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Background: Frailty is increasingly present in patients with acute myocardial infarction. The electronic Frailty Index (eFI) is a validated method of identifying vulnerable older patients in the community from routine primary care data. Our aim was to assess the relationship between the eFI and outcomes in older patients hospitalised with acute myocardial infarction., Study Design and Setting: Retrospective cohort study using the DataLoch Heart Disease Registry comprising consecutive patients aged 65 years or over hospitalised with a myocardial infarction between October 2013 and March 2021., Methods: Patients were classified as fit, mild, moderate, or severely frail based on their eFI score. Cox-regression analysis was used to determine the association between frailty category and all-cause mortality., Results: In 4670 patients (median age 77 years [71-84], 43% female), 1865 (40%) were classified as fit, with 1699 (36%), 798 (17%) and 308 (7%) classified as mild, moderate and severely frail, respectively. In total, 1142 patients died within 12 months of which 248 (13%) and 147 (48%) were classified as fit and severely frail, respectively. After adjustment, any degree of frailty was associated with an increased risk of all-cause death with the risk greatest in the severely frail (reference = fit, adjusted hazard ratio 2.87 [95% confidence intervals 2.24 to 3.66])., Conclusion: The eFI identified patients at high risk of death following myocardial infarction. Automatic calculation within administrative data is feasible and could provide a low-cost method of identifying vulnerable older patients on hospital presentation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society.)

Background: Myocardial infarction can be ruled out in patients with a single cardiac troponin measurement. Whether use of a uniform rule-out threshold has resulted in sex differences in care remains unclear., Objectives: The purpose of this study was to evaluate implementation of a uniform rule-out threshold in females and males with possible myocardial infarction, and to derive and validate sex-specific thresholds., Methods: The implementation of a uniform rule-out threshold (<5 ng/L) with a high-sensitivity cardiac troponin I assay was evaluated in consecutive patients presenting with possible myocardial infarction. The proportion of low-risk patients discharged from the emergency department and incidence of myocardial infarction or cardiac death at 30 days were determined. Sex-specific thresholds were derived and validated, and proportion of female and male patients were stratified as low-risk compared with uniform threshold., Results: In 16,792 patients (age 58 ± 17 years; 46% female) care was guided using a uniform threshold. This identified more female than male patients as low risk (73% vs 62%), but a similar proportion of low-risk patients were discharged from the emergency department (81% for both) with fewer than 5 (<0.1%) patients having a subsequent myocardial infarction or cardiac death at 30 days. Compared with a uniform threshold of <5 ng/L, use of sex-specific thresholds would increase the proportion of female (61.8% vs 65.9%) and reduce the proportion of male (54.8% vs 47.8%) patients identified as low risk., Conclusions: Implementation of a uniform rule-out threshold for myocardial infarction was safe and effective in both sexes. Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited., Competing Interests: Funding Support and Author Disclosures This work was supported by DataLoch, which is funded by the Data Driven Innovation program within the Edinburgh and South East Scotland City Region Deal. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge for the conduct of the High-STEACS trial. The HiSTORIC trial was funded by the British Heart Foundation (grant PG/15/51/31596) with support from British Heart Foundation Research Excellence Awards (awards RE/18/5/34216 and RE/18/6134217). The High-STEACS trial was funded by the British Heart Foundation (SP/12/10/29922). Dr Wereski is supported by Clinical Research Training Fellowship (MR/V007017/1) from the Medical Research Council. Drs Lowry and Doudesis are supported by Medical Research Council (MR/W000598/1; MR/N013166/1). Dr McDermott is supported by the British Heart Foundation Clinical Research Training Fellowship (FS/CRTF/23/24491). Dr Chapman is supported by a British Cardiovascular Interventional Society (BCIS) Advanced Coronary Intervention Fellowship. Dr Lee is supported by an ECAT/SCREDS Clinical Lectureship in Cardiology. Dr Anand is supported by a Clinical Lectureship from the Chief Scientist Office (PCL/18/05). Dr Mills is supported by the British Heart Foundation through a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966), and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation. Dr Kimenai is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/IBSRF/23/25161). The funders played no role in the design, conduct, data collection, analysis, or reporting of the trial. Dr Mills has received honoraria from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics; and is employed by the University of Edinburgh, who has received research funding from Abbott Diagnostics, Siemens Healthineers, and Roche Diagnostics unrelated to the current work. Dr Chapman is supported by a BCIS Advanced Coronary Intervention Fellowship, which is in part funded by Abbott Cardiovascular and Edwards Lifesciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Importance: Whether the diagnostic classifications proposed by the universal definition of myocardial infarction (MI) to identify type 1 MI due to atherothrombosis and type 2 MI due to myocardial oxygen supply-demand imbalance have been applied consistently in clinical practice is unknown., Objective: To evaluate the application of the universal definition of MI in consecutive patients with possible MI across 2 health care systems., Design, Setting, and Participants: This cohort study used data from 2 prospective cohorts enrolling consecutive patients with possible MI in Scotland (2013-2016) and Sweden (2011-2014) to assess accuracy of clinical diagnosis of MI recorded in hospital records for patients with an adjudicated diagnosis of type 1 or type 2 MI. Data were analyzed from August 2022 to February 2023., Main Outcomes and Measures: The main outcome was the proportion of patients with a clinical diagnosis of MI recorded in the hospital records who had type 1 or type 2 MI, adjudicated by an independent panel according to the universal definition. Characteristics and risk of subsequent MI or cardiovascular death at 1 year were compared., Results: A total of 50 356 patients were assessed. The cohort from Scotland included 28 783 (15 562 men [54%]; mean [SD] age, 60 [17] years), and the cohort from Sweden included 21 573 (11 110 men [51%]; mean [SD] age, 56 [17] years) patients. In Scotland, a clinical diagnosis of MI was recorded in 2506 of 3187 patients with an adjudicated diagnosis of type 1 MI (79%) and 122 of 716 patients with an adjudicated diagnosis of type 2 MI (17%). Similar findings were observed in Sweden, with 970 of 1111 patients with adjudicated diagnosis of type 1 MI (87%) and 57 of 251 patients with adjudicated diagnosis of type 2 MI (23%) receiving a clinical diagnosis of MI. Patients with an adjudicated diagnosis of type 1 MI without a clinical diagnosis were more likely to be women (eg, 336 women [49%] vs 909 women [36%] in Scotland; P < .001) and older (mean [SD] age, 71 [14] v 67 [14] years in Scotland, P < .001) and, when adjusting for competing risk from noncardiovascular death, were at similar or increased risk of subsequent MI or cardiovascular death compared with patients with a clinical diagnosis of MI (eg, 29% vs 18% in Scotland; P < .001)., Conclusions and Relevance: In this cohort study, the universal definition of MI was not consistently applied in clinical practice, with a minority of patients with type 2 MI identified, and type 1 MI underrecognized in women and older persons, suggesting uncertainty remains regarding the diagnostic criteria or value of the classification.

Objective: To evaluate the impact of implementing a high sensitivity assay for cardiac troponin I on long term outcomes in patients with suspected acute coronary syndrome., Design: Secondary observational analysis of a stepped wedge, cluster randomised controlled trial., Setting: 10 secondary and tertiary care centres in Scotland, UK., Participants: 48 282 consecutive patients with suspected acute coronary syndrome. Myocardial injury was defined as any high sensitivity assay result for cardiac troponin I >99th centile of 16 ng/L in women and 34 ng/L in men., Intervention: Hospital sites were randomly allocated to either early (n=5 hospitals) or late (n=5 hospitals) implementation of a high sensitivity cardiac troponin I assay with sex specific diagnostic thresholds., Main Outcome Measure: The main outcome was myocardial infarction or death at five years., Results: 10 360 patients had cardiac troponin concentrations greater than the 99th centile, of whom 1771 (17.1%) were reclassified by the high sensitivity assay. The five year incidence of subsequent myocardial infarction or death before and after implementation of the high sensitivity assay was 29.4% (5588/18 978) v 25.9% (7591/29 304), respectively, in all patients (adjusted hazard ratio 0.97, 95% confidence interval 0.93 to 1.01), and 63.0% (456/720) v 53.9% (567/1051), respectively, in those reclassified by the high sensitivity assay (0.82, 0.72 to 0.94). After implementation of the high sensitivity assay, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischaemic myocardial injury (0.83, 0.75 to 0.91) but not in those with type 1 or type 2 myocardial infarction (0.92, 0.83 to 1.01 and 0.98, 0.84 to 1.14)., Conclusions: Implementation of a high sensitivity cardiac troponin I assay in the assessment of patients with suspected acute coronary syndrome was associated with a reduced risk of subsequent myocardial infarction or death at five years in those reclassified by the high sensitivity assay. Improvements in outcome were greatest in patients with non-ischaemic myocardial injury, suggesting a broader benefit beyond the identification of myocardial infarction., Trial Registration: ClinicalTrials.gov NCT01852123., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: this study was supported by the British Heart Foundation.; KKL has received honorariums from Abbott Diagnostics; ASVS has received speaker fees from Abbott Diagnostics; and NLM has received honorariums or consultancy fees from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, LumiraDx, and Psyros Diagnostics. All other authors declare no financial relationships with any organisations that might have an interest in the submitted work in the previous three years and no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

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).)

Aims: Whether a single cardiac troponin measurement can safely rule out myocardial infarction in patients presenting within a few hours of symptom onset is uncertain. The study aim was to assess the performance of troponin in early presenters., Methods and Results: In patients with possible myocardial infarction, the diagnostic performance of a single measurement of high-sensitivity cardiac troponin I at presentation was evaluated and externally validated in those tested ≤3, 4-12, and >12 h from symptom onset. The limit-of-detection (2 ng/L), rule-out (5 ng/L), and sex-specific 99th centile (16 ng/L in women; 34 ng/L in men) thresholds were compared. In 41 103 consecutive patients [60 (17) years, 46% women], 12 595 (31%) presented within 3 h, and 3728 (9%) had myocardial infarction. In those presenting ≤3 h, a threshold of 2 ng/L had greater sensitivity and negative predictive value [99.4% (95% confidence interval 99.2%-99.5%) and 99.7% (99.6%-99.8%)] compared with 5 ng/L [96.5% (96.2%-96.8%) and 99.3% (99.1%-99.4%)]. In those presenting ≥3 h, the sensitivity and negative predictive value were similar for both thresholds. The sensitivity of the 99th centile was low in early and late presenters at 71.4% (70.6%-72.2%) and 92.5% (92.0%-93.0%), respectively. Findings were consistent in an external validation cohort of 7088 patients., Conclusion: In early presenters, a single measurement of high-sensitivity cardiac troponin I below the limit of detection may facilitate the safe rule out of myocardial infarction. The 99th centile should not be used to rule out myocardial infarction at presentation even in those presenting later following symptom onset., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Although guidelines recommend fixed cardiac troponin thresholds for the diagnosis of myocardial infarction, troponin concentrations are influenced by age, sex, comorbidities and time from symptom onset. To improve diagnosis, we developed machine learning models that integrate cardiac troponin concentrations at presentation or on serial testing with clinical features and compute the Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) score (0-100) that corresponds to an individual's probability of myocardial infarction. The models were trained on data from 10,038 patients (48% women), and their performance was externally validated using data from 10,286 patients (35% women) from seven cohorts. CoDE-ACS had excellent discrimination for myocardial infarction (area under curve, 0.953; 95% confidence interval, 0.947-0.958), performed well across subgroups and identified more patients at presentation as low probability of having myocardial infarction than fixed cardiac troponin thresholds (61 versus 27%) with a similar negative predictive value and fewer as high probability of having myocardial infarction (10 versus 16%) with a greater positive predictive value. Patients identified as having a low probability of myocardial infarction had a lower rate of cardiac death than those with intermediate or high probability 30 days (0.1 versus 0.5 and 1.8%) and 1 year (0.3 versus 2.8 and 4.2%; P < 0.001 for both) from patient presentation. CoDE-ACS used as a clinical decision support system has the potential to reduce hospital admissions and have major benefits for patients and health care providers., (© 2023. The Author(s).)

Background: The 99th centile of cardiac troponin, derived from a healthy reference population, is recommended as the diagnostic threshold for myocardial infarction, but troponin concentrations are strongly influenced by age. Our aim was to assess the diagnostic performance of cardiac troponin in older patients presenting with suspected myocardial infarction., Methods: In a secondary analysis of a multicenter trial of consecutive patients with suspected myocardial infarction, we assessed the diagnostic accuracy of high-sensitivity cardiac troponin I at presentation for the diagnosis of type 1, type 2, or type 4b myocardial infarction across 3 age groups (<50, 50-74, and ≥75 years) using guideline-recommended sex-specific and age-adjusted 99th centile thresholds., Results: In 46 435 consecutive patients aged 18 to 108 years (mean, 61±17 years), 5216 (11%) had a diagnosis of myocardial infarction. In patients <50 (n=12 379), 50 to 74 (n=22 380), and ≥75 (n=11 676) years, the sensitivity of the guideline-recommended threshold was similar at 79.2% (95% CI, 75.5-82.9), 80.6% (95% CI, 79.2-82.1), and 81.6% (95% CI, 79.8-83.2), respectively. The specificity decreased with advancing age from 98.3% (95% CI, 98.1-98.5) to 95.5% (95% CI, 95.2-95.8), and 82.6% (95% CI, 81.9-83.4). The use of age-adjusted 99th centile thresholds improved the specificity (91.3% [90.8%-91.9%] versus 82.6% [95% CI, 81.9%-83.4%]) and positive predictive value (59.3% [57.0%-61.5%] versus 51.5% [49.9%-53.3%]) for myocardial infarction in patients ≥75 years but failed to prevent the decrease in either parameter with increasing age and resulted in a marked reduction in sensitivity compared with the use of the guideline-recommended threshold (55.9% [53.6%-57.9%] versus 81.6% [79.8%-83.3%]., Conclusions: Age alters the diagnostic performance of cardiac troponin, with reduced specificity and positive predictive value in older patients when applying the guideline-recommended or age-adjusted 99th centiles. Individualized diagnostic approaches rather than the adjustment of binary thresholds are needed in an aging population.

Background: Diagnostic pathways for myocardial infarction rely on fixed troponin thresholds, which do not recognise that troponin varies by age, sex, and time within individuals. To overcome this limitation, we recently introduced a machine learning algorithm that predicts the likelihood of myocardial infarction. Our aim was to evaluate whether this algorithm performs well in routine clinical practice and predicts subsequent events., Methods: The myocardial-ischaemic-injury-index (MI 3 ) algorithm was validated in a prespecified exploratory analysis using data from a multi-centre randomised trial done in Scotland, UK that included consecutive patients with suspected acute coronary syndrome undergoing serial high-sensitivity cardiac troponin I measurement. Patients with ST-segment elevation myocardial infarction were excluded. MI 3 incorporates age, sex, and two troponin measurements to compute a value (0-100) reflecting an individual's likelihood of myocardial infarction during the index visit and estimates diagnostic performance metrics (including area under the receiver-operating-characteristic curve, and the sensitivity, specificity, negative predictive value, and positive predictive value) at the computed score. Model performance for an index diagnosis of myocardial infarction (type 1 or type 4b), and for subsequent myocardial infarction or cardiovascular death at 1 year was determined using the previously defined low-probability threshold (1·6) and high-probability MI 3 threshold (49·7). The trial is registered with ClinicalTrials.gov, NCT01852123., Findings: In total, 20 761 patients (64 years [SD 16], 9597 [46%] women) enrolled between June 10, 2013, and March 3, 2016, were included from the High-STEACS trial cohort, of whom 3272 (15·8%) had myocardial infarction. MI 3 had an area under the receiver-operating-characteristic curve of 0·949 (95% CI 0·946-0·952) identifying 12 983 (62·5%) patients as low-probability for myocardial infarction at the pre-specified threshold (MI 3 score <1·6; sensitivity 99·3% [95% CI 99·0-99·6], negative predictive value 99·8% [99·8-99·9]), and 2961 (14·3%) as high-probability at the pre-specified threshold (MI 3 score ≥49·7; specificity 95·0% [94·6-95·3], positive predictive value 70·4% [68·7-72·0]). At 1 year, subsequent myocardial infarction or cardiovascular death occurred more often in high-probability patients than low-probability patients (520 [17·6%] of 2961 vs 197 [1·5%] of 12 983], p<0·0001)., Interpretation: In consecutive patients undergoing serial cardiac troponin measurement for suspected acute coronary syndrome, the MI 3 algorithm accurately estimated the likelihood of myocardial infarction and predicted subsequent adverse cardiovascular events. By providing individual probabilities the MI 3 algorithm could improve the diagnosis and assessment of risk in patients with suspected acute coronary syndrome., Funding: Medical Research Council, British Heart Foundation, National Institute for Health Research, and NHSX., Competing Interests: Declaration of interests NLM has received honoraria or consultancy from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and LumiraDx. KKL has received honoraria from Abbott Diagnostics. ASVS's institution (the University of Edinburgh) has received speaker fees from Abbott Diagnostics. JWP has undertaken consultancy for Abbott Diagnostics. MPT has received consulting fees, honoraria, or payment from Abbott, Roche, and Siemens; funding for clinical research from Radiometer; and participated on a data safety monitoring board or an advisory board for Abbott, Radiometer, Roche, and Siemens. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Although the 99th percentile is the recommended diagnostic threshold for myocardial infarction, some guidelines also advocate the use of higher troponin thresholds to rule in myocardial infarction at presentation. It is unclear whether the magnitude or change in troponin concentration can differentiate causes of myocardial injury and infarction in practice., Methods: In a secondary analysis of a multicenter randomized controlled trial, we identified 46 092 consecutive patients presenting with suspected acute coronary syndrome without ST-segment-elevation myocardial infarction. High-sensitivity cardiac troponin I concentrations at presentation and on serial testing were compared between patients with myocardial injury and infarction. The positive predictive value and specificity were determined at the sex-specific 99th percentile upper reference limit and rule-in thresholds of 64 ng/L and 5-fold of the upper reference limit for a diagnosis of type 1 myocardial infarction., Results: Troponin was above the 99th percentile in 8188 patients (18%). The diagnosis was type 1 or type 2 myocardial infarction in 50% and 14% and acute or chronic myocardial injury in 20% and 16%, respectively. Troponin concentrations were similar at presentation in type 1 (median [25th-75th percentile] 91 [30-493] ng/L) and type 2 (50 [22-147] ng/L) myocardial infarction and in acute (50 [26-134] ng/L) and chronic (51 [31-130] ng/L) myocardial injury. The 99th percentile and rule-in thresholds of 64 ng/L and 5-fold upper reference limit gave a positive predictive value of 57% (95% CI, 56%-58%), 59% (58%-61%), and 62% (60%-64%) and a specificity of 96% (96%-96%), 96% (96%-96%), and 98% (97%-98%), respectively. The absolute, relative, and rate of change in troponin concentration were highest in patients with type 1 myocardial infarction ( P <0.001 for all). Discrimination improved when troponin concentration and change in troponin were combined compared with troponin concentration at presentation alone (area under the curve, 0.661 [0.642-0.680] versus 0.613 [0.594-0.633])., Conclusions: Although we observed important differences in the kinetics, cardiac troponin concentrations at presentation are insufficient to distinguish type 1 myocardial infarction from other causes of myocardial injury or infarction in practice and should not guide management decisions in isolation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01852123.

BACKGROUND: Collaboration for the Diagnosis and Evaluation of Acute Coronary Syndrome (CoDE-ACS) is a validated clinical decision support tool that uses machine learning with or without serial cardiac troponin measurements at a flexible time point to calculate the probability of myocardial infarction (MI). How CoDE-ACS performs at different time points for serial measurement and compares with guideline-recommended diagnostic pathways that rely on fixed thresholds and time points is uncertain. METHODS: Patients with possible MI without ST-segment-elevation were enrolled at 12 sites in 5 countries and underwent serial high-sensitivity cardiac troponin I concentration measurement at 0, 1, and 2 hours. Diagnostic performance of the CoDE-ACS model at each time point was determined for index type 1 MI and the effectiveness of previously validated low- and high-probability scores compared with guideline-recommended European Society of Cardiology (ESC) 0/1-hour, ESC 0/2-hour, and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome) pathways. RESULTS: In total, 4105 patients (mean age, 61 years [interquartile range, 50-74]; 32% women) were included, among whom 575 (14%) had type 1 MI. At presentation, CoDE-ACS identified 56% of patients as low probability, with a negative predictive value and sensitivity of 99.7% (95% CI, 99.5%-99.9%) and 99.0% (98.6%-99.2%), ruling out more patients than the ESC 0-hour and High-STEACS (25% and 35%) pathways. Incorporating a second cardiac troponin measurement, CoDE-ACS identified 65% or 68% of patients as low probability at 1 or 2 hours, for an identical negative predictive value of 99.7% (99.5%-99.9%); 19% or 18% as high probability, with a positive predictive value of 64.9% (63.5%-66.4%) and 68.8% (67.3%-70.1%); and 16% or 14% as intermediate probability. In comparison, after serial measurements, the ESC 0/1-hour, ESC 0/2-hour, and High-STEACS pathways identified 49%, 53%, and 71% of patients as low risk, with a negative predictive value of 100% (99.9%-100%), 100% (99.9%-100%), and 99.7% (99.5%-99.8%); and 20%, 19%, or 29% as high risk, with a positive predictive value of 61.5% (60.0%-63.0%), 65.8% (64.3%-67.2%), and 48.3% (46.8%-49.8%), resulting in 31%, 28%, or 0%, who require further observation in the emergency department, respectively. CONCLUSIONS: CoDE-ACS performs consistently irrespective of the timing of serial cardiac troponin measurement, identifying more patients as low probability with comparable performance to guideline-recommended pathways for MI. Whether care guided by probabilities can improve the early diagnosis of MI requires prospective evaluation. [ABSTRACT FROM AUTHOR]

Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction. The goal of this study was to derive and validate a risk stratification tool for the prediction of death or future myocardial infarction in patients with type 2 myocardial infarction. The T2-risk score was developed in a prospective multicenter cohort of consecutive patients with type 2 myocardial infarction. Cox proportional hazards models were constructed for the primary outcome of myocardial infarction or death at 1 year using variables selected a priori based on clinical importance. Discrimination was assessed by area under the receiving-operating characteristic curve (AUC). Calibration was investigated graphically. The tool was validated in a single-center cohort of consecutive patients and in a multicenter cohort study from sites across Europe. There were 1,121, 250, and 253 patients in the derivation, single-center, and multicenter validation cohorts, with the primary outcome occurring in 27% (297 of 1,121), 26% (66 of 250), and 14% (35 of 253) of patients, respectively. The T2-risk score incorporating age, ischemic heart disease, heart failure, diabetes mellitus, myocardial ischemia on electrocardiogram, heart rate, anemia, estimated glomerular filtration rate, and maximal cardiac troponin concentration had good discrimination (AUC: 0.76; 95% CI: 0.73-0.79) for the primary outcome and was well calibrated. Discrimination was similar in the consecutive patient (AUC: 0.83; 95% CI: 0.77-0.88) and multicenter (AUC: 0.74; 95% CI: 0.64-0.83) cohorts. T2-risk provided improved discrimination over the Global Registry of Acute Coronary Events 2.0 risk score in all cohorts. The T2-risk score performed well in different health care settings and could help clinicians to prognosticate, as well as target investigation and preventative therapies more effectively. (High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome [High-STEACS]; NCT01852123) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Patients with suspected acute coronary syndrome in whom myocardial infarction has been excluded are at risk of future adverse cardiac events.Objectives: This study evaluated the usefulness of high-sensitivity cardiac troponin I (hs-cTnI) to select patients for further investigation after myocardial infarction has been excluded.Methods: This is a prospective cohort study of patients presenting to the emergency department with suspected acute coronary syndrome and hs-cTnI concentrations below the sex-specific 99th percentile. Patients were recruited in a 2:1 fashion, stratified by peak hs-cTnI concentration above and below the risk stratification threshold of 5 ng/L. All patients underwent coronary computed tomography angiography (CCTA) after hospital discharge.Results: Overall, 250 patients were recruited (61.4 ± 12.2 years 31% women) in whom 62.4% (156 of 250 patients) had coronary artery disease (CAD). Patients with intermediate hs-cTnI concentrations (between 5 ng/L and the sex-specific 99th percentile) were more likely to have CAD than those with hs-cTnI concentrations <5 ng/L (71.9% [120 of 167 patients] vs 43.4% [36 of 83 patients]; odds ratio: 3.33; 95% CI: 1.92-5.78). Conversely, there was no association between anginal symptoms and CAD (63.2% [67 of 106 patients] vs 61.8% [89 of 144 patients]; odds ratio: 0.92; 95% CI: 0.48-1.76). Most patients with CAD did not have a previous diagnosis (53.2%; 83 of 156 patients) and were not on antiplatelet and statin therapies (63.5%; 99 of 156 patients) before they underwent CCTA.Conclusions: In patients who had myocardial infarction excluded, CAD was 3× more likely in those with intermediate hs-cTnI concentrations compared with low hs-cTnI concentrations. In such patients, CCTA could help to identify those with occult CAD and to target preventative treatments, thereby improving clinical outcomes. [ABSTRACT FROM AUTHOR]