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BACKGROUND The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score

Background We aimed to establish diagnostic criteria for bleeding independently associated with mortality after noncardiac surgery (BIMS) defined as bleeding during or within 30 days after noncardiac surgery that is independently associated with mortality within 30 days of surgery, and to estimate the proportion of 30-day postoperative mortality potentially attributable to BIMS. Methods This was a prospective cohort study of participants ≥45 yr old having inpatient noncardiac surgery at 12 academic hospitals in eight countries between 2007 and 2011. Cox proportional hazards models evaluated the adjusted relationship between candidate diagnostic criteria for BIMS and all-cause mortality within 30 days of surgery. Results Of 16 079 participants, 2.0% (315) died and 36.1% (5810) met predefined screening criteria for bleeding. Based on independent association with 30-day mortality, BIMS was identified as bleeding leading to a postoperative haemoglobin Conclusions Bleeding independently associated with mortality after noncardiac surgery (BIMS), defined as bleeding that leads to a postoperative haemoglobin Clinical trial registration NCT00512109.

Background We developed a biomarker algorithm encompassing the clinical chemistry score (CCS; which includes the combination of a random glucose concentration, an estimated glomerular filtration rate and high-sensitivity cardiac troponin; hs-cTn) with the Ortho Clinical Diagnostics hs-cTnI assay (CCS-serial) and compared it to the cutoffs derived from Ortho Clinical Diagnostics 0/1 h (h) algorithm for 7-day myocardial infarction (MI) or cardiovascular (CV)-death. Methods The study cohort was an emergency department (ED) population (n = 906) with symptoms suggestive of acute coronary syndrome (ACS) who had two Ortho hs-cTnI results approximately 3 h apart. Diagnostic parameters (sensitivity/specificity/negative predictive value; NPV/positive predictive value; PPV) were derived for the CCS-serial and the 0/1 h algorithm for 7-day MI/CV-death. A safety analysis was performed for patients in the rule-out arms of the algorithms for 30-day MI/death. Results The CCS-serial algorithm yielded 100% sensitivity/NPV (32% low-risk) and 95.7% specificity/65% PPV (11% high-risk). The 0/1 h algorithm-cutoffs yielded sensitivity/NPV/specificity/PPV of 97.8%/99.4%/91.3%/50%, which classified 38% of patients as low-risk and 16% of patients as high-risk. Four patients (1.2%) in the 0/1 h algorithm-cutoff rule-out arm had a 30-day MI/death outcome as compared to zero patients in the CCS-serial rule-out arm (p = 0.06). Conclusion Both the CCS-serial and 0/1 h algorithm cutoffs yield high NPVs with a similar proportion of patients identified as low-risk. These data may be useful for sites who are unable to collect samples at 0/1 h in the emergency department.

Background: For patients investigated for suspected acute coronary syndrome, there is uncertainty if a single measurement of high-sensitivity cardiac troponin I (hs-cTnI) at emergency department (ED) presentation can identify patients at both low and high risk for mortality. Methods: We included consecutive adult patients in the ED who had a Clinical Chemistry Score (CCS) taken at presentation (ie, combination of glucose, creatinine for estimated glomerular filtration rate determination, and hs-cTnI assay) in a Canadian city between 2012 and 2013. Outcomes were 3-month, 1-year, and 5-year all-cause mortality using the provincial death registry. Mortality rates and test performance (eg, sensitivity and specificity) with 95% confidence intervals (CIs) were obtained for the CCS or hs-cTnI assay alone using established cutoffs for these tests. Results: Our cohort included 5974 patients with a 1-year mortality rate of 17.2% (95% CI, 16.2-18.3). A CCS ≥ 1 yielded a sensitivity of 99.2% (95% CI, 98.4-99.6) compared with the hs-cTnI ≥ 5 ng/L cutoff sensitivity of 88.4% (95% CI, 86.3-90.3), with the mortality rate being significantly lower for patients with CCS < 1 (2.0%; 95% CI, 0.9-4.0) vs patients with hs-cTnI < 5 ng/L (5.0%; 95% CI, 4.2-6.0) at 1 year (P = 0.01). A CCS of 5 also yielded a higher specificity (88.5%; 95% CI, 87.5-89.3) compared with hs-cTnI > 26 ng/L (83.9%; 95% CI, 82.9-84.9), with no difference in mortality rates (37.4% vs 36.3%; P = 0.66). This trend was consistent at 3-month and 5-year mortality. Conclusion: For patients in the ED with a potential cardiac issue, using the CCS cutoffs can better identify patients at low and high risk for mortality than using published cutoffs for hs-cTnI alone. Résumé: Contexte: Dans le cas des patients chez qui l’on soupçonne un syndrome coronarien aigu, des doutes subsistent à savoir si la mesure de la troponine I cardiaque à haute sensibilité (TnIc-hs) à l’arrivée au service des urgences peut, à elle seule, permettre de repérer les patients présentant un risque de mortalité faible ou élevé. Méthodologie: L’étude portait sur les patients adultes qui se sont présentés consécutivement au service des urgences dans une ville canadienne entre 2012 et 2013 et pour lesquels un score CCS (Clinical Chemistry Score, ou score des paramètres biochimiques cliniques, c’est-à-dire glycémie, créatininémie [aux fins du calcul du débit de filtration glomérulaire estimé] et dosage de la TnIc-hs) a été établi à leur arrivée. Les critères d’évaluation étaient la mortalité toutes causes confondues à 3 mois, à 1 an et à 5 ans, déterminée à partir des actes de décès inscrits au registre provincial. Les taux de mortalité et la fiabilité des tests (sensibilité et spécificité) avec des intervalles de confiance (IC) à 95 % ont été déterminés pour le score CCS et pour le dosage de la TnIc-hs seulement au moyen des valeurs seuils établies pour ces tests. Résultats: La cohorte réunissait 5 974 patients, et le taux de mortalité à 1 an s’établissait à 17,2 % (IC à 95 % : 16,2-18,3). Un score CCS ≥ 1 a été associé à une sensibilité de 99,2 % (IC à 95 % : 98,4-99,6) comparativement à 88,4 % (IC à 95 % : 86,3-90,3) pour une valeur seuil de TnIc-hs ≥ 5 ng/l, le taux de mortalité à 1 an étant significativement plus bas chez les patients ayant un score CCS < 1 (2,0 %; IC à 95 % : 0,9-4,0) que chez ceux ayant un taux de TnIc-hs < 5 ng/l (5,0 %; IC à 95 % : 4,2-6,0) (p = 0,01). Un score CCS de 5 a en outre été associé à une plus grande spécificité (88,5 %; IC à 95 % : 87,5-89,3) qu’un taux de TnIc-hs > 26 ng/l (83,9 %; IC à 95 % : 82,9-84,9); il n’y avait pas de différence entre les taux de mortalité (37,4 % vs 36,3 %; p = 0,66). Les résultats relatifs à la mortalité à 3 mois et à 5 ans concordaient avec cette tendance. Conclusion: Dans le cas des patients admis au service des urgences en raison d’un problème cardiaque potentiel, les valeurs seuils du score CCS peuvent permettre de mieux repérer les patients qui présentent un risque de mortalité faible ou élevé, comparativement aux seules valeurs seuils publiées des taux de TnIc-hs.

High-sensitivity cardiac troponin (hs-cTn) assays enhance detection of lower circulating troponin concentrations, but the impact on outcomes in clinical practice is unclear. Our objective was to compare outcomes of chest pain patients discharged from emergency departments (EDs) using hs-cTn and conventional troponin (cTn) assays.We conducted an observational study of chest pain patients aged 40-105 years who presented to an ED from April 1, 2013, to March 31, 2017, and were discharged home. We compared 30-day and 1-year outcomes of EDs that used hs-cTn versus cTn assays. The primary outcome was a composite of all-cause death, myocardial infarction or unstable angina. Comparisons were conducted with (1) no adjustment; (2) adjustment for demographic, socioeconomic, and hospital characteristics; and (3) full clinical adjustment.Among the 394,910 patients, 62,138 (15.7%) were evaluated at hs-cTn EDs and 332,772 (84.3%) were evaluated at cTn EDs. Patients discharged from hs-cTn EDs were less likely to have diabetes, hypertension, or prior heart disease. At 30 days, the unadjusted primary outcome rate was lower in hs-cTn EDs (0.9% vs 1.0%, P .001). The 30-day hazard ratios for the primary outcome were 0.84 (95% CI 0.77-0.92) for no adjustment and 0.98 (95% CI 0.88-1.08) for full adjustment. Over 1 year, patients discharged from hs-cTn EDs had significantly fewer primary outcomes (3.7% vs 4.1%, P .001) and lower hazard ratio (0.93; 95% CI 0.89-0.98) even after full adjustment.Hs-cTn testing was associated with a significantly lower adjusted hazard of myocardial infarction, angina, and all-cause hospitalization at 1 year but not 30 days.

Guidelines published in 2021 have supported natriuretic peptide (NP) testing for the prognostication in patients with acute coronary syndrome (ACS) and for the diagnosis of chronic and acute heart failure (HF). Our objective was to determine if the addition of N-terminal pro B-type NP (NT-proBNP) and glucose to high-sensitivity cardiac troponin (hs-cTn) could better identify emergency department (ED) patients with potential ACS at low- and high-risk for a serious cardiovascular outcome over the next 72 h. The presentation sample in two different ED cohorts which enrolled patients with symptoms suggestive of ACS within six hours of pain onset (Cohort-1, n = 126 and Cohort-2, n = 143) that had Abbott hs-cTnI, Roche hs-cTnT, NT-proBNP and glucose were evaluated for NT-proBNP alone and combined with hs-cTn and glucose for the primary outcome (composite which included death, myocardial infarction, HF, serious arrhythmia and refractory angina) via receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC) and diagnostic estimates derived. The AUC for NT-proBNP for the primary outcome was 0.68 (95% confidence interval (CI): 0.59–0.76) and 0.75 (95%CI: 0.67–0.82) in Cohort-1 and 2, respectively, with the 125 ng/L cutoff yielding a higher sensitivity (≥75%) as compared to the 300 ng/L cutoff (≥58%). Using the 125 ng/L cutoff for NT-proBNP with the published glucose and hs-cTn cutoffs for risk-stratification produced a new score (GuIDER score for Glucose, Injury and Dysfunction in the Emergency-setting for cardiovascular-Risk) and yielded higher AUCs as compared to NT-proBNP (p < 0.05). GuIDER scores of 0 and 5 using either hs-cTnI/T yielded sensitivity estimates of 100% and specificity estimates > 92% for the primary outcome. A secondary analysis assessing MI alone in the overall population (combined Cohorts 1 and 2) also achieved 100% sensitivity for MI with a GuIDER cutoff ≥ 2, ruling-out 48% (Roche) and 38% (Abbott) of the population at presentation for MI. Additional studies are needed for the GuIDER score in both the acute and ambulatory setting to further refine the utility, however, the preliminary findings reported here may present a pathway forward for inclusion of NP testing for ruling-out serious cardiac events and MI in the emergency setting.

Serial high-sensitivity cardiac troponin (hsTn) testing in the emergency department (ED) and the intensive cardiac care unit may assist physicians in ruling out or ruling in acute myocardial infarction (MI). There are three major algorithms proposed for high-sensitivity cardiac troponin I (hsTnI) using serial measurements while incorporating absolute concentration changes for MI or death following ED presentation. We sought to determine the diagnostic estimates of these three algorithms and if one was superior in two different Canadian ED patient cohorts with serial hsTnI measurements. An undifferentiated ED population (Cohort-1) and an ED population with symptoms suggestive of acute coronary syndrome (ACS, Cohort-2) were clinically managed with non-hsTn testing with the hsTnI testing performed in real-time with physicians blinded to these results (i.e., hsTnI not reported). The three algorithms evaluated were the European Society of Cardiology (ESC), the High-STEACS pathway, and the COMPASS-MI algorithm. The diagnostic estimates were derived for each algorithm for the 30-day MI/death outcome for the rule-out and rule-in arm in each cohort and compared to proposed diagnostic benchmarks (i.e., sensitivity ≥ 99.0% and specificity ≥ 90.0%) with 95% confidence intervals (CI). In Cohort-1 (n = 2966 patients, 15.3% had outcome) and Cohort-2 (n = 935 patients, 15.6% had outcome), the algorithm that obtained the highest sensitivity (97.8%, 95% CI: 96.0–98.9 and 98.6%, 95% CI: 95.1–99.8, respectively) in both cohorts was COMPASS-MI. Only Cohort-2 with both the ESC and COMPASS-MI algorithms exceeded the specificity benchmark (97.0%, 95% CI: 95.5–98.0 and 96.7%, 95% CI: 95.2–97.8, respectively). Patient selection for serial hsTnI testing will affect specificity estimates, with no algorithm achieving a sensitivity ≥ 99% for 30-day MI or death.

Background The coronavirus disease 2019 (COVID-19) pandemic caused a halt to in-person ambulatory care. We evaluated how the reduction in access to care affected HbA1c testing and patient HbA1c levels. Methods HbA1c data from 11 institutions were extracted to compare testing volume and the percentage of abnormal results between a pre-pandemic period (January-June 2019, period 1) and a portion of the COVID-19 pandemic period (Jan-June 2020, period 2). HbA1c results greater than 6.4% were categorized as abnormal. Results HbA1C testing volumes decreased in March, April and May by 23, 61 and 40% relative to the corresponding months in 2019. The percentage of abnormal results increased in April, May and June (25, 23, 9%). On average, we found that the frequency of abnormal results increased by 0.31% for every 1% decrease in testing volume (p Conclusion HbA1c testing volume for outpatients decreased by up to 70% during the early months of the pandemic. The decrease in testing was associated with an increase in abnormal HbA1c results.

Background Heart-type fatty acid binding protein (H-FABP), a low molecular weight protein found primarily in myocardial tissue, has been identified as a potential biomarker in the detection of acute coronary syndrome and acute kidney injury. To further investigate clinical utility, we sought to establish an upper reference limit (URL) of H-FABP within a healthy U.S. population. Methods Serum samples of healthy donors were acquired from the AACC Universal Sample Bank. We analyzed 355 samples for H-FABP concentration using the Randox Laboratories immunoturbidimetric assay on the Roche Cobas 8000 series analyzer. Results The final sample population consisted of individuals aged 18–74 y, with 170 males and 185 females. The distribution of the population exhibited a strong positive skew, affecting outlier analysis and URL determination. The 97.5th-percentile URL was found to be 7.4 ng/ml (95% CI: 6.3–9.2), while the 99th-percentile URL was 12.1 ng/ml (8.6–14.9). Conclusion As the URL for H-FABP is highly affected by population distribution and outlier removal, final determination for an assay cutoff should be made in the context of clinical utility, either as a standalone assay or in conjunction with other biomarkers, and the desired clinical sensitivity and specificity.

We have recently detailed that the Ortho Clinical Diagnostics (OCD) hsTnI assay can yield non-reproducible elevated concentrations in patients with an acute phase response [1] , [2] , [3] , [4] , [5] , [6] . Early in these investigations, an initial repeat testing of 10 patient samples (EDTA plasma) from the emergency department (ED) at the Juravinski Hospital and Cancer Centre identified one poor repeat measurement (coefficient of variation (CV)>20%) at a concentration above the upper limit of normal (ULN) which prompted further investigation.

Background Cancer is a systemic catabolic condition affecting skeletal muscle and fat. We aimed to determine whether cardiac atrophy occurs in this condition and assess its association with cardiac function, symptoms, and clinical outcomes. Methods Treatment naïve metastatic non‐small cell lung cancer patients (n = 50) were assessed prior to and 4 months after commencement of carboplatin‐based palliative chemotherapy. Methods included echocardiography for left ventricular mass (LVM) and LV function [LV ejection fraction, global longitudinal strain (GLS), diastolic function], computed tomography to quantify skeletal muscle and total adipose tissue, Eastern Cooperative Oncology Group Performance Status (ECOG‐PS), validated questionnaires for dyspnoea and fatigue, plasma biomarkers, tumour response to therapy, and overall survival. Results During 112 ± 6 days, the median change in LVM was −8.9% [95% confidence interval (95% CI) −10.8 to −4.8, P < 0.001]. Quartiles of LVM loss were −20.1%, −12.9%, −4.8%, and +5.5%. Losses of muscle, adipose tissue, and LVM were frequently concurrent; LVM loss > median value was associated with loss of skeletal muscle [odds ratio (OR) = 4.5, 95% CI: 1.4–14.8, P=0.01] and loss of total adipose tissue (OR = 10.0, 95% CI: 2.7–36.7, P < 0.001). LVM loss was associated with decreased GLS (OR = 6.6, 95% CI: 1.9–22.7, P=0.003) but not with LV ejection fraction or diastolic function. In the population overall, plasma levels of C‐reactive protein (P=0.008), high sensitivity troponin T (hs‐TnT) (P=0.03), and galectin‐3 (P=0.02) increased over time, while N‐terminal pro B‐type natriuretic peptide and hs‐cTnI did not change over time. C‐reactive protein was the only biomarker associated with LVM loss but at the univariate level only. Independent predictors of LVM loss were prior weight loss (adjusted OR = 10.2, 95% CI: 2.2–46.9, P=0.003) and tumour progression (adjusted OR = 14.6, 95% CI: 1.4–153.9, P=0.02). LVM loss was associated with exacerbations of fatigue (OR = 6.6, 95% CI: 1.9–22.7, P=0.003), dyspnoea (OR = 9.3, 95% CI: 2.4–35.8, P

Background: Data regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes.Methods: In 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation–validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days.Results: Among 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set.Conclusions: A risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes. (Funded by the German Center for Cardiovascular Research [DZHK]; ClinicalTrials.gov numbers, NCT00470587, NCT02355457, NCT01852123, NCT01994577, and NCT03227159; and Australian New Zealand Clinical Trials Registry numbers, ACTRN12611001069943, ACTRN12610000766011, ACTRN12613000745741, and ACTRN12611000206921.)

OBJECTIVES Using data from the CORONARY trial (n = 4752), we evaluated the incidence and prognostic significance of myocardial infarction (MI) applying different definitions based on peak postoperative creatine kinase-MB isoenzyme and cardiac troponin levels. We then aimed to identify the peak cardiac troponin during the first 3 postoperative days that was independently associated with a 2-fold increase in 30-day mortality. METHODS To combine different assays, we analysed cardiac troponins in multiples of their respective upper limit of normal (ULN). We identified the lowest threshold with a hazard ratio (HR) >2 for 30-day mortality independent of EuroSCORE and on- versus off-pump surgery. RESULTS Depending on the definition used based on creatine kinase-MB, the incidence of MI after coronary artery bypass grafting (CABG) ranged from 0.6% to 19% and the associated HRs for 30-day mortality ranged from 2.7 to 6.9. Using cardiac troponin (1528 patients), the incidence of MI ranged from 1.7% to 13% depending on the definition used with HRs for 30-day mortality ranging from 5.1 to 7.2. The first cardiac troponin threshold we evaluated, 180xULN, was associated with an adjusted HR for 30-day mortality of 7.6 [95% confidence interval (CI) 3.4–17.1] when compared to CONCLUSIONS Our results illustrate that the incidence and prognosis of a post-CABG MI varies based on the definition used. Validated post-CABG MI diagnostic criteria formulated from their independent association with important clinical outcomes are needed.

Elevated cardiac troponin concentrations in people with critical illness are associated with an increased risk of death. We aimed to assess the feasibility of a larger study to ascertain the utility of cardiac troponin as a prognostic tool for mortality in critically ill patients. Patients admitted to participating intensive care units during the one-month enrolment period were eligible. We excluded cardiac surgical patients and patients who were admitted and either died or were discharged within 12 hr. In enrolled patients, we measured high-sensitivity cardiac troponin I (hs-cTnI) and obtained electrocardiograms to ascertain the incidence of myocardial infarction (MI) and isolated troponin elevation. Our feasibility objectives were to measure recruitment rate, the proportion of patients who consented under a deferred consent model, and time required for data collection and study procedures. Over a four-week enrolment period, 280 patients were enrolled using a deferred consent model. We obtained subsequent consent from 81% of patients. Study procedures and data collection required 1.7 hr per participant. Overall, 86 (38%) suffered a MI, 23 (10%) had an isolated hs-cTnI elevation, and 117 (52%) had no hs-cTnI elevation. The crude hospital mortality rate was 10% without an hs-cTnI elevation, 29% with an isolated hs-cTnl elevation (relative risk [RR]) 2.2; 95% confidence interval [CI], 1.0 to 6.0) and 29% with an MI (RR, 2.6; 95% CI, 1.4 to 5.1). Myocardial injury with elevated hs-cTnI concentrations and MIs occur frequently during critical illness. This pilot study has established the feasibility of conducting a large-scale investigation addressing this issue.

Background Manufacturers of high-sensitivity cardiac troponin (hs-cTn) assays have restricted use of what sample types or matrices are acceptable to use for measurement. Our goal was to evaluate the comparability of the Siemens ADVIA Centaur hs-cTnI assay across different matrices and under different storage conditions. Methods Three different QC-plasma matrices were evaluated for imprecision Results Over 16-weeks the SDs were ≤1.0 ng/L for QCs ranging from 5.0 to 8.3 ng/L. Across the reference interval there was excellent agreement between lithium heparin plasma and serum for the Siemens hs-cTnI assay (slope=0.98/intercept=–0.1), however, cTnI concentrations were proportionally lower in EDTA as compared to lithium heparin plasma (slope=0.90, 95% CI: 0.88–0.92). In lithium heparin plasma the Siemens hs-cTnI concentrations were higher than the Abbott hs-cTnI concentrations (slope=1.26/intercept=–0.2). Stability of cTnI in lithium heparin plasma as compared in serum and EDTA plasma appeared more labile, with decreases ≥20% in concentrations evident as early as 1-day in storage at RT. Conclusions There is excellent agreement in concentrations between lithium heparin plasma and serum with the Siemens ADVIA Centaur hs-cTnI assay; however, cTnI concentrations in EDTA plasma are lower. Reference intervals and clinical studies in EDTA plasma for the Centaur hs-cTnI assay are required before clinical use.

Combination of lymphocyte count and not the serological response with high-sensitivity cardiac troponin for risk stratification in patients with possible COVID-19.

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%, 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%, 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%, 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations.

High-sensitivity cardiac troponin (hs-cTn) testing has enabled physicians to make earlier diagnostic and prognostic decisions in the hospital setting than previous cardiac troponin assays. Analytical improvements have permitted one to measure cardiac troponin precisely in the nanogram per litre (ng/L) range with hs-cTn assays which has resulted in fast 0/1-h and 0/2-h algorithms for ruling-in and ruling-out myocardial infarction. Although analytical interferences that affect the reporting of hs-cTn are uncommon, not all hs-cTn assays are designed the same nor have undergone the same clinical and analytical validations. Here, after investigating an initial case of discrepant hs-cTnI results, we report that patients with an acute phase response (e.g., patients with inflammatory or infectious illnesses) can yield high and non-reproducible results with the Ortho Clinical Diagnostics hs-cTnI assay. Compared to Abbott Diagnostics hs-cTnI, Ortho Clinical Diagnostics hs-cTnI assay misclassifies biochemical injury in approximately 10% of the population being assessed for myocardial injury with imprecise results in approximately half of this population (i.e., 5%). In conclusion, caution is warranted in interpreting Ortho Clinical Diagnostics hs-cTnI alone in patients being evaluated for myocardial injury, especially in patients whose primary presentation is related to an acute phase response and not an acute coronary syndrome symptom.

Background Numerous studies have documented reduced access to patient care due to the COVID-19 pandemic, including access to diagnostic or screening tests, prescription medications, and treatment for an ongoing condition. In the context of clinical management for venous thromboembolism, this could result in suboptimal therapy with warfarin. We aimed to determine the impact of the pandemic on utilization of International Normalized Ratio (INR) testing and the percentage of high and low results. Methods INR data from 11 institutions were extracted to compare testing volume and the percentage of INR results ≥3.5 and ≤1.5 between a pre-pandemic period (January–June 2019, period 1) and a portion of the COVID-19 pandemic period (January–June 2020, period 2). The analysis was performed for inpatient and outpatient cohorts. Results Testing volumes showed relatively little change in January and February, followed by a significant decrease in March, April, and May, and then returned to baseline in June. Outpatient testing showed a larger percentage decrease in testing volume compared to inpatient testing. At 10 of the 11 study sites, we observed an increase in the percentage of abnormal high INR results as test volumes decreased, primarily among outpatients. Conclusion The COVID-19 pandemic impacted INR testing among outpatients which may be attributable to several factors. Increased supratherapeutic INR results during the pandemic period when there was reduced laboratory utilization and access to care is concerning because of the risk of adverse bleeding events in this group of patients. This could be mitigated in the future by offering drive-through testing and/or widespread implementation of home INR monitoring.

Objectives This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Methods Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer’s claims. Results All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer’s claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Conclusions Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0–3 g/L free hemoglobin), leading to falsely low cTn recovery up to 3 ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10–2000 ng/mL (41–8,180 nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged late in 2019 causing COVID-19 (coronavirus disease-2019) may adversely affect the cardiovascular system. Publications from Asia, Europe, and North America have identified cardiac troponin as an important prognostic indicator for patients hospitalized with COVID-19. We recognized from publications within the first 6 months of the pandemic that there has been much uncertainty on the reporting, interpretation, and pathophysiology of an increased cardiac troponin concentration in this setting. Content The purpose of this mini-review is: a) to review the pathophysiology of SARS-CoV-2 and the cardiovascular system, b) to overview the strengths and weaknesses of selected studies evaluating cardiac troponin in patients with COVID-19, and c) to recommend testing strategies in the acute period, in the convalescence period and in long-term care for patients who have become ill with COVID-19. Summary This review provides important educational information and identifies gaps in understanding the role of cardiac troponin and COVID-19. Future, properly designed studies will hopefully provide the much-needed evidence on the path forward in testing cardiac troponin in patients with COVID-19.

BACKGROUND: The ability to rule out or in a major adverse cardiac event (MACE) in patients with suspected acute coronary syndrome at emergency department (ED) presentation would be beneficial to patient care and the health care system. The clinical chemistry score (CCS) was evaluated in this context. METHODS: This diagnostic accuracy study evaluated 2 different ED cohorts with suspected acute coronary syndrome. For patients in cohort 1, who presented to the ED of 3 hospitals in Hamilton, Ontario, between May and August 2013, retrospective measurements were taken using the Ortho Clinical Diagnostics high-sensitivity cardiac troponin I (hs-cTnI) assay; for patients in cohort 2, who presented to the ED of the same 3 hospitals in Hamilton between November 2012 and February 2013, an ED cardiac presentation blood test panel was performed with the Abbott Diagnostics hs-cTnI assay. The sensitivity and specificity of the CCS (cut-offs of ≥ 1 and 5) and hs-cTnI alone (published cut-offs) were compared for MACE (composite of death, myocardial infarction, unstable angina, revascularization) at 30 days for both cohorts and at 90 days for cohort 2. RESULTS: The incidence of MACE at 30 days was higher in cohort 1 (n = 1058) (19.4%, 95% confidence interval [CI] 16.8%–22.2%) than in cohort 2 (n = 5974) (14.6%, 95% CI 13.6%–15.6%). In cohort 1, a CCS of 1 or above yielded a sensitivity of 99.5% (95% CI 97.3%–99.9%). The sensitivity with an Ortho hs-cTnI cut-off of 1 ng/L or above was 91.2% (95% CI 86.5%–95.7%). The specificity of a CCS of 5 (97.8%, 95% CI 96.5%–98.7%) was higher than when the overall 99th-percentile cut-off for the Ortho hs-cTnI assay (> 11 ng/L; 90.1%, 95% CI 87.9%–92.0%) was used. A similar pattern was observed in cohort 2 at 30 days and persisted at 90 days with the Abbott hs-cTnI assay. INTERPRETATION: The CCS derived with 2 different hs-cTnI assays and ED populations yielded higher sensitivity and specificity estimates for MACE than hs-cTnI alone. An intervention study is needed to evaluate the impact of the CCS at both the patient and hospital levels. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT01994577

Background Myocardial injury after noncardiac surgery (MINS) is common and is associated with postoperative major cardiac events and 30-day mortality. We have previously established the diagnostic criteria for MINS with the 4th-generation cardiac troponin T assay (TnT) and 5th-generation high-sensitivity TnT assay (hsTnT) based on prognostically relevant thresholds. Little is known about diagnostic criteria for MINS using the high-sensitivity troponin I (hsTnI) assay. Purpose To determine hsTnI thresholds associated with 30-day major cardiac events and death after noncardiac surgery. Methods We performed a nested prospective biobank cohort study of 4545 patients from the VISION Study. Patients were aged ≥45 years and underwent in-patient noncardiac surgery under regional or general anesthesia. Patients had samples collected and frozen preoperatively, and on postoperative days 1, 2 and 3. We measured hsTnI on thawed preoperative and postoperative samples. We used iterative Cox proportional hazard models to determine peak postoperative hsTnI thresholds independently associated with major cardiac events (i.e., composite of death, non-fatal cardiac arrest, congestive heart failure within 30 days and non-fatal myocardial infarction from postoperative days 4–30). Results Major cardiac events occurred in 89/4545 (2.0%) patients. Peak hsTnI values of Conclusion A hsTnI elevation within the first 3 days after noncardiac surgery independently predicts major cardiac events at 30 days. A peak postoperative hsTnI ≥75 ng/L was associated with a 6-fold increase in the risk of subsequent major cardiac events at 30 days as compared to peak postoperative hsTnI Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Siemens Healthcare Diagnostics Inc. Canadian Institutes of Health Research

For patients with chest pain who are deemed clinically to be low risk and discharged home from the emergency department (ED), it is unclear whether further laboratory tests can improve risk stratification. Here, we investigated the utility of a clinical chemistry score (CCS), which comprises plasma glucose, the estimated glomerular filtration rate, and high-sensitivity cardiac troponin (I or T) to generate a common score for risk stratification. In a cohort of 14,676 chest pain patients in the province of Ontario, Canada and who were discharged home from the ED (November 2012&ndash, February 2013 and April 2013&ndash, September 2015) we evaluated the CCS as a risk stratification tool for all-cause mortality, plus hospitalization for myocardial infarction or unstable angina (primary outcome) at 30, 90, and 365 days post-discharge using Cox proportional hazard models. At 30 days the primary outcome occurred in 0.3% of patients with a CCS &lt, 2 (n = 6404), 0.9% of patients with a CCS = 2 (n = 4336), and 2.3% of patients with a CCS &gt, 2 (n = 3936) (p &lt, 0.001). At 90 days, patients with CCS &lt, 2 (median age = 52y (IQR = 46&ndash, 60), 59.4% female) had an adjusted HR = 0.51 (95% confidence interval (CI) = 0.32&ndash, 0.82) for the composite outcome and patients with a CCS &gt, 2 (median age = 74y (IQR = 64&ndash, 82), 48.0% female) had an adjusted HR = 2.80 (95%CI = 1.98&ndash, 3.97). At 365 days, 1.3%, 3.4%, and 11.1% of patients with a CCS &lt, 2, 2, or &gt, 2 respectively, had the composite outcome (p &lt, 0.001). In conclusion, the CCS can risk stratify chest pain patients discharged home from the ED and identifies both low- and high-risk patients who may warrant different medical care.

BackgroundThe effect of hemodialysis on cardiac biomarkers is unclear. We sought to evaluate the degree and causes of intradialytic variability of high sensitivity troponin I (hs-TnI), galectin-3 (gal-3), and heart-type fatty acid binding protein (hFABP).Methodshs-TnI, gal-3, and hFABP were prospectively measured pre-dialysis and post-dialysis for 1 week every month for 6 months in 178 prevalent adult hemodialysis patients at a single center in Hamilton, Canada. The degree of change from pre-dialysis to post-dialysis for each cardiac biomarker was estimated with multilevel linear regression models.ResultsThe median change in the concentration of hs-TnI during hemodialysis was −1 ng/L (interquartile range [IQR] −1 to 2 ng/L) while gal-3 and hFABP changed by −36.3 ng/mL (IQR −27.7 to −46.8 ng/mL) and −19.41 ng/mL (IQR −13.61 to −26.87 ng/mL), respectively. The median (IQR) percentage intradialytic changes for hs-TnI, gal-3, and hFABP were 2.6% (−4.4% to 12.5%), −59.8% (−54.7% to −64.8%) and −35.3% (−28.4% to −42.1%), respectively. Ultrafiltration was associated with an increase in concentration of hs-TnI, gal-3, and hFABP (mean 0.99 ng/L, 1.05 ng/mL, and 1.9 ng/mL per L ultrafiltration, respectively, P ConclusionsUltrafiltration volume and hemodialysis treatment time influenced hs-TnI, gal-3, and hFABP concentrations during hemodialysis and should be considered when interpreting their measurement.

Highlights • SARS-CoV-2 serology offers limited clinical utility for individuals. • SARS-CoV-2 serology may be useful for seroprevalence studies. • Claims regarding protective immunity or infectivity cannot be made using serology. • Assay clinical sensitivity and specificity should approach 100%. • Harmonized reporting of SARS-CoV-2 serology minimizes result misinterpretation., Clinical laboratories across the world are working to validate and perform testing for SARS-CoV-2 antibodies. Herein, we present interim consensus guidance for Canadian clinical laboratories testing and reporting SARS-CoV-2 serology, with emphasis on the capabilities and limitations of these tests and recommendations for interpretative comments in an effort to achieve harmonized laboratory practices. The consensus document provides a broad overview of topics including sample type and contamination risk; kinetics of antibody response to COVID-19 and the impact on serology testing; clinical utility of SARS-CoV-2 serology testing; clinical performance of commercial laboratory-based assays commonly deployed in North America; recommendations for interim reporting; utility of SARS-CoV-2 antibody testing for pediatric patients; and utility of point-of-care testing. The information is based on the current literature and is subject to change as additional information becomes available.

As 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).The 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.The 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.The 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.

Background Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. Methods/Design CODE-MI (hs-cTn—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. Conclusions This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.

Cardiovascular disease (CVD) continues to be an important cause of death throughout the world. Diagnostic tests, in particular blood-based biomarkers, have played an integral role in CVD for over 60 years, especially for the diagnosis of acute myocardial infarction (AMI), where initially the enzymatic activity of serum aspartate aminotransferase was demonstrated to be increased in patients with AMI. Since the turn of the millennium, however, cardiac troponin has taken a prominent role and is considered the most optimal blood-based biomarker to be used in the diagnosis of AMI. In addition, the prevalence of heart failure (HF) in the population has increased, with projections in the United States suggesting close to a 50% increase in the HF prevalence from 2012 to 2030, resulting in more than 8 million adults living with HF. This chapter will discuss cardiovascular pathologies, in particular AMI and HF, as well as biomarkers used for detection and management of these patients including troponin, creatine kinase-MB, myoglobin, BNP, and N-terminal-proBNP, as well as others.

Concurrent with the introduction of cardiac troponin measurements into the diagnostic definition of myocardial infarction (MI), clinicians and laboratory professionals signaled a clear clinical need for improved analytical quality. This was an important precipitant for developing high-sensitivity cardiac troponin (hs-cTn) assays, currently used in rapid algorithms guiding investigations of patients presenting to the emergency department with possible MI. The hs-cTn assays were also important for the detection and monitoring of low-grade chronic myocardial injury, a condition that has been linked to increased long-term risk of cardiovascular morbidity and mortality. This review summarizes the general recommendations for defining analytical performance specifications while providing relevant clinical situations related to analytical performance. Importantly, outcome studies suggest analytical quality performance for hs-cTn is sufficient for early discharge of patients investigated for possible MI. However, bias due to change in calibrators or reagents may significantly affect the percentage of patients discharged. Biological variation data is suitable for defining performance specifications when hs-cTn measurements are used for diagnosing and monitoring chronic myocardial injury. Further improvement in analytical performance for hs-cTn testing may result in even faster decision making in the emergency setting; while also identifying those with chronic injury at risk for an adverse cardiac event. publishedVersion

International recommendations on high-sensitivity cardiac troponin (hs-cTn) testing recommend that laboratories select only one sample type for testing. We evaluated the Siemens ADVIA Centaur hs-cTnI assay in serum and thereby provide information on imprecision, long-term storage stability, freeze-thaw stability, method comparison to other hs-cTnI assays, and clinical performance.Patients with chest pain onset6 h who already had Roche hs-cTnT, Beckman hs-cTnI and Abbott hs-cTnI results recorded and had non-thawed and frozen serum aliquots formed the study population (n = 134 patients with 305 serum aliquots obtained at either 0, 3 or 6 h stored below -70 °C since 2003) for measurement with the Siemens hs-cTnI assay in 2018. Receiver-operating characteristic curve analyses for myocardial infarction (MI) using the highest obtained hs-cTn concentration was performed. Additional comparison testing on serum samples stored frozen (at -70 °C for1 month in 2018) for the Siemens and Abbott hs-cTnI assays were performed, as well as precision testing in serum pools and freeze-thaw stability testing.The Siemens hs-cTnI assay had an area under the curve (AUC) of 0.978 (95%CI: 0.937-0.996) for MI in the study cohort (Roche hs-cTnT AUC = 0.965 and Abbott AUC = 0.973). The Siemens hs-cTnI assay yielded higher cTnI concentrations than the other hs-cTn assays, with the same proportional bias (slope = 1.4) between the Siemens and Abbott hs-cTnI assays obtained from serum samples collected in 2003 and 2018. Over 3 months, a low serum pool of 3.5 ng/l achieved a CV of 20% (SD = 0.7, n = 42) and a high serum pool of 820 ng/l achieved a CV of 2.3% (SD = 20, n = 42). Three different serum pools recovered within 10% from baseline concentration after 5 freeze-thaw cycles for the Siemens hs-cTnI assay.In serum, the Siemens ADVIA Centaur hs-cTnI assay had excellent clinical performance for MI in an early chest pain onset population, acceptable precision at normal and highly elevated cTnI concentrations, long-term storage stability (15 y storage below -70 °C) and acceptable freeze-thaw stability, all of which supports serum as an acceptable sample type to use in clinical studies and in clinical practice.