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.     

Release kinetics of serum cardiac troponin i in ischemic myocardial injury

Objectives: The study was undertaken to evaluate the release kinetics of cardiac troponin I (c-cTn-I) in ischemic myocardial injury.

Design and Methods: The reference range for cTn-I was established by determination of cTn-I in sera and plasma obtained from 622 healthy volunteers (Group 1). cTn-I was compared to: (a) Creatine kinase (CK) MB mass and myoglobin in 12 patients with severe skeletal muscle damage (Group 2); (b) CK-MB activity in 48 patients with myocardial infarction (MI) receiving intravenous thrombolysis (Group 3) (in this group, an additional 43 patients with MI were analyzed separately to characterize cTn-I patterns in thrombolyzed and nonthrombolyzed populations); and in 44 patients with unstable angina (Group 4).

Results: In Groups 1 and 2, no positive results (0.1 μg/L) were obtained. In Group 3, the time-courses of cTn-I were mostly monophasic in form. A pathologic increase occurred earlier in cTn-I than in CK-MB activity (p = 0.0002); the period with increased cTn-I was longer (p = 0.001), the overall sensitivity of cTn-I (93.9%) was higher than that of CK-MB activity (p = 0.00001). cTn-I was more sensitive at admission (p = 0.0004). In additional patients, the cTn-I peak occurred and cTn-I disappeared significantly later in nonthrombolyzed than in the thrombolyzed group. In Group 4, positive tests results were detected in 45% of patients for cTn-I, 16% for CK-MB activity, and 32% for CK-MB mass.

Conclusions: The cTn-I assay appears to be ideally suited for the detection of ischemic myocardial injury in complex clinical situations because of its high specificity; cTn-I indicates myocardial tissue damage in patients with unstable angina and is superior to CK-MB activity and mass in this respect.     

The Prognostic Significance of Troponin I and Troponin T

Abstract. Objectives : To determine and compare the prognostic abilities of early, single-sample measurements of cardiac troponin I (cTn-I), cardiac troponin T (cTn-T), creatine kinase-MB (CK-MB) among 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 2 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 3 markers for predicting AEs. Results : Among the 401 study patients, 105 AEs occurred in 67 patients. cTn-I, cTn-T, and CK-MB were all significantly predictive of AEs, with RRs of 3.87 (2.39, 6.26), 3.03 (1.92, 4.79), and 6.45 (4.74, 8.77), respectively. For prediction of AEs, sensitivity for each of the 3 markers was low (cTn-I = 15.38, cTn-T = 24.62, CK-MB = 15.38), while specificity was high (cTn-I = 97.62, cTn-T = 93.15, CK-MB = 99.70). No significant difference in predictive ability was found between cTn-I and cTn-T. However, a positive CK-MB result was a stronger predictor of AEs than either cTn-I (p = 0.01) or cTn-T (p = 0.001). Conclusions : No significant difference in predictive abilities was found between cTn-I and cTn-T. However, routine testing for both CK-MB and either of the troponins may optimize early identification of high-risk patients so they may be targeted for a higher level of care and consideration of more aggressive therapies.     

Evaluation of ck-mb isoform analysis for early diagnosis of myocardial infarction

Measurement of CK-MB and its isoforms by high-voltage electrophoresis has been proposed as a sensitive test for early detection of myocardial infarction (MI). We performed a prospective study of this test in 231 patients presenting to the Emergency Department with symptoms consistent with ischemic chest pain. Blood specimens were obtained at 0, 1, and 3 h following presentation, and plasma was immediately frozen and analyzed within 1 week by high-voltage electrophoresis for total CK-MB and isoforms. The test was considered positive whenever total CK-MB was elevated (>6 U/L) or the cardiac isoform MB₂ was relatively increased (MB₂ > 2 U/L and MB₂/MB₁ > 1.7). This test had a sensitivity of 68% overall and 55% for specimens collected within 3 h of symptom onset. It was positive within 3 h of presentation in 36/39 (92%) of patients with confirmed MI. Specificity was 92% overall and did not vary with time after symptoms. The CK-MB alone, at the cutoff of 6 U/L, had lower sensitivity overall (56%; p = 0.01) and within 3 h of onset (39%; p = 0.03), and higher specificity overall (98%; p < 0.001). Lowering the cutoff for CK-MB alone to match the sensitivity of the isoform test caused a greater loss of specificity. It is concluded that analysis of CK-MB by high-voltage electrophoresis is an effective method for rapid diagnosis of MI, with the isoform analysis enhancing early sensitivity.     

心肌标志物作用的系统分析

目的：获取心肌生化标记物的最佳应用证据。方法：查循、浏览对心肌肌酸激酶同工酶MB（CK－MB）、肌红蛋白、心肌肌钙蛋白T（cTnT）和心肌肌钙蛋白I（cTnI）用于诊断心肌梗塞（MI）和对急性冠状动脉综合症分级的系统评价和Meta－分析的文献资料。结果：在症状发生后的12－48小时采样分析CK－MB质量对于诊断MI的临床灵敏度和牧场划性分别是98．8％和89．6％。肌红蛋白有高的阴性预示值,在症状发生后的2－6小时采样分析有高的临床灵敏度。在症状发生后的12采样cTnI,诊断MI的临床灵敏度和特异性分别是98．2％和68．8％,其临床特异性降低与检测到微小心肌受损有关。结论：cTnT和cTnI比CK－MB对诊断心肌梗死和预测急性冠状动脉综合症危险性更有价值。     

A multi-marker approach for the prediction of adverse events in patients with acute coronary syndromes

BACKGROUND: Cardiac troponin T (cTnT), high sensitivity C-reactive protein (hs-CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) have emerged as strong predictors of adverse events among patients presenting with acute coronary syndromes (ACS). We evaluated the prognostic performance of each of these markers, individually, and in combination in patients presenting to the emergency department (ED) with ACS symptoms. METHODS: Serum samples were obtained from 422 consenting patients presenting to the ED with symptoms of acute coronary syndrome (ACS) and subsequently tested for cTnT, NT-proBNP, myoglobin, CK-MB, and hs-CRP. Adverse events (AEs) occurring within 30 days (death, myocardial infarction, unstable angina and the need for revascularization procedures) were recorded and ROC curves were constructed. RESULTS: AEs occurred in 42 patients (10%). Relative risk, cut-off, and predictive values for each biomarker were determined statistically, with the exception of cTnT, where the concentration meeting the 99th percentile of a healthy population with a 10% coefficient of variation (0.03 ng/ml) was used. These cut-off values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and relative risk (RR) were calculated. Sensitivity and RR for a panel of cTnT and NT-proBNP were 78.6% (66.2-91.0) and 4.7 (2.3-9.5), respectively. CONCLUSIONS: If used alone, cTnT appeared to have greater prognostic value when compared to hs-CRP, NT-proBNP, myoglobin or CK-MB. The combination of cTnT and NT-proBNP performed better than the combination of cTnT and hs-CRP. When cTnT, NT-proBNP and hs-CRP were used as a panel, there was no significant improvement in prognostic performance over using cTnT and NT-proBNP together. Thus, in patients with suspected ACS, the measurement of both cTnT and NT-proBNP may have enhanced prognostic performance over using either marker in isolation.     

Prospective evaluation of emergency department patients with potential coronary syndromes using initial absolute CK-MB vs. CK-MB relative index

We compared the predictive properties of an initial absolute creatine kinase-MB (CK-MB) to creatine kinase-MB relative index (CK-MB RI) for detecting acute myocardial infarction (AMI), acute coronary syndromes (ACS), and serious cardiac events (SCE). Consecutive patients > 24 years of age with chest pain who received an electrocardiogram (EKG) as part of their Emergency Department (ED) evaluation had CK and CK-MB drawn at presentation. Patients were followed prospectively during their hospital course. The main outcome was AMI, ACS or SCE (death, AMI, dysrhythmias, CHF, PTCA/stent, CABG) within 30 days. The sensitivity, specificity, PPV and NPV of CK-MB and CK-MB RI to predict AMI, ACS, and SCE were calculated with 95% CIs. We enrolled 2028 patients. There were 105 patients (5.2%) with AMI, 266 (13.1%) with ACS, and 150 with SCE (7.4%). Absolute CK-MB had a higher sensitivity than CK-MB RI for AMI (52.0 vs. 46.9, respectively), ACS (23.5 vs. 20.8, respectively), and SCE (39.6 vs. 36.0, respectively), but a lower specificity than CK-MB RI for AMI (93.2 vs. 96.1, respectively), ACS (93.1 vs. 96.1, respectively) and SCE (93.3 vs. 96.3, respectively); and lower PPV for AMI (35.7 vs. 46.5, respectively), ACS (42.0 vs. 53.4, respectively) and SCE (38.5 vs. 50.5, respectively). The negative predictive values were similar for all outcomes. We conclude that the risk stratification of ED chest pain patients by absolute CK-MB has higher sensitivity, similar NPV, but a lower specificity and PPV than CK-MB relative index for detection of AMI, ACS, and SCE. The optimal test depends upon the relative importance of the sensitivity or specificity for clinical decision-making in an individual patient.     

Value of a single troponin T at the time of presentation as compared to serial CK-MB determinations in patients with suspected myocardial ischemia

BACKGROUND: Prior studies with cardiac markers have focused predominantly on subjects presenting to the emergency department with chest pain or unstable angina, and have relied on serial markers for the diagnosis of acute myocardial infarction. We evaluated the diagnostic utility of a single cardiac troponin T (cTnT) determination at the time of presentation as compared to serial creatine kinase (CK) MB determinations in a broad spectrum of patients with suspected myocardial ischemia. METHODS: A total of 267 consecutive patients presenting to the emergency department with suspected myocardial ischemia had a single, blinded cTnT determination drawn at the time of presentation to the emergency department in addition to routine serial electrocardiographic and CK-MB determinations. RESULTS: The specificity (93.7% vs. 87.1%; p<0.05) and positive predictive value (80.0% vs. 69.4%; p<0.05) of a single cTnT determination were superior to that of serial CK-MB determinations without compromising sensitivity. Forty-six percent of patients with confirmed myocardial infarction and an abnormal cTnT at presentation had a normal initial CK-MB determination. Conversely, 20% of patients without acute coronary syndromes had an abnormal CK-MB determination in the setting of a normal cTnT. The initial cTnT was abnormal in all patients with confirmed myocardial infarction and a symptom duration of at least 3.5 h. CONCLUSIONS: In a heterogeneous population of patients with suspected myocardial ischemia, the initial cTnT determination drawn at the time of presentation is a powerful diagnostic tool that, when used in context with symptom duration, allows for more rapid and accurate triage of patients than serial CK-MB determinations.     

Enhancing the diagnostic performance of troponins in the acute care setting

Background: Current guidelines define cardiac troponin I (TnI) as an indicator of necrosis when the concentration exceeds the 99% upper limit of a healthy reference population, a reference value near the assay's lowest detectable level. We assessed the utility of a modified TnI cutoff point derived from a population at low risk for coronary artery disease (CAD) and evaluated its utility in determining acute myocardial infarction (MI). Methods: A modified TnI cutoff point was derived by the receiver operating characteristic (ROC) curve from 737 consecutive patients who underwent serial TnI measurements for exclusion of MI. Creatinine kinase isoenzyme MB (CK-MB) evolutionary change was used to define MI. The new derived cutoff point was validated using another subset of 320 patients who were evaluated for MI. Results: ROC-derived TnI cutoff point (A) was 0.65 μg/L, and its performance was compared to the recommended cutoff point ([B] 0.15 μg/L). Cutoff point A had greater specificity (94.5% vs. 86.9%, p < 0.001) but slightly lower sensitivity (96.5% vs. 100%, p < 0.01). Cutoff point A provided significantly greater positive predictive value (PPV) for MI (74.1% vs. 55.5%, p < 0.0001) and fewer false-positive errors, while preserving comparable negative predictive value (NPV) (98.9% vs. 100%). Conclusion: A higher cutoff point derived from a reference population of patients at low risk for CAD may improve the TnI performance assay. The PPV for diagnosis of MI was significantly higher and false-positive values were fewer without affecting the NPV. The more reliable diagnosis of MI may have resulted, which, in turn, may have significant clinical and economic implications.     

Assessment of Heart Rate Turbulence in the Acute Phase of Myocardial Infarction for Long-Term Prognosis

SADE, E., et al .: Assessment of Heart Rate Turbulence in the Acute Phase of Myocardial Infarction for Long-Term Prognosis. This study is designed to assess the value of heart rate turbulence (HRT) in the acute phase of MI for prediction of long-term mortality risk. The study included 128 consecutive acute MI patients with 24-hour Holter recordings to evaluate HRT (turbulence onset and slope), SDNN, mean RR interval, and ventricular premature beat frequency. LVEF was evaluated by two-dimensional echocardiography. Data from 117 patients (mean age 58 ± 11 years ) were available for further analysis. Twelve patients died during follow-up (mean 312 ± 78 days ). Although SDNN < 70 ms was the most powerful predictor of mortality among all presumed risk factors (hazard ratio 20 [95% CI 2.6–158]; P = 0.004) in univariate Cox regression analysis, in multivariate analysis LVEF ≤ 0.40 and turbulence slope ≤2.5 ms/RR interval were the only independent predictors of mortality (hazard ratio 6.9 [95% CI 1.8–26]; P = 0.006, hazard ratio 7.3 [95% CI 1.4–37]; P = 0.016, respectively). Addition of HRT parameters for LVEF increased remarkably the positive predictive value (60%) without any decrease in the negative predictive value (92%). Blunted HRT reaction within the first 24 hours of acute MI is an independent predictor of long-term mortality. Furthermore, its predictive power is comparable and also additive to that of LVEF. (PACE 2003; 26[Pt. I]:544–550)     

Diagnosis of perioperative myocardial infarction by considering relationship of postoperative electrocardiogram changes and enzyme increases after coronary bypass operation

We report the results of enzyme determinations in sera from 88 patients, 65 of whom showed inconspicuous reconvalescence, 14 who had myocardial infarction within 24 h (MI 1) after bypass surgery, and nine with myocardial infarction between 24 and 48 h postoperatively (MI 2). We wanted to determine whether the consequent measurement of activities of total creatine kinase (CK), CK isoenzyme MB (CK-MB), lactate dehydrogenase, alpha-hydroxybutyrate dehydrogenase, and aspartate aminotransferase, conducted as a part of routine laboratory diagnostics, provided meaningful information for diagnosing infarcts besides that obtained from the electrocardiogram. The postoperative mean values of the enzyme activities in blood were significantly different among the three groups; however, only a combined evaluation of CK and CK-MB by means of a discriminant analysis allowed the prediction of MI (sensitivity: MI 1 = 98.5%, MI 2 = 95.4%; specificity: MI 1 = 71.4%, MI 2 = 81.8%). CK greater than 600 U/L or CK-MB greater than 45 U/L supports the diagnosis of acute MI.     

高敏感性肌钙蛋白T检测在急性非ST段抬高型心肌梗死早期诊断中的意义

目的:探索高敏感性肌钙蛋白T(hs-cTnT)对急性非ST段抬高型心肌梗死(NSTEMI)的早期诊断价值。方法:入选88例发病在6h以内的高度怀疑非ST段抬高型急性冠脉综合征的患者,入院即刻抽取静脉血检测hs-cTnT,并与肌钙蛋白I(cTnI)及肌酸激酶同工酶(CK-MB)检测结果进行比较,诊断性能用ROC曲线及AUC表示,并根据hs-cTnT、cTnI和CK-MB的阳性率,得出对NSTEMI诊断的灵敏度、特异度等。结果:(1)NSTEMI患者hs-cTnT、cTnI及CK-MB明显高于不稳定型心绞痛患者(P<0.001)。(2)根据ROC曲线分析,hs-cTnT、cTnI和CK-MB的AUC分别为0.908、0.851、0.789,95%可信区间分别为0.832～0.985、0.763～0.939、0.695～0.883。(3)hs-cTnT以14pg/mL为诊断临界点时,灵敏度为77.8%,特异度为96.7%,阳性预测值为91.3%,阴性预测值为96.8%。而cTnI诊断临界点为0.08ng/mL时,灵敏度为37.0%,特异度为96.7%,阳性预测值为83.3%,阴性预测值为77.6%。CK-MB以4ng/mL为诊断临界点时,灵敏度为25.9%,特异度为93.4%,阳性预测值为63.6%,阴性预测值为79.2%。结论:hs-cTnT对NSTEMI的早期诊断性能优于cTnI和CK-MB,有利于早期筛选NSTEMI患者并及时对其进行治疗。     

Ability of myoglobin to predict mortality in patients admitted for exclusion of myocardial infarction

Background

Myoglobin can be used as an early marker to diagnose myocardial infarction (MI); and although nonspecific for myocardial necrosis, it seems to be a strong mortality predictor. Because myoglobin elevations are often present in patients with renal insufficiency, it is possible that the predictive value of myoglobin is secondary to identifying patients with renal insufficiency.

Methods

Consecutive patients admitted for MI exclusion without ST elevation on the initial electrocardiogram underwent serial assessment of cardiac markers (creatine kinase [CK], CK–myocardial band [MB], and troponin I [TnI]). Myoglobin was assessed at the time of admission and/or 3 hours later. Renal insufficiency was defined as a creatinine clearance <60 mL/min. Multivariate analysis was performed to identify predictors of 30-day and 1-year all-cause mortality.

Results

A total of 3461 patients were included in the analysis. Overall 30-day and 1-year mortality was 2.4% and 9.7%. Myoglobin was elevated in 675 (20%), CK-MB in 421 (12%), and TnI in 517 (15%). Among the 993 patients with renal insufficiency, myoglobin was elevated in 43%, CK-MB in 17%, and TnI in 21%. Independent predictors of 30-day and 1-year mortality were similar and included age ≥65 years, prior MI, and an ischemic electrocardiogram, whereas myoglobin was the strongest multivariate predictor (odds ratio [OR] 2.8, 95% confidence interval [CI] 2.1-3.7), including those with renal insufficiency (OR 2.3, 95% CI 1.6-3.4). Troponin I had borderline predictive value (P = .08, OR 1.4, 95% CI 0.96-2.0), whereas CK-MB was not predictive in either group.

Conclusions

Despite the absence of cardiac specificity, an elevated myoglobin strongly predicts mortality, even in patients with renal insufficiency.     

应用ROC曲线分析cTnI和CK-MB对AMI的诊断价值

目的应用ROC曲线分析肌钙蛋白I(cTnI)和CK-MB对心肌梗死(AM)的诊断价值。方法胶体金免疫层析法(GICA)测定病例组与健康对照组的血清cTnI,血清CK-MB测定采用速率法,并对cTnI和CK-MB进行统计学比较(t检验)和ROC分析。结果cTnI在心肌梗死诊断中的敏感度为96.2%,特异度为93.9%,阳性结果预测值为94.4%,准确度为95,1%;CK-MB的敏感度为84.9%,特异度为95.9%阳性结果预测值为91.8%,准确度为90.2%;cTnI的ROC曲线下面积AUC=0.97,CK-MB的AUC=0.89。结论胶体金免疫层析法(CICA)测定cTnI可以作为诊断心肌梗死的快速诊断指标,并优于CK-MB指标。     

Susceptibility of erythrocyte lipids to oxidation and erythrocyte antioxidant status in myocardial infarction

Objective: We evaluated the erythrocyte lipid susceptibility to oxidation and erythrocyte antioxidant status in patients with myocardial infarction (MI).

Design and methods: Patients with MI were divided into two group according to the severity of the disease as severe (n = 30) or milder (n = 25). Malondialdehyde as a marker of lipid peroxidation was measured to show the lipid susceptibility to oxidation. Erythrocytes were stressed in vitro by hydrogen peroxide acting as the oxidative agents for 120 min. After designated time, erythrocyte MDA production was significantly higher in patients with severe MI than in controls and in patients with milder MI (p< 0.001, p< 0.001, respectively). Antioxidant status was determined by measuring the reduced glutathione levels and glutathione peroxidase activity of erythrocyte.

Results: In patients with MI, antioxidant status was significantly lower than in controls, and there was no significant difference between the patient groups.

Conclusion: Determination of erythrocyte lipid susceptibility to oxidation may be a useful in vitro test to evaluate the degree of oxidative stress in myocardial infarction.     

Creatine kinase MM isoforms in serum after cardiac surgery

We evaluated creatine kinase (CK; EC 2.7.3.2) MM3:MM1 isoform ratios in the serum of cardiac patients immediately after cardiac surgery for the diagnosis of perioperative myocardial injury. The mean ratio was 4.8 (range, 1.4-10.7) in 22 patients who had postoperative myocardial complications and 4.6 (1.3-9.6) in 66 patients who did not. By the first postoperative day the ratio had decreased substantially in both groups of patients. The isoform ratio did not correlate with the concentration of total CK, CK-MB, total lactate dehydrogenase (LD), or the incidence of LD1:LD2 or LD5:LD2 ratio reversal. Of these measurements, CK-MB and LD concentrations differed most between the groups of patients; parallel testing of CK-MB and LD showed an optimized sensitivity and specificity of 77% and 87%, respectively. We conclude that analysis for CK-MM isoforms does not add information in the period immediately after cardiac surgery; concentrations of CK-MB and LD correlate with myocardial injury, but the sensitivity and specificity of these measurements may not be high enough for clinical utility.     

Serial Creatine Kinase-MB Results Are a Sensitive Indicator of Acute Myocardial Infarction in Chest Pain Patients with Nondiagnostic Electrocardiograms: The Second Emergency Medicine Cardiac Research Group Study

Objective : To determine the test performance characteristics of serial creatine kinase-MB (CK-MB) mass measurements for acute myocardial infarction (MI) in patients presenting to the ED with chest pain and nondiagnostic ECGs. Methods : A prospective, observational test performance study was conducted. Hemodynamically stable patients aged ≥25 years with chest discomfort, but without ECGs diagnostic for MI, were enrolled at 7 university teaching hospitals. Presenting ECGs showing >1-mV ST-segment elevation in ≥2 electrically contiguous leads were considered diagnostic for MI; patients with diagnostic ECGs on presentation were excluded. Real-time, serial CK-MB mass levels were obtained using a rapid serum immunochernical assay at the time of ED presentation (0-hour) and 3 hours later (3-hour). The following testing schemes were evaluated for their sensitivity and specificity for detection of MI during patient evaluation in the ED: 1) an elevated (≥8 ng/mL) presenting CK-MB level; 2) an elevated presenting and/or 3-hour CK-MB level; 3) a significant increase (i.e., ≥3 ng/mL) within the range of normal limits for CK-MB concentrations during the 3-hour period (A CK-MB); andor 4) development of ST-segment elevation during the 3 hours (second ECG). Results : Of the 1,042 patients enrolled, 777 (74.6%) were hospitalized, including all 67 MI patients (8.6% of admissions). As a function of duration of time in the ED, the test performance characteristics of serial CK-MBs for MI (and cumulative data for the additional ECG) were: 0-hour CK-MB Plus 3-hour CK-MB Plus A CK-MB Plus Second ECG Sensitivity 38/67 = 57% 59/67 = 88% 62/67 = 93% 64/67 = 96% (95% CI) (44–69%) (78–95%) (83–98%) (88–99%) Specificity 9431976 = 97% 9351976 = 96% 9291976 = 95% 9311976 = 95% (95% CI) (95–98%) (94–97%) (94–96%) (94–97%) The 0-hour to 3-hour CK-MB positive and negative predictive values were 52% to 55% and 96% to 99%, respectively. The sensitivities of serial CK-MB results as a function of the interval following chest discomfort onset were: Interval Since Onset Sensitivity (95% CI) Interval Since Onset Sensitivity (95% CI) Less than 3 hours 38% (21–58%) 6 hours to 12 hours 92% (78–98%) 3 hours to 6 hours 75% (60–87%) More than 12 hours 100% (77–100%) Conclusion : Serial CK-MB monoclonal antibody mass measurements in the ED can identify MI patients with initially nondiagnostic ECGs. CK-MB sensitivity significantly increases over 3 hours of observation of stable chest discomfort patients in the ED; it also increases as a function of the total interval from onset until enzyme measurement.     

Microcirculatory significance of periprocedural myocardial necrosis after percutaneous coronary intervention assessed by the index of microcirculatory resistance

This study sought to investigate the relationship between the index of microcirculatory resistance (IMR) and periprocedural myocardial necrosis in patients with unstable angina pectoris (UAP). Fifty-seven UAP patients undergoing elective percutaneous coronary intervention (PCI) of a single lesion were recruited. A pressure–temperature sensor wire was used to measure IMR immediately after PCI. Total creatine kinase-MB (CK-MB) and troponin I (TNI) were measured every 8 h after PCI until they began to decline. Of the 57 patients studied, 22 had periprocedural myocardial infarction (MI) according to TNI. Post-PCI IMR >31 U had 86 % sensitivity and 91 % specificity for predicting periprocedural MI. There are a strong positive correlation between IMR and peak TNI (r = 0.805, p = 0.001), and a moderate positive correlation between IMR and peak CK-MB (r = 0.608, p = 0.003). Periprocedural myocardial injury, even in small area, during reperfusion is associated with impaired microcirculatory integrity as evaluated by IMR. Post-PCI IMR is independent predictive of developing periprocedural MI in patients with UAP, and, therefore, potentially enables a triage of higher risk patients to more intensive therapy.     

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.     

Leukocytosis: A New Look at an Old Marker for Acute Myocardial Infarction

Objective: To determine the test performance of leukocytosis for identifying acute myocardial infarction (AMI) in patients with nondiagnostic ECGs, admitted to rule out AMI. Methods: A retrospective, comparative test performance study was conducted using patients admitted to a university teaching hospital to rule out AMI. Clinical and laboratory information was reviewed and hospital laboratory ranges were used to define threshold elevations: total creatine kinase (CK), 275 U/L; CK-MB, 7.5 μg/L; white blood cell (WBC) count, 11.5 × 10⁹/L; and absolute neutrophil count (ANC), 8.0 × 10⁹. Sensitivity, specificity, and predictive values of the total CK, CK-MB, WBC count, and ANC were calculated, and receiver operating characteristic (ROC) curves constructed. Test performances of marker combinations also were determined. Results: The initial WBC count was significantly higher for the subjects who had AMI (11.1 vs 8.8 × 10⁹/L, p < 0.001). For the 688 subjects who had nondiagnostic ECGs, sensitivities for the initial total CK, CK-MB, WBC, and ANC were 39%, 73%, 35%, and 36%, respectively, while the corresponding specificities were 94%, 93%, 85%, and 86%. Logistic regression analysis confirmed leukocytosis as an independent predictor of AMI (adjusted odds ratio 4.08, 95% CI 1.73–9.63). While CK-MB alone was 73% sensitive for AMI, the decision rule of either an elevated CK-MB or an elevated WBC count increased this sensitivity to 88% (corresponding specificity 79%). Similarly, while CK-MB alone was 93% specific for AMI, the combination of an elevated CK-MB and an elevated WBC count increased this specificity to 99% (corresponding sensitivity 20%). Conclusions: Leukocytosis is significantly associated with AMI, and is a weak but independent laboratory predictor of this condition. In this preliminary study of admitted patients suspected of AMI, the combination of the WBC and the CK-MB may have, additional diagnostic value over an isolated CK-MB result. Neither parameter in isolation was satisfactorily sensitive for AMI. Prognostic assessment of the role of the WBC count in clinical decision making should address its complementary role to that of other clinical and ancillary test parameters.