Methods of the PivotaL triAl of the Atellica VTLi point of care emergencY dePartment high sensitivity troponin evalUationS.

BACKGROUND: The Atellica® VTLi point-of-care (POC) High Sensitivity Cardiac Troponin-I (hs-cTnI) assay is intended for use as an aid in the diagnosis of myocardial infarction (MI). Our primary objective is to assess its diagnostic performance in patients presenting with suspected acute coronary syndrome (ACS). METHODS: This prospective observational study will enrol ∼1500 patients at ∼20 U.S. Emergency Departments. After informed consent, adults (>21 years of age) with suspected ACS, and no prior enrollment in this study, will provide a fingerstick and venous blood sample within 2 h of ED presentation, >2 to ≤4 h, and >4 to ≤9 h (max. blood draw = 60 mL). HEART and EDACS scores will be prospectively documented. Patients without the first blood draw may be enrolled if the second draw was obtained. Capillary and venous whole blood will undergo Atellica VTLi assay testing, with remaining venous sample processed to plasma and run. All results will be blinded to the clinical care team. Site operators will undergo a 3-day familiarization period. Quality control testing will be performed daily. At 30 ± 3 days, patient mortality status, major adverse cardiac events, and rehospitalizations will be determined. A clinical endpoint adjudication committee, blinded to hs-cTnI VTLi result, will define the final diagnosis. Sensitivity, specificity, and predictive values will describe the assay performance. RESULTS: We expect study completion within 114 weeks of enrollment of the first patient. CONCLUSIONS: It is anticipated that the Atellica VTLi hs-cTnI assay validation study will define a performance equivalent to lab-based hs-cTnI, with results within ∼8 min at the point of care.

Prognosis is worse with elevated cardiac troponin in nonacute coronary syndrome compared with acute coronary syndrome.

BACKGROUND: Cardiac troponin (cTn) can be elevated in many patients presenting to the emergency department (ED) with chest pain but without a diagnosis of acute coronary syndrome (ACS). We compared the prognostic significance of cTn in these different populations. METHODS: We retrospectively analyzed the CHOPIN study, which enrolled patients who presented to the ED with chest pain. Patients were grouped as ACS, non-ACS cardiovascular disease, noncardiac chest pain and chest pain not otherwise specified (NOS). We examined the prognostic ability of cTnI for the clinical endpoints of mortality and major adverse cardiovascular event (MACE; a composite of acute myocardial infarction, unstable angina, revascularization, reinfarction, and congestive heart failure and stroke) at 180-day follow-up. RESULTS: Among 1982 patients analyzed, 14% had ACS, 21% had non-ACS cardiovascular disease, 31% had a noncardiac diagnosis and 34% had chest pain NOS. cTnI elevation above the 99th percentile was observed in 52, 18, 6 and 7% in these groups, respectively. cTnI elevation was associated with mortality and MACE, and their relationships were more prominent in noncardiac diagnosis and chest pain NOS than in ACS and non-ACS cardiovascular diagnoses for mortality, and in non-ACS patients than in ACS patients for MACE (hazard ratio for doubling of cTnI 1.85, 2.05, 8.26 and 4.14, respectively; P for interaction 0.011 for mortality; 1.04, 1.23, 1.54 and 1.42, respectively; P for interaction <0.001 for MACE). CONCLUSION: In patients presenting to the ED with chest pain, cTnI elevation was associated with a worse prognosis in non-ACS patients than in ACS patients.

Finding acute coronary syndrome with serial troponin testing for rapid assessment of cardiac ischemic symptoms (FAST-TRAC): a study protocol.

OBJECTIVE: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department. METHODS: The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician's clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00880802.

Utility of COVID-19 antigen testing in the emergency department.

BACKGROUND: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis. METHODS: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. RESULTS: From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID-19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms >2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. CONCLUSIONS: The BinaxNOW point-of-care test has good sensitivity and excellent specificity for the detection of COVID-19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks.

A Multicenter Evaluation of a Point-of-Care Blood Glucose Meter System in Critically Ill Patients.

BACKGROUND: Our purpose was to evaluate the performance of the ACCU-CHEK® Inform II blood glucose monitoring system (Roche Diagnostics GmbH) compared with the perchloric acid hexokinase (PCA-HK) comparator method on the cobas® 6000 analyzer (Roche Diagnostics International Ltd) in critically ill patients. METHODS: Overall, 476 arterial (376 pediatric/adult, 100 neonate), 375 venous, and 100 neonatal heel-stick whole-blood samples were collected and evaluated from critical care settings at 10 US hospitals, including the emergency department, medical and surgical intensive care units (ICUs), and neonatal and pediatric ICUs. The ACCU-CHEK Inform II system was evaluated at 2 cutoff boundaries: boundary 1 was ≥95% of results within ±12 mg/dL of the reference (samples with blood glucose <75 mg/dL) or ±12% of the reference (glucose ≥75 mg/dL), and boundary 2 was ≥98% of results within ±15 mg/dL or ±15% of the reference. Clinical performance was assessed by evaluating sample data using Parkes error grid, Monte Carlo simulation, and sensitivity and specificity analyses to estimate clinical accuracy and implications for insulin dosing when using the ACCU-CHEK Inform II system. RESULTS: Proportions of results within evaluation boundaries 1 and 2, respectively, were 96% and 98% for venous samples, 94% and 97% for pediatric and adult arterial samples, 84% and 98% for neonatal arterial samples, and 96% and 100% for neonatal heel-stick samples. Clinical evaluation demonstrated high specificity and sensitivity, with low risk of potential insulin-dosing errors. CONCLUSIONS: The ACCU-CHEK Inform II system demonstrated clinically acceptable performance against the PCA-HK reference method for blood glucose monitoring in a diverse population of critically ill patients in US care settings.

Biomarkers Enhance Discrimination and Prognosis of Type 2 Myocardial Infarction.

BACKGROUND: The observed incidence of type 2 myocardial infarction (T2MI) is expected to increase with the implementation of increasingly sensitive cTn assays. However, it remains to be determined how to diagnose, risk-stratify, and treat patients with T2MI. We aimed to discriminate and risk-stratify T2MI using biomarkers. METHODS: Patients presenting to the emergency department with chest pain, enrolled in the CHOPIN study (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction), were retrospectively analyzed. Two cardiologists adjudicated type 1 MI (T1MI) and T2MI. The prognostic ability of several biomarkers alone or in combination to discriminate T2MI from T1MI was investigated using receiver operating characteristic curve analysis. The biomarkers analyzed were cTnI, copeptin, MR-proANP (midregional proatrial natriuretic peptide), CT-proET1 (C-terminal proendothelin-1), MR-proADM (midregional proadrenomedullin), and procalcitonin. The prognostic utility of these biomarkers for all-cause mortality and major adverse cardiovascular event (a composite of acute myocardial infarction, unstable angina pectoris, reinfarction, heart failure, and stroke) at 180-day follow-up was also investigated. RESULTS: Among the 2071 patients, T1MI and T2MI were adjudicated in 94 and 176 patients, respectively. Patients with T1MI had higher levels of baseline cTnI, whereas those with T2MI had higher baseline levels of MR-proANP, CT-proET1, MR-proADM, and procalcitonin. The area under the receiver operating characteristic curve for the diagnosis of T2MI was higher for CT-proET1, MR-proADM, and MR-proANP (0.765, 0.750, and 0.733, respectively) than for cTnI (0.631). Combining all biomarkers resulted in a similar accuracy to a model using clinical variables and cTnI (0.854 versus 0.884, P=0.294). Addition of biomarkers to the clinical model yielded the highest area under the receiver operating characteristic curve (0.917). Other biomarkers, but not cTnI, were associated with mortality and major adverse cardiovascular event at 180 days among all patients, with no interaction between the diagnosis of T1MI or T2MI. CONCLUSIONS: Assessment of biomarkers reflecting pathophysiologic processes occurring with T2MI might help differentiate it from T1MI. All biomarkers measured, except cTnI, were significant predictors of prognosis, regardless of the type of myocardial infarction.

Myocardial Infarction Can Be Safely Excluded by High-sensitivity Troponin I Testing 3 Hours After Emergency Department Presentation.

BACKGROUND: The accuracy and speed by which acute myocardial infarction (AMI) is excluded are an important determinant of emergency department (ED) length of stay and resource utilization. While high-sensitivity troponin I (hsTnI) >99th percentile (upper reference level [URL]) represents a "rule-in" cutpoint, our purpose was to evaluate the ability of the Beckman Coulter hsTnI assay, using various level-of-quantification (LoQ) cutpoints, to rule out AMI within 3 hours of ED presentation in suspected acute coronary syndrome (ACS) patients. METHODS: This multicenter evaluation enrolled adults with >5 minutes of ACS symptoms and an electrocardiogram obtained per standard care. Exclusions were ST-segment elevation or chronic hemodialysis. After informed consent was obtained, blood samples were collected in heparin at ED admission (baseline), ≥1 to 3, ≥3 to 6, and ≥6 to 9 hours postadmission. Samples were processed and stored at -20°C within 1 hour and were tested at three independent clinical laboratories on an immunoassay system (DxI 800, Beckman Coulter). Analytic cutpoints were the URL of 17.9 ng/L and two LoQ cutpoints, defined as the 10 and 20% coefficient of variation (5.6 and 2.3 ng/L, respectively). A criterion standard MI diagnosis was adjudicated by an independent endpoint committee, blinded to hsTnI, and using the universal definition of MI. RESULTS: Of 1,049 patients meeting the entry criteria, and with baseline and 1- to 3-hour hsTnI results, 117 (11.2%) had an adjudicated final diagnosis of AMI. AMI patients were typically older, with more cardiovascular risk factors. Median (IQR) presentation time was 4 (1.6-16.0) hours after symptom onset, although AMI patients presented ~0.5 hour earlier than non-AMI. Enrollment and first blood draw occurred at a mean of ~1 hour after arrival. To evaluate the assay's rule-out performance, patients with any hsTnI > URL were considered high risk and were excluded. The remaining population (n = 829) was divided into four LoQ relative categories: both hsTnI < LoQ (Lo-Lo cohort); first hsTnI < LoQ and 2nd > LoQ (Lo-Hi cohort); first > LoQ and second < LoQ (Hi-Lo cohort); or both > LoQ (Hi-Hi cohort). In patients with any hsTnI result <20% CV LoQ (Groups 1-3), n = 231 (23.9% ruled out), AMI negative predictive value (NPV) was 100% (95% confidence interval [CI] = 98.9% to 100%). In patients with any hsTnI below the 10% LoQ, n = 611 (58% rule out), AMI NPV was 100% (95% CI = 99.5% to 100%). Of the Hi-Hi cohort (i.e., no hsTnI below the 10% LoQ, but both < URL), there were four AMI patients, NPV was 98.2% (95% CI = 95.4% to 99.3%), and sensitivity was 96.6. CONCLUSIONS: Patients presenting >3 hours after the onset of suspected ACS symptoms, with at least two Beckman Coulter Access hsTnI < URL and at least one of which is below either the 10 or the 20% LoQ, had a 100% NPV for AMI. Two hsTnI values 1 to 3 hours apart with both < URL, but also >LoQ had inadequate sensitivity and NPV.

Renal Function and Scaled Troponin in Patients Presenting to the Emergency Department with Symptoms of Myocardial Infarction.

BACKGROUND: Cardiac troponins are often found to be elevated in patients with renal dysfunction, even in the absence of acute myocardial injury. The objective of this report was to characterize the scaled troponin values and proportion of adjudicated acute myocardial infarction (AMI) among patients with and without renal dysfunction. METHODS: The data was from a multicenter prospective study including patients presenting to the emergency department with symptoms of AMI. Troponin measurements were standardized across various assays by calculating the observed results as multiples of the assay-specific 99th percentile upper limit of normal. Patients with an estimated glomerular filtration rate (eGFR; calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) <60 mL/min/1.73 m2 were considered to have renal dysfunction. RESULTS: Of 430 included patients, 249 (58%) were male and 181 (42%) were female, with a mean age of 55.9 ± 12.3 and 57.3 ± 12.8 years, respectively. Eighty-seven (20.2%) had renal dysfunction. The proportions of patients with at least one scaled troponin value above the 99th percentile cut-off point among patients with and without renal dysfunction were 40 (45.9%) and 81 (23.6%) respectively (p < 0.001). The proportions of patients with an adjudicated diagnosis of AMI among those with and without renal dysfunction were 20.7 and 18.7%, respectively (p = 0.67). Using scaled troponins, by the second test there was >5X and by the third test >15X separation in the excursion of troponin among those with AMI compared to those without. CONCLUSIONS: One or more elevated troponin values are common in those with renal dysfunction. Scaled troponins for eGFR groups were similar, indicating that the use of this interpretative technique is applicable in discerning AMI for those with and without renal dysfunction.

Interpretation of positive troponin results among patients with and without myocardial infarction.

Measuring cardiac troponins is integral to diagnosing acute myocardial infarction (AMI); however, troponins may be elevated without AMI, and the use of multiple different assays confounds comparisons. We considered characteristics and serial troponin values in emergency department chest pain patients with and without AMI to interpret troponin excursions. We compared serial troponin in 124 AMI and non-AMI patients from the observational Performance of Triage Cardiac Markers in the Clinical Setting (PEARL) study who presented with chest pain and had at least one troponin value exceeding the 99th percentile of normal. Because 8 assays were used during data collection, we employed a method of scaling the troponin value to the corresponding assay's 99th percentile upper reference limit to standardize the results. In 81 AMI patients, 96% had elevated troponin at the first test following initial elevation, compared to 73% of the 43 non-AMI patients (P < 0.001). Scaling troponin to the 99th percentile of normal yielded a median value that was 4.8 [2.2, 14.1] times higher than the 99th percentile cutpoint among AMI patients, compared to 2.3 [1.5, 6.5] times higher among non-AMI patients (P = 0.04). The rise in serial scaled troponin values distinguished the AMI patients. Scaling to the 99th percentile was useful for comparing troponin when different assays were utilized.

Absolute and relative changes (delta) in troponin I for early diagnosis of myocardial infarction: Results of a prospective multicenter trial.

OBJECTIVES: We investigated absolute and relative cardiac troponin I (TnI) delta changes, optimal sampling protocols, and decision thresholds for early diagnosis of myocardial infarction (MI). Serial cardiac biomarker values demonstrating a rise and/or fall define MI diagnosis; however the magnitude of change, timing, and diagnostic accuracy of absolute versus relative (percentage) deltas remains unsettled. METHODS: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent symptoms of acute coronary syndrome at 14 medical centers. Diagnosis was adjudicated by an independent central committee. RESULTS: Elevated TnI above a threshold of 0.03ng/mL demonstrated significant diagnostic efficacy (AUC 0.96). For patients with TnI<0.03ng/mL and symptom onset≥8h, 99.1% (NPV) were diagnosed with conditions other than MI. Absolute delta performed significantly better than relative delta at 1-3h (AUC 0.84 vs 0.69), 3-6h (0.85 vs 0.73), and 6-9h (0.91 vs 0.79). Current recommendations propose ≥20% delta within 3-6h; however, results were optimized using an absolute delta of 0.01 or 0.02ng/mL. Sensitivity results for absolute delta at 1-3h and 3-6h (75.8%, 78.3%) were superior to relative delta (48.0%, 61.3%). NPV (rule out) was 99.6% when baseline TnI<0.03ng/mL and absolute delta TnI<0.01ng/mL. CONCLUSIONS: Absolute delta performed significantly better than relative delta at all time intervals. Baseline TnI and absolute delta may be used in conjunction to estimate probability of MI. Consensus recommendations are supported for sampling on admission and 3h later, repeated at 6h in patients when clinical suspicion remains high.

Diagnostic performance of cardiac Troponin I for early rule-in and rule-out of acute myocardial infarction: Results of a prospective multicenter trial.

OBJECTIVES: To compare emergency department TnI serial sampling intervals, determine optimal diagnostic thresholds, and report representative diagnostic performance characteristics for early rule-in and rule-out of MI. METHODS: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent ischemic symptoms suggestive of acute coronary syndromes at 14 medical centers. Diagnosis was adjudicated by an independent central committee. RESULTS: TnI ≥0.03ng/mL provided 96.0% sensitivity and 89.4% specificity at 1-3h after admission, and 94.9% sensitivity and 86.7% specificity at 3-6h. NPV (rule-out, non-MI) was 99.5% at 1-3h, and 99.0% at 3-6h when TnI is <0.03ng/mL. NPV was 99.1% when TnI is <0.03ng/mL and time of symptom onset is ≥8h. Approximately 50-58% (PPV) of patients with TnI ≥0.03ng/mL were diagnosed with MI, depending upon time from onset or admission; PPVs emphasize the importance of serial samples and delta TnI (rising or falling pattern) when low cutoffs are used. Nevertheless, even a single elevated TnI value increased the risk of MI. As TnI values rose, the probability of MI increased. Values ≥0.20ng/mL were associated with nearly 90% probability of MI. CONCLUSIONS: We report a large multicenter prospective adjudicated trial assessing troponin for early rule-in and rule-out using the Universal Definition of MI and conducted in primary care hospital-associated emergency departments. Our study demonstrates high diagnostic accuracy at early observation times, and reinforces consensus recommendations for sampling on admission and 3h later, repeated at 6h when clinical suspicion remains high.

Residents' performance in the interpretation of on-call "triple-rule-out" CT studies in patients with acute chest pain.

RATIONALE AND OBJECTIVES: To evaluate the performance of radiology residents in the interpretation of on-call, emergency "triple-rule-out" (TRO) computed tomographic (CT) studies in patients with acute chest pain. MATERIALS AND METHODS: The study was institutional review board-approved and Health Insurance Portability and Accountability Act compliant. Data from 617 on-call TRO studies were analyzed. Dedicated software enables subspecialty attendings to grade discrepancies in interpretation between preliminary trainee reports and their final interpretation as "unlikely to be significant" (minor discrepancies) or "likely to be significant" for patient management (major discrepancies). The frequency of minor, major and all discrepancies in resident's TRO interpretations was compared to 609 emergent non-electrocardiography (ECG)-synchronized chest CT studies using Pearson χ(2) test. RESULTS: Minor discrepancies occurred more often in the TRO group (9.1% vs. 3.9%, P < .001), but there was no difference in the frequency of major discrepancies (2.1% vs. 2.8%, P = .55). Minor discrepancies in the TRO group most commonly resulted from missed extrathoracic findings with missed liver lesions being the most frequent. Major discrepancies mostly encompassed cardiac and extracardiac vascular findings but did not result in unnecessary interventions, significant immediate changes in management, or adverse patient outcomes. CONCLUSIONS: On-call resident interpretation of TRO CT studies in patients with acute chest pain is congruent with final subspecialty attending interpretation in the overwhelming majority of cases. The rate of discrepancies likely to affect patient management in this domain is not different from emergent non-ECG-synchronized chest CT.

Differences in coronary artery disease by CT angiography between patients developing unstable angina pectoris vs. major adverse cardiac events.

OBJECTIVE: CT angiography (CTA) has prognostic value in patients. But it is unknown whether differences in atherosclerosis by CTA predict the development of unstable angina pectoris (UAP) vs. major adverse cardiac events (MACE). METHODS: We followed patients undergoing CTA as part of their acute chest pain work-up. Primary outcome was the development of UAP or MACE (cardiac death, myocardial infarction, revascularization) during a minimum follow-up of 12-months. CTAs were assessed for extent and composition of coronary plaque and stenosis. Ordinal regression with a 3-level outcome (no events, UAP, MACE) was applied. RESULTS: Among 315 patients, 22 developed UAP and 31 MACE. While UAP patients had higher atherosclerosis burden with respect to all assessed features compared to patients with no events (p ≤ 0.02), only mixed plaque extent was significantly different between UAP and MACE patients (p=0.02). The odds ratio was 4.55 for being in a higher disease-level comparing patients with low extent to those with no mixed plaque, and 3.02 comparing patients with high to those with low. These findings remained after adjustments for potential confounders. CONCLUSION: The extent of mixed coronary plaque is different between patients who develop UAP vs. MACE, supporting the hypothesis that it is a more culprit morphology.

Atherosclerotic plaque burden in cocaine users with acute chest pain: analysis by coronary computed tomography angiography.

Chest pain associated with cocaine use represents an increasing problem in the emergency department (ED). Cocaine use has been linked to the acute coronary syndrome (ACS) and acute myocardial infarction (AMI). We used coronary computed tomography angiography (cCTA) to evaluate the prevalence, severity and composition of atherosclerotic lesions in cocaine users. We studied 78 patients with non-occasional cocaine use (52 men, 44 ± 7 years, 23 under the acute influence) and acute chest pain but without ACS, who had undergone cCTA in the ED. Patients were matched one-to-one by gender, race, symptoms, and risk-factors with a control cohort (n = 78; 52 men, 45 ± 6 years) not using cocaine. Each coronary segment was evaluated for the presence and composition (calcified, non-calcified, partially calcified) of atherosclerotic plaque and for stenosis. The prevalence of coronary stenosis was not significantly different between patients with and without cocaine use (13% versus 5%, P > 0.05). However, cocaine users on average had significantly more atherosclerotic plaques (0.44 ± 0.88 versus 0.29 ± 0.83, P < 0.05) and a tendency towards more calcified (0.64 ± 1.23 versus 0.55 ± 1.22, P > 0.05) and non-calcified plaques (0.26 ± 0.63 versus 0.17 ± 0.57, P > 0.05), yet not reaching statistical significance. Furthermore, cocaine users had significantly more partially calcified plaques (0.41 ± 0.61 versus 0.17 ± 0.41, P < 0.05) and higher partially calcified plaque volume (59.7 ± 33.3 mm(3) versus 25.6 ± 12.6 mm(3), P < 0.05). Thus, cocaine users tend to have more pronounced coronary atherosclerosis compared to patients without cocaine use at the time of presentation with acute chest pain.

Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction).

OBJECTIVES: The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99 th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED). BACKGROUND: Copeptin is secreted from the pituitary early in the course of AMI. METHODS: This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99 th percentile 40 ng/l; 10% coefficient of variation 0.03 µg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results. RESULTS: AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001). CONCLUSIONS: Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws.

Incremental prognostic value of different components of coronary atherosclerotic plaque at cardiac CT angiography beyond coronary calcification in patients with acute chest pain.

PURPOSE: To systematically evaluate the incremental predictive value of cardiac computed tomographic (CT) angiography beyond the assessment of coronary artery calcium (CAC) in patients who present with acute chest pain but without evidence of acute coronary syndrome (ACS). MATERIALS AND METHODS: The human research committee approved this study and waived the need for individual written informed consent. The study was HIPAA compliant. A total of 458 patients (36% male; mean age, 55 years ± 11) with acute chest pain at low to intermediate risk for coronary artery disease underwent coronary calcification assessment with cardiac CT angiography. All patients who did not experience ACS at index hospitalization were followed for instances of a major adverse cardiac event (MACE), such as a myocardial infarct, revascularization, cardiac death, or angina requiring hospitalization. CAC score and cardiac CT angiography were used to derive the presence and extent of atherosclerotic plaque (calcified, noncalcified, or mixed), and obstructive lesions (>50% luminal narrowing) were related to outcomes by using univariate and adjusted Cox proportional hazards models. RESULTS: Of the 458 patients, 70 (15%) experienced MACE (median follow-up, 13 months). Patients with no plaque at cardiac CT angiography remained free of events during the follow-up period, while 11 (5%) of 215 patients with no CAC had MACE. The extent of plaque was the strongest predictor of MACE independent of traditional risk factors (hazard ratio [HR], 151.77 for four or more segments containing plaque as compared with those containing no plaque; P < .001). Patients with mixed plaque were more likely to experience MACE (HR, 86.96; P = .002) than those with exclusively noncalcified plaque (HR, 58.06; P = .005) or exclusively calcified plaque (HR, 32.94; P = .02). CONCLUSION: The strong prognostic value of cardiac CT angiography is incremental to its known diagnostic value in patients with acute chest pain without ACS and is independent of traditional risk factors and CAC.

Coronary atherosclerosis in African American and white patients with acute chest pain: characterization with coronary CT angiography.

PURPOSE: To use coronary computed tomographic (CT) angiography to compare the prevalence, extent, and composition of coronary atherosclerotic lesions in African American and white patients with acute chest pain. MATERIALS AND METHODS: The institutional review board waived the requirement for informed consent for this retrospective, HIPAA-compliant matched-cohort study. The authors analyzed the CT angiographic data of 301 patients (150 consecutive African American patients; 151 white control patients; mean age, 55 years ± 11 [standard deviation]; 33% male) with acute chest pain. Each coronary artery segment was evaluated for presence of atherosclerotic plaque, plaque composition (calcified, noncalcified, or mixed), and stenosis. In addition, the noncalcified plaque volume was quantified by using a threshold-based automated algorithm. The presence and extent of atherosclerotic plaque were compared between the groups by using univariate and multivariate regression analyses. RESULTS: While there was no significant difference between the African American and white patients with respect to presence of any plaque (118 [79%] of 150 vs 112 [74%] of 151 patients, respectively; P = .36) or presence of stenosis (26 [17%] vs 37 [24%] patients, respectively; P = .13), the African American patients had a significantly higher prevalence (96 [64%] vs 62 [41%] patients, respectively; P < .001) and volume (median volume, 2.2 vs 1.4 mL, respectively; P < .001) of noncalcified plaque, independent of diabetes and other cardiovascular risk factors (odds ratio, 2.45; 95% confidence interval: 1.52, 4.04). In contrast, the African American patients had a lower prevalence of calcified plaque (39 [26%] vs 68 [45%] white patients, P = .001). CONCLUSION: Study results suggest that atherosclerotic plaque burden and composition, as measured by using coronary CT angiography, differ between African American and white patients, with relatively more noncalcified disease in African Americans and more calcified disease in white individuals. Further research is warranted to determine whether CT plaque characterization can improve cardiac risk prediction in African Americans.

Cardiac CT in the assessment of acute chest pain in the emergency department.

OBJECTIVE: The purpose of this article is to describe the current role of ECG-synchronized CT in the evaluation of patients with acute chest pain (triple rule-out) in the emergency department. We discuss clinical contexts of the chest pain algorithm, technical improvements that have enabled CT to attain its current role for this application, scan protocols and radiation considerations, the evidence base regarding diagnostic and prognostic performance, and initial data on the cost-effectiveness of this promising emerging test. CONCLUSION: Currently available evidence suggests that CT-based approaches with modern scan technology are safe, accurate, and potentially cost-saving, although large-scale clinical trials are needed to ascertain the precise role of CT in the evaluation of acute chest pain.