103 Is it Safe to Use a High Sensitivity Troponin T Assay for Early “Rule Out” in Patients with Suspected Acute Coronary Syndrome?

Early diagnosis of acute myocardial infarction is important, but only 20% of emergency admissions for chest pain will actually have an acute myocardial infarction. High-sensitivity cardiac troponin assays may allow rapid rule out of myocardial infarction and avoid unnecessary hospital admissions. To assess the clinical effectiveness and cost-effectiveness of high-sensitivity cardiac troponin assays for the management of adults presenting with acute chest pain, in particular for the early rule-out of acute myocardial infarction. Sixteen databases were searched up to September 2019. Review methods followed published guidelines. Studies were assessed for quality using appropriate risk-of-bias tools. The bivariate model was used to estimate summary sensitivity and specificity for meta-analyses involving four or more studies; otherwise, random-effects logistic regression was used. The health economic analysis considered the long-term costs and quality-adjusted life-years associated with different troponin testing methods. The de novo model consisted of a decision tree and a state-transition cohort model. A lifetime time horizon (of 60 years) was used. Thirty-seven studies (123 publications) were included in the review. The high-sensitivity cardiac troponin test strategies evaluated are defined by the combination of four factors (i.e. assay, number and timing of tests, and threshold concentration), resulting in a large number of possible combinations. Clinical opinion indicated a minimum clinically acceptable sensitivity of 97%. When considering single test strategies, only those using a threshold at or near to the limit of detection for the assay, in a sample taken at presentation, met the minimum clinically acceptable sensitivity criterion. The majority of the multiple test strategies that met this criterion comprised an initial rule-out step, based on high-sensitivity cardiac troponin levels in a sample taken on presentation and a minimum symptom duration, and a second stage for patients not meeting the initial rule-out criteria, based on presentation levels of high-sensitivity cardiac troponin and absolute change after 1, 2 or 3 hours. Two large cluster randomised controlled trials found that implementation of an early rule-out pathway for myocardial infarction reduced length of stay and rate of hospital admission without increasing cardiac events. In the base-case analysis, standard troponin testing was both the most effective and the most costly. Other testing strategies with a sensitivity of 100% (subject to uncertainty) were almost equally effective, resulting in the same life-year and quality-adjusted life-year gain at up to four decimal places. Comparisons based on the next best alternative showed that for willingness-to-pay values below £8455 per quality-adjusted life-year, the Access High Sensitivity Troponin I (Beckman Coulter, Brea, CA, USA) [(symptoms > 3 hours AND < 4 ng/l at 0 hours) OR (< 5 ng/l AND Δ < 5 ng/l at 0 to 2 hours)] would be cost-effective. For thresholds between £8455 and £20,190 per quality-adjusted life-year, the Elecsys® Troponin-T high sensitive (Roche, Basel, Switzerland) (< 12 ng/l at 0 hours AND Δ < 3 ng/l at 0 to 1 hours) would be cost-effective. For a threshold > £20,190 per quality-adjusted life-year, the Dimension Vista® High-Sensitivity Troponin I (Siemens Healthcare, Erlangen, Germany) (< 5 ng/l at 0 hours AND Δ < 2 ng/l at 0 to 1 hours) would be cost-effective. High-sensitivity cardiac troponin testing may be cost-effective compared with standard troponin testing. This study is registered as PROSPERO CRD42019154716. This project was funded by the National Institute for Health Research (NIHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 25, No. 33. See the NIHR Journals Library website for further project information.

How Low Can We Go? The High-Sensitivity Cardiac Troponin Debate

Biomarkers in the triage of chest pain: are we making progress?

An Approach to Investigating Discordant High-Sensitivity Cardiac Troponin I Results

High-sensitivity cardiac troponin testing has received much hype over the last decade. Substantial focus on high-sensitivity cardiac troponin testing has occurred due to the combination of diagnostic company marketing, different...

linical implications of measurable cardiac troponin (cTn) within the reference interval in emergency department patients remain uncertain. Using highsensitivity (hs) cTnI, our goals were 3-fold. First, we examined clinical features of patients with hs-cTnI within sex-specific reference intervals. Second, we examined the prognostic impact of hs-cTnI within sex-specific reference intervals using baseline and serial measurements. Third, using hs-cTnI reference change values (RCVs; biological variation), we determined the prognostic impact of serial changes within sex-specific intervals.

Each year, about 6 million people with acute chest pain present to the emergency department (ED) in the US for diagnostic evaluation. Comparable data are reported from Europe: during the last 20-year period, the number of hospital admissions due to chest pain has tripled in the United Kingdom. In current guidelines, the presence or absence of acute myocardial infarction (MI) is diagnosed by prudent balancing elements of patient history, 12-lead electrocardiogram (ECG) recordings, and dynamic changes of cardiac troponin (cTn) levels above recommended cutoff levels within a 3 h observational period (1). Of note, the majority of these patients does not have MI, but need time consuming evaluation. Due to diagnostic uncertainty and the lack to rule out MI rapidly, some of those patients are being hospitalized. To reduce the length of stay in the ED and the hospital, new diagnostic pathways are welcome to accelerate the diagnostic evaluation of affected patients with chest pain in the ED (2). Thus, the report of the High-STEACS trial (High-sensitivity cardiac troponin I at presentation in patients with suspected acute coronary syndrome: a cohort study) recently published in The Lancet is welcome and of major importance (3).

A Rule-Out Strategy Based on High-Sensitivity Troponin and HEART Score Reduces Hospital Admissions

Myocardial infarction after major surgery is frequent, drives outcome, and consumes health resources. Specific prediction and detection of perioperative myocardial infarction is an unmet clinical need. With the widespread use of high-sensitive cardiac troponin T assays, positive tests become frequent, but their diagnostic or prognostic impact is arguable. We, therefore, studied the association of routinely determined pre- and postoperative high-sensitive cardiac troponin T with the occurrence of major adverse cardiac events. This study was a prospective non-interventional trial. This study was conducted at Hannover Medical School in Germany. A total of 455 patients undergoing open vascular surgery were followed for 30 days for the occurrence of major adverse cardiac events. None. Preoperative and 24-hour postoperative high-sensitive cardiac troponin T measurements and the respective changes were correlated to medical history and the occurrence of major adverse cardiac events (cardiovascular death, myocardial infarction, and ischemia). Pre- and postoperative high-sensitive cardiac troponin T measurements demonstrated a majority of patients with detectable troponin levels preoperatively and an increase over the 24 hours after surgery. The level of high-sensitive cardiac troponin T was significantly associated with preexisting diseases that constitute the Lee's Revised Cardiac Risk Index. A preoperative high-sensitive cardiac troponin T greater than or equal to 17.8 ng/L and a perioperative high-sensitive cardiac troponin T change greater than or equal to 6.3 ng/L are independently associated with the occurrence of major adverse cardiac events. Adding high-sensitive cardiac troponin T absolute change to the Revised Cardiac Risk Index improves the risk predictive accuracy of the score as evidenced by increased area under receiver operating characteristic and significant reclassification effects. The risk predictive power of high-sensitive cardiac troponin T change in addition to the Revised Cardiac Risk Index could facilitate 1) detection of patients at highest risk for perioperative myocardial ischemia, 2) evaluation and development of cardioprotective therapeutic strategies, and 3) decisions for admission to and discharge from high-density care units.

High sensitivity cardiac troponin T and interleukin‐6 predict adverse cardiovascular events and mortality in anticoagulated patients with atrial fibrillation: a rebuttal

High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the optimal approach is uncertain. We compared the European Society of Cardiology rule-out pathway with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients. Patients with suspected acute coronary syndrome (n=1218) underwent high-sensitivity cardiac troponin I measurement at presentation and 3 and 6 or 12 hours. We compared the European Society of Cardiology pathway (<99th centile at presentation or at 3 hours if symptoms <6 hours) with a pathway developed in the High-STEACS study (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) population (<5 ng/L at presentation or change <3 ng/L and <99th centile at 3 hours). The primary outcome was a comparison of the negative predictive value of both pathways for index type 1 myocardial infarction or type 1 myocardial infarction or cardiac death at 30 days. We evaluated the primary outcome in prespecified subgroups stratified by age, sex, time of symptom onset, and known ischemic heart disease. The primary outcome occurred in 15.7% (191 of 1218) patients. In those less than the 99th centile at presentation, the European Society of Cardiology pathway ruled out myocardial infarction in 28.1% (342 of 1218) and 78.9% (961 of 1218) at presentation and 3 hours, respectively, missing 18 index and two 30-day events (negative predictive value, 97.9%; 95% confidence interval, 96.9-98.7). The High-STEACS pathway ruled out 40.7% (496 of 1218) and 74.2% (904 of 1218) at presentation and 3 hours, missing 2 index and two 30-day events (negative predictive value, 99.5%; 95% confidence interval, 99.0-99.9; P<0.001 for comparison). The negative predictive value of the High-STEACS pathway was greater than the European Society of Cardiology pathway overall (P<0.001) and in all subgroups, including those presenting early or known to have ischemic heart disease. Use of the High-STEACS pathway incorporating low high-sensitivity cardiac troponin concentrations rules out myocardial infarction in more patients at presentation and misses 5-fold fewer index myocardial infarctions than guideline-approved pathways based exclusively on the 99th centile. URL: http://clinicaltrials.gov. Unique identifier: NCT01852123.

In patients with suspected acute coronary syndrome high-sensitivity cardiac tropnonin T is used for rapid patient triage. Some acute coronary syndrome patients assigned to the observe zone based on high-sensitivity cardiac troponin T after 1 h require further diagnostic testing. Fast-strain encoded CMR imaging with breathing maneuvers may accelerate diagnostic work-up and identify patients suffering from acute coronary syndrome. Patients presenting with acute chest pain (high-sensitivity cardiac troponin T level 5–52 ng/L) were prospectively enrolled (consecutive sampling, time of recruitment: 09/18–06/19). Fast-strain-encoded imaging was performed within the 1-h timeframe (0 h/1 h algorithm) prior to 2nd high-sensitivity troponin T lab results. Images were acquired at rest as well as after 1-min of hyperventilation followed by a short breath-hold. In 108 patients (59 male; mean age: 57 ± 17y) the mean study time was 17 ± 3 min. An abnormal strain response after the breathing maneuver (persistent/increased/new onset of increased strain rates) correctly identified all 17 patients with a high-sensitivity troponin T dynamic (0 h/1 h algorithm) and explanatory significant coronary lesions, while in 86 patients without serologic or angiographic evidence for severe coronary artery disease the strain response was normal (sensitivity 100%, specificity 94.5%; 5 false positive results). The number of dysfunctional segments (strain > − 10%) proved to be a quantifiable marker for identifying patients with acute coronary syndrome. In patients with suspected acute coronary syndrome and inconclusive initial high-sensitivity troponin T, fast-strain-encoded imaging with a breathing maneuver may safely and rapidly identify patients with acute coronary syndrome, without the need for vasodilators, stress, or contrast agents.

Background: The HEART score consists of a simple test designed to stratify patients who consult the emergency departmentfor chest pain, according to their risk of presenting an acute coronary syndrome in the short term. It was initially createdwith a fourth-generation troponin, but the advent of high-sensitivity cardiac troponin T required its incorporation into thescore and the re-evaluation of its behavior.Objectives: The aim of this study was to evaluate the behavior of the HEART score with high sensitivity cardiac troponin T.Methods: A prospective study was conducted including 1,464 patients who consulted at the emergency department due chestpain, with a non-ST-segment elevation electrocardiogram. The incidence of MACE (composite of acute myocardial infarction,death and revascularization) at 30 days was evaluated.Results: The index classified 739 patients (50.5%) as low risk, 515 (35.2%) as intermediate risk and 210 (14.3%) as high riskpatients. The composite of acute myocardial infarction, death and revascularization incidence was 1.35% in the first group,20%, in the second group and 71%, in the third group (log-rank test p<0.001). The area under the global curve for the compositeof acute myocardial infarction, death and revascularization was 0.91 (0.89-0.93).Conclusions: The HEART score using high-sensitivity cardiac troponin T has a great capacity to classify patients with chestpain according to their risk of presenting cardiovascular events in the short term.

Determinants of High-Sensitivity Troponin T Among Patients with a Noncardiac Cause of Chest Pain

The new European Society of Cardiology guidelines to rule-in and rule-out acute myocardial infarction (AMI) in the emergency department include a rapid assessment algorithm based on high-sensitivity cardiac troponin and sampling at 0 and 1 hour. Emergency department physicians require high sensitivity to confidently rule-out AMI, whereas cardiologists aim to minimize false-positive results. High-sensitivity troponin I and T assays were used to measure troponin concentrations in patients presenting with chest-pain symptoms and being investigated for possible acute coronary syndrome at hospitals in New Zealand, Australia, and Canada. AMI outcomes were independently adjudicated by at least 2 physicians. The European Society of Cardiology algorithm performance with each assay was assessed by the sensitivity and proportion with AMI ruled out and the positive predictive value and proportion ruled-in. There were 2222 patients with serial high-sensitivity troponin T and high-sensitivity troponin I measurements. The high-sensitivity troponin T algorithm ruled out 1425 (64.1%) with a sensitivity of 97.1% (95% confidence interval [CI], 94.0%-98.8%) and ruled-in 292 (13.1%) with a positive predictive value of 63.4% (95% CI, 57.5%-68.9%).The high-sensitivity troponin I algorithm ruled out 1205 (54.2%) with a sensitivity of 98.8% (95% CI, 96.4%-99.7%)) and ruled-in 310 (14.0%) with a positive predictive value of 68.1% (95% CI, 62.6%-73.2%). The sensitivity of the European Society of Cardiology rapid assessment 0-/1-hour algorithm to rule-out AMI with high-sensitivity troponin may be insufficient for some emergency department physicians to confidently send patients home. These algorithms may prove useful to identify patients requiring expedited management. However, the positive predictive value was modest for both algorithms.