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Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hs-cTn)-based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays., Methods: In 2,575 patients presenting to the emergency department with suspected MI, two ensembles of machine-learning models using single or serial concentrations of six different hs-cTn assays were derived to estimate the individual MI probability (ARTEMIS model). Discriminative performance of the models was assessed using area under the receiver operating characteristic curve (AUC) and logLoss. Model performance was validated in an external cohort with 1688 patients and tested for global generalizability in 13 international cohorts with 23,411 patients., Results: Eleven routinely available variables including age, sex, cardiovascular risk factors, electrocardiography, and hs-cTn were included in the ARTEMIS models. In the validation and generalization cohorts, excellent discriminative performance was confirmed, superior to hs-cTn only. For the serial hs-cTn measurement model, AUC ranged from 0.92 to 0.98. Good calibration was observed. Using a single hs-cTn measurement, the ARTEMIS model allowed direct rule-out of MI with very high and similar safety but up to tripled efficiency compared to the guideline-recommended strategy., Conclusion: We developed and validated diagnostic models to accurately estimate the individual probability of MI, which allow for variable hs-cTn use and flexible timing of resampling. Their digital application may provide rapid, safe and efficient personalized patient care., Trial Registration Numbers: Data of following cohorts were used for this project: BACC ( www., Clinicaltrials: gov ; NCT02355457), stenoCardia ( www., Clinicaltrials: gov ; NCT03227159), ADAPT-BSN ( www.australianclinicaltrials.gov.au ; ACTRN12611001069943), IMPACT ( www.australianclinicaltrials.gov.au , ACTRN12611000206921), ADAPT-RCT ( www.anzctr.org.au ; ANZCTR12610000766011), EDACS-RCT ( www.anzctr.org.au ; ANZCTR12613000745741); DROP-ACS ( https://www.umin.ac.jp , UMIN000030668); High-STEACS ( www., Clinicaltrials: gov ; NCT01852123), LUND ( www., Clinicaltrials: gov ; NCT05484544), RAPID-CPU ( www., Clinicaltrials: gov ; NCT03111862), ROMI ( www., Clinicaltrials: gov ; NCT01994577), SAMIE ( https://anzctr.org.au ; ACTRN12621000053820), SEIGE and SAFETY ( www., Clinicaltrials: gov ; NCT04772157), STOP-CP ( www., Clinicaltrials: gov ; NCT02984436), UTROPIA ( www., Clinicaltrials: gov ; NCT02060760)., (© 2023. The Author(s).)

Background High-sensitivity cardiac troponin (hs-cTn)-based diagnostic algorithms are recommended for the management of patients with suspected myocardial infarction (MI) without ST elevation. Although mirroring different phases of myocardial injury, falling and rising troponin patterns (FPs and RPs, respectively) are equally considered by most algorithms. We aimed to compare the performance of diagnostic protocols for RPs and FPs, separately. Methods and Results We pooled 2 prospective cohorts of patients with suspected MI and stratified patients to stable, FP, and RP during serial sampling separately for hs-cTnI and hs-cTnT and applied the European Society of Cardiology 0/1- and 0/3-hour algorithms comparing the positive predictive values to rule in MI. Overall, 3523 patients were included in the hs-cTnI study population. The positive predictive value for patients with an FP was significantly reduced compared with patients with an RP (0/1-hour: FP, 53.3% [95% CI, 45.0-61.4] versus RP, 76.9 [95% CI, 71.6-81.7]; 0/3-hour: FP, 56.9% [95% CI, 42.2-70.7] versus RP, 78.1% [95% CI, 74.0-81.8]). The proportion of patients in the observe zone was larger in the FP using 0/1-hour (31.3% versus 55.8%) and 0/3-hour (14.6% versus 38.6%) algorithms. Alternative cutoffs did not improve algorithm performances. Compared with stable hs-cTn, the risk for death or MI was highest in those with an FP (adjusted hazard ratio [HR], hs-cTnI 2.3 [95% CI, 1.7-3.2]; RP adjusted HR, hs-cTnI 1.8 [95% CI, 1.4-2.4]). Findings were similar for hs-cTnT tested in 3647 patients overall. Conclusions The positive predictive value to rule in MI by the European Society of Cardiology 0/1- and 0/3-hour algorithms is significantly lower in patients with FP than RP. These are at highest risk for incident death or MI. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT02355457, NCT03227159.

Background: Early graft failure (EGF) after coronary artery bypass grafting (CABG) occurs in up to 12% of grafts, but is often clinically unapparent. EGF may result in perioperative myocardial infarction with consequently increased mortality. The aim of the present study was to analyze the incidence of clinically apparent EGF in patients undergoing CABG and the influence on mortality., Methods: We analyzed outcomes of consecutive patients undergoing CABG from January 2015 to December 2018 with respect to postoperative emergency coronary angiography (CAG) due to suspected EGF and 30-day mortality. Patients with CAG-documented EGF were matched to patients without EGF to examine predictors of mortality., Results: The analysis included 5638 patients undergoing CABG. Eighty-six patients (1.5%) underwent emergency CAG due to suspected EGF. Clinically apparent EGF was observed in 61 of these patients (70.9%), whereas 14 (16.3%) had a culprit lesion in a native coronary artery. The majority of patients (n = 45; 52.3%) were treated with percutaneous coronary intervention and 31 (36%) underwent re-do CABG. The remaining patients were treated conservatively. The 30-day mortality rate of suspected EGF patients undergoing CAG was 22.4% (n = 19), which was higher than the mortality rate of 2.8% overall (P<.001); this remained higher after matching the EGF patients with the control group (11 [20.4%] vs 2 [4.0%]; P=.02)., Conclusion: Emergency CAG after CABG is rare and is primarily carried out in patients with EGF. The 30-day mortality rate of these patients is high, and EGF is an independent predictor of mortality. Perioperative CAG with subsequent treatment is mandatory in these patients.

Aims: Anaemia is common in patients with acute myocardial infarction (MI). We investigated the association of high-sensitivity cardiac troponin (hs-cTn) and haemoglobin (Hb) and the influence of anaemia on the performance of diagnostic protocols for suspected MI., Methods and Results: Patients with suspected MI were consecutively enrolled at a tertiary centre. Final diagnoses were independently adjudicated by two cardiologists. Performance measures of hs-cTn-based algorithms were compared for anaemic and non-anaemic patients (Hb <12 g/dL in women and <13 g/dL in men). The influence of anaemia on survival (median follow-up 1.7 years) was investigated using multivariable cox-regression analysis and the association of Hb and hs-cTn by multivariable linear regression analysis. Overall, 2223 patients were included, of whom 415 (18.7%) had anaemia. In anaemic patients, the incidence of MI was similar; however, chronic myocardial injury was significantly more prevalent (20.1% vs. 48.2%). The negative predictive value to rule-out MI was similar for both algorithms and all assays in patients with anaemia, although the positive predictive value to rule-in MI was partly reduced for the 0/3-h algorithm. Fewer anaemic patients were triaged after 1 h. Anaemia was an independent predictor of death. Adjusted for patient characteristics, Hb was significantly associated with hs-cTn. By providing a point-based tool, the Hb-associated hs-cTn concentration and thus chronic myocardial injury may be predicted., Conclusion: Anaemia partly affects the rule-in, but not the rule-out of MI in hs-cTn-based diagnostic protocols. Hs-cTn concentrations and thus chronic myocardial injury may be predicted by clinical variables and Hb., Trial Registration: clinicaltrials.gov (NCT02355457 and NCT03227159)., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

In recent decades, treatments for myocardial infarction (MI), such as stem and progenitor cell therapy, have attracted considerable scientific and clinical attention but failed to improve patient outcomes. These efforts indicate that more rigorous mechanistic and functional testing of potential MI therapies is required. Recent studies have suggested that augmenting post-MI lymphatic growth via VEGF-C administration improves cardiac function. However, the mechanisms underlying this proposed therapeutic approach remain vague and untested. To more rigorously test the role of lymphatic vessel growth after MI, we examined the post-MI cardiac function of mice in which lymphangiogenesis had been blocked genetically by pan-endothelial or lymphatic endothelial loss of the lymphangiogenic receptor VEGFR3 or global loss of the VEGF-C and VEGF-D ligands. The results obtained using all 3 genetic approaches were highly concordant and demonstrated that loss of lymphatic vessel growth did not impair left ventricular ejection fraction 2 weeks after MI in mice. We observed a trend toward excess fluid in the infarcted region of the left ventricle, but immune cell infiltration and clearance were unchanged with loss of expanded lymphatics. These studies refute the hypothesis that lymphangiogenesis contributes significantly to cardiac function after MI, and suggest that any effect of exogenous VEGF-C is likely to be mediated by nonlymphangiogenic mechanisms.

Myocardial infarction (MI) not only defines acute MI with obstructed coronary arteries (T1MI) but also myocardial necrosis caused by myocardial oxygen supply/demand mismatch as type 2 MI (T2MI); only T1MI patients benefit from an early invasive management. Myeloid-related protein(MRP)-8/14 is a biomarker described in various inflammatory diseases and in MI patients. Here we evaluate the potential of MRP-8/14 and high-sensitivity troponin I (hs-cTnI) to differentiate T2MI from T1MI. Patients with final diagnosis NSTEMI (n = 254; 33.1% female) enrolled in a prospective biomarker registry between 08/2011 and 10/2016 were analysed. Median baseline MRP-8/14 levels were higher in T2MI (n = 55; 3.37(1.88-6.48)μg/mL) than in T1MI (n = 199; 2.4 [1.4-3.79]μg/mL) (p = .013) patients, in contrast to hs-cTnI (T2MI:52[11.65-321.4]ng/L vs. T1MI:436.5 [61.25-1973.8]ng/L; p < .001). To detect the strength of this association odds ratios(OR) were calculated with MRP-8/14 yielding 2.13(1.16-3.92; p = .015) to predict T2MI and 0.47(0.26-0.87; p = .015) for T1MI. As expected, hs-cTnI yielded an OR of to predict T2MI 0.34(0.17-0.65; p = .001) and 2.98(1.53-5.81; p = .001) for T1MI. Both markers show comparable and independent results if adjust to hs-cTnI/MRP-8/14, TIMI risk score and CRP. T2MI is associated with higher MRP-8/14 and lower hs-cTnI concentrations than T1MI. Our data suggest that MRP-8/14 as a marker of inflammation might provide usable discriminatory information complementing hs-cTnI in a diagnostic procedure evaluating the type of MI directly upon hospital admission., Competing Interests: Declaration of competing interest C.W.H. received lecture or consulting honoraria from Astra Zeneca, Bayer, Boehringer Ingelheim, GSK, Daiichi-Sankyo and Pfizer-Bristol-Myers Squibb; speaker fees and honoraria from Abbott Vascular. H.N. received Speaker's fees from Abbott Vascular and Elixir Medical and institutional research grants from Abbott Vascular and Elixir Medical. C.L. received lecture or consulting honoraria from Abbott, Astra Zeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer-Bristol-Myers Squibb. T.K. received speaker fees from Abbott and ThermoFischer and consulting honoraria from Roche and BRAHMS. All other authors have nothing to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: Patients with diabetes mellitus (DM) have elevated levels of high-sensitivity cardiac troponin (hs-cTn). We investigated the diagnostic performance of the European Society of Cardiology (ESC) algorithms to rule out or rule in acute myocardial infarction (AMI) without ST-elevation in patients with DM., Research Design and Methods: We prospectively enrolled 3,681 patients with suspected AMI and stratified those by the presence of DM. The ESC 0/1-h and 0/3-h algorithms were used to calculate negative and positive predictive values (NPV, PPV). In addition, alternative cutoffs were calculated and externally validated in 2,895 patients., Results: In total, 563 patients (15.3%) had DM, and 137 (24.3%) of these had AMI. When the ESC 0/1-h algorithm was used, the NPV was comparable in patients with and without DM (absolute difference [AD] -1.50 [95% CI -5.95, 2.96]). In contrast, the ESC 0/3-h algorithm resulted in a significantly lower NPV in patients with DM (AD -2.27 [95% CI -4.47, -0.07]). The diagnostic performance for rule-in of AMI (PPV) was comparable in both groups: 0/1-h (AD 6.59 [95% CI -19.53, 6.35]) and 0/3-h (AD 1.03 [95% CI -7.63, 9.7]). Alternative cutoffs increased the PPV in both algorithms significantly, while improvements in NPV were only subtle., Conclusions: Application of the ESC 0/1-h algorithm revealed comparable safety to rule out AMI comparing patients with and without DM, while this was not observed with the ESC 0/3-h algorithm. Although alternative cutoffs might be helpful, patients with DM remain a high-risk population in whom identification of AMI is challenging and who require careful clinical evaluation., (© 2019 by the American Diabetes Association.)

: High-sensitivity troponin has proven to be a promising biomarker for the prediction of future adverse cardiovascular events. We aimed to assess the prognostic value of high-sensitivity troponin I (hs-TnI) on admission in patients with suspected acute myocardial infarction (AMI) analyzed by a novel (Singulex Clarity cTnI) and established hs-TnI assay (ARCHITECT STAT hs-TnI, Abbott). Hs-TnI was measured in a total of 2332 patients from two prospective cohort studies presenting to the emergency department with suspected AMI. The prognostic impact for overall and cardiovascular mortality of both hs-TnI assays was assessed in the total patient cohort as well as in the subgroups of patients with AMI ( n = 518) and without AMI (non-AMI) ( n = 1814). Patients presenting with highest hs-TnI levels showed higher overall and cardiovascular mortality rates compared to those with lower troponin levels, irrespective of the assay used. Both hs-TnI assays indicated association with overall mortality according to adjusted hazard ratio (HR) among the entire study population (HR for Singulex assay: 1.16 (95% CI 1.08-1.24) and HR for Abbott assay: 1.17 (95% CI 1.09-1.25)). This finding was particularly pronounced in non-AMI patients, whereas no association between hs-TnI and overall mortality was found in AMI patients for either assay. In non-AMI patients, both assays equally improved risk prediction for cardiovascular mortality beyond conventional cardiovascular risk factors. Hs-TnI is independently predictive for adverse outcomes in patients with suspected AMI, especially in the subset of patients without confirmed AMI. There was no difference between the established and the novel assay in the prediction of mortality., Competing Interests: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis ( p  < 0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity. Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.

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.)., (Copyright © 2019 Massachusetts Medical Society.)

Background Patients with chronic kidney disease ( CKD ) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction ( AMI ) without ST -segment elevation ( NSTE ). In patients with CKD , troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE - AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE - AMI . Methods and Results Two cohorts, 1494 patients from a prospective cohort study with high-sensitivity troponin I (hs- cTnI ) measurements and 7059 cases from a clinical registry with high-sensitivity troponin T (hs- cTnT ) measurements, were analyzed. The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m 2 ). The registry data set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE - AMI than non- CKD patients. The specificities of hs- cTnI and hs- cTnT to detect NSTE - AMI were reduced with CKD (0.82 versus 0.91 for hs- cTnI and 0.26 versus 0.73 for hs- cTnT ) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out AMI in 69% (hs- cTnI ) and 55% (hs- cTnT ) of CKD patients. Conclusions The diagnostic performance of high-sensitivity cardiac troponins in patients with CKD with suspected NSTE - AMI is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.

Increased adrenomedullin (ADM) levels are associated with various cardiac diseases such as myocardial infarction (MI). ADM is cleaved off from the full-length precursor protein proadrenomedullin (ProADM) during its posttranslational processing. To date, no biological effect of ProADM is reported, while ADM infusion leads to antiapoptotic effects and improved cardiac function. Using an MI mouse model, we found an induction of ProADM gene as well as protein expression during the early phase of MI. This was accompanied by apoptosis and increasing inflammation, which substantially influence the post-MI remodeling processes. Simulating ischemia in vitro, we demonstrate that ProADM expression was increased in cardiomyocytes and cardiac fibroblasts. Subsequently, we treated ischemic cardiomyocytes with either ProADM or ADM and found that both proteins increased survival. This effect was diminishable by blocking the ADM 1 receptor. To investigate whether ProADM and ADM play a role in the regulation of cardiac inflammation, we analyzed chemokine expression after treatment of cells with both proteins. While ProADM induced an expression of proinflammatory cytokines, thus promoting inflammation, ADM reduced chemokine expression. On leukocytes, both proteins repressed chemokine expression, revealing antiinflammatory effects. However, ProADM but not ADM dampened concurrent activation of leukocytes. Our data show that the full-length precursor ProADM is biologically active by reducing apoptosis to a similar extent as ADM. We further assume that ProADM induces local inflammation in affected cardiac tissue but attenuates exaggerated inflammation, whereas ADM has low impact. Our data suggest that both proteins are beneficial during MI by influencing apoptosis and inflammation., Competing Interests: The authors declare no conflict of interest.

Background: Mortality is high among patients undergoing hemodialysis for whom cardiac troponin concentration is a strong predictor of outcome. Modern troponin assays allow measurement of very low concentrations., Study Design: Using data from a randomized controlled trial, a cohort analysis to evaluate the prognostic value of very low cardiac troponin T (TnT) concentrations., Setting & Participants: 1,255 patients with end-stage renal disease and type 2 diabetes mellitus undergoing maintenance hemodialysis from the German Diabetes and Dialysis Study (4D) who had a median follow-up of 4 years., Index Test, Reference Test, and Outcome: Cardiac TnT was measured using a high-sensitivity assay (hs-TnT) and a conventional assay (conventional TnT) in a subpopulation (n=1,034) with valid measurements for both assays. Outcome measures were all-cause mortality and a composite cardiovascular end point including cardiac death, myocardial infarction, or stroke., Results: Among the 1,034 study participants, 505 died and 377 had a cardiovascular event. Both hs-TnT and conventional TnT concentrations were associated with mortality and cardiovascular events in models adjusted for cardiovascular risk factors and dialysis-associated variables. 455 (44%) patients with very low TnT concentrations (hs-TNT < 50ng/L) would have been classified as normal by the conventional TnT assay. Among these patients, hs-TnT concentrations were also associated with mortality., Limitations: The study of patients with type 2 diabetes may limit generalizability. These findings have not been externally validated., Conclusions: In patients with type 2 diabetes mellitus receiving hemodialysis, cardiac TnT is associated with long-term mortality and cardiovascular outcomes. Concentrations of TnT not measurable with acceptable precision using a conventional TnT assay were associated with a poor prognosis when measured using a high-sensitivity assay., (Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

The use of cardiac troponins (cTn) is the gold standard for diagnosing myocardial infarction. Independent of myocardial infarction (MI), however, sex, age and kidney function affect cTn levels. Here we developed a method to adjust cTnI levels for age, sex, and renal function, maintaining a unified cut-off value such as the 99 th percentile. A total of 4587 individuals enrolled in a prospective longitudinal study were used to develop a model for adjustment of cTn. cTnI levels correlated with age and estimated glomerular filtration rate (eGFR) in males/females with r age  = 0.436/0.518 and with r eGFR  = -0.142/-0.207. For adjustment, these variables served as covariates in a linear regression model with cTnI as dependent variable. This adjustment model was then applied to a real-world cohort of 1789 patients with suspected acute MI (AMI) (N = 407). Adjusting cTnI showed no relevant loss of diagnostic information, as evidenced by comparable areas under the receiver operator characteristic curves, to identify AMI in males and females for adjusted and unadjusted cTnI. In specific patients groups such as in elderly females, adjusting cTnI improved specificity for AMI compared with unadjusted cTnI. Specificity was also improved in patients with renal dysfunction by using the adjusted cTnI values. Thus, the adjustments improved the diagnostic ability of cTnI to identify AMI in elderly patients and in patients with renal dysfunction. Interpretation of cTnI values in complex emergency cases is facilitated by our method, which maintains a single diagnostic cut-off value in all patients.

Introduction: Impaired renal function, reflected by estimated glomerular filtration rate (eGFR) or cystatin C, is a strong risk predictor in the presence of acute myocardial infarction (AMI). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of acute kidney injury. uNGAL might also be a good predictor of outcome in patients with cardiovascular disease. Aim of the present study was to evaluate the prognostic value of uNGAL compared to eGFR and cystatin C in patients with suspected AMI., Methods: 1818 patients were enrolled with suspected AMI. Follow-up information on the combined endpoint of death or non-fatal myocardial infarction was obtained 6months after enrolment and was available in 1804 patients. 63 events (3.5%) were registered., Results: While cystatin C and eGFR were strong risk predictors for the primary endpoint even adjusted for several variables, uNGAL was not independently associated with outcome: When applied continuously uNGAL was associated with outcome but did not remain a statistically significant predictor after several adjustments (i.e. eGFR). By adding cystatin C or uNGAL to GRACE risk score variables, only cystatin C could improve the predictive value while uNGAL showed no improvement., Conclusion: We could show that cystatin C is an independent risk predictor in patients with suspected AMI and cystatin C can add improvement to the commonly used GRACE risk score. In contrast uNGAL is not independently associated with outcome and seems not to add further prognostic information to GRACE risk score., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Treatment of patients presenting with possible acute myocardial infarction (AMI) is based on timely diagnosis and proper risk stratification aided by biomarkers. We aimed at evaluating the predictive value of GDF-15 in patients presenting with symptoms suggestive of AMI., Methods: Consecutive patients presenting with suspected AMI were enrolled in three study centers. Cardiovascular events were assessed during a follow-up period of 6 months with a combined endpoint of death or MI., Results: From the 1818 enrolled patients (m/f = 1208/610), 413 (22.7%) had an acute MI and 63 patients reached the combined endpoint. Patients with MI and patients with adverse outcome had higher GDF-15 levels compared with non-MI patients (967.1pg/mL vs. 692.2 pg/L, p<0.001) and with event-free patients (1660 pg/mL vs. 756.6 pg/L, p<0.001). GDF-15 levels were lower in patients with SYNTAX score ≤ 22 (797.3 pg/mL vs. 947.2 pg/L, p = 0.036). Increased GDF-15 levels on admission were associated with a hazard ratio of 2.1 for death or MI (95%CI: 1.67-2.65, p<0.001) in a model adjusted for age and sex and of 1.57 (1.13-2.19, p = 0.008) adjusted for the GRACE score variables. GDF-15 showed a relevant reclassification with regards to the GRACE score with an overall net reclassification index (NRI) of 12.5% and an integrated discrimination improvement (IDI) of 14.56% (p = 0.006)., Conclusion: GDF-15 is an independent predictor of future cardiovascular events in patients presenting with suspected MI. GDF-15 levels correlate with the severity of CAD and can identify and risk-stratify patients who need coronary revascularization.

Background: The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date., Methods: The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta)., Results: The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women., Conclusions: The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction.

Aims: Serial measurements of high-sensitivity troponin are used to rule out acute myocardial infarction (AMI) with an assay specific cutoff at the 99th percentile. Here, we evaluated the performance of a single admission troponin with a lower cutoff combined with a low risk electrocardiogram (ECG) to rule out AMI., Methods: Troponin I measured with a high-sensitivity assay (hs-TnI) was determined at admission in 1040 patients presenting with suspected AMI (BACC study). To rule out AMI we calculated the negative predictive value (NPV) utilizing the optimal hs-TnI cutoff combined with a low risk ECG. The results were validated in 3566 patients with suspected AMI [2-h Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker (ADAPT) studies]. Patients were followed for 6 or 12 months., Results: 184 of all patients were diagnosed with AMI. An hs-TnI cutoff of 3 ng/L resulted in a NPV of 99.3% (CI 97.3-100.0), ruling out 35% of all non-AMI patients. Adding the information of a low risk ECG resulted in a 100% (CI 97.5-100.0) NPV (28% ruled out). The 2 validation cohorts replicated the high NPV of this approach. The follow-up mortality in the ruled out population was low (0 deaths in BACC and Stenocardia, 1 death in ADAPT)., Conclusions: A single hs-TnI measurement on admission combined with a low risk ECG appears to rule out AMI safely without need for serial troponin testing., Trial Registration: www.clinicaltrials.gov (NCT02355457)., (© 2016 American Association for Clinical Chemistry.)

High sensitive cardiac troponin assays have become the gold standard in the diagnosis of an acute type 1 myocardial infarction (MI) in the absence of ST-segment elevation. Several acute or chronic conditions that impact cardiac troponin levels in the absence of a MI might lead to a misdiagnosis of MI. For example, patients with impaired renal function as well as elderly patients often present with chronically increased cardiac troponin levels. Therefore, the diagnosis of MI type 1 based on the 99th percentile upper limit of normal threshold is more difficult in these patients. Different diagnostic approaches might help to overcome this limitation of reduced MI specificity of sensitive troponin assays. First, serial troponin measurement helps to differentiate chronic from acute troponin elevations. Second, specific diagnostic cut-offs, optimized for a particular patient group, like elderly patients, are able to regain specificity. Such an individualized use and interpretation of sensitive cardiac troponin measurements improves diagnostic accuracy and reduces the amount of misdiagnosed MI type 1.

Background: Common ECG criteria such as ST-segment changes are of limited value in patients with suspected acute myocardial infarction (AMI) and bundle branch block or wide QRS complex. A large proportion of these patients do not suffer from an AMI, whereas those with ST-elevation myocardial infarction (STEMI) equivalent AMI benefit from an aggressive treatment. Aim of the present study was to evaluate the diagnostic information of cardiac troponin I (cTnI) in hemodynamically stable patients with wide QRS complex and suspected AMI., Methods: In 417 out of 1818 patients presenting consecutively between 01/2007 and 12/2008 in a prospective multicenter observational study with suspected AMI a prolonged QRS duration was observed. Of these, n = 117 showed significant obstructive coronary artery disease (CAD) used as diagnostic outcome variable. cTnI was determined at admission., Results: Patients with significant CAD had higher cTnI levels compared to individuals without (median 250ng/L vs. 11ng/L; p<0.01). To identify patients needing a coronary intervention, cTnI yielded an area under the receiver operator characteristics curve of 0.849. Optimized cut-offs with respect to a sensitivity driven rule-out and specificity driven rule-in strategy were established (40ng/L/96ng/L). Application of the specificity optimized cut-off value led to a positive predictive value of 71% compared to 59% if using the 99th percentile cut-off. The sensitivity optimized cut-off value was associated with a negative predictive value of 93% compared to 89% provided by application of the 99th percentile threshold., Conclusion: cTnI determined in hemodynamically stable patients with suspected AMI and wide QRS complex using optimized diagnostic thresholds improves rule-in and rule-out with respect to presence of a significant obstructive CAD.

Copeptin is the C-terminal end of pre-provasopressin released equimolar to vasopressin into circulation and recently discussed as promising cardiovascular biomarker amendatory to established markers such as troponins. Vasopressin is a cytokine synthesized in the hypothalamus. A direct release of copeptin from the heart into the circulation is implied by data from a rat model showing a cardiac origin in hearts put under cardiovascular wall stress. Therefore, evaluation of a potential release of copeptin from the human heart in acute myocardial infarction (AMI) has been done.

Background: The limit of detection (LoD) is the minimal amount of a substance that can be consistently detected. In the diagnosis of acute myocardial infarction (AMI) many patients present with troponin concentrations below the LoD of contemporary sensitive cardiac troponin I (cs-cTnI) assays. These censored values below the LoD influence the diagnostic performance of these assays compared to highly sensitive cTnI (hs-cTnI) assays. Therefore we assessed the impact of a new approach for interpolation of the left-censored data of a cs-cTnI assay in the evaluation of patients with suspected AMI., Methods: Our posthoc analysis used a real world cohort of 1818 patients with suspected MI. Data on cs-cTnI was available in 1786 patients. As a comparator the hs-cTnI version of the assay was used. To reconstruct quantities below the LoD of the cs-cTnI assay, a gamma regression approach incorporating the GRACE (Global Registry of Acute Coronary Events) score variables was used., Results: Censoring of cs-cTnI data below the LoD yielded weaker diagnostic information [area under the curve (AUC), 0.781; 95% CI, 0.731-0.831] regarding AMI compared to the hs-cTnI assay (AUC, 0.949; CI, 0.936-0.961). Use of our model to estimate cs-cTnI values below the LoD showed an AUC improvement to 0.921 (CI, 0.902-0.940). The cs-cTnI LoD concentration had a negative predictive value (NPV) of 0.950. An estimated concentration that was to be undercut by 25% of patients presenting with suspected AMI was associated with an improvement of the NPV to 0.979., Conclusions: Estimation of values below the LoD of a cs-cTnI assay with this new approach improves the diagnostic performance in evaluation of patients with suspected AMI., (© 2015 American Association for Clinical Chemistry.)

Background: The introduction of modern troponin assays has facilitated diagnosis of acute myocardial infarction due to improved sensitivity with corresponding loss of specificity. Atrial fibrillation (AF) is associated with elevated levels of troponin. The aim of the present study was to evaluate the diagnostic performance of troponin I in patients with suspected acute coronary syndrome and chronic AF., Methods: Contemporary sensitive troponin I was assayed in a derivation cohort of 90 patients with suspected acute coronary syndrome and chronic AF to establish diagnostic cut-offs. These thresholds were validated in an independent cohort of 314 patients with suspected myocardial infarction and AF upon presentation. Additionally, changes in troponin I concentration within 3 hours were used., Results: In the derivation cohort, optimized thresholds with respect to a rule-out strategy with high sensitivity and a rule-in strategy with high specificity were established. In the validation cohort, application of the rule-out cut-off led to a negative predictive value of 97 %. The rule-in cut-off was associated with a positive predictive value of 88 % compared with 71 % if using the 99th percentile cut-off. In patients with troponin I levels above the specificity-optimized threshold, additional use of the 3-hour change in absolute/relative concentration resulted in a further improved positive predictive value of 96 %/100 %., Conclusions: Troponin I concentration and the 3-hour change in its concentration provide valid diagnostic information in patients with suspected myocardial infarction and chronic AF. With regard to AF-associated elevation of troponin levels, application of diagnostic cut-offs other than the 99th percentile might be beneficial.

Objective: To determine the release kinetics of different biomarkers with potential as novel early ischaemic biomarkers in patients with acute coronary syndrome (ACS); it is difficult to establish the detailed release kinetics in patients with acute myocardial infarction (AMI)., Methods: We analysed the release kinetics of soluble fms-like tyrosine kinase (sFlt-1), ischaemia modified albumin (IMA), and heart-type fatty acid binding protein (hFABP) in patients with hypertrophic obstructive cardiomyopathy who were undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n=21) undergoing TASH were included. Blood samples were collected before TASH and 15, 30, 45, 60, 75, 90, and 105 min and 2, 4, 8, and 24 h after TASH. sFlt-1 and hFABP were quantified in serum, and IMA was quantified in plasma using immunoassays., Results: sFLT-1 and hFABP increased significantly 15 min after induction of AMI vs baseline as follows: sFlt-1, 3657.5 ng/L (IQR 2302.3-4475.0) vs 76.0 ng/L (IQR 71.2-88.8) (p<0.001); hFABP, 9.0 ng/mL (IQR 7.0-15.4) vs 4.6 ng/mL (IQR 3.4-7.1) (p<0.001). sFlt-1 demonstrated a continuous decrease after the 15th min. hFABP showed a continuous increase until the 8th hour with a decline afterwards. The IMA concentrations increased significantly 30 min after induction of AMI vs baseline, with values of 26.0 U/mL (IQR 21.8-38.6) vs 15.6 U/mL (IQR 10.1-24.7) (p=0.02), and then decreased after 75 min., Conclusions: sFlt-1 and hFABP increased very early after induction of myocardial ischaemia, showing different release kinetics. The additional information provided by these findings is helpful for developing their potential combined use with cardiac troponins in patients with suspected AMI.

Aims: This systematic review aimed to investigate the diagnostic accuracy of combined cardiac troponin (cTn) and copeptin assessment in comparison to cTn alone for early rule-out of acute myocardial infarction (AMI)., Methods: Primary studies were eligible if they evaluated diagnostic accuracy for cTn with and without copeptin in patients with symptoms suggestive of AMI. AMI was defined according to the universal definition, using detection of cTn as a marker for myocardial necrosis. Eligible studies were identified by searching electronic databases (Medline, EMBASE, Science Citation Index Expanded, CINAHL, Pascal, and Cochrane) from inception to March 2013, reviewing conference proceedings and contacting field experts and the copeptin manufacturer., Results: In 15 studies totalling 8740 patients (prevalence of AMI 16%), adding copeptin improved the sensitivity of cTn assays (from 0.87 to 0.96, p=0.003) at the expense of lower specificity (from 0.84 to 0.56, p<0.001). In 12 studies providing data for 6988 patients without ST-segment elevation, the summary sensitivity and specificity estimates were 0.95 (95% CI 0.89 to 0.98) and 0.57 (95% CI 0.49 to 0.65) for the combined assessment of cTn and copeptin. When a high-sensitivity cTnT assay was used in combination with copeptin, the summary sensitivity and specificity estimates were 0.98 (95% CI 0.96 to 1.00) and 0.50 (95% CI 0.42 to 0.58)., Conclusion: Despite substantial between-study heterogeneity, this meta-analysis demonstrates that copeptin significantly improves baseline cTn sensitivity. Management studies are needed to establish the effectiveness and safety of measuring copeptin in combination with high-sensitivity cTnT for early rule-out of AMI without serial testing.

Context: Introduction of highly sensitive troponin assays into clinical practice has substantially improved the evaluation of patients with chest pain., Objective: To evaluate the diagnostic performance of a highly sensitive troponin I (hsTnI) assay compared with a contemporary troponin I (cTnI) assay and their serial changes in the diagnosis of acute myocardial infarction (AMI)., Design, Setting, and Patients: A total of 1818 patients with suspected acute coronary syndrome were consecutively enrolled at the chest pain units of the University Heart Center Hamburg, the University Medical Center Mainz, and the Federal Armed Forces Hospital Koblenz, all in Germany, from 2007 to 2008. Twelve biomarkers including hsTnI (level of detection, 3.4 pg/mL) and cTnI (level of detection, 10 pg/mL) were measured on admission and after 3 and 6 hours., Main Outcome Measures: Diagnostic performance for AMI of baseline and serial changes in hsTnI and cTnI results at 3 hours after admission to the emergency department., Results: Of the 1818 patients, 413 (22.7%) were diagnosed as having AMI. For discrimination of AMI, the area under the receiver operating characteristic (ROC) curve was 0.96 (95% CI, 0.95-0.97) for hsTnI on admission and 0.92 (95% CI, 0.90-0.94) for cTnI on admission. Both were superior to the other evaluated diagnostic biomarkers. The use of hsTnI at admission (with the diagnostic cutoff value at the 99th percentile of 30 pg/mL) had a sensitivity of 82.3% and a negative predictive value (for ruling out AMI) of 94.7%. The use of cTnI (with the diagnostic cutoff value at the 99th percentile of 32 pg/mL) at admission had a sensitivity of 79.4% and a negative predictive value of 94.0%. Using levels obtained at 3 hours after admission, the sensitivity was 98.2% and the negative predictive value was 99.4% for both hsTnI and cTnI assays. Combining the 99th percentile cutoff at admission with the serial change in troponin concentration within 3 hours, the positive predictive value (for ruling in AMI) for hsTnI increased from 75.1% at admission to 95.8% after 3 hours, and for cTnI increased from 80.9% at admission to 96.1% after 3 hours., Conclusions: Among patients with suspected acute coronary syndrome, hsTnI or cTnI determination 3 hours after admission may facilitate early rule-out of AMI. A serial change in hsTnI or cTnI levels from admission (using the 99th percentile diagnostic cutoff value) to 3 hours after admission may facilitate an early diagnosis of AMI.

Background and Purpose: Chest pain units (CPUs) were established primarily in the United States with the aim of reducing hospital admissions and costs, whilst improving quality of life and patient care. Clinical trials have shown that these units are safe and practical; however, there was a need to investigate to what extent patients are satisfied with the care in CPUs. The aim of this study is to evaluate the experiences of patients receiving CPU care and routine emergency department (ED) treatment for acute chest pain., Patients and Methods: Patients presenting with acute chest pain at the ED between May 2004 and June 2005 and at the CPU between July 2005 and May 2006 were evaluated in this retrospective analysis. Standardized data collection using all available clinical data as well as telephone follow-up was carried out. Evaluation was carried out on a school-mark basis and a quality assessment was performed., Results: Of the total population, 479 patients (323 male, 156 female) were treated in the ED, whereas 1176 (743 male, 433 female) in the CPU. In the ED, 26 patients (5.4%) were diagnosed as ST segment elevation myocardial infarction (STEMI), 39 (8.1%) as non-ST segment elevation myocardial infarction (NSTEMI) and 16 (3.3%) as unstable angina pectoris (UAP). In 398 patients (83.1%) acute coronary syndrome (ACS) could be ruled out. In the CPU, the incidence of STEMI was 74 (6.3%), of NSTEMI 141 (12%) and of UAP 153 (13%). ACS was excluded in 808 patients (68.7%). Data on satisfaction with in-hospital treatment was available in 78.5% of cases. In the CPU, 92.2% of the patients judged their treatment as excellent/good, 5.9% as appropriate and 1.9% as poor. The distribution of satisfaction in the ED was significantly lower with 78.6% excellent/good, 18.5% appropriate and 2.9% poor., Conclusion: The establishment of a CPU at the University Medical Center of Mainz demonstrated a higher level of patient satisfaction compared to the treatment of patients with acute chest pain in the general ED.

Objectives: Early identification of myocardial infarction in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation., Background: The aim of the current investigation is to test whether determination of copeptin, an indirect marker for arginin-vasopressin, adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infarction., Methods: Between January 2007 and July 2008, patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study. Copeptin, troponin T (TnT), myoglobin, and creatine kinase-myocardial band were determined at admission and after 3 and 6 h., Results: Of 1,386 (66.4% male) enrolled patients, 299 (21.6%) had the discharge diagnosis of acute myocardial infarction, 184 (13.3%) presented with unstable angina, and in 903 (65.2%) an acute coronary syndrome could be excluded. Combined measurement of copeptin and TnT on admission improved the c-statistic from 0.84 for TnT alone to 0.93 in the overall population and from 0.77 to 0.9 in patients presenting within 3 h after chest pain onset (CPO) (p < 0.001). In this group the combination of copeptin with a conventional TnT provided a negative predictive value of 92.4%., Conclusions: In triage of chest pain patients, determination of copeptin in addition to troponin improves diagnostic performance, especially early after CPO. Combined determination of troponin and copeptin provides a remarkable negative predictive value virtually independent of CPO time and therefore aids in early and safe rule-out of myocardial infarction., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction., Methods: In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission., Results: For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. With the use of the sensitive troponin I assay (cutoff value, 0.04 ng per milliliter) on admission, the clinical sensitivity was 90.7%, and the specificity was 90.2%. The diagnostic accuracy was virtually identical in baseline and serial samples, regardless of the time of chest-pain onset. In patients presenting within 3 hours after chest-pain onset, a single sensitive troponin I assay had a negative predictive value of 84.1% and a positive predictive value of 86.7%; these findings predicted a 30% rise in the troponin I level within 6 hours. A troponin I level of more than 0.04 ng per milliliter was independently associated with an increased risk of an adverse outcome at 30 days (hazard ratio, 1.96; 95% confidence interval, 1.27 to 3.05; P=0.003)., Conclusions: The use of a sensitive assay for troponin I improves early diagnosis of acute myocardial infarction and risk stratification, regardless of the time of chest-pain onset., (2009 Massachusetts Medical Society)

Objective: The objective of the study was to compute a cost-effectiveness ratio relating the economic cost of trandolapril to the number of effectiveness units (i.e. life-years) gained., Design and Setting: The trandolapril cardiac evaluation (TRACE) study was a prospective placebo-controlled clinical trial designed to determine the long term effect of the oral angiotensin-converting enzyme (ACE) inhibitor trandolapril in postinfarction patients with left ventricular dysfunction. We used the individual data of the TRACE trial to compute a cost-effectiveness ratio relating the economic cost of trandolapril to the number of life-years saved. The analysis was differential and was conducted from a payer perspective in a French setting. Costs were computed from individual data related to the use of resources during the TRACE trial. For drug treatments, we chose French public prices, and for hospitalisations, we used the mean cost as determined by the diagnosis related group (DRG) from the 1996 Programme de Médicalisation des Systémes d'Information (PMSI) database from the French Ministry of Health. Life expectancy was estimated through an accelerated failure-time model with an exponential distribution specification; we made the conservative hypothesis that the effect of trandolapril on mortality after the end of the trial was nil. We assessed the standard deviation and the 95% confidence interval (CI) of the ratio through its bootstrap distribution., Results: The incremental cost-effectiveness ratio of treating patients with trandolapril rather than with placebo was estimated as 4910 French francs (FF) per life-year saved. Discounting both costs and health effects led to ratio of FF6950 per life-year saved. The bootstrap estimate of the ratio reached FF5950 and the 95% CI was FF5650 to FF6250 per life-year saved., Conclusions: These results could be considered as highly cost effective, even though our estimation was very close to the design and the conditions of the TRACE trial. Nevertheless, we showed that this trial constitutes a favourable case for economic evaluation.

We examined 221 patients with postmyocardial infarctions 8 weeks after MI using radionuclide ventriculography (RNVA) at rest (EFR) and during supine submaximal exercise (delta EF). Mortality rates were evaluated 2 1/2 and 3 1/2 years later by interviewing patients and/or their homephysicians. Sixteen patients were dead (6.7%) 2 1/2 years after MI, 28 (12.7%) were dead after 3 1/2 years. Thirty percent of patients with a resting EF less than 30% had died 2 1/2 years after MI, and 40% were dead within 3 1/2 years. The mortality rate was significantly higher than in patients who had EF greater than or equal to 30% 8 weeks after MI. Patients with a decrease of delta EF (greater than or equal to 5%) showed a 2 1/2 year mortality of 10.8% and after 3 1/2 years of 18.5%. Mortality was significantly higher in patients with decreasing EF during exercise than in those who increased their EF during exercise. This prognostic value of EFR and delta EF was compared with other parameters (angina pectoris, ECG at rest and during exercise, heart volume, Holter ECG, floating catheter PCP [rest and exercise], coronary angiography). Radionuclide ventriculography at rest and during exercise showed a tendency to be the best determining factor for prognosis, and is therefore recommended to determine prognosis in post-MI patients.

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 highsensitivity 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 th a t 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.) [ABSTRACT FROM AUTHOR]