RESUMEN

OBJECTIVES: This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. METHODS: LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. RESULTS: The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. CONCLUSIONS: Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

Asunto(s)

Asunto(s)

RESUMEN

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.

Asunto(s)

Asunto(s)

Asunto(s)

RESUMEN

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 (<60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods. 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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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 <0.05). T2MIs were more likely to be diagnosed using subjective criteria (symptoms alone) than T1MI (42% vs. 12%, p <0.0001). Patients with objective T2MI, but not subjective T2MI, had a two-fold increase in early mortality compared with myocardial injury, with 30- and 60-day hazard ratios (95% confidence interval) of 2.3 (0.9, 6.2) and 2.0 (0.9, 4.7) respectively. 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.

Asunto(s)

RESUMEN

BACKGROUND: 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. OBJECTIVES: This study sought to examine single measurement hs-cTnI to identify patients at low and high risk for acute myocardial infarction (MI). METHODS: 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. RESULTS: 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%. CONCLUSIONS: 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.

Asunto(s)

Asunto(s)

RESUMEN

OBJECTIVE: Our objective was to examine the appropriateness of cardiac troponin (cTn) testing among patients with cTn increases. METHODS: 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 increases >99th percentile and analyzed using both contemporary and high-sensitivity (hs) cTnI assays according to sub-specialty, diagnoses, and symptoms. RESULTS: Appropriateness 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%). CONCLUSIONS: 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.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

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, 0.70-0.79). 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.

Asunto(s)

RESUMEN

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<30 ml/min per 1.73 m2; n=81) and 40%-41% on dialysis (n=78). Positive predictive values decreased with decreasing renal function from 51%-57% with normal function to 27%-42% with severely impaired function and 15%-32% on dialysis. Receiver operating characteristic curve areas trended lower at baseline and 3 hours with renal impairment. Mortality increased significantly with increasing hs-cTnI tertile (1.3%, 6.0%, and 10.4%, respectively). Patients with hs-cTnI concentration exceeding concentrations in the 99th percentiles had a mortality rate (11.7%) significantly higher than that of patients with concentrations between 99th percentile concentrations and limit of detection (6.2%) or below limit of detection (1.1%). Renal dysfunction and dialysis reduced the rule-in performance but not the rule-out performance of hs-cTnI for myocardial infarction, and mortality increased in patients with higher hs-cTnI concentrations and any level of renal dysfunction.

Asunto(s)

RESUMEN

Objective To evaluate how selection of patients for high sensitivity cardiac troponin testing affects the diagnosis of myocardial infarction across different healthcare settings.Design Prospective study of three independent consecutive patient populations presenting to emergency departments.Setting Secondary and tertiary care hospitals in the United Kingdom and United States.Participants High sensitivity cardiac troponin I concentrations were measured in 8500 consecutive patients presenting to emergency departments: unselected patients in the UK (n=1054) and two selected populations of patients in whom troponin testing was requested by the attending clinician in the UK (n=5815) and the US (n=1631). The final diagnosis of type 1 or type 2 myocardial infarction or myocardial injury was independently adjudicated.Main outcome measures Positive predictive value of an elevated cardiac troponin concentration for a diagnosis of type 1 myocardial infarction.Results Cardiac troponin concentrations were elevated in 13.7% (144/1054) of unselected patients, with a prevalence of 1.6% (17/1054) for type 1 myocardial infarction and a positive predictive value of 11.8% (95% confidence interval 7.0% to 18.2%). In selected patients, in whom troponin testing was guided by the attending clinician, the prevalence and positive predictive value were 14.5% (843/5815) and 59.7% (57.0% to 62.2%) in the UK and 4.2% (68/1631) and 16.4% (13.0% to 20.3%) in the US. Across both selected patient populations, the positive predictive value was highest in patients with chest pain, with ischaemia on the electrocardiogram, and with a history of ischaemic heart disease.Conclusions When high sensitivity cardiac troponin testing is performed widely or without previous clinical assessment, elevated troponin concentrations are common and predominantly reflect myocardial injury rather than myocardial infarction. These observations highlight how selection of patients for cardiac troponin testing varies across healthcare settings and markedly influences the positive predictive value for a diagnosis of myocardial infarction.

Asunto(s)

RESUMEN

OBJECTIVES: 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. METHODS: 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/1.73m2) were measured, along with identification of statin use, to better define normality. 99th percentile URLs were determined by the non-parametric (NP), Harrell-Davis Estimator (HDE) and Robust (R) methods. RESULTS: 355 men and 339 women remained after exclusions. Overall<50% 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. CONCLUSIONS: 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.

Asunto(s)

RESUMEN

BACKGROUND: We examined the diagnostic performance of high-sensitivity cardiac troponin I (hs-cTnI) vs contemporary cTnI with use of the 99th percentile alone and with a normal electrocardiogram (ECG) to rule out acute myocardial infarction (MI) and serial changes (deltas) to rule in MI. METHODS: We included consecutive patients presenting to a US emergency department with serial cTnI onclinical indication. Diagnostic performance for acute MI, including MI subtypes, and 30-day outcomes were examined. RESULTS: Among 1631 patients, MI was diagnosed in 12.9% using the contemporary cTnI assay and in 10.4% using the hs-cTnI assay. For ruling out MI, contemporary cTnI ≤99th percentile at 0, 3, and 6 h and a normal ECG had a negative predictive value (NPV) of 99.5% (95% CI, 98.6-100) and a sensitivity of 99.1% (95% CI, 97.4-100) for diagnostic and safety outcomes. Serial hs-cTnI measurements ≤99th percentile at 0 and 3 h and a normal ECG had an NPV and sensitivity of 100% (95% CI, 100-100) for diagnostic and safety outcomes. For ruling in MI, contemporary cTnI measurements had specificities of 84.4% (95% CI, 82.5-86.3) at presentation and 78.7% (95% CI, 75.4-82.0) with serial testing at 0, 3, and 6 h, improving to 89.2% (95% CI, 87.1-91.3) by using serial cTnI changes (delta, 0 and 6 h) >150%. hs-cTnI had specificities of 86.9% (95% CI, 85.1-88.6) at presentation and 85.7% (95% CI, 83.5-87.9) with serial testing at 0 and 3 h, improving to 89.3% (95% CI, 87.3-91.2) using a delta hs-cTnI (0 and 3 h) >5 ng/L. CONCLUSIONS: hs-cTnI and contemporary cTnI assays are excellent in ruling out MI following recommendations predicated on serial testing and the 99th percentile with a normal ECG. For ruling in MI, deltas improve the specificity. ClinicalTrials.gov Identifier: NCT02060760.

Asunto(s)

RESUMEN

BACKGROUND: Studies addressing patients with type 2 myocardial infarction and myocardial injury, including the impact of using high-sensitivity (hs) cardiac troponin (cTn) assays on their incidence are needed. METHODS: Ours is a prospective, observational US cohort study. Consecutive emergency department patients with serial cTnI measurements were studied. Outcomes included 180-day mortality and major adverse cardiac events, including 2-year follow-up for those with myonecrosis. RESULTS: Among 1640 patients, using a contemporary cTnI assay, 30% (n = 497) had ≥1 cTnI >99th percentile, with 4.7% (n = 77), 8.5% (n = 140), and 17% (n = 280) classified as type 1 myocardial infarction, type 2 myocardial infarction, and myocardial injury, respectively. Compared with patients without myonecrosis, 180-day mortality was higher for type 2 myocardial infarction (4% vs 13%, P < .0001) (adjusted hazard ratio 2.7; 95% confidence interval, 1.6-4.8; P = .0005) and myocardial injury (4% vs 11%, P < .0001) (adjusted hazard ratio 1.8; 95% confidence interval, 1.1-3.0; P = .02), both with mortality >20% at 2 years. Predictors of 2-year mortality for type 2 myocardial infarction included age, congestive heart failure, and beta-blockers. Relative to the contemporary cTnI assay, hs-cTnI had less myonecrosis (30% vs 26%, P = .003) and acute myocardial infarction (13.2% vs 10.8%, P = .032), including fewer type 2 myocardial infarctions (8.5% vs 6.3, P = .01), with no difference in myocardial injury (17% vs 15%, P = .1). CONCLUSIONS: cTnI increases are encountered in approximately a third of patients, the majority due to nonatherothrombotic conditions. Compared with patients without myonecrosis, type 2 myocardial infarction and myocardial injury have worse short-term outcomes, with mortality rates >20% at 2 years. hs-cTnI assay does not lead to more myocardial injury or infarction.

Asunto(s)

RESUMEN

BACKGROUND: This study examined the performance of single high-sensitivity cardiac troponin I (hs-cTnI) measurement strategies to rule out acute myocardial infarction. METHODS: This was a prospective, observational study of consecutive patients presenting to the emergency department (n = 1631) in whom cTnI measurements were obtained using an investigational hs-cTnI assay. The goals of the study were to determine 1) negative predictive value (NPV) and sensitivity for the diagnosis of acute myocardial infarction, type 1 myocardial infarction, and type 2 myocardial infarction; and 2) safety outcome of acute myocardial infarction or cardiac death at 30 days using hs-cTnI less than the limit of detection (LoD) (<1.9 ng/L) or the High-STEACS threshold (<5 ng/L) alone and in combination with normal electrocardiogram (ECG). RESULTS: Acute myocardial infarction occurred in 170 patients (10.4%), including 68 (4.2%) type 1 myocardial infarction and 102 (6.3%) type 2 myocardial infarction. For hs-cTnI

Asunto(s)