HEART Score Recalibration Using Higher Sensitivity Troponin T.

STUDY OBJECTIVE: We examined the diagnostic performance of a recalibrated History, Electrocardiogram, Age, Risk factors, Troponin (HEART), and Thrombolysis in Myocardial Infarction (TIMI) score in patients with suspected acute cardiac syndrome (ACS). Recalibration of troponin thresholds was performed, including shifting from the 99th percentile to the limit of detection (LOD) or to the limit of quantification (LOQ) We compared the discharge potential and safety of the recalibrated composite scores using a single presentation high-sensitivity cardiac troponin (hs-cTn) T to the conventional scores and with a LOD/LOQ troponin strategy alone. METHODS: We undertook a 2-center prospective cohort study in the United Kingdom (UK) (2018) (Clinicaltrials.gov NCT03619733) to specifically assess recalibrated risk scores (shifting the troponin subset scoring from 99th percentile to LOD [UK]) and combined the results of this with secondary analyses of 2 prospective cohort studies in the UK (2011) and the United States (2018, using LOQ rather than LOD). The primary outcome was major adverse cardiovascular events (MACE), defined as adjudicated type 1 myocardial infarction (MI), urgent coronary revascularization, and all-cause death, at 30 days. We evaluated the original scores using hs-cTn below the 99th percentile and recalibrated scores using hs-cTn

Diagnostic Accuracy of a New High-Sensitivity Troponin I Assay and Five Accelerated Diagnostic Pathways for Ruling Out Acute Myocardial Infarction and Acute Coronary Syndrome.

STUDY OBJECTIVE: This diagnostic accuracy study describes the performance of 5 accelerated chest pain pathways, calculated with the new Beckman's Access high-sensitivity troponin I assay. METHODS: High-sensitivity troponin I was measured with presentation and 2-hour blood samples in 1,811 patients who presented to an emergency department (ED) in Australia. Patients were classified as being at low risk according to 5 rules: modified accelerated diagnostic protocol to assess patients with chest pain symptoms using troponin as the only biomarker (m-ADAPT), the Emergency Department Assessment of Chest Pain Score (EDACS) pathway, the History, ECG, Age, Risk Factors, and Troponin (HEART) pathway, the No Objective Testing Rule, and the new Vancouver Chest Pain Rule. Endpoints were 30-day acute myocardial infarction and acute coronary syndrome. Measures of diagnostic accuracy for each rule were calculated. RESULTS: Data included 96 patients (5.3%) with acute myocardial infarction and 139 (7.7%) with acute coronary syndrome. The new Vancouver Chest Pain Rule and No Objective Testing Rule had high sensitivity for acute myocardial infarction (100%; 95% confidence interval [CI] 96.2% to 100% for both) and acute coronary syndrome (98.6% [95% CI 94.9% to 99.8%] and 99.3% [95% CI 96.1% to 100%]). The m-ADAPT, EDACS, and HEART pathways also yielded high sensitivity for acute myocardial infarction (96.9% [95% CI 91.1% to 99.4%] for m-ADAPT and 97.9% [95% CI 92.7% to 99.7%] for EDACS and HEART), but lower sensitivity for acute coronary syndrome (≤95.0% for all). The m-ADAPT, EDACS, and HEART rules classified more patients as being at low risk (64.3%, 62.5%, and 49.8%, respectively) than the new Vancouver Chest Pain Rule and No Objective Testing Rule (28.2% and 34.5%, respectively). CONCLUSION: In this cohort with a low prevalence of acute myocardial infarction and acute coronary syndrome, using the Beckman's Access high-sensitivity troponin I assay with the new Vancouver Chest Pain Rule or No Objective Testing Rule enabled approximately one third of patients to be safely discharged after 2-hour risk stratification with no further testing. The EDACS, m-ADAPT, or HEART pathway enabled half of ED patients to be rapidly referred for objective testing.

Rapid Rule-out of Acute Myocardial Infarction With a Single High-Sensitivity Cardiac Troponin T Measurement Below the Limit of Detection: A Collaborative Meta-analysis.

Background: High-sensitivity assays for cardiac troponin T (hs-cTnT) are sometimes used to rapidly rule out acute myocardial infarction (AMI). Purpose: To estimate the ability of a single hs-cTnT concentration below the limit of detection (<0.005 µg/L) and a nonischemic electrocardiogram (ECG) to rule out AMI in adults presenting to the emergency department (ED) with chest pain. Data Sources: EMBASE and MEDLINE without language restrictions (1 January 2008 to 14 December 2016). Study Selection: Cohort studies involving adults presenting to the ED with possible acute coronary syndrome in whom an ECG and hs-cTnT measurements were obtained and AMI outcomes adjudicated during initial hospitalization. Data Extraction: Investigators of studies provided data on the number of low-risk patients (no new ischemia on ECG and hs-cTnT measurements <0.005 µg/L) and the number who had AMI during hospitalization (primary outcome) or a major adverse cardiac event (MACE) or death within 30 days (secondary outcomes), by risk classification (low or not low risk). Two independent epidemiologists rated risk of bias of studies. Data Synthesis: Of 9241 patients in 11 cohort studies, 2825 (30.6%) were classified as low risk. Fourteen (0.5%) low-risk patients had AMI. Sensitivity of the risk classification for AMI ranged from 87.5% to 100% in individual studies. Pooled estimated sensitivity was 98.7% (95% CI, 96.6% to 99.5%). Sensitivity for 30-day MACEs ranged from 87.9% to 100%; pooled sensitivity was 98.0% (CI, 94.7% to 99.3%). No low-risk patients died. Limitation: Few studies, variation in timing and methods of reference standard troponin tests, and heterogeneity of risk and prevalence of AMI across studies. Conclusion: A single hs-cTnT concentration below the limit of detection in combination with a nonischemic ECG may successfully rule out AMI in patients presenting to EDs with possible emergency acute coronary syndrome. Primary Funding Source: Emergency Care Foundation.

Sex-specific versus overall cut points for a high sensitivity troponin I assay in predicting 1-year outcomes in emergency patients presenting with chest pain.

OBJECTIVE: To evaluate the incidence of major adverse cardiac events (MACE) at 1 year in emergency department (ED) patients with possible acute coronary syndromes, stratified by high sensitivity troponin (hs-cTnI) concentrations using sex-specific cut points compared with overall cut points. METHODS: In a multicentre observational study of 2841 patients, presentation hs-cTnI concentrations were categorised using sex-specific (women 16 ng/L; men 34 ng/L) and overall (26 ng/L) cut points. The primary outcome was MACE occurring within 1 year of presentation. Patients with hs-cTnI values concentrations within these categories were reported by sex and 1-year MACE. Net reclassification improvement (NRI) was computed to measure the change in prediction after altering the hs-cTnI cut points, and was calculated separately for events and non-events. RESULTS: Application of sex-specific 99th percentile cut points rather than the overall cut point of 26 ng/L, reclassified 25 females from having a non-elevated troponin to having an elevated troponin, and 29 males from having an elevated troponin value to having a non-elevated troponin value on presentation. Of these, 7 (28.0%) females and 12 (41.4%) males had a 1-year MACE. There was no reclassification improvement for those with or without 1-year MACE (NRIevents=-1.5%, 95% CI -4.0% to 1.1%; NRInon-events -0.04%, 95% CI -0.5% to 0.4%). CONCLUSIONS: Sex-specific cut points improve the identification of women but not men at risk for 1-year MACE. The net-effect across the whole ED population with possible cardiac chest pain is minimal. Lowering the clinical cut point for both sexes may be appropriate for prognostic purposes. TRIAL REGISTRATION NUMBER: ISRCTN No. 21109279, ACTRN12609000283279.

Identifying Patients Suitable for Discharge After a Single-Presentation High-Sensitivity Troponin Result: A Comparison of Five Established Risk Scores and Two High-Sensitivity Assays.

STUDY OBJECTIVE: We compare the ability of 5 established risk scores to identify patients with suspected acute coronary syndromes who are suitable for discharge after a modified single-presentation high-sensitivity troponin result. METHODS: This was a prospective observational study conducted in a UK district general hospital emergency department. Consecutive adults recruited with suspected acute coronary syndrome for whom attending physicians determined evaluation with serial troponin testing was required. Index tests were definitions of low risk applied to modified Goldman, Thrombolysis in Myocardial Infarction (TIMI), Global Registry of Acute Cardiac Events (GRACE), History, ECG, Age, Risk Factors, Troponin (HEART), and Vancouver Chest Pain Rule risk scores, incorporating either high-sensitivity troponin T or I results. The endpoint was acute myocardial infarction within 30 days. A test sensitivity threshold for acute myocardial infarction of 98% was chosen. Clinical utility was defined as a negative predictive value greater than or equal to 99.5% and identification of greater than 30% suitable for discharge. RESULTS: Nine hundred fifty-nine patients underwent high-sensitivity troponin T analysis and 867 underwent high-sensitivity troponin I analysis. In the high-sensitivity troponin T group, 79 of 959 (8.2%) had an acute myocardial infarction and 66 of 867 (7.6%) in the high-sensitivity troponin I group. Two risk scores (GRACE <80 and HEART ≤3) did not have the potential to achieve a sensitivity of 98% with high-sensitivity troponin T, and 3 scores (Goldman ≤1, TIMI ≤1, and GRACE <80) with high-sensitivity troponin I. A TIMI score of 0 or less than or equal to 1 and modified Goldman score less than or equal to 1 with high-sensitivity troponin T, and TIMI score of 0 and HEART score of less than or equal to 3 with high-sensitivity troponin I had the potential to achieve a negative predictive value greater than or equal to 99.5% while identifying greater than 30% of patients as suitable for immediate discharge. CONCLUSION: With established risk scores, it may be possible to identify greater than 30% of patients suitable for discharge, with a negative predictive value greater than or equal to 99.5% for the diagnosis of acute myocardial infarction, using a single high-sensitivity troponin test result at presentation. There is variation in high-sensitivity troponin assays, which may have implications in introducing rapid rule-out protocols.

'Chest pain typicality' in suspected acute coronary syndromes and the impact of clinical experience.

BACKGROUND: Physicians rely upon chest pain history to make management decisions in patients with suspected acute coronary syndromes, particularly where the diagnosis is not immediately apparent through electrocardiography and troponin testing. The objective of this study was to establish the discriminatory value of "typicality of chest pain" and the effect of clinician experience, for the prediction of acute myocardial infarction and presence of significant coronary artery disease. METHODS: This prospective single-center observational study was undertaken in a UK General Hospital emergency department. We recruited consecutive adults with chest pain and a nondiagnostic electrocardiogram, for whom the treating physician determined that delayed troponin testing was necessary. Using their own clinical judgment, physicians recorded whether the chest pain described was typical or atypical for acute coronary syndrome. Physicians were defined as "experienced" or "novice" according to postgraduate experience. Acute myocardial infarction was adjudicated using a high-sensitivity troponin (hs-cTn) assay, whereas coronary artery disease was adjudicated angiographically. RESULTS: Overall, 912 patients had typicality of chest pain assessed, of whom 114/912 (12.5%) had an acute myocardial infarction and 157/912 (17.2%) underwent angiography. In patients undergoing angiography, 90/157 (57.3%) had hs-cTn elevation, of whom 60 (66.7%) had significant coronary artery disease. Sixty-seven of 157 (42.7%) patients had angiography without hs-cTn elevation; of these, 31 (46.2%) had significant coronary artery disease. For the diagnosis of acute myocardial infarction, chest pain typicality had an area under the curve (AUC) of 0.54 (95% confidence interval [CI], 0.49-0.60). For the prediction of significant coronary artery disease with hs-cTn elevation AUC: 0.54 (95% CI, 0.40-0.67), and without hs-cTn elevation AUC: 0.45 (95% CI, 0.31-0.59). When assessed by experienced physicians, specificity for the diagnosis of acute myocardial infarction was higher at 65.8% (95% CI, 63.1%-68.7%) vs 55.4% (95% CI, 53.9%-56.8%) for novices. CONCLUSIONS: Subjective interpretation of "typicality of chest pain" is of limited discriminatory value in the assessment of suspected acute coronary syndromes, in the context of a nondiagnostic electrocardiogram. Greater clinical experience improves accuracy as a rule-in tool but does not improve overall discriminatory ability.

A novel diagnostic protocol to identify patients suitable for discharge after a single high-sensitivity troponin.

OBJECTIVE: To establish whether a novel accelerated diagnostic protocol (ADP) for suspected acute coronary syndrome (ACS) could successfully identify low-risk patients suitable for discharge after a single high-sensitivity troponin T (hs-cTnT) taken at presentation to the emergency department. We also compared the diagnostic accuracy of this ADP with strategies using initial undetectable hs-cTnT. METHODS: This prospective observational study evaluated the ability of the Triage Rule-out Using high-Sensitivity Troponin (TRUST) ADP to identify low-risk patients with suspected ACS. The ADP incorporated a single presentation hs-cTnT of <14 ng/L, a non-ischaemic ECG and a modified Goldman risk score. Diagnostic performance of the ADP was compared with the detection limit cut-offs of hs-cTnT (<5 ng/L and <3 ng/L). The primary end point was fatal/non-fatal acute myocardial infarction (AMI) within 30 days. RESULTS: 960 participants were recruited, mean age 58.0 years, 80 (8.3%) had an AMI. The TRUST ADP classified 382 (39.8%) as low-risk with a sensitivity for identifying AMI of 98.8% (95% CI 92.5% to 99.9%). hs-cTnT detection limits (<5 ng/L and <3 ng/L) had a sensitivity of 100% (94.3 to 100) and 100% (94.4 to 100), respectively. The TRUST ADP identified more patients suitable for early discharge at 39.8% vs 29.3% (<5 ng/L) and 7.9% (<3 ng/L) (p<0.001) with a lower false-positive rate for AMI detection; specificity 43.3% (95% CI 42.7% to 43.4%) vs 32.0% (95% CI 31.5% to 32.0%) and 8.6% (95% CI 8.1% to 8.6%), respectively. CONCLUSIONS: The TRUST ADP, which incorporates structured risk-assessment and a single presentation hs-cTnT blood draw, has potential to allow early discharge in 40% of patients with suspected ACS and has greater clinical utility than undetectable hs-cTnT strategies. TRIAL REGISTRATION NUMBER: ISRCTN No. 21109279.

High-sensitivity cardiac troponins: no more 'negatives'.

According to recently published expert guidelines, cardiac troponins are the only accepted biomarkers to define acute myocardial infarction. New high sensitivity cardiac troponin assays provide exciting opportunities for early rule-out and rule-in strategies and for identifying high-risk patients early in their presentation to guide early treatment and intervention. This review briefly discusses the history of troponin testing, before going on to cover clinical uses of the new highly sensitive assays in the early assessment of acute myocardial infection. Common clinical pitfalls with the use of these assays are discussed, as is the use of highly sensitive troponins more widely as prognostic markers. Likely future developments in this area are discussed.