Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2†h.

BACKGROUND AND AIMS: Strategies to assess patients with suspected acute myocardial infarction (AMI) using a point-of-care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay may expedite emergency care. A 2-h POC hs-cTnI strategy for emergency patients with suspected AMI was derived and validated. METHODS: In two international, multi-centre, prospective, observational studies of adult emergency patients (1486 derivation cohort and 1796 validation cohort) with suspected AMI, hs-cTnI (Siemens Atellica® VTLi) was measured at admission and 2 h later. Adjudicated final diagnoses utilized the hs-cTn assay in clinical use. A risk stratification algorithm was derived and validated. The primary diagnostic outcome was index AMI (Types 1 and 2). The primary safety outcome was 30-day major adverse cardiac events incorporating AMI and cardiac death. RESULTS: Overall, 81 (5.5%) and 88 (4.9%) patients in the derivation and validation cohorts, respectively, had AMI. The 2-h algorithm defined 66.1% as low risk with a sensitivity of 98.8% [95% confidence interval (CI) 89.3%-99.9%] and a negative predictive value of 99.9 (95% CI 99.2%-100%) for index AMI in the derivation cohort. In the validation cohort, 53.3% were low risk with a sensitivity of 98.9% (95% CI 92.4%-99.8%) and a negative predictive value of 99.9% (95% CI 99.3%-100%) for index AMI. The high-risk metrics identified 5.4% of patients with a specificity of 98.5% (95% CI 96.6%-99.4%) and a positive predictive value of 74.5% (95% CI 62.7%-83.6%) for index AMI. CONCLUSIONS: A 2-h algorithm using a POC hs-cTnI concentration enables safe and efficient risk assessment of patients with suspected AMI. The short turnaround time of POC testing may support significant efficiencies in the management of the large proportion of emergency patients with suspected AMI.

Determination of Clinically Acceptable Analytical Variation of Cardiac Troponin at Decision Thresholds.

BACKGROUND: Clinical decision-making for risk stratification for possible myocardial infarction (MI) uses high-sensitivity cardiac troponin (hs-cTn) thresholds that range from the limit of detection to several-fold higher than the upper reference limit (URL). To establish a minimum analytical variation standard, we can quantify the effect of variation on the population clinical measures of safety (sensitivity) and effectiveness [proportion below threshold, or positive predictive value (PPV)]. METHODS: From large datasets of patients investigated for possible MI with the Abbott hs-cTnI and Roche hs-cTnT assays, we synthesized datasets of 1 000 000 simulated patients. Troponin concentrations were randomly varied several times based on absolute deviations of 0.5 to 3 ng/L and relative changes of 2% to 20% around the low-risk threshold (5 ng/L) and URLs, respectively. RESULTS: For both assays at the low-risk thresholds, there were negligible differences in sensitivity (<0.3%) with increasing analytical variation. The proportion of patients characterized as low risk reduced by 30% to 29% (Roche) and 53% to 44% (Abbott). At the URL, increasing analytical variation also did not change sensitivity; the PPV fell by less than 3%. For risk stratification, increased delta thresholds (change between serial troponin concentrations) increased sensitivity at the cost of a decreased percentage of patients below the delta threshold, with the largest changes at the greatest analytical variation. CONCLUSIONS: At the low-risk threshold, analytical variation up to 3 ng/L minimally impacted the safety metric (sensitivity) but marginally reduced effectiveness. Similarly, at the URL even relative variation up to 25% minimally impacted safety metrics and effectiveness. Analytical variation for delta thresholds did not negatively impact sensitivity but decreased effectiveness.

Analytical verification of the Atellica VTLi point of care high sensitivity troponin I assay.

OBJECTIVES: The Siemens Point-of-Care Testing (POC) Atellica® VTLi high-sensitivity troponin I (hsTnI) device has been previously validated. Verification independently provides evidence that an analytical procedure fulfils concordance with laboratory assays, imprecision, and hemolysis interference requirements. METHODS: Five whole blood samples spanning the measuring interval were analysed 20 times in succession. Hemolysis interference was assessed at three troponin concentrations by spiking five hemolysate concentrations to plasma to achieve free hemoglobin concentrations 35-1,000 mg/dL. Concordance between whole blood (VTLi) and plasma on laboratory analysers (Beckman, Roche, Siemens) was assessed by Pearson correlation and kappa statistics at the (LOQ) and upper reference limit (URL). This was repeated for frozen plasma samples. RESULTS: Coefficients of variation for whole blood were <10 % for whole blood troponin concentrations of 9.2 and 15.9 ng/L, thus below the URL. Hemolysis positively interfered; at 250 mg/dL affecting the low troponin sample (+3 ng/L; +60 %) and high troponin sample (+37 ng/L; +24 %). Correlation coefficients were 0.98, 0.90 and 0.97 between VTLi and Beckman, Roche and Siemens assays respectively. Corresponding kappa statistics were 0.80, 0.73 and 0.84 at the LOQ and 0.70, 0.44 and 0.67 at the URL. CONCLUSIONS: Concordances between VTLi and laboratory assays were at least non-inferior to those between laboratory assays. Imprecision met manufacturer claims and was consistent with a high sensitivity assay. There is potential for hemolysis interference, highlighting the need for quality samples. The results support performance characteristics previously reported in validation studies, and the device offers acceptable performance for use within intended medical settings.

External validation of a rapid algorithm using high-sensitivity troponin assay results for evaluating patients with suspected acute myocardial infarction.

OBJECTIVE: We sought to validate the clinical performance of a rapid assessment pathway incorporating the Siemens Atellica IM high sensitivity cardiac troponin I (hs-cTnI) assay in patients presenting to the emergency department (ED) with suspected acute myocardial infarction (AMI). METHODS: This was a multicentre prospective observational study of adult ED patients presenting to five Australian hospitals between November 2020 and September 2021. Participants included those with symptoms of suspected AMI (without ST-segment elevation MI on presentation ECG). The Siemen's Atellica IM hs-cTnI laboratory-based assay was used to measure troponin concentrations at admission and after 2-3 hours and cardiologists adjudicated final diagnoses. The HighSTEACS diagnostic algorithm was evaluated, incorporating hs-cTnI concentrations at presentation and absolute changes within the first 2 to 3 hours. The primary outcome was index AMI, including type 1 or 2 non-ST segment elevation MI (NSTEMI) or ST-elevation MI (STEMI) following presentation. 30-day major adverse cardiac outcomes (including AMI, urgent revascularisation or cardiac death) were also reported. The trial was registered with the Australian and New Zealand Clinical Trials Registry. RESULTS: 1994 patients were included. The average age was 56.2 years (SD=15.6), and 44.9% were women. 118 (5.9%) patients had confirmed index AMI. The 2-hour algorithm defined 61.3% of patients as low risk. Sensitivity was 99.1% (94.0%-99.9%) and negative predictive value was 99.9% (99.3%-100%). 24.4% of patients were deemed intermediate risk. When applying the parameters for high risk, 252 (14.3%) were identified, with a specificity of 91.5% (88.7%-93.6%) and a PPV of 42.0% (35.6-48.7%). CONCLUSIONS: A 2-hour algorithm based on the HighSTEACS strategy using the Siemens Atellica IM hs-cTnI laboratory-based assay enables safe and efficient risk assessment of emergency patients with suspected AMI. TRIAL REGISTRATION NUMBER: ACTRN12621000053820.

Performance of the European Society of Cardiology 0/1-Hour, 0/2-Hour, and 0/3-Hour Algorithms for Rapid Triage of Acute Myocardial Infarction : An International Collaborative Meta-analysis.

BACKGROUND: The 2020 European Society of Cardiology (ESC) guidelines recommend using the 0/1-hour and 0/2-hour algorithms over the 0/3-hour algorithm as the first and second choices of high-sensitivity cardiac troponin (hs-cTn)-based strategies for triage of patients with suspected acute myocardial infarction (AMI). PURPOSE: To evaluate the diagnostic accuracies of the ESC 0/1-hour, 0/2-hour, and 0/3-hour algorithms. DATA SOURCES: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from 1 January 2011 to 31 December 2020. (PROSPERO: CRD42020216479). STUDY SELECTION: Prospective studies that evaluated the ESC 0/1-hour, 0/2-hour, or 0/3-hour algorithms in adult patients presenting with suspected AMI. DATA EXTRACTION: The primary outcome was index AMI. Twenty unique cohorts were identified. Primary data were obtained from investigators of 16 cohorts and aggregate data were extracted from 4 cohorts. Two independent authors assessed each study for methodological quality. DATA SYNTHESIS: A total of 32 studies (20 cohorts) with 30 066 patients were analyzed. The 0/1-hour algorithm had a pooled sensitivity of 99.1% (95% CI, 98.5% to 99.5%) and negative predictive value (NPV) of 99.8% (CI, 99.6% to 99.9%) for ruling out AMI. The 0/2-hour algorithm had a pooled sensitivity of 98.6% (CI, 97.2% to 99.3%) and NPV of 99.6% (CI, 99.4% to 99.8%). The 0/3-hour algorithm had a pooled sensitivity of 93.7% (CI, 87.4% to 97.0%) and NPV of 98.7% (CI, 97.7% to 99.3%). Sensitivity of the 0/3-hour algorithm was attenuated in studies that did not use clinical criteria (GRACE score <140 and pain-free) compared with studies that used clinical criteria (90.2% [CI, 82.9 to 94.6] vs. 98.4% [CI, 88.6 to 99.8]). All 3 algorithms had similar specificities and positive predictive values for ruling in AMI, but heterogeneity across studies was substantial. Diagnostic performance was similar across the hs-cTnT (Elecsys; Roche), hs-cTnI (Architect; Abbott), and hs-cTnI (Centaur/Atellica; Siemens) assays. LIMITATION: Diagnostic accuracy, inclusion and exclusion criteria, and cardiac troponin sampling time varied among studies. CONCLUSION: The ESC 0/1-hour and 0/2-hour algorithms have higher sensitivities and NPVs than the 0/3-hour algorithm for index AMI. PRIMARY FUNDING SOURCE: National Taiwan University Hospital.

International Validation of the Canadian Syncope Risk Score : A Cohort Study.

BACKGROUND: The Canadian Syncope Risk Score (CSRS) was developed to predict 30-day serious outcomes not evident during emergency department (ED) evaluation. OBJECTIVE: To externally validate the CSRS and compare it with another validated score, the Osservatorio Epidemiologico della Sincope nel Lazio (OESIL) score. DESIGN: Prospective cohort study. SETTING: Large, international, multicenter study recruiting patients in EDs in 8 countries on 3 continents. PARTICIPANTS: Patients with syncope aged 40 years or older presenting to the ED within 12 hours of syncope. MEASUREMENTS: Composite outcome of serious clinical plus procedural events (primary outcome) and the primary composite outcome excluding procedural interventions (secondary outcome). RESULTS: Among 2283 patients with a mean age of 68 years, the primary composite outcome occurred in 7.2%, and the composite outcome excluding procedural interventions occurred in 3.1% at 30 days. Prognostic performance of the CSRS was good for both 30-day composite outcomes and better compared with the OESIL score (area under the receiver-operating characteristic curve [AUC], 0.85 [95% CI, 0.83 to 0.88] vs. 0.74 [CI, 0.71 to 0.78] and 0.80 [CI, 0.75 to 0.84] vs. 0.69 [CI, 0.64 to 0.75], respectively). Safety of triage, as measured by the frequency of the primary composite outcome in the low-risk group, was higher using the CSRS (19 of 1388 [0.6%]) versus the OESIL score (17 of 1104 [1.5%]). A simplified model including only the clinician classification of syncope (cardiac syncope, vasovagal syncope, or other) variable at ED discharge-a component of the CSRS-achieved similar discrimination as the CSRS (AUC, 0.83 [CI, 0.80 to 0.87] for the primary composite outcome). LIMITATION: Unable to disentangle the influence of other CSRS components on clinician classification of syncope at ED discharge. CONCLUSION: This international external validation of the CSRS showed good performance in identifying patients at low risk for serious outcomes outside of Canada and superior performance compared with the OESIL score. However, clinician classification of syncope at ED discharge seems to explain much of the performance of the CSRS in this study. The clinical utility of the CSRS remains uncertain. PRIMARY FUNDING SOURCE: Swiss National Science Foundation & Swiss Heart Foundation.

Application of High-Sensitivity Troponin in Suspected Myocardial Infarction.

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.).

Use of the Theoretical Domains Framework to explore factors influencing paediatric fever management practices and antipyretic use in New Zealand emergency departments.

AIM: To explore factors influencing fever management practices and antipyretic use among New Zealand Emergency Department (ED) doctors and nurses using the Theoretical Domains Framework (TDF). METHODS: Cross-sectional survey of doctors and nurses across 11 New Zealand EDs. The questionnaire examined eight of 12 TDF domains, based on a generic questionnaire validated to assess TDF-based determinants of health-care professional behaviour. Relevant domains were identified by the frequency of beliefs; the presence of conflicting beliefs within a domain; and the likely strength of impact of a belief on paediatric fever management in the ED. RESULTS: About 602 participants (243 doctors, 353 nurses and 6 unknown) completed the survey (response rate 47.5%). Over half (351/591, 59.6%, 95% confidence interval (CI) 55.5-63.5%) knew the content of clinical practice guidelines regarding antipyretic use in febrile children (TDF Domain Knowledge), or had been trained to ensure antipyretics are given to febrile children only if they appear distressed (347/592, 58.6%, 95% CI 54.5-62.6%) (Skills). Over 40% (246/590, 95% CI 37.7-45.8%) aim to reduce the fever before discharge (Goals). Most (444/591, 75.1%, 95% CI 71.4-78.6%) participants felt capable of explaining appropriate antipyretic use to parents/care givers (Beliefs about Capabilities). Only a minority (155/584, 26.5%, 95% CI 23.0-30.3%) thought that they can ensure antipyretics are given to febrile children only if they appear distressed when the ED is busy (Environmental Context and Resources). CONCLUSIONS: Using the TDF, we identified factors influencing fever management practices and antipyretic use in the ED. These factors can guide the design of targeted, theory-informed knowledge translation strategies.

Sensitivity of modern multislice CT for subarachnoid haemorrhage at incremental timepoints after headache onset: a 10-year analysis.

BACKGROUND: CT performed within 6 hours of headache onset is highly sensitive for the detection of subarachnoid haemorrhage (SAH). Beyond this time frame, if the CT is negative for blood, a lumbar puncture is often performed. Technology improvements in image noise reduction, resolution and motion artefact have enhanced the performance of multislice CT (MSCT) and may have further improved sensitivity. We aimed to describe how the sensitivity to SAH of modern MSCT changes with time from headache onset. METHODS: This was a retrospective analysis of electronic data collected as part of routine care among all patients presenting to Christchurch Hospital diagnosed with a SAH between 1 January 2008 and 31 December 2017. Patients were imaged with MSCT. The primary outcome was the proportion of patients with spontaneous aneurysmal SAH (identified via coding and confirmed by clinical and radiological records) that had a positive MSCT. The secondary outcome was the proportion of patients with any type of spontaneous SAH that had a positive MSCT. RESULTS: There were 347 patients with an SAH of whom 260 were aneurysmal SAH. MSCT identified 253 (97.3%) of all aneurysmal SAH and 332 (95.7%) of all SAH. The sensitivity of MSCT was 99.6% (95% CI 97.6 to 100) for aneurysmal SAH and 99.0% (95% CI 97.1 to 99.8) for all SAH at 48 hours after headache onset. At 24 hours after headache onset, the sensitivity for aneurysmal SAH was 100% (95% CI 98.3 to 100). CONCLUSION: These data suggest that it may be possible to extend the timeframe from headache onset within which modern MSCT can be used to rule out aneurysmal SAH.

Thunderclap headache syndrome presenting to the emergency department: an international multicentre observational cohort study.

BACKGROUND: Most headache presentations to emergency departments (ED) have benign causes; however, approximately 10% will have serious pathology. International guidelines recommend that patients describing the onset of headache as 'thunderclap' undergo neuroimaging and further investigation. The association of this feature with serious headache cause is unclear. The objective of this study was to determine if patients presenting with thunderclap headache are significantly more likely to have serious underlying pathology than patients with more gradual onset and to determine compliance with guidelines for investigation. METHODS: This was a planned secondary analysis of an international, multicentre, observational study of adult ED patients presenting with a main complaint of headache. Data regarding demographics, investigation strategies and final ED diagnoses were collected. Thunderclap headache was defined as severe headache of immediate or almost immediate onset and peak intensity. Proportion of patients with serious pathology in thunderclap and non-thunderclap groups were compared by χ² test. RESULTS: 644 of 4536 patients presented with thunderclap headache (14.2%). CT brain imaging and lumbar puncture were performed in 62.7% and 10.6% of cases, respectively. Among patients with thunderclap headache, serious pathology was identified in 10.9% (95%CI 8.7% to 13.5%) of cases-significantly higher than the proportion found in patients with a different headache onset (6.6% (95% CI 5.9% to 7.4%), p<0.001.). The incidence of subarachnoid haemorrhage (SAH) was 3.6% (95% CI 2.4% to 5.3%) in those with thunderclap headache vs 0.3% (95% CI 0.2% to 0.5%) in those without (p<0.001). All cases of SAH were diagnosed on CT imaging. Non-serious intracranial pathology was diagnosed in 87.7% of patients with thunderclap headache. CONCLUSIONS: Thunderclap headache presenting to the ED appears be associated with higher risk for serious intracranial pathology, including SAH, although most patients with this type of headache had a benign cause. Neuroimaging rates did not align with international guidelines, suggesting potential need for further work on standardisation.

Presentation, Treatment and Long-Term Outcomes of a Multidisciplinary Acute Atrial Fibrillation Pathway: A 12-Month Follow-Up Study.

AIM: Atrial fibrillation/flutter (AF/AFL) is associated with high rates of emergency department (ED) visits and acute hospitalisation. A recently established multidisciplinary acute AF treatment pathway seeks to avoid hospital admissions by early discharge of haemodynamically stable, low risk patients from the ED with next-working-day return to a ward-based AF clinic for further assessment. We conducted a preliminary analysis of the clinical outcomes of this pathway. METHODS: We retrospectively reviewed clinical records of all patients assessed at the AF clinic at Christchurch Hospital, New Zealand, over a 12-month period. Data related to presentation, patient characteristics, treatment, and 12-month outcomes were analysed. RESULTS: A total of 143 patients (median age 65, interquartile range: 57-74 years, 59% male, 87% European) were assessed. Of these, 87 (60.8%) presented with their first episode of AF/AFL. Spontaneous cardioversion occurred in 41% at ED discharge, and this increased to 73% at AF clinic review. Electrical cardioversion was subsequently performed in 16 patients (11.2%), and 16 (11.2%) ultimately required hospital admission (eight to facilitate electrical cardioversion). At a median of 1 day, 83.9% were discharged from the AF clinic in sinus rhythm. During 12-month follow-up, there were 25 AF-related hospitalisations (20 patients, 14%) and one patient underwent electrical cardioversion; additionally, one patient had had a stroke and eight had bleeding complications giving a combined outcome rate of 6.3%. CONCLUSION: Utilising a rate-control strategy with ED discharge and early return to a dedicated AF clinic can safely prevent the majority of hospitalisations, avert unnecessary procedures, and facilitate longitudinal care.

Long-term outcomes in patients with pulmonary embolism: results from a longitudinal cohort study.

BACKGROUND: Patients with pulmonary embolism (PE) have increased mortality in short-term; however, long-term prognosis is not well defined. AIM: In this long-term cohort study, we aimed to determine if PE was associated with increased risk of mortality or serious clinical events (SCE). Secondary aims were to ascertain predictors of mortality and SCE. METHODS: Patients admitted with clinical suspicion of PE were prospectively recruited from July 2002 to May 2003 and followed up until March 2015. Clinical outcomes in patients with PE were compared to those without PE. SCE was defined as composite of mortality, malignancy, cardiovascular events, recurrent venous thromboembolism and chronic thromboembolic pulmonary hypertension. RESULTS: A total of 501 patients with median follow up of 11.9 years (interquartile range 3.91-12.28) was included. PE was diagnosed in 104 (20.7%) patients. Overall, 45.9% died and 57.1% developed SCE during follow up, with no significant difference in PE and no-PE groups (both P > 0.5). Major determinants of mortality were age (hazard ratio (HR) 1.06 per year, 95% confidence interval (CI) 1.05-1.08), malignancy (HR 2.19, 95% CI 1.64-2.91) and congestive heart failure (HR 1.72, 95% CI 1.23-2.42). Factors associated with increased risk of SCE were age (HR 1.05 per year, 95% CI 1.04-1.06), malignancy (HR 1.93, 95% CI 1.48-2.52) and congestive heart failure (HR 1.77, 95% CI 1.29-2.43). In patients without PE, elevated D-dimer concentration was not found to be associated with diagnosis of malignancy during follow up (HR 1.31, 95% CI 0.55-3.12). CONCLUSIONS: In this prospective study, we did not find association between PE and risk of all-cause mortality or SCE. Major determinants of poor clinical outcomes were advancing age and underlying comorbidities.

Machine Learning to Predict the Likelihood of Acute Myocardial Infarction.

BACKGROUND: Variations in cardiac troponin concentrations by age, sex, and time between samples in patients with suspected myocardial infarction are not currently accounted for in diagnostic approaches. We aimed to combine these variables through machine learning to improve the assessment of risk for individual patients. METHODS: A machine learning algorithm (myocardial-ischemic-injury-index [MI3]) incorporating age, sex, and paired high-sensitivity cardiac troponin I concentrations, was trained on 3013 patients and tested on 7998 patients with suspected myocardial infarction. MI3 uses gradient boosting to compute a value (0-100) reflecting an individual's likelihood of a diagnosis of type 1 myocardial infarction and estimates the sensitivity, negative predictive value, specificity and positive predictive value for that individual. Assessment was by calibration and area under the receiver operating characteristic curve. Secondary analysis evaluated example MI3 thresholds from the training set that identified patients as low risk (99% sensitivity) and high risk (75% positive predictive value), and performance at these thresholds was compared in the test set to the 99th percentile and European Society of Cardiology rule-out pathways. RESULTS: Myocardial infarction occurred in 404 (13.4%) patients in the training set and 849 (10.6%) patients in the test set. MI3 was well calibrated with a very high area under the receiver operating characteristic curve of 0.963 [0.956-0.971] in the test set and similar performance in early and late presenters. Example MI3 thresholds identifying low- and high-risk patients in the training set were 1.6 and 49.7, respectively. In the test set, MI3 values were <1.6 in 69.5% with a negative predictive value of 99.7% (99.5-99.8%) and sensitivity of 97.8% (96.7-98.7%), and were ≥49.7 in 10.6% with a positive predictive value of 71.8% (68.9-75.0%) and specificity of 96.7% (96.3-97.1%). Using these thresholds, MI3 performed better than the European Society of Cardiology 0/3-hour pathway (sensitivity, 82.5% [74.5-88.8%]; specificity, 92.2% [90.7-93.5%]) and the 99th percentile at any time point (sensitivity, 89.6% [87.4-91.6%]); specificity, 89.3% [88.6-90.0%]). CONCLUSIONS: Using machine learning, MI3 provides an individualized and objective assessment of the likelihood of myocardial infarction, which can be used to identify low- and high-risk patients who may benefit from earlier clinical decisions. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au. Unique identifier: ACTRN12616001441404.

B-Type Natriuretic Peptides and Cardiac Troponins for Diagnosis and Risk-Stratification of Syncope.

BACKGROUND: The utility of BNP (B-type natriuretic peptide), NT-proBNP (N-terminal proBNP), and hs-cTn (high-sensitivity cardiac troponin) concentrations for diagnosis and risk-stratification of syncope is incompletely understood. METHODS: We evaluated the diagnostic and prognostic accuracy of BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations, alone and against those of clinical assessments, in patients >45-years old presenting with syncope to the emergency department in a prospective diagnostic multicenter study. BNP, NT-proBNP, hs-cTnT and hs-cTnI concentrations were measured in a blinded fashion. Cardiac syncope, as adjudicated by 2 physicians based on all information available including cardiac work-up and 1-year follow-up, was the diagnostic end point. EGSYS (Evaluation of Guidelines in Syncope Study), a syncope-specific diagnostic score, served as the diagnostic comparator. Death and major adverse cardiac events at 30 and 720 days were the prognostic end points. Major adverse cardiac events were defined as death, cardiopulmonary resuscitation, life-threatening arrhythmia, implantation of pacemaker/implantable cardioverter defibrillator, acute myocardial infarction, pulmonary embolism, stroke/transient ischemic attack, intracranial bleeding, or valvular surgery. ROSE (Risk Stratification of Syncope in the Emergency Department), OESIL (Osservatorio Epidemiologico della Sincope nel Lazio), SFSR (San Fransisco Syncope Rule), and CSRS (Canadian Syncope Risk Score) served as the prognostic comparators. RESULTS: Among 1538 patients eligible for diagnostic assessment, cardiac syncope was the adjudicated diagnosis in 234 patients (15.2%). BNP, NT-proBNP, hs-cTnT, and hs-cTnI were significantly higher in cardiac syncope versus other causes (P<0.01). The diagnostic accuracy for cardiac syncope, as quantified by the area under the curve, was 0.77 to 0.78 (95% CI, 0.74-0.81) for all 4 biomarkers, and superior to EGSYS (area under the curve, 0.68 [95%-CI 0.65-0.71], P<0.001). Combining BNP/NT-proBNP with hs-cTnT/hs-cTnI further improved diagnostic accuracy to an area under the curve of 0.81 (P<0.01). BNP, NT-proBNP, hs-cTnT, and hs-cTnI cut-offs, achieving predefined thresholds for sensitivity and specificity (95%), allowed for rule-in or rule-out of ≈30% of all patients. A total of 450 major adverse cardiac events occurred during follow-up. The prognostic accuracy of BNP, NT-proBNP, hs-cTnI, and hs-cTnT for major adverse cardiac events was moderate-to-good (area under the curve, 0.75-0.79), superior to ROSE, OESIL, and SFSR, and inferior to CSRS. CONCLUSIONS: BNP, NT-proBNP, hs-cTnT, and hs-cTnI concentrations provide useful diagnostic and prognostic information in emergency department patients with syncope. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT01548352.

Incidence, characteristics, determinants, and prognostic impact of recurrent syncope.

AIMS: The aim of this study is to characterize recurrent syncope, including sex-specific aspects, and its impact on death and major adverse cardiovascular events (MACE). METHODS AND RESULTS: We characterized recurrent syncope in a large international multicentre study, enrolling patients ≥40 years presenting to the emergency department (ED) with a syncopal event within the last 12 h. Syncope aetiology was centrally adjudicated by two independent cardiologists using all information becoming available during syncope work-up and long-term follow-up. Overall, 1790 patients were eligible for this analysis. Incidence of recurrent syncope was 20% [95% confidence interval (CI) 18-22%] within the first 24 months. Patients with an adjudicated final diagnosis of cardiac syncope (hazard ratio (HR) 1.50, 95% CI 1.11-2.01) or syncope with an unknown aetiology even after central adjudication (HR 2.11, 95% CI 1.54-2.89) had an increased risk for syncope recurrence. Least Absolute Shrinkage and Selection Operator regression fit on all patient information available early in the ED identified >3 previous episodes of syncope as the only independent predictor for recurrent syncope (HR 2.13, 95% CI 1.64-2.75). Recurrent syncope carried an increased risk for death (HR 1.87, 95% CI 1.26-2.77) and MACE (HR 2.69, 95% CI 2.02-3.59) over 24 months of follow-up, however, with a time-dependent effect. These findings were confirmed in a sensitivity analysis excluding patients with syncope recurrence or MACE before or during ED evaluation. CONCLUSION: Recurrence rates of syncope are substantial and vary depending on syncope aetiology. Importantly, recurrent syncope carries a time-dependent increased risk for death and MACE. TRIAL REGISTRATION: BAsel Syncope EvaLuation (BASEL IX, ClinicalTrials.gov registry number NCT01548352).

The Asia-Pacific Society of Cardiology (APSC) Expert Committee Consensus Recommendations for Assessment of Suspected Acute Coronary Syndrome Using High-Sensitivity Cardiac Troponin T in the Emergency Department.

The Asia-Pacific Society of Cardiology (APSC) high-sensitivity troponin T (hs-TnT) consensus recommendations and rapid algorithm were developed to provide guidance for healthcare professionals in the Asia-Pacific region on assessing patients with suspected acute coronary syndrome (ACS) using a hs-TnT assay. Experts from Asia-Pacific convened in 2 meetings to develop evidence-based consensus recommendations and an algorithm for appropriate use of the hs-TnT assay. The Expert Committee defined a cardiac troponin assay as a high-sensitivity assay if the total imprecision is ≤10% at the 99th percentile of the upper reference limit and measurable concentrations below the 99th percentile are attainable with an assay at a concentration value above the assay's limit of detection for at least 50% of healthy individuals. Recommendations for single-measurement rule-out/rule-in cutoff values, as well as for serial measurements, were also developed. The Expert Committee also adopted similar hs-TnT cutoff values for men and women, recommended serial hs-TnT measurements for special populations, and provided guidance on the use of point-of-care troponin T devices in individuals suspected of ACS. These recommendations should be used in conjunction with all available clinical evidence when making the diagnosis of ACS.

Concussive Symptoms Following Pediatric Mild Traumatic Brain Injury.

OBJECTIVES: To determine the proportion of children with postconcussive symptoms (PCSs) and to explore the influence of noninjury and injury factors on parents' PCS report at 3 months postinjury. DESIGN: A cross-sectional analysis of the 3-month postinjury data from a larger, prospective, longitudinal study. METHODS: Parents and their child aged 2 to 12 years who presented at the emergency department with either a mild traumatic brain injury (mTBI) or a superficial injury to the head (SIH) were recruited. Parents reported their child's symptoms at the time of injury and at 3 months postinjury. Child, family/parent, and injury characteristics were considered as potential predictors. Logistic regression was conducted to determine which factors increase the likelihood of parents' PCS report. RESULTS: At 3 months postinjury, 30% and 13% of children in the mTBI and SIH groups exhibited 1 or more symptoms, respectively. On the other hand, 18% (mTBI) and 8% (SIH) continued to have ongoing problems when 2 or more symptoms were considered at follow-up. The final model, which included child's sex, injury group, number of symptoms at the time of injury, and parental stress, had a significant predictive utility in determining parents' report of 1 or more symptoms at follow-up. Only parental stress continued to be a significant predictor when considering 2 or more symptoms at 3 months postinjury. CONCLUSIONS: Children with mTBI have worse outcomes than children with SIH at follow-up, with parents more likely to report 1 or more ongoing symptoms if their children had an mTBI. Postinjury assessment of parental stress and ongoing symptom monitoring in young children with mTBI will allow for timely provision of support for the family.

Factors influencing physician risk estimates for acute cardiac events in emergency patients with suspected acute coronary syndrome.

BACKGROUND: Emergency physicians frequently assess risk of acute cardiac events (ACEs) in patients with undifferentiated chest pain. Such estimates have been shown to have moderate to high sensitivity for ACE but are conservative. Little is known about the factors implicitly used by physicians to determine the pretest probability of risk. This study sought to identify the accuracy of physician risk estimates for ACE in patients presenting to the ED with chest pain and to identify the demographic and clinical information emergency physicians use in their determination of patient risk. METHODS: This study used data from two prospective studies of consenting adult patients presenting to the ED with symptoms of possible acute coronary syndrome. ED physicians estimated the pretest probability of ACE. Multiple linear regression analysis was used to identify predictors of physician risk estimates. Logistic regression was used to determine whether there was a correlation between physicians' estimated risk and ACE. RESULTS: Increasing age, male sex, abnormal ECG features, heavy/crushing chest pain and risk factors were correlated with physician risk estimates. Physician risk estimates were consistently found to be higher than the expected proportion of ACE from the sampled population. CONCLUSION: Physicians systematically overestimate ACE risk. A range of factors are associated with physician risk estimates. These include factors strongly predictive of ACE, such as age and ECG characteristics. They also include other factors that have been shown to be unreliable predictors of ACE in an ED setting, such as typicality of pain and risk factors.

CSANZ Position Statement on the Evaluation of Patients Presenting With Suspected Acute Coronary Syndromes During the COVID-19 Pandemic.

A pandemic of Coronavirus-19 disease was declared by the World Health Organization on March 11, 2020. The pandemic is expected to place unprecedented demand on health service delivery. This position statement has been developed by the Cardiac Society of Australia and New Zealand to assist clinicians to continue to deliver rapid and safe evaluation of patients presenting with suspected acute cardiac syndrome at this time. The position statement complements, and should be read in conjunction with, the National Heart Foundation of Australia & Cardiac Society of Australia and New Zealand: Australian Clinical Guidelines for the Management of Acute Coronary Syndromes 2016: Section 2 'Assessment of Possible Cardiac Chest Pain'.

Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction.

BACKGROUND: Combining 2 signals of cardiomyocyte injury, cardiac troponin I (cTnI) and T (cTnT), might overcome some individual pathophysiological and analytical limitations and thereby increase diagnostic accuracy for acute myocardial infarction with a single blood draw. We aimed to evaluate the diagnostic performance of combinations of high-sensitivity (hs) cTnI and hs-cTnT for the early diagnosis of acute myocardial infarction. METHODS: The diagnostic performance of combining hs-cTnI (Architect, Abbott) and hs-cTnT (Elecsys, Roche) concentrations (sum, product, ratio, and a combination algorithm) obtained at the time of presentation was evaluated in a large multicenter diagnostic study of patients with suspected acute myocardial infarction. The optimal rule-out and rule-in thresholds were externally validated in a second large multicenter diagnostic study. The proportion of patients eligible for early rule-out was compared with the European Society of Cardiology 0/1 and 0/3 hour algorithms. RESULTS: Combining hs-cTnI and hs-cTnT concentrations did not consistently increase overall diagnostic accuracy as compared with the individual isoforms. However, the combination improved the proportion of patients meeting criteria for very early rule-out. With the European Society of Cardiology 2015 guideline recommended algorithms and cut-offs, the proportion meeting rule-out criteria after the baseline blood sampling was limited (6% to 24%) and assay dependent. Application of optimized cut-off values using the sum (9 ng/L) and product (18 ng2/L2) of hs-cTnI and hs-cTnT concentrations led to an increase in the proportion ruled-out after a single blood draw to 34% to 41% in the original (sum: negative predictive value [NPV] 100% [95% confidence interval (CI), 99.5% to 100%]; product: NPV 100% [95% CI, 99.5% to 100%]) and in the validation cohort (sum: NPV 99.6% [95% CI, 99.0-99.9%]; product: NPV 99.4% [95% CI, 98.8-99.8%]). The use of a combination algorithm (hs-cTnI <4 ng/L and hs-cTnT <9 ng/L) showed comparable results for rule-out (40% to 43% ruled out; NPV original cohort 99.9% [95% CI, 99.2-100%]; NPV validation cohort 99.5% [95% CI, 98.9-99.8%]) and rule-in (positive predictive value [PPV] original cohort 74.4% [95% Cl, 69.6-78.8%]; PPV validation cohort 84.0% [95% Cl, 79.7-87.6%]). CONCLUSIONS: New strategies combining hs-cTnI and hs-cTnT concentrations may significantly increase the number of patients eligible for very early and safe rule-out, but do not seem helpful for the rule-in of acute myocardial infarction. CLINICAL TRIAL REGISTRATION: URL (APACE): https://www.clinicaltrial.gov . Unique identifier: NCT00470587. URL (ADAPT): www.anzctr.org.au . Unique identifier: ACTRN12611001069943.