Sensitive Troponin Assays Research Articles

Comparing analytical outliers and the percent of emergency department patients with results above the 99th percentile upper reference limit for 2 conventional and one high sensitivity troponin assay

ObjectivesWe compared rates of analytical outliers, and percent of emergency department (ED) patients with cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL), for two conventional and one high sensitivity cTn assay. MethodsWe measured 3008 samples from 1931 ED patients by Roche e411 4th generation Troponin T (cTnT); and Abbott STAT Troponin I (cTnI) and high sensitivity troponin I (hscTnI) on an Architect i2000. Within 24h of initial measurement, samples were aliquoted, re-centrifuged, and repeated in duplicate by all methods. Outliers were defined as one or both replicates exceeding initial value by a critical difference (CD): where CD=z×2×SDanalytical (z=3.29 at a probability of 0.0005), and at least one replicate on a different side of 99th percentile URL compared to initial value. We also assessed percent of ED patients with values >99th percentile by all methods (excluding outliers), using both sex-neutral and sex-specific hscTnI URL. ResultsThe outlier rate for cTnI (3.66%) was significantly higher than the outlier rate for either cTnT (0.33%) or hscTnI (0.47%) (p<0.0001). More ED patients (33%) had elevated cTnT values compared to either cTnI (25%) or hscTnI (29%). Application of sex-specific URL did not change the percent of ED patients with >99th percentile hscTnI values. ConclusionAbbott STAT cTnI had more analytic outliers than Roche cTnT or Abbott hscTnI. Compared to cTnT, use of hscTnI will significantly decrease the percent of ED patients with elevated cTn values without increasing analytical outliers.

Serum Cardiac Troponin T Levels in Asymptomatic Elderly Nursing Home Residents

BackgroundThe definition of myocardial infarction relies on elevated troponin levels. However, elevated levels of high sensitive cardiac troponin (hs-cTnT) assays have been reported in elderly patients without acute myocardial infarction. We sought to determine whether elevated hs-cTnT levels have a prognostic value in stable elderly subjects without any acute illness. MethodsThe study cohort included residents of a nursing home who were asymptomatic without any acute medical problem. Serum hs-cTnT levels were measured, and participants were divided into high and low hs-cTnT groups. We measured hs-cTnT levels of young healthy volunteers as well and compared them with hs-cTnT levels of those nursing home residents. ResultsFifty-seven nursing home residents and 14 young volunteers were included in the study. The average age of nursing home residents was 83 ± 14 years, compared with 37 ± 3 years of the volunteers. Levels of hs-cTnT were significantly higher in the elderly compared with the volunteers (0.02 ± 0.016 ng/mL vs 0.005 ± 0.0003 ng/mL; P < .001); accordingly, we chose a cutoff of 0.02 ng/mL hs-cTnT and divided the 57 patients into 2 subgroups for further evaluation. After adjustment for age, gender, and glomerular filtration rate, the hs-cTnT was still an independent predictor of 1-year mortality (relative risk 2.04 [95% conficence interval, 2.009-29.45], P = .003). ConclusionsMild elevations of hs-cTnT levels are common in elderly patients, and hs-cTnT level is an independent marker of mortality risk in this population. For patients older than 70 years, a different hs-cTnT cutoff is required (eg, higher than 0.014 ng/mL).

Developing a value proposition for high-sensitivity troponin testing

Laboratories are looking for ways that they can identify and deliver value through their service rather than just provide high quality test results. One way to demonstrate value has been described in the form of a value proposition where the application of a laboratory test is described explicitly in terms of the process of care and the patient outcomes. We have applied this concept to the use of high sensitivity troponin assays for the assessment of patients with suspected acute coronary syndrome. From a previously described framework we use a checklist to describe the various steps in the complete intervention or clinical pathway, demonstrating how the test should be used, highlighting key evidence in the literature that supports the intervention and list some of the measures which can be used to assess how well the intervention is being adopted and implemented. While the value proposition concept is based on the foundations of evidence based medicine it also requires collaboration between the laboratory and other stakeholders including clinicians to ensure that appropriate resources are applied across the complete clinical pathway in order to ensure its effectiveness.

High sensitivity troponin in the management of tachyarrhythmias.

The introduction of the highly sensitive troponin (hs-trop) assays into clinical practice has allowed for the more rapid diagnosis or exclusion of type 1 myocardial infarctions (T1MI) by clinicians, in addition type 2 myocardial infarctions (T2MI) are now more frequently detected. Tachyarrhythmias are one of the common causes of T2MI, the medium and long term outcome for this cohort of T2MI is yet to be clarified. Retrospective review of consecutive patients admitted with a diagnosis of either (a) non ST-elevation myocardial infarction (NSTEMI) or (b) tachyarrhythmia was performed. Data were collected on patient demographics and investigations. Patient mortality status was recorded through the Personal Demographics Service (PDS) via NHS Digital. A total of 704 patients were eligible for inclusion to the study. 264 patients were included in the study with a final discharge diagnosis of NSTEMI and 440 patients with a final discharge diagnosis of tachyarrhythmia. There was a significantly higher peak troponin in NSTEMI patients compared to the tachyarrhythmia troponin positive group (4552ng/L vs 571ng/L, p<0.001). Mortality was significantly higher in the troponin positive tachyarrhythmia patients than the troponin negative patients (54 vs 34, 26.2% vs 14.5%, log rank p=0.003), furthermore, the mortality of NSTEMI and troponin positive tachyarrhythmia patients was similar (55 vs 54, 20.8% vs 26.2%, log rank p=0.416). Only one patient (0.14%) was given a formal diagnosis of T2MI. These data suggest that troponin positive tachyarrhythmia is not a benign diagnosis, and has a mortality rate similar to NSTEMI. Formal labeling as T2MI is rare in real life practice. More investigation into the detection and management of T2MI and troponin positive arrhythmia patients is now warranted.

Significance of High-Sensitivity Troponin T After Elective External Direct Current Cardioversion for Atrial Fibrillation or Atrial Flutter

External transthoracic direct current (DC) cardioversion is a commonly used method of terminating cardiac arrhythmias. Previous research has shown that DC cardioversion resulted in myocardial injury as evidenced by increased levels of cardiac troponin, even though only minimally. Many of these studies were based on the outdated monophasic defibrillators and older, less sensitive troponin assays. This study aimed to assess the effect of external transthoracic DC cardioversion on myocardial injury as measured by the change in the new high-sensitivity cardiac troponin T (hs-cTnT) using the more modern biphasic defibrillators. Patients who were admitted for elective DC cardioversion for atrial fibrillation or atrial flutter were recruited. Hs-cTnT levels were taken before cardioversion and at 6 hours after cardioversion. A total of 120 cardioversions were performed. Median (twenty-fifth to seventy-fifth interquartile range) cumulative energy was 161 J (155 to 532 J). A total of 49 (41%) patients received a cumulative energy of 300 J or higher. The median hs-cTnT level before cardioversion was 7 ng/L (4 to 11 ng/L) and that after cardioversion was 7 ng/L (4 to 10 ng/L). A Wilcoxon signed-rank test showed no significant difference between pre- and post-cardioversion hs-cTnT levels (Z = -0.940, p = 0.347). In conclusion, external DC cardioversion did not result in myocardial injury within the first 6 hours as measured by high-sensitivity troponin T. Patients who are cardioverted and are found to have a significant increase in cardiac troponin after cardioversion should be assessed for causes of myocardial injury and not assumed to have myocardial injury due to the cardioversion itself.

TCT-629 The Association Between HsTrop and Tachyarrhythmias: Type 1 or Type 2 MI? The STRIPE-MI Study

The introduction of highly sensitive troponin (HsTrop) assays into clinical practice has resulted in a significant increase in the frequency of type 1 (T1MI) & type 2 (T2MI) myocardial infarction (MI) diagnoses in clinical practice. The accurate differential diagnosis of T1MI & T2MI is essential in

Sensitive Troponin I and Stress Testing in the Emergency Department for the Early Management of Chest Pain Using 2-Hour Protocol.

Despite improvements in identifying high-risk patients with non-ST segment ACS (acute coronary syndrome), low risk patients presenting with atypical chest pain and non-diagnostic Electrocardiogram (ECG) continued to undergo unnecessary admissions and testing. Since 1992, our chest pain protocol included using 4-hour serial biomarkers from ED admission in combination with stress testing to evaluate these patients. Our study aimed at determining whether a new accelerated diagnostic protocol using sensitive cardiac troponin I (cTnI) 2 hours after admission to the ED followed by stress testing is safe and effective in emergency settings, allowing for appropriate triage, earlier discharge and reducing costs. We conducted a single center randomized trial at Presence St. Francis Hospital Chest pain center in Evanston, Illinois enrolling sixty-four consecutive patients with atypical chest pain and non-diagnostic ECG, participants were randomized to accelerated 2 hrs protocol or our pre-existing 4-hrs protocol. Sixty patients completed the protocol and were randomized to either a 2-hour (29 patients) or 4-hour protocol using both I-STAT and PATHFAST cTnI (31 Patients). Troponin I was evaluated at 0 and at 2 hours from ED presentation with and additional draw for patients in the 4-hour rule out-group. Patients with normal serial biomarkers were then evaluated with stress testing and qualified for earlier discharge if the stress test was negative, while those with a positive biomarker at any time were admitted. Thirty-six patients had exercise treadmill stress test and 24 patients had either nuclear or Echo stress test. Fifty-three patients had a normal stress test and were discharged home. One patient in the 4-hour group with normal serial troponins developed ventricular tachycardia/fibrillation during the recovery period of a regular stress test. Six patients had a positive PATHFAST cTnI and a normal I-STAT cTnI at 2-hours. Two out of these six patients evaluated by coronary angiography. One patient had severe tortuous coronaries but no significant obstructive lesion and one had a severe CAD who needed Coronary artery bypass grafting (CABG). Three of the six patients had a normal stress test and one patient decided to leave without further testing. None of the patients with a normal stress test had a major cardiac event or adverse cardiac outcome at six-month follow up. This study demonstrates that the 2 hours accelerated protocol using high sensitivity Troponin assay at 0 and 2 hours with comprehensive clinical evaluation and ECG followed by stress testing might be successful in identifying low-risk patient population who may benefit from early discharge from ED reducing associated costs and length of stay.

The prognostic value of highly sensitive cardiac troponin assays for adverse events in men and women with stable heart failure and a preserved vs. reduced ejection fraction.

Circulating biomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). Given the current lack of biomarkers in HF with preserved ejection fraction (HFpEF), we aimed to investigate the prognostic performance of the newly developed high-sensitivity (hs) assays for cardiac troponin I (hsTnI) compared with troponin T (hsTnT) for adverse events in HFpEF vs. HF with reduced ejection fraction (HFrEF). Findings in these two HF subgroups were also compared with those in the recently defined HF with mid-range ejection fraction (HFmrEF) subgroup. Both hsTnI and hsTnT were measured in 1096 patients with HFrEF [left ventricular ejection fraction (LVEF) <50%; n = 853] or HFpEF (LVEF ≥50%; n = 243) enrolled in the Singapore Heart Failure Outcomes and Phenotypes (SHOP) study. Both troponin assays were more strongly associated with the composite endpoint (all-cause mortality or first rehospitalization for HF) in HFpEF than in HFrEF. The hsTnT assay provided the greatest additional prognostic value in HFpEF in comparison with hsTnI and NT-proBNP. TnI was more strongly associated with composite events in men with HFpEF [hazard ratio (HR) 3.33, 95% confidence interval (CI) 1.82-6.09; P < 0.001 per standard deviation (SD) increase in log-transformed hsTnI] than in women with HFpEF (HR 1.35, 95% CI 0.94-1.93; P = 0.10 per SD increase in log-transformed hsTnI). There is a potential role for the prognostic use of high-sensitivity troponin assays, particularly hsTnT, in men and women with HFpEF. The predictive association of hsTnI with outcome appears strongest in men with HFpEF.

The Prognostic Value of Heart Type Fatty Acid Binding Protein in Patients with Suspected Acute Coronary Syndrome: A Systematic Review.

Background:Heart type fatty acid protein (HFABP) is a cytosolic protein released early after acute coronary syndrome (ACS) even in the absence of myocardial necrosis.Objectives:The purpose of this systematic review was to determine whether HFABP levels in patients with suspected, or confirmed ACS, improve risk stratification when added to established means of risk assessment.Methods:We searched Medline, Pubmed and Embase databases from inception to July 2015 to identify prospective studies with suspected or confirmed ACS, who had HFABP measured during the index admission with at least 1 month follow up data. A prognostic event was defined as all-cause mortality or acute myocardial infarction (AMI).Results:7 trials providing data on 6935 patients fulfilled inclusion criteria. There were considerable differences between studies and this was manifest in variation in prognostic impact of elevated HFABP(Odds ratio range 1.2-15.2 for death). All studies demonstrated that HFABP provide unadjusted prognostic information and in only one study this was negated after adjusting for covariates. A combination of both negative troponin and normal HFABP conferred a very low event rate. No study evaluated the incremental value of HFABP beyond that of standard risk scores. Only one study used a high sensitive troponin assay.Conclusion:There was marked heterogeneity in prognostic impact of HFABP in ACS between studies reflecting differences in sampling times and population risk. Prospective studies of suspected ACS with early sampling of HFABP in the era of high sensitivity troponin are necessary to determine the clinical value of HFABP. HFABP should not currently be used clinically as a prognostic marker in patients with suspected ACS.

Abstract 4030A: S-PLEXSM Troponin I assay with fg/mL sensitivity

Abstract Cardiovascular toxicity is a potential complication of multiple anticancer therapies. Some drugs, such as anthracyclines, have been implicated in irreversible cardiac dysfunction. Cardiac troponin is a specific and sensitive marker of myocardial injury. Serum and plasma concentrations of troponin are often below the limits of detection in apparently healthy individuals. Sensitivity of troponin assays has improved by two orders of magnitude over the last several years, but few assays can detect basal levels of serum troponin in more than 50% of apparently healthy individuals, limiting the utility of the assay for early detection of low levels of cardiac damage. S-PLEX is a novel ultrasensitive immunoassay platform based on MSD’s MULTI-ARRAY® electrochemiluminescence technology. An S-PLEX cardiac troponin I assay was developed and analytically characterized for research use. Serum and plasma samples from 24 apparently healthy individuals, 90 individuals with cardiovascular complications, and 25 individuals receiving anthracycline chemotherapy were measured. The assay required 25 μL of sample per measurement and was run on the MESO® SECTOR S 600 and MESO QuickPlex® SQ 120 instruments. The lower limit of detection was determined to be 10 fg/mL and the limits of quantitation ranged from 31 fg/mL to 160,000 fg/mL. The assay was anchored to the NIST reference material SRM 2921. Control samples run at 3 levels (n=8 per plate, 8 plates, 2 days, 2 operators) had total CVs of 7% to 8% (n=64). Spike recovery and dilution linearity had recoveries between 80% and 120%. Specificity of the assay was demonstrated by analyte depletion using several commercially available anti-troponin specific antibodies. There was no detectable cross-reactivity to skeletal troponin. As expected, troponin I serum or plasma concentrations were high (~10,000 fg/mL to &amp;gt;160,000 fg/mL) for 90 individuals with cardiovascular complications. Troponin I serum concentrations in 25 samples from individuals receiving anthracycline chemotherapy had a median concentration of 306 fg/mL and a range of &amp;lt;10 to 5,820 fg/mL, comparable to a set of apparently healthy specimens (n=24) with a median concentration of 226 fg/mL and a range of &amp;lt;10 to 4,330 fg/mL. The S-PLEX troponin I assay was capable of detecting troponin in 44 of the 49 samples from individuals with no known cardiovascular disease. In conclusion, we have developed a highly specific and sensitive cardiac troponin I assay that is capable of accurately measuring the cardiac troponin I protein concentration in samples from individuals with known cardiovascular disease, as well as 90% of the apparently healthy individuals tested. This assay can be used to study low levels of cardiac troponin I in serum and plasma samples and may provide a useful research tool for the detection of cardiac troponin I, a biomarker linked to cardiac damage. Citation Format: Anahit Aghvanyan, Louis Gardner, Animesh Shukla, Thomas Miller, Su Wang, Sheldon Grove, Andrew Chow, Jessica Suschak, Sarah Wheeler, Anu Mathew, Martin K. Stengelin, Jacob N. Wohlstadter. S-PLEXSM Troponin I assay with fg/mL sensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4030A. doi:10.1158/1538-7445.AM2017-4030A

Unstable Angina in the Era of Cardiac Troponin Assays with Improved Sensitivity—A Clinical Dilemma

BackgroundThere is an expectation that with the adoption of more sensitive cardiac troponin (cTn) assays, unstable angina would become a rarity. However, recent data from the SWEDEHEART registry demonstrated that 15% of patients admitted with non-ST-elevation acute coronary syndrome still were regarded as having unstable angina. We aimed to further investigate the clinical characteristics and outcome of these patients. MethodsThis was a retrospective, registry-based analysis (SWEDEHEART) including 3204 unstable patients, 18,194 non-ST-elevation myocardial infarction (NSTEMI) patients, and 977 controls without acute cardiovascular disease. All patients had available data on peak cTnT levels (more sensitive assay) and 1-year outcome. ResultsThe annual proportions of patients with unstable angina (2009-2013) among those with non-ST-elevation acute coronary syndrome ranged from 9.4% to 15.3%. Only 1239 unstable angina patients (39.7%) had a peak cTnT level ≤14 ng/L. Patients with unstable angina tended to be younger than those with NSTEMI but had higher prevalence of most cardiovascular risk factors and more advanced coronary artery disease. Compared with controls, the adjusted hazard ratios (95% confidence interval) regarding major cardiovascular events were 2.97 (1.30-6.78) and 5.44 (2.54-11.65) in unstable angina patients with peak cTnT ≤14 ng/L and >14 ng/L, respectively. ConclusionThe diagnosis of unstable angina is still commonly used, even in the era of more sensitive cTn assays. Minor cTnT elevation is common, which makes unstable angina difficult to distinguish from NSTEMI. Patients with unstable angina have a nonneglectable cardiovascular risk. We suggest that the clinical management of patients presenting with unstable symptoms should depend on their estimated cardiovascular risk rather than on strictly applied diagnostic criteria.

Use of copeptin for rapid rule-out of acute myocardial infarction.

Copeptin is currently understood as a quantitative marker of endogenous stress. It rises rapidly in multiple acute disorders including acute myocardial infarction. As a single variable, it has only modest diagnostic accuracy for acute myocardial infarction. However, the use of copeptin within a dual-marker strategy together with conventional cardiac troponin increases the diagnostic accuracy and particularly the negative predictive value of cardiac troponin alone for acute myocardial infarction. The rapid rule-out of acute myocardial infarction is the only application in acute cardiac care mature enough to merit consideration for routine clinical care. However, the dual-marker approach seems to provide only very small incremental value when used in combination with sensitive or high-sensitivity cardiac troponin assays. This review aims to update and educate regarding the potential and the procedural details, as well as the caveats and challenges of using copeptin in clinical practice.

69 Do high sensitivity troponin assays actually result in a shorter hospital stay in a real world clinical setting?

BackgroundHospitals face an immense bed pressure this winter. Admission to hospital for rule-out of MI is common, and early rule-out may expedite patient turnover.AimsTo assess the time to discharge following...

67 Reducing chest pain admissions using a 1 hour high-sensitivity troponin-t pathway

Introduction Chest pain is the most common presenting complaint to emergency departments in the United Kingdom. Existing management pathways for suspected Acute Coronary Syndrome utilise serial cardiac troponin measurement, typically at admission and again at 6 or 12 hours, often necessitating inpatient admission. Recent work has validated the use of a high sensitivity Troponin assay to enable risk stratification using presentation and 1 hour Troponin concentrations, with a view to reducing admissions and facilitating safe, early discharge. Methods A 1 hour troponin pathway was implemented in a District General Hospital (DGH) at Gloucestershire Royal Hospital, using a High Sensitivity Troponin-T assay (hs-cTnT, Elecsys assay, Roche Diagnostics®). This was trialled in the Emergency Department for 56 consecutive hours. Patients with suspected ACS had a plasma hs-cTnT concentration measured at presentation, and if necessary a repeat test was performed at 1 hour. Patients were then stratified using the 1 hour Troponin pathway into low, medium and high risk groups. All instances of hs-cTnT performed for 112 consecutive hours were included in analysis, 56 hours of the trial period and 56 hours of control data for comparison. We reviewed the cases to assess the performance and safety of the 1 hour troponin pathway using primary outcome data of discharge rates and subsequent myocardial infarction or death within 30 days. Results 140 patients had a hs-cTnT performed. 51 cases did not present with chest pain or were admitted with a non-ACS diagnosis and were excluded from further analysis. During the trial period 21 (54%) of patients were discharged directly home from the Emergency Department, compared with 15 (30%) during the control period (p=0.02; n-1 two-proportion (Asâ€i2) analysis). There were no documented cases of subsequent myocardial infarction or death within 30 days follow up. Conclusions There was a substantial increase in the percentage of patients discharged home from the Emergency Department during the 1 hour Troponin trial compared with the control period, demonstrating that this pathway facilitates rapid decision making and early discharge. Our estimate is that a further 3 admissions could have been avoided during the trial period if the pathway had been strictly implemented, and we predict that further education and familiarity for the Emergency Department staff will improve this. There were no cases of acute myocardial infarction or death in our cohort at 30 days, meaning that patient safety does not appear to be comprised. To our knowledge this is the first trial of a 1 hour Troponin pathway in a UK DGH, and demonstrates that a 1 hour model can be applied to an unselected population and can safely reduce acute hospital admissions.

HIGH-SENSITIVITY CARDIAC TROPONIN AND THE CLASSIFICATION OF MYOCARDIAL INFARCTION

Background: Guidelines recommend classification of myocardial infarction due to plaque rupture (type 1) or myocardial oxygen supply-demand mismatch (type 2). Whether more sensitive cardiac troponin assays can help to differentiate between subtypes is uncertain. Methods: Consecutive patients (n=4,

Fast track protocols using highly sensitive troponin assays for ruling out and ruling in non-ST elevation acute coronary syndrome.

The introduction of "highly sensitive" cardiac troponin assays (hsTn) has reinforced the evidence that only serial testing incorporated in running algorithms allows a more accurate diagnosis of acute myocardial infarction. In this report, we consider the available evidence supporting the use of fast track protocols for ruling out and ruling in non-ST elevation myocardial infarction (NSTEMI) and compare it with the content of recently released guideline by the European Society of Cardiology, noting some uncomfortable aspects that need urgent clarification and/or revision. Firstly, the guideline drafters have to reconsider the available evidence that does not permit to assign the same class and level of evidence to the very well-validated 0-3 h algorithm and to the 0-1 h algorithm. In agreement with the validity of available data, the limitations of fast track protocols, in particular of the 0-1 h algorithm for NSTEMI rule-in, calls for caution. Secondly, as the current diagnostics guidance by the UK National Institute for Health and Care Excellence recommends, rapid diagnostic protocols should be performed only using well-validated hsTn; recommending the use of an assay before being commercially available is not fair and scientifically sound.

Comparison of high sensitive and conventional troponin assays in diagnosis of acute myocardial infarction

Abstract Introduction We aimed to compare the positive predictive values (PPV) and negative predictive values (NPV) of four cardiac troponin assays in the diagnosis of AMI in Turkish population. Methods This study is an observational comparative study, which is performed between 2012 and 2013 (527 patients). Troponin levels were measured with chemiluminescence Cobas troponin T assay, immunofluorescence Triage troponin I assay and immunochromatographic Toyo troponin I assay. Results Sensitivity and specificity of immunofluorometric assay (Radiometer) are 56.82% and 71.34%; immunochromatographic assay (Toyo) are 29.4% and 88.62%, immunofluorescence assay (Triage) are 47.13% and 76.12%, chemiluminescence assay (Roche) are 60.49 and 67.42%, respectively. PPV, NPV and positive likelihood ratios (LR+) of immunofluorometric assay (Radiometer) are 45.5%, 79.7% and 1.98, immunochromatographic assay (Toyo) are 51.5%, 75.4% and 2.58, immunofluorescence assay (Triage) are 46.5%, 76.6% and 1.97, chemiluminescence assay (Roche) are 45.8%, 78.9% and 1.86, respectively. In four assays, troponin levels were statistically significant higher in AMI positive group in comparison to negative group (p&lt;0.001 for all). Conclusion There was no statistically significant difference between these troponin methods in comparisons of PPV and NPV in the diagnosis of AMI, but low sensitivity of Triage and Toyo assays should be considered.

Myocardial Infarction Type 2 and Myocardial Injury.

The development and implementation of sensitive and high-sensitivity cardiac troponin assays has not only expedited the early ruling in and ruling out of acute myocardial infarction, but has also contributed to the identification of patients at risk for myocardial injury with necrosis, as confirmed by the presence of cardiac troponin concentrations above the 99th percentile. Myocardial injury with necrosis may occur either in the presence of overt ischemia from myocardial infarction, or in the absence of overt ischemia from myocardial injury accompanying other conditions. Myocardial infarction type 2 (T2MI) has been a focus of attention; conceptually T2MI occurs in a clinical setting with overt myocardial ischemia where a condition other than an acute atherothrombotic event is the major contributor to a significant imbalance between myocardial oxygen supply and/or demand. Much debate has surrounded T2MI and its interrelationship with myocardial injury. We provide a detailed overview of the current concepts and challenges regarding the definition, diagnosis, management, and outcomes of T2MI, as well as the interrelationship to myocardial injury, and emphasize several critical clinical concepts for both clinicians and researchers moving forward. T2MI and myocardial injury are frequently encountered in clinical practice and are associated with poor outcomes in both the short term and long term. Diagnostic strategies to facilitate the clinical distinction between ischemic myocardial injury with or without an acute atheroma-thrombotic event vs non-ischemic-mediated myocardial injury conditions are urgently needed, as well as evidence-based therapies tailored toward improving outcomes for patients with T2MI.

Early Rule-Out and Rule-In Strategies for Myocardial Infarction.

Patients with chest pain comprise a large proportion of emergency presentations and place a major burden on healthcare resources. Therefore, efforts to safely and rapidly identify those with and without acute myocardial infarction (AMI) are needed. The challenge for clinicians is to accurately identify patients with acute coronary syndromes, while balancing the need to safely and rapidly reassure and discharge those without serious conditions. This review summarizes the evidence to date on optimum accelerated strategies for the rule-in and rule-out of AMI, using strategies focused on optimum use of troponin results. Evidence based on both sensitive and highly sensitive troponin assay results is presented. The use of novel biomarkers is also addressed and the combination of biomarkers with other clinical information in accelerated diagnostic strategies is discussed. The majority of patients, who are not at risk of myocardial infarction or other serious harm, may be suitable for discharge directly from the emergency setting using approaches focused on troponin algorithms and accelerated diagnostic protocols. Evidence about the clinical and health economic impact of use of such strategies is needed, as they may have major benefits for both patients and healthcare providers.

Strategies to overcome misdiagnosis of type 1 myocardial infarction using high sensitive cardiac troponin assays.

High sensitive cardiac troponin assays have become the gold standard in the diagnosis of an acute type 1 myocardial infarction (MI) in the absence of ST-segment elevation. Several acute or chronic conditions that impact cardiac troponin levels in the absence of a MI might lead to a misdiagnosis of MI. For example, patients with impaired renal function as well as elderly patients often present with chronically increased cardiac troponin levels. Therefore, the diagnosis of MI type 1 based on the 99th percentile upper limit of normal threshold is more difficult in these patients. Different diagnostic approaches might help to overcome this limitation of reduced MI specificity of sensitive troponin assays. First, serial troponin measurement helps to differentiate chronic from acute troponin elevations. Second, specific diagnostic cut-offs, optimized for a particular patient group, like elderly patients, are able to regain specificity. Such an individualized use and interpretation of sensitive cardiac troponin measurements improves diagnostic accuracy and reduces the amount of misdiagnosed MI type 1.