Introduction: Rapid diagnostic algorithms using high-sensitivity cardiac troponin can rapidly diagnose or exclude acute myocardial infarction (MI). However, multiple algorithms have been proposed and it is unclear if some outperform others. The objective of this study was to prospectively compare the diagnostic performance of 1- and 2-hour algorithms in clinical practice in a Canadian population. Methods: Emergency department patients with chest pain had high-sensitivity cardiac troponin-T (hs-cTnT) collected on presentation and 1- and 2-hours later at a single academic tertiary hospital and regional percutaneous coronary intervention site over a 2-year period. The primary outcome was index MI, the secondary outcome was 30-day major adverse cardiac events (MACE). All outcomes were 2 physician adjudicated. Results: We enrolled 1,167 patients with hs-cTnT collected on ED presentation. Of these, 350 had a valid 1-hour and 550 had a 2-hour hs-cTnT sample. Index MI prevalence was ~11%. Sensitivity of the 1- and 2-hour algorithms for index MI was 97.3% (95% CI 85.8-99.9%) and 100% (95% CI 91.6-100%) and for 30-day MACE was 80.9% (95% CI 66.7-90.9%) and 83.3% (95% CI 73.2-90.8%), respectively. The 1-hour algorithm was 96.3% specific for index MI (95% CI 93.8-98.2%) whereas specificity for the 2-hour algorithm was 97.9% (95% CI 96.3-100%). Both algorithms classified about one-quarter of patients in an indeterminate observational zone with an ~11% MI prevalence. Conclusion: Both the 1- and 2-hour algorithms were highly sensitive and specific for MI, but were less sensitive for 30-day MACE. However, the 2-hour algorithm trended toward better performance, likely because its larger delta cutoffs reduce the risk of misclassification owing to analytic variability. These findings suggest algorithms using larger delta cutoffs may provide a greater margin of safety. Further comparative evaluation of rapid diagnostic algorithms using different cutoffs and characterization of patients in the observational zone is warranted.

Introduction: Very low high-sensitivity troponin-T (hs-cTnT) concentrations on presentation can rule out acute myocardial infarction (AMI), but the ability to identify patients at low risk of 30-day major adverse cardiac events (MACE) is less clear. This study examines the sensitivity of low concentrations of hs-cTnT on presentation to rule out 30-day MACE. Methods: This prospective cohort study enrolled emergency department chest pain patients with non-ischemic ECGs who underwent AMI rule-out with an hs-cTnT assay. The primary outcome was 30-day MACE; secondary outcomes were individual MACE components. Because guidelines recommend using a single hs-cTnT strategy only for patients with more than 3-hours since symptom onset, a subgroup analysis was performed for this population. Outcomes were adjudicated based on review of medical records and telephone follow-up. Results: Of 1,167 patients enrolled, 125 (10.7%) experienced 30-day MACE and 97 (8.3%) suffered AMI on the index visit. More than one-third (35.6%) had presenting hs-cTnT concentrations below the limit of detection (5ng/L), which was 94.4% (95%CI 88.8-97.7%) sensitive for 30-day MACE and 99.0% (95%CI 94.5-100%) sensitive for index AMI. Of 292 (25.0%) patients with hs-cTnT < 5ng/L and at least 3-hours since symptom onset, only 3 experienced 30-day MACE (sensitivity 97.6%, 95%CI 93.2-100%) and none suffered AMI within 30-days (sensitivity 100%, 95%CI 96.3-100%). Conclusion: Among patients with non-ischemic ECGs and >3-hours since symptom onset, low hs-cTnT concentrations on presentation confer a very low risk of 30-day MACE. In the absence of a high risk clinical presentation, further risk stratification is likely to be low yield.

Introduction: Chest pain is one of the most common presenting complaints to emergency departments (EDs) across the world, and the exclusion of acute myocardial infarction (AMI) using troponin testing is central to the care of many of these patients. While testing strategies using conventional troponin assays require repeat testing over many hours to avoid missed diagnoses, high-sensitivity troponin (hs-cTn) assays may be able to exclude AMI in a large proportion of patients with a single result at presentation. This objective of this study is to validate the ability of very low concentrations of hs-cTn at presentation to exclude AMI in ED chest pain patients. Methods: This prospective cohort study was conducted at a single urban tertiary center and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. A high-sensitivity troponin result (Roche Elecsys hs-cTnT) was obtained in all patients at presentation. The primary outcome was AMI on the index visit. Secondary outcomes included 30-day AMI and major adverse cardiac events (MACE - including AMI, revascularization or cardiac death). Electronic medical records were reviewed and telephone follow-up was obtained for all patients at 30-days to ensure relevant events were captured. Two physician adjudication (board-certified emergency physician and cardiologist) was obtained for all outcomes. This study was REB approved. Results: A total of 1,167 patients were enrolled from August 2014 September 2016, of which 191 (16.3%) patients had an initial troponin below the limit of blank (LoB, <3 ng/L) and 416 (32.8%) were below the limit of detection (LoD, <5 ng/L). The sensitivity of a single troponin below the LoB (<3 ng/L) for index AMI was 100% (95% CI 96.2%-100%) and for 30-day AMI was 100% (95% CI 96.4-100%). The sensitivity of a troponin below the LoD (<5 ng/L) for index AMI was 97.9% (95% CI 92.7%-99.8%) and for 30-day AMI was 98.0% (95% CI 93.0-99.8%). Sensitivity for 30-day MACE at both cutoffs was lower: 98.4% (95% CI 94.3-99.8%) for <3 ng/L, and 94.4% (95% CI 88.8-97.7%) for <5 ng/L, respectively; however, negative predictive values remained high at both cutoffs: <3 ng/L, 99.0% (95% CI 96.3-99.9%) and <5 ng/L, 98.3% (95% CI 96.6-99.3%). Conclusion: A high sensitivity troponin T result below the LoB (<3 ng/L) is highly sensitive for excluding AMI and identifies patients at low risk of 30-day MACE. A result below the LoB (<5 ng/L) will identify a larger population of patients as low risk but has a greater risk of missed AMI and MACE.

Introduction: Ruling out acute myocardial infarction (AMI) using serial troponin testing is central to the care of many emergency department (ED) patients with chest pain. While diagnostic strategies using conventional troponin assays require repeat sampling over many hours to avoid missed diagnoses, serial high-sensitivity troponin (hs-cTn) assays may be able to exclude AMI in most patients within 1 or 2 hours. However, many of the initial studies deriving and validating these rapid diagnostic algorithms had all hs-cTn samples analyzed in a central core lab likely representing optimal assay performance. This objective of this study is to validate a 1-hour rapid diagnostic algorithm to exclude AMI in ED chest pain patients using an hs-cTn assay in real world practice. Methods: This prospective cohort study was conducted at a single urban tertiary center and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. A high-sensitivity troponin result (Roche Elecsys hs-cTnT) was obtained in all patients at ED presentation and 1-hour later. The primary outcome was AMI on the index visit. Secondary outcomes included 30-day AMI and 30-day major adverse cardiac events (MACE - including AMI, revascularization or cardiac death). Electronic medical records were reviewed and telephone follow-up was obtained for all patients at 30-days to ensure relevant events were captured. Two physician adjudication (board-certified emergency physician and cardiologist) was obtained for all outcomes. The study was REB approved. Results: A total of 350 patients were enrolled from August 2014 September 2016 with 1-hour serial hs-cTnT results, of which 219 (62.6%) met the 1-hour rapid diagnostic algorithm low risk criteria (time 0h hs-cTnT <12ng/L and delta 1h <3ng/L). The sensitivity of the 1-hour low risk criteria for index AMI was 97.2% (95% CI 85.5%-99.9%) and for 30-day AMI was 97.3% (95% CI 85.8-99.9%). The sensitivity of the low risk criteria for 30-day MACE was lower 80.9% (95% CI 66.7-90.9%) but maintained a high negative predictive value, 95.9% (95% CI 92.3-98.1%). Conclusion: A 1-hour rapid diagnostic algorithm using an hs-cTnT assay was highly sensitive for AMI on the index visit and successfully identified patients at low risk of 30-day AMI; however, sensitivity for 30-day MACE was much lower. Of note, the 1-hour algorithm appears to be less sensitive for both AMI and 30-day MACE than a 2-hour algorithm validated in the same population.

Introduction: Ruling out acute myocardial infarction (AMI) using serial troponin testing is central to the care of many emergency department (ED) patients with chest pain. While diagnostic strategies using conventional troponin assays require repeat sampling over many hours to avoid missed diagnoses, serial high-sensitivity troponin (hs-cTn) assays may be able to exclude AMI in most patients within 1 or 2 hours. However, many of the initial studies deriving and validating these rapid diagnostic algorithms had all hs-cTn samples analyzed in a central core lab likely representing optimal assay performance. This objective of this study is to validate a 2-hour rapid diagnostic algorithm to exclude AMI in ED chest pain patients using an hs-cTn assay in real world practice. Methods: This prospective cohort study was conducted at a single urban tertiary center and regional percutaneous coronary intervention site in Calgary, Alberta. Patients were eligible for enrolment if they presented to the ED with chest pain, were 25-years or older and required biomarker testing to rule out AMI at the discretion of the attending emergency physician. Patients were excluded if they had clear acute ischemic ECG changes, new arrhythmia or renal failure requiring hemodialysis. A high-sensitivity troponin result (Roche Elecsys hs-cTnT) was obtained in all patients at ED presentation and 2-hours later. The primary outcome was AMI on the index visit. Secondary outcomes included 30-day AMI and 30-day major adverse cardiac events (MACE - including AMI, revascularization or cardiac death). Electronic medical records were reviewed and telephone follow-up was obtained for all patients at 30-days to ensure relevant events were captured. Two physician adjudication (board-certified emergency physician and cardiologist) was obtained for all outcomes. This study was REB approved. Results: A total of 549 patients were enrolled from August 2014 September 2016 with 2-hour serial hs-cTnT results, of which 349 (63.6%) met the 2-hour rapid diagnostic algorithm low risk criteria (time 0 h/2 h hs-cTnT <14 ng/L and delta 2 h <4 ng/L). The sensitivity of the 2-hour low risk criteria for index AMI was 98.4% (95% CI 91.3%-100%) and for 30-day AMI was 98.4% (95% CI 91.6-100%). The sensitivity for 30day MACE was lower 84.4% (95% CI 74.4-91.7%) but maintained a high negative predictive value, 96.6% (95% CI 94.1-98.2%). Conclusion: A 2-hour rapid diagnostic algorithm using an hs-cTnT assay was highly sensitive for AMI on the index visit and successfully identified patients at low risk of 30-day AMI. Sensitivity for MACE was lower, reminding us that while biomarker-only rapid diagnostic algorithms excel at ruling out AMI, careful clinical risk stratification is needed to avoid missed MACE events.