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.     

External validation of the clinical chemistry score

BackgroundCombining high-sensitivity cardiac troponin (hs-cTn) with estimated glomerular filtration rate and glucose within the Clinical Chemistry Score (CCS) could help in the assessment of patients with suspected acute myocardial infarction (AMI).MethodsIn patients presenting with suspected AMI to the emergency department, we aimed to externally validate the performance of the CCS in a prospective international multicenter study and to directly compare the diagnostic and prognostic performance of the CCS with hs-cTnT and hs-cTnI baseline levels alone using a single cut-off approach. The diagnostic endpoint was diagnostic accuracy for AMI as centrally adjudicated by two independent cardiologists including cardiac imaging and serial hs-cTnT/I measurements. The prognostic endpoint was 30-day AMI or death.ResultsAMI was the final diagnosis in 620/3827 patients (16.2%) adjudicated with hs-cTnT and 599 patients (15.7%) adjudicated with hs-cTnI. The CCS resulted in high diagnostic accuracy for AMI and prognostic accuracy for 30-days AMI/death as quantified by the area under the receiver-operating characteristic curve (AUC), using hs-cTnT 0.90 (95%CI 0.89–0.91) and 0.89 (95%CI 0.88–0.90), using hs-cTnI 0.91 (95%Cl 0.90–0.92) and 0.90 (95%CI 0.89–0.91) respectively. E.g. a CCS of 0 points resulted in a sensitivity of 99.8% (95%CI 99.1–100%) for rule-out of index AMI and 99.5% (95%CI 98.5–100%) for AMI/death at 30 days for hs-cTnT and 99.8% (95%CI 98.9–100%) and 99.6% (95%CI 98.6–100%) using hs-cTnI.Overall, the single hs-cTnT/I measurement approach provided comparable diagnostic (sensitivity 99.5–99.7%) and prognostic (sensitivity 98.9–99.5%) performance versus the CCS.InterpretationThe CCS provided high diagnostic and prognostic performance also in this independent large validation cohort. A single hs-cTnT/I measurement approach for rule-out MI yielded similar estimates.     

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.     

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.     

Suspected myocardial infarction in the emergency department: An evaluation of clinical thresholds for the Beckman Coulter Access hsTnI high-sensitivity cardiac troponin I assay

Objective

The primary objective was to determine rapid rule-out (RRO) criteria for the outcome of myocardial infarction (MI) using the Beckman Coulter Access high-sensitivity cardiac troponin I (hs-cTnI) assay. Secondary objectives were to explore cut-points for rapid rule-in (RRI) and amount of change at 3-h (3-h delta) indicative of MI.

Methods

A retrospective study included ED patients with suspected MI between June and September 2019. hs-cTnI levels were performed at baseline and after 3 h. The performance benchmark for RRO criteria was a negative predictive value (NPV) for MI with a lower 95% confidence limit >99%, and for RRI and 3-h delta cut-points was a positive predictive value (PPV) for MI >70%. Delta calculation required rising hs-cTnI levels, with at least one above the 99th percentile of the upper reference limit. Analyses utilised receiver operating characteristic (ROC) curves and contingency tables.

Results

Baseline hs-cTnI levels from 935 patients were available for RRO analyses. Of tested criteria, baseline hs-cTnI <6 ng/L (females) or <11 ng/L (males) plus symptom onset >2 h met the performance benchmark (NPV: 100% [95% confidence interval 99–100]). hs-cTnI levels were available for RRI and 3-h delta analyses from 935 and 52 patients, respectively. A 3-h delta cut-point >35 ng/L met the performance benchmark (PPV: 81% [95% confidence interval 58–95]) but no RRI cut-point did so.

Conclusions

For the Beckman Coulter Access hs-cTnI assay, RRO criteria of baseline hs-cTnI <6 ng/L (females) or <11 ng/L (males) plus symptom onset >2 h met our performance benchmark. A 3-h delta cut-point >35 ng/L met the performance benchmark, but poor precision means further adequately powered research is required.     

Superiority of high sensitivity cardiac troponin T vs. I for long-term prognostic value in patients with chest pain; data from the Akershus cardiac Examination (ACE) 3 study

BackgroundCardiac troponins (cTn) are essential in the diagnostic assessment of non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Elevated concentrations of cTnT and cTnI predict cardiovascular events in non-acute settings, but the individual troponin isotype association with long-term mortality in patients with suspected unstable angina pectoris (UAP) is less clear.MethodsPatients hospitalized with chest pain between June 2009 and December 2010 were included in the Akershus Cardiac Examination 3 Study and followed for median 6.6 (IQR 6.2-7.1) years. The index diagnosis was adjudicated by an independent committee as NSTE-myocardial infarction (NSTEMI), UAP or non-ACS. Blood samples were collected within 24 h of admission and analyzed with high sensitivity assays for cTnT (hs-cTnT, Roche) and cTnI (hs-cTnI, Singulex).ResultsOf 402 patients included, 74 (18%) were classified as NSTEMI, 88 (22%) UAP and 240 (60%) non-ACS. hs-cTnI concentrations were detectable in all patients (median 3 [IQR 1–11] ng/L), while hs-cTnT concentrations were above the level of blank in 205 (51%) (median 3 [IQR 3–16] ng/L). In patients with UAP, both log₂-transformed hs-cTnT and hs-cTnI were associated with all-cause mortality in analyses that adjusted for other risk factors: HR 2.40 [95% CI 1.75–3.30], p < 0.001 and HR 1.44 [1.14–1.81], p = 0.002. There were no significant sex-dependent differences in the association between hs-cTnT or hs-cTnI and outcome. Time dependent receiver-operating characteristics area under the curve was 0.85 (95% CI 0.79–0.92) for hs-cTnT and 0.74 (0.64–0.84) for hs-cTnI, p = 0.008 for difference between values.ConclusionsHigher concentrations of hs-cTnT and hs-cTnI were both associated with all-cause mortality in patients with UAP, but the association with outcome was stronger for hs-cTnT than for hs-cTnI.     

现场快速检测高敏肌钙蛋白在老年急性心肌梗死早期的临床诊断价值

目的:观察现场快速检测高敏肌钙蛋白I(hs-cTnI)在急诊老年胸痛患者人群中的表达情况,并评价其对急性心肌梗死(AMI)的诊断效能.方法:选择2018年6月-2021年5月期间我院急诊科收治的胸痛疑似急性冠脉综合征(ACS)而行现场快速检测hs-cTnI的315例老年患者作为研究对象,观察hs-cTnI在老年急性胸痛...     

Comparison of high sensitivity troponin T and I assays in the diagnosis of non-ST elevation acute myocardial infarction in emergency patients with chest pain

Objectives

Concentrations of troponin measured with high sensitivity troponin assays are raised in a number of emergency department (ED) patients; however many are not diagnosed with acute myocardial infarction (AMI). Clinical comparisons between the early use (2 h after presentation) of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) assays for the diagnosis of AMI have not been reported.

Design and methods

Early (0 h and 2 h) hs-cTnT and hs-cTnI assay results in 1571 ED patients with potential acute coronary syndrome (ACS) without ST elevation on electrocardiograph (ECG) were evaluated. The primary outcome was diagnosis of index AMI adjudicated by cardiologists using the local cTnI assay results taken ≥ 6 h after presentation, ECGs and clinical information. Stored samples were later analysed with hs-cTnT and hs-cTnI assays.

Results

The ROC analysis for AMI (204 patients; 13.0%) for hs-cTnT and hs-cTnI after 2 h was 0.95 (95% CI: 0.94–0.97) and 0.98 (95% CI: 0.97–0.99) respectively. The sensitivity, specificity, PLR, and NLR of hs-cTnT and hs-cTnI for AMI after 2 h were 94.1% (95% CI: 90.0–96.6) and 95.6% (95% CI: 91.8–97.7), 79.0% (95% CI: 76.8–81.1) and 92.5% (95% CI: 90.9–93.7), 4.48 (95% CI: 4.02–5.00) and 12.86 (95% CI: 10.51–15.31), and 0.07 (95% CI: 0.04–0.13) and 0.05 (95% CI:0.03–0.09) respectively.

Conclusions

Exclusion of AMI 2 h after presentation in emergency patients with possible ACS can be achieved using hs-cTnT or hs-cTnI assays. Significant differences in specificity of these assays are relevant and if using the hs-cTnT assay, further clinical assessment in a larger proportion of patients would be required.     

Using high sensitivity cardiac troponin values in patients with SARS-CoV-2 infection (COVID-19): The Padova experience

BackgroundThe spectrum of Coronavirus Disease 2019 (COVID-19) is broad and thus early appropriate risk stratification can be helpful. Our objectives were to define the frequency of myocardial injury using high-sensitivity cardiac troponin I (hs-cTnI) and to understand how to use its prognostic abilities.MethodsRetrospective study of patients with COVID-19 presenting to an Emergency Department (ED) in Italy in 2020. Hs-cTnI was sampled based on clinical judgment. Myocardial injury was defined as values above the sex-specific 99th percentile upper reference limits (URLs). Most data is from the initial hospital value.Results426 unique patients were included. Hs-cTnI was measured in 313 (73.5%) patients; 85 (27.2%) had myocardial injury at baseline. Patients with myocardial injury had higher mortality during hospitalization (hazard ratio = 9 [95% confidence interval (CI) 4.55–17.79], p < 0.0001). Multivariable analysis including clinical and laboratory variables demonstrated an AUC of 0.942 with modest additional value of hs-cTnI. Myocardial injury was associated with mortality in patients with low APACHE II scores (<13) [OR (95% CI): 4.15 (1.40, 14.22), p = 0.014] but not in those with scores > 13 [OR (95% CI): 0.48 (0.08, 2.65), p = 0.40]. Initial hs-cTnI < 5 ng/L identified 33% of patients that were at low risk with 97.8% sensitivity (95% CI 88.7, 99.6) and 99.2% negative predictive value. Type 1 myocardial infarction (MI) and type 2 MI were infrequent.Conclusionshs-cTnI at baseline is a significant predictor of mortality in COVID-19 patients. A value < 5 ng/L identified patients at low risk.     

Clinical evaluation of Ortho Clinical Diagnostics high-sensitivity cardiac Troponin I assay in patients with symptoms suggestive of acute coronary syndrome

BackgroundAs more companies obtain regulatory approval for high-sensitivity cardiac troponin (hs-cTn) assays there is an urgent need for independent analytical and clinical evaluations. To this end, we have evaluated Ortho Clinical Diagnostics’ hs-cTnI assay and compared it to their contemporary cTnI-ES assay in emergency department (ED) patients with suspected acute coronary syndrome (ACS).MethodsThe study cohort consisted of ED patients (n = 906) with symptoms suggestive of ACS who had Ortho hs-cTnI and cTnI-ES results at presentation and 3 h (with calculated delta (0–3 h) defined as the absolute concentration difference between paired results). The primary composite outcome was 7-day myocardial infarction (MI) or cardiovascular death, with secondary analyses performed for 7-day MI and index-MI. Analytical imprecision testing (i.e., coefficient of variation; CV), receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC), and diagnostic parameters (sensitivity/specificity/predictive values) were calculated.ResultsThe hs-cTnI assay had superior precision compared to the cTnI-ES assay below 5 ng/L in EDTA plasma (hs-cTnI CV ≤ 15% versus cTnI-ES CV ≥ 85%). The AUCs were higher for hs-cTnI as compared to cTnI-ES at 0 h (0.88 vs. 0.85), 3 h (0.94 vs. 0.92), and the delta (0–3 h) value (0.91 vs. 0.85) for the primary composite outcome (p < 0.05). At 3 h, the sensitivity/specificity for index-MI was ≥97%/≥82%, for 7-day MI was ≥89%/≥84%, and for the primary composite outcome was ≥90%/≥85% using the manufacturer’s sex-specific 99th-percentile cutoffs.ConclusionThe Ortho hs-cTnI assay has superior analytical and clinical performance over their contemporary cTnI-ES assay in evaluating ED patients with symptoms suggestive of ACS.     

Gender-specific reference values for high-sensitivity cardiac troponin T and I in well-phenotyped healthy individuals and validity of high-sensitivity assay designation

ObjectiveTo determine gender-specific reference limits of high-sensitivity (hs) cardiac troponins (cTn) and validity of hs assay designation for both genders.MethodsAfter screening with a questionnaire, 827 presumably healthy individuals were further selected based on clinical criteria (n = 740), clinical criteria plus cardiac imaging including stress magnetic resonance imaging or stress echocardiography (n = 726), and extended cardio-pulmonary parameters (n = 626). Blood samples were measured with hs-cTnT (Roche Diagnostics) on a cobas e602 analyzer as well as hs-cTnI (Abbott Diagnostics) on an ARCHITECT_i2000_SR. The impact of health definition, statistical methods, instrument selection and limit of detection (LoD) on overall and gender-specific 99th percentiles was assessed.ResultsMedian age was 56 years (50.9% female) for the total study cohort. 99th percentiles for females and males ranged between 13.1 and 13.3 ng/L and 16.8–19.9 ng/L for hs-cTnT as well as 10.3–12.5 ng/L and 27.4–29.7 ng/L for hs-cTnI depending on health definition. Utilization of stricter health definition criteria reduced the difference of the gender-specific 99th percentiles between males and females for hs-cTnT to 3.7 ng/L (males 16.8 ng/L, females 13.1 ng/L), whereas the difference rather increased for hs-cTnI to 19.4 ng/L (males 29.7 ng/L, females 10.3 ng/L). Values > LoD could be measured in the majority of males and females using hs-TnT (81.4–83.3% and 96.5–96.9%, respectively). In contrast, values > LoD could not be observed in the majority of females using hs-cTnI (38.4–41.1%).ConclusionsIn a well-phenotyped healthy cohort, reference values for hs-cTnT were slightly higher, whereas hs-cTnI cut-offs were considerably lower than previously observed. Gender differences were more pronounced in hs-cTnI than in hs-cTnT and were further reduced for hs-cTnT by application of stricter health definition criteria. Contrary to hs-cTnI, hs-cTnT fulfilled criteria for hs designation for both genders.     

Performance of cardiac troponins within the HEART score in predicting major adverse cardiac events at the emergency department

BackgroundThis study compared the performance of a single blood draw of high-sensitivity troponin T (hsTnT), high-sensitivity troponin I (hsTnI) and conventional troponin I (cTnI) within a modified HEART score for predicting 30-day MACE at Emergency Department (ED) presentation, and established local reference norms for all three assays by determining the cut-off point which yielded the highest sensitivity and negative predictive value for acute myocardial infarction and 30-day MACE.MethodsThis single-center prospective cohort study recruited chest pain patients at the ED, whose hsTnT, hsTnI and cTnI were taken on admission. Subjects were classified into low and non-low risk group according to their modified HEART score, with MACE as the primary endpoint. Receiver-operating characteristic (ROC) curves were generated, area under the curves (AUCs) were calculated; the performance characteristics were determined.ResultsThe performance of modified HEART scores was comparable among the three assays for 30-day MACE (84.9–87.0% sensitivity, 95.6–96.0% NPV, 95%CI) and none of these had very high AUC and specificity (AUC 0.70–0.71, 53.7–56.7% specificity, 95% CI). The modified HEART score using a single blood draw of either hsTnT (3.9 ng/L), hsTnI (0.9 ng/L) or cTnI (0.0 ng/L) at presentation yielded a sensitivity of 100% for 30-day MACE.ConclusionThe modified HEART score using a single blood draw of either hsTnT, hsTnI or cTnI was equally effective in risk-stratifying chest pain patients for safe discharge. The theoretical cut-off points yielding 100% sensitivity are potentially useful (when achieved) for safely discharging low risk patients with undifferentiated chest pain in the ED.     

Differential associations of cardiac troponin T and cardiac troponin I with coronary artery pathology and dynamics in response to short-duration exercise

BackgroundWe aimed to assess the associations between cardiac troponin (cTn) T and I concentrations, physical exercise and the presence and severity of angiographic coronary artery disease (CAD) in patients evaluated for suspected chronic coronary syndrome (CCS).Methods and resultsAll patients performed an exercise stress test on a bicycle ergometer and underwent invasive coronary angiography with weighted anatomical evaluation using the Gensini score. Blood samples were collected before and after exercise and analysed with high-sensitivity (hs) cTnT and cTnI assays.Of 297 patients (median age 62 (Quartile [Q]1–3 56–69) years, 35% female), 46% were categorized as “severe CAD” (Gensini score ≥ 20).Resting hs-cTnT and hs-cTnI concentrations were detectable in 88% and 100% of patients, with medians of 6 (Q1-3 4–9) ng/L and 1.5 (0.9–2.4) ng/L, respectively.In adjusted normalized linear regression analyses, higher resting concentrations were associated with increasing Gensini score (hs-cTnT: B 0.19, 95% Confidence Interval [CI] [0.09–0.41], p < 0.001; hs-cTnI: B 0.18, [0.06–0.30], p = 0.002).The area under the receiver operating characteristics curve for predicting severe CAD was 0.72 (95% CI [0.66–0.78]) and 0.68 (0.62–0.74) for resting hs-cTnT and hs-cTnI, p = 0.11 for difference.The median (Q1-3) relative increase in hs-cTnT and hs-cTnI concentrations were 5 (0–12) % and 13 (3–27) %, respectively, with no significant associations with CAD severity.ConclusionsIn patients with suspected CCS, higher hs-cTn concentrations at rest were associated with increasing angiographic severity of CAD, without any significant differences between the troponin isotypes. Post-exercise hs-cTn concentrations did not have discriminatory power for CAD.     

Performance evaluation of Siemens ADVIA Centaur and Roche MODULAR Analytics E170 Total 25-OH Vitamin D assays

ObjectivesTo evaluate the newly developed Roche MODULAR Analytics E170 Total Vitamin D and the Siemens ADVIA Centaur® Vitamin D Total assays.Materials and MethodsAssays were evaluated using the Clinical and Laboratory Standards Institute protocols. Split patient samples were compared with LC-MS/MS and DiaSorin LIAISON assays (n = 79 including 15 specimens with detectable endogenous 25-OH vitamin D₂). Assay accuracy was also evaluated using the Vitamin D External Quality Assessment Scheme (DEQAS) samples.ResultsThe ADVIA Centaur and E170 assays demonstrated maximum total CVs of 14.1% and 5.9%, respectively. Both showed excellent linearity (R² > 0.99). The ADVIA Centaur assay demonstrated interference with bilirubin at 800 μmol/L, hemolysis at 1.25 g/L, and triglycerides at 2.8 mmol/L. Compared to LC-MS/MS, the ADVIA Centaur assay demonstrated a R² value of 0.893, average bias of ? 8.8%; the E170 assay an R² value of 0.872, average bias of 14.3% with underestimation of 25-OH vitamin D₂. Compared to the LIAISON assay, the ADVIA Centaur assay demonstrated an R² value of 0.781, average bias of ? 17.3%; the E170 assay an R² value of 0.823, average bias of 11.4%. The ADVIA Centaur and E170 assays demonstrated a biases of < 20% in 10/10 and 8/10 DEQAS samples, respectively.ConclusionsThe ADVIA Centaur and E170 vitamin D assays demonstrated acceptable linearity, imprecision, and accuracy. The E170 assay demonstrated consistent underestimation of 25-OH vitamin D₂ levels. Compared with LC-MS/MS, the ADVIA Centaur assay demonstrated a higher R² value and a smaller average bias than the E170 assay.     

High-sensitivity cardiac troponin I and risk of incident atrial fibrillation hospitalisation in an Australian community-based cohort: The Busselton health study

ObjectiveThe identification of individuals at risk of atrial fibrillation (AF) remains a challenge. We investigated whether high-sensitive cardiac troponin I (hs-cTnI) is an independent predictor of incident atrial fibrillation (AF) hospitalisation in an Australian community-based cohort.MethodsSerum hs-cTnI was measured in 1641 men and 2189 women in the Busselton Health Study 1994/1995 Cohort aged 25–84 years at baseline. Data on incident AF hospitalisation over 20 years follow-up were obtained by data linkage.ResultsHs-cTnI was detectable (>1.2 ng/L) in 65.5% of participants (males 81.4%, females 53.6%) at baseline. There were 179 (10.9%) AF events in men and 208 (9.5%) in women. In the multivariable-adjusted model, hs-cTnI was a significant predictor of AF event with hazard ratio 1.21 (95% CI 1.11–1.32, P < 0.001) in the whole cohort, 1.17 (95% CI 1.01–1.35, P = 0.037) in men and 1.22 (95% CI 1.08–1.37, P = 0.001) in women for a doubling of baseline hs-cTnI. In women, a graded and significant increase in risk of AF was observed across hs-cTnI categories from ≥1.3 ng/L, whereas in men only the highest category (≥6.0 ng/L) had significantly increased risk compared with individuals with hs-cTnI ≤1.2 ng/L. Addition of categorical hs-cTnI to standard risk factors for AF improved risk estimation in females (C-statistic increment 0.006, P = 0.04) but not males (increment 0.005, P = 0.12) and net reclassification improvement was not significant in either sex.ConclusionsHigh-sensitive cTnI level is an independent predictor of incident AF hospitalisation in a community-based cohort but does not improve risk stratification.     

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.     

Rapid rule out of acute myocardial infarction in the observe zone using a combination of presentation N-terminal pro-B-type natriuretic peptide and high-sensitivity cardiac troponin I

Background and aimsThe release of N-terminal pro-B-type natriuretic peptide (NT-proBNP) is strongly triggered by myocardial ischemia. We aimed to investigate whether the addition of NT-proBNP to high-sensitivity cardiac troponin (hs-cTnI) at presentation could provide better performance in risk stratification and thus early rule-out of acute myocardial infarction (AMI) in patients of the “observe zone”.MethodsEmergency department (ED) patients presenting with symptoms suspicious for AMI were consecutively enrolled. Blood samples were obtained at presentation and tested for hs-cTnI and NT-proBNP. All available medical records pertaining to the patient from ED presentation to 30-day follow-up were used for adjudication of the primary outcome. The incremental diagnostic value added by NT-proBNP to hs-cTnI was evaluated by receiver operating characteristic (ROC) analysis, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI). Sensitivity, specificity, positive and negative predictive values were used to assess the diagnostic accuracy of different approaches for early rule out.ResultsOf the 165 patients we analyzed, 55 (33.3%) had index AMI. For hs-cTnI alone, area under the curve for index AMI was not significantly increased after adding NT-proBNP (0.773 vs 0.809; p = .076). Adjustment of hs-cTnI by NT-proBNP improved the predictive value of hs-cTnI, showed by cNRI (0.418, 95%CI 0.102–0.735, p = .009) and IDI (0.055, 95%CI 0.017–0.092, p = .004). Compared to hs-cTnI, the combined test identified 14% more patients as low-risk and safe for early discharge.ConclusionsCombination of presentation hs-cTnI and NT-proBNP provided better predictive performance for AMI in patients of the observe zone presenting with symptoms of chest pain as compared to hs-cTnI alone. The combined test outperformed hs-cTnI by correctly identifying nearly 14% more patients as low-risk and safe for early discharge. Future multi-center studies are needed to verify the results and to determine the best clinical use of the combination of NT-proBNP and hs-cTnI in the early diagnosis of AMI.     

Ideal high sensitivity troponin baseline cutoff for patients with renal dysfunction

ObjectiveHigh-sensitivity cardiac troponin assays (hs-cTn) aid in diagnosis of myocardial infarction (MI). These assays have lower specificity for non-ST Elevation MI (NSTEMI) in patients with renal disease. Our objective was to determine an optimized cutoff for patients with renal disease.MethodsWe conducted an a priori secondary analysis of a prospective FDA study in adults with suspected MI presenting to 29 academic urban EDs between 4/2015 and 4/2016. Blood was drawn 0, 1, 2–3, and 6–9 h after ED arrival. We recorded cTn and estimated glomerular filtrate rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation. The primary endpoint was NSTEMI (Third Universal Definition of MI), adjudicated by physicians blinded to hs-cTn results. We generated an adjusted hscTn rule-in cutoff to increase specificity.Results2505 subjects were enrolled; 234 were excluded. Patients were mostly male (55.7%) and white (57.2%), median age was 56 years 472 patients [20.8%] had an eGFR <60 mL/min/1.73 m2. In patients with eGFR <15 mL/min/1.73 m2, a baseline rule-in cutoff of 120 ng/L led to a specificity of 85.0% and Positive Predictive Value (PPV) of 62.5% with 774 patients requiring further observation. Increasing the cutoff to 600 ng/L increased specificity and PPV overall and in every eGFR subgroup (specificity and PPV 93.3% and 78.9%, respectively for eGFR <15 mL/min/1.73m²), while increasing the number (79) of patients requiring observation.ConclusionsAn eGFR-adjusted baseline rule-in threshold for the Siemens Atellica hs-cTnI improves specificity with identical sensitivity. Further study in a prospective cohort with higher rates of renal disease is warranted.     

Combining high-sensitivity cardiac troponin and B-type natriuretic peptide in the detection of inducible myocardial ischemia

BackgroundSingle biomarker approaches provide only moderate accuracy in the non-invasive detection of exercise-induced myocardial ischemia. We therefore assessed the combination of the two most promising single biomarkers: high-sensitivity cardiac troponin I (hs-cTnI) and B-type natriuretic peptide (BNP).MethodsConsecutive patients with suspected myocardial ischemia referred to stress myocardial perfusion single-photon emission tomography imaging (MPI) were enrolled. Clinical judgment (CJ) of the treating cardiologist regarding myocardial ischemia, quantified using a visual analogue scale, and blood concentrations of hs-cTnI and BNP were determined before and after stress. The presence of myocardial ischemia was adjudicated by independent cardiologists using MPI, blinded to biomarker measurements. Death and acute myocardial infarction (AMI) during follow-up were the prognostic endpoints.ResultsAmong 1142 consecutive patients inducible myocardial ischemia was found in 456 (40%) of all patients. For the detection of inducible myocardial ischemia, CJ before exercise stress testing (CJb) showed an area under the receiver-operating-characteristics curve (AUC) of 0.66 (95%CI 0.63–0.69), hs-cTnI 0.70 (95%CI 0.67–0.73, p = 0.07 vs CJb), and BNP 0.66 (95%CI 0.62–0.69, p = 0.98). The use of a dual-biomarker strategy combining hs-cTnI and BNP with CJb did not provide a significant advantage over the combination of hs-cTnI alone and CJb (AUC 0.74, 95%CI 0.72–0.77 vs AUC 0.74, 95%CI 0.71–0.77, p = 0.16). Hs-cTnI showed good prognostic value for AMI (HR 1.6, 95%CI 1.3–1.9), and BNP for death (HR 1.6, 95%CI 1.3–2.1).ConclusionA dual-biomarker strategy combing BNP and hs-cTnI does not further increase diagnostic accuracy on top of clinical judgment and hs-cTnI alone.Summary and highlightsWe included 1142 consecutive patients with suspected inducible ischemia, and evaluated the added value of the biomarkers high-sensitivity cardiac troponin (hs-cTn) and B-type natriuretic peptide (BNP), alone and in combination, on top of clinical judgment.Clinical trial registrationBiochemical and Electrocardiographic Signatures in the Detection of Exercise-induced Myocardial Ischemia (BASEL VIII), NCT01838148, https://clinicaltrials.gov/ct2/show/NCT01838148     

Gender-based differences of copeptin alone or combined with troponin for early rule-out of non-ST-elevation myocardial infarction

BackgroundLittle is known about the role of gender in the dual biomarker strategy using copeptin and troponin for the early rule-out of non-ST-elevation myocardial infarction (NSTEMI). We aimed to evaluate gender-based differences on copeptin levels, combined negative predictive value (NPV) and predictors of copeptin elevation at admission.MethodsBiomarkers were measured in 852 adult patients presenting to the emergency department with chest pain and suspected NSTEMI. Logistic regression analyses on predictors of copeptin elevation were evaluated by gender.ResultsOverall, 362 women (42.5%) and 490 men (57.5%) were included. Copeptin levels were higher in men (median 7.36 pmol/L vs. 4.8 pmol/L; P < .001). Men had a similar NPV (100%) as women (99.6%, CI: 98.8–100) using the dual biomarker rule-out strategy and when compared to troponin alone (men, NPV = 98.7%, CI: 97.5–99.8; and women, NPV = 98.7%, CI: 97.5–100). Multivariate logistic regression showed positive association of male gender with copeptin elevation (OR = 2.37; CI: 1.61–3.49; P < .001). In men, diastolic blood pressure was a negative predictor of copeptin elevation (OR = 0.98, 95% CI: 0.96–0.99), while positive predictors were current MI (OR = 2.16, 95% CI: 1.19–3.91), chronic renal insufficiency (OR = 3.58, 95% CI: 1.33–9.62), and atrial fibrillation (OR = 2.56, 95% CI: 1.23–5.32), respectively (all P < .05). In women, current MI (OR = 2.98, CI: 1.23–7.24), atrial fibrillation (OR = 2.90, CI: 1.26–6.70) and syncope-like events (OR = 7.56, CI: 2.26–25.30) were significant predictors of copeptin elevation.ConclusionsMen with suspected NSTEMI have higher copeptin levels. The dual biomarker rule-out strategy has a similar performance in both male and female patients. Certain predictors of copeptin elevation are gender-specific.