Early Diagnostic Efficiency of Cardiac Troponin I and Troponin T for Acute Myocardial Infarction

Objective : To compare the early diagnostic efficiency of the cardiac troponin I (cTn-I) level with that of the cardiac troponin T (cTn-T) level, as well as the creatine kinase (CK), CK-MB, and myoglobin levels, for acute myocardial infarction (AMI) in patients without an initially diagnostic ECG presenting to the ED within 24 hours of the onset of their symptoms. Methods : A prospective, observational, cohort study was performed involving chest pain patients admitted to a large urban community hospital. Participants were consecutive consenting ED chest pain patients ≥30 years of age. Exclusions included duration of symptoms >24 hours, inability to complete data collection, receipt of CPR, and ST-segment elevation on the initial ECG. Measurements included levels of cTn-I, cTn-T, CK, CK-MB, and myoglobin at the time of presentation and 1, 2, 6, and 12–24 hours after presentation as well as presenting ECG and clinical follow-up. Confirmation of the diagnosis of AMI was based on World Health Organization criteria. Results : Of the 177 patients included in the study, 27 (15%) were diagnosed as having AMIs. The sensitivities of all 5 biochemical markers for AMI were poor at the time of ED presentation (3.7–33.3%) but rose significantly over the study period. The sensitivity of cTn-T was significantly better than that of cTn-I over the initial 2 hours, but both markers' sensitivities were low (<60%) during this time frame. The cTn-I was significantly more specific for AMI than was the cTn-T, but not significantly better than CK-MB or myoglobin. Likelihood ratio analysis showed that the biochemical markers with the highest positive likelihood ratios for AMI during the first 2 hours following ED presentation were myoglobin and CK-MB. From 6 through 24 hours, the positive likelihood ratios for cTn-I, CK-MB, and myoglobin were superior to those of CK and cTn-T. Conclusions : cTn-I, CK-MB, and myoglobin are significantly more specific for AMI than are CK and cTn-T. Myoglobin is the biochemical marker having the highest combination of sensitivity, specificity, and negative predictive value for AMI within 2 hours of ED presentation. Neither cTn-I nor cTn-T offers significant advantages over myoglobin and CK-MB in the early (≤2 hours) initial screening for AMI. The cardiac troponins are of benefit in identifying AMI ≤6 hours after presentation.     

Evaluation of a Bedside Whole-blood Rapid Troponin T Assay in the Emergency Department

Objective : To evaluate the performance of a new bedside whole-blood rapid assay for cardiac troponin T (cTnT) in patients presenting to the ED with symptoms consistent with acute coronary ischemia. Methods : A prospective, observational trial was performed in 8 participating medical centers. Serial blood samples were obtained on presentation to the ED and 3 and 6 hours later. The cTnT whole-blood rapid assays were performed immediately at the site. Treating physicians and patients were blinded to the results of the rapid assays. Serum samples were analyzed at the core laboratory for serum cTnT, creatine kinase (CK)-MB, and myoglobin. The sensitivity of the rapid assay for detecting acute myocardial infarction (AMI) was compared with the sensitivities of serum cTnT, CK-MB, and myoglobin assays. Results : Of 721 patients, 102 were diagnosed as having AMI. The median elapsed time from symptom onset to ED arrival was 3 hours. The sensitivities of the rapid assay for detecting AMI were 19.6%, 59.0%, and 69.7% at 0, 3, and 6 hours, respectively. The sensitivities of the serum cTnT assay (p-values for comparison with the rapid assay for cTnT) were 25.0% (p = 0.18), 69.6% (p = 0.04), and 79.8% (p = 0.02) at 0, 3, and 6 hours, respectively. The CK-MB and myoglobin sensitivities were 21.9%, 64.5%, and 81.0%; and 43.8%, 77.4%, and 71.4%, respectively. There were 7 patients with AMI who had negative rapid assay readings and positive serum cTnT levels; 4 of these patients were enrolled at the same site. Twenty patients not diagnosed as having AMI had at least one positive rapid assay. Fourteen of these 20 patients had a diagnosis of clinically relevant cardiac disease. Conclusions : The sensitivity of this whole-blood rapid cTnT assay for detecting AMI is comparable to that of current serum assays and offers the advantage of providing rapid bedside results. Discrepancies between serum and whole-blood assays for cTnT noted in this study may indicate the need for further education for the test reader prior to patient use.     

Evaluation of a New Assay for Cardiac Troponin I vs Creatine Kinase-MB for the Diagnosis of Acute Myocardial Infarction

Objective : To compare a new assay for cardiac troponin I (cTn-I) with an assay for creatine kinase-MB (CK-MB) for the diagnosis of acute myocardial infarction (AMI).
Methods : A prospective cross-sectional study of patients presenting with symptoms consistent with cardiac ischemia was performed at a university teaching hospital. Serum sampling for cTn-I and CK-MB was performed at 0, 1, 3, 8, and 16 hours after presentation. Normal values were defined as CK-MB ≤ 7 ng/mL and a relative index ≤ 2%, cTn-I ≤ 1.4 ng/mL. Final diagnosis was made using World Health Organization criteria, including standard enzyme sampling. Consecutive patients with AMI were compared with a randomly selected subset of patients without AMI to determine the sensitivity and specificity of the cTn-I and CK-MB assays for AMI, stratified by time from symptom onset. The ability of the biochemical cardiac markers obtained within 6 hours of symptom onset to predict later complications or need for interventions was assessed using odds ratios (ORs).
Results : Thirty-five patients who had AMI were compared with 136 patients who did not have AMI. The sensitivities and specificities of the cTn-I and CK-MB assays, stratified by time from symptom onset, were: Patients who had elevations in either CK-MB or cTn-I within 6 hours of symptom onset were at increased risk for cardiovascular complications and/or interventions (CK-MB, OR 5.8; cTn-I, OR 6.3).
Conclusion : cTn-I was as sensitive and specific for AMI as was CK-MB in ED patients who presented within 24 hours of symptom onset. However, cTn-I was more sensitive in patients who presented ≥ 24 hours after symptom onset. Elevations of either marker within 6 hours of symptom onset predict an increased risk of complications and/or need for interventions.     

Variance Cardiography for Emergency Department Evaluation of Chest Pain Patients

Objective: To determine the test performance of 24–lead variance cardiography (VC), an ECG technique that measures QRS morphologic variability, for ED evaluation of chest pain associated with coronary artery disease (CAD).
Methods: A prospective, single–blind study of VC was performed in a community teaching hospital ED. All chest pain patients (>30 years of age) who, after initial emergency physician evaluation, were believed to have pain of potential cardiac etiology and were admitted to the hospital were eligible. Exclusion criteria included obvious noncardiac etiology for discomfort, bundle–branch block, atrial fibrillation, and incomplete subsequent cardiac evaluation. After initial evaluation and stabilization, VC was obtained. The numerical output of VC was a CAD index (CADI). Serum myoglobin and creatine kinase (CK)–MB levels were obtained at the time of presentation and after one, two, and six hours. Hospital records were reviewed to determine final diagnosis and in–hospital evaluation results.
Results: Fifty–two of 75 eligible patients had complete data. Final diagnoses were as follows: 27/52 (52%), noncardiac; 13/52 (25%), acute myocardial infarction (AMI); and 12/52 (23%), unstable angina due to CAD. Twenty–three percent (12/52) of the patients had CADIs < 75. Eleven of these were found to have noncardiac origins for their chest pain. The twelfth patient had a 12–lead ECG revealing AMI and had been given thrombolytic therapy with subsequent reperfusion prior to VC. Using a CADI < 75 as the cutoff for a negative study, VC alone had a negative predictive value of 92%, a sensitivity of 96%, a positive predictive value of 60%, and a specificity of 41%.
Conclusion: A CADI < 75, in addition to clinical impression and initial ECG, may identify chest pain patients who do not have significant CAD. Further prospective assessment of VC is warranted.     

Prospective Assessment of Presenting Serum Markers for Cardiac Risk Stratification

Objective: To quantify the association of initial ED serum cardiac markers with the risk for life-threatening events (LEs) or need for lifesaving interventions (Lis) or administration of IV nitroglycerin.
Methods: A prospective, observational study was performed using a cohort of hemodynamically stable, hospitalized patients (age > 25 years) presenting with nontraumatic chest discomfort. Patients with ST-segment elevation on their initial ECGs were excluded. Presenting serum samples were assayed for serum myoglobin and creatine kinase-MB isomer (CK-MB) using the Opus and Stratus systems. Target cases were defined as patients having LEs (e.g., cardiogenic shock, ventricular fibrillation, cardiac arrest), requiring Lis (e.g., intubation, cardioversion, pacing, reperfusion therapy), or needing IV nitroglycerin within 48 hours. Manufacturer's thresholds defined abnormal marker levels. Abnormal ECGs were defined using the Brush criteria.
Results: Of the 178 eligible patients, 44 (25%) were target cases . Most (55%) target cases had blood drawn for assays within four hours of chest discomfort onset. The relative risk and sensitivity of the serum markers and the ECG for target cases follow:
Of the seven patients with an LE/LI, six had blood drawn four hours or less after symptom onset; two LE/LI patients had abnormal myoglobin levels' no LE/LI patient had an abnormal CK-MB level.
Conclusions: Isolated serum myoglobin and CK-MB levels obtained at patient ED presentation were not strongly associated with the 48-hour risk for LEs, Lis, or the use of IV nitroglycerin. Future studies of risk stratification should address the merits of serial serum marker measurements that extend up to 12 hours beyond patient symptom onset.     

Diagnostic performance of initial salivary alpha-amylase activity for acute myocardial infarction in patients with acute chest pain

Background

To rule out acute myocardial infarction (AMI) in chest pain patients constitutes a diagnostic challenge to emergency department (ED) physicians.

Study Objectives

To evaluate the diagnostic value of measuring salivary alpha-amylase (sAA) activity for detecting AMI in patients presenting to the ED with acute chest pain.

Methods

sAA activity was measured in a prospective cohort of 473 consecutive adult patients within 4 h of onset of chest pain. Comparisons were made between patients with a final diagnosis of AMI and those with non-AMI. Univariate analysis and multiple logistic regression model were used to identify independent clinical predictors of AMI.

Results

Initial sAA activity in the AMI group (n = 85; 266 ± 127.6 U/mL) was significantly higher than in the non-AMI group (n = 388; 130 ± 92.8 U/mL, p < 0.001). sAA activity levels were also significantly higher in patients with ST elevation AMI (n = 53) compared to in those with non-ST elevation AMI (n = 32) (300 ± 141.1 vs. 210 ± 74.1 U/mL, p < 0.001). The area under the receiver operating characteristic curve of sAA activity for predicting AMI in patients with acute chest pain was 0.826 (95% confidence interval [CI] 0.782–0.869), with diagnostic odds ratio 10.87 (95% CI 6.16–19.18). With a best cutoff value of 197.7 U/mL, the sAA activity revealed moderate sensitivity and specificity as an independent predictor of AMI (78.8% and 74.5%).

Conclusions

High initial sAA activity is an independent predictor of AMI in patients presenting to the ED with chest pain.     

Myoglobin for Early Risk Stratification of Emergency Department Patients with Possible Myocardial Ischemia

OBJECTIVES: To determine and compare the prognostic abilities of early, single-sample myoglobin measurement with that of creatine kinase-MB (CK-MB), with cardiac troponin T (cTnT), and with physician judgment in the absence of marker results among emergency department (ED) patients with possible myocardial ischemia. METHODS: Prospective collection of clinical and serologic data using an identity-unlinked technique from patients with possible myocardial ischemia at two urban EDs. Outcome data concerning the occurrence of adverse events (AEs) during the 14 days after enrollment were used to calculate and compare the relative risks (RRs) and predictive values (with 95% confidence intervals) of the various markers for predicting AEs. RESULTS: Among 396 analyzed patients, 65 (16.4%) accrued 104 AEs, including 13 deaths (3.3%) and 31 (7.8%) myocardial infarctions. Myoglobin predicted AEs (RR = 3.36 [95% CI = 2.19 to 5.15]) with significantly higher sensitivity (50.8% [95% CI = 38.6 to 62.9]) than either CK-MB (15.4% [95% CI = 6.6 to 24.2]) or cTnT (24.6% [95% CI = 14.1 to 35.1]), but with lower specificity (81.9% [95% CI = 77.7 to 86.0]; CK-MB = 99.7% [95% CI = 99.1 to 100]; cTnT = 93.1% [95% CI = 90.3 to 95.8]). Myoglobin had prognostic ability among patients with chest pain (3.86 [95% CI = 2.39 to 6.22]) and atypical (non-chest pain) presentations (2.71 [95% CI = 1.09 to 6.71]), including those with a nondiagnostic electrocardiogram (3.11 [95% CI = 1.44 to 6.69]). The combination of myoglobin and physician decision making identified 63 of the 65 patients (96.9% [95% CI = 92.7 to 100]) with subsequent AEs. CONCLUSIONS: The early prognostic sensitivity of myoglobin may allow identification of some high-risk patients missed by physician judgment, CK-MB, and cTnT. Myoglobin should be considered for use in the ED based on both its diagnostic and prognostic abilities.     

Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB.

Heart-type fatty acid-binding protein (H-FABP) is a low molecular weight cytoplasmic protein and present abundantly in the myocardium. When the myocardium is injured, as in the case of myocardial infarction, low molecular weight cytoplasmic proteins including H-FABP are released into the circulation and H-FABP is detectable in a blood sample. We have already developed a direct sandwich-ELISA for quantification of human H-FABP using two distinct types of monoclonal antibodies specific for human H-FABP. In this study we investigated the clinical validity of H-FABP as a biochemical diagnostic marker in the early phase of acute myocardial infarction (AMI). To evaluate the diagnostic usefulness of H-FABP in the early phase of AMI, blood samples were obtained from the following patients within 12 hours after the appearance of symptoms, and serum levels of H-FABP were compared with those of conventional diagnostic markers, such as myoglobin and creatine kinase isoenzyme MB (CK-MB). Blood samples were collected from patients with confirmed AMI (n=140), patients with chest pain who were afterwards not classified as AMI by normal CK-MB levels (non-AMI) (n=49) and normal healthy volunteers (n=75). The serum concentration of H-FABP was quantified with our direct sandwich-ELISA. The concentration of myoglobin mass was measured with a commercial RIA kit. The serum CK-MB activity was determined with an immuno-inhibition assay kit. The overall sensitivity of H-FABP, within 12 hours after the appearance of symptoms, was 92.9%, while it was 88.6% with myoglobin and 18.6% with CK-MB. The overall specificity of H-FABP was 67.3%, while it was 57.1% with myoglobin and 98.0% with CK-MB. The diagnostic efficacy rates with these markers were 86.2% (H-FABP), 80.4% (myoglobin) and 39.2% (CK-MB), respectively. The diagnostic validity of H-FABP was further assessed by receiver operating characteristic (ROC) curve analysis. The area under the curve (AUC) of H-FABP was 0.921, which was significantly greater than with myoglobin (AUC: 0.843) and CK-MB (AUC: 0.654). These parameters, such as sensitivity, specificity, diagnostic efficacy and diagnostic accuracy, obtained for patients with chest pain within 3 hours and/or 6 hours after the onset of symptoms were almost the same as those for patients within 12 hours after symptoms. H-FABP is more sensitive than both myoglobin and CK-MB, more specific than myoglobin for detecting AMI within 12 hours after the onset of symptoms, and shows the highest values for both diagnostic efficacy and ROC curve analysis. Thus, H-FABP has great potential as an excellent biochemical cardiac marker for the diagnosis of AMI in the early phase.     

Multimarker Panel to Rule Out Acute Coronary Syndromes in Low-risk Patients

Objectives: To test novel markers of acute coronary syndrome (ACS), monocyte chemoattractant protein-1 (MCP), myeloperoxidase (MPO), C-reactive protein (CRP), and brain natriuretic peptide (BNP) in low-risk emergency department (ED) patients who were evaluated for ACS in a chest pain unit (CPU).
Methods: A convenience sample of 414 patients underwent CPU evaluation, including provocative testing, and were followed prospectively for 45 days for ACS, which was defined as death, myocardial infarction (MI), revascularization, or >60% coronary artery stenosis prompting new medical treatment, adjudicated by three blinded reviewers. Published diagnostic thresholds were used to calculate diagnostic indices for each marker and for the multimarker panel.
Results: The prevalence of ACS was 7 in 414 (1.7%; 95% CI = 0.7% to 3.5%). Only MCP demonstrated a negative likelihood ratio [LR(–)] of less than 0.5, with a sensitivity of 85% (95% CI = 42% to 99%), specificity of 72% (95% CI = 67% to 76%), and LR(–) of 0.20 (95% CI = 0.04 to 0.71). For MPO, CRP, and BNP, LR(–) was 0.89 (95% CI = 0.26 to 2.05), 0.79 (95% CI = 0.40 to 1.01), and 0.90 (95% CI = 0.51 to 1.03), respectively. The sensitivity, specificity, and LR(–) of an abnormal multimarker panel were 86% (95% CI = 42% to 100%), 17% (95% CI = 13% to 21%), and 0.84 (95% CI = 0.15 to 3.12), respectively.
Conclusions: The prevalence of ACS was very low but was similar to reports from other CPUs. BNP and CRP had high specificities, but had limited sensitivities, whereas MPO had a low specificity. Only MCP had a low LR(–) and should be studied further. The combined multimarker panel had an unexpectedly low sensitivity and specificity, yielding an LR(–) of 0.84, suggesting that the panel would not be an efficient screening test to decrease unnecessary CPU testing.     

心型脂肪酸结合蛋白在急性心肌梗死早期诊断中价值

目的探讨血浆心型脂肪酸结合蛋白(heart-type fatty acid-binding protein,H-FABP)对早期诊断急性心肌梗死(acute myocardial infarction,AMI)的意义。方法发病6h内以急性胸痛就诊的疑似AMI患者83例,根据出院诊断分为AMI组32例与非AMI组51例,非AMI组又分为不稳定型心绞痛33例(UAP组)与非心源性胸痛18例(NCCP组),选择体检健康者40名为对照组,采用ELISA法检测各组血清H-FABP水平,并与传统心肌标志物的诊断效能进行比较。结果 AMI组血清H-FABP水平明显高于非AMI组和对照组(P均<0.01);ROC曲线显示,H-FABP的AUC为0.954(95%CI:0.912～0.997),H-FABP诊断AMI的最佳截断值为6.65ng/mL;H-FABP诊断发病6h内AMI的敏感度、特异度、阴性预测值及准确率分别为90.26%,80.39%,93.18%,84.34%;敏感度、阴性预测值及准确率明显高于传统心肌标志物肌红蛋白、肌酸激酶同工酶和肌钙蛋白I(P<0.05)。结论 H-FABP对发病早期的AMI有较好诊断价值。     

Electrocardiographic ST-segment Elevation The Diagnosis of Acute Myocardial Infarction by Morphologic Analysis of the ST Segment

Acute myocardial infarction (AMI) is one of many causes of ST-segment elevation (STE) in emergency department (ED) chest pain (CP) patients. The morphology of STE may assist in the correct determination of its cause, with concave patterns in non-AMI syndromes and non-concave waveforms in AMI. OBJECTIVES: To determine the impact of STE morphologic analysis on AMI diagnosis and the ability of this technique to separate AMI from non-infarction causes of STE. METHODS: The electrocardiograms (ECGs) of consecutive ED adult CP patients (with three serial troponin I determinations) were interpreted in two-step fashion by six attending emergency physicians (EPs): 1) the determination of STE by three EPs followed by 2) STE morphologic analysis (either concave or non-concave) in those patients with STE. The impact of STE morphology analysis was investigated in the identification of AMI and non-AMI causes of STE. Acute myocardial infarction was diagnosed by abnormal serum troponin I values (>0.1 mg/dL) followed by a rise and fall of the serum marker; STE diagnoses of non-AMI causes were determined by medical record review. Interobserver reliability concerning STE morphology was determined. Study inclusion criteria included at least three troponin values performed in serial fashion no more frequently than every three hours, initial ED ECG, ED diagnosis, and final hospital diagnosis. RESULTS: Five hundred ninety-nine CP patients were entered in the study, with 171 (29%) individuals having STE on their ECGs. Of the 171 patients who had STE, 56 had AMI, 50 had unstable angina pectoris (USAP), and 65 had non-coronary final diagnoses. Forty-nine patients had non-concave STE, 46 with AMI and three with USAP; no patient with a non-coronary diagnosis had a non-concave STE morphology. The sensitivity and specificity of the non-concave STE morphology for AMI diagnoses were 77% and 97%, respectively; the positive and negative predictive values for non-concave morphology in AMI diagnoses were 94% and 88%, respectively. Interobserver reliability in the STE morphology determination revealed a kappa coefficient of 0.87. CONCLUSIONS: A non-concave STE morphology is frequently encountered in AMI patients. While the sensitivity of this pattern for AMI diagnosis is not particularly helpful, the presence of this finding in adult ED chest pain patients with STE strongly suggests AMI. This technique produces consistent results among these EPs.     

Emergency Department CK-MB: A Predictor of Ischemic Complications

ABSTRACT
Objective : To demonstrate that a positive CK-MB in the emergency department (ED) predicts an increased risk for complications of myocar-dial ischemia in patients admitted to the hospital for evaluation of chest pain.
Methods : 53 academic and community hospital EDs participated in this prospective observational cohort analysis of 5,120 patients with chest pain without ST-segment elevation on the initial ED 12-lead electrocardiogram. All patients were admitted for evaluation of chest pain in one of the participating hospitals as part of the National Cooperative CK-MB Project. Patients were stratified by whether or not they had an elevated CK-MB level in the ED. CK-MB measurements were made on ED presentation and two hours later. Patient medical records were reviewed for inpatient diagnoses—myocardial infarction (MI) or other diagnosis —and for ischemic complications—cardiac-related death, recurrent or delayed in-hos-pital MI, significant ventricular arrhythmias, new conduction defects, congestive heart failure, and cardiogenic shock.
Results : 369 (7.2%) of the 5,120 patients had MI. The proportion of patients with any complication in the MI group was 24%, while the complication rate in the non-MI group was 0.4%. In all patients, regardless of final diagnosis, the relative risk of any complication was 16.1 (95% CI 11.0–23.6) in those with a positive ED CK-MB versus negative ED CK-MB patients. Similarly, the relative risk of death was 25.4 (95% CI 10.8— 60.2) in positive ED CK-MB versus negative ED CK-MB patients.
Conclusions : Multicenter data support the hypothesis that CK-MB measurements can help risk-stratify ED chest pain patients whose initial ECGs are without diagnostic ST-segment elevation.     

Impact of Community Intervention to Reduce Patient Delay Time on Use of Reperfusion Therapy for Acute Myocardial Infarction Rapid Early Action for Coronary Treatment (REACT) Trial

BACKGROUND: Reperfusion therapy for acute myocardial infarction (AMI) is a time-dependent intervention that can reduce infarct-related morbidity and mortality. Out-of-hospital patient delay from symptom onset until emergency department (ED) presentation may reduce the expected benefit of reperfusion therapy. OBJECTIVE: To determine the impact of a community educational intervention to reduce patient delay time on the use of reperfusion therapy for AMI. METHODS: This was a randomized, controlled community-based trial to enhance patient recognition of AMI symptoms and encourage early ED presentation with resultant increased reperfusion therapy rates for AMI. The study took place in 44 hospitals in 20 pair-matched communities in five U.S. geographic regions. Eligible study subjects were non-institutionalized patients without chest injury (aged > or =30 years) who were admitted to participating hospitals and who received a hospital discharge diagnosis of AMI (ICD 410); n = 4,885. For outcome assessment, patients were excluded if they were without survival data (n = 402), enrolled in thrombolytic trials (n = 61), receiving reperfusion therapy >12 hours after ED arrival (n = 628), or missing symptom onset or reperfusion times (n = 781). The applied intervention was an educational program targeting community organizations and the general public, high-risk patients, and health professionals in target communities. The primary outcome was a change in the proportion of AMI patients receiving early reperfusion therapy (i.e., within one hour of ED arrival or within six hours of symptom onset). Trends in reperfusion therapy rates were determined after adjustment for patient demographics, presenting blood pressure, cardiac history, and insurance status. Four-month baseline was compared with the 18-month intervention period. RESULTS: Of 3,013 selected AMI patients, 40% received reperfusion therapy. Eighteen percent received therapy within one hour of ED arrival (46% of treated patients), and 32% within six hours of symptom onset (80% of treated patients). No significant difference in the trends in reperfusion therapy rates was attributable to the intervention, although increases in early reperfusion therapy rates were noted during the first six months of the intervention. A significant association of early reperfusion therapy use with ambulance use was identified. CONCLUSIONS: Community-wide educational efforts to enhance patient response to AMI symptoms may not translate into sustained changes in reperfusion practices. However, an increased odds for early reperfusion therapy use during the initiation of the intervention and the association of early therapy with ambulance use suggest that reperfusion therapy rates can be enhanced.     

Evaluation of a point-of-care assay for cardiac markers for patients suspected of acute myocardial infarction

BACKGROUND: Creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) are important biomarkers for the diagnosis and rule-out of acute myocardial infarction (AMI) of patients who presented to the emergency department (ED) with chest pain. With new rapid ED assessment protocols, there is increasing pressure to produce results with a short turnaround time (TAT), and point-of-care (POC) testing is one alternative for providing fast results. METHODS: In a multicenter study, we evaluated the analytical precision, sensitivity and specificity of the RAMP (Response Biomedical) CK-MB and cTnI POC assays and compared results against the Triage (Biosite) POC and the Dimension RxL (Dade Behring) central-laboratory assays on 365 subjects, including 185 patients suspected of AMI, and determined the normal range on 180 healthy individuals. At one site, the clinical sensitivity and specificity were estimated in 121 patients and healthy subjects with AMI using the European Society of Cardiology (ESC)/American College of Cardiology (ACC) definition of AMI. Results from healthy individuals and those with ST elevation and non-ST elevation AMI were included in a receiver operating characteristic (ROC) curve analysis. RESULTS: Intra- and total imprecision ranged from 7.2% to 11.4% for cTnI at 0.22, 1 and 5 ng/ml and 4.8% to 8.6% for CK-MB at 7, 14 and 25 ng/ml. The upper limit of linearity was 32 ng/ml with an average recovery of 105% for cTnI and 80 ng/ml with a 106% recovery for CK-MB. The lower limit of detection was 0.03 ng/ml (10% coefficient of variance [CV] = 0.21 ng/ml) for cTnI and 0.32 ng/ml for CK-MB. The upper reference limit (normal range) was < 0.03 ng/ml for cTnI and 0-3.7 ng/ml for CK-MB. Analytical correlation against Dimension RxL were RAMP=(0.456 x RxL) + 0.11 (r = 0.988, n = 364) for cTnI and RAMP=(0.966 x RxL) + 0.60 (r = 0.986, n = 363) for CK-MB and against Triage, RAMP=(0.626 x Triage) + 0.164 (r = 0.969, n = 364) for cTnI and RAMP=(0.845 x RxL) - 0.495 (r = 0.952, n = 363) for CK-MB. On 39 AMI and 67 non-AMI patients, the clinical sensitivity, specificity and diagnostic efficiency of the cTnI and CK-MB RAMP assays were not significantly different from predicate assays. CONCLUSIONS: The RAMP cardiac marker assays are alternatives to other FDA-cleared central laboratory and POC testing devices.     

The Relationship of Plasma Glucose and HbA1c Levels among Emergency Department Patients with No Prior History of Diabetes Mellitus

Objectives: Patients without a history of diabetes mellitus may be incidentally found to be hyperglycemic in the emergency department (ED). If the hyperglycemia is due to undiagnosed diabetes, then an opportunity for detection exists. Hemoglobin A1c (HbA1c) provides a weighted average of blood glucose levels over the past several months; high HbA1c levels could indicate diabetes. The objective of this study was to determine whether hyperglycemia in ED patients without a history of diabetes was associated with higher HbA1c levels.
Methods: This was a prospective nonconsecutive case series of adults aged 18 years or older presenting to the ED with acute illness for whom a plasma glucose sample was drawn for clinical management. A history of diabetes/hyperglycemia or current symptoms of diabetes excluded patients. HbA1c levels were analyzed for a glucose cutoff of 110 mg/dL; the data were further analyzed using additional glucose cutoffs. Based on the Third National Health and Nutrition Examination Survey outpatient screening data, an HbA1c level ≥6.2% was considered elevated (sensitivity of 63% and specificity of 97% for identifying diabetes).
Results: There were 541 patients enrolled; the glucose level correlated with the HbA1c level ( r = 0.60, p < 0.001). Among the 331 patients with a glucose level ≥110 mg/dL, 22.4% had an elevated HbA1c level; among the 210 patients with a glucose level < 110 mg/dL, 7.6% had an elevated HbA1c level. There were few patients ( n = 13) with a glucose level ≥200 mg/dL, but most (85%) had an elevated HbA1c level. Among the 140 patients with a mildly elevated glucose level (110–125 mg/dL), 16.4% had an elevated HbA1c level.
Conclusions: Elevated HbA1c levels are found in ED patients with elevated random plasma glucose values. ED patients with hyperglycemia may warrant referral for diabetes testing.     

A Truncated E-code System for Injury Surveillance in the Emergency Department: Description and Clinometric Testing

Objectives: ED injury surveillance requires accurate information about mechanism. This study explored the clinometric properties of an E-code system specifically designed to track ED injuries.
Methods: All patients assessed in the ED had cause-of-injury information documented using a truncated E-code system. Patient records were hand-searched to determine coding compliance. A selection of 98 charts (50 injury/48 noninjury) were coded by 7 physicians, 2 nurses, and 2 nosologists. Agreements (interrater and intrarater) on the diagnosis of trauma and exact E-codes were determined (using kappa; κ).
Results: E-coding compliance was high (overall 90%: 95% CI: 85–93%), and accuracy of injury classification was 99%. Compared with an expert's coding, agreement on injury classification was excellent for physicians (κ = 0.91; 95% CI: 0.80–1.0), nurses (κ = 0.88; 95% CI: 0.75–1.0), and nosologists (κ = 0.92; 95% CI: 0.81–1.0). Agreement was substantial for the exact E-codes between physicians (κ = 0.77; 95% CI: 0.60- 0.94) and nurses (κ = 0.72; 95% CI: 0.54–0.90). Recode reliability was also excellent for physicians (κ = 0.88; 95% CI: 0.75–1.0) and nurses (κ = 0.96; 95% CI: 0.88–1.0).
Conclusions: Injury coding using a truncated E-code system can provide valid and reliable data from the ED. Differences between nurses, physicians, and nosologists in the ability to accurately code using this system were minimal, thus eliminating the need for additional staff and resources.     

Six-hour versus 12-hour protocols for AMI: CK-MB in conjunction with myoglobin

The objective was to test the hypothesis that a protocol using myoglobin and creatine kinase-MB (CK-MB) can rapidly and safely exclude myocardial infarction (MI). The study used a prospective, convenience cohort of ED patients with clinically suspected myocardial ischemia. Myoglobin was measured on presentation, 2 and 6 hours later; CK-MB was measured on presentation, 6, 12, and 18 hours later. Of 519 patients, 76 (15%) had MIs, all of whom "ruled in" within 12 hours using a combination of myoglobin and CK-MB, for a sensitivity of 100% (95% CI, 95% to 100%), specificity of 92% (95% CI, 89% to 94%), LR (+) of 12 (95% CI, 9 to 16), and an LR (-) of 0.03 (95% CI, 0.0 to 0.05). Of the 76 patients with MIs, 73 ruled in with a 6 hour protocol, also using a combination of CK-MB and myoglobin, for a sensitivity of 96% (95% CI, 89% to 99%), specificity of 92% (95% CI, 89% to 94%), LR (+) of 11 (95% CI, 8 to 16), and an LR (-) of 0.04 (95% CI, 0.01 to 0.12). Our results support the hypothesis that, using an abbreviated protocol with CK-MB and myoglobin, MI can be reliably ruled out in ED patients with suspected ischemia.     

Proteomic approach to the diagnosis of acute coronary syndrome: preliminary results

BACKGROUND: Cardiac multimarker strategy is recommended by the IFCC, ESC and the ACC for an early risk stratification in non-ST-segment elevation (NSTE) ECG patients with chest pain. A new approach, based on protein biochip array technology, performs simultaneously: cTnI, CK-MB, myoglobin, CAIII, GFBB and FABP using a single chip. METHODS: We evaluated the analytical performance of the Randox-Evidence Investigator -biochip cardiac panel according to IFCC recommendations and NCCLS guidelines; a preliminary clinical evaluation was carried out on chest pain NSTE ECG patients, to evaluate the accuracy of the multimarker approach in an early diagnosis of AMI, related to the final diagnosis (ACC/ESC criteria). RESULTS: Troponin, CK-MB and FABP methods provide reproducible within-run and between-day results (total % CVs from 5.9% to 9.7%), and myoglobin and CAIII methods showed the total % CVs from 16.4% to 25.8%. Our preliminary clinical data suggests that FABP had a better diagnostic performance (sensibility = 100%) than myoglobin (sensibility = 75%) to detect AMI in the first hours after the onset of the chest pain and myoglobin/CAIII ratio (specificity = 92.9%) improved the myoglobin specificity. CONCLUSIONS: Cardiac markers have different diagnostic roles and, in this contest, biochip technology could be an interesting approach supporting clinical expectations.     

A new immunoassay for the measurement of myoglobin in serum

Because the concentration of serum myoglobin (Mb) increases within 2 to 4 hours after the first sign of acute myocardial infarction, it has been proposed as an early marker of the condition. Our aim was to evaluate a new assay that provides a rapid, quantitative determination of Mb (Baxter Stratus Myoglobin) based on the radial partition technique. We compared the results obtained by this technique with those from nephelometric and radioimmunoassay methods. A significant agreement was observed, the correlation coefficients (r) being 0.999 and 0.996, respectively. The method evaluated provided good reproducibility with CVs between 3.14% and 4.87%, and its linearity and analytical sensitivity were satisfactory. The clinical evaluation of this assay demonstrates that Mb increases in serum of patients with acute myocardial infarction before total creatine kinase and creatine kinase MB isoenzyme. Mb concentration shows an early peak and earlier return to normal values after the necrosis compared to enzymatic activities. Moreover the assay is rapid and fully automated. The method is therefore considered appropriate for contributing to the early diagnosis of AMI in clinical laboratories. © 1994 Wiley-Liss, Inc.     

Evaluation of a new automated system for the determination of ck-mb isoforms

We evaluated a new analyzer (Cardio REP) specifically designed for cardiac CK-MB isoenzyme and isoforms activity, with a performance time of 24 minutes. Ten AMI patients, with times elapsed between the onset of chest pain and admission to hospital ranging from 30 minutes to 4 hours, were monitored every 3–4 hours until the 16th hour of hospitalization. In each serum sample, in addition to total CK-MB and CK-MB isoforms measured by the Cardio REP analyzer, we also assayed total CK activity, CK-MB activity by immunoinhibition method, CK-MB mass concentration, CK-MB isoforms by REP method, troponin T, and myoglobin. The precision study demonstrated acceptable within assay and between assay CVs% for total CK-MB (8.1 and 10.4), MB₁ (9.1 and 14.2), and MB₂ (9.1 and 8.2) isoforms. The method was found to be linear up to 371 U/L for MB₂ isoform fraction and up to 516 U/L for total CK-MB. Results for CK-MB obtained with the Cardio REP correlated well with those for CK-MB activity obtained with the immunoinhibition method (r = 0.869) and those of CK-MB mass concentration (r = 0.923). The sensitivity of the Cardio REP CK isoforms method was found to be greater than that of the REP CK isoforms method. Time to first increased value of MB₂/MB₁ ratio and MB₂ isoform was earlier in comparison to that for CK-MB mass concentrations and similar to that for myoglobin, a marker that, however, lacks specificity. The diagnostic efficiency of CK-MB isoforms and the availability of a real-time, fully automated method for their measurement suggest the utilization of this biochemical marker in emergency for the early diagnosis of AMI.