Jaffe, Allan S.

Abstract Introduction Analytical outliers occur with most troponin assays and can adversely affect patient management. We developed a system to detect analytical outliers for the Roche Troponin T (cTnT) Gen 5 assay using repeat analysis of samples manifesting changing values over 2 to 6 hours. Methods In our ED practice, troponins are collected at baseline, 2 hours, and at times at 6 hours in plasma separator tubes and processed on the Roche Cobas e411 (Indianapolis, IN). When troponin values change by ≥10 ng/L or ≤10 ng/L in the 2- or 6-hour sample compared to baseline, the sample that produced the result is repeated. If initial and repeat values differ by > ±5 ng/L (cTnT <100 ng/L) or ±5% (cTnT ≥100 ng/L), the initial value is deemed to be an analytical outlier. Outliers are confirmed by a third measurement. Results Since March 2018, 19 of 17,154 (0.11%) troponin samples analyzed have been labeled outliers. Outliers were falsely elevated in 14 cases and falsely decreased in 5. Mean (range) of initial cTnT values for outliers was 39 ng/L (18-621 ng/L), with only one initial value >100 ng/L. All changes could affect analysis of change over time. Eleven of 19 outliers were outside gender-specific reference interval on both samples and thus did not cause a change from abnormal to normal. Repeat measurements on 8 of 19 outliers were within the URL, which may have greater clinical consequences. Conclusions Repeat analysis upon observation of changing values allows detection of analytical outliers in real time, prior to reporting results. These outliers are almost always clinically significant in terms of interpretation of changing values and at times change patients from above to below the URL. If we tested more than just changing samples, we might detect still more outliers.

Abstract The IFCC Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) has directives and initiatives focused on providing evidence-based educational resources to aid and improve understanding around key analytical and clinical aspects of cardiac biomarkers used in clinical practice and the research setting. As a task force, we have previously published position statements and recommendations focused on use and analytical aspects of high-sensitivity cardiac troponin assays. The current educational document is the first from the C-CB highlighting important biochemical, analytical, and clinical aspects as they relate to the natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro–B-type natriuretic peptide (NT-proBNP), with a focus on heart failure.

Abstract Aims To evaluate sex-specific disparities in acute kidney injury (AKI) complicating acute myocardial infarction-related cardiogenic shock (AMI-CS) in the United States. Methods and results This was a retrospective cohort study from 2000 to 2014 from the National Inpatient Sample (20% sample of all hospitals in the United States). Patients &gt;18 years admitted with a primary diagnosis of AMI and concomitant CS that developed AKI were included. The endpoints of interest were the prevalence, trends, and outcomes of men and women with AKI in AMI-CS. Multivariable hierarchical logistic regression was used to control for confounding, and a two-sided P &lt; 0.05 was considered statistically significant. During this 15 year period, 440 257 admissions with AMI-CS met the inclusion criteria, with AKI noted in 155 610 (35.3%). Women constituted 36.3% of the cohort and were older, of non-White race, and with higher co-morbidity compared with men. Women with AKI less often received coronary angiography (59% vs. 66%), percutaneous coronary intervention (39% vs. 43%), mechanical circulatory support (39% vs. 48%), mechanical ventilation (49% vs. 54%), and haemodialysis (9% vs. 10%) compared with men (all P &lt; 0.001). Adjusted in-hospital mortality was higher in women—odds ratio 1.16 (95% confidence interval 1.14–1.19); P &lt; 0.001—compared with men. Women had shorter lengths of stay (12 ± 14 vs. 13 ± 14 days), lower hospital costs ($150 071 ± 180 796 vs. $181 260 ± 209 674), and were less often discharged to home (19% vs. 31%) (all P &lt; 0.001). Conclusions Women with AKI in AMI-CS received fewer cardiac and non-cardiac interventions, had higher in-hospital mortality, and were less often discharged to home compared with men.

Abstract

Background Invasive angiography in the setting of cardiac troponin elevation may reveal non-obstructive coronary arteries leading to uncertainty in diagnosis. Cardiac MR (CMR) may aid in diagnosis, however, the spectrum of diagnostic findings in the patient presenting with symptoms of cardiac ischaemia, elevated cardiac biomarkers and a negative invasive coronary angiogram is yet to be completely described. Methods We queried the Mayo Clinic, Rochester inpatient record from 1 January 2000 to 31 December 2016 to identify patients who: (1) had an elevated troponin T during admission, (2) underwent coronary angiography within 30 days of troponin T elevation which was considered negative for obstructive coronary arterial disease and (3) underwent CMR within 30 days of troponin T elevation. CMR diagnoses were classified as either (1) myocarditis, (2) small area myocardial infarction, (3) stress cardiomyopathy, (4) non-ischaemic cardiomyopathy or (5) normal. Results Of 215 patients, the spectrum of disease seen on CMR was myocarditis (32%), small area infarction (22%), non-ischaemic cardiomyopathy (20%) and stress cardiomyopathy (9.3%). Conclusion In the largest single-centre study assessing the role of CMR in patients admitted with elevated troponin T with a non-obstructive coronary disease on an angiogram, small area infarction was seen in 22% of patients.

Background The recent introduction of high‐sensitivity cardiac troponin (hs‐cTn) assays has allowed clinicians to measure hs‐cTn before and after cardiac stress testing, but the hs‐cTn release pattern and potential utility in identifying inducible myocardial ischemia are unclear. We thus conducted a systematic review and meta‐analysis to improve our understanding of hs‐cTn release associated with exercise and pharmacological stress testing. Methods and Results Studies published between January 2008 and July 2016 that reported hs‐cTn change values (high‐sensitivity cardiac troponin T [hs‐cTnT] or high‐sensitivity cardiac troponin I [hs‐cTnI]) in relation to cardiac stress testing were searched and reviewed by 2 independent screeners. Primary outcomes were pooled estimates of absolute and relative hs‐cTn changes after cardiac stress test, stratified by the presence of inducible myocardial ischemia. This meta‐analysis included 11 studies (n=2432 patients). After exercise stress testing, hs‐cTnT increased by 0.5 ng/L or 11% (6 studies, n=406) and hs‐cTnI by 2.4 ng/L or 41% (4 studies, n=365) in patients with inducible myocardial ischemia versus hs‐cTnT by 1.1 ng/L or 18% (8 studies, n=629; P =0.29) and hs‐cTnI by 1.8 ng/L or 72% (4 studies, n=831; P =0.61) in patients who did not develop inducible myocardial ischemia. After pharmacological stress test, hs‐cTnT changed by −0.1 ng/L or −0.4% (6 studies, n=251) and hs‐cTnI by 2.4 ng/L or 32% (2 studies, n=108) in patients with inducible myocardial ischemia versus hs‐cTnT by 0.7 ng/L or 11% (5 studies, n=443, P =0.44) and hs‐cTnI by 1.7 ng/L or 38% (2 studies, n=116; P =0.62) in patients who did not develop inducible myocardial ischemia. Conclusions hs‐cTn rising patterns after exercise and pharmacological stress testing appear inconsistent and comparably small, and do not appear to be correlated with inducible myocardial ischemia.

Abstract BACKGROUND The universal definition of myocardial infarction (UDMI) standardizes the approach to the diagnosis and management of myocardial infarction. High-sensitivity cardiac troponin testing is recommended because these assays have improved precision at low concentrations, but concerns over specificity may have limited their implementation. METHODS We undertook a global survey of 1902 medical centers in 23 countries evenly distributed across 5 continents to assess adoption of key recommendations from the UDMI. Respondents involved in the diagnosis and management of patients with suspected acute coronary syndrome completed a structured telephone questionnaire detailing the primary biomarker, diagnostic thresholds, and clinical pathways used to identify myocardial infarction. RESULTS Cardiac troponin was the primary diagnostic biomarker at 96% of surveyed sites. Only 41% of centers had adopted high-sensitivity assays, with wide variation from 7% in North America to 60% in Europe. Sites using high-sensitivity troponin more frequently used serial sampling pathways (91% vs 78%) and the 99th percentile diagnostic threshold (74% vs 66%) than sites using previous-generation assays. Furthermore, high-sensitivity institutions more often used earlier serial sampling (≤3 h) and accelerated diagnostic pathways. Fewer than 1 in 5 high-sensitivity sites had adopted sex-specific thresholds (18%). CONCLUSIONS There has been global progress toward the recommendations of the UDMI, particularly in the use of the 99th percentile diagnostic threshold and serial sampling. However, high-sensitivity assays are still used by a minority of sites, and sex-specific thresholds by even fewer. Additional efforts are required to improve risk stratification and diagnosis of patients with myocardial infarction.