BACKGROUND:Sex-specific diagnostic thresholds for high-sensitivity cardiac troponin (hs-cTn) assays are recommended by international guidelines for the diagnosis of myocardial infarction (MI). We assessed the performance of sex-specific single-sample rule-out thresholds for identifying low-risk patients in the emergency department. METHODS:The derivation cohort comprised patients ≥18 years presenting with suspected MI to 2 Norwegian hospitals between 2015 and 2020 with 0-hour hs-cTnT (Roche) and high-sensitivity cardiac troponin I (Abbott and Siemens) measurements available. The primary endpoint was type 1 MI at index encounter. Diagnoses were adjudicated using assay-specific criteria per the Fourth Universal Definition of Myocardial Infarction. Sex-specific single-sample rule-out thresholds were derived, compared with guideline-recommended uniform thresholds, and externally validated in an independent and comparable British cohort. RESULTS:Among 1896 patients [median age 62 (25th-75th percentile 52-72) years; 39% female], MI occurred in 12.5%-12.8% males and 8.8%-9.2% females, depending on the adjudication assay.For each assay, more females had hs-cTn concentrations below the uniform single-sample thresholds, yet these thresholds did not achieve >99% sensitivity in females. Sex-specific adjustment achieved >99% sensitivity at cutoffs of <4 and <7 ng/L (Roche); <1 and <6 ng/L (Abbott); <2 and <7 ng/L (Siemens) for females and males, respectively. Sex-specific thresholds reduced rule-out proportions in females (from 29%-60% to 10%-32%) and increased them in males (from 17%-53% to 45%-64%). Trends were similar in the validation cohort of 1948 patients. CONCLUSIONS:Uniform single-sample rule-out thresholds reveal marked sex differences in MI risk stratification. Sex-specific hs-cTn thresholds could improve safety in females and efficiency in males. CLINICALTRIALS.GOV REGISTRATION NUMBERS:NCT02620202; NCT01852123.

INTRODUCTION:Expression of the cytokine growth differentiation factor 15 (GDF-15) is up-regulated in conditions of tissue injury and stress. We evaluated if GDF-15 predicts obstructive coronary artery disease (CAD) or need for revascularization within 30 days and 12 months in low/intermediate risk patients with acute chest pain. MATERIALS AND METHODS:We included 537 hospitalized patients who had high-sensitivity troponin T (hs-cTnT) < 99th percentile and underwent coronary CT angiography (CCTA). Odds ratios (ORs) and 95 % confidence intervals (CI) were calculated by logistic regression analyses and are reported per standard deviation increment of GDF-15 (log-transformed). RESULTS:The median (25th-75th percentile) age was 56 (49-65) years, 217 (40.4 %) were women, 83 (15.5 %) had obstructive CAD at CCTA. In total 49 (9.1 %) patients underwent revascularization within 30 days and 52 (9.7 %) within 12 months. In age and sex adjusted analysis GDF-15 was a significant predictor with ORs (95 % CI) of 1.35 (1.05-1.73), 1.39 (1.06-1.83) and 1.41 (1.07-1.84) for obstructive CAD, revascularization within 30 days and 12 months, respectively. However, after adjustment for clinical covariables, the ORs of GDF-15 were no longer statistically significant for either outcome (P ≥ 0.07). Adding hs-cTnT levels alone to the age and sex adjusted model also rendered the ORs of GDF-15 non-significant (P ≥ 0.31). CONCLUSIONS:In patients with acute chest pain but without acute myocardial infarction, GDF-15 did not substantially improve the identification of obstructive CAD or need for revascularization within 30 days and 12 months. Our findings question the clinical usefulness of GDF-15 for prognostication of low-risk patients with acute chest pain.

BACKGROUND:This study simulates how assay-specific bias influences the diagnostic performance of 0/1-h accelerated diagnostic protocols (ADPs) for 3 different high-sensitivity cardiac troponin (hs-cTn) assays. METHODS:We included 1493 patients presenting with chest pain. hs-cTnT (Roche Diagnostics), hs-cTnI from Abbott Diagnostics (hs-cTnI-A), and Siemens Healthineers (hs-cTnI-S) were measured at admission. The absolute total error observed in a state-of-the-art EQA study were added to the admission concentrations, producing 6 new variables being adjusted for maximum possible bias (if analytical variation is 0) (+biasmean, +biasmax95%CI, +biasmin95%CI, -biasmean, -biasmax95%CI, -biasmin95%CI). The influence of this "worst-case scenario" bias was compared after calculating sensitivity, specificity, negative and positive predictive values, and rule-out proportion for 30-day myocardial infarction or death for the observed and bias-adjusted hs-cTn concentrations. RESULTS:For 0-h rule-out, hs-cTnI-S and hs-cTnT had a sensitivity of >99.0%, compared to 97.7% for hs-cTnI-A. After adding the bias, sensitivity was unchanged for hs-cTnI-S (99.5%), but lower for hs-cTnT (95.5%), and hs-cTnI-A (96.2%). For the 0-/1-h algorithm, adding bias reduced sensitivity to 95.5% for hs-cTnT, while both hs-cTnI algorithms were unchanged (100.0%). Rule-out proportions for 0 h ranged from 0% to 60.0% for hs-cTnT, 28.2%-62.7% for hs-cTnI-A, and 3.5%-35.5% for hs-cTnI-S. For the 0-/1-h algorithm, ranges were 57.7%-75.8% (hs-cTnT), 52.8%-67.5% (hs-cTnI-A), and 45.7%-61.2% (hs-cTnI-S). CONCLUSION:Analytical bias of hs-cTn assays affects the clinical rule-out rate of the 0/1-h ADPs more than the diagnostic sensitivity. Bias may have a greater influence on the proportion of patients requiring hospital admission and may contribute to the heterogeneity of the reported rule-out rates of current ADPs. ClinicalTrials.gov Registration Number: NCT02620202.

Aims This prospective, two-centre study derived and validated predictive algorithms for the Siemens Atellica IM high-sensitivity cardiac troponin I (hs-cTnI) assay in the emergency department (ED). Methods and results Algorithms for predicting 30-day myocardial infarction (MI) Types 1 and 2 and death or non-ST-elevation MI (NSTEMI, Types 1 and 2) at index admission were developed from a derivation cohort of 1896 patients and validated using a synthetic data set with nearly 1 million patient cases. Performance was compared with the European Society of Cardiology algorithms for hs-cTnT (Roche Diagnostics) and hs-cTnI (Abbott Diagnostics). An admission hs-cTnI concentration < 5 ng/L had a negative predictive value (NPV) and sensitivity for 30-day MI or death of 99.5-99.7% and 98.1-98.8%, respectively, in the derivation cohort and validation data set. The NPV and sensitivity were >= 99.7% and >= 98.8% for ruling out index NSTEMI. A 0- to 1-h algorithm with baseline hs-cTnI concentration < 10 ng/L and Delta change < 3 ng/L had NPV of >= 99.5% and sensitivity >= 97.3% for predicting 30-day MI or death and a >= 99.5% sensitivity and NPV for index NSTEMI. Rule-in algorithms of either 0-h hs-cTnI >= 120 ng/L or 0- to 1-h Delta change >= 12 ng/L had positive predictive value >= 73% and specificity > 96% for 30-day MI or death and index NSTEMI. The results were comparable with established hs-cTn algorithms. Conclusion This study presents Siemens Atellica hs-cTnI algorithms for diagnosis and risk prediction in the ED with performance comparable with established hs-cTnT (Roche) and hs-cTnI (Abbott) algorithms.

Background: There are limited data regarding the utility of follow-up cardiac troponin (cTn) measurements after admission for acute chest pain and how long-term stability of myocardial injury and prognostic value differ when using cardiac troponin T (cTnT) or I (cTnI). Methods: We measured high-sensitivity (hs)-cTnT (Roche Diagnostics) and hs-cTnI (Siemens Healthineers) during hospitalization for acute chest pain and after 3 months. Acute myocardial injury was defined as concentrations > sex-specific upper reference limit (URL) during hospitalization and <= URL at 3-months. Chronic myocardial injury (CMI) was defined as concentrations > URL at both time points. Patients were followed from the 3-month sampling point for a median of 1586 (IQR 1161-1786) days for a primary composite endpoint of all-cause mortality, myocardial infarction (MI), revascularization, and heart failure, and a secondary endpoint of all-cause mortality. Results: Among 754 patients, 33.8% (hs-cTnT) and 19.2% (hs-cTnI) had myocardial injury during hospitalization. The rate of CMI was 5 times higher by hs-cTnT (20%) assay than hs-cTnI (4%), while acute myocardial injury was equally common; 14% (hs-cTnT) and 15% (hs-cTnI), respectively (6% and 5% when excluding index non-ST-elevation MI (NSTEMI). For hs-cTnT, peak index concentration, 3-month concentration and classification of CMI predicted the primary endpoint; hazard ratios (HRs) 1.38 (95% CI 1.20-1.58), 2.34 (1.70-3.20), and 2.31 (1.30-4.12), respectively. For hs-cTnI, peak index concentration predicted the primary endpoint; HR 1.14 (1.03-1.25). This association was nonsignificant after excluding index NSTEMI. Conclusions: Acute myocardial injury is equally frequent, whereas CMI is more prevalent using hs-cTnT assay than hs-cTnI. Measuring hs-cTnT 3 months after an acute chest pain episode could assist in further long-term risk assessment.

Percutaneous coronary intervention (PCI) has come a long way since Andreas Gründzig performed coronary angioplasty for the first time in 1977 (1).The problem of restenosis and dissection with acute lumen loss or occlusion has, by far, been tackled by coronary stenting (2). Subsequently, drug eluting stents (DES) have proven to be superior to bare metal stents (BMS) in terms of restenosis and target vessel revascularization (TVR) (3). The use of newer generations of DES is also associated with improved survival (4). At present, nearly all stents used are DES. As more and more complex lesions are treated with PCI, there is a constant demand for improvement in stent technology and performance (5).

Background Acute chest pain is associated with an increased risk of death and cardiovascular events even when acute myocardial infarction (AMI) has been excluded. Growth differentiation factor-15 (GDF-15) is a strong prognostic marker in patients with acute chest pain and AMI, but the prognostic value in patients without AMI is uncertain. This study sought to investigate the ability of GDF-15 to predict long-term prognosis in patients presenting with acute chest pain without AMI. Methods In total, 1320 patients admitted with acute chest pain without AMI were followed for a median of 1523 days (range: 4 to 2208 days). The primary end point was all-cause mortality. Secondary end points included cardiovascular (CV) death, future AMI, heart failure hospitalization, and new-onset atrial fibrillation (AF). Results Higher concentrations of GDF-15 were associated with increased risk of death from all causes (median concentration in non-survivors vs survivors: 2124 pg/mL vs 852 pg/mL, P < 0.001), and all secondary end points. By multivariable Cox regression, GDF-15 concentration >= 4th quartile (compared to <4th quartile) remained an independent predictor of all-cause death (adjusted hazard ratio (HR): 2.75; 95% CI, 1.69-4.45, P < 0.001), CV death (adjusted HR: 3.74; 95% CI, 1.31-10.63, P = 0.013), and heart failure hospitalization (adjusted HR: 2.60; 95% CI, 1.11-6.06, P = 0.027). Adding GDF-15 to a model consisting of established risk factors and high-sensitivity cardiac troponin T (hs-cTnT) led to a significant increase in C-statistics for prediction of all-cause mortality. Conclusions Higher concentrations of GDF-15 were associated with increased risk of mortality from all causes and risk of future CV events.

Introduction: The cytokine growth differentiation factor 15 (GDF-15) is expressed in several tissues including cardiomyocytes, and is up-regulated in conditions of tissue injury and stress. Hypothesis: We hypothesized that serum GDF-15 can predict obstructive CAD and need of revascularization among acutely admitted chest pain patients. Further, we assessed whether the combination of GDF-15 and coronary artery calcium (CAC) scoring could identify a subgroup with low risk of obstructive CAD, in whom a full coronary CT angiography (CCTA) could be avoided. Methods: GDF-15 was measured, using the assay on Cobas e801 (Roche Diagnostics), in 537 patients with chest pain and high-sensitivity cardiac troponin T concentrations ≤99th percentile. All participants underwent CAC scoring and CCTA. Obstructive CAD was defined as >50% lumen diameter narrowing. Associations of GDF-15 with obstructive CAD and 30-days revascularization were calculated by multivariable logistic regression adjusting for age, sex, smoking, hypertension, HbA1c, LDL-cholesterol, GFR and prior AMI. We also evaluated whether GDF-15 could improve sensitivity and negative predictive value (NPV) of CAC=0 for ruling out the presence of obstructive CAD. Results: The median (25th-75th percentile) age was 56 (49-65) years, 217 (40.4%) of the patients were women, 83 (15.5%) had obstructive CAD, and 49 (9.1%) had revascularization within 30 days. After multivariable adjustment, elevated GDF-15 (≥1200pg/mL) predicted obstructive CAD at baseline with OR (95%CI) of 2.23 (1.14-4.36), p=0.02. The OR (95%CI) for 30-days revascularization was 2.33 (1.08-5.03), p=0.03. For CAC=0, we observed a sensitivity (95%CI) and NPV (95%CI) of 94.0% (86.5%-98.0%) and 98.0% (95.3%-99.3%) in ruling out obstructive CAD. For patients having both CAC=0 and GDF-15 levels below median (<730pg/mL), sensitivity (95%CI) and NPV (95%CI) for obstructive CAD were 97.6% (91.6%-99.7%) and 98.7 (95.2%-99.8%), respectively. Conclusions: Elevated serum GDF-15 predicts obstructive CAD and 30 days revascularization among patients with chest pain, but without AMI. The combination of low GDF-15 levels and CAC=0 appears promising for the identification of low-risk patients, who can possibly be discharged without a full CCTA.

Background: Cardiac troponin (cTn) concentrations and the associated long-term cardiovascular risk differ between women and men in the general population. Research question: In patients with acute chest pain, does the prognostic value of cTn differ between sexes as assessed by different cTn assays? Methods: This prospective cohort study included 1500 patients (906 men and 594 women) admitted with suspected NSTE-ACS. Admission cTn was measured with three different high-sensitivity assays: hs-cTnT (Roche), hs-cTnI (Siemens) and hs-cTnI (Abbott). Patients were followed for a median of 1687 (range 4-2208) days. The primary endpoint was a composite of all-cause mortality, myocardial infarction, revascularization and heart failure. The secondary endpoint was all-cause mortality. Discriminatory performance was calculated by the receiver-operating characteristics area under the curve (ROC-AUC) whilst prognostic value was calculated by hazard ratios (HR) in unadjusted and adjusted Cox proportional hazard models. Results: The primary endpoint occurred in 18.1% of men and 15.0% of women. The secondary endpoint occurred in 10.3% of men and 8.9% of women. Women were older than men (median 65 years vs. 59 years, P<0.001), and had higher cTn concentrations (P<0.001 for all assays). All cTn assays had significantly higher discriminatory value in women compared to men for both endpoints (Table 1). Ln-transformed cTn for all assays were associated with increased risk of the primary endpoint and all-cause mortality in both sexes. Unadjusted HRs were higher in women than men with increasing hs-cTn, while in multivariate Cox model the adjusted HRs exhibited similar values between sexes (both endpoints) with no interaction between sex (P>0.05 for all) (Table 1). Conclusions: In patients with suspected with NSTE-ACS, there is a difference in the discriminatory value of hs-cTn, but no clear trend between sexes regarding its prognostic in adjusting for a range of factors, including age.

OBJECTIVES:Chronic myocardial injury (CMI) is defined as stable concentrations of cardiac troponin T or I (cTnT or cTnI) above the assay-specific 99th percentile upper reference limit (URL) and signals poor outcome. The clinical implications of diagnosing CMI are unclear. We aimed to assess prevalence and association of CMI with long-term prognosis using three different high-sensitivity cTn (hs-cTn) assays. METHODS:A total of 1,292 hospitalized patients without acute myocardial injury had cTn concentrations quantified by hs-cTn assays by Roche Diagnostics, Abbott Diagnostics and Siemens Healthineers. The median follow-up time was 4.1 years. The prevalence of CMI and hazard ratios for mortality and cardiovascular (CV) events were calculated based on the URL provided by the manufacturers and compared to the prognostic accuracy when lower percentiles of cTn (97.5, 95 or 90), limit of detection or the estimated bioequivalent concentrations between assays were used as cutoff values. RESULTS:There was no major difference in prognostic accuracy between cTnT and cTnI analyzed as continuous variables. The correlation between cTnT and cTnI was high (r=0.724-0.785), but the cTnT assay diagnosed 3.9-4.5 times more patients with having CMI based on the sex-specific URLs (TnT, n=207; TnI Abbott, n=46, TnI Siemens, n=53) and had higher clinical sensitivity and AUC at the URL. CONCLUSIONS:The prevalence of CMI is highly assay-dependent. cTnT and cTnI have similar prognostic accuracy for mortality or CV events when measured as continuous variables. However, a CMI diagnosis according to cTnT has higher prognostic accuracy compared to a CMI diagnosis according to cTnI.

Introduction: Biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has essentially focused on platelets. Follow-up (FU) time has been short, whereas in the current study, focus has been on endothelial function during both short- and long-term PAR-1 inhibition. Aim: To assess short- and long-term effects of vorapaxar (V) as compared to Placebo (PL) on the following biomarkers: Angiopoietin-2 (ANGPT2), Angiopoietin-like 4 (ANGPTL4), VEGF, ICAM-1, VCAM-1, E-Selectin (ESEL), von Willebrand Factor (VWF), Thrombomodulin (TM), PAI-1 and PAI-2. Methods: In an independent collective subproject performed in Norway, post-MI patients at steady state were recruited from the “Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients with Atherosclerosis” (TRA2ᵒP-TIMI 50) and NSTEMI patients were recruited from the “Thrombin Receptor Antagonist for Clinical Event Reduction in acute coronary syndrome” (TRACER) trial. Biomarkers were measured in duplicate by enzyme immunoassays (EIA) in citrated plasma at one month follow-up and at study completion (median 2.3 years) for subjects recruited from both trials. Results: Biomarkers were measured in 265 consecutive patients [age median 62.0 years (Q1-Q3: 55.0-68.0 years), males 83%] with at least one change from baseline value. Among these, biomarkers were available at both short- and long-term follow-up in 221 subjects. ANGPT2 increased significantly in V as compared to PL at 1-month follow-up in the total population (p=0.034), and in males in both post-MI (p=0.031) and NSTEMI subjects (p=0.012), respectively. ANGPTL4 increased (p=0.028) and PAI-2 decreased (p=0.025) significantly in the total population in favor of V at final FU. In the total post-MI subgroup and among males of that group, a short-term significant increase in ESEL in favor of V was observed, p=0.029 and p=0.018, respectively. Also, a transient significant increase in VWF (p=0.032) in favor of V was seen at one month in NSTEMI patients. Conclusions: Significant changes suggesting potential harmful effects in some biomarkers were observed during 1-month and long-term PAR-1 inhibition as compared to placebo in post-MI and acute coronary syndrome patients.

Aims This study tested the hypothesis that combining stress-induced biomarkers (copeptin or glucose) with high-sensitivity cardiac troponin (hs-cTn) increases diagnostic accuracy for non-ST-elevation myocardial infarction (NSTEMI) in patients presenting to the emergency department. Methods and results The ability to rule-out NSTEMI for combinations of baseline hs-cTnT or hs-cTnI with copeptin or glucose was compared with the European Society of Cardiology (ESC) hs-cTnT/I-only rule-out algorithms in two independent (one Norwegian and one international multicentre) diagnostic studies. Among 959 patients (median age 64 years, 60.5% male) with suspected NSTEMI in the Norwegian cohort, 13% had NSTEMI. Adding copeptin or glucose to hs-cTnT/I as a continuous variable did not improve discrimination as quantified by the area under the curve {e.g. hs-cTnT/copeptin 0.91 [95% confidence interval (CI) 0.89-0.93] vs. hs-cTnT alone 0.91 (95% CI 0.89-0.93); hs-cTnI/copeptin 0.85 (95% CI 0.82-0.87) vs. hs-cTnI alone 0.93 (95% CI 0.91-0.95)}, nor did adding copeptin <9 mmol/L or glucose <5.6 mmol/L increase the sensitivity of the rule-out provided by hs-cTnT <5 ng/L or hs-cTnI <4 ng/L in patients presenting more than 3 h after chest pain onset (target population in the ESC-0 h-algorithm). The combination decreased rule-out efficacy significantly (both P < 0.01). These findings were confirmed among 1272 patients (median age 62 years, 69.3% male) with suspected NSTEMI in the international validation cohort, of which 20.7% had NSTEMI. A trend towards increased sensitivity for the hs-cTnT/I/copeptin combinations (97-100% vs. 91-97% for the ESC-0 h-rule-out cut-offs) was observed in the Norwegian cohort. Conclusion Adding copeptin or glucose to hs-cTnT/I did not increase diagnostic performance when compared with current ESC guideline hs-cTnT/I-only 0 h-algorithms.

Background Vorapaxar has been shown to reduce cardiovascular mortality in post myocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. Aim This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days' FU and beyond, in patients with coronary heart disease. Methods Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at-80 degrees C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and-2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). Results A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1 month FU (p = 0.034). Angiopoietin-like 4 increased (p = 0.028) and plasminogen activator inhibitor-2 decreased (p = 0.025) in favor of vorapaxar at final FU. In post MI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p = 0.029. Also, a short-term increase in von Willebrand factor (p = 0.032) favoring vorapaxar was noted in NSTEMI patients. Conclusion Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients.

Introduction: Patients presenting with acute chest pain may carry an increased risk of cardiovascular events even though myocardial infarction (MI) is excluded. Whether there are gender-related differences in the prognostic value of biomarkers in this patient population is unclear. Methods: We performed a post hoc analysis of the WESTCOR trial that included 1319 patients (779 male and 540 female) admitted with acute chest pain without MI. Biomarkers included peak high sensitivity cardiac troponin T (hs-cTnT), peak high sensitivity cardiac troponin I (hs-cTnI), N-terminal proB-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15) and C-reactive protein (CRP), all from Roche Diagnostics. Cox regression analysis was performed for ln-transformed biomarkers in unadjusted models and models adjusting for age, hypercholesterolemia, current smoking, diabetes, hypertension, previous MI and eGFR <60 ml/min/1.73m2 in predicting a combined endpoint of all-cause mortality, future MI and hospitalization for acute heart failure. Gender differences in C-statistics were also estimated. Results: During a median follow-up of 1545 days (range 4 - 2208), the endpoint occurred in 11% of females and 13% of males (p = 0.212). Peak biomarker levels are shown in Table 1a. In the unadjusted and adjusted Cox regression analysis, increasing levels of all biomarkers were associated with a higher risk of death and cardiovascular events in women, but the interaction by gender was only significant for NT-proBNP and GDF-15 ( Table 1b ). The C-statistic for prediction of the endpoint was significantly higher for hs-cTnI and GDF-15 in women than in men ( Table 1c ). For hs-cTnT, NT-proBNP and CRP the difference in C-statistic between genders was non-significant. Conclusion: Circulating concentrations of cardiac troponins, GDF-15 and NT-proBNP seem to be associated with a higher risk of death and cardiovascular events in women compared to men.

BACKGROUND The European Society of Cardiology (ESC) rule-out algorithms use cutoffs optimized for exclusion of non-ST elevation myocardial infarction (NSTEMI). We investigated these and several novel algorithms for the rule-out of non-ST elevation acute coronary syndrome (NSTE-ACS) including less urgent coronary ischemia. METHOD A total of 1504 unselected patients with suspected NSTE-ACS were included and divided into a derivation cohort (n = 988) and validation cohort (n = 516). The primary endpoint was the diagnostic performance to rule-out NSTEMI and unstable angina pectoris during index hospitalization. The secondary endpoint was combined MI, all-cause mortality (within 30 days) and urgent (24 h) revascularization. The ESC algorithms for high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) were compared to different novel low-baseline (limit of detection), low-delta (based on the assay analytical and biological variation), and 0-1-h and 0-3-h algorithms. RESULTS The prevalence of NSTE-ACS was 24.8%, 60.0% had noncardiac chest pain, and 15.2% other diseases. The 0-1/0-3-h algorithms had superior clinical sensitivity for the primary endpoint compared to the ESC algorithm (validation cohort); hs-cTnT: 95% vs 63%, and hs-cTnI: 87% vs 64%, respectively. Regarding the secondary endpoint, the algorithms had similar clinical sensitivity (100% vs 94%-96%) but lower clinical specificity (41%-19%) compared to the ESC algorithms (77%-74%). The rule-out rates decreased by a factor of 2-4. CONCLUSION Low concentration/low-delta troponin algorithms improve the clinical sensitivity for a combined endpoint of NSTEMI and unstable angina pectoris, with the cost of a substantial reduction in total rule-out rate. There was no clear benefit compared to ESC for diagnosing high-risk events.

AIMS Troponin-based algorithms are made to identify myocardial infarctions (MIs) but adding either standard acute coronary syndrome (ACS) risk criteria or a clinical risk score may identify more patients eligible for early discharge and patients in need of urgent revascularization. METHODS AND RESULTS Post-hoc analysis of the WESTCOR study including 932 patients (mean 63 years, 61% male) with suspected NSTE-ACS. Serum samples were collected at 0, 3, and 8-12 h and high-sensitivity cTnT (Roche Diagnostics) and cTnI (Abbott Diagnostics) were analysed. The primary endpoint was MI, all-cause mortality, and unplanned revascularizations within 30 days. Secondary endpoint was non-ST-elevation myocardial infarction (NSTEMI) during index hospitalization. Two combinations were compared: troponin-based algorithms (ESC 0/3 h and the High-STEACS algorithm) and either ACS risk criteria recommended in the ESC guidelines, or one of eleven clinical risk scores, HEART, mHEART, CARE, GRACE, T-MACS, sT-MACS, TIMI, EDACS, sEDACS, Goldman, and Geleijnse-Sanchis. The prevalence of primary events was 21%. Patients ruled out for NSTEMI and regarded low risk of ACS according to ESC guidelines had 3.8-4.9% risk of an event, primarily unplanned revascularizations. Using HEART score instead of ACS risk criteria reduced the number of events to 2.2-2.7%, with maintained efficacy. The secondary endpoint was met by 13%. The troponin-based algorithms without evaluation of ACS risk missed three-index NSTEMIs with a negative predictive value (NPV) of 99.5% and 99.6%. CONCLUSION Combining ESC 0/3 h or the High-STEACS algorithm with standardized clinical risk scores instead of ACS risk criteria halved the prevalence of rule-out patients in need of revascularization, with maintained efficacy.

Background Cardiac troponin (cTn) permits early rule‐out/rule‐in of patients admitted with possible non–ST‐segment–elevation myocardial infarction. In this study, we developed an admission and a 0/1 hour rule‐out/rule‐in algorithm for a troponin assay with measurable results in >99% of healthy individuals. We then compared its diagnostic and long‐term prognostic properties with other protocols. Methods and Results Blood samples were collected at 0, 1, 3, and 8 to 12 hours from patients admitted with possible non–ST‐segment–elevation myocardial infarction. cTnT (Roche Diagnostics), cTnI(Abbott) (Abbott Diagnostics), and cTnI(sgx) (Singulex Clarity System) were measured in 971 admission and 465 1‐hour samples. An admission and a 0/1 hour rule‐out/rule‐in algorithm were developed for the cTnI(sgx) assay and its diagnostic properties were compared with cTnTESC (European Society of Cardiology), cTnI(Abbott)ESC, and 2 earlier cTnI(sgx) algorithms. The prognostic composite end point was all‐cause mortality and future nonfatal myocardial infarction during a median follow‐up of 723 days. non–ST‐segment–elevation myocardial infarction prevalence was 13%. The novel cTnI(sgx) algorithms showed similar performance regardless of time from symptom onset, and area under the curve was significantly better than comparators. The cTnI(sgx)0/1 hour algorithm classified 92% of patients to rule‐in or rule‐out compared with ≤78% of comparators. Patients allocated to rule‐out by the prior published 0/1 hour algorithms had significantly fewer long‐term events compared with the rule‐in and observation groups. The novel cTnI(sgx)0/1 hour algorithm used a higher troponin baseline concentration for rule‐out and did not allow for prognostication. Conclusions Increasingly sensitive troponin assays may improve identification of non–ST‐segment–elevation myocardial infarction but could rule‐out patients with subclinical chronic myocardial injury. Separate protocols for diagnosis and risk prediction seem appropriate.