Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I

Boeddinghaus, Jasper; Nestelberger, Thomas; Twerenbold, Raphael; Wildi, Karin; Badertscher, Patrick; Cupa, Janosch; Bürge, Tobias; Mächler, Patrick; Corbière, Sydney; Grimm, Karin; Giménez, María Rubini; Puelacher, Christian; Shrestha, Samyut; Flores, Dayana; Fuhrmann, Jakob; Hillinger, Petra; Sabti, Zaid; Honegger, Ursina; Schaerli, Nicolas; Kozhuharov, Nikola; Rentsch, Katharina; Miró, Òscar; López, Beatriz; Martín‐Sánchez, Francisco Javier; Rodríguez‐Adrada, Esther; Morawiec, Beata; Kawecki, Damian; Ganovská, Eva; Pařenica, Jiří; Lohrmann, Jens; Kloos, Wanda; Buser, Andreas; Geigy, Nicolas; Keller, Dagmar I.; Oßwald, Stefan; Reichlin, Tobias; Müeller, Christian

doi:10.1161/circulationaha.116.025661

Cited by 142 publications

(78 citation statements)

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“…Secondly, these data raise important questions about the applicability of the quoted ULN as an arbiter of type 1 acute myocardial infarction in patients who do not give a typical history consistent with this diagnosis. Previous evidence for using “negative” hs-cTnI levels to “rule out” acute myocardial infarction is clear cut and robust 14151632. The Fourth Universal Definition3 recommends a diagnosis of acute myocardial infarction when there is clinical evidence of acute myocardial ischaemia and when an increase or decrease in cardiac troponin levels is detected.…”

Section: Discussionmentioning

confidence: 99%

“…Previous literature in this field has confirmed the use of the newer hs-cTn assays for early exclusion of acute myocardial infarction in a robust and safe manner 14151632. However, interpretation of a single hs-cTnI concentration above the supplied ULN as being an indicator of acute myocardial infarction, and, more specifically, type 1 myocardial infarction, by frontline clinical staff could lead to misdiagnosis and inappropriate investigations and treatment.…”

Section: Discussionmentioning

confidence: 99%

“…Recent trial data confirm the veracity of using early cardiac troponin concentrations to confidently exclude a diagnosis of acute myocardial infarction13141516; however, the assumption that a concentration greater than the recommended threshold implies acute myocardial infarction (and in particular type 1 myocardial infarction) is often inappropriate.…”

Section: Introductionmentioning

confidence: 99%

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True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study

Mariathas

Allan

Ramamoorthy

et al. 2019

BMJ

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ObjectiveTo determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital.DesignProspective, observational cohort study.SettingUniversity Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017.Participants20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons.Main outcome measuresDistribution of hs-cTnI concentrations of all study participants and specifically the 99th centile.ResultsThe 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer’s quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN.ConclusionsOf 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation.Trial registrationClinicaltrials.govNCT03047785.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study

Mariathas

Allan

Ramamoorthy

et al. 2019

BMJ

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“…Numerous strategies have been tested and some even recommended within regional guidelines, but controversy remains about optimum deployment of these early rule-out approaches. [9][10][11][12] The next UDMI update offers an opportunity to better harmonize the approach to the safe use of early rule-out thresholds below the 99 th percentile, analogous to the third UDMI's standardization of the diagnostic threshold for myocardial infarction.…”

Section: Discussionmentioning

confidence: 99%

Global Adoption of High-Sensitivity Cardiac Troponins and the Universal Definition of Myocardial Infarction

Anand

Shah

Beshiri

et al. 2018

Preprint

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Word count abstract: 302Words count main text: 1,198 Tables and Figures: 3 References: 15Key words: high-sensitivity cardiac troponin; myocardial infarction; universal definition; guidelines; global . CC-BY-NC-ND 4.0 International license It is made available under a (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/371138 doi: bioRxiv preprint first posted online Jul. 17, 2018; 2 Abstract Importance: The third Universal Definition of Myocardial Infarction aimed to standardize the approach to the diagnosis and management of myocardial infarction. High-sensitivity cardiac troponin testing was recommended, as these assays have improved precision at low concentrations, but concerns over specificity may have limited implementation.Objective: To determine the global adoption of high-sensitivity cardiac troponin assays and key recommendations from the Universal Definition. Results: Cardiac troponin was the primary diagnostic biomarker for myocardial infarction at 96% of all sites surveyed. Only 41% of centers had adopted high-sensitivity cardiac troponin assays, with wide variation from 7% in North America to 60% in Europe. Sites using highsensitivity assays more frequently employed serial sampling pathways (91% vs. 78%) and the 99 th percentile diagnostic threshold (74% vs. 66%) when compared to sites using the previous generation of troponin assays. Furthermore, sites using high-sensitivity assays more often used earlier serial sampling (≤3 hours) and accelerated diagnostic pathways. However, fewer than 1 in 5 sites using high-sensitivity assays had adopted sex-specific thresholds (18%).

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“…Unlike earlier generations of cTn assays which require at least 6 h from the onset of symptoms before cTn is detectable in the blood, the hs-cTn assays can detect cTn at a much earlier stage [27,[40][41][42]. This has led to the development of several strategies for the assessment of patients with suspected MI based on serial testing of cTn that can rule out MI already after 1 h, or 2 h [28][29][30][31][42][43][44]. The concept relies on that the positive predictive value for MI increases with increasing changes in cTn concentrations, and that the negative predictive value for MI is very high if there is no, or minimal changes in cTn concentrations between the two time-points.…”

Section: Rule-in and Rule-out Of Myocardial Infarctionmentioning

confidence: 99%

Clinical implications of high‐sensitivity cardiac troponins

Holzmann

2018

J Intern Med

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Cardiac troponin assays have become more sensitive over the years leading to the clinical introduction of high-sensitivity cardiac troponin assays in 2010. Their use has revolutionized the assessment of patients with chest pain in the emergency department by allowing earlier rule-in and rule-out of myocardial infarction leading to shorter stays in the emergency department and reduced admissions for chest pain. The incidence of myocardial infarction has increased slightly, and patients with myocardial infarction diagnosed with high-sensitivity cardiac troponins have been found to have a reduced risk of reinfarction, though without an impact on survival. High-sensitivity cardiac troponins are powerful predictors of long-term mortality and cardiovascular disease in the general population as well as in patients with chest pain with or without cardiovascular disease. The increase in risk for death and cardiovascular disease associated with high-sensitivity cardiac troponins is graded and starts already at detectable levels, well below the upper normal level. The aim of this review was to describe the clinical use and consequences of the introduction of high-sensitivity cardiac troponins. In addition, the importance of persistently elevated troponin levels for prognosis and what investigations may be appropriate to perform in patients with stable troponin elevations are discussed.

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Direct Comparison of 4 Very Early Rule-Out Strategies for Acute Myocardial Infarction Using High-Sensitivity Cardiac Troponin I

Abstract: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00470587.

Cited by 142 publications

References 39 publications

True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study

True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study

Global Adoption of High-Sensitivity Cardiac Troponins and the Universal Definition of Myocardial Infarction

Clinical implications of high‐sensitivity cardiac troponins

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