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Requests for reprints should be addressed to Allan S. Jaffe, MD, Mayo Clinic, Division of Cardiovascular Diseases, Gonda 468, 200 1st St, SW, Rochester, MN 55905.
The recent approval of the fifth-generation cardiac troponin T assay, which has characteristics clinically of a high-sensitivity assay, has led to concern that the problems of increased sensitivity will be greater than the benefits. This will not be the case if cardiology, emergency medicine, and laboratory medicine combine to develop procedures for use of the assay. We advocate sex-specific 99th percentile upper reference limit values of 15 ng/L for men and 10 ng/L for women. We suggest a 2-hour rule-out strategy, including a value less than the 99th percentile upper reference limit and the lack of a change in values of <4 ng/L. Those with values >100 ng/L and or a changing pattern of values ≥10 ng/L are a population much more likely to have acute myocardial infarction. Most of the increment in elevated values will occur not in those with acute coronary problems but in those with primary cardiac disease like heart failure and those with primary noncardiac problems. The former belong on a cardiac service because they are at high risk. The latter should have therapy on the service most apt to provide optimal care for their primary diagnosis, with cardiac consultation as needed.
ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
Because of our work in this area we often are asked how to optimize the advantages of more rapid evaluations for suspected myocardial infarction, while avoiding the potential problems related to the increased sensitivity of the assay. This article provides an evidence-based synopsis to guide clinicians in the use of hs-cTnT in acute cardiac care. It is not a review, although we will provide a rationale for our recommendations. We have advocated approaches that minimize patient risk. We will not address the many additional important uses of hs-cTnT in primary and secondary prevention that will become applicable over time.
Analytic Characteristics
Some key analytic characteristics must be understood to use high-sensitivity assays properly
IFCC Task Force on Clinical Applications of Cardiac Bio-Markers Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care.
and can be found at IFCC.org. The hs-cTnT assay is an enzyme-linked immunosorbent assay with 2 monoclonal antibodies to amino acids 125-131 and 136-147 for the biotinylated tag antibody; the latter is a mouse–human chimera.
Table 1Key Analytic Characteristics of the hs-cTnT Assay
Analytic Characteristic
Definition
Value(s) (ng/L) According to Manufacturer
Comment
Cobas e 411
Cobas e 601 and cobas e 602
Limit of blank, LoB
Highest cTn concentration found in samples containing no analyte
3 ng/L
2.5 ng/L
Values cannot be reported in the United States.
Limit of detection, LoD
Lowest cTn concentration distinguishable from the LoB in samples containing a low cTn concentration
5 ng/L
3 ng/L
Values cannot be reported in the United States.
Limit of quantitation, LoQ
Lowest concentration with a %CV ≤20%
6 ng/L
Below this threshold, total imprecision (%CV) is generally not acceptable for clinical practice. FDA will only allow reporting to this level.
99th percentile upper reference limit
Concentration threshold endorsed by clinical practice guidelines to support the diagnosis of acute myocardial injury and myocardial infarction
Suggested thresholds:
Overall: 19 ng/L
Overall: 14 ng/L
Women: 14 ng/L
Women: 10 ng/L
Men: 22 ng/L
Men: 15 ng/L
CV = coefficient of variation; FDA = US Food and Drug Administration; hs-cTnT = high-sensitivity cardiac troponin T.
Compared with the fourth-generation assay, a value of 30 ng/L (values for hs-cTn assays are reported as whole numbers in ng/L) with hs-cTnT equates to a value of 0.01 ng/mL.
The assays are harmonized at values >100 ng/L; a value of 100 ng/L is the same as 0.1 ng/mL. We term these values “anchor values.”
The International Federation of Clinical Chemistry criteria indicate that hs-cTn assays should have a coefficient of variation <10% at the 99th percentile upper reference limit (URL) and detect values above the limit of detection (LoD) in ≥50% of normal subjects.
IFCC Task Force on Clinical Applications of Cardiac Bio-Markers Cardiac troponin assays: guide to understanding analytical characteristics and their impact on clinical care.
The limit of quantitation (LoQ) is the lowest concentration measureable with a coefficient of variation ≤ 20%. This is the lowest limit the FDA will allow to be reported. For hs-cTnT, the manufacturer reports a LoB and LoD of 3 ng/L and 5 ng/L, respectively, for the cobas e 411 analyzer, and 2.5 ng/L and 3 ng/L for the cobas e 601 and cobas e 602 analyzers. The LoQ is 6 ng/L for both.
The 99th Percentile of hs-cTnT and the Use of Sex-Specific Cutoffs
The 99th percentile of cTn is the concentration endorsed by clinical practice guidelines to support the diagnosis of acute myocardial injury and acute myocardial infarction.
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients without persistent ST-segment elevation of the European Society of Cardiology (ESC).
2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
In all studies men have higher 99th percentiles than women (Table 2) (supplemental references available online). Following our review of the studies and our own recent evaluation of an American Association of Clinical Chemistry universal sample bank, we endorse the use of the values of 10 ng/L for women and 15 ng/L for men, as advocated in the original assay validation studies.
This allows prior literature to be applied in the United States. We concur with the recommendations of the Universal Definition and the International Federation of Clinical Chemistry TF-CB to use sex-specific 99th percentile values for hs-cTn assays.
Mair J., Lindahl B., Müller C., et al. What to do when you question cardiac troponin values. Eur Heart J Acute Cardiovasc Care. doi:10.1177/2048872617708973.
If suspected, an additional sample should be sent to the laboratory to consider recentrifugation, dilution studies, and/or incubation with heterophilic blocking reagents or polyethylene glycol precipitation to remove high-molecular mass interferents; or testing with an alternative hs-cTn assay for mismatch.
Mair J., Lindahl B., Müller C., et al. What to do when you question cardiac troponin values. Eur Heart J Acute Cardiovasc Care. doi:10.1177/2048872617708973.
For hs-cTnT, analytic interferences include 1) hemolysis, which can falsely lower hs-cTnT concentrations; 2) the potential effect of biotin, an over-the-counter water-soluble B-complex vitamin that can lead to potential false-negative results; and 3) occasional false-positive increases related to skeletal muscle disease.
Mair J., Lindahl B., Müller C., et al. What to do when you question cardiac troponin values. Eur Heart J Acute Cardiovasc Care. doi:10.1177/2048872617708973.
Risk-Stratification Strategies in Acute Cardiac Care
Our recommendations are predicated on the data with hs-cTnT on the assumption that careful clinical judgment will be applied at every step. No approach that ignores this important clinical caveat can ever be successful.
Numerous studies confirm the use of the LoB and/or LoD to rule out acute myocardial injury using a single hs-cTnT measurement at presentation, with high sensitivity and negative predictive value (NPV).
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.
A recent meta-analysis including 9241 patients showed that nearly one-third of patients qualify, with a pooled sensitivity and NPV of 98.7% (95% confidence interval [CI], 96.6-99.5) and 99.3% (95% CI, 97.3-99.8) in low-risk patients.
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.
The strategy should be reserved for low-risk patients and those who present at least 2 hours after the onset of symptoms because of data suggesting caution in early presenters.
This approach benefits from the sensitive detection of myocardial injury and also from the fact that the comorbidities that lead to atherosclerosis cause increases in hs-cTnT within the normal range.
In the United States, approaches using the LoB or LoD cannot be used because the imprecision of the assay at these concentrations exceeds 20%, and the FDA will only allow reporting down to the LoQ of 6 ng/L. The first study that probed whether a value of 6 ng/L can be used achieved a sensitivity of only 96.6% (95% CI, 94.6-97.8) for major adverse cardiac events,
McRae A.D., Innes G., Graham M., et al. Undetectable concentrations of an FDA-approved high-sensitivity cardiac troponin T assay to rule out acute myocardial infarction at emergency department arrival. Acad Emerg Med. doi:10.1111/acem.13229.
What is an acceptable risk of major adverse cardiac event in chest pain patients soon after discharge from the Emergency Department?: a clinical survey.
This is not surprising given that when one repeats samples at these low concentrations there is often a change, with potential for misclassification based on whether the value is above or below the suggested cutoff.
Effect of repeat measurements of high-sensitivity cardiac troponin on the same sample using the European Society of Cardiology 0-hour/1-hour or 2-hour algorithms for early rule-out and rule-in for myocardial infarction.
However, because imprecision at low levels improves with better instrumentation, we suspect that single hs-cTn measurements below the LoD will be used to expedite evaluation of low-risk patients.
At present the one use of single-sample rule-outs is in patients with symptom onset ≥6 hours from presentation, without symptom recurrence, in whom a normal hs-cTnT concentration <99th percentile effectively rules out acute myocardial injury.
Ruling-Out Acute Myocardial Infarction: Serial-Measurement Strategies and Accelerated Diagnostic Pathways
The rapid identification of patients at low risk using hs-cTnT seems possible using various approaches, including the use of serial measurements at 0 hours and 1 to 2 hours after presentation.
We have concerns about the 1-hour rule-out proposed by the European Society of Cardiology guidelines, partly owing to the very small change criteria of <3 ng/L to rule-out and >5 ng/L to rule-in.
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients without persistent ST-segment elevation of the European Society of Cardiology (ESC).
We have pointed out that 1) the imprecision of the assay makes such a distinctions problematic, and 2) very few early presenters were included in these studies.
Thus we do not recommend the 1-hour rule-out strategy. We endorse a 2-hour rule-out protocol, especially for low-risk patients. Assessment of risk can be done using a validated clinical risk score and/or a 12-lead electrocardiogram (ECG). A recent collaborative analysis confirmed that a normal ECG with serial measurements at 0/2 hours <99th percentile with a Thrombolysis in Myocardial Infarction score ≤1 has a high sensitivity and NPV to exclude acute myocardial infarction and 30-day major adverse cardiac events.
We recommend that clinicians integrate serial hs-cTnT measurements at 0/2 hours (less than or equal to the sex-specific 99th percentiles) in the absence of a change in values of 4 ng/L and combine that with a normal or nonischemic ECG and the patient's history or preferably a validated risk score to identify patients at low risk for early discharge. This approach, although conservative, would identify in whom an additional (third) sample at 4 hours may be needed.
For high-risk patients and those who present early after the onset of symptoms, clinical judgment may mandate additional samples in the interest of patient safety. Our recommended approach is shown in the Figure.
FigureHow to use the high-sensitivity cardiac troponin T (hs-cTnT) assay for the evaluation of patients with possible acute myocardial infarction. MI = myocardial infarction; STEMI = ST-segment elevation myocardial infarction; URL = upper refence limit.
The lower the hs-cTn concentration, however, the less likely it is that coronary artery disease is present. This may help in triaging patients with possible unstable angina and should inform clinicians about who might and who might not require additional testing (ie, those with very low hs-cTn values rarely have positive stress tests and/or obstructive coronary artery disease).
Sensitive troponin assays in patients with suspected acute coronary syndrome: results from the multicenter rule out myocardial infarction using computed assisted tomography II trial.
acute myocardial infarction is diagnosed when there is clinical evidence of acute myocardial ischemia and a rise and/or fall of cTn with at least one value greater than the sex-specific 99th percentile. Increases in hs-cTnT >99th percentile are consistent with myocardial injury but are not sufficient for a diagnosis of acute myocardial infarction. Many other acute and/or chronic etiologies can lead to increases >99th percentile.
A variety of approaches have been suggested to facilitate the diagnosis of acute myocardial infarction for hs-cTn assays, including the use of very high concentrations (approximately 5 times the upper reference limit for hs-cTnT) and/or increasing patterns of elevations (delta cTn). These approaches enrich the population at risk for acute myocardial infarction and thus improve specificity but provide a less than ideal positive predictive value (PPV). When one applies criteria to patients with chest pain using either the 0/1- or 0/2-hour hs-cTnT algorithms, an approach combining a baseline value ≥52 (0/1 hour) or 53 (0/2 hours) ng/L with a delta change ≥5 ng/L (0/1 hour) or ≥10 ng/L (0/2 hours) offers diagnostic specificities ranging from approximately 96% to 99% but PPVs from approximately 78% to 85%.
To apply such approaches to a broader, more diverse group of patients as seen in United States and in hospitalized patients, these criteria need substantial modification.
For hs-cTnT, a value exceeding approximately 50 ng/L may be reasonable for those presenting with chest pain and suspected acute myocardial infarction but will be too low for those with end-stage renal disease and the very elderly, as well as those with critical illness. These patients have high baseline values and are rarely included in chest pain triage studies. To functionally use the approach of a high value to suggest acute myocardial infarction, we suggest that patients with possible ischemic symptoms with hs-cTnT concentrations >100 ng/L be considered for additional cardiovascular evaluations (Figure, Table 3). This concentration identifies a high-risk cohort, with some data suggesting a specificity >99% and PPV approximately 90% for acute myocardial infarction.
We do not recommend the use of multiple different cut-off values for triaging high-risk patients across different patient subsets and/or parts of a given institution. For patients with these high hs-cTnT concentrations, in addition to acute myocardial infarction, other conditions in addition to chronic elevations to consider include myocarditis or stress cardiomyopathy.
Table 3Recommendations for Implementation
1.
Multidisciplinary involvement: We suggest a multidisciplinary program, involving emergency, laboratory, and cardiovascular medicine be initiated to determine the optimal way to implement high-sensitivity assays. Critical aspects should include peer education, protocols, and logistics and processes necessary for implementation.
2.
Education is key: It should focus on understanding that these tests offer the opportunity to expedite the evaluation of patients with suspected acute MI, potentially reducing overcrowding in emergency departments and observation units and saving costs if appropriately used.
3.
Education: It is essential to understand and educate that an increased hs-cTnT >99th percentile does not equate to acute MI, but rather that such increases are consistent with myocardial injury, a condition that may be acute or chronic with numerous cardiac and noncardiac etiologies.
4.
Laboratory result reporting: Whole numbers in ng/L should be used for reporting. We advocate the use of sex-specific 99th percentiles.
5.
Ruling-out acute myocardial injury: We recommend an approach integrating serial hs-cTnT measurements at 0/2 hours, in which if both samples are less than or equal to thesex-specific 99th percentiles in the absence of changes <4 ng/L in low-risk (see risk-assessment below) patients, then acute MI can be safely ruled out.
6.
Risk assessment: This must integrate clinical, electrocardiogram, and hs-cTnT information.
7.
Markedly increased hs-cTnT concentrations identify patients at high risk: Values >100 ng/L can be used to potentially expedite the triage of patients at high risk to cardiac consultation, admission, and/or further testing.
8.
Delta hs-cTnT to improve the rule-in for MI: Absolute changes (ng/L) are recommended with a change of >10 ng/L on serial measurements (0/2 hours) recommended to identify patients at higher risk for acute MI. A change of 12 ng/L can be used at 6 hours.
9.
Triaging: For patients with clearer symptoms suggestive of ACS and marked increases (>100 ng/L) or dynamic changes (>10 ng/L) on serial testing (0/2 hours), care should follow ACS practice guidelines. For those with primary cardiovascular problems and increased hs-cTnT, elevations identify a high-risk population, most often requiring hospital admission. For those without primary cardiovascular problems and increased hs-cTnT, these patients often have myocardial injury or type 2 MI. Their care is optimized by being cared for by the service that can care best for their primary problem; they may not require admission to cardiac services.
10.
Appropriate orders: We advocate that cTn measurements be timed consistently after a patient's history/examination and assessment of the clinical presentation.
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients without persistent ST-segment elevation of the European Society of Cardiology (ESC).
The literature suggests that absolute criteria (ng/L) are better than percentage (%) or “relative” criteria, especially in patients who present with elevated baseline hs-cTnT.
In search for the Holy Grail: suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction: a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association.
We advocate the conservative criteria of a 10-ng/L change over a 2-hour period to improve the diagnostic specificity for acute myocardial infarction.
Three additional points are critical. The first is that for patients who do not rule-out or rule-in for acute myocardial injury belong to what has been called an “intermediate zone.” They require additional evaluation. An additional, third hs-cTnT value in another 2 hours will often clarify the situation. A criteria of a change of 12 ng/L is suggested to identify patients at higher risk of myocardial infarction.
In search for the Holy Grail: suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction: a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association.
Second, it should be appreciated that patients who present late after the onset of symptoms (after 12 hours) may be on the downslope of the time–concentration curve, where it is difficult to observe a changing pattern over a short period owing to the slower change in values. In some studies as many as 26% of patients with acute myocardial infarction have presented in this manner.
That said, this concern cannot become the response to every unchanging hs-cTnT value. Finally, some patients may have values that are increasing even if they fail to exceed the 99th percentile URL (eg, a man with a change of 7 ng/L, from 6 ng/L to 13 ng/L, but an overall value below the 99th percentile URL). Alternatively, there will be some patients who have increases that cause the values to exceed the 99th percentile URL but who do not manifest a change of 10 ng/L (eg, a woman with a change of only 5 ng/L but a value above the 99th percentile URL of 10 ng/L). These patients could be at substantial risk and require careful scrutiny and likely additional samples for measurement of hs-cTnT.
Triaging Patients with Elevated hs-cTnT Values
The first and most important step is to assess the pretest probability of atherothrombotic acute myocardial infarction before evaluating the hs-cTnT values. In patients with end-stage renal disease presenting with symptoms such as dyspnea, a hs-cTnT value of 50 ng/L has a very different connotation than the same value in a patient presenting with typical angina and no confounding issues. Marked increases (100 ng/L) on the initial sample portend a higher-risk and/or likelihood for acute myocardial infarction, for which prompt evaluation is warranted. Even in that situation a careful evaluation of the clinical presentation and perhaps serial testing may be necessary to distinguish myocardial injury (eg, from sepsis) from acute myocardial infarction.
Although the presence of dynamic changes increases the likelihood for acute myocardial infarction, dynamic changes also are noted in numerous other conditions, such as acute pulmonary embolism, Takosubo cardiomyopathy, and myocarditis.
For patients with definite acute myocardial infarction, care should follow clinical practice guideline recommendations.
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients without persistent ST-segment elevation of the European Society of Cardiology (ESC).
2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Guidelines suggest an invasive strategy is beneficial in patients with acute coronary syndromes and an elevated contemporary cTn value. For hs-cTnT, a comparable value to the 99th percentile URL for cTnT would be 30 ng/L. For those with values >30 ng/L, an invasive strategy will still likely be preferred. With values <30 ng/L, efforts toward further myocardial infarction subtype categorization should be made because lower hs-cTn values are common with type 2 myocardial infarction.
This condition can occur with or without concomitant coronary artery disease. Therapy is often best oriented toward remediation of the primary cardiovascular or noncardiovascular problem and not necessarily intervention. Thus, clinical judgment is suggested.
Many patients with comorbidities such as congestive heart failure or renal disease may have chronic myocardial injury, as evidenced by stable, chronic hs-cTnT increases >99th percentile. Nearly all patients on hemodialysis will have an elevated hs-cTnT, with the mean concentrations in stable dialysis patients often exceeding 50 ng/L.
In the Prospective comparison of angiotensin receptor neprilysin inhibitor (ARNI) with angiotensin receptor blocker (ARB) on Management Of heart failUre with preserved ejectioN fracTion (PARAMOUNT) clinical trial, hs-cTnT >99th percentile occurred in 55% of patients.
Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696.
These patients and others with stable hs-cTnT increases may or may not need hospitalization, depending on their clinical status. Further risk stratification for coronary artery disease and/or cardiovascular evaluation to assess the etiology of their hs-cTnT elevation may be necessary, often in the outpatient setting.
In addition, many groups of patients may have values of hs-cTnT >99th percentile, some even with a rising pattern suggestive of myocardial injury. These patients are at increased risk, and most should be admitted for cardiovascular care.
Using more sensitive assays, however, many patients whose problem is not primarily cardiac may also have elevated hs-cTnT values, some with a more chronic pattern and some with a dynamic pattern (eg, critical illness such as sepsis). These patients are at increased risk from their underlying primary problem and should receive care on the service best positioned to treat that disease entity and not necessarily admission to cardiology services. The fact they may have concomitant cardiac injury or even type 2 acute myocardial infarction does not mean the primary diagnosis is not the most important one. If hs-cTnT is high (>100 ng/L), cardiology consultation is recommended.
Potential Impact on Implementation
The potential impact on the frequency if hs-cTnT elevations and acute myocardial infarction diagnoses comparing the fourth-generation cTnT with the hs-cTnT assay suggests there may be an increase in elevated values from 22% with the standard assay to 36%. However, the incidence of acute myocardial infarction will change only modestly (from 18% to 22%) in association with a reciprocal reduction in the incidence of unstable angina (13% to 11%).
Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction.
That has been the experience in centers outside of the United States that have educated their clinicians in a joint effort between emergency medicine, cardiology, and laboratory medicine about how to use hs-cTnT.
Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction.
The use of the hs-cTnT assay will provide more robust and sensitive analytic data for clinicians. In addition to improvements in some chronic applications, if used thoughtfully it should improve care. The identification of patients at low risk for early discharge will be facilitated. The rule-in of acute myocardial injury will also be more rapid, and if the proper metrics (such as delta cTn) are used in clinical scenarios suggestive of acute myocardial ischemia, it will help identify patients with acute myocardial infarction in whom further therapeutic interventions should be considered. The triage of patients must rely on clinical context and their primary diagnosis and not on isolated hs-cTnT values, even if rising. Patients with marked hs-cTnT increases with values >100 ng/L deserve cardiac evaluation. The successful implementation of hs-assays in US practice will depend on education focused on how to best maximize the advantages and minimize the disadvantages of the test, with emphasis placed on appropriate ordering, serial testing, use of sex-specific 99th percentiles, delta cTn, and risk assessment using validated clinical risk scores and/or ECGs. Multidisciplinary collaboration, involving cardiology, emergency medicine, and laboratory medicine will be necessary to successfully adopt these assays into practice.
Apple F.S., Ler R., Murakami M.M. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem. 2012;58:1574-1581.
2.
Chenevier-Gobeaux C., Bailleul S., Mzabi A., Blanc M.C., Lefevre G. Upper reference limits of high-sensitivity cardiac troponin T in a general population: comparison with those of sensitive cardiac troponin I. Clin Lab. 2013;59:333-336.
3.
Collinson P.O., Heung Y.M., Gaze D., et al. Influence of population selection on the 99th percentile reference value for cardiac troponin assays. Clin Chem. 2012;58:219-225.
4.
Franzini M., Lorenzoni V., Masotti S., et al. The calculation of the cardiac troponin T 99th percentile of the reference population is affected by age, gender, and population selection: a multicenter study in Italy. Clin Chim Acta. 2015;438:376-381.
5.
Giannitsis E., Kurz K., Hallermayer K., Jarausch J., Jaffe A.S., Katus H.A. Analytical validation of a high-sensitivity cardiac troponin T assay. Clin Chem. 2010;56:254-261.
6.
Gore M.O., Seliger S.L., Defilippi C.R., et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol. 2014;63:1441-1448.
7.
Kimenai D.M., Henry R.M., van der Kallen C.J., et al. Direct comparison of clinical decision limits for cardiac troponin T and I. Heart. 2016;102:610-616.
8.
Ko D.H., Jeong T.D., Cho E.J., et al. The 99th percentile values of six cardiac troponin assays established for a reference population using strict selection criteria. Clin Chim Acta. 2017;464:1-5.
9.
Koerbin G., Tate J.R., Hickman P.E. Analytical characteristics of the Roche highly sensitive troponin T assay and its application to a cardio-healthy population. Ann Clin Biochem. 2010;4:524-528.
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Mingels A., Jacobs L., Michielsen E., Swaanenburg J., Wodzig W., van Dieijen-Vissed M. Reference population and marathon runner sera assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and I assays. Clin Chem. 2009;55:101-108.
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Mueller T., Egger M., Leitner I., Gabriel C., Haltmayer M., Dieplinger B. Reference values of galectin-3 and cardiac troponins derived from a single cohort of healthy blood donors. Clin Chim Acta. 2016;456:19-23.
12.
Saenger A.K., Beyrau R., Braun S., et al. Multicenter analytical evaluation of a high-sensitivity troponin T assay. Clin Chim Acta. 2011;412:748-754.
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Ungerer J.P., Tate J.R., Pretorius C.J. Discordance with 3 cardiac troponin I and T assays: implications for the 99th percentile cutoff. Clin Chem. 2016;62:1106-1114.
References
Hamm C.W.
Bassand J.P.
Agewall S.
et al.
ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC).
2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: task force for the management of acute coronary syndromes in patients without persistent ST-segment elevation of the European Society of Cardiology (ESC).
2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.
Mair J., Lindahl B., Müller C., et al. What to do when you question cardiac troponin values. Eur Heart J Acute Cardiovasc Care. doi:10.1177/2048872617708973.
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.
McRae A.D., Innes G., Graham M., et al. Undetectable concentrations of an FDA-approved high-sensitivity cardiac troponin T assay to rule out acute myocardial infarction at emergency department arrival. Acad Emerg Med. doi:10.1111/acem.13229.
What is an acceptable risk of major adverse cardiac event in chest pain patients soon after discharge from the Emergency Department?: a clinical survey.
Effect of repeat measurements of high-sensitivity cardiac troponin on the same sample using the European Society of Cardiology 0-hour/1-hour or 2-hour algorithms for early rule-out and rule-in for myocardial infarction.
Sensitive troponin assays in patients with suspected acute coronary syndrome: results from the multicenter rule out myocardial infarction using computed assisted tomography II trial.
In search for the Holy Grail: suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction: a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association.
Elevation in high-sensitivity troponin T in heart failure and preserved ejection fraction and influence of treatment with the angiotensin receptor neprilysin inhibitor LCZ696.
Impact of high-sensitivity cardiac troponin on use of coronary angiography, cardiac stress testing, and time to discharge in suspected acute myocardial infarction.
Conflict of Interest: YS has nothing to disclose at present; in the past was provided travel support without salary/honoraria by Roche Diagnostics. ASJ has consulted or is presently consulting for most of the major diagnostic companies and has in the past consulted for Roche Diagnostics.
Authorship: Both authors had access to the data and a role in writing the manuscript.
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