hsTn Assays Research Articles

Myocarditis in the modern era: analysing the impact of high-sensitivity troponin & C-reactive protein in predicting the extent of myocarditis and LV systolic dysfunction on cardiac magnetic resonance

Abstract Background The diagnostic yield of acute myocarditis has improved considerably since the advent of high-sensitivity troponin (hs-Tn) assays and adoption of the 2018 Lake Louise criteria for cardiac magnetic resonance (CMR)-based imaging for myocardial oedema and injury (1). Yet, a seminal 1997 study, predating these technological advances, remains widely cited for highlighting an absence of troponin rise in two-thirds of myocarditis cases (2). We hypothesize that all cases of myocarditis exhibit hs-Tn rise. However, whether such elevations in hs-Tn or inflammatory markers correlate with the extent of myocardial injury and left ventricular systolic dysfunction (LVSD) on CMR remain unclear. To provide insight into this, we examined a contemporary cohort of cases between 2019-2023. Methods Two authors independently conducted case-notes reviews to verify the diagnosis of myocarditis. CMR findings were stratified into regional (e.g. inferolateral) and global myocarditis (e.g. subepicardial LGE in all segments). This classification aimed to explore potential correlations with LVSD severity, peak hs-Tn and other inflammatory markers. Receiver operating characteristics (ROC) curves was calculated to determine any cut-off value for predicting CMR findings and adverse patient outcomes. Results 103 inpatients were clinically coded as ‘myocarditis’ upon discharge, but subsequent CMR (within 4 weeks) reclassified 23 patients into other causes (Figure 1). Analysis of the myocarditis cohort revealed a predominantly male population (76%) with median age 53, commonly presenting with chest pain without a viral prodrome (Figure 2A-D). Elevated hs-Tn levels were observed universally, with a median peak hs-TnT of 610ng/L (IQR 1081.5ng/L) and hs-TnI of 3820ng/L (IQR 12416ng/L). In contrast, peak CRP ranged between 2mg/L (normal) and 600mg/L. Global myocarditis was detected in 11/80 patients (13.8%); however, this finding did not correlate with adverse patient outcomes which included all-cause mortality (9.6%) and cardiac re-admissions within 12 months (9.6%, namely for chest pains). No arrhythmic deaths were noted. COVID was present in 4% on admission. CRP cut-off of 140mg/L predicted the occurrence of global myocarditis with a sensitivity of 72.7% and specificity of 87.0% (AUC 0.74, 95% CI 0.52-0.96, p=0.014) (Figure 2E). However, neither hs-Tn or CRP levels correlated with the degree of LVSD (Figure 2F) or adverse outcomes. This is likely limited by the small sample. Conclusion Although all cases of myocarditis exhibited raised hs-Tn, this did not correlate with the degree of LV systolic impairment on CMR. Myocarditis with regional LV involvement can have normal CRP levels, while a CRP cut-off >140mg/L may predict the occurrence of global myocarditis. However, CMR stratification into regional and global was not associated with adverse patient outcome within 12 months. A larger sample size is required to verify this finding, including longer term follow-ups.Flowchart of patients included in studyMain findings

Comparison of rapid test for high-sensitivity troponin I with laboratory high-sensitivity troponin T in patients with acute chest pain - a prospective monocentric study

Abstract Background and purpose High-sensitivity troponin (hs-Tn) assays are recommended for routine clinical use for diagnosis of acute coronary syndrome (ACS). However, laboratory hs-TnT can be elevated due to non-cardiac conditions, such as pulmonary embolism, skeletal muscle injury or chronic kidney disease. The aim of our study was to compare the diagnostic accuracy of the bed-side rapid hs-troponin I (hs-TnI) assay with hs-TnT measured by routine laboratory. Methods This prospective monocentric study was conducted at a tertiary hospital outpatient cardiac unit with an emergency clinic for patients with acute symptoms. A total of 129 patients were included between May 2021 and August 2022. Hs-TnI was measured via a bed-side test from whole blood directly in the emergency room, while hs-TnT was measured from plasma through the routine laboratory. Definite ACS was confirmed by coronary angiography. Patients were compared by grouping them into definitive diagnosis of ACS or no ACS. Hs-TnI as well as hs-TnT values were compared for accuracy and predictive values. Routine clinical parameters and comorbidities were documented and compared as well. Agreement between hs-TnI and hs-TnT was assessed by likelihood ratios and Bland Altman plot. Results Overall, 129 patients (65.1% male, 61.8 ± 15.6 years) with acute chest pain were analysed. Median hs-TnI was 7.0 ng/L (IQR: 2.7-15.8), while median hs-TnT was 14 ng/L (IQR: 7.0-31.0). Results for TnI were available faster (average: 1:14 h ± 0:54) compared to TnT. Coronary angiography confirmed ACS in 17 patients (13.2%) displaying significant coronary stenoses requiring intervention. The relative risk of ACS patients to have an elevated hs-TnI result was 6.59 compared to that of 2.29 for the hs-TnT test, meaning that a positive hs-TnI test was a better classifier for validated ACS than that of hs-TnT. Hs-TnI exhibited equivalent negative predictive value to hs-TnT (99%) for definite ACS diagnosis, but had comparatively higher positive predictive value (50.0 vs. 25.8%). Bland Altman plot of hs-TnI versus hs-TnT showed an average difference of -4.6 ng/L (95% CI: -12.4 to 3.2) between the tests. In 39 patients with chronic kidney disease (minimum stage 3a CKD) median hs-TnT (27.0 ng/L, IQR: 16.0-55.0) values were higher than hs-TnI (11.2 ng/L, IQR: 7.5-30.7). Conclusion Bed-side hs-TnI is comparable to hs-TnT with a high degree of agreement. Measurement of troponin I using the rapid bed-side hs-TnI assay possesses a shorter blood-draw-to-result-time than routine troponin T measurement.

Effectiveness of accelerated diagnostic protocols for reducing emergency department length of stay in patients presenting with chest pain: A systematic review and meta-analysis.

In recent years, there has been an increase in the use of accelerated diagnostic protocols (ADPs) and high-sensitivity troponin assays (hsTn) for the assessment of chest pain in emergency departments (EDs). This study aimed to quantitatively summarize the operational and clinical outcomes of ADPs implemented for patients with suspected cardiac chest pain. To be considered eligible for inclusion, studies must have implemented some form of ADP within the ED for evaluating adult (age ≥18 years) patients presenting with chest pain using Tn assays. The primary outcome was ED length of stay (LOS). Secondary outcomes included the proportion of patients admitted and the proportion with 30-day major adverse cardiac events (MACE). Thirty-seven articles involving 404,566 patients met the inclusion criteria, including five randomized controlled trials (RCTs) and 32 observational studies. A significant reduction in total ED LOS was reported in 22 observational studies and four RCTs. Emergency departments with longer baseline ED LOS showed significantly larger reductions in LOS after ADP implementation. This observed association persisted after adjusting for both the change in serial Tn measurement interval and transition from conventional Tn assay to an hsTn assay (β = -0.26; 95% CI, -0.43 to -0.10). Three studies reported an increase in the proportion of patients admitted after introducing an ADP, one of which was significant while 15 studies reported a significant decrease in admission proportion. There was moderate heterogeneity among the 13 studies that reported MACE proportions, with a non-significant pooled risk ratio of 0.95 (95% CI, 0.86-1.04). Implementation of ADPs for chest pain presentations decreases ED LOS, most noticeably within sites with a high baseline LOS; this decreased LOS is seen even in the absence of any change in troponin assay type. The decrease in LOS occurred alongside reductions in hospital admissions, while not increasing MACE. The observed benefits translated across multiple countries and health regions.

Imprecision and clinical performance of a whole blood high sensitivity point of care troponin I: the first prospective real-time study in suspected acute coronary syndrome

Abstract Introduction Implementation of accelerated diagnostic protocols (ADP) for suspected ACS, with resultant improvement in patient flow, will be facilitated by the use of point of care (POC) testing. To date there has been no published data on the use of a whole blood POC high sensitive troponin (hstn) in real time in a clinical environment. Methods In a nested sub-study of a pragmatic randomised controlled trial consecutive patients with suspected ACS and CP<12 hours duration, underwent sampling for quidell triage true POC hstn I whole blood and plasma (as well as a central laboratory hstn I [Siemens Attellica]. Subjects were randomised to ESC 0/1 and 0/3 hour ADP and had repeat whole blood and plasma POC tn I and laboratory hstn I at these time points. (ClinicalTrials.gov Identifier: NCT05322395). Assay imprecision was assessed by duplicate analysis of whole blood samples at seven levels. Final diagnosis was adjudicated based on all relevant clinical and imaging data together with hstn T as the diagnostic biomarker in clinical use. (Roche diagnostics, 10% coefficient of variation (CV) 3-5 ng/L, 99th percentile 14 ng/L) using the 4th universal definition of myocardial infarction (MI) Results 1157 patients consented and had both investigational POC whole blood and plasma (taken and analysed in real time) and central lab hstn I available. The mean age was 58, 48% were female and 15.4% patients had suffered a previous MI. Assay imprecision of whole blood POC quidel triage true revealed 10% CV at 8.6 ng/L, (>50% lower level than 99th percentile [20.4ng/l]) and a 20% CV at 1.2 ng/l). There was excellent overall agreement between laboratory hsTnI method and whole blood poc cTnI [Quidell triage true = 1.28cTnI Attelica +1.3]. ROC (receiver operator characteristics) curves were computed for each assay against adjudicated index MI to study clinical performance. At all time points there were excellent performance for whole blood POC: AUC 0.97 [95% CI 0.94-098]), 0.98 [95% CI 0.97-1.00] and 0.95 [95% CI0.92-0.98] at time 0 (presentation, figure), 1 and 3 hours respectively. There was statistical equivalence for performance of whole blood POC and plasma POC hstn I and laboratory hstn I Conclusion The POC whole blood quidell triage true demonstrates imprecision levels consistent with high sensitivity characteristics and has a clinical performance equivalent to an established and well validated laboratory hstn I. This is the first clinical validation of Whole blood POC hstn assay studied real-time in a clinical environment.

High medium-term incidence of major cardiovascular events in discharged patients with unstable angina.

This multicenter, prospective registry study included consecutive patients who underwent hsTn assays and were discharged with a diagnosis of NSTEACS. Patients were followed for two years. Outcomes were the occurrence of major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke), major bleeding, and all-cause mortality. Patients with UA and NSTEMI did not show differences in terms of the invasive interventions received, the coronary artery disease diagnosed, the type of revascularization performed, or the proportion presenting MACE (UA 18.1% vs. NSTEMI 18.9%; p=0.79). However, patients with NSTEMI had higher cardiovascular mortality at two years (UA 4% vs. NSTEMI 9.2%; p=0.012), as well as, all-cause mortality (UA vs. 7.9% vs. NSTEMI 16.4%; p=0.002). Medium-term incidence of MACE was similar in patients with UA and NSTEMI, but cardiovascular and all-cause mortality in NSTEMI patients was over twice that of patients with UA.

Temporal trends in acute coronary syndrome hospitalisation rates: a comparison of administrative diagnosis coding and cardiac biomarker testing

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Victor Chang Cardiac Research Institute. Background/aims Accurate monitoring of trends in acute coronary syndromes (ACS) provides important information on the impacts of primary and secondary prevention. Use of cardiac troponin (cTn) assays with increasing sensitivity and specificity during the past 20 years have likely increased the rates of diagnosis of myocardial infarction (MI), particularly NSTEMI. We aimed to determine the correlation of ICD-coded ACS hospitalisation rates with biomarker-classified ACS rates to inform population-level monitoring of ACS trends in Australia. Methods We used linked hospitalisation, emergency department, mortality, and pathology data from all tertiary hospitals in Western Australia (WA). We identified all patients aged >20years with a principal diagnosis of STEMI or NSTEMI (ICD-10-AM I21.0-I21.4) or unstable angina (UA) (ICD-10-AM I20.0) from 2001-2017. Creatine kinase (CK) and cTn test results including high-sensitivity (hs-Tn) assays were classified as elevated based on the ESC/AHA Universal Definition using the upper reference limit value for each assay. We calculated age-standardised rates (ASRs) for ICD-10 coded STEMI, NSTEMI and UA hospitalisations, and those which were cTn positive (cTn+), or any biomarker positive including CK (Bm+). We assessed annual ASR ratios over time (reference: ICD-coded rates) and estimated annual % changes in admissions using Poisson regression models adjusting for 5-year age-group and sex. Results The cohort comprised 143,231 ICD-coded ACS hospitalisations for 91,701 patients. 60.5% of the patients were male and 95.2% of the ACS hospitalisations had linked cardiac biomarker records. Despite slightly lower ASRs, Bm+ based rates were consistent with patterns in ICD-coded admissions in both MI sub-types (Figure) with no significant differences stratified by sex. Average annual decline in STEMI admissions was -3.7% (95% CI -4.1%,-3.4%) and -3.2% (95% CI -3.6%, -2.9%) in ICD-coded and Bm+ hospitalisations respectively. The annual rise in ICD-coded NSTEMI ASRs was 4.1% (95% CI 3.9%, 4.4%) which correlated with the 4.4% (95% CI 4.1%, 4.7%) annual rise in Bm+ ACS hospitalisations. The age-standardised rate ratios of ICD-coded to Bm+ were 1.27 and 1.28 for STEMI and NSTEMI respectively in 2001 and remained consistent at 1.29 and 1.30 for STEMI and NSTEMI respectively in 2017, although this was not the case for cTn+:ICD-coded rate ratios. There was an inverse trend between ASRs of ICD-coded NSTEMI and UA over the study period which correlated with use of increasingly sensitive cTn assays. The proportion of UA admissions with Bm+ was consistently low (21%) over the study period. Conclusions Despite shifts from CK to cTn and hs-Tn assays during our study period, the present study highlights the validity of using linked hospitalisation data to monitor long term trends in ACS based on cardiac biomarker positivity. Figure legend. Age-standardised hospitalisation rates by classification status in ACS subtypes.

Abstract 14155: Concomitant Use of Creatine Kinase MB and High-Sensitivity Troponin: What is the Cost?

Introduction: AHA/ACC guidelines recommend the use of serial high sensitivity troponin (hs-Tn) assays to assess for cardiac injury 1 and addition of CK-MB adds no benefit. However, in the clinical setting, CK-MB assays continues to be ordered concomitantly with hs-Tn in evaluation of suspected myocardial injury/infarction. We performed this study to determine whether the addition of CK-MB to hs-Tn alters diagnostic or therapeutic decisions and to determine its effect on patient outcomes. The financial aspects of this practice were also analyzed Methods: We performed a retrospective review of patients in the Geisinger Health care system from 2018 through 2021. Those having both a CK-MB and a hs-Tn drawn within 24 hours were included. Test results were categorized as concordant or discordant. Patient demographics, clinical profiles, medications and rates of diagnostic cardiac catheterization and subsequent PCI and primary admission and discharge diagnosis were collected from the EMR and analyzed. We used Medicare reimbursement data for estimates of financial impact. Results: A total of 18,727 unique patients had a CK-MB and hs-Tn performed within a 24-hour window. Of these, 49.1% (9,149) had concordant values and 50.9% (9,533) had discordant values. Of those with discordant results, 8,801 (92.3%) patients had abnormal hs-Tn result but normal CK-MB. Abnormal CK-MB with a normal hs-Tn was resulted in 840 patients (8.8%). There was a total of 42,276 CK-MB determinations during our study timeframe which averages out to 2.3 CK-MB/patient. Medicare reimbursement for CKMB is $11.55. Conclusions: This 3-year study demonstrates clinicians still frequently ordered CKMB in patients with concomitant hs-Tn determinations and 49.1%% results are concordant with hs-Tn results yielding no additional clinical information versus use of hs-Tn alone. The cost of this practice is estimated at $239,749.31 for the study period. Data on patients with discordant results and impact on decision process and cost is under analysis and will be available for presentation.

Agreement between four high-sensitivity cardiac troponin assays and non-invasive testing, clinical and quality of care outcomes based on the 2020 ESC guidelines: results from the ROMICAT II trial

Abstract Background Quality of care and safety of patients with suspected acute coronary syndrome (ACS) would greatly benefit if management was independent of which high-sensitivity cardiac troponin (hs-cTn) assay was used for risk stratification. Purpose To assess the agreement of 4 hs-cTn assays to risk stratify patients with suspected ACS using the ESC2020 Guidelines 0/2-hour algorithm, and to assess their associations with non-invasive diagnostic testing, clinical- and quality of care outcomes. Methods We analyzed blood samples obtained at emergency department (ED) presentation and 2 hours later from patients with suspected ACS enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography) II trial, using 4 hs-cTn assays (Roche Diagnostics, Elecsys 2010; Abbott Diagnostics, ARCHITECT i2000SR; Siemens Diagnostics, HsVista; Beckman Coulter, ACCESS). We determined the agreement between the assays to assign patients to rule-out, observe, and rule-in management pathways according to the ESC2020 Guidelines. Further, we assessed assay association with non-invasive diagnostic test findings and adjudicated clinical- and quality of care outcomes. Finally, we compared observed conventional troponin management with predicted management per ESC2020 guidelines using hs-cTn assays. Results Overall, assignment to ESC2020 Guideline management pathways among 238 patients with suspected ACS (age 52.7±8.0 years; 40.3% [96/238] female) was concordant across all hs-Tn assays in 74% of patients but differed for rule-out rates (89.9% vs 76.5% vs 78.6% vs 86.6%, p<0.001) and observation rates (6.7% vs 20.6% vs 17.7% vs 9.2%, p<0.001), but not for rule-in (3.4% vs 2.9% vs 3.8% vs 4.2%, p=0.623). Among those whose management recommendation was rule-out, 19.1–21.6% had obstructive CAD defined as coronary stenosis ≥50% on coronary CT angiography or inducible myocardial ischemia on perfusion imaging and 3.3–4.2% were diagnosed with ACS as adjudicated by independent panel. Predicted ED discharge rates based on hs-cTn assays were higher than those observed with conventional troponin (80.3% to 90.8% vs. 21.0%, respectively p<0.001). As a result, predicted costs of care were significantly lower based on strategies utilizing hs-cTn assays than with conventional troponin ($2,578±2,896 to $2,894±4,371 vs $3,889±4,833, respectively, p<0.001) Conclusion In a quarter of patients presenting to the ED with suspected ACS ESC2020 Guideline-based management may be different, depending on the hs-cTn assay. As compared to conventional troponin, hs-cTn is predicted to significantly increase direct ED discharges and lower costs of care. Funding Acknowledgement Type of funding sources: None.

Validation of a rapid diagnostic algorithm for diagnosis of myocardial infarction using a high-sensitivity cardiac troponin assay

Abstract Background As acute chest pain is one of the main reasons for presentation in emergency departments, early identification of patients with myocardial infarction (MI) is of crucial importance. Current guidelines recommend the application of rapid 0h/1h diagnostic algorithms using high-sensitivity cardiac troponin (hs-Tn) for the diagnosis of MI. Several hs-Tn assays have been evaluated and assay-specific algorithms have been developed, achieving great diagnostic performance. Yet, for some of these assays, existing data is limited. Objective We aimed to evaluate the diagnostic performance and prognostic value of a rapid 0/1h diagnostic algorithm for Access II hs-TnI as recommended by the European Society of Cardiology (ESC). Methods In the prospective Biomarkers in Acute Cardiac Care study enrolling patients presenting with suspected MI to the emergency department, we measured concentrations of Access II hs-TnI at presentation and after 1 hour. Final diagnoses were independently adjudicated by two cardiologists according to the 4th Universal Definition of MI using Elecsys hs-TnT. Parameters for diagnostic performance were calculated, when applying the ESC 0/1h algorithm. Additionally, to assess the prognostic utility of this ESC 0h/1h algorithm, we performed survival analyses for the composite of all-cause mortality and incident MI at three years, computing Kaplan-Meier-curves and Cox-regressions adjusted for common cardiovascular risk factors as well as pre-existing coronary artery disease and congestive heart failure. Results Of 1879 enrolled patients, 257 (14%) were diagnosed with NSTEMI. Median age was 63 years, 64.3% were males. When applying the ESC 0/1h algorithm using Access II hs-TnI, 44.5% of patients were ruled-out with a sensitivity of 97.7% (95% CI; 95.0, 99.1) and a negative predictive value (NPV) of 99.3% (95% CI; 98.4, 99.7). Similarly, 20.3% of patients were ruled-in with a specificity of 88.0% (95% CI; 86.3%, 89.6%) and a positive predictive value (PPV) of 50.8% (95% CI; 45.7, 55.9) whereas 35.1% remained in the observe group (Table 1). Three-year event rates differed substantially between patients triaged towards the rule-out (2.9%), observe (16.1%) and rule-in group (18.4%, log-rank p<0.001; Figure 1). Adjusted hazard ratios confirmed a significantly worse prognosis for patients in the observe group (HR 2.51 [95% CI; 1.56, 4.04], p=0.001) and rule-in group (HR 3.55 [95% CI; 2.18, 5.79], p<0.001), when compared to the rule-out group. Conclusion The ESC 0/1h algorithm for Access II hs-TnI allows a save and efficient rapid triage of patients with suspected MI and harbours prognostic utility for incident MI and all-cause mortality. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): German Center of Cardiovascular Research (DZHK)Abbott Diagnostics

Performance evaluation of the high sensitive troponin I assay on the Atellica IM analyser.

IntroductionThe Fourth Universal Definition of Myocardial Infarction Global Taskforce recommends the use of high sensitive troponin (hs-Tn) assays in the diagnosis of acute myocardial infarction. We evaluated the analytical performance of the Atellica IM High-sensitivity Troponin I Assay (hs-TnI) (Siemens Healthcare Diagnostics Inc., Tarrytown, USA) and compared its performance to other hs-TnI assays (Siemens Advia Centaur, Dimension Vista, Dimension EXL, and Abbott Architect (Wiesbaden, Germany)) at one or more sites across Europe.Materials and methodsPrecision, detection limit, linearity, method comparison, and interference studies were performed according to Clinical and Laboratory Standards Institute protocols. Values in 40 healthy individuals were compared to the manufacturer’s cut-offs. Sample turnaround time (TAT) was examined.ResultsImprecision repeatability CVs were 1.1–4.7% and within-lab imprecision were 1.8–7.6% (10.0–25,000 ng/L). The limit of blank (LoB), detection (LoD), and quantitation (LoQ) aligned with the manufacturer’s values of 0.5 ng/L, 1.6 ng/L, and 2.5 ng/L, respectively. Passing-Bablok regression demonstrated good correlations between Atellica IM analyser with other systems; some minor deviations were observed. All results in healthy volunteers fell below the 99th percentile URL, and greater than 50% of each sex demonstrated values above the LoD. No interference was observed for biotin (≤ 1500 µg/L), but a slight bias at 5.0 g/L haemoglobin and 50 ng/L Tn was observed. TAT from was fast (mean time = 10.9 minutes) and reproducible (6%CV).ConclusionsReal-world analytical and TAT performance of the hs-TnI assay on the Atellica IM analyser make this assay fit for routine use in clinical laboratories.

Contemporary Biomarker Strategies for Patients with Chest Pain.

This review focuses on the strengths and limitations of conventional and high-sensitivity troponin in the evaluation of patients with suspected acute coronary syndromes. High-sensitivity troponin (hsTn) assays represent a significant innovation over prior generation troponin assays. Owing to superior analytical precision, hsTn permits more rapid "rule-in" and "rule-out" of myocardial infarction. Furthermore, hsTn assays, in properly implemented clinical pathways, permit a reduction in the portion of patients requiring extended observation and testing.

Abstract 14266: Outcomes of Chest Pain Patients Following Application of a Validated High Sensitivity Troponin Algorithm: Comparison of 30 Day Death/ MI of Algorithm Concordant vs Discordant Discharges

Introduction: High sensitivity troponin (hsTn) assays effectively risk stratify patients with chest pain when a validated serial algorithm is utilized. Most of these algorithms require multiple draws for initial values in an intermediate range below a cutoff considered unequivocally consistent with MI. Little is known regarding outcomes of patients who are discharged following deviation from these algorithms. Hypothesis: Minor deviation from a validated hsTn algorithm may yield unacceptable outcomes in chest pain patients. Methods: Retrospective review of outcomes in patients presenting with chest pain to Geisinger Health System emergency departments and discharged based on application of a validated 0/1/3 hour hsTroponinT (hsTnT) algorithm over a 2-year period. We compared 30-day death/MI in patients who had hsTnT results that were consistent with “ruling out” (algorithm concordant) vs those who were discharged despite either equivocal hsTnT results or incomplete application of the algorithm (algorithm discordant). Patients who were admitted or met criteria for MI based on a peak hsTnT > 52ng/L were excluded. Results: Out of 10,342 patients discharged after hsTnT algorithm, 1,166 (11.3%) were algorithm-discordant. Thirty-day death/MI occurred in 13 (0.14%) of patients managed protocol concordant and 16 (1.37%)of patients managed protocol discordant (p<0.001). The 16 discordant pts with death/MI were algorithm-discordant due to either having only a single hsTnT draw (12) or a 0-1hr delta > 5ng/L (4). Comparing all patients with vs without 30day death/MI, univariate predictors included median age (66 vs 50yr, p<0.0001), prior CAD history (41.4 vs 17.5%, p=0.002), hyperlipidemia (44.8 vs 21.8%, p=0.006) and hsTnT algorithm discordance (55.2 vs 11.1%, p<0.001). A multivariable logistic regression model found that among univariate predictors only algorithm discordance was an independent predictor of 30-day death/MI (OR 6.42, p<0.001). Conclusions: Deviation from an hsTnT algorithm was associated significantly with increased 30 day cardiac events. This study highlights the importance of maintaining concordance with algorithm details when using hsTnT assays to triage chest pain patients.

EFFECTIVENESS AND FINANCIAL IMPACT OF A PROVINCIAL POLICY ELIMINATING ROUTINE USE OF CREATINE KINASE TESTING FOR WORK-UP OF SUSPECTED ACUTE CORONARY SYNDROME IN THE EMERGENCY DEPARTMENT

<h3>BACKGROUND</h3> Creatine kinase (CK) has long been a cornerstone in the diagnosis of ACS. However, it has been demonstrated that CK is not useful in the era of high-sensitivity troponin (hsTn) assays. In August 2020, a joint Choosing Wisely Manitoba® and Shared Health Manitoba practice change statement eliminating the routine use of CK for diagnosis of ACS was adopted. The policy was a written document highlighting that CK was an unnecessary test for ACS screening, and was distributed broadly to all health regions in Manitoba. We conducted a study to determine whether this policy change successfully reduced CK testing in emergency departments (EDs) across Manitoba, and the potential cost savings achieved. <h3>METHODS AND RESULTS</h3> A retrospective study was conducted using the Diagnostic Services Manitoba Laboratory Information Management System database. The total number of CK and hsTn tests ordered in all EDs across Manitoba were collected. As surrogates for total ED presentations and CK ordered for non-ACS indications, total number of CBCs and myoglobin tests were obtained. Data was collected 5-months (March 1 to July 31, 2020) prior to the policy change and 5-months (September 1 to January 31, 2021) following the policy change, which occurred in August 2020. Hypothesis testing was done with Chi square testing, with significance defined as p < 0.05. Prior to the policy change 88792 CBCs, 33079 hsTn, 2826 Myoglobin, and 20035 CK tests were ordered among all provincial EDs during the study period. Urban teaching hospitals ordered CK concurrently with hsTn 15.8% of the time, while it was ordered concurrently 33.1% of the time in peripheral EDs. Following the policy change, there was no difference in CBCs, hsTn, or myoglobins ordered, but there was a significant reduction in CK tests ordered (20035 vs 11840, p < 0.0001). There was a 54% relative reduction in CK use across the province following the policy change, (22.6% vs 12.2%; p < 0.0001). Individually, urban teaching hospitals decreased CK testing to 10.2%, while peripheral EDs decreased their CK testing to 15.3%. Based on a cost of $4/test, the 54% relative reduction in CK testing was estimated to result in a >$31000 in cost-savings over the course of a year. <h3>CONCLUSION</h3> The results of this study suggest that passive intervention through public health policy change is effective in reducing unnecessary testing across an entire health region.

Implementation of a High-Sensitivity Troponin-I Assay in an Academic Medical Center: A Qualitative and Quantitative Assessment.

To describe the clinical impact and lessons learned through implementation of a high sensitivity troponin (hsTn) assay. hsTn assays have received regulatory approval for use in the United States, and healthcare facilities are beginning to adopt these new assays. Questions remain about how to implement them and what effect they may have on demand for cardiovascular services. We conducted a mixed-methods implementation science-based investigation of hsTn adoption at a single academic medical center. We designed the investigation based on the Consolidated Framework for Implementation Research, exploring clinicians' perspectives on intervention characteristics, inner setting, individual characteristics, and process of implementation domains. Focus groups were conducted with clinicians from multiple service lines. Participants reported that the new hsTn assay did not fundamentally change processes of care such as cardiology consultations or inpatient admissions. Implementation was facilitated by leveraging the electronic medical record to provide useful suggestions for hsTn management at the point-of-care. The use of case-based teaching was considered most effective. Areas of ongoing concern included management of high-risk patients, outpatient follow-up, and feasibility of accelerated diagnostic protocols for early discharge from the emergency department. A decrease in the number of hsTn assays ordered was observed; no change was noted for admissions, cardiology consultations, or noninvasive cardiac imaging. A comprehensive educational campaign, based on multidisciplinary collaboration can effectively prepare clinicians for implementation of hsTn. New hsTn assays may not have any substantial effect on acute management of patients with cardiac complaints.

Abstract 17099: Implementation of a High Sensitivity Troponin-I Assay in an Academic Medical Center: A Qualitative and Quantitative Assessment

Background: High sensitivity troponin assays (hsTn) have received regulatory approval for use in the United States and health care facilities are beginning to adopt these new assays. Questions remain about how to implement these assays and what affect they may have on demand for cardiovascular services. Methods and Results: We conducted a mixed-methods implementation science-based investigation of hsTn adoption at a single academic medical center. We designed the investigation based on the Consolidated Framework for Implementation Research, exploring clinicians’ perspectives on intervention characteristics, inner setting, individual characteristics, and process of implementation domains. Focus groups were conducted with clinicians from multiple service lines. Participants reported that the new hsTn assay did not fundamentally change processes of care such as cardiology consultations or inpatient admissions. Implementation was facilitated by leveraging the electronic medical record to provide useful suggestions for hsTn management at the point-of-care. Participants expressed satisfaction with the multidisciplinary and collaborative approach taken to educating clinicians prior to implementation. The use of case-based teaching was considered most effective. Emergency department clinicians expressed greater confidence about decisions to discharge to home with the hsTn assay, compared to the older assay. Areas of ongoing concern included management of high risk patients, outpatient follow-up, and feasibility of accelerated diagnostic protocols for early discharge from the emergency department. Deidentified quantitative data on cardiovascular service use were gathered from administrative sources and analyzed on runcharts. A decrease in the number of hsTn assays ordered was observed; no change was noted for admissions, cardiology consultations, or noninvasive cardiac imaging. Conclusions: A comprehensive educational campaign, based on multidisciplinary collaboration can effectively prepare clinicians for implementation of hsTn. New hsTn assays may not have any substantial effect of acute management of patients with cardiac complaints. Many questions remain about best clinical practices for hsTn assays.

High-Sensitivity Troponins in Cardiovascular Disease.

Each new troponin assay generation is more sensitive, with recent generation high-sensitivity troponin (hsTn) assays able to detect minimal myocardial injury, even in asymptomatic patients. PURPOSE OF THE REVIEW: We reviewed recent information on the use of hsTn assays for assessing acute and chronic cardiovascular disease. RECENT FINDINGS: hsTn is used for early emergency department diagnosis, accelerating early discharge with a low event rate comparable if not better than current strategies. Low levels of hsTn are detected in a variety of chronic cardiac and non-cardiac conditions, non-disease conditions including heart failure, chemotherapy, and others. These elevations identify a population at increased risk for long-term cardiovascular events. However, management strategies remain unclear. hsTn has substantial advantages in emergency department use. They hold promise for identifying subclinical cardiac disease, with the potential for earlier intervention with the possibility of decreasing disease progression. Additional studies, however, are needed to determine if this strategy will lead to improved outcomes.

Multi-platform analytical evaluation of the Beckman Coulter Access high-sensitivity troponin I assay across different laboratory sites using Barricor plasma

ObjectivesPrevious analytical evaluations of the Beckman Coulter Access high sensitivity troponin (hsTn) I assay have focused on single platforms and laboratory sites. The purpose of this study was to determine assay robustness across different platforms at multiple sites, platform-specific characteristics, and equivalence to other hsTn methods in a large laboratory network. MethodsBarricor plasma was used to assess imprecision, linearity, sensitivity (limit of blank and detection, LOB/LOD), and comparability to the conventional AccuTnI+3 and other hsTn assays. Various studies were conducted across a total of 9 laboratories using Beckman DxI800 and Access2 platforms. ResultsWithin-laboratory precision was <10% across all target patient pool concentrations, however, DxI800 mean values were 20% higher than Access2 in the range of 3.6–44.9 ng/L. LOBs and LODs were lower on DxI800, 0.27 and 0.90 ng/L, respectively, compared to 2.9 and 3.2 ng/L, on Access2. Both showed excellent linearity across the full range. In method comparison to AccuTnI+3, DxI800 had a higher slope (0.9417 versus 0.8495) and positive bias (+18.1% versus −9.9%) compared to Access2, a trend further pronounced at concentrations <150 ng/L. At values <150 ng/L, there was good agreement with Abbott hsTnI (slope = 1.017, r = 0.932), but poor agreement with the Roche hsTnT assay (slope = 1.687, r = 0.589). Inter-laboratory split sample comparisons across 2 DxI800 and 7 Access2 sites showed close agreement, except at low concentrations <10 ng/L where DxI800 was 2.8 ng/L higher (p<0.001). ConclusionsThe Beckman hsTnI assay showed robust analytical performance across different laboratories and platforms. However, discrepancies between platforms were found at low concentrations where rapid acute myocardial infarction (AMI) rule-out decisions occur. These differences have important implications for AMI risk assessment, suggesting that laboratories should develop platform-specific parameters rather than using them interchangibly.

Identification of patients at higher risk for myocardial injury following elective coronary artery intervention.

To evaluate myocardial injury and infarction (MI) following elective percutaneous coronary intervention (PCI). The substantially higher analytical power of high-sensitivity troponin (hsTn) assays allows detection of minor cardiac troponin (cTn) levels, which may be useful in monitoring myocardial injury and guiding therapies. Serial hsTnT measurements were conducted in patients undergoing elective PCI and were related to the extent of coronary artery disease (CAD) as reflected by the SYNTAX score risk categories and American College of Cardiology/American Heart Association classification of coronary lesions. Myocardial injury and MI were diagnosed according to the second and third versions of universal MI definition. The study population consisted of 530 patients, who were grouped into low (41.3%), intermediate (35.4%), and high (23.3%) SYNTAX risk categories. The treated coronary lesions were classified into A 7.8%, B1 24.1%, B2 21.1%, C1 24.6%, and C2 22.4%. Postprocedural hsTnT increases correlated significantly with the complexity of treated coronary lesions (p < .05) and CAD magnitude (p < .05). Rates of MI type 4a according to the second and third MI definition criteria were 98 (27.5%) and 15 (4.2%) cases in patients with normal baseline hsTnT values (N = 357, 67.4%), as well as 137 (79.2%) and 27 (15.6%) cases in those with elevated baseline hsTnT values (N = 173, 32.6%), respectively. After elective PCI, cTn releases correlate significantly with lesion complexity and CAD extent. Use of hsTnT assay enables precise monitoring of PCI-related myocardial injury and may identify patients at higher risk for ischemic events, who may benefit from potent platelet inhibition, which needs to be investigated in randomized trials.

3303Classification of patients with acute chest pain by analytical benchmarks and subsequent management recommendations - A comparison of three highly-sensitivity troponin assays in the ROMICAT trials

Abstract Background Concordance of different highly-sensitive troponin (hsTn) assays in stratifying acute chest pain (ACP) patients according to analytical benchmarks and subsequent emergency department (ED) management recommendations are unknown. Methods We included patients enrolled in the ROMICAT (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography) I and II trials (n=624; 39.1% female; 52.8±10.0 years), who presented to the ED and were referred to further non-invasive diagnostic testing. In ROMICAT I, blood was obtained at 4 hours, and in ROMICAT II at ED presentation, and at 2 and 4 hours and was tested with three state-of-the-art hsTn assays (Roche Diagnostics, Elecsys 2010; Abbott ARCHITECT i2000SR; Siemens Diagnostics, HsVista). In a per sample analysis, we compared the concordance of assays for analytic benchmarks (below the level of detection (LOD)/LOD to 99th percentile/99th percentile to myocardial infarction (&lt;LOD], &gt;&lt;LOD], &gt;MI)/above MI). In a per patient analysis of serial hsTn testing in ROMICAT II, we determined concordance of management recommendations (rule out/observe/rule in) based on 2015ESC guidelines, results of coronary CT angiography and stress myocardial perfusion, and adjudicated endpoints of ACS. Results Overall, only 34.4% (353/1027) of samples were classified into the same benchmark category by all assays (table 1). In a per patient analysis, all assays agreed on the same of management recommendation in 25.3% (49/242) patients after the 1st hsTn, mostly driven by differences in discharge (6.6%, 21.1%, and 61.2%; respectively; all p&lt;0.001). The concordance of management recommendations improved significantly to 67.4% (163/242; p&lt;0.001) after the 2nd hsTn measurement but the final agreement for “observe” and “rule in” remained limited (13/90 and 5/18). Among patients in whom discharge was recommended, at least 18.8% (range: 18.8–21.0% across assays) had a positive imaging/stress test and at least 2.9% (range: 2.9–3.4%) had ACS. Table 1. Classification of measurements from three hsTn assays in 1027 samples of patients with ACP according to analytical benchmarks &lt;LOD LOD – 99th %tile* 99th %tile* – AMI** AMI**&lt; Roche Elecsys, n (%) 578 (56.3) 328 (31.9) 95 (9.3) 26 (2.5) Abbott ARCHITECT, n (%) 176 (17.1) 788 (76.7) 14 (1.7) 49 (4.8) Siemens Vista, n (%) 96 (9.4) 861 (83.9) 33 (3.2) 37 (3.6) *Assay specific 99th percentiles; **as per ESC 2015 guidelines. Conclusion Differences in hsTn assay concordance for analytical benchmarks and subsequent ED management recommendations in patients with ACP are substantial raising concerns about the lack of uniform management. Acknowledgement/Funding Fulbright Visiting Student Researcher Grant

5192Management and outcomes of patients with unstable angina with undetectable, normal, or intermediate hsTnT levels - A RAPID CPU substudy

Abstract Background Patients with unstable angina (UA) are regarded to be at low risk for future coronary events. Guidelines discourage routine coronary angiography and recommend early discharge after individualized risk stratification. The relative value of clinical risk indicators as compared to cardiac troponin (cTn) alone is unsettled in the era of high-sensitivity cardiac troponin (hsTn) assays. Purpose We aimed to investigate the clinical characteristics, therapies and outcomes of UA patients with different hsTnT concentrations. Methods During 12 months, 2,525 patients were enrolled. UA was defined as unstable symptoms and either undetectable (&lt;5 ng/L), normal (5–14 ng/L) or stable elevated hsTnT (15–51 ng/L). Follow up for 1-year mortality was available in 98.7%. Results A total of 280 patients (11.1%) received a diagnosis of UA. Mortality rates at 12 months were 0%, 1.9% and 6.9% in presence of undetectable, normal and stable elevated hsTnT. Elevated hsTnT &gt;99th percentile but not unstable symptoms carried an independent 3.25-fold (1.78–5.93) higher risk for all-cause death after adjustment for other clinical risk indicators or the GRACE score. Utilization of guideline recommended therapies was high albeit lower than for non-ST-elevation myocardial infarction (NSTEMI). Significantly fewer patients with UA received dual antiplatelet therapy (DAPT, odds ratio (OR): 0.51 [95% CI: 0.44–0.59], p&lt;0.0001), coronary angiography (CA, OR 0.79, [95% CI: 0.74–0.87], p&lt;0.0001), and percutaneous coronary intervention (PCI, OR 0.50, [95% CI: 0.40–0.61], p&lt;0.0001), compared to NSTEMI. However, prevalence of significant obstructive coronary artery disease (CAD) requiring PCI was 31.8%, even in patients with undetectable hsTnT, indicating the need for stress testing. Conclusions The current dichotomization of patients into UA and NSTEMI is no longer appropriate. Additional risk stratification seems warranted including the presence and magnitude of hsTn concentration and additional risk indicators. Acknowledgement/Funding Research Grant by Roche Diagnostics