J. Andruchow

Undetectable Concentrations of a Food and Drug Administration–approved High-sensitivity Cardiac Troponin T Assay to Rule Out Acute Myocardial Infarction at Emergency Department Arrival

Abstract Background The objective of this study was to quantify the sensitivity of very low concentrations of high‐sensitivity cardiac troponin T (hsTnT) at ED arrival for acute myocardial infarction (AMI) in a large cohort of chest pain patients evaluated in real‐world clinical practice. Methods This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs, excluding those with ST‐elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes were AMI at 7, 30, and 90 days. Secondary outcomes included major adverse cardiac events (MACE; all‐cause mortality, AMI, and revascularization) and the individual MACE components. Test characteristics were calculated for hsTnT values from 3 to 200 ng/L . Results A total of 7,130 patients met inclusion criteria. AMI incidences at 7, 30, and 90 days were 5.8, 6.0, and 6.2%. When the hsTnT assay was performed at ED arrival, the limit of blank of the assay (3 ng/L) ruled out 7‐day AMI in 15.5% of patients with 100% sensitivity and negative predictive value (NPV). The limit of detection of the assay (5 ng/L) ruled out AMI in 33.6% of patients with 99.8% sensitivity and 99.95% NPV for 7‐day AMI. The limit of quantification (the Food and Drug Administration [FDA]‐approved cutoff for lower the reportable limit) of 6 ng/L ruled out AMI in 42.2% of patients with 99.8% sensitivity and 99.95% NPV. The sensitivities of the cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.6, 97.4, and 96.6%, respectively. The NPVs of the cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.8, 99.5, and 99.4%, respectively. A secondary analysis was performed in a subgroup of 3,549 higher‐risk patients who underwent serial troponin testing. In this subgroup, a cutoff of 3 ng/L ruled out 7‐day AMI in 9.6% of patients with 100% sensitivity and NPV, a cutoff of 5 ng/L ruled out 7‐day AMI in 23.3% of patients with 99.7% sensitivity and 99.9% NPV, and a cutoff of 6 ng/L ruled out 7‐day AMI in 29.8% of patients with 99.7 and 99.9% NPV. In the higher‐risk subgroup, the sensitivities of cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.8, 97.4, and 96.6%, respectively. In this higher‐risk subgroup, the NPV of cutoffs of <3, <5, and <6 ng/L for 7‐day MACE were 99.7, 98.5, and 98.4%, respectively. Conclusions When used in real‐world clinical practice conditions, hsTnT concentrations < 6 ng/L (below the lower reportable limit for an FDA‐approved assay) at the time of ED arrival can rule out AMI with very high sensitivity and NPV. The sensitivity for MACE is unacceptably low, and thus a single‐troponin rule‐out strategy should only be used in the context of a structured risk evaluation.

Variability of renal colic management and outcomes in two Canadian cities

BACKGROUND Some centres favour early intervention for ureteral colic while others prefer trial of spontaneous passage, and relative outcomes are poorly described. Calgary and Vancouver have similar populations and physician expertise, but differing approaches to ureteral colic. We studied 60-day hospitalization and intervention rates for patients having a first emergency department (ED) visit for ureteral colic in these diverse systems. METHODS We used administrative data and structured chart review to study all Vancouver and Calgary patients with an index visit for ureteral colic during 2014. Patient demographics, arrival characteristics and triage category were captured from ED information systems, while ED visits and admissions were captured from linked regional hospital databases. Laboratory results were obtained from electronic health records and stone characteristics were abstracted from diagnostic imaging reports. Our primary outcome was hospitalization or urological intervention from 0 to 60 days. Secondary outcomes included ED revisits, readmissions and rescue interventions. Time to event analysis was conducted and Cox Proportional Hazards modelling was performed to adjust for covariate imbalance. RESULTS We studied 3283 patients with CT-defined stones. Patient and stone characteristics were similar for the cities. Hospitalization or intervention occurred in 60.9% of Calgary patients and 31.3% of Vancouver patients (p<0.001). Calgary patients had higher index intervention rates (52.1% v. 7.5%), and experienced more ED revisits and hospital readmissions during follow-up. The data suggest that outcome events were associated with overtreatment of small stones in one city and undertreatment of large stones in the other. CONCLUSIONS An early interventional approach was associated with higher ED revisit, hospitalization and intervention rates. If these events are markers of patient disability, then a less interventional approach to small stones and earlier definitive management of large stones may reduce system utilization and improve outcomes for patients with acute ureteral colic.

Profile of Roche’s Elecsys Troponin T Gen 5 STAT blood test (a high-sensitivity cardiac troponin assay) for diagnosing myocardial infarction in the emergency department

ABSTRACT Introduction: The Elecsys Troponin T Gen 5 STAT test (distributed in the United States (US) by Roche Diagnostics, Indianapolis, IN) is the first high-sensitivity cardiac troponin test approved for use by the FDA in the US (2017). Areas covered: The test offers clinicians the opportunity for more rapid decision-making for diagnosing myocardial infarction (MI) in the emergency department (ED). The Troponin T Gen 5 STAT test (labeled as TNT-G5ST on the reagent pack) is similar to the Troponin T hs STAT (TNT-HSST) and Troponin T hs (TNT-HS) tests that have been available outside the US since 2009. Collectively, these tests can all be considered as high-sensitivity cardiac troponin T (hs-cTnT) assays. Expert commentary: Studies performed in the US and throughout the world using 0 and 3 h blood draws for hs-cTnT testing in patients with possible MI have reliably achieved a sensitivity of >94% and negative predictive value of ≥99% for MI in the ED setting.

Age-adjusted D-dimer thresholds in the investigation of suspected pulmonary embolism: A retrospective evaluation in patients ages 50 and older using administrative data

OBJECTIVES D-dimer testing is an important component of the workup for pulmonary embolism (PE). However, age-related increases in D-dimer concentrations result in false positives in older adults, leading to potentially unnecessary imaging utilization. The objective of this study was to quantify the test characteristics of an age-adjusted D-dimer cut-off for ruling out PE in older patients investigated in actual clinical practice. METHODS This observational study used administrative data from four emergency departments from July 2013 to January 2015. Eligible patients were ages 50 and older with symptoms of PE who underwent D-dimer testing. The primary outcome was 30-day diagnosis of PE, confirmed by imaging reports. Test characteristics of the D-dimer assay were calculated using the standard reference value (500 ng/ml), the local reference value (470 ng/ml), and an age-adjusted threshold (10 ng/ml × patient’s age). RESULTS This cohort includes 6,655 patients ages 50 and older undergoing D-dimer testing for a possible PE. Of these, 246 (3.7%) were diagnosed with PE. Age-adjusted D-dimer cut-offs were more specific than standard cut-offs (75.4% v. 63.8%) but less sensitive (90.3% v. 97.2%). The false-negative risk in this population was 0.49% using age-adjusted D-dimer cut-offs compared with 0.15% with traditional cut-offs. CONCLUSION Age-adjusted D-dimer cut-offs are substantially more specific than traditional cut-offs and may reduce CT utilization among older patients with suspected PE. We observed a loss of sensitivity, with an increased risk of false-negatives, using age-adjusted cut-offs. We encourage further evaluation of the safety and accuracy of age-adjusted D-dimer cut-offs in actual clinical practice.

Sex-specific, high-sensitivity cardiac troponin T cut-off concentrations for ruling out acute myocardial infarction with a single measurement

OBJECTIVE Sex-specific diagnostic cut-offs may improve the test characteristics of high-sensitivity troponin assays for the diagnosis of myocardial infarction (MI). The objective of this study was to quantify test characteristics of sex-specific cut-offs of a single, high-sensitivity cardiac troponin T (hs-cTnT) assay for 7-day MI in patients with chest pain. METHODS This observational cohort study included consecutive emergency department (ED) patients with suspected cardiac chest pain from four Canadian EDs who had an hs-cTnT assay performed within 60 minutes of ED arrival. The primary outcome was MI at 7 days. We quantified test characteristics (sensitivity, negative predictive value [NPV], likelihood ratios and proportion of patients ruled out) for multiple combinations of sex-specific, rule-out cut-offs. We calculated the net reclassification index compared to universal rule-out cut-offs. RESULTS In 7,130 patients (3,931 men and 3,199 women), the 7-day MI incidence was 7.38% among men and 3.78% among women. Optimal sex-specific cut-offs (<8 ng/L for men and <7 ng/L for women) had a 98.5% sensitivity for MI and ruled out MI in 55.8% of patients. This would enable an absolute increase in the proportion of patients who were able to be ruled out with a single hs-cTnT of 13.2% to 22.2%, depending on the universal rule-out concentration used as a comparator. CONCLUSIONS Sex-specific hs-cTnT cut-offs for ruling out MI at ED arrival may improve classification performance, enabling more patients to be safely ruled out at ED arrival. However, differences between sex-specific and universal cut-off concentrations are within the variation of the assay, limiting the clinical utility of this approach. These findings should be confirmed in other data sets.

PL001: Derivation of a 2-hour high-sensitivity troponin T algorithm for rapid rule-out of acute myocardial infarction in emergency department chest pain patients

Introduction: The Ottawa SAH Rule was developed to identify patients at high-risk for subarachnoid hemorrhage (SAH) who require investigations and the 6-Hour CT Rule found that computed tomography (CT) was 100% sensitive for SAH 6 hours of headache onset. Together, they form the Ottawa SAH Strategy. Our objectives were to assess: 1) Safety of the Ottawa SAH Strategy and its 2) Impact on: a) CTs, b) LPs, c) ED length of stay, and d) CT angiography (CTA).Methods:We conducted a multicentre prospective before/after study at 6 tertiary-care EDs January 2010 to December 2016 (implementation July 2013). Consecutive alert, neurologically intact adults with a headache peaking within one hour were included. SAH was defined by subarachnoid blood on head CT (radiologists final report); xanthochromia in the cerebrospinal fluid (CSF); >1x106/L red blood cells in the final tube of CSF with an aneurysm on CTA. Results: We enrolled 3,669 patients, 1,743 before and 1,926 after implementation, including 185 with SAH. The investigation rate before implementation was 89.0% (range 82.9 to 95.6%) versus 88.4% (range 85.2 to 92.3%) after implementation. The proportion who had CT remained stable (88.0% versus 87.4%; p=0.60), while the proportion who had LP decreased from 38.9% to 25.9% (p<0.001), and the proportion investigated with CTA increased from 18.8% to 21.6% (p=0.036). The additional testing rate (i.e. LP or CTA) diminishedfrom 50.1% to 40.8% (p<0.001). The proportion admitted declined from 9.8% to 7.3% (p=0.008), while the mean length of ED stay was stable (6.2 +/− 4.0 to 6.4 +/− 4.1 hours; p=0.45). For the 1,201 patients with CT 6 hours, there was an absolute decrease in additional testing (i.e. LP or CTA) of 15.0% (46.6% versus 31.6%; p<0.001). The sensitivity of the Ottawa SAH Rule was 100% (95%CI: 98-100%), and the 6-Hour CT Rule was 95.3% (95%CI: 88.998.3) for SAH. Five patients with early CT had SAH with CT reported as normal: 2 unruptured aneuryms on CTA and presumed traumatic LP (determined by treating neurosurgeon); 1 missed by the radiologist on the initial interpretation; 1 dural vein fistula (i.e. non-aneuyrsmal); and 1 profoundly anemic (Hgb 63g/L). Conclusion: The Ottawa SAH Strategy is highly sensitive and can be used routinely when SAH is being considered in alert and neurologically intact headache patients. Its implementation was associated with a decrease in LPs and admissions to hospital.

Highly-sensitive troponin T algorithm facilitates early discharge of low-risk chest pain patients within 1 h of emergency department arrival.

Commentary on : Reichlin T, Twerenbold R, Wildi K, et al. Prospective validation of a 1-hour algorithm to rule-out and rule-in acute myocardial infarction using a high-sensitivity cardiac troponin T assay. CMAJ 2015;187:E243–52.[OpenUrl][1][Abstract/FREE Full Text][2] A large proportion of emergency department (ED) visits involve patients with symptoms of suspected acute coronary syndrome (ACS), although ACS within this population is relatively infrequent.1 Evaluation of suspected ACS includes serial ECG and biomarker testing over several hours and frequently involves admission for provocative or invasive cardiac testing.2 Strategies to rapidly identify and safely discharge low-risk patients are important to improve resource utilisation. This prospective cohort study of consecutive ED patients with suspected ACS was designed to validate a previously-derived3 1 h accelerated diagnostic algorithm for acute myocardial infarction (AMI) using a high-sensitivity cardiac troponin-T (hs-cTnT) assay. Patients underwent routine … [1]: {openurl}?query=rft.jtitle%253DCMAJ%26rft_id%253Dinfo%253Adoi%252F10.1503%252Fcmaj.141349%26rft_id%253Dinfo%253Apmid%252F25869867%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=ABST&journalCode=cmaj&resid=187/8/E243&atom=%2Febmed%2F20%2F4%2F144.atom