Myoglobin,creatine kinase MB isoforms and creatine kinase MB mass in early diagnosis of myocardial infarction in patients with acute chest pain

OBJECTIVES: Measurements of myoglobin and creatine kinase (CK)-MB isoforms have been suggested to be sensitive tests for the early diagnosis of myocardial infarction (MI). We have investigated the utility of myoglobin, creatine kinase (CK)-MB isoforms and creatine kinase MB mass (CK-MBm) in early diagnosis of MI using cardiac troponin T (cTnT) positivity as a reference. DESIGN AND METHODS: The study population comprised 440 patients who had had chest pain for less than 12 h. Patients were divided into cTnT negative (cTnT-) or cTnT positive (cTnT+) patients (concentration of cTnT >0.1 microg/L at two different time points during 72 h). RESULTS: At the time of admission to the emergency department receiver operating characteristics (ROC) curves of CK-MB isoforms and CK-MBm were not better than that of myoglobin. Six hours after admission CK-MB isoforms and CK-MBm provided statistically significantly larger areas under the curve (AUC) than myoglobin (p < 0.01). When ROC curves were related to the onset of chest pain (< 3 h, 3-6 h, and > 6 h) there were no significant differences between the cardiac markers studied. CONCLUSIONS: According to the present findings, CK-MB isoforms or myoglobin offer no advantage over CK-MBm as early markers of myocardial infarction.     

Laboratory diagnosis of patients with acute chest pain.

The enzyme activities of creatine kinase (CK), its isoenzyme MB (CK-MB) and of lactate dehydrogenase isoenzyme 1 (LD-1) have been used for years in diagnosing patients with chest pain in order to differentiate patients with acute myocardial infarction (AMI) from non-AMI patients. These methods are easy to perform as automated analyses, but they are not specific for cardiac muscle damage. During the early 90's the situation changed. First creatine kinase MB mass (CK-MB mass) replaced the measurement of CK-MB activity. Subsequently cardiac-specific proteins troponin T (cTnT) and troponin I (cTnI) appeared on the scene, displacing LD-1 analysis. However, troponin concentrations in blood increase only from four to six hours after onset of chest pain. Therefore a rapid marker such as myoglobin, fatty acid binding protein or glycogen phosphorylase BB could be used in early diagnosis of AMI. On the other hand, CK-MB isoforms alone may also be useful in rapid diagnosis of cardiac muscle damage. Myoglobin, CK-MB mass, cTnT and cTnI are nowadays widely used in diagnosing patients with acute chest pain. Myoglobin is not cardiac-specific and therefore requires supplementation with some other analyses such as troponins to support the myoglobin value. Troponins are very highly cardiac-specific. Only the sera of some patients with severe renal failure, which requires hemodialysis, have elevated cTnT and/or cTnI without there being any evidence of cardiac damage. On the other hand, the latest studies have shown that elevated troponin levels in sera of hemodialysis patients point to an increased risk of future cardiac events in a similar manner to the elevated troponin values in sera of patients with unstable angina pectoris. In addition, the bedside tests for cTnT and cTnI alone or together with myoglobin and CK-MB mass can be used instead of quantitative analyses in the diagnosis of patients with chest pain. These rapid tests are easy to perform and they do not require expensive instrumentation. For routine clinical laboratory practice we suggest that in diagnosis of patients with chest pain, myoglobin and CK-MB mass measurements should be performed whenever they are requested (24 h/day) and cTnT or cTnI on admission to the hospital and then 4-6 and 12 hours later.     

Diagnosis and risk stratification of patients with anginal pain and non-diagnostic electrocardiograms

Patients with acute chest pain suggestive of myocardial ischaemia, and normal or non-diagnostic electrocardiograms, form a difficult subgroup for diagnosis and early risk stratification. We prospectively evaluated the role of troponin T (cTnT), troponin I (cTnI), CKMB mass and myoglobin, in the diagnosis and risk stratification of 214 patients with acute chest pain of < or = 24 h and non-diagnostic or normal ECGs admitted directly to the Cardiac Unit of the Royal Victoria Hospital Belfast from the Mobile Coronary Care Unit or the Accident/Emergency Department. This was a single-centre prospective study, and follow-up (3 months) was complete for all patients. Blood was assessed for quantitative cTnT, cTnI, CKMB mass and myoglobin, and qualitative cTnT on admission and at 12 h. Diagnosis of index event and incidence of new cardiac events (death, non-fatal myocardial infarction, revascularization, or readmission for unstable angina) over 3 months were assessed. Based on standard criteria, myocardial infarction occurred in 37/214 (17%), and unstable angina in 72/214 (34%). At 12 h from admission, cardiac troponins had higher sensitivity for the diagnosis of acute coronary syndromes (myocardial infarction and unstable angina) than conventional markers (cTnI 48%, cTnT 38%, CKMB mass 30% or myoglobin 27%). At 3 months, a new cardiac event had occurred in 42/214 (20%). Significantly higher event rates occurred when any of the biochemical markers was elevated, but the statistical significance was highest for patients with elevated cTnI (p < 0.0001). Whilst gender, history of ischaemic heart disease (IHD), stress test response, cTnT, cTnI, CKMB mass and myoglobin were univariate predictors, cTnI at 12 h and stress test response were the only two independent significant predictors for a subsequent cardiac event at 3 months. Raised cTnI at 12 h after admission had the highest sensitivity for the diagnosis of acute coronary syndromes, and was independently associated with a 2-3 times increased risk of future cardiac events within 3 months among patients with acute chest pain suggestive of myocardial ischaemia but with normal or non-diagnostic ECGs.     

Time-dependent diagnostic performance of a rapid troponin T version 2 bedside test in patients with acute coronary syndromes

In a prospective trial, the diagnostic performance of the second version of the troponin T rapid assay (Trop T; cutoff 0.2 microg/L) was compared with the quantitative cardiac-specific troponin T assay (cTnT ELISA; cutoff 0.1 microg/L) and other established cardiac markers such as CK, CK-MB activity, CK-MB mass and myoglobin. Additionally, a 30-day follow-up was performed to determine the suitability of the Trop T assay and the reference markers for short-term risk stratification. Two-hundred-and-eighty-six consecutive patients with chest pain and suspected acute myocardial infarction (AMI) were enrolled in two CCU departments. Serial blood specimens were taken at admission and at 3, 6, 12, 24, 48, 72 and 96 h after admission. According to the biochemical criterion CK-MB mass, the patients were classified as having AMI in 154 patients (54%), unstable angina (UAP) in 72 patients (27%) and no evidence for acute cardiac ischemia in 55 patients (19%). Analytical method comparison of Trop T with cTnT ELISA (cutoff 0.1 microg/L) showed a good agreement, Trop T yielded only 4% false-negative and 3% false-positive results. The diagnostic performance of Trop T for the detection of AMI was only slightly inferior compared to cTnT ELISA. Beyond 12 h after admission, Trop T and cTnT ELISA maintained a sensitivity close to 100%, whereas the sensitivity of the other cardiac markers decreased sharply. The diagnostic sensitivity of Trop T for the detection of minor myocardial damage in UAP patients was the same as for cTnT ELISA. Death within 30 days' follow-up occurred only in AMI patients with a positive Trop T test result within the first 6 h after admission. The admission Trop T and cTnT ELISA were the only significant biochemical predictors of major cardiac events. In conclusion, these data show that Trop T has similar diagnostic sensitivity as cTnT ELISA and is a useful tool to confirm acute or subacute myocardial infarction. Trop T is an excellent marker in detecting minor myocardial damage in UAP patients and is suitable for short-term risk stratification.     

Validation of NACB and IFCC guidelines for the use of cardiac markers for early diagnosis and risk assessment in patients with acute coronary syndromes

BACKGROUND: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes. METHODS: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death. RESULTS: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up. CONCLUSIONS: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.     

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.     

Point-of-care testing: false elevation of cardiac troponin I assayed in the emergency department

In October 2007, an 18-year-old woman with no cardiac history was admitted to the emergency department for a major epigastric pain. The chest pain led to assay cardiac troponin I (cTnI) with the emergency department point-of-care testing analyzer (Stratus CS), which disclosed a value of 0.70 ng/mL, discordant with the atypical clinical presentation and the noncontributive electrocardiography. The biologist contacted for biological advice controlled cTnI with an Access II, which disclosed a value less than 0.04 ng/mL. These findings were confirmed with the discordant results of a new sample assayed on both analyzers. The interference of heterophilic antibodies (HAs) was suspected because these antianimal antibodies may lead to analytical errors in sandwich immunoassays using animal sources of immunoglobulins and can cause false-positive results. In this case, the HAs bind to the capture antibody and the conjugate antibody, simulating cTnI. The diagnosis of HA involvement was confirmed using Heterophilic Blocking Tube, a device that contains a blocking reagent composed of specific binders that attach HA. After treatment in Heterophilic Blocking Tube, the cTnI concentration measured by the Stratus CS decreased from 0.62 to 0.05 ng/mL. Finally, potentially invasive test or this patient's unnecessary hospitalization in cardiology was avoided. Our experience supports that collaboration between staffs of laboratories and medical departments owning point-of-care testing analyzers is essential to avoid mistaken diagnosis linked to analytical interferences and to ensure quality of results assayed outside the laboratory.     

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。     

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.     

A new chest pain strategy in Thunder Bay

Thunder Bay Regional Hospital (TBRH) developed a chest pain strategy (CPS) to support its emergency physicians in making the difficult clinical decisions required to properly evaluate and manage ED "chest pain" patients. This strategy was developed to ensure excellent patient care in a setting of diminished inpatient bed availability and increasing ED congestion. It focuses on rapid risk stratification, using history, electrocardiogram, physical examination and 3 new point-of-care cardiac markers: myoglobin, CK-MB mass, and cardiac troponin I. Following the introduction of the CPS in 1997, TBRH realized significant ($500 000/yr) institutional resource savings through a 60% decrease in the admission rate of non-myocardial infarction, non-unstable angina chest pain patients, a 30% decrease in ED chest pain evaluation time, and improved ED availability of monitored stretchers. The CPS has allowed TBRH to simultaneously decrease costs and improve patient care.     

Cardiac troponin: a critical review of the case for point-of-care testing in the ED

The measurement of cardiac troponin concentrations in the blood is a key element in the evaluation of patients with suspected acute coronary syndromes, according to current guidelines, and contributes importantly to the ruling in or ruling out of acute myocardial infarction. The introduction of point-of-care testing for cardiac troponin has the potential to reduce turnaround time for assay results, compared with central laboratory testing, optimizing resource use. Although, in general, many point-of-care cardiac troponin tests are less sensitive than cardiac troponin tests developed for central laboratory–automated analyzers, point-of-care systems have been used successfully within accelerated protocols for the reliable ruling out of acute coronary syndromes, without increasing subsequent readmission rates for this condition. The impact of shortened assay turnaround times with point-of-care technology on length of stay in the emergency department has been limited to date, with most randomized evaluations of this technology having demonstrated little or no reduction in this outcome parameter. Accordingly, the point-of-care approach has not been shown to be cost-effective relative to central laboratory testing. Modeling studies suggest, however, that reengineering overall procedures within the emergency department setting, to take full advantage of reduced therapeutic turnaround time, has the potential to improve the flow of patients through the emergency department, to shorten discharge times, and to reduce cost. To properly evaluate the potential contribution of point-of-care technology in the emergency department, including its cost-effectiveness, future evaluations of point-of-care platforms will need to be embedded completely within a local decision-making structure designed for its use.     

Cardiac markers: point of care testing.

Point-of-care (POC) or "near-patient" testing allows diagnostic assays to be performed in locations such as the emergency department or intensive care unit where treatment decisions are made and care is delivered based on the results of these assays. Presently, there exist POC immunoassays for several cardiac markers including creatine kinase MB (CK-MB), myoglobin, troponin I, and troponin T that yield qualitative and quantitative results comparable to traditional central lab assays. In the evaluation of emergency room patients with chest pain, POC cardiac markers may improve triage and clinical outcomes. Existing POC assays combining myoglobin and CK-MB have high sensitivity and specificity for diagnosing acute myocardial infarction and may provide the earliest identification of myocardial injury. POC Troponin T assays are the most studied POC cardiac marker assays. Along with POC troponin I assays, these tests provide more sensitive identification of myocardial injury and valuable prognostic information. Prior studies of POC cardiac marker assays have not addressed whether POC testing affects patient outcome or process of care. In situations in which caregivers base triage, treatment and monitoring decisions on time-sensitive diagnostic results, POC tests linked with improved triage and treatment strategies may improve resource utilization and clinical outcomes.     

Cardiospecificity of the 3<Superscript>rd</Superscript> generation cardiac troponin T assay during and after a 216 km ultra-endurance marathon run in Death Valley

Background The reasons for the appearance of cardiacspecific troponin (cTnT) after strenuous exercise are unclear. The aim of the present study was to evaluate the cardiospecificity of the 3^rd generation cardiac cTnT assay during and after an ultra-endurance race of 216 km at extreme environmental conditions in Death Valley. Study design and methods We measured serially cTnT, creatine kinase (CK), activity and mass of the isoenzyme MB of CK (CK-MB_act and CK-MB_mass), and myoglobin in 10 well-trained athletes before, repeatedly during and after the race. Results Six of 10 participants finished the race within a preset time of 60 hours. Postrace values of biochemical markers CK, CK-MB_act, CKMB_mass, and myoglobin were significantly increased compared to baseline (p<0.05). CK-MB_act increased from (median (25^th/ 75^thpercentile) 12 (10/13) U/L to 72 (32/110) U/L, CK-MB_mass from 3.9 (2.9/5.6) U/L to 65 (18/80) U/L and CK increased from median 136 (98/ 228) U/L to 3,570 (985/6,884) U/L respectively. Pre-race myoglobin was 27 (22/31) μg/l compared to 530 (178/657) μg/l after the run. One runner developed significant exercise-induced rhabdomyolysis with spontaneous recovery. cTnT values remained below the 99^th percentile reference limit in all athletes including the runner who developed significant rhabdomyolysis (peak CK 27,951 U/L). Conclusions Strenuous endurance exercise, even under extreme environmental conditions, does not result in structural myocardial damage in well-trained ultra-endurance athletes. We found no crossreactivity between cTnT and CK, neither in exercise-induced skeletal muscle trauma nor after rhabdomyolysis underscoring the excellent analytical performance of 3^rd generation cTnT assay.     

High-workload endurance training may increase serum ischemia-modified albumin concentrations.

The measurement of cardiac troponins has emerged as the biochemical "gold standard" for the diagnosis and management of patients with acute chest pain. However, earlier markers should support investigation strategies, as several patients with acute coronary syndrome might present with non-diagnostic concentrations. Ischemia-modified albumin (IMA), measured by the albumin cobalt binding (ACB) assay, was recently proposed for early detection of myocardial ischemia. To establish the potential influence of endurance training on the diagnostic approach to patients with suspected myocardial injury, cardiac troponin T (cTnT), creatine kinase isoenzyme MB (CK-MB), myoglobin and IMA were evaluated in healthy individuals subjected to different aerobic workloads. The concentrations of both IMA and CK-MB were significantly increased in athletes subjected to high-workload endurance training, whereas the concentration of cTnT and myoglobin was not influenced by physical exercise in the medium term. Taken together, our results demonstrate that demanding aerobic physical activity might influence the generation of IMA, which might be increased in the medium term following high-workload endurance training, while the concentration of other conventional markers of myocardial injury remains non-diagnostic.     

Myoglobin stratifies short-term risk in acute major pulmonary embolism

BACKGROUND: Concentrations of cardiac troponins can be elevated in acute pulmonary embolism (APE) indicating myocardial injury. Although concentration of myoglobin (MYO) increases after myocardial damage, even before detectable rise of cardiac troponin levels occurs, MYO was not evaluated in APE. Therefore, we assessed prevalence and prognostic significance of myoglobin in major APE. METHODS: We studied 46 patients (30 women, aged 61.9+/-17.8 years) with major APE defined with right ventricular dilatation. On admission serum myoglobin, and cardiac troponin T (cTnT) were measured. Serum MYO concentrations >58 ng/ml for women, and >72 ng/ml for men were considered abnormal. CTnT>0.01 ng/ml was regarded to indicate myocardial injury. RESULTS: MYO levels exceeding sex specific norms were found in 21/46 (45.7%) of patients, while detectable cTnT was found in 24/46 (52.1%) of patients. Seven patients died during hospitalization. Elevated MYO significantly predicted in-hospital mortality (OR 25, 95% CI 1.3-474.2), while increased cTnT concentration did not affect the survival. Among clinical and echocardiographic variables only older age indicated worse prognosis (OR 1.6, 95% CI 1.06-2.41). CONCLUSIONS: Myoglobin levels are elevated in serum on admission in almost half of patients with major APE. Elevated myoglobin level, marker of myocardial injury, is a powerful predictor of increased risk of fatal outcome in major pulmonary embolism.     

心肌钙蛋白T定性在急性冠状动脉综合征诊断上的应用

目的　评价心肌钙蛋白T (cTnT)在急性冠状动脉综合征的诊断价值。方法　收入急诊ICU的急性冠状动脉综合征病人分为 :AMI组和UAP组 ,抽取肘部静脉血 1ml立即注入肝素抗凝试管中 ,混匀。用德国宝灵曼中国有限公司提供的肌钙蛋白T灵敏检测试纸条进行定性检查。同时用放免分析方法测定血清CK、CK MB及AST。结果　AMI组cTnT阳性率为 70 6 % ,UAP组阳性率 16 7% ,两组阳性率对比有显著性差异性 (P <0 0 1)。结论　cTnT是反映心肌细胞损伤的灵敏性、特异性均较好的生化指标 ,cTnT定性检测可用于ACS早期鉴别诊断 ,其临床意义优于血清CK、CK MB及AST。     

Evaluation of the chemiluminescence immunoassays for the measurement of troponin I, myoglobin and CK-MB using the IMMULITE system in comparison to other measuring systems

We evaluated the chemiluminescence immunoassays for the detection of the cardiac markers troponin I, myoglobin and CK-MB on the IMMULITE System (Diagnostic Products Corporation) in comparison to the same analytes of other companies. The IMMULITE assays are two-site solid phase immunometric assays using a murine monoclonal capture antibody on the solid phase and a polyclonal antibody conjugated with alkaline phosphatase (except CK-MB monoclonal, murine) for detection. Precision was investigated using serum pools with a low, a cutoff and a high concentration of the respective analyte. The results were satisfactory with an intra-assay precision coefficient of variation, CV of 1.7% - 3.2% for troponin I, 2.6% - 5.1% for myoglobin, 2.7% - 5.3% for CK-MB and an interassay precision of 5.1% - 6.9% for troponin I, 5.7% - 7.3% for myoglobin and 3.8% - 8.4% for CK-MB. In linearity studies with various dilution steps, a mean value of 105% was found for troponin I, 103% for myoglobin and 117% for CK-MB. The average recovery was 85% for troponin I, 100% for myoglobin and 95% for CK-MB. The clinical validity of the assays in the diagnosis and therapy of myocardial infarction was investigated in 120 patients who were sent to the hospital with suspected myocardial infarction. Four hours after admission all patients with clinically verified myocardial infarction showed troponin I and troponin T values above the cutoff value. A maximum rate of 32% of the patients (IMMULITE Troponin I) with an instable angina pectoris showed troponin values above the cutoff for myocardial infarction (1.0 microg/L), 4 hours after admission. A cutoff-reduction to 0.2 pg/L for troponin I increased the number of patients to 45%. The negative predictive value was constantly 67%. The results obtained by IMMULITE assays were compared to the Elecsys cardiac assays (Roche Diagnostics) and the AxSYM-cardiac assays (Abbott Diagnostics). The highest correlation (r = 0.99) was found for IMMULITE Troponin I (DPC) and Troponin I (Abbott). The Abbott-Troponin I showed the highest diagnostic sensitivity within 4 hours after admission. All compared methods showed a similar diagnostic sensitivity (close to 100%) > 4 hours after admission. For all investigated methods the percentage of discrepant results decreased to a minimum 4 hours after admission.     

Performance of Multiple Cardiac Biomarkers Measured in the Emergency Department in Patients with Chronic Kidney Disease and Chest Pain

OBJECTIVE: To evaluate the individual components of a cardiac multimarker panel in the detection of acute myocardial infarction (AMI) in patients with chest pain across a spectrum of renal dysfunction. METHODS: A total of 817 consecutive patients evaluated for a possible AMI in the emergency department (ED) enrolled in a prospective study of cardiac biomarkers assessed using a point-of-care device with myoglobin (MYO), cardiac troponin I (cTnI), and creatine kinase myocardial band (CK-MB), recorded at 0, 1.5, 3, and 9 hours. This study did not exclude patients on the basis of renal dysfunction. Baseline renal function was available in 808 patients. Patients were stratified by corrected creatinine clearance (CorrCrCl) into quartiles, and those on dialysis (n = 51) were considered as a fifth comparison group. Those patients with advanced renal dysfunction (CorrCrCl < 47/mL/min/72 kg) or on dialysis had higher rates of diabetes, hypertension, and prior coronary disease. Agreement for the diagnosis of AMI was required of two independent cardiologists using criteria based on history, electrocardiogram, and central laboratory assessment of serial cardiac markers. RESULTS: More than 99% of all patients were admitted to a chest pain observation unit or the hospital. Mean MYO levels were elevated in the presence of renal dysfunction in those with and without myocardial infarction. Both MYO and CK-MB were correlated with CorrCrCl, (r = -0.36, p < 0.01, and r = -0.10, p = 0.01, respectively), while cTnI was not (r = -0.10, p = 0.12). Using multiple receiver operating characteristic curve testing, cTnI was found to be the most consistent marker across all strata of renal dysfunction, including end-stage renal disease on dialysis. The authors did not find a trend for false-positive cTnI and renal dysfunction. CONCLUSIONS: A point-of-care, rapid cardiac biomarker strategy utilizing cTnI is applicable and superior to MYO or CK-MB in the evaluation of chest pain in patients with renal dysfunction.     

Plasma or serum samples: measurements of cardiac troponin T and of other analytes compared.

Conflicting data in the literature concern possible differences in the immunochemical measurement of cardiac troponins, either in plasma or in serum. In order to address this specific point, 96 serum and heparin-plasma pairs were obtained for cardiac marker measurement [cardiac troponin T (cTnT); myoglobin (Myo) and creatine kinase-MB isoenzyme (CK-MB)]; 29 additional "common" analytes were measured in 77 such samples. The cardiac markers were measured by electrochemiluminescence (Elecsys 2010, Roche); the other analytes by established automated methods (Modular, Roche). Mean plasma/serum ratios for cTnT (0.95), creatine kinase-MB (1.01) and myoglobin (0.99) were comparable with those of the 29 common analytes (interval of means 0.83-1.05). The distribution of the plasma-serum differences also showed similarities between cardiac markers and other analytes. A few outlier plasma-serum differences (3-5%) were measured for both categories of analytes. Addition of heparin to serum (51 samples) caused decreased cTnT (mean ratio 0.92). In 3 of 51 such samples the cTnT decrease was more marked, but in a second sample from the same subjects (1 week later) such a prominent, heparin-induced loss of cTnT no longer appeared. In conclusion, plasma-serum differences in immuno-reactive cTnT compare with those observed for other analytes. In occasional heparin-plasma samples immunochemical measurement of cTnT may give exceptionally low values. However, in our sample group of 96 patients (cTnT lower or higher than the cut-off in, respectively, 24 and 72 patients), no misclassification occurred if plasma instead of serum cTnT values were considered.     

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.