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Background How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB). Methods The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (>URL 6.5%), NT-proBNP (>URL 125 ng/L) and eGFR ( Results Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women. Conclusions Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.

Limited data exist on rapid risk-stratification strategies using the U.S. Food and Drug Administration-cleared high-sensitivity cardiac troponin I (hs-cTnI) assays.This study sought to examine single measurement hs-cTnI to identify patients at low and high risk for acute myocardial infarction (MI).This was a prospective, multicenter, observational study of patients with suspected acute MI enrolled across 29 U.S. sites with hs-cTnI measured using the Atellica IM TnIH and ADVIA Centaur TNIH (Siemens Healthineers) assays. To identify low-risk patients, sensitivities and negative predictive values (NPVs) for acute MI and MI or death at 30 days were examined across baseline hs-cTnI concentrations. To identify high-risk patients, positive predictive values and specificities for acute MI were evaluated.Among 2,212 patients, acute MI occurred in 12%. The limits of detection or quantitation resulted in excellent sensitivities (range 98.6% to 99.6%) and NPVs (range 99.5% to 99.8%) for acute MI or death at 30 days across both assays. An optimized threshold of 5 ng/l identified almost one-half of all patients as low risk, with sensitivities of 98.6% (95% confidence interval: 97.2% to 100%) and NPVs of 99.6% (95% confidence interval: 99.2% to 99.9%) for acute MI or death at 30 days across both assays. For high-risk patients, hs-cTnI ≥120 ng/l resulted in positive predictive values for acute MI of ≥70%.Recognizing the continuous relationship between baseline hs-cTnI and risk for adverse events, using 2 Food and Drug Administration-cleared hs-cTnI assays, an optimized threshold of 5 ng/l safely identified almost one-half of all patients as low risk at presentation, with hs-cTnI ≥120 ng/l identifying high-risk patients.

Our objective was to examine the appropriateness of cardiac troponin (cTn) testing among patients with cTn increases.This is a planned secondary analysis of the Use of TROPonin In Acute coronary syndromes (UTROPIA, NCT02060760) observational cohort study. Appropriateness of cTn testing was adjudicated for emergency department patients with cTn increases99Appropriateness was determined from 1272 and 1078 adjudication forms completed for 497 and 422 patients with contemporary and hs-cTnI increases, respectively. Appropriateness of cTnI testing across adjudication forms was 71.5% and 72.0% for cTnI and hs-cTnI, respectively. Compared with emergency physicians, cardiologists were less likely to classify cTnI orders as appropriate (cTnI: 79% vs 56%, P.0001; hs-cTnI: 82% vs 51%, P.0001). For contemporary cTnI, appropriateness of 95%, 70%, and 39% was observed among adjudication forms completed by cardiologists for type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively; compared with 90%, 86%, and 71%, respectively, among emergency physicians. Similar findings were observed using hs-cTnI. Discordance in appropriateness adjudication forms occurred most frequently in cases of myocardial injury (62% both assays) or type 2 myocardial infarction (cTnI 31%; hs-cTnI 23%).Marked differences exist in the perception of what constitutes appropriate clinical use of cTn testing between cardiologists and emergency physicians, with emergency physicians more likely to see testing as appropriate across a range of clinical scenarios. Discordance derives most often from cases classified as myocardial injury or type 2 myocardial infarction.

Background Sofosbuvir use in patients with decompensated cirrhosis may be associated with reduced liver transplant waitlist mortality and reduced need for transplant. Methods Data from the Scientific Registry of Transplant Recipients were linked with a national database of pharmacy claims. All adult patients on the liver transplant waitlist on January 1, 2014, or added to the list during 2014, with hepatitis C virus as reason for listing were identified (2009 patients). A subgroup of 1093 unique patients had consistent pharmacy claim capture and observations. We compared patients who were and were not treated with all sofosbuvir-based regimens. Results During the study period, 154 patients received sofosbuvir-based regimens. These patients had lower model for end-stage liver disease scores and significantly longer waiting times. We found a trend toward significance for more sofosbuvir-treated than untreated patients being removed from the waitlist due to improved condition (4.54% vs 3.19%, p=0.03). In a propensity score-adjusted analysis, sofosbuvir-treated patients were less likely to undergo transplant (hazard ratio 0.57, 95% confidence interval 0.37-0.89, p=0.01). Conclusion During the study period reflecting early sofosbuvir use, few liver transplant candidates received sofosbuvir. Use was associated with lower incidence of transplant and a trend toward more waitlist removals due to improved condition.

No abstract available Keywords: United States; acute coronary syndrome; biomarkers; myocardial infarction; triage; troponin.

Aims: First, describe how acute myocardial infarction criteria are used to diagnose type 1 (T1MI) and 2 (T2MI) myocardial infarction. Second, determine whether subjective or objective criteria are used for T2MI. Third, examine outcomes for T2MI based on the presence or absence of objective evidence of myocardial ischemia compared with myocardial injury. Methods and results: Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational, cohort study involving 1640 consecutive emergency department patients with serial high-sensitivity cardiac troponin I among whom 74 (4.5%) had T1MI, 103 (6.3%) T2MI, and 245 (15%) myocardial injury. Compared with T1MI, patients with T2MI were less likely to have ischemic symptoms (97% vs. 83%), Q waves (24% vs. 1%), new ST-T wave changes (74% vs. 51%), new regional wall motion abnormality (64% vs. 11%), and a culprit lesion on coronary angiography (59% vs. 0%) (all p Conclusions: Among patients with T2MI, many cases are diagnosed using subjective criteria. The presence of objective evidence of myocardial ischemia may identify a higher-risk group of T2MI patients in whom early outcomes are worse than myocardial injury. Emphasis on using objective evidence of myocardial ischemia to diagnose T2MI may result in a more precise and specific disease definition.

Our purpose was to determine a) overall and sex-specific 99th percentile upper reference limits (URL) and b) influences of statistical methods and comorbidities on the URLs.Heparin plasma from 838 normal subjects (423 men, 415 women) were obtained from the AACC (Universal Sample Bank). The cobas e602 measured cTnT (Roche Gen 5 assay); limit of detection (LoD), 3ng/L. Hemoglobin A1c (URL 6.5%), NT-proBNP (URL 125ng/L) and eGFR (60mL/min/1.73m355 men and 339 women remained after exclusions. Overall50% of subjects had measureable concentrations ≥ LoD: 45.6% no exclusion, 43.5% after exclusion; compared to men: 68.1% no exclusion, 65.1% post exclusion; women: 22.7% no exclusion, 20.9% post exclusion. The statistical method used influenced URLs as follows: pre/post exclusion overall, NP 16/16ng/L, HDE 17/17ng/L, R not available; men NP 18/16ng/L, HDE 21/19ng/L, R 16/11ng/L; women NP 13/10ng/L, HDE 14/14ng/L, R not available.We demonstrated that a) the Gen 5 cTnT assay does not meet the IFCC guideline for high-sensitivity assays, b) surrogate biomarkers significantly lowers the URLs and c) statistical methods used impact URLs. Our data suggest lower sex-specific cTnT 99th percentiles than reported in the FDA approved package insert. We emphasize the importance of detailing the criteria used to include and exclude subjects for defining a healthy population and the statistical method used to calculate 99th percentiles and identify outliers.

Measures of cardiac troponin (cTn) may have lower specificity for myocardial infarction in patients with CKD. We examined the diagnostic accuracy of baseline and serial high-sensitivity cTnI (hs-cTnI) measurements for myocardial infarction and 30- and 180-day mortality according to renal function. hs-cTnI was measured (Abbott assay) using sex-specific 99th percentiles (women, 16 ng/L; men, 34 ng/L) in 1555 adults presenting to the emergency department with symptoms suggesting ischemia (NCT02060760). Myocardial infarction was adjudicated along universal definition classification. Renal function did not significantly affect sensitivity or negative predictive values. Specificity decreased with impaired renal function from 93%–95% with normal function (eGFR≥90 ml/min per 1.73 m2; n=722) to 57%–61% with severely impaired renal function (eGFR

Rationale & Objective The associations between ischemic stroke and time to dialysis initiation and/or death in adults with late-stage chronic kidney disease (CKD) have not been explored. We sought to measure the rate and factors associated with stroke in CKD stages 4 and 5 (CKD4-5) and assess the association of stroke with initiation of dialysis and death. Study Design Retrospective cohort. Setting & Participants Patients with CKD4-5 in Medicare 2007 to 2014. Exposure or Predictor Ischemic stroke in CKD4-5. Outcomes Initiation of maintenance dialysis or death. Analytical Approach Cox proportional hazard modeling assessed factors associated with ischemic stroke. A matched analysis (stroke/no stroke) estimated the cumulative incidence of incident kidney failure and death, treated as competing events. Simulations using a state transition model determined differences in expected time to kidney failure or death and death alone for patients with and without stroke with CKD5. Results 123,251 patients with CKD4 and 22,054 with CKD5 were identified. Mean ages were 81.0 and 79.2 years, respectively. Female sex (HRs of 1.21 [95% CI, 1.12-1.31] and 1.39 [95% CI, 1.04-1.86] for CKD4 and CKD5, respectively) and black race (HRs of 1.25 [95% CI, 1.12-1.39] and 1.12 [95% CI, 0.80-1.58] for CKD4 and CKD5, respectively) were factors associated with ischemic stroke. Rates for 30-day mortality were 13.3% and 18.8%, and for 1-year mortality, 40.0% and 38.2%. For patients with CKD5, kidney failure or death occurred an average of 3.6 months sooner for patients with an ischemic stroke, and death (irrespective of kidney failure), a mean of 24.3 months sooner. Limitations Study design cannot determine causality; lack of data for stroke severity. Conclusions Female sex and black race were associated with increased risk for stroke in CKD4 and CKD5. In CKD5, stroke was associated with a shorter time to kidney failure or death by nearly 4 months, and to death, by more than 2 years.

Background The incidence and impact of acute infection among patients with type 1 (T1MI) and 2 myocardial infarction (T2MI) is not well known. Inflammation and increased procoagulant activity can lead to T1MI, whereas cytokine release can cause hemodynamic alterations affecting myocardial oxygen consumption and contribute to T2MI. Purpose Determine the incidence and prognostic impact of acute infection among patients with T1MI and T2MI. Methods Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational cohort study involving 1,640 consecutive emergency department patients with serial cardiac troponin (cTn) I measurements obtained on clinical indication. The incidence of acute infection, antibiotic use, and/or laboratory evidence of infection were examined among patients with T1MI and T2MI. 5-year cumulative survival curves were plotted using the Kaplan-Meier method, frequencies were compared via Chi-Square, and a multivariate cox-proportional hazards model was used to assess the impact of infection on mortality. Results Among 217 patients with acute MI (T1MI, n=77 and T2MI, n=140), acute infection occurred in 63 (29%) of patients. Acute infection was more common in patients with T2MI than T1MI (35% vs. 18%, p=0.009). The predominant source of infection was pneumonia (59%), followed by urinary tract infections (11%). Patients with T2MI were also more likely than T1MI to have sepsis (11% vs. 1%, p=0.012), bacteremia (30% vs. 18%, p=0.057), and antibiotic use (35% vs. 17%, p=0.005). At 5-years, patients with acute MI and acute infection had a higher mortality rate than patients without infection (49% vs. 25%, p=0.0006) (Figure). Among the 31 deaths in MI patients with acute infection, most deaths were non-cardiac (65%) and occurred in those with T2MI (77%). Following adjustment for age, sex, and comorbidities in a Cox proportional hazards model, acute infection was an independent predictor of death (hazard ratio: 2.2, 95% CI: 1.3–3.5, p=0.0016). Conclusion Acute infection occurs in almost a third of patients that are diagnosed with acute MI during the index hospitalization. Most infections are due to pneumonia and occur most often in patients classified as having T2MI. Acute infection is an independent risk factor for 5-year mortality, with nearly half of all patients with acute MI in whom concomitant acute infection is present during the index hospitalization dead at 5-years. Most deaths are non-cardiac and the vast majority occur in patients with T2MI. Acknowledgement/Funding Abbott Diagnostics and Hennepin Healthcare Research Institute (formerly MMRF)e

Background Few studies address long-term outcomes among patients with type 2 myocardial infarction (T2MI). It has been suggested that patients with T2MI with concomitant stable ischemic heart disease are at higher-risk. Purpose Our goals were two-fold. First, to examine 5-year mortality rates and mode of death among patients with type 1 (T1MI) and T2MI. Second, to evaluate the prognostic impact of coronary artery disease (CAD) on long-term outcomes among patients with T2MI. Methods Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational cohort study involving 1,640 consecutive emergency department patients with serial cardiac troponin (cTn) I measurements obtained on clinical indication. 5-year death rates, including mode of death, were examined among patients with T1MI and T2MI. CAD was defined as the presence of any of the following: history of CAD, prior MI, prior coronary artery bypass graft surgery, prior percutaneous coronary intervention, prior coronary stenting, or documented CAD (≥50%) on index admission angiography. Results Among 1640 patients, acute MI was diagnosed in 217 patients, including 77 (4.7%) classified as T1MI and 140 (8.5%) as T2MI. At 5-years, 23% (n=18) of patients with T1MI had died, with 61% (n=11) categorized as cardiac deaths. For T2MI, 37% (n=52) had died at 5-years, with 36% (n=19) categorized as cardiac deaths. Patients with T2MI had a higher 5-year mortality than T1MI (37% vs 23%, p=0.038) (Figure, Panel A), with T2MI more likely than T1MI to die from non-cardiac causes (64% vs. 39%, p=0.04). CAD was present in 22% (n=31) of patients with T2MI and associated with worse outcomes (p=0.0496) (Figure, Panel B). Conclusion T2MI has worse long term outcomes than T1MI. The predominant mode of death among patients with T2MI is non-cardiac. However, approximately 40% of deaths are cardiac. Further, we confirm the presence of CAD identifies a subset of patients with T2MI at high-risk. Acknowledgement/Funding Abbott Diagnostics and Hennepin Healthcare Research Institute (formerly MMRF)

We sought to determine the prevalence and correlates of conventional and expanded adverse childhood experiences (ACEs), including exposure to violence and racism, in perinatal women with mental illness. 133 perinatal women with mental illness completed the original ACEs (conventional ACEs) survey and the 6-question adverse environmental experiences (expanded ACEs) survey from the Philadelphia ACEs study. Associations between racial groups and ACE scores, mental health and psychosocial variables were evaluated. Subjects were predominantly white (68%) and married/partnered (66%), and 57% had at least 4 conventional ACEs. Compared to White women, Black women were significantly more likely to report conventional and expanded ACEs including experiencing racism and witnessing violence. Early life adversity was exceedingly common among pregnant and postpartum women with moderate to severe mental illness. Childhood exposure to racism and environmental trauma are important risk categories for perinatal mental illness.

BACKGROUND: Despite adverse prognoses of type 2 myocardial infarction and myocardial injury, an effective, practical risk stratification method remains an unmet clinical need. We sought to develop an efficient clinical bedside tool for estimating the risk of major adverse cardiovascular events at 180 days for this patient population. METHODS: The derivation cohort included patients with type 2 myocardial infarction or myocardial injury admitted to a tertiary hospital between 2012 and 2013 (n = 611). The primary outcome was a major adverse cardiovascular event (death or readmission for heart failure or myocardial infarction). The score included clinical variables significantly associated with the outcome. External validation was conducted using the UTROPIA cohort (n = 401). RESULTS: The TARRACO Score included cardiac troponin (cTn) concentrations and 5 independent clinical predictors of adverse cardiovascular events: age, hypertension, absence of chest pain, dyspnea, and anemia. The score exhibited good discriminative accuracy (area under the curve = 0.74; 95% CI, 0.700.79). Patients were classified into low-risk (score 0-6) and high-risk (score >= 7) categories. Major adverse cardiovascular events rates were 5 times more likely in high-risk patients compared with those at low risk (78.9 vs 15.4 events/100 patient-years, respectively; logrank P < .001). The external validation showed equivalent prognostic capacity (area under the curve=0.71, 0.65-0.78). CONCLUSION: A novel risk score based on bedside clinical variables and cTn concentrations allows risk stratification for death and cardiac-related rehospitalizations in patients with type 2 myocardial infarctions and myocardial injury. This score identifies patients at the highest risk of adverse events, a subset of patients who may benefit from close observation, medical intensification, or both. (C) 2018 Elsevier Inc. All rights reserved.