High-sensitivity Cardiac Troponin Assays Research Articles

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays.

This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer's claims. All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer's claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0-3g/L free hemoglobin), leading to falsely low cTn recovery up to 3ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10-2000ng/mL (41-8,180nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

Comparing conventional and high sensitivity troponin T measurements in identifying adverse cardiac events in patients admitted to an Asian emergency department chest pain observation unit.

BackgroundHigh sensitive cardiac troponin assays can be used for prediction of major adverse cardiac events (MACE) in patients with chest pain.MethodsWe included patients with symptoms suggestive of acute coronary syndrome in the emergency department observation unit. We compared the accuracy of conventional troponin T (cTnT) with high sensitive troponin T (hsTnT) at various ranges, as well as the utility of hsTnT and cTnT in prediction of 30-day and 1-year MACE.Results1023 patients were included (68.1% male, median age 56 years). There were 2712 hsTnT and cTnT values compared. hsTnT had a higher AUC than cTnT for 30-day and 1-year MACE. The optimal cut-off of 0-hour hsTnT for 30-day (PPV 34%, NPV 96.6%) and 1-year MACE (PPV 40.2%, NPV 94.2%) was 16 ng/L.For 844 patients who had values for both 0 and 2 h hsTnT, we proposed a rule-out cut-off of 0 and 2 h hsTnT < 16 ng/L (NPV 97.0%, 95%CI 95.5–98.1%) and a rule-in cut-off of 0 and 2 h hsTnT ≥ 26 ng/L (PPV 58.8%, 95%CI 40.7%-75.4%) for 30-day MACE. Negative 0–2 h delta-hsTnT had poor predictive discriminant capabilities on 30-day (PPV 8.2%) and 1-year MACE (PPV 12.3%).ConclusionThe cut off values of hsTnT used in the 0 and 2-hour algorithm to rule-out (16 ng/L) and rule-in MACE (26 ng/L) are in the range that previous cTnT assays are unable to measure accurately. Risk scores can be used to further improve NPV of the rule-out group. A fall in hsTnT level acutely is not predictive of MACE.

Disagreement between Cardiac Troponin Tests Yielding a Higher Incidence of Myocardial Injury in the Emergency Setting.

Differences in patient classification of myocardial injury between high-sensitivity cardiac troponin (hs-cTn) assays have largely been attributed to assay design and analytical sensitivity aspects. Our objective was to compare Ortho Clinical Diagnostics’ (OCD) hs-cTnI assay to OCD’s contemporary/conventional assay (cTnI ES) and another hs-cTnI assay (Abbott hs-cTnI) in samples obtained from different emergency departments (EDs). Two different sample types were evaluated (lithium heparin and ethylenediaminetetraacetic acid (EDTA) plasma) in a non-selected ED population (study 1, n = 469 samples) and in patients for which ED physicians ordered cardiac troponin testing (study 2, n = 1147 samples), from five different EDs. The incidence of injury in study 1 was higher with the OCD hs-cTnI assay (30.9%; 95% CI: 26.9 to 35.2) compared to that of the Abbott hs-cTnI (17.3%; 95% CI: 14.1 to 21.0) and the OCD cTnI ES (15.4%; 95% CI: 12.4 to 18.9) assays, with repeat testing identifying 4.8% (95% CI: 3.0 to 7.5) of the OCD hs-cTnI results with poor reproducibility. In study 2, 4.6% (95% CI: 3.5 to 6.0) of the results were not reported for the OCD hs-cTnI assay (i.e., poor reproducibility) with 12.7% (95%CI: 8.7 to 17.8) of the OCD hs-cTnI results positive for injury being negative for injury with the Abbott hs-cTnI assay. In summary, the OCD hs-cTnI assay yields higher rates of biochemical injury with a higher rate of poor reproducible results in different ED populations.

High-Sensitivity Cardiac Troponin on Presentation to Rule Out Myocardial Infarction: A Stepped-Wedge Cluster Randomized Controlled Trial.

High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the safety and efficacy of this approach is uncertain. We investigated whether an early rule-out pathway is safe and effective for patients with suspected acute coronary syndrome. We performed a stepped-wedge cluster randomized controlled trial in the emergency departments of 7 acute care hospitals in Scotland. Consecutive patients presenting with suspected acute coronary syndrome between December 2014 and December 2016 were included. Sites were randomized to implement an early rule-out pathway where myocardial infarction was excluded if high-sensitivity cardiac troponin I concentrations were <5 ng/L at presentation. During a previous validation phase, myocardial infarction was ruled out when troponin concentrations were <99th percentile at 6 to 12 hours after symptom onset. The coprimary outcome was length of stay (efficacy) and myocardial infarction or cardiac death after discharge at 30 days (safety). Patients were followed for 1 year to evaluate safety and other secondary outcomes. We enrolled 31 492 patients (59±17 years of age [mean±SD]; 45% women) with troponin concentrations <99th percentile at presentation. Length of stay was reduced from 10.1±4.1 to 6.8±3.9 hours (adjusted geometric mean ratio, 0.78 [95% CI, 0.73-0.83]; P<0.001) after implementation and the proportion of patients discharged increased from 50% to 71% (adjusted odds ratio, 1.59 [95% CI, 1.45-1.75]). Noninferiority was not demonstrated for the 30-day safety outcome (upper limit of 1-sided 95% CI for adjusted risk difference, 0.70% [noninferiority margin 0.50%]; P=0.068), but the observed differences favored the early rule-out pathway (0.4% [57/14 700] versus 0.3% [56/16 792]). At 1 year, the safety outcome occurred in 2.7% (396/14 700) and 1.8% (307/16 792) of patients before and after implementation (adjusted odds ratio, 1.02 [95% CI, 0.74-1.40]; P=0.894), and there were no differences in hospital reattendance or all-cause mortality. Implementation of an early rule-out pathway for myocardial infarction reduced length of stay and hospital admission. Although noninferiority for the safety outcome was not demonstrated at 30 days, there was no increase in cardiac events at 1 year. Adoption of this pathway would have major benefits for patients and health care providers. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03005158.

Effect of racing on cardiac troponin I concentration and associations with cardiac rhythm disturbances in Standardbred racehorses

Introduction/ObjectivesAccumulating evidence indicates intense exercise can be associated with myocardial damage. Investigating the impact of maximal effort on myocardium and exploring possible association of injury with rhythm disturbance requires a high-sensitivity cardiac troponin assay. The objectives of this study were: (1) to determine the effect of racing on serum cardiac troponin I (cTnI) in Standardbred horses using a high-sensitivity assay; (2) to determine the 99th percentile of cTnI in healthy horses and investigate the effect of demographic variables on cTnI prevailing pre-race in Standardbred horses using a validated high-sensitivity assay and a contemporary assay, and; (3) to explore associations between exercise-associated arrhythmia and cTnI concentration. AnimalsRacehorses (n = 145). Materials and methods≤ 2 h pre-race, cTnI concentrations were measured in 158 race starts. Electrocardiogram (ECG) monitoring was applied during racing and race recovery and screened for complex ventricular arrhythmia. Associations between cTnI prevailing before racing concentration, age, sex, and gait were investigated. Demographic and performance variables were evaluated for associations with cTnI concentration post-race and rhythm disturbance. ResultsIncidence of arrhythmia was 11.6% (16 horses). A significant increase in median (interquartile range) cTnI concentration of 1.36 (0.49–2.81) ng/L was found post-race (p < 0.0001). Serum cardiac troponin I (cTnI) concentration prevailing pre-race was positively associated with increasing age, and gait. Serum cardiac troponin I prevailing post-race was positively associated with concentration prevailing pre-race. Interaction between arrhythmia and finishing distanced revealed horses finishing distanced and experiencing arrhythmia displayed higher cTnI release than with the presence of either alone. ConclusionsRacing increased cTnI concentration. Horses finishing distanced and also exhibiting arrhythmia may be experiencing myocardial compromise.

Trends Over Time in the Incidences of ST-Segment Elevation Myocardial Infarction and Non-ST-Segment Elevation Myocardial Infarction During the Past Decade in a Rural Japanese High-Aged Population.

In developed countries, the incidence of non-ST-segment elevation myocardial infarction (NSTEMI) has outpaced that of ST-segment elevation myocardial infarction (STEMI). However, whether this trend is observed in Japan, in which the aging of society is rapidly progressing, remains to be elucidated. This study retrospectively investigated the trends over time in the incidence of acute coronary syndrome (ACS) between August 2009 and July 2019 at 2 institutions in Izumo City (in rural Japan), which has an elderly population. Crude and age-sex-adjusted incidences of total ACS, STEMI, and non-ST-segment elevation-ACS (NSTE-ACS; including NSTEMI and unstable angina pectoris) were calculated for each year. In the total population, factors associated with the development of NSTEMI were evaluated by multivariate analysis. In total, 1,087 patients were enrolled. The age-adjusted incidence of NSTE-ACS in male patients aged ≥75 years showed a significantly increasing trend. The proportion of NSTEMI per total ACS cases showed a significantly increasing trend over the entire study period. In the multivariate analysis, pre-development use of ≥3 medications for comorbidities was associated with the development of NSTEMI, independent of high-sensitivity cardiac troponin assay use. This study demonstrated an increasing trend in the incidence of NSTEMI in a rural high-aged Japanese population. In addition to the widespread use of high-sensitivity cardiac troponin assays, early medication use for comorbidities might have contributed to this trend.

An Updated Meta-Analysis on the European Society of Cardiology 0/1-Hour Algorithm's Efficacy and Safety Outcomes

Background: In 2011, the European Society of Cardiology (ESC) has recommended the 0/1-hour algorithm with high-sensitivity cardiac troponin assays to diagnose acute myocardial infarction. However, there is no defined difference between high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI). Methods: We conducted the first meta-analysis of randomized controlled trials and observation studies from inception to 13 August 2021 that evaluated the 0/1-hour algorithm with hs-cTnT or hs-cTnI. The statistical analysis was performed using R version 3.6.3 with packages “metaprop” and “metafor”. We constructed two-by-two tables, pooled studies by a random-effects model using proportion, and calculated sensitivity, NPV, specificity, and PPV with 95% confidence intervals (CI). Results: Two RCTs and 15 observational studies were included with total of 17,883 patients and a median weighted follow-up period of 267 days. For hs-cTnT-Roche, the rates of pooled sensitivity was 98% (95% CI 94-99, I2 =87%), NPV was 99% (95% CI 98-100%, I2 =88%), specificity was 93% (95% CI 90-96%, I2 =98%), and PPV was 61% (95% CI 44-75%, I2 =98%). On the other hand, hs-cTnI-Pooled had a sensitivity of 99% (95% CI 97-99%, I2 =48%), NPV of 100% (95% CI 100-100%, I2 =41%), specificity of 95% (95% CI 94-97%, I2 =95%), PPV of 68% (95% CI 63-73%, I2 =71%) Conclusion: Assays of hs-cTnI-Pooled have higher values of sensitivity, NPV, specificity, and PPV when compared to hs-cTnT-Roche.

The role of cardiac testing with the 0/1-hour high-sensitivity cardiac troponin algorithm evaluating for acute myocardial infarction

The role of cardiac testing in the 3 zones (rule-out, observation, and rule-in) of the 0/1-hour algorithm to evaluate for acute myocardial infarction (AMI) has not been well studied. This study evaluated the 0/1-hour algorithm with a high-sensitivity cardiac troponin (hs-cTnI) assay and investigated cardiac testing in the 3 zones. Patients (n = 552) at a single urban center were enrolled if they were evaluated for AMI. Blood samples were obtained at presentation, 1 hour, and 3 hours for hs-cTnI. Follow-up at 30 to 45 days for death/AMI was done. The results of echocardiograms, stress testing, and coronary angiography were recorded. In total, 45 (8.2%) had AMI (27 Type 1 and 18 Type 2) during the index hospitalization while at follow-up death/AMI occurred in 11 (2.0%) of patients. The rule-out algorithm had a negative predictive value for AMI of 99.6% while the rule-in zone had a positive predictive value of 56.6%. The MACE rate at follow-up was 0.4% for those in the rule-out group. There were 6/95 (6.3%) abnormal stress tests in the rule-out zone and 4 of these were false positives. The 0/1-hour algorithm had high diagnostic sensitivity and negative predictive value for AMI, and adverse events were very low in patients in the rule-out zone. Noninvasive testing in rule-out zone patients had low diagnostic yield.

Implementation of High-Sensitivity and Point-of-Care Cardiac Troponin Assays into Practice: Some Different Thoughts.

BackgroundThe primary role of the International Federation of Clinical Chemistry (IFCC) Committee on Clinical Application of Cardiac Bio-Markers (C-CB) is to provide educational materials about cardiac biomarker use, emphasizing high-sensitivity cardiac troponin assays.ContentThis mini-review, regarding high-sensitivity cardiac and point-of-care troponin assays, addresses 1) new IFCC C-CB/AACC Academy laboratory practice recommendations; 2) new and updated concepts from the Fourth Universal Definition of Myocardial Infarction; 3) the role of point-of-care assays in practice and research; 4) regulatory challenges concerning point-of-care assays; e) testing in the COVID-19 world.SummaryImplementation of high-sensitivity cardiac troponin assays makes a difference now and into the future in clinical practice and research. Providing point-of-care high-sensitivity cardiac troponin assays and optimizing studies to allow clearance of these assays by regulatory agencies, in a timely fashion, may provide improved patient management and outcomes.

Early Rule-Out Strategies in the Emergency Department Utilizing High-Sensitivity Cardiac Troponin Assays.

Over the past decade, intense collaboration between academic investigators and the diagnostic industry have allowed the integration of high-sensitivity cardiac troponin (hs-cTn) assays into clinical practice worldwide. The hs-cTn assays, with their increased diagnostic accuracy for acute myocardial infarction (AMI), have facilitated the maturation of early rule-out strategies. The first iteration was complex and required the combination of a biomarker panel, the electrocardiogram, and a clinical risk score and allowed the safe rule-out of AMI in only 10% of patients with acute chest pain. In contrast, the latest iterations, including the European Society of Cardiology (ESC) 0/1-h algorithm, are simple. They are based on hs-cTn concentrations only and allow the safe rule-out or rule-in of AMI in up to 75% of patients. The purposes of this minireview are (a) to describe the best validated hs-cTn-based strategies for early rule-out of AMI, (b) to discuss the advantages and limitations of the different strategies, (c) to identify patient subgroups requiring particular attention, (d) to recognize challenges for widespread clinical implementation, and (e) to provide guidance on strategies for their safe and effective clinical implementation. Physicians and institutions may choose among several well-validated rule-out algorithms. The ESC 0/1-h algorithm for hs-cTnT or hs-cTnI seems to be the most attractive option today. It best balances safety and efficacy, and it has been derived and validated for all currently available hs-cTnT/I assays, facilitating widespread clinical implementation.

Optimizing the Use of High-Sensitivity Troponin Assays for the Early Rule-out of Myocardial Infarction in Patients Presenting with Chest Pain: A Systematic Review.

We assessed the accuracy and clinical effectiveness of high-sensitivity cardiac troponin (hs-cTn) assays for early rule-out of non-ST-segment elevation myocardial infarction (NSTEMI) in adults presenting with acute chest pain. Sixteen databases were searched to September 2019. Review methods followed published guidelines. The bivariate model was used to estimate summary sensitivity and specificity with 95% confidence intervals for meta-analyses involving 4 or more studies, otherwise random-effects logistic regression was used. Thirty-seven studies (124 publications) were included in the review. The hs-cTn test strategies evaluated in the included studies were defined by the combination of 4 factors (assay, number of tests, timing of tests, and threshold concentration or change in concentration between tests). Clinical opinion indicated a minimum acceptable sensitivity of 97%. A single test at presentation using a threshold at or near the assay limit of detection could reliably rule-out NSTEMI for a range of hs-cTn assays. Serial testing strategies, which include an immediate rule-out step, increased the proportion ruled out without loss of sensitivity. Finally, serial testing strategies without an immediate rule-out step had excellent sensitivity and specificity, but at the expense of the option for immediate patient discharge. Test strategies that comprise an initial rule-out step, based on low hs-cTn concentrations at presentation and a minimum symptom duration, and a second step for those not ruled-out that incorporates a small absolute change in hs-cTn at 1, 2, or 3 hours, produce the highest rule-out rates with a very low risk of missed NSTEMI. CRD42019154716.

Type 2 Myocardial Infarction: Evolving Approaches to Diagnosis and Risk-Stratification.

Type 2 myocardial infarction (T2MI) is frequently encountered in clinical practice and associated with adverse outcomes. T2MI occurs most frequently due to noncoronary etiologies that alter myocardial oxygen supply and/or demand. The diagnosis of T2MI is often confused with acute nonischemic myocardial injury, in part because of difficulties in delineating the nature of symptoms and misunderstandings about disease categorization. The use of objective features of myocardial ischemia using electrocardiographic (ECG) or imaging abnormalities may facilitate more precise T2MI diagnosis. High-sensitivity cardiac troponin (hs-cTn) assays allow rapid MI diagnosis and risk stratification, yet neither maximum nor delta values facilitate differentiation of T2MI from T1MI. Several investigational biomarkers have been evaluated for T2MI, but none have robust data. There is interest in evaluating risk profiles among patients with T2MI. Clinically, the magnitude of maximum and delta cTn values as well as the presence and magnitude of ischemia on ECG or imaging is used to indicate disease severity. Scoring systems such as GRACE, TIMI, and TARRACO have been evaluated, but all have limited to modest performance, with substantial variation in time intervals used for risk-assessment and endpoints used. The diagnosis of T2MI requires biomarker evidence of acute myocardial injury and clear clinical evidence of acute myocardial ischemia without atherothrombosis. T2MIs are most often caused by noncoronary etiologies that alter myocardial oxygen supply and/or demand. They are increasingly encountered in clinical practice and associated with poor short- and long-term outcomes. Clinicians require novel biomarker or imaging approaches to facilitate diagnosis and risk-stratification.

Abstract 17152: Artificial Intelligence ECG for the Detection of Cardiac Injury as Confirmed by High Sensitivity Cardiac Troponin T-Concentrations

Background: High-sensitivity cardiac troponin (hs-cTn) assays quantify cTn in patients at very low concentrations. Myocyte injury due to ischemia or other pathologies cause blood levels to increase, which is prognostic. A noninvasive, rapid, broadly available, home-based test to detect hs-cTn increases would facilitate risk-stratification. Since myocyte injury is associated with ECG changes, we hypothesized an artificial intelligence ECG (AI-ECG) could non-invasively predict current or impending hs-cTnT elevations. Objective: To develop an AI-ECG convolutional neural network (CNN) to detect an abnormal hs-cTnT (5 th Gen cTnT, Roche Diagnostics) concentration using a 12-lead ECG, and a single lead ECG (lead I), which would enable smartphone, home-based detection. Methods: We developed single lead and 12-lead ECG CNNs to detect a) hs-cTnT concentrations that were at or above the 6ng/L limit that can be reported b) above the 99 th percentile upper limits of &gt;15ng/L for men and &gt;10ng/L for women. All ECGs were recorded within one hour of the hs-cTnT measurements. We used 73,012 ECG and hs-cTnT pairs from 47,542 unique patients to train the network, 9031 ECGs from 5,811 patients for internal validation to optimize hyperparameters, and 18,276 ECG and hs-cTnT pairs from 11,904 different patients as a holdout test set to determine the area under the receiver-operator curve (AUC). Results: The mean age was 63.9±17.5 years, and 30,348 of the 59,446 patients (51%) were male. Of the 91,288 hs-cTnT pairs 73,271 (80.2%) were above 6ng/L and 50,799 (55.6%) are above the 99 th percentile. In the test set, the AUC for the detection of a hs-cTnT level higher than 6ng/L was 0.88 using the 12 lead ECG and 0.834 with the single lead. For the detection of hs-cTnT level above of 99 th percentile, the 12 lead ECG AUC was 0.853 and the single lead was 0.806. Conclusion: The AI-ECG permits detection of levels of hs-cTnT consistent with myocardial injury. This may allow a home-based, non-invasive test that would be massively scalable and could further enhance rapid-risk stratification and patient triage with potentially significant cost reductions and enable novel triage strategies at sites without hs-cTn assays.

Rise and fall of high-sensitivity cardiac troponin T after coronary artery bypass grafting surgery in relation to current definitions of myocardial infarction: a systematic review and meta-analysis

Abstract Background Cardiac troponins are the preferred biomarkers for the diagnosis of myocardial infarction (MI) and play an important role in coronary artery bypass grafting (CABG) related MI (type 5 MI). Different cut-off values, as defined by multiples of the 99th percentile upper reference limit (URL) for isolated and non-isolated troponin elevations have been proposed. Also, these definitions are based on arbitrarily chosen and varying values (3rd and 4th Universal definition: 10xURL, Society for Cardiovascular Angiography and Interventions (SCAI): 35 and 70xURL) and electrocardiographical or imaging findings. In addition to the controversy in MI definitions, the introduction of high-sensitivity cardiac troponin (hs-cTn) assays and their subsequent lower thresholds warrant a thorough re-assessment of hs-cTn dynamics after CABG. Purpose To evaluate the rise and fall of hs-cTn after CABG in relation to the definitions of myocardial infarction. Methods Studies published between 2008 and 2020 reporting hs-cTn concentrations in relation to CABG were searched through Pubmed and reviewed by 2 independent screeners. The search terms were “coronary artery bypass” AND “high-sensitivity cardiac troponin”, including alternative names and abbreviations. Inclusion criteria were the use of a hs-cTn assay in the postoperative phase, either for cardiac troponin T or I. This study was performed in agreement with the PRISMA guidelines. Results Out of 37 screened studies, 15 studies were included (2860 patients). The overall preoperative hs-cTnT concentration (median, 25th-75th percentile) was 43.5 (16.3–57.9) ng/L. Subsequently, in &amp;gt;80% of CABG patients, preoperative hs-cTnT was elevated &amp;gt;14 ng/L. Hs-cTnT was highly variable over time, with a peak of 408.7 (14.9–717.2) ng/L 6–8 h after CABG. Postoperative peak hs-cTnT concentrations rose &amp;gt;10xURL (Universal definition) in 100% of CABG patients. Peak hs-cTnT &amp;gt;35xURL and ±20% &amp;gt;70xURL (SCAI definition) during the first 48 h was 30% and ∼20%, respectively (estimated from data depicted in Figure 1). Electrocardiographic and imaging findings were available for only 1 study (554 patients). Overall 30-day mortality was 1.7 (0.8–4.0)%, reported by 7 studies (2291 patients). Data regarding the association of hs-cTnT and clinical outcome was reported by 1 study. As only 4 studies (217 patients) reported on the results of hs-cTnI, using assays from different vendors, a meta-analysis for hs-cTnI could not be performed. Conclusion The different definitions of type 5 MI propose arbitrarily chosen cTn cut-off values, varying enormously between the definitions. The current thresholds may not apply to the majority of CABG patients, since &amp;gt;80% had elevated preoperative hs-cTnT. Furthermore, hs-cTnT obtained within 48 h after CABG is highly variable over time. Therefore, further research is needed to establish clinically relevant hs-cTn thresholds and timing of sampling for a more accurate diagnosis of CABG procedure related MI. Figure 1 Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ZonMw Veni grant

Family history of coronary artery disease is associated with acute coronary syndrome in 28,188 chest pain patients

The value of family history of coronary artery disease (CAD) in diagnosing acute coronary syndrome (ACS) in chest pain patients is uncertain, especially in relation to high-sensitivity assays for cardiac troponin T (hs-cTnT), which have improved ACS diagnostics. Our objective was to investigate the association between verified family history of CAD and ACS in chest pain patients, overall and in different strata of initial hs-cTnT. Data on chest pain patients visiting four emergency departments in Sweden during 2013-2016 were cross-referenced with national registers of kinship, diseases and prescriptions. Family history of early CAD was defined as the occurrence of myocardial infarction or coronary revascularization before the age of 55 years in male and 65 years in female first-degree relatives. The outcome was combined including ACS and cardiovascular death within 30 days of presentation. Of 28,188 patients, 4.7% of patients had ACS. In total, 8.2% and 32.4% had a family history of early and ever-occurring CAD, respectively. Family history of CAD was positively associated with the outcome, independently of age, gender, cardiovascular risk factors and electrocardiogram findings. The strongest association was observed for family history of early CAD (odds ratio 1.62, 95% confidence interval 1.35-1.94). Stronger associations were observed in young patients (e.g. <65 years) and in patients with non-elevated initial hs-cTnT levels (p-value for interaction = 0.004 and 0.001, respectively). Family history of CAD is associated with ACS in chest pain patients, especially in patients of young age or with non-elevated initial hs-cTnT levels.

Sex-specific effects of implementing a high-sensitivity troponin I assay in patients with suspected acute coronary syndrome: results from SWEDEHEART registry

Using high-sensitivity cardiac troponin (hs-cTn) assays with sex-specific 99th percentiles may improve management of patients with suspected acute myocardial infarction (AMI). We investigated the impact of transitioning from a conventional troponin I assay to a high-sensitivity assay with sex-specific thresholds, in patients with suspected acute coronary syndrome admitted to Swedish coronary care units. Based on data from SWEDEHEART registry (females, n = 4,819/males, n = 7,670), we compared periods before and after implementation of hs-cTnI assay (Abbott) using sex-specific 99th percentiles. We investigated differences on discharge diagnosis, in-hospital examinations, treatments, and clinical outcome. Upon implementation of the hs-cTnI assay, proportion of patients with troponin levels above diagnostic AMI threshold increased in women and men by 24.3% versus 14.8%, respectively. Similarly, incidence of AMI increased by 11.5% and 9.8%. Diagnostic interventions and treatments increased regardless of sex. However, these associations did not persist following multivariable adjustment, probably due to the effect of temporal management trends during the observation period. Overall, no risk reduction on major adverse cardiovascular events was observed (HR: 0.91 [95% CI 0.80–1.03], P = 0.126). The implementation of hs-cTnI assay together with sex-specific 99th percentiles was associated with an increase in incidence of AMI regardless of sex, but had no major impact on clinical management and prognosis.

Optimal Detection of Acute Myocardial Injury and Infarction with Cardiac Troponin: Beyond the 99th Percentile, into the High-Sensitivity Era.

Cardiac troponin (cTn) is the biomarker of choice for the diagnosis of acute myocardial infarction (MI); use of this biomarker has centered around the 99th percentile upper reference limit (URL) for healthy populations. Recent development and regulatory approval of high-sensitivity cardiac troponin (hs-cTn) assays have required a fresh look at utilization of the 99th percentile URL. This review covers issues regarding the 99th percentile URL and approaches for use of cTn as biomarker for detecting cardiac injury and diagnosis of acute myocardial infarction. Development of hs-cTn assays has allowed determination and use of sex-specific 99th percentile URLs for assessing cardiac injury and increased the utility of cTn values below the 99th percentile URL. This improved analytical performance for hs-cTn assays has allowed for development of accelerated diagnostic protocols (ADPs) for rapid assessment and disposition of patients based on serial sampling of cTn for use in acute MI diagnosis as soon as 0-1h after clinical presentation. The 99th percentile URLs of cTn is essential for detecting cardiac injury; however, use of the 99th percentile URLs in the era of hs-cTn results may be modified. ADPs have the potential to substantially decrease the time many patients spend under evaluation for acute MI, thereby potentiating improvement in patient satisfaction, decreased healthcare costs, and reducing the burden on emergency departments.

Ideal high sensitivity troponin baseline cutoff for patients with renal dysfunction.

High-sensitivity cardiac troponin assays (hs-cTn) aid in diagnosis of myocardial infarction (MI). These assays have lower specificity for non-ST Elevation MI (NSTEMI) in patients with renal disease. Our objective was to determine an optimized cutoff for patients with renal disease. We conducted an a priori secondary analysis of a prospective FDA study in adults with suspected MI presenting to 29 academic urban EDs between 4/2015 and 4/2016. Blood was drawn 0, 1, 2-3, and 6-9h after ED arrival. We recorded cTn and estimated glomerular filtrate rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration equation. The primary endpoint was NSTEMI (Third Universal Definition of MI), adjudicated by physicians blinded to hs-cTn results. We generated an adjusted hscTn rule-in cutoff to increase specificity. 2505 subjects were enrolled; 234 were excluded. Patients were mostly male (55.7%) and white (57.2%), median age was 56years 472 patients [20.8%] had an eGFR <60mL/min/1.73m2. In patients with eGFR <15mL/min/1.73m2, a baseline rule-in cutoff of 120ng/L led to a specificity of 85.0% and Positive Predictive Value (PPV) of 62.5% with 774 patients requiring further observation. Increasing the cutoff to 600ng/L increased specificity and PPV overall and in every eGFR subgroup (specificity and PPV 93.3% and 78.9%, respectively for eGFR <15mL/min/1.73m2), while increasing the number (79) of patients requiring observation. An eGFR-adjusted baseline rule-in threshold for the Siemens Atellica hs-cTnI improves specificity with identical sensitivity. Further study in a prospective cohort with higher rates of renal disease is warranted.

Analytical and clinical characterization of a novel high-sensitivity cardiac troponin assay in a United States population

BackgroundCardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and clinical diagnostic characteristics of the ACCESS hsTnI assay in a United States (US) population. MethodsAll measurements and studies were conducted using a lithium heparin matrix. Sex-specific 99th percentile upper reference limits (URLs) were determined for 1089 healthy women (54.6%) and men using non-parametric statistics. High-sensitivity (hs) performance was assessed to determine if the total CV was ≤10% at sex-specific URLs, and if ≥50% of cTnI values for each sex exceeded the assay’s limit of detection (LoD). Precision, analytical measurement range, high-dose hook effect, and endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization included serial sampling of 1854 suspected AMI subjects presenting to 14 US Emergency Departments. AMI was adjudicated by a panel of expert cardiologists. The study’s only exclusion was end stage renal disease. Results99th percentile URLs were 11.6-, 19.8- and 17.5-ng/L for respective female, male and all-subject populations. Total %CV was <8% from 6.8 to 19,000 ng/L, and <6% at sex-specific 99th percentiles; ≥99% of ACCESS hsTnI values for each sex exceeded the LoD. No high-dose hook effect or endogenous/exogenous interferences were identified. A comparison of Baseline samples collected at ≤1 h and any-time after presentation, found 4% lower sensitivity for AMI than with earlier sampling. For 1–9 h post presentation, the sensitivity was >90%, specificity >85%; and negative and positive predictive value were ≥99% and >60%, respectively. ConclusionAnalytical and clinical performance of the ACCESS hsTnI assay meets the definition of a hs cTn method. The ACCESS hsTnI assay has good precision over a wide range, no significant interferences, and sensitivity >90% and NPV ≥99%. Performance is appropriate for aiding in AMI diagnosis.

Clinical evaluation of Ortho Clinical Diagnostics high-sensitivity cardiac Troponin I assay in patients with symptoms suggestive of acute coronary syndrome

BackgroundAs more companies obtain regulatory approval for high-sensitivity cardiac troponin (hs-cTn) assays there is an urgent need for independent analytical and clinical evaluations. To this end, we have evaluated Ortho Clinical Diagnostics’ hs-cTnI assay and compared it to their contemporary cTnI-ES assay in emergency department (ED) patients with suspected acute coronary syndrome (ACS). MethodsThe study cohort consisted of ED patients (n = 906) with symptoms suggestive of ACS who had Ortho hs-cTnI and cTnI-ES results at presentation and 3 h (with calculated delta (0–3 h) defined as the absolute concentration difference between paired results). The primary composite outcome was 7-day myocardial infarction (MI) or cardiovascular death, with secondary analyses performed for 7-day MI and index-MI. Analytical imprecision testing (i.e., coefficient of variation; CV), receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC), and diagnostic parameters (sensitivity/specificity/predictive values) were calculated. ResultsThe hs-cTnI assay had superior precision compared to the cTnI-ES assay below 5 ng/L in EDTA plasma (hs-cTnI CV ≤ 15% versus cTnI-ES CV ≥ 85%). The AUCs were higher for hs-cTnI as compared to cTnI-ES at 0 h (0.88 vs. 0.85), 3 h (0.94 vs. 0.92), and the delta (0–3 h) value (0.91 vs. 0.85) for the primary composite outcome (p < 0.05). At 3 h, the sensitivity/specificity for index-MI was ≥97%/≥82%, for 7-day MI was ≥89%/≥84%, and for the primary composite outcome was ≥90%/≥85% using the manufacturer’s sex-specific 99th-percentile cutoffs. ConclusionThe Ortho hs-cTnI assay has superior analytical and clinical performance over their contemporary cTnI-ES assay in evaluating ED patients with symptoms suggestive of ACS.