial InfarctionUniversal definition of myocardial infarction. Circulation. 2007; 116: 2634-2653 Crossref PubMed Scopus (2122) Google Scholar ). With the advent of the high-sensitive (hs) cardiac troponin T (cTnT) and I (cTnI) assays, however, a paradigm shift has occurred in the detection of myocardial stress, injury, ischemia, and infarction, as well as in the clinical management of patients with slightly increased troponin concentrations in blood. At variance with the traditional cardiac troponin cTnT assay (Roche Diagnostics; Basel, Switzerland), whose traditional cutoff is 0.03 μg/L, the 10%-Coefficient of Variation (CV) cutoff concentration of the new hs-cTnT immunoassay from Roche Diagnostics is as low as 0.009 μg/L, which is even lower than the 99th percentile value of the reference population (0.016 μg/L, diagnostic cutoff) ( 3 Mingels A. Jacobs L. Michielsen E. Swaanenburg J. Wodzig W. van Dieijen-Visser M. Reference population and marathon runner sera assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and I assays. Clin Chem. 2009; 55: 101-108 Crossref Scopus (246) Google Scholar ). Likewise, cTnT, the 10%-CV concentration of a new hs-cardiac Troponin I (cTnI) assay (Hs-cTnI assay, Beckman Coulter; Fullerton, CA, USA), has been reported to be as low as 8.66 ng/L, with 99th percentile estimates in lithium, heparin, serum, and ethylenediaminetetraacetic acid plasma of 9.20, 8.00, and 8.60 ng/L, respectively (the 99th percentile limit of the traditional Beckman Coulter AccuTnI assay is 0.04 μg/L) ( 4 Kavsak P.A. MacRae A.R. Yerna M.J. Jaffe A.S. Analytic and clinical utility of a next-generation, highly sensitive cardiac troponin I assay for early detection of myocardial injury. Clin Chem. 2009; 55: 573-577 Crossref PubMed Scopus (141) Google Scholar ).

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

Objectives Long-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. Methods In 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). Results Subjects 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). Conclusion Early 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.

Analytic and Clinical Utility of a Next-Generation, Highly Sensitive Cardiac Troponin I Assay for Early Detection of Myocardial Injury

Improvements in cardiac troponin (cTn) assays have increased the rapidity with which clinicians can identify patients with changing cTn concentrations (rise or fall) indicative of acute myocardial injury. The aim of the present study was to characterize a new, high-sensitivity cTnI (hs-cTnI) assay and examine whether increased sensitivity can result in still earlier detection of evolving injury. We determined the limit of detection, precision profiles, and preliminary estimates of the 99th percentile for the Beckman Coulter hs-cTnI assay in 125 healthy individuals (age <55 years, 54% male). We compared AccuTnI and hs-cTnI to assess whether change criteria for early concentration changes (i.e., > or =3SD for low concentrations and 20% difference for concentrations >0.10 microg/L) were exceeded in the first 2 specimens (median time between specimens, 1 h; 25th-75th percentile, 1-3 h) from subjects with symptoms suggestive of cardiac ischemia (n = 290). The limit of detection for the hs-cTnI assay was 2.06 ng/L, and the 20% CV and 10% CV concentrations were 2.95 and 8.66 ng/L, respectively. The preliminary 99th percentile estimates in lithium heparin, serum, and EDTA plasma were 9.20, 8.00, and 8.60 ng/L, respectively. In 108 patients with myocardial injury based on the peak AccuTnI concentration, applying the change criteria on the 2 earliest specimens identified 81% (95% CI 73%-88%) of patients using the hs-cTnI assay compared to 62% (53%-71%) using the AccuTnI assay (P < 0.001). Although more extensive validation studies are required, this Beckman Coulter hs-cTnI assay appears to detect patients with evolving myocardial injury earlier.

Clinical Performance of Two Highly Sensitive Cardiac Troponin I Assays

The aim of this study was to compare the clinical performance of 2 sensitive cTnI assays with 10% CV imprecision below the 99th percentile upper reference limit. We measured cardiac troponin and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in a random sample of the Global Use of Strategies To Open Occluded Coronary Arteries (GUSTO) IV cohort (n = 1251). Outcome data of 1-year mortality and the composite endpoint DMI [death and/or myocardial infarction (MI) within 30 days] were available in all patients. The 99th percentile of a healthy population was estimated from the Sweden Women and Men and Ischemic Heart Disease (SWISCH) cohort (n = 442). We measured cardiac troponin I (cTnI) using the Access AccuTnI (Beckman Coulter) and Centaur TnI Ultra (Siemens Healthcare Diagnostics) and NT-proBNP using the Elecsys 2010 (Roche Diagnostics). Applying the 10% CV cutoff, the sensitivity of the Access AccuTnI assay in identifying DMI and death was higher than that of the Centaur TnI Ultra (P = 0.02 and P < 0.001), and the AccuTnI assay also identified more patients at risk (P < 0.001) and with poor outcome. Applying the 99th percentile cutoffs, AccuTnI identified more patients at risk than the Centaur TnI (P < 0.001) and with significant differences in outcome. Significantly more patients with cardiac troponins below the cutoffs as measured by Centaur TnI had increased NT-proBNP concentrations (P < 0.001) compared with AccuTnI. The AccuTnI assay identified more patients at risk than the Centaur cTnI Ultra assay. Our results demonstrate the clinical potential of high-sensitivity cardiac troponin assays for the identification of patients at risk of dying from cardiovascular disease.

Value of Cardiac Troponin I Cutoff Concentrations below the 99th Percentile for Clinical Decision-Making

The aim of this study was to evaluate factors influencing the 99th percentile for cardiac troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease. We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined cTnI cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (FRagmin and Fast Revascularization during InStability in Coronary artery disease) study at 6 months after these patients had suffered acute coronary syndrome. Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 microg/L to 0.028 microg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Whereas the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9-5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7-4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction. The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute coronary syndrome patients and therefore may be preferable for risk stratification.

Pathophysiologic mechanisms of persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome

Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients. Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 microg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation. Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.

Persistent Cardiac Troponin I Elevation in Stabilized Patients After an Episode of Acute Coronary Syndrome Predicts Long-Term Mortality

In patients with non-ST-elevation acute coronary syndrome, any troponin elevation is associated with an increased risk for cardiovascular events. However, the prevalence and prognostic importance of persistent troponin elevation in stabilized patients after an episode of non-ST-elevation acute coronary syndrome are unknown and were therefore assessed in this study. Cardiac troponin I (cTnI) was measured in 1092 stabilized patients at 6 weeks and 3 and 6 months after enrollment in the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC-II) trial. cTnI was analyzed with the Access AccuTnI assay with the application of different prognostic cutoffs. Outcomes were assessed through 5 years. Elevated cTnI levels >0.01 microg/L were found in 48% of the study patients at 6 weeks, in 36% at 6 months, and in 26% at all 3 measurements. cTnI elevation was associated with increased age and other cardiovascular high-risk features. The lowest tested cTnI cutoff (0.01 microg/L) was prognostically most useful and was independently predictive of mortality (hazard ratio, 2.1 [95% confidence interval, 1.3 to 3.3]; P=0.001) on multivariable analysis adjusted for cardiovascular risk factors and randomization to an invasive versus noninvasive treatment strategy, whereas it was related to myocardial infarction only on univariate analysis. Persistent minor cTnI elevation can be detected frequently in patients stabilized after an episode of non-ST-elevation acute coronary syndrome with the use of a sensitive assay. Elevated cTnI levels >0.01 microg/L predict mortality during long-term follow-up. Our results emphasize the importance of further troponin testing in non-ST-elevation acute coronary syndrome patients after hospital discharge.

PO1-24 HEPATIC CELL-SPECIFIC ATP-BINDING CASSETTE (ABC) TRANSPORTER PROFILING IDENTIFIES PUTATIVE NOVEL CANDIDATES FOR MACROPHAGE CHOLESTEROL HOMEOSTASIS IN MICE

Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients.Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 μg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation.Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.

Earlier detection of myocardial infarction by an improved cardiac TnI assay

Objectives: The aim of this study was to establish the diagnostic sensitivity of combinations of well-selected monoclonal antibodies (mAbs) against cardiac troponin I (cTnI) to allow an earlier rule-in of acute coronary syndrome (ACS) patients. Design and methods: Using several combinations of mAbs, four new experimental cTnI immunoassays were evaluated to analyze plasma samples from 62 patients suffering from angina (16/62), patients having a chest pain of extracardiovascular origin (19/62) and ACS without ST elevation (NSTE-ACS) (27/62). Results: Assay 2, which relies on a capture mAb directed against the central part of cTnI and two conjugated mAbs directed against the N-ter region, provided the best clinical sensitivity. In 11 out of 27 patients with NSTE-ACS, it detected an early rise of cTnI within 0 and 1 h upon admission, contributing to the detection of 53% of samples found to be negative by the reference AccuTnI Assay upon admission (Beckman Coulter), thereby reducing the delay in diagnosis. Conclusions: Assay 2 can identify early cTnI elevation in NSTE-ACS, possibly facilitating the rule-in procedure for these patients once the assay is automated.

Evaluation of clinical performance of cardiac troponin I in diagnosis and prognosis of non-ST elevation acute coronary syndromes

目的 评价心肌肌钙蛋白Ⅰ(cTnI)对非ST段抬高心肌梗死(NSTEMI)的诊断价值,并探讨其与非ST段抬高急性冠状动脉综合征(NSTEACS)近期和远期预后的关系.方法 cTnI测定采用新一代Beckman Coulter AccuTnI化学发光试剂盒;应用操作者工作特征曲线(ROC曲线)分析cTnI对NSTEMI的诊断的敏感度和特异度;同时应用ROC曲线比较不同生化标志物对NSTEMI诊断价值;将269例NSTEACS患者以cTnI水平0.04 μg/L为分界点进行分组,比较cTnI升高组和cTnI正常组30 d内和1年内急性心肌梗死和/或心源性死亡事件的发生情况.结果 ROC曲线分析结果显示诊断NSTEMI的最佳cut-off值为0.1 μg/L,此界值诊断的敏感度和特异度为91.4%和89.3%;肌酸激酶及其同工酶MB、乳酸脱氢酶和α-羟丁酸脱氢酶各指标的诊断敏感度和特异度均低于cTnI;单因素分析显示cTnI升高组30 d内和1年内复合心脏事件的发生率(3.61%和6.02%)较cTnI正常组(均为0)显著升高(P＜0.05);多因素分析显示校正高血压、糖尿病、高脂血症、陈旧心肌梗死、心电图改变等危险因素后,cTnI升高是30 d内发生复合心脏事件的独立危险因子,风险比值(OR)=8.175,95%可信区间(CI)为1.014～65.917,P=0.049;也是1年内发生复合心脏事件的独立预告因子,OR=2.612,95% CI为1.164～5.859,P=0.02.结论 Beckman公司出品的cTnI对NSTEMI的诊断具有较高的敏感度和特异度,对NSTEACS患者的预后判断具有重要价值。

Comparison of Cardiac Troponin I Immunoassays Variably Affected by Circulating Autoantibodies

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. 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). 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). 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.

Clinical performance of three cardiac troponin assays in patients with unstable coronary artery disease (a FRISC II substudy)

The assay of cardiac-specific troponins (cTroponins) is a sensitive and specific means to diagnose myocardial injury. Several assays for the measurement of cardiac-specific troponin I (cTnI), but only 1 for the assay of cardiac specific troponin T (cTnT), are commercially available. The aim of this study was to compare 3 of these assays (i.e., Access AccuTnI [cTnI], AxSym [cTnI], and Elecsys 3 rd generation [cTnI]) and their clinical performances in a group of patients (n = 1,763) with unstable coronary artery disease (Fragmin and fast Revascularisation during InStability in Coronary artery disease [FRISC II] trial). Clinical events after 1-year follow-up, such as death and death and/or acute myocardial infarction, were recorded and the effects of invasive or noninvasive treatment evaluated in relation to cTroponin levels. Overall the 2 cTnI methods showed good correlation (r s = 0.96), whereas correlations to the cTnT assay were somewhat lower (r s = 0.93). Patients with nonelevated levels, as measured with any of the 3 biomarkers, had a significantly better prognosis than patients with elevated levels (p <0.001). A cohort of 10% to 12.4% of patients with a poor prognosis was identified only by the Access AccuTnI assay. Invasive treatment reduced clinical events only in the group of patients with elevated cTroponin levels. We conclude that stratification of patients with unstable coronary artery disease by means of cTroponin measurements is important in clinical management. It is also apparent that assays with superior sensitivity, such as the Access AccuTnI, identify more patients with poor prognosis who are candidates for early invasive procedures.