Percentile Upper Reference Limit Research Articles

Age- and sex-specific 99th percentile upper reference limits for high-sensitivity cardiac troponin T in Chinese older people: Real-world data mining

BackgroundThis study aims to investigate the impact of age and sex on high-sensitivity cardiac troponin T (hs-cTnT) and establish 99th percentile upper reference limits (URLs) in older individuals utilizing large-scale real-world data. Methods40,530 outpatient hs-cTnT results were obtained from the laboratory database from January 1, 2018, to December 31, 2023. Our study included 4,199 elderly outpatients (aged ≥ 60) without cardiovascular disease or other heart-related chronic conditions. Nested analysis of variance was used to explore the necessity of partitioning reference intervals (RIs) by sex and age groups. RIs were established by the refineR algorithm and assessed based on ≤ 10% test results of validation data set outside the new RIs. ResultsRIs for hs-cTnT in the older population needed to be partitioned by sex and age groups ([standard deviation ratio] SDRage = 0.75; SDRsex = 0.49). URLs in older Chinese adults were 21.8 ng/L for males, 16.5 ng/L for females, and 20.7 ng/L for the overall participant group. URLs for males aged 60–69, 70–79, and ≥ 80 were 13.7, 19.4, and 31.0 ng/L, respectively. Female values were 10.1, 17.2, and 22.0 ng/L. Importantly, manufacturer-reported RIs do not suffice for Chinese individuals aged ≥ 70. Validation data showed that 2.7–5.2% of test results fell outside the new RIs, confirming the validity of the results. ConclusionThis study establishes age- and sex-specific 99th percentile URLs for hs-cTnT in Chinese older individuals, thereby enhancing the accuracy of clinical assessments.

Frequency and Prognostic Value of Acute Periprocedural Myocardial Injury in Elective Percutaneous Coronary Interventions

Background. Periprocedural myocardial injury (PMI) is an acute complication of percutaneous coronary interventions (PCI) in patients with stable coronary artery disease. Its frequency and relationship with the prognosis of the disease are especially important in elective interventions due to the low risk of ischemic events in this cohort of patients. However, according to the literature, there are significant differences in the criteria for PMI and type 4a myocardial infarction (MI), and, accordingly, their frequency and their prognostic value. Aim. To study the frequency and magnitude of PMI during elective PCI in terms of the level of periprocedural increase in cardiospecific biomarkers, as well as to determine the relationship of PMI with long-term adverse events in patients with chronic coronary artery disease. Materials and methods. A single-center open retrospective cohort study was conducted, which included 435 patients (367/84.4 % men, mean age 58.3±8.6 years) from the elective PCI registry. PMI was diagnosed with an increase in the level of creatine phosphokinase MB fraction (CK-MB) or or cardiac troponin I (cTn I) >1×99 percentile URL (Upper Reference Limit), while the level of increase in biomarkers >1, 2, 3, 4 or >5×99 percentile URL was recorded. An increase in biomarkers >5x99 URL percentile was assessed as a large PMI, and in the presence of clinical and imaging evidence of new loss of viable myocardium, as periprocedural MI type 4a. Depending on the level of periprocedural increase in biomarkers, the relative risk (RR) of developing long-term (within 5 years after index PCI) adverse cardiovascular events, death, as well as clinically significant bleeding and newly diagnosed malignant oncological diseases was calculated. In addition, the correlation between PMI and the above endpoints was summarized using Kaplan-Meier analysis. Results. The frequency of periprocedural PMI diagnosed by increased biomarkers >1×99 percentile URL was 40.2 %, >2×99 percentile URL — 9.7 %, >3×99 percentile URL — 6.7 %, >4×99 percentile URL — 4.8 %, >5×99 percentile URL — 3.5 %, type 4a MI — in 2 patients (0.46 %). An association of “major” PMI (>5x99 percentile URL) with cardiovascular complications within 3 years after elective PCI, including fatal ones, was revealed: for acute myocardial infarction (AMI), RR — 6.516, confidence interval (CI) [2.375-17.881]; for death from cardiovascular causes RR — 6.538, CI [1.695-25.227]. An association of “moderate” PMI (>3, but <5 ×99 URL percentile) with acute ischemic events within 3 years after elective PCI was shown: for AMI, RR was 4.073, CI [1.598 — 10.378]. An association of “minor” AKI (>1, but <5 ×99 URL percentile) with acute ischemic events within 3 years after elective PCI was shown: for AMI, RR was 4.073, CI [1.598 — 10.378]. An association of “minor” AKI (>1, but <3 ×99 URL percentile) with newly diagnosed malignant oncological diseases within 5 years after index PCI was revealed: RR 2.319; CI [1.248- 4.310]. An association of late thrombotic events, such as stent thrombosis (index and re-interventions), stent occlusion (index and non-index) as a reason for re-intervention within 5 years after index PCI, was found with most PMI subgroups. Kaplan-Meier analysis of the dependence of clinically significant bleeding within 5 years after index PCI on the development of “moderate” PMI (p=0.003), as well as the association of non-cardiovascular death within 5 years after index PCI with “minor” PMI (p= 0.007). Conclusion. Registration of periprocedural increase in cardiac biomarkers should be carried out during planned PCI not only for the purpose of diagnosing and predicting acute and late ischemic events, but also for assessing the risk of developing stent occlusion, clinically significant bleeding and prognostically important comorbidities in the long-term (5-year) period in order to identification of groups of patients requiring active monitoring, additional examination and selection of an optimal treatment regimen at the outpatient stage of rehabilitation.

Impact of the ESC Cardio-Oncology Guidelines Biomarker Criteria on Incidence of Cancer Therapy–Related Cardiac Dysfunction

BackgroundThe impact of recent consensus definitions of cancer therapy–related cardiac dysfunction (CTRCD) from the European Society of Cardiology cardio-oncology guidelines on the reported incidence of CTRCD has not yet been assessed. ObjectivesThe aim of this study was to assess the: 1) cumulative incidence; 2) point prevalence during and after adjuvant therapy; and 3) prognostic value of CTRCD as defined by different asymptomatic CTRCD guideline criteria. MethodsThe cumulative incidence and point prevalence of CTRCD were retrospectively assessed in 118 patients participating in the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial. Asymptomatic CTRCD was assessed using alternative cardiac troponin (cTn) 99th percentile upper reference limits (URLs) to define cTnT and cTnI elevation. ResultsThe cumulative incidence of moderate or severe CTRCD was low (1.7%), whereas the cumulative incidence of mild asymptomatic CTRCD was higher and differed markedly according to the biomarker criteria applied, ranging from 49.2% of patients when cTnT greater than the sex-specific 99th percentile URL was used to define cTn elevation to 9.3% when sex-neutral cTnI was used. The point prevalence of CTRCD was highest at the end of anthracycline therapy (47.8%) and was driven primarily by asymptomatic cTn elevation. CTRCD during adjuvant therapy was not prognostic for CTRCD at extended follow-up of 24 months (Q1-Q3: 21-29 months) after randomization. ConclusionsMild asymptomatic CTRCD during adjuvant breast cancer therapy was frequent and driven mainly by cTn elevation and was not prognostic of subsequent CTRCD. The incidence of mild, asymptomatic CTRCD differed markedly depending on the cTn assay and whether sex-neutral or sex-dependent URLs were applied. (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy [PRADA]; NCT01434134)

Analytical evaluation of the novel Mindray high sensitivity cardiac troponin I immunoassay on CL-1200i.

The current study was designed to evaluate the analytical performance of the new Mindray highly sensitive cardiac troponin I (hs-cTnI) chemiluminescent immunoassay on Mindray CL-1200i, as a thorough validation of novel hs-cTnI methods is required before introduction into clinical practice. The evaluation of the analytical performance of this hs-cTnI immunoassay encompassed the calculation of the limit of blank (LOB), limit of detection (LOD), functional sensitivity, imprecision, linearity, 99th percentile upper reference limit (URL) and concordance with another previously validated hs-cTnI chemiluminescent immunoassay. The LOB and LOD were 0.32 and 0.35 ng/L, whilst the functional sensitivity (expressed as cTnI value with <10 % imprecision), was 0.35 ng/L. The linearity was excellent throughout a wide range of clinically measurable values (r=1.00 between 0.8 and 9,726.9 ng/mL). The intra-assay, inter-assay and total imprecision were 1.1-1.3 %, 5.5-8.1 % and 5.6-8.2 %, respectively. The 99th percentile URL calculated using residual plasma from 246 ostensibly healthy blood donors was 9.2 ng/L (4.3 ng/L in women vs. 12.3 ng/L in men). The Spearman's correlation between Mindray hs-cTnI and Access hs-TnI was 0.97, with mean bias of 7.2 % (95 % CI, 2.6-11.9 %). Although we failed to confirm the very optimistic analytical characteristics previously reported for this method, our evaluation of the novel Mindray hs-cTnI immunoassay on CL-1200i demonstrated that the overall performance is comparable to that of other commercially available hs-cTnI techniques, making it a viable alternative to other methods.

Evaluation of analytical and clinical performance of the AFIAS Tn-I plus assay - a new point-of-care

Background The objective of this evaluation was to determine the analytical and clinical performance of the AFIAS point-of-care (POC) Tn-I Plus assay (Boditech Med Inc). Design and methods Limit of detection (LOD), limit of quantification (LOQ), repeatability, reproducibility, inter- and intra-individual CV were evaluated using the CLSI guidelines. The study was also designed to estimate the 99th percentile upper reference limit (URL) and to assess the diagnostic sensitivity and specificity. Results The precision repeatability CVs were 6.7–8.5% and reproducibility was 7.5–7.6%. The LOD and LOQ were consistent with the manufacturer’s specified values of 0.010 ng/mL and 0.030 ng/mL, respectively. The 99th percentile URLs for males (aged 18–75 years) and females (aged 17–65 years) in serum were 0.0300 ng/mL (7.8% CV) and 0.0239 ng/mL (9.4% CV) respectively. Overall 99th percentile URL was 0.0296 ng/mL (8.2% CV). For the overall apparently healthy population, the percentage of measurable cardiac troponin I (cTn-I) values below the 99th percentile (i.e. 0.0296 ng/mL) and above the assay’s LOD (= 0.010 ng/mL) was 47,68% (391/820 samples). The diagnostic sensitivity and specificity were 100% with 95% CI (97% − 100%) and 95.2% with 95% CI (93.6% − 96.5%), respectively. No significant differences were observed for the diagnosis of acute myocardial infarction (AMI) between AFIAS Tn-I plus and Abbott ARCHITECT High Sensitive Troponin-I. Conclusion The clinical performance of AFIAS Tn-I Plus assay for AMI is comparable to the established Abbott ALINITY STAT High Sensitive Troponin-I. This assay is suitable for routine use in clinical laboratories.

CytogeneticsComparability of Beckman Coulter Access Cardiac Troponin I Assays

Abstract Cardiac troponins (cTn) are the most sensitive and specific biomarkers of myocardial injury. The rise and/or fall of cardiac troponins above the 99th percentile of the upper reference limit (URL) is required in the assessment of acute myocardial infarction. In our institution, high sensitivity troponin I (hsTnI) is performed on four Access 2 Immunoassay Systems and three DXI 800 Access Immunoassay Systems. As a regional medical center, we accept patients from outside hospitals where contemporary cardiac troponin I (cTnI) were performed. The results from different assays and platforms may disagree and lead to incorrect explanation of the results as false rise and/or fall of cTn. To harmonize results among these assays, we analyzed the variation between the two assays of cTnI and hsTnI, and the concordance of same assay hsTnI on different instruments using patient specimens. To investigate the between-method variance, 424 patient specimens with troponin levels ranging from 0-23370 ng/L were used to measure both cTnI and hsTnI on DXI 800 instruments. To investigate the within-method agreement, 43 patient specimens with troponin levels ranging from 2-114394 ng/L were used to measure hsTnI on Access 2 and DXI instruments. The between-method comparison of cTnI and hsTnI on DXI showed a slope of 1.003 with intercept of -43.31 and correlation coefficient (CC) of 0.9590. The mean bias was -5.1%, which was within the analytical imprecision range determined in our laboratory (2.2%-10.7%). However, comparison of cTnI and hsTnI in patients with troponin &amp;lt;20ng/L (n=103), the 99th percentile of the URL for males, showed the slope was 1.325 with intercept of -0.97 and CC of 0.7462. The mean bias was 1.91 (21.53%), which was much larger than the analytical imprecision. This is consistent with the fact that cTnI results are not reliable at the lower level due to the imprecision problem. Comparison of cTnI and hsTnI in patients with troponin &amp;gt;20ng/L (n=321) showed the slope was 1.006 with intercept of –60.09 and CC of 0.9576. The mean bias was -54.30 (-5.23%), which was within the analytical imprecision range. The within-method comparison of hsTnI on Access 2 and DXI 800 showed the slope was 1.138 with intercept of -633.0 and CC of 0.9888. The mean bias was 2126.4 (10.6%), within the analytical imprecision range. These data indicate that cTnI results above the 99th percentile URL are comparable with hsTnI results if both are tested on DXI 800, and hsTnI results tested on Access 2 and DXI 800 are comparable. Thus, to use the cardiac troponins assay properly, we suggest the laboratory report cardiac troponins with the assay and instrument names to reduce confusion during results comparison.

Performance evaluation of a novel high-sensitivity cardiac troponin T assay: analytical and clinical perspectives.

To evaluate the analytical characteristics of anovel high-sensitivity cardiac troponin T (hs-cTnT) test onthe automatic light-initiated chemiluminescent assay (LiCA®) system, and validated its diagnostic performance for non-ST-segment elevation myocardial infarction (NSTEMI). Studies included an extensive analytical evaluation and established the 99th percentile upper reference limit (URL) from apparently healthy individuals, followed by a diagnostic performance validation for NSTEMI. Sex-specific 99th percentile URLs were 16.0 ng/L (1.7 % CV: coefficient of variation) for men (21-92 years) and 13.4 ng/L (2.0 % CV) for women (23-87 years) in serum, and 30.6 ng/L (0.9 % CV) for men (18-87 years) and 20.2 ng/L (1.4 %CV) for women (18-88 years) in heparin plasma. Detection rates in healthy individuals ranged from 98.9 to 100 %. An excellent agreement was identified between LiCA® and Elecsys® assays with a correlation coefficient of 0.993 and mean bias of-0.7 % (-1.8-0.4 %) across the full measuring range, while the correlation coefficient and overall bias were 0.967 and-1.1 % (-2.5-0.3 %) for the lower levels of cTnT (10-100 ng/L), respectively. At the specific medical decision levels (14.0 and 52.0 ng/L), assay difference was estimated to be <5.0 %. No significant difference was found between these two assays in terms of area under curve (AUC), sensitivity and specificity, negative predictive value (NPV) and positive predictive value (PPV) for the diagnosis of NSTEMI. LiCA® hs-cTnT is a reliable 3rd-generation (level4) high-sensitivity assay for detecting cardiac troponin T. The assay is acceptable for practical use in the diagnosis of NSTEMI.

A-009 Analytical Concordance of High-Sensitivity Cardiac Troponin I and T Assays in Patients From the CONTRAST Trial Presenting to an Emergency Department

Abstract Background There are limited data on the analytical concordance of high-sensitivity cardiac troponin (hs-cTn) T and hs-cTnI assays. The goal of this study was to evaluate the concordance of one hs-cTnT and one hs-cTnI assay relative to each assay’s limit of quantitation (LoQ) and 99th percentile upper reference limit (URL). Methods The Comparison of Troponin I and T Assays Trial (CONTRAST) NCT03214029 is an observational study that evaluated the concordance of two FDA-cleared hs-cTn assay concentrations measured at presentation (0 h) and 2 h by the Abbott ARCHITETCT i2000 hs-cTnI (clinically used assay) and Roche cobas 601 Gen 5 hs-cTnT (measured for investigational purposes) from consecutively enrolled patients presenting to an urban US medical center with symptoms suggestive of ischemia. Concordance at presentation (0 h) was assessed relative to each assay’s FDA-cleared reporting concentration (LoQ), and FDA-cleared sex-specific 99th percentile URLs. The incidence of myocardial injury, defined as at least one concentration above the 99th percentile URL over serial sampling, was also evaluated. Results At presentation hs-cTn concentrations &amp;lt;LoQs (Abbott 3.5 ng/L, Roche 6 ng/L) were 834/2270 (37%) and 530/2270 (23%), respectively. The concordance of results &amp;lt;LoQ was 81%. The Abbott assay showed a higher percent of concentrations below both female and male URLs than did the Roche assay. For females, concentrations below the sex-specific 99th percentile URLs were 707/945 (75%) for Abbott hs-cTnI (16 ng/L) and 545/945 (58%) for Roche hs-cTnT (14 ng/L, P &amp;lt; 0.03). For males, concentrations below the sex-specific 99th percentile URLs were 1100/1325 (83%) for Abbott hs-cTnI (34 ng/L) and 900/1325 (68%) for Roche hs-cTnT (22 ng/L). The concordance of results below the sex-specific 99th percentile URLs for both assays was 80%. Among males with presentation concentrations &amp;lt;URL, the incidence of myocardial injury (hs-cTn &amp;gt;URL at 2 h) was approximately two-fold greater for the Roche hs-cTnT (59/900, 6.2%) than Abbott hs-cTnI (31/1110, 2.8%). Females with presentation concentrations &amp;lt;URL showed similar rates of myocardial injury at 2 h for the Roche (24/545 [4.4%]) and Abbott assays (36/707 [5.1%]). Conclusion We report a 20% discordance between Abbott hs-cTnI and Roche hs-cTnT assays in detecting myocardial injury at respective 99th percentile URLs and at each assays’ FDA allowed LoQ reporting limit.

A-011 High Sensitive Troponin Assays for Differentiating the Patients with Unstable Angina from Stable Angina

Abstract Background There have been no cardiac biomarkers used in the diagnosis of unstable angina. In this study, we examined high sensitive troponin T and I as a marker to differentiate the patients with unstable angina from the patients with stable angina. Methods A total of 816 patients (59 AMI, 94 unstable angina, 99 stable angina, 623 healthy individuals) were included. All patients had glomerular filtration rate of ≥60 mL/min/1.73 m2. Leftover serum samples were obtained from the patients who visited The Catholic University of Korea, St Vincent’s Hospital from April to November, 2019. Cardiac troponin was measured using Beckman Coulter Access high sensitivity cTnI assay, Abbott Architect high sensitive TnI assay, and Roche Elecsys Troponin T-high sensitive assay. Results The 99th percentile URLs (Upper Reference Limits) of Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT are 9.8 ng/L, 17.9 ng/L, and 16.4 ng/L, respectively. In the 99 patients with stable angina, 9.1% (9/99), 5.1% (5/99), and 6.1% (6/99) of the patients showed higher values than each the 99th percentile URL with Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT, respectively. In the 94 patients with unstable angina, 24.5% (23/94), 24.5% (23/94), and 25.5% (24/94) showed higher values than each the 99th percentile URL with Beckman Coulter cTnI, Abbott cTnI, and Roche cTnT, respectively. There are significant differences between the frequencies of the patients with stable angina and unstable angina showing higher values of cardiac troponins than each the 99th percentile URL. Conclusion High sensitive troponins could be a useful marker for the differentiation of the patients with unstable angina from stable angina.

Evaluation of the analytical and clinical performance of a new high-sensitivity cardiac troponin I assay: hs-cTnI (CLIA) assay.

Cardiac troponin (cTn) is the key biomarker for diagnosis of acute coronary syndrome (ACS). We performed a complete assessment of the high-sensitivity cardiac troponin I (hs-cTnI) (CLIA) assay on the analytical performance and clinical diagnostic performance, which was compared with Abbott ARCHITECT hs-cTnI assay. Sex-specific 99th percentile upper reference limits (URLs) were determined from a healthy population of 424 males and 408 females. High-sensitivity performance was assessed by examining the imprecision at sex-specific URLs and the detectable results above LoD in a cohort of healthy population. The diagnostic performance of the hs-cTnI (CLIA) assay was validated in a population of 934 patients with suspected ACS. The 99th percentile URLs were 15.3 ng/L for female, 31.3 ng/L for male and 24.2 ng/L for overall population. The total imprecision near the sex-specific 99th percentile URLs were <5 %. 76.74 % of females, 97.12 % of males and 86.69 % of overall population had cTnI values exceeding the LoD, which met the criteria of high-sensitivity troponin assay. Nocross-reactivity or interference was identified. The diagnostic sensitivity, specificity, PPV, NPV, and AUC of hs-cTnI (CLIA) assay were 97.97 , 90.70, 79.02, 99.21 % and 0.9885, respectively, which were comparable to ARCHITECT hs-cTnI assay. hs-cTnI (CLIA) assay is a high-sensitivity troponin I method with high precision, sensitivity and specificity. The clinical diagnostic performance of hs-cTnI (CLIA) is comparable to the established ARCHITECT hs-cTnI assay. Mindray's hs-cTnI (CLIA) assay is an attractive alternative for diagnosis of myocardial infarction with a high level of accuracy and safety.

The association of cardiac troponin and cardiovascular events in patients with concomitant heart failure preserved ejection fraction and atrial fibrillation

BackgroundLimited data are available for risk stratification in patients with atrial fibrillation (AF) and combined heart failure with preserved ejection fraction (HFpEF). We aimed to explore the prognostic utility of high-sensitivity cardiac troponin I (hs-cTnI) in patients with newly detected AF and concomitant HFpEF.MethodsFrom August 2014 to December 2016, 2,361 patients with newly detected AF were polled in a retrospective single-center registry. Of which, 634 patients were eligible for HFpEF diagnosis (HFA-PEFF score ≥ 5) and 165 patients were excluded with exclusion criteria. Finally, 469 patients are classified into elevated or non-elevated hs-cTnI groups based on the 99th percentile upper reference limit (URL). The primary outcome was the incidence of major adverse cardiac and cerebrovascular events (MACCE) during follow-up.ResultsIn 469 patients, 295 were stratified into the non-elevated hs-cTnI group (< 99th percentile URL of hs-cTnI) and 174 were placed in the elevated hs-cTnI group (≥ 99th percentile URL of hs-cTnI). The median follow-up period was 24.2 (interquartile range, 7.5–38.6) months. During the follow-up period, 106 patients (22.6%) in the study population experienced MACCE. In a multivariable Cox regression model, the elevated hs-cTnI group had a higher incidence of MACCE (adjusted hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.08–2.55; p = 0.03) and coronary revascularization-caused readmission (adjusted HR, 3.86; 95% CI, 1.39–15.09; p = 0.02) compared with the non-elevated hs-cTnI group. The incidence of heart failure-caused readmission tended to occur more frequently in the elevated hs-cTnI group (8.5% versus 15.5%; adjusted HR, 1.52; 95% CI, 0.86–2.67; p = 0.08).ConclusionsOne-fifth of patients with AF and concomitant HFpEF experienced MACCE during follow-up, and elevated hs-cTnI was independently associated with higher risk of MACCE, as driven by heart failure and revascularization-caused readmission. This finding suggested that hs-cTnI may be a useful tool in individualized risk stratification of future cardiovascular events in patients with AF and concomitant HFpEF.

Results from healthy donors for novel point-of-care high-sensitivity troponin test

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction This study evaluates healthy donor values of a novel high-sensitivity troponin test, an 8-minute whole blood assay performed with fingerstick or Lithium-heparin samples using a handheld sized platform designed for Point-of-Care or in-lab measurements. In accordance with the Fourth Universal Definition of Myocardial Infarction, whole blood 99th percentile upper reference limits (URLs) and 50th percentile (median) values for healthy individuals were characterised per gender; values were established for fingerstick, venous whole blood, and plasma. Purpose To determine 99th percentile URLs for hs-cTnI in healthy donors as myocardial injury cut-off for use in clinical trials and clinical practice. The median values were determined to confirm high-sensitivity performance in all matrices. Methods Whole blood from consented healthy subjects, 22 to 85 years (n=810), were collected across 5 clinical sites. Subjects taking cardiac history/medications or having abnormal hemoglobin A1c, NT-proBNP, and eGFR values were excluded. hs-cTnI values were determined in capillary (fingerstick), Li-Heparin venous whole blood, and venous Li-Heparin plasma matrices. Sex-specific and overall 99th percentile URLs using the recommended non-parametric approach and median values for each sample matrix were determined. Results Statistical outliers were eliminated by the Dixon-Reed test, prior to calculating the 99th percentile and median values. There was no significant difference between the three sample types. The median results are tabulated below: as expected, the female values are lower than the male values (p &amp;lt;0.01). These data additionally show that &amp;gt;50% of results exceed the assays limit of detection [ref .1] for all matrices, confirming this assay is a high-sensitive assay for troponin-I. Conclusion The novel hs-cTnI system is the first that demonstrates high-sensitivity cTnI performance in fingerstick, whole blood and plasma matrices. Quality measurements in all three matrices translates to use with confidence in emergency department and other diagnosis and triage settings. Hence, the data presented here are of relevance to current and future studies and clinical implementation of this device. Table 1: median hs-cTnI values in healthy subject, % of subjects above LoD (limit of detection) and %CV at 99th URL.

Prolonged infusion of bivalirudin after elective percutaneous coronary intervention protects against procedural myocardial injury (a COBER study)—a randomized trial

Procedural myocardial injury (PMI), which is the most common complication of elective percutaneous coronary intervention (ePCI), is associated with future adverse cardiac events. In this randomized pilot trial, we assessed the effects of prolonged use of the anti-coagulant bivalirudin on PMI after ePCI. Patients undergoing ePCI were randomized into the following two groups: the bivalirudin use during operation group (BUDO, 0.75 mg/kg bolus plus 1.75 mg/kg/h) and the bivalirudin use during and after operation for 4 h (BUDAO, 0.75 mg/kg bolus plus 1.75 mg/kg/h). Blood samples were collected before and 24 h after ePCI (per 8 h). The primary outcome, PMI, was defined as an increase in post-ePCI cardiac troponin I (cTnI) levels of > 1 × 99th% upper reference limit (URL) when the pre-PCI cTnI was normal or a rise in cTnI of > 20% of the baseline value when it was above the 99th percentile URL, but it was stable or falling. Major PMI (MPMI) was defined as a post-ePCI cTnI increase of > 5 × 99th% URL. A total of 330 patients were included (n = 165 per group). The incidences of PMI and MPMI were not significantly higher in the BUDO group than in the BUDAO group (PMI: 115 [69.70%] vs. 102 [61.82%], P = 0.164; MPMI: 81 [49.09%] vs. 70 [42.42%], P = 0.269). However, the absolute change in cTnI levels (calculated as the peak value 24 h post-PCI minus the pre-PCI value) was notably larger in the BUDO group (0.13 [0.03, 1.95]) than in the BUDAO group (0.07 [0.01, 0.61]) (P = 0.045). Moreover, the incidence of bleeding events was similar between the two groups (BUDO: 0 [0.00%]; BUDAO: 2 [1.21%], P = 0.498). Prolonged infusion of bivalirudin for 4 h after ePCI reduces PMI severity without increasing the risk of bleeding.ClinicalTrials.gov.Number: NCT04120961, 09/10/2019.

Myocardial Injury Thresholds for 4 High-Sensitivity Troponin Assays in a Population-Based Sample of US Children and Adolescents.

Myocardial injury is an important pediatric diagnosis. Establishing normative data from a representative pediatric sample is vital to provide accurate upper reference limits (URLs) for defining myocardial injury using high-sensitivity cardiac troponin. Among participants 1 to 18 years of age in the 1999-2004 National Health and Nutrition Examination Survey, we measured high-sensitivity troponin T using one assay (Roche) and high-sensitivity troponin I using 3 assays (Abbott, Siemens, and Ortho). In a strictly defined healthy subgroup, we estimated 97.5th and 99th percentile URLs for each assay using the recommended nonparametric method. Of 5695 pediatric participants, 4029 met criteria for the healthy subgroup (50% males; mean age 12.6 years). Our 99th percentile URL estimates for all 4 high-sensitivity troponin assays among children and adolescents were lower than the manufacturer-reported URLs (derived from adults). The 99th percentile URLs (95% CI) were 15 ng/L (95% CI, 12-17) for high-sensitivity troponin T, 16 ng/L (95% CI, 12-19) for high-sensitivity troponin I with the Abbott assay, 38 ng/L (95% CI, 25-46) for high-sensitivity troponin I with the Siemens assay, and 7 ng/L (95% CI, 5, 12) for high-sensitivity troponin I with the Ortho assay. The 95% CIs for age-, sex-, and race and ethnicity-specific 99th percentile URLs overlapped. However, the 97.5th percentile URL for each assay was measured with superior statistical precision (ie, tighter 95% CIs) and demonstrated differences by sex. For male compared with female children and adolescents, 97.5th percentile URLs were 11 ng/L (95% CI, 10-12) versus 6 ng/L (95% CI, 6-7) for high-sensitivity troponin T, 9 ng/L (95% CI, 7-10) versus 5 ng/L (95% CI, 4-6) for high-sensitivity troponin I with the Abbott assay, 21 ng/L (95% CI, 18-25) versus 11 ng/L (95% CI, 9-13) for high-sensitivity troponin I with the Siemens assay, and 4 ng/L (95% CI, 3-5) versus 2 ng/L (95% CI, 1-3) for high-sensitivity troponin I with the Ortho assay. In contrast to the 99th percentiles, the point estimates of 97.5th percentile pediatric URLs for high-sensitivity troponin were also much more stable to differences in the analytic approaches taken to estimate URLs. Because myocardial infarction is rare in children and adolescents, the use of statistically more precise and reliable sex-specific 97.5th percentile high-sensitivity troponin URLs might be considered to define pediatric myocardial injury.

Ethnicity and sex-specific 99th percentile upper reference limits of high-sensitivity cardiac troponin I among adults in Xinjiang, China

ObjectivesTo determine the 99th percentile upper reference limit (URL) of high-sensitivity cardiac troponin I (hs-cTnI) in a healthy population in Xinjiang, China, and investigate the impact of ethnicity, sex, and age on this limit. Design and MethodsFrom September 2018 to March 2022, 5,090 Han and Uyghur adults aged 20–79 years were recruited. After questionnaire screening, 2,970 participants with physical and/or laboratory normality were enrolled. Participants recruited between September 2018 and October 2021 (2,109/2,970) were evaluated by ARCHITECTi2000 to determine the 99th percentile URL of hs-cTnI. The results were then validated in 861/2,970 participants recruited from November 2021 to March 2022. A criterion of ≤ 10% of test results falling outside the original determined value was used to determine whether the newly established reference intervals were valid. ResultsThe hs-cTnI concentration was higher among Uyghurs than among Han participants (p < 0.001). The 99th percentile URLs were 17.52 ng/L for all participants, 18.96 ng/L for Uyghur, and 16.93 ng/L for Han. Hs-cTnI concentration was also correlated with sex and age. In the Han and Uyghur groups, male participants had a higher hs-cTnI concentration than female participants (p < 0.001); the 99th percentile URLs of hs-cTnI among male and female participants were 17.80 vs. 13.67 ng/L and 19.47 vs. 16.52 ng/L, respectively. Stratified by age, hs-cTnI concentrations were higher in participants aged > 60 years than in those of other age categories (p < 0.001), in both the Han and Uyghur groups. Finally, <2% of these test results exceeded the newly established reference, validating the results. ConclusionsThis study established the 99th percentile URLs of hs-cTnI in the Xinjiang. Ethnicity and sex influence the value and should be considered.

Diagnoses and Outcomes of Patients with Suspicion of Acute Coronary Syndrome and Raised High Sensitive Troponin I: A Single Center Study from Pakistan.

Objectives Troponins are classically raised in acute coronary syndrome (ACS) although other cardiovascular and non-cardiovascular causes are recognized. We aimed to see the association of high sensitivity (Hs) Troponin I values exceeding the sex-specific 99th percentile upper reference limit (URL) with diagnoses, emergency department (ED) outcomes, 30-day outcomes of admitted patients and predictors of ACS in both genders. Materials and Methods A retrospective study of all patients presenting to the emergency department from January 2019 to April 2021 with suspicion of ACS and Hs-Troponin I values greater than the sex-specific 99th percentile URL. Statistical Analysis SPSS version 24 was used, Pearson's chi-square tests, Fisher's exact test, Kruskal-Wallis test, Mann-Whitney U test, and odds ratios, including the 95% confidence intervals, for each characteristic were used for analysis. A p -value of < 0.05 was considered significant. Results There were a total of 5,982 patients (3,031 males, 2,951 females), out of which 878 patients were admitted under the cardiology specialty. In patients who were admitted to the ward, mortality was higher in females (8.2%) with less than a 10-fold rise in Hs-Troponin I while similar in both genders (7.6%) in patients with Hs-troponin I greater than 10-fold of sex-specific 99th percentile URL. Raised low-density lipoprotein-cholesterol was a significant factor associated with 2.4 times higher odds of ACS. Conclusion Women with Hs-Troponin values up to 10 times the URL, i.e., 15.6-160 ng/L have higher mortality than their male counterparts. LDL-cholesterol is a significant risk factor for ACS which should be controlled for its prevention.

Association of High-Sensitivity Troponin I with Cardiac and Cerebrovascular Events in Patient after Ischemic Stroke

Introduction: Early recognition and risk stratification of cardiovascular events are necessary in patients after ischemic stroke. Recent evidence suggests that elevated high-sensitive cardiac troponin is a predictor of mortality and vascular events. Therefore, we aimed to explore the prognostic role of high-sensitive cardiac troponin I (hs-TnI) on mortality and cardiovascular outcomes in patients after ischemic stroke. Methods: From August 2014 to July 2017, 1,506 patients with acute ischemic stroke were pulled consecutively in a retrospective single-center registry. Of these, 1,019 patients were selected and classified into the elevated or non-elevated hs-TnI groups according to hs-TnI level of 99th percentile upper reference limit (URL) at the time of admission for ischemic stroke. The primary outcome was a major adverse cardiac and cerebrovascular event (MACCE) during follow-up. Results: Among 1,019 patients, 708 patients were non-elevated hs-TnI group (<99th percentile URL of hs-TnI) and 311 patients were elevated hs-TnI group (≥99th percentile URL of hs-TnI). The median follow-up period was 22.5 (interquartile range 5.0–38.8) months. In a multivariable Cox regression model, the elevated hs-TnI group has a higher risk of MACCE (adjusted hazard ratio [HR]: 3.12; 95% confidence interval [CI]: 2.33–4.17; p < 0.01), all-cause mortality (adjusted HR: 4.15; 95% CI: 2.47–6.99; p < 0.01) and readmission caused by coronary revascularization (adjusted HR: 3.12; 95% CI: 1.41–6.90; p < 0.01), heart failure (adjusted HR: 2.76; 95% CI: 1.38–5.51; p < 0.01), and stroke (adjusted HR: 1.73; 95% CI: 1.07–2.78; p = 0.02) compared with the non-elevated hs-TnI group. Conclusions: Elevated hs-TnI is independently associated with higher mortality and cardiac and cerebrovascular events in patients with ischemic stroke and may serve as a valuable prognostic factor in management after ischemic stroke.

High-Sensitivity Cardiac Troponin I Levels Below 99th Percentile Upper Reference Limit in Patients Presenting with Suspicion of Acute Coronary Syndrome (ACS) in Emergency Department at a Tertiary Care Hospital in Karachi, Pakistan.

Troponin I levels are biomarkers of choice for diagnosis of acute myocardial infarction (AMI). However, prognostic significance of values below the 99th percentile upper reference limit (URL) in patients presenting with symptoms suggestive of Acute coronary syndrome (ACS) need further evaluation. The objectives of the study were to find the association of High sensitivity (hs)-Troponin I values below 99th percentile URL with age and the Emergency Department (ED) outcome, to determine single cut-off for safe discharge of these patients from the ED and to determine the 30-day outcome of the patients admitted under cardiac speciality. This is a retrospective study of patients presenting with suspicion of ACS in the ED between January 2019 till April 2021 and hs-Troponin I values below 99th percentile URL. Among 15,441 patients, 8034 (52%) were males and 7407 (48%) were females. 9677 (63%) of the patients had hs-Troponin I values < 5 ng/L while 5764 (37%) had values between 5 ng/L and 99th percentile URL. Higher hs-Troponin I values were associated with a worse ED outcome. Serial troponin I levels were performed in only 2.4% of the cohort. Receiver operating characteristics for ACS demonstrated an AUC of 0.84 at a cut off value of 12.75 ng/L, with sensitivity (76.9%) and specificity was 75.1%. The 30-day outcome of the patients admitted under cardiac speciality revealed no mortality in either group. An overall single cut-off value of 12.75 ng/L can be used in our population for ruling our ACS provided it is unaccompanied by other supportive clinical and ECG findings.

Analytical Considerations in Deriving 99th Percentile Upper Reference Limits for High-Sensitivity Cardiac Troponin Assays: Educational Recommendations from the IFCC Committee on Clinical Application of Cardiac Bio-Markers.

The International Federation of Clinical Chemistry Committee on Clinical Application of Cardiac Bio-Markers provides evidence-based educational documents to facilitate uniform interpretation and utilization of cardiac biomarkers in clinical laboratories and practice. The committee's goals are to improve the understanding of certain key analytical and clinical aspects of cardiac biomarkers and how these may interplay in clinical practice. Measurement of high-sensitivity cardiac troponin (hs-cTn) assays is a cornerstone in the clinical evaluation of patients with symptoms and/or signs of acute cardiac ischemia. To define myocardial infarction, the Universal Definition of Myocardial Infarction requires patients who manifest with features suggestive of acute myocardial ischemia to have at least one cTn concentration above the sex-specific 99th percentile upper reference limit (URL) for hs-cTn assays and a dynamic pattern of cTn concentrations to fulfill the diagnostic criteria for MI. This special report provides an overview of how hs-cTn 99th percentile URLs should be established, including recommendations about prescreening and the number of individuals required in the reference cohort, how statistical analysis should be conducted, optimal preanalytical and analytical protocols, and analytical/biological interferences or confounds that can affect accurate determination of the 99th percentile URLs. This document also provides guidance and solutions to many of the issues posed.

Analytical and clinical performance evaluation of a new high-sensitivity cardiac troponin I assay.

To validate the analytical performance and diagnostic accuracy for non-ST-segment elevation myocardial infarction (NSTEMI) with a new high-sensitivity cardiac troponin I (hs-cTnI) assay on the automated light-initiated chemiluminescent assay (LiCA®) platform. Comprehensive analytical validations were performed, and the 99th percentile upper reference limit (URL) from apparently healthy individuals were established. We evaluated the diagnostic performance of the assay for NSTEMI. The limit of quantitation (LoQ) were 1.9ng/L (20% CV) and 5.1ng/L (10% CV). The sex-specific 99th percentile URLs were 17.6ng/L (4.2% CV) for men (age 20-79y) and 14.2ng/L (4.9% CV) for women (age 19-89y) in serum, 14.4ng/L (4.9% CV) for men (age 19-88y) and 12.9ng/L (5.2% CV) for women (age 19-87y) in plasma, respectively. Detection rates in healthy individuals were from 98.7 to 99.1%. The correlation coefficient and median bias between LiCA and Architect were 0.985 and 0.1% (-2.0-2.9%) in full analytical range of serum specimens. In lower range (<100ng/L), LiCA had an overall positive bias 6.7% (-1.6-13.3%), R=0.949. At the specific medical decision levels (15.2, 26.2 and 64.0ng/L), assay difference was estimated to be <10%. No significant differences on AUC, sensitivity and specificity, NPV and PPV were found between LiCA and Architect for the diagnosis of NSTEMI. LiCA hs-cTnI is a precise, highly sensitive and specific assay that meets the requirement of a 3rd generation (level 4) high-sensitivity method. The diagnostic accuracy of LiCA assay for NSTEMI is comparable to the established Architect hs-cTnI assay.