Implementation of high-sensitivity troponin with a rapid diagnostic algorithm reduces emergency department length of stay for discharged patients.

INTRODUCTION: High sensitivity troponin (hs-cTn) and diagnostic algorithms are used to rapidly triage patients with symptoms of acute myocardial infarction in emergency departments (ED). However, few studies have evaluated the impact of simultaneously implementing hs-cTn and a rapid rule-out algorithm on length of stay (LOS). METHODS: We assessed the impact of transitioning from contemporary cTnI to hs-cTnI in 59,232 ED encounters over three years. hs-cTnI was implemented with an orderable series that included baseline, two-, four-, and six-hour specimens collected at provider discretion and operationalized with an algorithm to calculate the change in hs-cTnI from baseline and provide interpretations of "insignificant", "significant," or "equivocal." Patient demographics, results, chief complaint, disposition, and ED LOS were captured from the electronic medical record. RESULTS: cTnI was ordered for 31,875 encounters prior to hs-cTnI implementation and 27,357 after. The proportion of cTnI results above the 99th percentile upper reference limit decreased from 35.0% to 27.0% for men and increased from 27.8% to 34.8% for women. Among discharged patients, the median LOS decreased by 0.6 h (0.5-0.7). LOS among discharged patients with a chief complaint of chest pain decreased by 1.0 h (0.8-1.1) and further decreased by 1.2 h (1.0-1.3) if the initial hs-cTnI was below the limit of quantitation. The rate of acute coronary syndrome upon re-presentation within 30 days did not change post-implementation (0.10% versus 0.07%). CONCLUSION: Implementation of an hs-cTnI assay with a rapid rule-out algorithm decreased ED LOS among discharged patients, particularly among those with a chief complaint of chest pain.

Predicting Postoperative Troponin in Patients Undergoing Elective Hip or Knee Arthroplasty: A Comparison of Five Cardiac Risk Prediction Tools.

Background: Elderly patients undergoing hip or knee arthroplasty are at a risk for myocardial injury after noncardiac surgery (MINS). We evaluated the ability of five common cardiac risk scores, alone or combined with baseline high-sensitivity cardiac troponin I (hs-cTnI), in predicting MINS and postoperative day 2 (POD2) hs-cTnI levels in patients undergoing elective total hip or knee arthroplasty. Methods: This study is ancillary to the Genetics-InFormatics Trial (GIFT) of Warfarin Therapy to Prevent Deep Venous Thrombosis, which enrolled patients 65 years and older undergoing elective total hip or knee arthroplasty. The five cardiac risk scores evaluated were the atherosclerotic cardiovascular disease calculator (ASCVD), the Framingham risk score (FRS), the American College of Surgeon's National Surgical Quality Improvement Program (ACS-NSQIP) calculator, the revised cardiac risk index (RCRI), and the reconstructed RCRI (R-RCRI). Results: None of the scores predicted MINS in women. Among men, the ASCVD (C-statistic of 0.66; p=0.04), ACS-NSQIP (C-statistic of 0.69; p=0.01), and RCRI (C-statistic of 0.64; p=0.04) predicted MINS. Among all patients, spearman correlations (r s) of the risk scores with the POD2 hs-cTnI levels were 0.24, 0.20, 0.11, 0.11, and 0.08 for the ASCVD, Framingham, ACS-NSQIP, RCRI, and R-RCRI scores, respectively, with p values of <0.001, <0.001, <0.001, 0.006, and 0.025. Baseline hs-cTnI predicted MINS (C-statistics: 0.63 in women and 0.72 in men) and postoperative hs-cTnI (r s = 0.51, p=0.001). Conclusion: In elderly patients undergoing elective hip or knee arthroplasty, several of the scores modestly predicted MINS in men and correlated with POD2 hs-cTnI.

Serial cardiac biomarkers for risk stratification of patients with COVID-19.

OBJECTIVES: Several studies have demonstrated an association between elevated cardiac biomarkers and adverse outcomes in patients with COVID-19. However, the prognostic and predictive capability of a multimarker panel in a prospectively collected, diverse "all-comers" COVID-19 population has not been fully elucidated. DESIGN & METHODS: We prospectively assessed high sensitivity cardiac troponin I (hsTnI), NT-pro B-type Natriuretic Peptide (NT-proBNP), Galectin-3 (Gal-3), and procalcitonin (PCT) in 4,282 serial samples from 358 patients admitted with symptomatic, RT-PCR confirmed SARS-CoV-2 infection. Outcomes examined were 30-day in-hospital mortality and requirement for intubation within 10 days. RESULTS: Baseline hsTnI had the highest AUC for predicting 30-day mortality (0.81; 95% CI, 0.73-0.88), followed by NT-proBNP (0.80; 0.74-0.86), PCT (0.77; 0.70-0.84), and Gal-3 (0.68; 0.60-0.76). HsTnI < 3.5 ng/L at baseline identified patients at low risk for in-hospital mortality (NPV 95.9%, sensitivity 97.3%) and 10-day intubation (NPV 90.4%, sensitivity 88.5%). Continuous, log-2 increases in troponin concentration were associated with reduced survival (p < 0.001) on Kaplan-Meier curves and increased risk of 30-day mortality: HR 1.26 (1.16-1.37) in univariate and 1.19 (1.03-1.4) in multivariate models. Time-varying doubling of concentrations of hsTnI and Gal-3 were associated with increased risk of 30-day mortality (adjusted HR 1.21, 1.06-1.4, and 1.92, 1.40-2.6). CONCLUSION: HsTnI, NT-proBNP, Gal-3, and PCT are elevated at baseline in patients that have worse outcomes from COVID-19. HsTnI was the only independent predictor of 30-day mortality and intubation. Time-varying, doubling in hsTnI and Gal-3 further aided in prognostication of adverse outcomes. These results support the use of hsTnI for triaging patients with COVID-19.

Adequacy of hemodialysis in acute kidney injury: Real-time monitoring of dialysate ultraviolet absorbance vs. blood-based Kt/Vurea.

BACKGROUND: Current guidelines recommend monitoring the adequacy of hemodialysis (HD) treatments in patients with acute kidney injury (AKI). Blood-based methods for calculating urea such as reduction ratio (URR) and single-pool Kt/Vurea (spKt/Vurea) require pre- and post-HD blood urea nitrogen (BUN) measurements. This study aims to compare real-time monitoring of urea clearance using dialysate ultraviolet absorbance (UV) with laboratory-measured spKt/Vurea. METHODS: We conducted a single-center, retrospective study among hospitalized patients with AKI, who required intermittent hemodialysis (IHD). Those patients whose dialysis dose was simultaneously monitored by spKt/Vurea and UV-absorbance (UV-spKt/Vurea) were included in the study. The statistical correlation between both methods was assessed by means of the Pearson moment product correlation, Mann-Whitney U-test and Bland-Altman analysis of agreement. RESULTS: Thirty patients with AKI were evaluated. There was no statistical difference between the mean spKt/Vurea calculated by traditional methods and the mean UV-spKt/Vurea. (1.37 ± 0.37 vs. 1.28 ± 0.36, P = 0.12, CI: 95%). A Pearson moment correlation analysis revealed a close agreement between both methods (r = 0.79, P < 0.001). Furthermore, Bland-Altman analysis showed that >95% of the data points were confined within the upper and lower levels of agreement. CONCLUSION: In this pilot study of patients with AKI, UV-spKt/Vurea correlated with standard blood-based spKt/Vurea and may be a useful tool to monitor dialysis adequacy. Larger studies evaluating multiple UV and blood-based measurements per patient and a more diverse AKI population are needed to confirm this initial observation.

On the Basis of Race: The Utility of a Race Factor in Estimating Glomerular Filtration.

BACKGROUND: Glomerular filtration rate (GFR) is a measure of the combined rate of filtration of all functional nephrons in the kidney. Measurement of GFR is used in the clinic to detect, stratify, and monitor progression of kidney dysfunction, and also serves as a prognostic tool for staging chronic kidney disease (CKD). The gold standard method for measuring GFR is by plasma or urine clearance of exogenous filtration markers, but this is not feasible in routine clinical practice. The most commonly used method to assess GFR is using equations for estimated GFR (eGFR). CONTENT: Addition of a race factor to eGFR equations has been recommended to optimize performance for Black individuals. Here, we review the basis of the race-based equation and assess its utility and widespread applicability. SUMMARY: Although evidence supporting the performance of a race factor exists in the unique populations in which these estimation equations were derived, more studies are needed to assess the need, or lack thereof, for race factors for all ethnicities. Furthermore, ethnicity is complex and likely cannot be qualified with a 2-level descriptor.

Comparison of Two Commercially Available Fentanyl Screening Immunoassays for Clinical Use.

BACKGROUND: Fentanyl is a synthetic opioid associated with illicit drug use and overdose deaths. The SEFRIA Immunalysis (IAL) and ARK fentanyl assays are both FDA-cleared, open channel immunoassays for fentanyl detection in urine. However, limited data are available in the literature comparing these assays. The objective of this study was to perform a direct comparison of these two fentanyl immunoassays. METHODS: IAL and ARK fentanyl immunoassays were performed on a Roche Cobas e602 automated chemistry analyzer. Repeatability and total imprecision were compared by diluting fentanyl into urine at concentrations above, below, and at the manufacturers' cutoffs of 1.0 ng/mL. Cross-reactivity was assessed for norfentanyl and the fentanyl analogs acetylfentanyl, acrylfentanyl, and furanylfentanyl. Concordance was assessed in 90 patient samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the gold standard. RESULTS: Repeatability varied from 11.4%-17.8% on the IAL assay and 2.8%-5.5% on the ARK assay. Total imprecision was 18.9%-40.7% on the IAL assay and 2.9%-6.4% on the ARK assay. Both assays cross-reacted with acetylfentanyl (∼100%), acrylfentanyl (∼100%), and furanylfentanyl (∼20%), but only the ARK assay cross-reacted with norfentanyl (∼3%). An admixture of 0.5 ng/mL fentanyl and 6 ng/mL norfentanyl produced a positive result on the ARK assay. Total concordance between IAL and ARK for 90 tested patient samples was 93% (kappa = 0.85). Relative to LC-MS/MS, the IAL assay had a concordance of 90% (kappa = 0.79) and the ARK assay had a concordance of 94% (kappa = 0.88). Including norfentanyl in the LC-MS/MS confirmation increased the concordance of the ARK to 96% (kappa = 0.90). CONCLUSIONS: The ARK assay recognized the metabolite norfentanyl, demonstrated superior precision, and had better concordance with LC-MS/MS compared to the IAL assay.

High-Sensitivity Cardiac Troponin After Cardiac Stress Test: A Systematic Review and Meta-Analysis.

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.

Multicenter assessment of a hemoglobin A1c point-of-care device for diagnosis of diabetes mellitus.

OBJECTIVE: A multisite investigation compared the analytical performance of a point-of-care (POC) HbA1c device with multiple commonly used HbA1c laboratory methods and an NGSP (National Glycohemoglobin Standardization Program) reference method. RESEARCH DESIGN AND METHODS: The Afinion AS100 POC device analyzed HbA1c using 618 EDTA whole blood excess patient specimens with clinically indicated HbA1c testing. Results were compared to measurements across five clinical laboratories and the NGSP reference method. Precision was evaluated over 8-10 consecutive days for low-, mid-, and high-range HbA1c specimens at all five sites. RESULTS: Over a wide range of HbA1c values (4.0%-15% HbA1c), 97.1% of the POC results and 94.5% of routine laboratory results fell within the target value of ±6% of the NGSP reference method results. The POC HbA1c results at 6.5% exhibited a total relative bias of -0.6% (-0.04% HbA1c) compared to the reference method while the aggregate of laboratory methods displayed a relative bias of -0.9% (-0.06% HbA1c). The total imprecision of the POC results ranged from 0.74-2.13% CV across the analytic measurement range compared to 0.81-3.23% CV for the routine laboratory methods. CONCLUSIONS: The accuracy and precision of the Afinion POC HbA1c method was comparable to the laboratory HbA1c methods supporting the FDA's recent approval of the Afinion HbA1c Dx device for use in the diagnosis of diabetes.

Diagnostic concordance between NT-proBNP and BNP for suspected heart failure.

OBJECTIVES: BNP and NT-proBNP are viewed as comparable in their ability to diagnose and monitor HF in clinical guidelines. However, no recent large-scale study has directly established diagnostic concordance between BNP and NT-proBNP. This study sought to assess diagnostic concordance of BNP and NT-proBNP for ruling in and ruling out heart failure (HF). METHODS: Simultaneous BNP and NT-proBNP testing was performed on 2729 patient samples with routinely ordered BNP testing. Hospital location, age, sex, creatinine, BNP and NT-proBNP were also recorded. Recommended cutoffs for BNP and NT-proBNP for ruling in and out HF were used for assessing diagnostic concordance and correlation. RESULTS: In the ED setting, concordance between BNP and NT-proBNP was 0.695 (95% CI, 0.668-0.723) by weighted kappa using the recommended cutoffs for the acute setting. In non-ED patients, the concordance was 0.642 (95% CI, 0.580-0.705) using non-acute setting cutoffs. In the ED setting, patients with eGFR <60 mL/min/1.73m2 had lower overall concordance (0.626; 95% CI 0.580-0.672) compared to those with eGFR >60 mL/min/1.73m2 (0.707, 95% CI 0.669-0.744). Patients with an eGFR <15 mL/min/1.73m2 had a much higher ratio of NT-proBNP to BNP than patients with eGFR >60 mL/min/1.73m2 (17.0 vs. 4.7, P < .001). Linear regression revealed an r2 of 0.52 in the ED setting and 0.49 in the non-ED setting between BNP and NT-proBNP. For 368 patients with multiple measurements of natriuretic peptides, 19.7% of paired temporal measurements had an increase in one peptide and a decrease in the other. CONCLUSION: The current cutoffs for diagnosing HF for NT-proBNP and BNP have relatively low diagnostic concordance and correlation, particularly among patients with chronic kidney disease.

Quality Control Practices for Chemistry and Immunochemistry in a Cohort of 21 Large Academic Medical Centers.

OBJECTIVES: In the United States, minimum standards for quality control (QC) are specified in federal law under the Clinical Laboratory Improvement Amendment and its revisions. Beyond meeting this required standard, laboratories have flexibility to determine their overall QC program. METHODS: We surveyed chemistry and immunochemistry QC procedures at 21 clinical laboratories within leading academic medical centers to assess if standardized QC practices exist for chemistry and immunochemistry testing. RESULTS: We observed significant variation and unexpected similarities in practice across laboratories, including QC frequency, cutoffs, number of levels analyzed, and other features. CONCLUSIONS: This variation in practice indicates an opportunity exists to establish an evidence-based approach to QC that can be generalized across institutions.

Postoperative Myocardial Injury and Inflammation Is Not Blunted by a Trial of Atorvastatin in Orthopedic Surgery Patients.

BACKGROUND: Orthopedic patients are at risk for adverse postoperative cardiovascular outcomes. QUESTIONS/PURPOSES: This pilot randomized controlled trial (RCT) of atorvastatin vs. placebo in orthopedic surgery patients was performed in order to assess: (1) the prevalence of perioperative myocardial injury; (2) the effect of atorvastatin on perioperative inflammation; and (3) the feasibility of performing a large RCT of statin therapy in orthopedic patients. METHODS: Hip fracture (hip Fx) and total hip and knee replacement (THR and TKR) patients were randomized 1:1 to atorvastatin 40 mg daily vs. placebo, starting preoperatively and continuing until postoperative day (POD) 45. High-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) were measured preoperatively and on POD 2. Patients were monitored for adverse events until POD 90. RESULTS: Five hundred fifty-six patients were screened, 22 were recruited (4 hip Fx, 11 THR, 7 TKR), and 2 withdrew. Most (80%) had detectable hs-cTnI (> 1.1 pg/mL) preoperatively. Twenty percent had a perioperative rise in hs-cTnI (≥ 10 pg/mL), which was not blunted by atorvastatin. Hs-CRP rose in 19/20 patients, and IL-6 rose in all patients. However, atorvastatin did not blunt the rise in these inflammatory biomarkers. On POD 2, IL-6 and hs-cTnI levels correlated (ρ = 0.59, p = 0.02). Recruitment was limited by the high prevalence of statin use in the screened population and a high prevalence of exclusions among hip fracture patients. CONCLUSION: Perioperative myocardial injury and inflammation are common in orthopedic patients and do not appear to be reduced in those randomized to atorvastatin. TRIAL REGISTRATION: NCT02197065.