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Abstract Background Several high-sensitivity cardiac troponin (cTn) assays have been cleared by the United States (US) Food and Drug Administration (FDA) for clinical use. Although some of them have been used outside the US for some time, there is limited experience thus far across US sites. Following FDA clearance of the Roche 5th Gen cTnT assay in January 2017, a multicenter US regional healthcare system introduced this more sensitive cTnT assay into clinical practice in September 2018. Purpose To examine cTn testing patterns, incidence of acute myocardial infarction (MI), and resource utilization before and after implementation of the 5th Gen cTnT assay across a large US healthcare system. Methods Using electronic-health records reporting software (Cogito SlicerDicer, EPIC), administrative data was examined to evaluate the transition (4-months before and after implementation) from the 4th to 5th Gen cTnT assays across 16 hospitals but not the major hub hospital of the system that transitioned at a separate time. Adult patient visits (emergency and hospital encounters), cTnT testing, incidence of chest discomfort and acute MI, and resource utilization, including hospital admissions, were examined during the transition period. Results 98,558 adult ED patient visits occurred during an 8-month period across 16 hospitals, including 50,485 and 48,073 patient visits before (5/12/18 – 9/11/18) and after (9/12/18 – 1/11/19) implementation of the 5th Gen cTnT assay respectively. cTnT testing occurred in 20% (range 8.9–34.8%) of all ED visits, with testing performed in the absence of chest pain in 54% (range 37–67%) of cases. Acute MI was diagnosed in 5.6% (n=561) of cases using the 4th Gen cTnT assay as compared to 6.6% (n=608) of cases using the 5th Gen cTnT assay (absolute difference 1.0%, 95% CI: 0.32–1.68, p=0.004). Much of the increase in MI diagnoses were in women (2.2% vs. 2.8%, p=0.008). The proportion of ED patients requiring hospital admission did not differ between pre- and post-implementation periods (24.1% vs. 23.6%, p=0.4); however, among the subset of patients with chest pain, fewer admissions occurred post-implementation (17.9% vs. 15.8%, p=0.006). There was no increase in echocardiography (9.3% vs. 8.4%), coronary angiography (2.9% vs. 3.1%), or cardiac consultations (7.3% vs. 7.3%) utilization post-implementation. Conclusions Cardiac troponin testing occurs in nearly 20% of ED visits in a large multicenter regional healthcare system. About half of all tests are ordered in the absence of chest pain, with a low MI rate observed among the patients undergoing testing. Following implementation of the 5th Gen cTnT assay, testing rates/patterns remained unchanged, with a small but significant increase in MI diagnoses, primarily due to more women being diagnosed with MI. Fewer ED patients with chest pain required admission. Despite using a more sensitive cTn assay, hospital admissions and resource utilization did not increase post-implementation.

Abstract The use of soluble cardiac biomarkers such as NT-proBNP and troponin has revolutionized prognostication for patients with AL amyloidosis and led to their use in the Mayo 2004 and 2012 staging systems. Novel soluble markers with different phenotypic targets may further improve this approach. Soluble ST2 (sST2), which is the circulating form of the IL-33 receptor, has been shown to be a marker of cardiac remodelling and fibrosis, is predictive of mortality in patients with congestive heart failure, and is predictive of risk of GVHD and GVHD mortality. Samples of blood of patients with AL amyloidosis collected and frozen at -20C under a biobank IRB protocol were retrieved and sST2 measured. Patients were eligible for present study if they had a research sample collected within 90 days of their AL amyloidosis diagnosis. We have validated that values do not change significantly with storage at -20C over a 90 day period. Concentrations of sST2 were determined using a novel high-sensitivity sandwich immunoassay (Presagew ST2; Critical Diagnostics, San Diego, CA, USA). The sST2 assay had within-run and total coefficients of variation of <7.5% and 13.0% across its measurement range. Samples from 273 consecutive patients meeting diagnostic criteria for AL amyloidosis seen at our institution from 1/9/2010 to 12/22/2011 were evaluated. Median age was 63. 58% were male. One hundred and thirty have died over 33.9 months. Correlation between sST2 and the other biomarkers was modest with correlation coefficients of 0.48 and 0.20 for NT-proBNP and Troponin T, respectively. Patients with sST2 above and below the median of 27.2 ng/mL (6.3-596) had significant differences in 2 year overall survival: 71.2% to 39% (figure). In multivariate modeling sST2’s prognostic value was independent of the Mayo 2004 and the Mayo 2012 cardiac biomarker staging systems, the latter of which also includes prognostic information relating to plasma cell burden. In these multivariate models, sST2 median had a RR of 2.4, (95%CI 1.6, 3.6 p<0.001) with the Mayo 2004 Staging system (RR of 2.9, 95%CI 2.1, 4.1p<0.001); and sST2 median had a RR of 2.2 (95%CI 1.5, 3.4, p<0.001) with the Mayo 2012 staging system (RR 1.9, 95%CI 1.6, 2.3, p<0.001). A larger cohort including patients with longer follow up will be presented at the meeting as will gender specific cut off values and a comparison of our values with those previously used to prognosticate in patients with heart failure. sST2 appears to be a novel powerful prognostic factor for patients with AL amyloidosis. Because sST2 functions as a decoy receptor, which neutralizes the benefits of IL-33, it may play a role in the deleterious phenotype seen in patients with AL, i.e. myocardial hypertrophy and reduction of contractility. Disclosures: Saenger: Critical Diagnostics : Research Funding; Roche: Research Funding. Jaffe:Critical Diagnostics: Consultancy, Research Funding; Roche: Consultancy.

Abstract Abstract 2887 Introduction: Cardiac involvement is the major cause of death in patients with immunoglobulin light chain amyloidosis (AL). Detection of cardiac involvement and risk stratification has been facilitated by cardiac biomarkers like troponin T (cTnT) and N-terminal brain natriuretic peptide (NT-proBNP). A novel high sensitivity cTnT (hs-cTnT) assay has been developed, and we evaluated its diagnostic use with three questions in mind: 1) How do the cTnT and hs-cTnT perform in the AL amyloid staging system? 2) Does higher sensitivity add significant additional value in terms of prognosticating outcomes for patients with AL amyloidosis? 3) Can the current AL amyloidosis staging system be further improved upon? Methods: Stored serum samples (-20°C) from 224 pts with AL were analyzed for concentrations of hsTnT, TnT, and NT-proBNP on the E170 Modular analyzer (Roche Diagnostics, Penzberg, Germany). 99th percentile reference limits were <0.014 and <0.010 mcg/L for hsTnT and TnT, respectively. Results: Median values for hsTnT, TnT, and NT-proBNP were 38 ng/L (range 0–075.4), 0.017 mcg/L (<0.0–0.904), and 1230 ng/L (0–32, 226), respectively. The correlation coefficient between hsTnT and TnT was 0.972. Those classified by echocardiographic parameters as having (n=143) or not having (n=81) cardiac involvement had TnT concentrations of 0.04 and 0.01 mcg/L and hsTnT levels of 52.2 and 15.6 ng/L, respectively. The direct numeric result from the hs-cTnT result CANNOT merely be substituted for a cTnT result in the Mayo AL staging system since 14% of patients would be misclassified. The performance of the receiver operation curve derived hs-cTnT cut-point of 54 ng/L is a slight improvement over the direct substitution of 35 ng/L if replacement of one assay for another is required. An alternate staging option using hs-cTnT alone—using the two thresholds14 ng/L and 54 ng/L (figure)—performs as well as either the original Mayo AL staging system or a derivative system incorporating hs-cTnT with respective relative risks of death (95%CI) of 3.6 (2.3, 5.7), 3.8 (2.5, 5.9), and 3.3 (2.2, .50). On multivariate analysis, our newly described alternate 3 level, hs-cTnT alone staging system is independent of other factors including period of diagnosis, type of therapy, and NT-proBNP value, the last of which dropped out of the model. Alternate models using NT-proBNP and cTnT were explored, but none performed better than the original staging system or the new hs-cTnT system. Conclusion: The direct numeric result from the hs-cTnT result cannot merely be substituted for a cTnT result in the Mayo amyloid staging system. Consideration could be made for AL staging systems using hs-cTnT alone and relegating the NT-proBNP for measuring cardiac response. Disclosures: Jaffe: Roche: Consultancy.

One-third of peripheral T-cell lymphomas are “not otherwise specified” (PTCL-NOS), but they have been subdivided into 2 subgroups based on gene expression profiling. Amador and colleagues generated an immunohistochemical algorithm that parallels the molecular separation of PTCL-NOS and provides useful prognostic information.

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.