Pivotal findings for a high-sensitivity cardiac troponin assay: Results of the HIGH-US study.

BACKGROUND: Cardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and diagnostic accuracy of the Atellica IM TnIH assay to determine high-sensitivity performance and appropriate diagnostic performance for clinical use. METHODS: Sex-specific 99th percentile upper reference limits (URLs) were determined for a healthy cohort of 1007 women and 1000 men using non-parametric statistics. High-sensitivity performance was assessed by examining if imprecision was ≤10% at sex-specific URLs and if ≥50% of cTnI values for each sex exceeded the assay's limit of detection (LoD) with the AACC Universal Sample Bank. Precision, high-dose hook effect, endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization was with 2494 suspected AMI subjects presenting to emergency departments across the United States. AMI was adjudicated by expert cardiologists and emergency medicine physicians. There were no comorbidity exclusions. RESULTS: 99th percentile URLs were 34 ng/L, 53 ng/L and 45 ng/L for the female, male and overall populations, respectively. Total imprecision was <5% from 12 ng/L to 16,000 ng/L; ≥55% of cTnI values for each sex exceeded the LoD. No high-dose hook or endogenous/exogenous interferences were identified. After 2.5-3.5 h post presentation the sensitivity and specificity were >90%; negative and positive predictive value were ≥98% and >60%, respectively. Non-AMI subjects with comorbidities and values exceeding 99th percentile URLs had absolute and percent change at 2-4 h that were lower than AMI patients with comorbidities (p = 0.001). CONCLUSION: The Atellica IM TnIH assay is a high-sensitivity method and demonstrates clinical performance appropriate for AMI diagnosis.

Trial design for assessing analytical and clinical performance of high-sensitivity cardiac troponin I assays in the United States: The HIGH-US study.

BACKGROUND: High-sensitivity cardiac troponin I (hs-cTnI) assays have been developed that quantify lower cTnI concentrations with better precision versus earlier generation assays. hs-cTnI assays allow improved clinical utility for diagnosis and risk stratification in patients presenting to the emergency department with suspected acute myocardial infarction. We describe the High-Sensitivity Cardiac Troponin I Assays in the United States (HIGH-US) study design used to conduct studies for characterizing the analytical and clinical performance of hs-cTnI assays, as required by the US Food and Drug Administration for a 510(k) clearance application. This study was non-interventional and therefore it was not registered at clinicaltrials.gov. METHODS: We conducted analytic studies utilizing Clinical and Laboratory Standards Institute guidance that included limit of blank, limit of detection, limit of quantitation, linearity, within-run and between run imprecision and reproducibility as well as potential interferences and high dose hook effect. A sample set collected from healthy females and males was used to determine the overall and sex-specific cTnI 99th percentile upper reference limits (URL). The total coefficient of variation at the female 99th percentile URL and a universally available American Association for Clinical Chemistry sample set (AACC Universal Sample Bank) from healthy females and males was used to examine high-sensitivity (hs) performance of the cTnI assays. Clinical diagnosis of enrolled subjects was adjudicated by expert cardiologists and emergency medicine physicians. Assessment of temporal diagnostic accuracy including sensitivity, specificity, positive predictive value, and negative predictive value were determined at presentation and collection times thereafter. The prognostic performance at one-year after presentation to the emergency department was also performed. This design is appropriate to describe analytical characterization and clinical performance, and allows for acute myocardial infarction diagnosis and risk assessment.

Critical Care Air Transport Team severe traumatic brain injury short-term outcomes during flight for Operation Iraqi Freedom/Operation Enduring Freedom.

INTRODUCTION: Our understanding of the expertise and equipment required to air transport injured soldiers with severe traumatic brain injuries (TBIs) continue to evolve. METHODS: We conducted a retrospective chart review of characteristics, interventions required and short-term outcomes of patients with severe TBI managed by the US Air Force Critical Care Air Transport Teams (CCATTs) deployed in support of Operation Iraqi Freedom and Operation Enduring Freedom between 1 June 2007 and 31 August 2010. Patients were cared for based on guidelines given by the Brain Trauma Foundation and the Joint Theater Trauma System by non-neurosurgeon physicians with dedicated neurocritical care training. We report basic characteristics, injuries, interventions required and complications during transport. RESULTS: Intracranial haemorrhage was the most common diagnosis in this cohort. Most injuries were weapon related. During this study, there were no reported in-flight deaths. The majority of patients were mechanically ventilated. There were 45 patients who required at least one vasopressor to maintain adequate tissue perfusion, including four patients who required three or more. Some patients required intracranial pressure (ICP) management, treatment of diabetes insipidus and/or seizure prophylaxis medications. CONCLUSIONS: Air transport personnel must be prepared to provide standard critical care but also care specific to TBIs, including ICP control and management of diabetes insipidus. Although these patients and their potential complications are traditionally managed by neurosurgeons, those providers without neurosurgical backgrounds can be provided this training to help fill a wartime need. This study provides data for the future development of air transport guidelines for validating and clearing flight surgeons.

Combination of Goldman risk and initial cardiac troponin I for emergency department chest pain patient risk stratification.

BACKGROUND: Accurate identification of low-risk emergency department (ED) chest pain patients who may be safe for discharge has not been well defined. Goldman criteria have reliably risk-stratified patients but have not identified any subset safe for ED release. Cardiac troponin I (cTnI) values have also been shown to risk-stratify patients but have not identified a subset safe for ED release. OBJECTIVE: To test the hypothesis that ED chest pain patients with a Goldman risk of < or =4% and a single negative cTnI (< or =0.3 ng/mL) at the time of ED presentation would be safe for discharge [<1% risk for death, acute myocardial infarction (AMI), revascularization]. METHODS: A prospective cohort study was performed in which consecutive ED chest pain patients were enrolled from July 1999 to November 2000. Data collected included patient demographics, medical and cardiac history, electrocardiogram, and creatine kinase-MB and cTnI. Goldman risk stratification score was calculated while patients were still in the ED. Hospital course was followed daily. Telephone follow-up occurred at 30 days. The main outcome was death, AMI, or revascularization (percutaneous transluminal coronary angioplasty/stents/coronary artery bypass grafting) within 30 days. RESULTS: Of 2,322 patients evaluated, 998 had both a Goldman risk < or =4% and a cTnI < or =0.3 ng/mL. During the initial hospitalization, 37 patients met the composite endpoint (3.7%): 6 deaths (0.7%), 17 AMIs (1.7%), 18 revascularizations (1.8%). Between the time of hospital discharge and 30-day follow-up, 15 patients met the composite endpoint: 4 deaths (0.4%), 6 AMIs (0.6%), and 5 revascularizations (0.5%). Overall, 49 patients met the composite endpoint (4.9%; 95% CI = 3.6% to 6.2%): 10 deaths (1.0%; 95% CI = 0.4% to 1.6%); 23 AMIs (2.3%; 95% CI = 1.4% to 3.2%), and 23 revascularizations (2.3%; 95% CI = 1.4% to 3.2%) within 30 days of presentation. CONCLUSIONS: The combination of two risk stratification modalities for ED chest pain patients (Goldman risk < or =4% and cTnI < or =0.3 ng/mL) did not identify a subgroup of chest pain patients at <1% risk for death, AMI, or revascularization within 30 days.