Contemporary cTnI Assay Research Articles

No increase in the incidence of cardiac troponin I concentration above the 99th percentile by Siemens Centaur high-sensitivity compared to the contemporary assay

BackgroundThis study aimed to compare the incidence of cardiac troponin I (cTnI) concentrations above the limit of quantification (LOQ) and the sex-specific 99th percentile upper reference limits (URLs) between the Ultra contemporary cTnI assay and the high-sensitivity (hs-cTnI) assay on Siemens Centaur in patients evaluated in the emergency department (ED) and inpatient at a U.S. urban academic hospital. MethodsA retrospective study was performed in an unselected patient cohort who presented to the hospital with symptoms suggestive of myocardial injury. All clinically ordered samples for cTnI assay (n = 1,056, LOQ 0.03 µg/L, URL 0.04 µg/L) were simultaneously tested on the hs-cTnI assay (LOQ 2.5 ng/L; URL 58 ng/L and 39 ng/L for male and female, respectively). ResultsThe incidence of elevated cTnI above the 99th percentile URL in males measured by the hs-cTnI assay was significantly lower compared to the cTnI assay (31.4% vs. 38.7%, p = 0.016), whereas there was no difference in females (27.4% vs. 30.2%, p = 0.35) in all the patient samples. In ED patient samples (n = 718), the incidence of elevated cTnI above the sex-specific 99th percentile URL was not significantly different between the hs-cTnI and contemporary cTnI assays in either sex (male: hs-cTnI 16.6% vs. cTnI 21.5%, p = 0.13; female: hs-cTnI 19.6% vs. cTnI 21.1%, p = 0.66). The agreement between the two assays was 93.5% (kappa = 0.798). Results were confirmed in an independent patient cohort measured by the same instruments at another hospital. ConclusionOur study suggests that implementation of the hs-cTnI assay would not lead to an increase in the proportion of elevated cTnI above the 99th percentile in the emergency department and other inpatient units.

Biological Variation of Cardiac Troponins in Health and Disease: A Systematic Review and Meta-analysis.

Many studies have assessed the biological variation (BV) of cardiac-specific troponins (cTn), reporting widely varying within-subject BV (CVI) estimates. The aim of this study was to provide meta-analysis-derived BV estimates for troponin I (cTnI) and troponin T (cTnT) for different sampling intervals and states of health. Relevant studies were identified by a systematic literature search. Studies were classified according to their methodological quality by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Meta-analyses of BIVAC-compliant studies were performed after stratification by cTn isoform, exclusion of results below the limit of detection, states of health, and sampling interval to deliver reference change values (RCV), index of individuality (II) and analytical performance specifications (APS) for these settings. Sixteen and 15 studies were identified for cTnI and cTnT, respectively, out of which 6 received a BIVAC grade A. Five studies had applied contemporary cTnI assays, but none contemporary cTnT. High-sensitivity (hs-) cTnI and cTnT delivered similar estimates in all settings. Long-term CVI estimates (15.1; 11.3%) derived from healthy individuals were higher than short-term (4.3%; 5.3%) for hs-cTnI and hs-cTnT, respectively, although confidence intervals overlapped. Estimates derived from diseased subjects were similar to estimates in healthy individuals for all settings. This study provides robust estimates for hs-cTnI and hs-cTnT applicable for different clinical settings and states of health, allowing for the use of RCV both to aid in the diagnosis of myocardial injury and for prognosis. BV-based APS appear too strict for some currently available technologies.

How to choose a point-of-care testing for troponin.

BackgroundPoint‐of‐care (POC) cTn assays are needed when the central laboratory is unable to provide timely results to the emergency department. Many POC devices are available. The prospect of choosing them is daunting. In order to provide a quick decision‐making reference for POC cTn device selection comparing them to the central laboratory, seven POC devices commonly employed by emergency department were evaluated.MethodsFirstly, we reviewed all devices package inserts. Secondly, we evaluated several POC cTn assays for imprecision, linearity, and correlation with central laboratory assays according to CLSI EP protocols. The linear regression analyses were performed only for the detectable concentrations. Five cTnI devices (Alere Triage, BioMerieux Vidas, Mitsubishi Pathfast, ReLIA TZ‐301, and Radiometer AQT90) were evaluated against a contemporary cTnI assay (Beckman Access II Accu TnI). Two cTnT assays (Radiometer AQT90 and Roche Cobas h232) were compared to a high‐sensitivity (hs) cTnT method (Roche Cobas e601).ResultsFor cTn levels around the 99th percentile upper reference limits (URLs) of the comparator assays, imprecision could not be assessed for the Alere, BioMerieux, and Cobas h232 as they gave undetectable readings due to a lack of assay sensitivity. Imprecision (CV) was unacceptably high for the ReLIA (33.3%). On account of this precision metric, these four assays were deemed unsuitable. Regression analyses showed acceptable linearity for all the POC devices. The correlation coefficients for ReLIA, BioMerieux, Cobas h232, and Radiometer cTnT were >0.95. Unlike the cTnT devices, the cTnI assays employ different capture and detection antibodies leading to non‐commutable results. The POC cTn results were concordant with their comparator—Radiometer cTnT 90%, Pathfast cTnI 85%, and Radiometer cTnI 75%.ConclusionOur study provides the procedure and essential data to guide selection of a POC cTn device. Of the point‐of‐care devices, methods evaluated Radiometer AQT90 (cTnI and cTnT) and Pathfast might be considered.

P1731High-sensitivity troponin with sex-specific thresholds in suspected acute coronary syndrome

Abstract Background/Introduction Major disparities between women and men in the diagnosis, management and outcome of acute coronary syndrome are well recognised. Whether sex-specific diagnostic thresholds for myocardial infarction will address these differences is uncertain. Purpose To evaluate the impact of implementing a high-sensitivity cardiac troponin I (hs-cTnI) assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome. Methods In a stepped-wedge, cluster-randomized controlled trial across ten hospitals we evaluated the implementation of a hs-cTnI assay in 48,282 (47% women) consecutive patients with suspected acute coronary syndrome. During a validation phase the hs-cTnI assay results were suppressed and a contemporary cTnI assay with a single threshold was used to guide care. Myocardial injury was defined as any hs-cTnI concentration >99th centile of 16 ng/L in women and 34 ng/L in men. The primary outcome was myocardial infarction after the initial presentation or cardiovascular death at 1 year. In this prespecified analysis, we evaluated outcomes in men and women before and after implementation of the hs-cTnI assay. Results Use of the hs-cTnI assay with sex-specific thresholds increased myocardial injury in women by 42% (from 3,521 (16%) to 4,991 (22%)) and by 6% in men (from 5,068 (20%) to 5,369 (21%)). Whilst treatment increased in both sexes, women with myocardial injury remained less likely than men to undergo coronary revascularisation (15% versus34%), or to receive dual anti-platelet (26% versus43%), statin (16% versus26%) or other preventative therapies (P<0.001 for all). The primary outcome occurred in 18% (369/2,072) and 17% (488/2,919) of women with myocardial injury during the validation and implementation phase respectively (adjusted hazard ratio 1.11, 95% confidence interval 0.92 to 1.33), compared to 18% (370/2,044) and 15% (513/3,325) of men (adjusted hazard ratio 0.85, 95% confidence interval 0.71 to 1.01). Patient management Conclusion Use of sex-specific thresholds identified five-times more additional women than men with myocardial injury, such that the proportion of women and men with myocardial injury is now similar. Despite this increase, women received approximately half the number of treatments for coronary artery disease as men and their outcomes were not improved. Acknowledgement/Funding The British Heart Foundation

Comparability and precision of four oncological methods on seven immunochemistry analysers

Siemens Healthcare Diagnostics has four commercially available assays on different analytical platforms using different methodologies to generate signal. We assessed the analytical performance of the Dimension EXL hs-cTnI assay (LOCI method) across different matrices and compared it to two different acridinium ester-based hs-cTnI assays (ADVIA Centaur and Abbott ARCHITECT).The analytical sensitivity and precision below the 99th-percentile was determined for the Dimension EXL hs-cTnI assay. Method comparisons were performed between the Dimension EXL contemporary cTnI and the hs-cTnI assays, between different matrices for the EXL hs-cTnI assay (serum, lithium heparin and EDTA plasma), and between different hs-cTnI assays (EXL versus ADVIA Centaur or Abbott ARCHITECT) using non-parametric analyses.The limit of blank and detection were 0.9 ng/L and 1.7 ng/L, respectively, with imprecision of 5.8% at 8.6 ng/L and 3.2% at 47.5 ng/L. Comparison between the EXL contemporary cTnI and hs-cTnI assay (range: 2.6–4214 ng/L) yielded proportional lower concentrations for the hs-cTnI assay (slope = 0.86; 95%CI: 0.81 to 0.96, n = 40); however, there was no difference in concentrations below 100 ng/L between the assays (median difference = −2.7 ng/L; 95%CI: −9.8 to 9.3). Passing-Bablok regression analysis with EDTA plasma yielded proportionally higher concentrations with the EXL hs-cTnI versus Abbott hs-cTnI (slope = 1.45; 95%CI: 1.02–1.86, n = 40) with proportionally lower concentrations with EDTA versus lithium heparin plasma with the EXL hs-cTnI assay alone (slope = 0.93; 95%CI: 0.90 to 0.99, n = 40). Comparison with Abbott hs-cTnI concentrations below 100 ng/L in the three matrices, indicated that the EXL hs-cTnI assay yielded higher concentrations (median difference range: 3.4–9.4 ng/L), with differences also evident when comparing the EXL hs-cTnI assay to the ADVIA Centaur hs-cTnI assay.The Siemens EXL hs-cTnI assay meets the analytical criteria for a high-sensitivity assay, with assay specific cutoffs important to maximize clinical performance.

Analytical characterization of the Siemens Dimension EXL high-sensitivity cardiac troponin I assay

BackgroundSiemens Healthcare Diagnostics has four commercially available assays on different analytical platforms using different methodologies to generate signal. We assessed the analytical performance of the Dimension EXL hs-cTnI assay (LOCI method) across different matrices and compared it to two different acridinium ester-based hs-cTnI assays (ADVIA Centaur and Abbott ARCHITECT). MethodsThe analytical sensitivity and precision below the 99th-percentile was determined for the Dimension EXL hs-cTnI assay. Method comparisons were performed between the Dimension EXL contemporary cTnI and the hs-cTnI assays, between different matrices for the EXL hs-cTnI assay (serum, lithium heparin and EDTA plasma), and between different hs-cTnI assays (EXL versus ADVIA Centaur or Abbott ARCHITECT) using non-parametric analyses. ResultsThe limit of blank and detection were 0.9 ng/L and 1.7 ng/L, respectively, with imprecision of 5.8% at 8.6 ng/L and 3.2% at 47.5 ng/L. Comparison between the EXL contemporary cTnI and hs-cTnI assay (range: 2.6–4214 ng/L) yielded proportional lower concentrations for the hs-cTnI assay (slope = 0.86; 95%CI: 0.81 to 0.96, n = 40); however, there was no difference in concentrations below 100 ng/L between the assays (median difference = −2.7 ng/L; 95%CI: −9.8 to 9.3). Passing-Bablok regression analysis with EDTA plasma yielded proportionally higher concentrations with the EXL hs-cTnI versus Abbott hs-cTnI (slope = 1.45; 95%CI: 1.02–1.86, n = 40) with proportionally lower concentrations with EDTA versus lithium heparin plasma with the EXL hs-cTnI assay alone (slope = 0.93; 95%CI: 0.90 to 0.99, n = 40). Comparison with Abbott hs-cTnI concentrations below 100 ng/L in the three matrices, indicated that the EXL hs-cTnI assay yielded higher concentrations (median difference range: 3.4–9.4 ng/L), with differences also evident when comparing the EXL hs-cTnI assay to the ADVIA Centaur hs-cTnI assay. ConclusionThe Siemens EXL hs-cTnI assay meets the analytical criteria for a high-sensitivity assay, with assay specific cutoffs important to maximize clinical performance.

Analytical Concordance of Diverse Point-of-Care and Central Laboratory Troponin I Assays.

Cardiac troponin I (cTnI) 99th percentile cutoffs, used in the diagnosis of acute myocardial infarction, are not standardized across cTnI assays. We compared 3 point-of-care (POC) and 1 central laboratory contemporary cTnI assays against the Abbott high-sensitivity (hs) cTnI to evaluate the analytical concordance and the feasibility of using a single cutoff value for all assays. Fresh blood samples collected from 102 inpatients in the coronary care unit were measured on central laboratory instruments (Beckman Coulter DxI AccuTnI+3 TnI, Abbott Architect hs-TnI) and cTnI POC analyzers (Alere Triage Troponin I, Radiometer AQT90, Abbott i-STAT). Agreement and correlation between the contemporary cTnI assays and hs-cTnI assay were assessed using regression analysis. Proportional bias was assessed using Bland-Altman plots. Concordance between the contemporary cTnI and hs-cTnI assays was determined by diagnostic contingency tables at specific cutoffs. Most POC cTnI assays had excellent correlation with the Abbott hs-cTnI method (r 2 = 0.955-0.970) except for Alere Triage (r 2 = 0.617), while proportional bias is evident between all cTnI assays. Overall concordance between POC contemporary cTnI assays and hs-cTnI assay was 80% to 90% at their respective 99th percentile cutoffs. The concordance increased to 90% to 95% when a fixed cutoff of 0.03 to 0.05 ng/mL was used across the assays. This study demonstrates poor analytical concordance between cTnI assays at the 99th percentile and supports the notion of a single clinical decision limit for cTnI and consequently standardization of diagnostic protocols despite the analytical differences among these assays.

Type 1 and 2 Myocardial Infarction and Myocardial Injury: Clinical Transition to High-Sensitivity Cardiac Troponin I

BackgroundStudies addressing patients with type 2 myocardial infarction and myocardial injury, including the impact of using high-sensitivity (hs) cardiac troponin (cTn) assays on their incidence are needed. MethodsOurs is a prospective, observational US cohort study. Consecutive emergency department patients with serial cTnI measurements were studied. Outcomes included 180-day mortality and major adverse cardiac events, including 2-year follow-up for those with myonecrosis. ResultsAmong 1640 patients, using a contemporary cTnI assay, 30% (n = 497) had ≥1 cTnI >99th percentile, with 4.7% (n = 77), 8.5% (n = 140), and 17% (n = 280) classified as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Compared with patients without myonecrosis, 180-day mortality was higher for type 2 myocardial infarction (4% vs 13%, P < .0001) (adjusted hazard ratio 2.7; 95% confidence interval, 1.6-4.8; P = .0005) and myocardial injury (4% vs 11%, P < .0001) (adjusted hazard ratio 1.8; 95% confidence interval, 1.1-3.0; P = .02), both with mortality >20% at 2 years. Predictors of 2-year mortality for type 2 myocardial infarction included age, congestive heart failure, and beta-blockers. Relative to the contemporary cTnI assay, hs-cTnI had less myonecrosis (30% vs 26%, P = .003) and acute myocardial infarction (13.2% vs 10.8%, P = .032), including fewer type 2 myocardial infarctions (8.5% vs 6.3, P = .01), with no difference in myocardial injury (17% vs 15%, P = .1). ConclusionscTnI increases are encountered in approximately a third of patients, the majority due to nonatherothrombotic conditions. Compared with patients without myonecrosis, type 2 myocardial infarction and myocardial injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs-cTnI assay does not lead to more myocardial injury or infarction.

Incidence of Undetectable, Measurable, and Increased Cardiac Troponin I Concentrations Above the 99th Percentile Using a High-Sensitivity vs a Contemporary Assay in Patients Presenting to the Emergency Department.

We compared the incidence of undetectable [below the limit of detection (LoD)], measurable (LoD to 99th percentile), and increased cardiac troponin I (cTnI) concentrations above the 99th percentile between Abbott high-sensitivity cTnI (hs-cTnI) and contemporary cTnI assays in a US emergency department population. Patients (n = 2100) presenting to the emergency department who had serial cTnI (0, 3, 6, 9 h) measurements ordered on clinical indication were enrolled. Contemporary cTnI [Abbott Architect used clinically; 99th percentile: 0.030 μg/L (30 ng/L)] and hs-cTnI [Abbott investigational; sex-specific 99th percentiles: female (F) 16 ng/L, male (M) 34 ng/L] assays simultaneously measured fresh EDTA plasma. The hs-cTnI assay measured fewer undetectable cTnI concentrations compared to the contemporary cTnI assay across baseline (F: 31% vs 47%, M: 22% vs 40%) and serial (F: 21% vs 46%; M: 19% vs 54%) measurements. Conversely, the proportion of measurable cTnI concentrations was higher using hs-cTnI compared to contemporary cTnI assay across both baseline (F: 46% vs 31%; M: 60% vs 33%) and serial (F: 48% vs 28%; M: 83% vs 40%) measurements. The overall proportion of patients with increased cTnI concentrations above the 99th percentile was not significantly different between the contemporary (31%) and hs-cTnI (26%) assays (P = 0.09). In patients presenting to the emergency department, the use of the Abbott hs-cTnI assay provides clinicians with more numeric cTnI concentrations. This occurs via a shift from results below the LoD to those between the LoD and the 99th percentile and does not increase in the number of cTnI concentrations above the 99th percentile.

A practical approach for the validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a North American city

ObjectivesDespite several publications on the analytical performance of high-sensitivity cardiac troponin (hs-cTn) assays, there has been little information on how laboratories should validate and implement these assays into clinical service. Our study provides a practical approach for the validation and implementation of a hs-cTn assay across a large North American City. Design and methodsValidation for the Abbott ARCHITECT hs-cTnI assay (across 5 analyzers) consisted of verification of limit of blank (LoB), precision (i.e., coefficient of variation; CV) testing at the reported limit of detection (LoD) and within and outside the 99th percentile, linearity testing, cTnI versus hs-cTnI patient comparison within and between analyzers (Passing and Bablok and non-parametric analyses). Education, clinical communications, and memorandums were issued in advance to inform all staff across the city as well as a selected reminder the day before live-date to important users. All hospitals switched to the hs-cTnI assay concurrently (the contemporary cTnI assay removed) with laboratory staff instructed to repeat samples previously measured with the contemporary cTnI assay with the hs-cTnI assay only by physician request. ResultsAcross the 5 analyzers and 6 reagent packs the overall LoB was 0.6ng/L (n=60) with a CV of 33% at an overall mean of 1.2ng/L (n=60; reported LoD=1.0ng/L), with linearity demonstrated from 45,005ng/L to 1.1ng/L. Precision testing with a normal patient-pool QC material (mean range across 5 analyzers was 3.9–4.4ng/L) yielded a range of CVs from 7% to 10% (within-run) and CVs from 7% to 18% (between-run) with the high patient-pool QC material (mean range across 5 analyzers was 29.6–36.3ng/L) yielding a range of CVs from 2% to 5% (within-run) and CVs from 4% to 8% (between-run). There was agreement between hs-cTnI versus cTnI with the patient samples (slope ranges: 0.89–1.03; intercept ranges: 1.9–3.8ng/L), however, the median CV on patient samples <100ng/L across the analyzers was 5.6% for hs-cTnI versus 18.7% for the contemporary assay (p<0.001). Following the switch to hs-cTnI testing, no requests for repeat measurements were received. ConclusionsValidation and implementation of hs-cTnI testing across multiple sites requires collaboration within the laboratories and between hospital laboratories and clinical staff.

Impact of Statin Use on Exercise-Induced Cardiac Troponin Elevations

Marathon running commonly causes a transient elevation of creatine kinase and cardiac troponin I (cTnI). The use of statins before marathon running exacerbates the release of creatine kinase from skeletal muscle, but the effect of statin use on exercise-induced cTnI release is unknown. We therefore measured cTnI concentrations in statin-using (n= 30) and nonstatin-using (n= 41) runners who participated in the 2011 Boston Marathon. All runners provided venous blood samples the day before, within an hour of finishing, and 24hours after the marathon. cTnI was assessed at each time point via both a contemporary cTnI and high-sensitivity cTnI (hsTnI) assay. Before the marathon, cTnI was detectable in 99% of runners with the use of the hsTnI assay. All participants completed the marathon (finish time: 4:04:09 ± 0:41:10), and none had symptoms of an acute coronary syndrome. cTnI increased in all runners (p <0.001) immediately after the marathon, and half (hsTnI= 54% vs contemporary cTnI= 47%) exceeded the diagnostic cut-point for an acute myocardial infarction. Statin use did not affect the magnitude of cTnI release (group*time p= 0.47) or the incidence of runners with cTnI elevation greater than the diagnostic cut-point for myocardial infarction (57% vs 51%, p= 0.65). In addition, there was no significant association between statin potency and cTnI release (r= 0.09, p= 0.65). In conclusion, marathon-induced cTnI increases are not altered by statin use.

Peri-operative troponin monitoring using a prototype high-sensitivity cardiac troponin I (hs-cTnI) assay: comparisons with hs-cTnT and contemporary cTnI assays

Non-cardiac surgery is associated with major vascular complications and higher incidences of elevated plasma troponin (cTn) concentration. Goal-directed therapy (GDT) is a stroke volume (SV)-guided approach to intravenous (IV) fluid therapy that improves tissue perfusion, oxygenation and reduces post-operative complications. In patients undergoing major gastro-intestinal surgery, we compared high sensitive and contemporary troponin assays and correlated results with patient outcome. Patients (n = 135) were randomized to receive IV fluid, guided by either the central venous pressure (CVP group, n = 45) or SV (± dopexamine inotrope, n = 45 per group). Serum was obtained pre- and post-operatively (0, 8 and 24 h) for troponin analysis by a prototype hs-cTnI assay (Abbott Laboratories), hs-cTnT (Roche Diagnostics) and contemporary cTnI (Beckman Coulter) assays. All troponin measurements were increased (P ≤ 0.05) post-operatively but there was no difference (P > 0.05) amongst treatments. Post-operative increases were reported more frequently (P ≤ 0.05) and earlier with hs-cTnI. Temporal increases (P ≤ 0.05) were reported in patients with and without complications for hs-cTnI/T assays but only in the complications group for cTnI measurements. Elevations ≥99th centile occurred most often (P ≤ 0.05) for hs-cTnT measurements but with similar frequency for both outcome groups (all assays). Only the hs-cTnI assay showed an increased relative risk of mortality (P ≤ 0.05) for elevations ≥99th centile Our study may suggest a possible preference for the hs-cTnI assay in the peri-operative setting; however, our findings should be verified for larger cohort studies where emerging reference range data is incorporated for improving risk prediction with hs-cTn assays.

Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome

The study sought to compare the clinical performance of two more sensitive cardiac troponin (cTn) assays, a novel high-sensitivity (hs) troponin T assay and a contemporary cTnI assay. We measured hs-cTnT (Roche TnThs) and cTnI (Siemens Centaur Ultra) on presentation in 1,384 patients with suspected acute coronary syndrome (ACS) who underwent early invasive strategy within 24h after presentation. Kaplan-Meier, Cox proportional hazards, and receiver-operating characteristic (ROC) analysis was used to compare their prognostic performance for the prediction of all-cause death and death/MI (myocardial infarction) after a median of 271days. We also compared the diagnostic performance of these assays on presentation for early diagnosis of non-STEMI. Both hs-cTnT and cTnI were independently predictive of long-term death (OR 3.51 vs. 2.19) and the composite of death/MI (OR 9.24 vs. 3.61), across the spectrum of ACS and in patients without ACS. When used as a continuous variable, ROC analysis demonstrated significantly higher areas under the curve (AUC) for hs-cTnT as compared to cTnI for the prediction of death/MI (0.721 vs. 0.672, P=0.024), a trend to better prediction of all-cause death (0.721 vs. 0.672, P=0.093) and significantly higher AUC for early diagnosis of non-STEMI (0.965 vs. 0.901, P<0.001). Using the 99th percentile cutoff for hs-cTnT and cTnI, both assays enable prediction of adverse long-term outcomes and earlier diagnosis of non-STEMI. Used as a continuous variable, the hs-cTnT assay showed superior performance compared to the cTnI assay, especially in regard to prognosis.

High-Sensitivity Cardiac Troponin: Hype, Help, and Reality

Articles in The New England Journal of Medicine get tremendous publicity, some justified and some not. Recently, 2 articles and an editorial (1)(2)(3) were published about the use of “high-sensitivity” cardiac troponin (cTn).1 These articles are welcome because they emphasize important concepts for clinicians. Some aspects, however, require clarification. Here we examine these articles and separate out new data from hype. No. Most of the assays used are contemporary assays (4), including the Siemens Ultra and Abbott Architect assays. Two new assays were included, both from Roche: a hs-cTnT assay (1) and a first description of a cTnI assay. There are no analytical data to evaluate the cTnI assay, but it appears similar to contemporary cTnI assays at best. The new hs-cTnT assay (2) is a novel high-sensitivity assay. Although there are no published analytical studies of the assay, there are several clinical publications. The hs-cTnT assay appears more analytically sensitive (4) than the others (see “What Does the Future Hold?” below). Despite that, the hs-cTnT assay was not statistically better clinically than the other assays for detection of acute myocardial infarction (AMI) (1). They are not novel. The findings are more robust because larger patient groups were used. But the concept is not new that if one uses ( a ) sensitive contemporary assays as opposed to many presently available insensitive assays and ( b ) the 99th percentile cutoff recommended by guidelines groups, then early diagnosis occurs frequently. It is the use of the 99th percentile value as a decision cutpoint that is key for early diagnosis. Similar findings were reported in 2006 and confirmed. The New England Journal of Medicine results (1)(2) are impressive, which likely reflects differences in the populations studied. Hopefully, the publicity associated with The New England Journal of Medicine …

The impact of the ESC/ACC redefinition of myocardial infarction and new sensitive troponin assays on the frequency of acute myocardial infarction

The prevalence of acute myocardial infarction (AMI) has increased due to the recent definitions, but the magnitude of this effect using contemporary highly sensitive troponin assays is unclear. The objective of this study is to compare the diagnosis of AMI using a contemporary troponin I (cTnI) biomarker and the 2003 American Heart Association (AHA) case definition with diagnoses made using the 1994 World Health Organization MONICA definition. Contemporary troponin I measurements were performed with the Beckman Coulter AccuTnI assay (Chaska, MN) on plasma specimens originally assayed in 1996 for creatine kinase (CK)-MB mass from 486 emergency department patients presenting within 24 hours of onset of symptoms suggestive of cardiac ischemia. In a subgroup of 258 patients with 2 specimens drawn at least 6 hours apart (the AHA "adequate set of biomarkers"), AMI prevalence using CK-MB was 19.4% (95% CI 15.0-24.7) based on MONICA and 19.8% (15.4-25.1) based on the AHA case definition using the criterion for change of > or = 20% between specimens. Using cTnI as the biomarker of choice, under the AHA definition, the prevalence increased to as high as 35.7% (30.1-41.7, a relative increase of 84%, P < .001) using the 99th percentile cutoff. In 121 patients with a lower index of suspicion and without the requisite 6-hour interval between measurements, positivity increased from 5% with CK-MB by MONICA up to 12% to 16% with cTnI by AHA. A highly sensitive contemporary cTnI assay used with the AHA case definition results in a 62% to 84% increase in the frequency of AMI diagnosis compared with MONICA criteria.

The linearity of reference standard values in the radial immunodiffusion assay of human C4 ( β1E globulin)

The prevalence of acute myocardial infarction (AMI) has increased due to the recent definitions, but the magnitude of this effect using contemporary highly sensitive troponin assays is unclear. The objective of this study is to compare the diagnosis of AMI using a contemporary troponin I (cTnI) biomarker and the 2003 American Heart Association (AHA) case definition with diagnoses made using the 1994 World Health Organization MONICA definition.Contemporary troponin I measurements were performed with the Beckman Coulter AccuTnI assay (Chaska, MN) on plasma specimens originally assayed in 1996 for creatine kinase (CK)–MB mass from 486 emergency department patients presenting within 24 hours of onset of symptoms suggestive of cardiac ischemia.In a subgroup of 258 patients with 2 specimens drawn at least 6 hours apart (the AHA “adequate set of biomarkers”), AMI prevalence using CK-MB was 19.4% (95% CI 15.0-24.7) based on MONICA and 19.8% (15.4-25.1) based on the AHA case definition using the criterion for change of ≥20% between specimens. Using cTnI as the biomarker of choice, under the AHA definition, the prevalence increased to as high as 35.7% (30.1-41.7, a relative increase of 84%, P < .001) using the 99th percentile cutoff. In 121 patients with a lower index of suspicion and without the requisite 6-hour interval between measurements, positivity increased from 5% with CK-MB by MONICA up to 12% to 16% with cTnI by AHA.A highly sensitive contemporary cTnI assay used with the AHA case definition results in a 62% to 84% increase in the frequency of AMI diagnosis compared with MONICA criteria.