Derivation and Validation of Thresholds Using Synthetic Data Methods for Single-Test Screening of Emergency Department Patients with Possible Acute Myocardial Infarction Using a Point-of-Care Troponin Assay.

BACKGROUND: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal. We aimed to demonstrate a process incorporating both real and synthetic data for deriving such thresholds using a novel pre-production high-precision point-of-care assay. METHODS: cTnI concentrations were measured from thawed plasma using the Troponin I Next (TnI-Nx) assay (i-STAT; Abbott) in adults on arrival to the emergency department with symptoms suggestive of AMI. The primary outcome was an AMI or cardiac death within 30 days. We used internal-external validation with synthetic data production based on clinical and demographic data, plus the measured TnI-Nx concentration, to derive and validate decision thresholds for TnI-Nx. The target low-risk threshold was a sensitivity of 99% and a high-risk threshold specificity of >95%. RESULTS: In total, 1356 patients were included, of whom 191 (14.1%) had the primary outcome. A total of 500 synthetic data sets were constructed. The mean low-risk threshold was determined to be 5 ng/L. This categorized 38% (95% CI, 6%-68%) to low-risk with a sensitivity of 99.0% (95% CI, 98.6%-99.5%) and a negative predictive value of 99.4% (95% CI, 97.6%-99.8%). A similarly derived high-risk threshold of 25 ng/L had a specificity of 95.0% (95% CI, 94.8%-95.1%) and a positive predictive value of 74.8% (95% CI, 71.5%-78.0%). CONCLUSIONS: With the TnI-Nx assay, we successfully demonstrated an approach using synthetic data generation to derive low-risk thresholds for safe and effective screening.

Personalized diagnosis in suspected myocardial infarction.

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).

Diagnostic and prognostic performance of the ratio between high-sensitivity cardiac troponin I and troponin T in patients with chest pain.

BACKGROUND: Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context. METHODS: We calculated the hs-cTn I/T ratio in 888 chest pain patients having hs-cTnI (Abbott Laboratories) or hs-cTnT (Roche Diagnostics) concentrations above the respective 99th percentile at 2 hours from presentation. All patients were followed for one year regarding mortality. RESULTS: The median hs-cTn I/T ratio was 3.45 (25th, 75th percentiles 1.80-6.59) in type 1 MI patients (n = 408 ☯46.0%]), 1.18 (0.81-1.90) in type 2 MI patients (n = 56 ☯6.3%]) and 0.67 (0.39-1.12) in patients without MI. The hs-cTn I/T ratio provided good discrimination of type 1 MI from no type 1 MI (area under the receiver-operator characteristic curve 0.89 ☯95% confidence interval 0.86-0.91]), of type 1 MI from type 2 MI (area under the curve 0.81 ☯95% confidence interval 0.74-0.87]), and was associated with type 1 MI in adjusted analyses. The hs-cTn I/T ratio provided no consistent prognostic value. CONCLUSIONS: The hs-cTn I/T ratio appears to be useful for early diagnosis of type 1 MI and its discrimination from type 2 MI in chest pain patients presenting with elevated hs-cTn. Differences in hs-cTn I/T ratio values may reflect variations in hs-cTn release mechanisms in response to different types of myocardial injury.

Reducing Patient Risk and Enhancing Care Through the Development and Implementation of a New Chest Pain Pathway, Expedited by and for the COVID-19 Era.

The COVID-19 pandemic raised major concerns relating to hospital capacity and cross-infection patients and staff in the Emergency Department (ED) of a metropolitan hospital servicing a population of ~500,000. We determined to reduce length of stay and admissions in patients presenting with symptoms of possible myocardial infarction; the most common presentation group. After establishing stakeholder consensus, the existing accelerated diagnostic pathway (ADP) based on the ED Assessment of Chest-pain Score (EDACS), electrocardiogram, and troponin measurements with a high-sensitivity assay (hs-cTn) on presentation and two hours later (EDACS-ADP) was modified to stream patients following an initial troponin measure as follows: (i) to a very-low risk group who could be discharged home without follow-up or further testing, and (ii) to a low-risk group who could be discharged with next-day follow-up community troponin testing. Simulations were run in an extensive research database to determine appropriate hs-cTnI and EDACS thresholds for risk classification. This COVID-ADP was developed in ~2-weeks and was implemented in the ED within a further 3-weeks. A comparison of all chest pain presentations for the 3 months prior to implementation of the COVID-ADP to 3 months following implementation showed that there was a 64.7% increase in patients having only one troponin test in the ED, a 30-minute reduction of mean length of stay of people discharged home from the ED, and a 24.3% reduction in hospital admissions of patients ultimately diagnosed with non-cardiac chest pain.

Early kinetic profiles of troponin I and T measured by high-sensitivity assays in patients with myocardial infarction.

The early concentration kinetic profiles of cardiac troponin in patients with non-ST-elevated myocardial infarction (NSTEMI) measured by high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have not been described. In intermediate-to-high-risk of NSTEMI patients we measured serial cTn concentrations on ED arrival, at 1, 2, 3, 6-12, 24 and 48-hours with hs-cTnI and hs-cTnT assays. Log-normal curves were fitted to concentrations from time from symptom onset, and the time to rule-out decision thresholds estimated (hs-cTnI: 2 ng/L and 5 ng/L; hs-cTnT: 5 ng/L). Among 164 patients there were 58 NSTEMI. The hs-cTnI to hs-cTnT ratio increased linearly over the first 6-12 h following symptom onset. The estimated times from symptom onset to the 2 ng/L and 5 ng/L thresholds for hs-cTnI were 1.8 (0.1-3.1) and 1.9 (1.1-3.5) hours, and to the 5 ng/L threshold for hs-cTnT 1.9 (1.1-3.8) hours. The estimated time to exceed 5 ng/L was ≥3 hours in 32.6% (95%CI: 20.0% to 48.1%) cases for hs-cTnI and 33.3% (19.6% to 50.0%) for hs-cTnT. cTnI concentrations increased at a much more rapid rate than cTnT concentrations in patients with NSTEMI. Concentrations of a high proportion of patients took longer than 3 hours from symptom onset to exceed the 5 ng/L rule-out decision threshold.

Validity of a Novel Point-of-Care Troponin Assay for Single-Test Rule-Out of Acute Myocardial Infarction.

Importance: Emergency department (ED) investigations of patients with suspected acute myocardial infarction (AMI) are time consuming, partly because of the turnaround time of laboratory tests. Current point-of-care troponin assays shorten test turnaround times but lack precision at lower concentrations. Development of point-of-care troponin assays with greater analytical precision could reduce the decision-making time in EDs for ruling out AMI. Objective: To determine the clinical accuracy for AMI of a single troponin concentration measured on arrival to ED with a new-generation, higher precision point-of-care assay with a 15-minute turnaround time. Design, Setting, and Participants: This observational study occurred at a single urban regional ED. Adults presenting acutely from the community to the ED with symptoms suggestive of AMI were included. Troponin concentrations were measured on ED arrival with both a novel point-of-care assay (i-STAT TnI-Nx; Abbott Point of Care) and a high-sensitivity troponin I assay (Architect hs-cTnI; Abbott Diagnostics). Main Outcomes and Measures: The primary outcome was type 1 AMI during index presentation. We compared the discrimination ability of the TnI-Nx assay with the hs-cTnI assay using the area under receiver operator characteristic curve (AUC) and sensitivity, negative predictive value, and the proportion of negative test results at thresholds with 100% sensitivity. Results: Of 354 patients (255 [72.0%] men; mean [SD] age, 62 [12] years), 57 (16.1%) experienced an AMI. Eighty-five patients (24.0%) presented to the ED less than 3 hours after symptom onset. No difference was found between the AUC of the TnI-Nx assay (0.975 [95% CI, 0.958-0.993]) and the hs-cTnI assay (0.970 [95% CI, 0.949 to 0.990]; P = .46). A TnI-Nx assay result of less than 11 ng/L identified 201 patients (56.7%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 98.2%-100%). In comparison, an hs-cTnI assay result of less than 3 ng/L identified 154 patients (43.5%) as low risk, with a sensitivity of 100% (95% CI, 93.7%-100%) and a negative predictive value of 100% (95% CI, 97.6%-100%). Conclusions and Relevance: A novel point-of-care troponin assay that can produce a result 15 minutes after blood sampling had comparable discrimination ability to an hs-cTnI assay for ruling out AMI after a single blood test. Use in the ED may facilitate earlier decision making and could expedite the safe discharge of a large proportion of low-risk patients.

Detectable High-Sensitivity Cardiac Troponin within the Population Reference Interval Conveys High 5-Year Cardiovascular Risk: An Observational Study.

BACKGROUND: Increased cardiac troponin I or T detected by high-sensitivity assays (hs-cTnI or hs-cTnT) confers an increased risk of adverse prognosis. We determined whether patients presenting with putatively normal, detectable cTn concentrations [> limit of detection and < upper reference limit (URL)] have increased risk of major adverse cardiovascular events (MACE) or all-cause mortality. METHODS: A prospective 5-year follow-up of patients recruited in the emergency department with possible acute coronary syndrome (ACS) and cTn concentrations measured with hs-cTnI (Abbott) and hs-cTnT (Roche) assays. Cox regression models were generated with adjustment for covariates in those without MACE on presentation. Hazard ratios (HRs) for hs-cTn were calculated relative to the HRs at the median concentration. RESULTS: Of 1113 patients, 836 were without presentation MACE. Of these, 138 incurred a MACE and 169 died during a median 5.8-year follow-up. HRs for MACE at the URLs were 2.3 (95% CI, 1.7-3.2) for hs-cTnI and 1.8 (95% CI, 1.3-2.4) for hs-cTnT. Corresponding HRs for mortality were 1.7 (95% CI, 1.2-2.2) for hs-cTnI and 2.3 (95 % CI, 1.7-3.1) for hs-cTnT. The HR for MACE increased with increasing hs-cTn concentration similarly for both assays, but the HR for mortality increased at approximately twice the rate for hs-cTnT than hs-cTnI. Patients with hs-cTnI ≥10 ng/L or hs-cTnT ≥16 ng/L had the same percentage of MACE at 5-year follow-up (33%) as patients with presentation MACE. CONCLUSIONS: Many patients with ACS ruled out and putatively normal but detectable hs-cTnI concentrations are at similar long-term risk as those with MACE. hs-cTnT concentrations are more strongly associated with 5-year mortality than hs-cTnI.

ICare-ACS (Improving Care Processes for Patients With Suspected Acute Coronary Syndrome): A Study of Cross-System Implementation of a National Clinical Pathway.

BACKGROUND: Efforts to safely reduce length of stay for emergency department patients with symptoms suggestive of acute coronary syndrome (ACS) have had mixed success. Few system-wide efforts affecting multiple hospital emergency departments have ever been evaluated. We evaluated the effectiveness of a nationwide implementation of clinical pathways for potential ACS in disparate hospitals. METHODS: This was a multicenter pragmatic stepped-wedge before-and-after trial in 7 New Zealand acute care hospitals with 31 332 patients investigated for suspected ACS with serial troponin measurements. The implementation was a clinical pathway for the assessment of patients with suspected ACS that included a clinical pathway document in paper or electronic format, structured risk stratification, specified time points for electrocardiographic and serial troponin testing within 3 hours of arrival, and directions for combining risk stratification and electrocardiographic and troponin testing in an accelerated diagnostic protocol. Implementation was monitored for >4 months and compared with usual care over the preceding 6 months. The main outcome measure was the odds of discharge within 6 hours of presentation RESULTS: There were 11 529 participants in the preimplementation phase (range, 284-3465) and 19 803 in the postimplementation phase (range, 395-5039). Overall, the mean 6-hour discharge rate increased from 8.3% (range, 2.7%-37.7%) to 18.4% (6.8%-43.8%). The odds of being discharged within 6 hours increased after clinical pathway implementation. The odds ratio was 2.4 (95% confidence interval, 2.3-2.6). In patients without ACS, the median length of hospital stays decreased by 2.9 hours (95% confidence interval, 2.4-3.4). For patients discharged within 6 hours, there was no change in 30-day major adverse cardiac event rates (0.52% versus 0.44%; P=0.96). In these patients, no adverse event occurred when clinical pathways were correctly followed. CONCLUSIONS: Implementation of clinical pathways for suspected ACS reduced the length of stay and increased the proportions of patients safely discharged within 6 hours. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/ (Australian and New Zealand Clinical Trials Registry). Unique identifier: ACTRN12617000381381.

Heart Fatty Acid Binding Protein and cardiac troponin: development of an optimal rule-out strategy for acute myocardial infarction.

BACKGROUND: Improved ability to rapidly rule-out Acute Myocardial Infarction (AMI) in patients presenting with chest pain will promote decongestion of the Emergency Department (ED) and reduce unnecessary hospital admissions. We assessed a new commercial Heart Fatty Acid Binding Protein (H-FABP) assay for additional diagnostic value when combined with cardiac troponin (using a high sensitivity assay). METHODS: H-FABP and high-sensitivity troponins I (hs-cTnI) and T (hs-cTnT) were measured in samples taken on-presentation from patients, attending the ED, with symptoms triggering investigation for possible acute coronary syndrome. The optimal combination of H-FABP with each hs-cTn was defined as that which maximized the proportion of patients with a negative test (low-risk) whilst maintaining at least 99 % sensitivity for AMI. A negative test comprised both H-FABP and hs-cTn below the chosen threshold in the absence of ischemic changes on the ECG. RESULTS: One thousand seventy-nine patients were recruited including 248 with AMI. H-FABP < 4.3 ng/mL plus hs-cTnI < 10.0 ng/L together with a negative ECG maintained >99 % sensitivity for AMI whilst classifying 40.9 % of patients as low-risk. The combination of H-FABP < 3.9 ng/mL and hs-cTnT < 7.6 ng/L with a negative ECG maintained the same sensitivity whilst classifying 32.1 % of patients as low risk. CONCLUSIONS: In patients requiring rule-out of AMI, the addition of H-FABP to hs-cTn at presentation (in the absence of new ischaemic ECG findings) may accelerate clinical diagnostic decision making by identifying up to 40 % of such patients as low-risk for AMI on the basis of blood tests performed on presentation. If implemented this has the potential to significantly accelerate triaging of patients for early discharge from the ED.

Effectiveness of EDACS Versus ADAPT Accelerated Diagnostic Pathways for Chest Pain: A Pragmatic Randomized Controlled Trial Embedded Within Practice.

STUDY OBJECTIVE: A 2-hour accelerated diagnostic pathway based on the Thrombolysis in Myocardial Infarction score, ECG, and troponin measures (ADAPT-ADP) increased early discharge of patients with suspected acute myocardial infarction presenting to the emergency department compared with standard care (from 11% to 19.3%). Observational studies suggest that an accelerated diagnostic pathway using the Emergency Department Assessment of Chest Pain Score (EDACS-ADP) may further increase this proportion. This trial tests for the existence and size of any beneficial effect of using the EDACS-ADP in routine clinical care. METHODS: This was a pragmatic randomized controlled trial of adults with suspected acute myocardial infarction, comparing the ADAPT-ADP and the EDACS-ADP. The primary outcome was the proportion of patients discharged to outpatient care within 6 hours of attendance, without subsequent major adverse cardiac event within 30 days. RESULTS: Five hundred fifty-eight patients were recruited, 279 in each arm. Sixty-six patients (11.8%) had a major adverse cardiac event within 30 days (ADAPT-ADP 29; EDACS-ADP 37); 11.1% more patients (95% confidence interval 2.8% to 19.4%) were identified as low risk in EDACS-ADP (41.6%) than in ADAPT-ADP (30.5%). No low-risk patients had a major adverse cardiac event within 30 days (0.0% [0.0% to 1.9%]). There was no difference in the primary outcome of proportion discharged within 6 hours (EDACS-ADP 32.3%; ADAPT-ADP 34.4%; difference -2.1% [-10.3% to 6.0%], P=.65). CONCLUSION: There was no difference in the proportion of patients discharged early despite more patients being classified as low risk by the EDACS-ADP than the ADAPT-ADP. Both accelerated diagnostic pathways are effective strategies for chest pain assessment and resulted in an increased rate of early discharges compared with previously reported rates.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis.

BACKGROUND: Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS: MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS: From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION: High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Cardiac biomarkers in acute myocardial infarction.

Each year, a large number of patients are seen in the Emergency Department with presentations necessitating investigation for possible acute myocardial infarction. Patients can be stratified by symptoms, risk factors and electrocardiogram results but cardiac biomarkers also have a prime role both diagnostically and prognostically. This review summarizes both the history of cardiac biomarkers as well as currently available (established and novel) assays. Cardiac troponin, our current "gold standard" biomarker criterion for the diagnosis of myocardial infarction has high sensitivity and specificity for this diagnosis and therapies instituted in patients with elevated troponin have been shown to influence outcomes. Other markers of myocardial necrosis, inflammation and neurohormonal activity have also been shown to have either diagnostic or prognostic utility, but none have been shown to be superior to troponin. The measurement of multiple biomarkers and the use of point of care markers may accelerate current diagnostic protocols for the assessment of such patients.

A 2-hour thrombolysis in myocardial infarction score outperforms other risk stratification tools in patients presenting with possible acute coronary syndromes: comparison of chest pain risk stratification tools.

BACKGROUND: Accelerated diagnostic pathways for risk stratification of patients presenting to the emergency department with potential acute coronary syndromes may identify very-low-risk patients safe for early discharge to outpatient care. METHODS: Patients presenting with potential acute coronary syndrome to the emergency department were prospectively enrolled between November 2007 and April 2010. Patient characteristics in conjunction with 0- and 2-hour biomarkers and electrocardiograms were analyzed according to a 2-hour thrombolysis in myocardial infarction (TIMI) score and 9 other accelerated diagnostic pathways. The primary outcome was acute coronary syndrome by 30 days. RESULTS: Of 1,000 patients, 362 (36.2%) had a primary outcome. A pathway comprising electrocardiogram, prior ischemic heart disease, 0/2-hour troponin/creatine kinase MB fraction/myoglobin identified the highest proportion (25.0%) as low risk, with 96.1% sensitivity for the primary outcome. A pathway comprising electrocardiogram, history of ischemic heart disease, typical vs atypical symptoms, 0/2-hour troponin was the safest, with 99.7% sensitivity for the primary outcome, but only 9.0% were low risk. A pathway comprising the TIMI score with 0/2-hour troponin and electrocardiograms identified 15.5% as low risk, with a sensitivity of 99.2% for the primary outcome. This compares with standard care in which none were for outpatient care but, 3.3% had a primary outcome postdischarge within 30 days. CONCLUSION: In this relatively high-risk population, a 2-hour TIMI score safely identified significant numbers of patients suitable for early discharge to outpatient care.

A new improved accelerated diagnostic protocol safely identifies low-risk patients with chest pain in the emergency department.

OBJECTIVES: To assess whether the accelerated diagnostic protocol (ADP) studied in the Asia Pacific Evaluation of Chest Pain Trial (ASPECT) could be optimized to effectively risk stratify patients with symptoms suggestive of acute coronary syndrome (ACS) and allow early discharge of very-low-risk patients. METHODS: Patients presenting to the emergency department (ED) with chest pain were prospectively enrolled between November 2007 and April 2010. Blood samples were analyzed at 0 and 2 hours postpresentation with a point-of-care multimarker panel (POC-MMP; troponin I [TnI], creatine kinase myocardial band [CKMB] isoenzyme fraction, and myoglobin) and a high-sensitivity cardiac troponin T assay (hsTnT). Patients received standard care. The original ADP (Thrombolysis in Myocardial Infarction [TIMI] risk score = 0, no ischemic electrocardiogram [ECG] changes, and the multimarker panel negative) was compared with an ADP using the point of care TnI only, hsTnT only, or TIMI risk score = 0 to 1. Primary outcome was ACS within 30 days. RESULTS: Of the 1,000 patients recruited, 362 (36.2%) had ACS. There were 12.3% identified as low risk by the original ADP with a sensitivity for ACS of 99.2% (95% confidence interval [CI] = 97.5% to 99.8%). The ADP with the point of care TnI only or hsTnT had the same sensitivity, but identified more patients for discharge (15.0% vs. 12.3%). Including patients with a TIMI risk score of 1 identified more patients as low risk (19.7%), but with a lower sensitivity (97.0% vs. 99.2%). CONCLUSIONS: An ADP consisting of a TIMI risk score of 0, no new ECG changes, and negative troponin at 0 and 2 hours postpresentation safely identifies patients at low risk of ACS, in whom discharge without further evaluation can be considered.

ST2 has diagnostic and prognostic utility for all-cause mortality and heart failure in patients presenting to the emergency department with chest pain.

BACKGROUND: Elevated ST2 predicts future heart failure and/or death in patients with pulmonary diseases, heart failure, acute dyspnea, and acute coronary syndromes. This study assesses both diagnostic and prognostic utility of ST2 in patients with chest pain. METHODS AND RESULTS: From November 2007 to April 2010, 995 patients attending the Emergency Department with chest pain were prospectively recruited. Troponin I (TnI), B-type natriuretic peptide (BNP), creatine kinase-myocardial band (CKMB), myoglobin, and ST2 were measured at 0 and 2 hours. The diagnostic utility of ST2 for heart failure and prognostic utility for primary outcome of death and/or heart failure by 18 months was assessed. Elevated ST2 had sensitivity 73.5% (55.8%-86.4%) and specificity 79.6% (79.0%-80.1%) for acute heart failure (n = 34) [compared with BNP sensitivity 88.2% (73.6%-95.3%), specificity 66.2% (65.7%-66.4%)]. Elevated ST2 conveyed risk of 18-month primary outcome (n = 110), with an adjusted hazard ratio (HR) of 1.9 (1.2-3.2), compared with BNP HR 2.8 (1.4-5.7), myoglobin HR 1.9 (1.1-3.3), TnI HR 1.7 (1.0-2.7), and CKMB HR 0.9 (0.5-1.7). When ST2 and BNP were both elevated, risk was greater than if either marker was elevated in isolation (P < .001). CONCLUSIONS: ST2 was more specific for acute heart failure than BNP. ST2 is independently predictive of future death and/or heart failure and has incremental utility in combination with BNP.

Diagnostic and prognostic utility of early measurement with high-sensitivity troponin T assay in patients presenting with chest pain.

BACKGROUND: High-sensitivity troponin assays are now available for clinical use. We investigated whether early measurement with such an assay is superior to a conventional assay in the evaluation of acute coronary syndromes. METHODS: Patients presenting to an emergency department with chest pain who did not have ST-segment elevation were prospectively recruited from November 2007 to December 2010. Patients underwent serial testing with a conventional cardiac troponin I assay. Samples were also obtained at presentation and two hours later for measurement of troponin T levels using a high-sensitivity assay. The primary outcome was diagnosis of myocardial infarction on admission; secondary outcomes were death, myocardial infarction and heart failure at one year. RESULTS: Of the 939 patients enrolled in the study, 205 (21.8%) had myocardial infarction. By two hours after presentation, the high-sensitivity troponin T assay at the cut-off point of the 99th percentile of the general population (14 ng/L) had a sensitivity of 92.2% (95% confidence interval [CI] 88.1%-95.0%) and a specificity of 79.7% (95% CI 78.6%-80.5%) for the diagnosis of non-ST-segment myocardial infarction. The sensitivity of the assay at presentation was 100% among patients who presented four to six hours after symptom onset. By one year, the high-sensitivity troponin T assay was found to be superior than the conventional assay in predicting death (hazard ratio [HR] 5.4, 95% CI 2.7-10.7) and heart failure (HR 27.8, 95% CI 6.6-116.4), whereas the conventional assay was superior in predicting nonfatal myocardial infarction (HR 4.0, 95% CI 2.4-6.7). INTERPRETATION: The high-sensitivity troponin T assay at the cut-off point of the 99th percentile was highly sensitive for the diagnosis of myocardial infarction by two hours after presentation and had prognostic utility beyond that of the conventional assay. To rule out myocardial infarction, the optimal time to test a second sample using the high-sensitivity troponin T level may be four to six hours after symptom onset, but this finding needs verification in future studies before it can become routine practice.

Early dynamic change in high-sensitivity cardiac troponin T in the investigation of acute myocardial infarction.

BACKGROUND: The definition of acute myocardial infarction (AMI) requires a rise and/or fall in troponin with 1 or more results ≥99th percentile of the reference range. How much troponin must change has not been specified. We ascertained whether dynamic changes (δ) in high-sensitivity troponin T (hs-TnT) improved diagnostic and prognostic test performance in the emergency department. METHODS: We recruited 939 patients with symptoms suggestive of acute coronary syndrome (without ST elevation). hs-cTnT was measured at 0 h and 2 h after presentation. End-points were admission diagnosis of AMI and 1-year adverse events (composite of death, AMI, revascularization). RESULTS: Diagnostic specificity of 0-2-h hs-cTnT for AMI (incurred by 200 patients) improved from 79.8% (78.8%-80.5%) by using the 99th percentile alone to 94.2% (92.9%-95.4%) when we also included a δ ≥20%, but diagnostic sensitivity decreased from 94.5% (90.7%-96.9%) to 49.5% (44.6%-53.9%). With the inclusion of those patients with a δ ≥20% when 0-2-h hs-cTnT was <99th percentile, in addition to any with concentrations ≥99th percentile, diagnostic sensitivity increased to 97.5% (94.4%-98.9%). hs-cTnT ≥99th percentile predicted adverse events (incurred by 111 patients), adjusted hazard ratio 1.9 (1.2-2.8), whereas a δ ≥20% did not, hazard ratio 1.1 (0.7-1.7). CONCLUSIONS: Diagnostic specificity of hs-cTnT improved with the use of a δ ≥20% in those patients with concentrations ≥99th percentile, but at a cost of a large reduction in sensitivity. Diagnostic sensitivity improved with the use of a δ ≥20% in patients with 0-2-h concentrations <99th percentile. Both approaches may be required for optimum rule-in and rule-out strategies, respectively. The δ criteria seem to be less useful for medium-term risk stratification.

Comparison of high sensitivity and contemporary troponin assays for the early detection of acute myocardial infarction in the emergency department.

BACKGROUND: Current guidelines define acute myocardial infarction (AMI) by the rise and/or fall of cardiac troponin with ≥1 value above the 99th percentile. Past troponin assays have been unreliable at the lower end of the range. Highly sensitive assays have therefore been developed to increase the clinical sensitivity for detection of myocardial injury. METHODS: Three hundred and thirty-two patients with chest pain suggestive of AMI were prospectively recruited between November 2006 and April 2007. Serial blood samples were analysed to compare Roche Elecsys high sensitivity troponin T (hsTnT), Abbott Architect troponin I 3rd generation (TnI 3) and Roche Elecsys troponin T (TnT) for the diagnosis of AMI. RESULTS: One hundred and ten (33.1%) patients were diagnosed with AMI. Test performance for the diagnosis of AMI, as quantified by receiver operating characteristic area under the curve (95% confidence intervals) for baseline/follow-up troponins were as follows: hsTnT 0.90 (0.87-0.94)/0.94 (0.91-0.97), TnI 3 0.88 (0.84-0.92)/0.93 (0.90-0.96) and TnT 0.80 (0.74-0.85)/0.89 (0.85-0.94). hsTnT was superior to TnT (P < 0.001/0.013 at baseline/follow-up) but equivalent to TnI 3. For patients with a final diagnosis of AMI, baseline troponins were raised in more patients for hsTnT (83.6%) than TnI 3 (74.5%) and TnT (62.7%). A delta troponin of ≥20% increased the specificity of hsTnT from 80.6% to 93.7% but reduced sensitivity from 90.9% to 71.8%. CONCLUSION: hsTnT was superior to TnT but equivalent to TnI 3 for the diagnosis of AMI. Serial troponin measurement increased test performance. hsTnT was the most likely to be raised at baseline in those with AMI. A delta troponin increases specificity but reduces sensitivity.

High sensitivity troponin outperforms contemporary assays in predicting major adverse cardiac events up to two years in patients with chest pain.

BACKGROUND: Previous studies have shown a risk of subsequent major adverse cardiovascular events (MACEs) in patients with suspected acute coronary syndromes (ACSs) and elevated cardiac troponin. The aim of this study was to compare prognostic utility of high-sensitivity troponin with contemporary troponin assays in such patients. METHODS: In total, 332 patients with suspected ACS were investigated between November 2006 and April 2007; all were followed for two years. Blood samples were analysed to compare Roche Elecsys high-sensitivity troponin T (hsTnT), Abbott Architect troponin I 3rd generation (TnI 3) and Roche Elecsys troponin T (TnT), for the prediction of MACE (composite of cardiovascular death, non-fatal myocardial infarction and revascularization). RESULTS: Sixty-eight patients (20.5%) experienced MACE between discharge and two years. Receiver operating characteristic (ROC) curve derived area under the ROC curve (95% confidence intervals) for baseline hsTnT were 0.70 (0.63-0.76), TnI 3 0.66 (0.59-0.73) and TnT 0.61 (0.53-0.69). hsTnT (P = 0.001) was superior to TnT and TnI 3 trended (P = 0.094) to superiority but were equivalent to each other. hsTnT best stratified patients with cumulative event rates for two-year MACE of 35.6% for levels ≥99th percentile, 17.9% for levels between the limit of detection (LOD) and 99th percentile and 5.4% for levels

The performance of high sensitivity troponin for the diagnosis of acute myocardial infarction is underestimated.

BACKGROUND: Many papers evaluating high sensitivity troponin assays make the diagnosis of myocardial infarction based on conventional troponin assays in clinical use at the time of recruitment. Such analyses often do not show superiority of high sensitivity assays compared with contemporary assays meeting precision guidelines. METHODS: Three hundred and twenty-two patients presenting to the emergency department between November 2006 and April 2007 for evaluation for acute coronary syndrome had serial (0 h and >6 h) bloods taken to compare troponin assays (Roche hsTnT, Abbott TnI, Roche TnT and Vitros TnI). The diagnosis of myocardial infarction was made using each troponin assay separately with which that same assay was analysed for diagnostic performance. RESULTS: The rate of myocardial infarction would be 38.9% using serial hsTnT, 31.3% using serial Abbott TnI, 27.1% using serial TnT and 26.4% using serial Vitros TnI. The baseline sensitivities (0 h) are 89.9% (85.2-93.3) for hsTnT, 77.9% (71.0-87.5) for Abbott TnI, 73.0% (65.6-78.7) for TnT and 86.8% (74.6-94.4%) for Vitros TnI. The specificities (peak 0 h and >6 h samples) are 93.1% (91.2-93.1) for hsTnT, 88.3% (86.5-88.3) for Abbott TnI, 92.2% (90.5-92.2) for TnT and 90.6% (70.1-90.6) for Vitros TnI. CONCLUSIONS: hsTnT has superior sensitivity for myocardial infarction than even assays at or near guideline precision requirements (Abbott and Vitros TnI). The specificity of hsTnT assay is not as poor as previous analyses suggest.