Biochemical marker for myocardial injury

Recently, the general idea of the acute coronary syndrome (ACS) that includes acute myocardial infarction and unstable angina has been established. ACC/AHA guidelines in 1996 and 1999 had emphasized the importance of the initial diagnosis and the early treatment in acute myocardial infarction. We presented about the recent advances in "injured myocardial marker" around the ACS in this paper. The sensitivity and specificity for detecting myocardial injury by troponin T and I(TnT and TnI) were superior compared with those in creatinine kinase (CK) and CK-MB. Easy rapid detection system by using whole blood was useful in the diagnosis a high risk cases in ACS. Measurement of TnT and TnI are recommended the use in the emergency room. A guideline for a diagnosis of acute myocardial infarction had a revision (ACC/ESC) on 2000. Biochemical markers of TnT & TnI were recommended as the first step for defining the myocardial injury. Unstable angina pectoris with a minimal myocardial injury (rise in CK under two times) was defined acute myocardial infarction. As for the measurement of the myocardial injury, rapid detection and accuracy & specificity may enhance the value of modality. In future, inflammation marker such as the high sensitivity CRP and an activated platelet may be thought to become important.     

Strategies for the early diagnosis of acute myocardial infarction using biochemical markers

We evaluated different diagnostic strategies for the early diagnosis of acute myocardial infarction, combining sensitivity and specificity of different markers evaluated singly and using combination testing in parallel and serial modes. Myoglobin, cardiac troponin I (TnI), creatine kinase (CK), and CK-MB mass were tested in blood samples from 26 patients with acute myocardial infarction collected at admission (T0; mean = 3.3 hours from the onset of chest pain) and 3 and 6 hours later. The comparison group was made up of 70 patients with renal failure, skeletal muscle diseases, stable angina, unstable angina, and chest pain of nonischemic origin. Single tests showed different sensitivities in relation to the different release kinetics; myoglobin was the most sensitive (69% at T0) although less specific (46%), and TnI showed the highest specificity (90%) and a sensitivity of 54%. Combination testing in a parallel mode using myoglobin and TnI or CK-MB had the same sensitivity and specificity as myoglobin tested singly. The best combination in a serial mode is myoglobin and TnI (at T0 sensitivity, 54%; specificity, 98%), as confirmed by the analysis of the positive predictive value, the negative predictive value, and the accuracy evaluated as a function of different disease prevalences.     

Establishment of a cut-off value for the diagnosis of acute myocardial infarction using a new CK-MB activity measurement reagent containing anti-MtCK antibody

CK-MB is an important marker for the diagnosis of acute myocardial infarction (AMI). Since mitochondrial CK (MtCK) is universally present in the blood of healthy individuals, it is known to positively affect the measurement of CK-MB using the immunoinhibition method, causing false-positive results. We performed basic evaluation of ACCURAS AUTO CK-MB MtO, a new reagent containing anti-MtCK antibody that inhibits MtCK activity, and attempted to calculate a cut-off CK-MB level to diagnose AMI. The measurement was performed in samples submitted to the Clinical Laboratory of our center for the measurement of CK-MB. This method was confirmed to have satisfactory basic attributes concerning the reproducibility, linearity, lower detection limit, and effects of interfering substances. When 2886 samples were examined using this and conventional methods, the results of the two methods were correlated in some but not in others. In the samples that showed no correlation, MtCK was demonstrated by isozyme analysis using electrophoresis. The AUC calculated from the ROC curve in AMI patients was 0.912 with this method and 0.861 with the conventional method. The sensitivity and specificity of the new method were higher than those of the conventional method. The cut-off value determined by ROC analysis was 7.7 U/l using the new method and 13.6 U/l using the conventional method, causing an increase in false-positive results compared with the cut off value of 25 U/l widely used for the conventional method to date. However, the cut-off value for the new method that yielded a specificity comparable to 99.1%, which is the specificity of the conventional method using a cut-off value of 25 U/l, was 12 U/l. With a cut-off value of 12 U/l, the sensitivity was improved compared with that employing the conventional method, and both the sensitivity and specificity became comparable to those of the CK-MB mass method. This method is very useful for the accurate measurement of CK-MB activity.     

Financial impact of a rapid CK-MB-specific immunoassay on the diagnosis of myocardial infarction

The purpose of this study was twofold. First, we evaluated the financial impact of a rapid, monoclonal antibody-based CK-MB mass assay (Stratus, Dade Division, Baxter Laboratories, Miami, Fla) for the direct measurement of CK-MB in serum samples from 65 patients admitted to the coronary care unit with the possible diagnosis of acute myocardial infarction. Second, we evaluated retrospectively the Stratus assay and an activity assay (electrophoresis) for CK-MB in the following patient categories: acute myocardial infarction treated with and without thrombolytic therapy, angina, congestive heart failure, skeletal muscle trauma, and the acutely ill without acute myocardial infarction. The advantageous features of the Stratus mass assay were as follows. First, the laboratory was able to perform the assay more frequently because of the short assay time per specimen (less than 10 minutes) without additional personnel. This had a substantial impact on the clinician's ability to diagnose acute myocardial infarction and to move patients out of an intensive care unit at substantial financial savings to the patient, the hospital, or the third-party payer. Second, the Stratus assay was able to detect low levels of CK-MB (1 to 2 micrograms/L) in the presence of low total creatine kinase activity (less than 100 U/L). Third, the Stratus assay showed no interference due to very-high-total creatine kinase activities (greater than 100,000 U/L), CK-BB, macro-creatine kinase, and mitochondrial creatine kinase.     

Cardiac troponin I and CK-MB mass after cardiac surgery with cardiopulmonary bypass

Cardiac troponin I (cTnI) assay is used in the diagnosis of myocardial infarction after cardiac surgery. Variations in the cut-off value have been reported even with the same assay method. The aim of this work is to investigate the release profile of cTnI and CK-MB mass after cardiac surgery and to determine the cut-off value of cTnI and CK-MB mass allowing the diagnosis of perioperative myocardial infarction. In patients without postoperative cardiac complication, the cTnI peak was observed 24 hours after surgery both in coronary artery bypass grafting and in valve replacement. Moreover, the amount of cTnI released within the three hours after surgery is 2.5 fold higher in valve replacement than in coronary artery bypass grafting. The CK-MB peak was observed 3 hours after surgery in the two surgical procedures. In these patients, cTnI and CK-MB concentrations increased with the cross clamp time duration. In patients with postoperative myocardial infarction, the cTnI and CK-MB peaks were observed 24 hours after surgery. Diagnosis of perioperative myocardial infarction can be performed with a sensitivity of 100% at 24 hours with cut-off values of 32 and 7 microg/L for CK-MB and cTnI, respectively, both with Stratus (Dade Behring) and Immulite (DPC) analysers.     

血清心肌型脂肪酸结合蛋白快速检测急性心肌梗死的敏感度和特异度分析

目的:分析血清心肌型脂肪酸结合蛋白(H-FABP)快速检测对急性心肌梗死(AMI)早期诊断的敏感度和特异度。方法:53例胸痛患者,经确诊分为AMI组(包括发病<6h和6～12h两亚组)和非AMI组,平行检测H-FABP、肌红蛋白(MYO)、心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB),计算H-FABP等指标诊断AMI的敏感度和特异度。结果:H-FABP诊断发病<6h AMI的敏感度为85.71%,与MYO的80.95%相近,明显高于cTnI的47.62%和CK-MB的52.38%,差异有统计学意义(P<0.05);AMI发病6～12h,H-FABP诊断AMI的敏感度为100.00%,略高于MYO、cTnI和CK-MB(均为92.86%),但差异无统计学意义(P>0.05)。H-FABP等指标诊断AMI的特异度无论非AMI组还是健康对照组,各指标间差异均无统计学意义(P>0.05)。结论:H-FABP对AMI早期诊断有较高的敏感度和特异度,可作为AMI早期筛查及诊断指标。     

Heart-type, fatty-acid binding protein can be a diagnostic marker in acute coronary syndromes

OBJECTIVES: Chest pain is one of the most common complaints among patients admitted to emergency departments. Cardiac troponins, CK-MB and myoglobin, which are used routinely in the diagnosis of acute coronary syndrome (ACS), are not elevated in the initial hours of ACS--precluding their usefulness in the early diagnosis. The aim of this study is to determine the efficacy of H-FABP compared to myoglobin and CK-MB in the early diagnosis of ACS. METHODS: Sixty-seven patients with ACS were enrolled in the study. An initial blood sample was obtained for CK-MB, cTnT, myoglobin and H-FABP. At the fourth, eighth, and 12th hours, repeat ECGs and cardiac enzyme samples were obtained. H-FABP test was repeated at the fourth hour. RESULTS: H-FABP has sensitivity equal to that of CK-MB and superior to that of myoglobin (97.6%, 96.7%, 85.4%, respectively) on the first hour. This trend extends to the fourth hour of myocardial injury as well. H-FABP was more specific than CK-MB, myoglobin and troponin T at the first hour (38.5%, 34.6%, 34.6%, 23.1%, respectively), whereas its specificity at the fourth hour was equal to those of CK-MB and troponin T and exceeded that of myoglobin. CONCLUSIONS: It can be suggested that in patients with an initial diagnosis of ACS and within 20 hours from symptom onset, H-FABP levels may be measured. For this purpose, point-of-care H-FABP test may be utilized, which has the advantage of bedside testing and rapid test results.     

Discordant results of CK-MB and troponin I measurements: a review of 14 cases

In the course of a clinical comparison involving 204 parallel total creatine kinase (CK), creatine kinase-MB isoenzyme (CK-MB), and cardiac troponin I (cTnI) measurements, 12 patients were identified in whom cTnI was elevated while total CK was normal, as well as 2 patients in whom CK-MB was elevated while cTnI was normal. CK-MB relative index was elevated in 6 of the twelve cTnI-positive patients with normal total CK; only 2 of these patients had a discharge diagnosis of acute myocardial infarction (AMI). All of the 12 patients in this group had medical conditions that are associated with greater risk for acute cardiac events. Both patients with normal cTnI but elevated total CK and CK-MB index had chronic renal insufficiency; one of these patients had a positive stress test and a diagnosis of AMI. The other cTnI-negative patient died 2 days after admission, and autopsy revealed evidence of ischemic changes, but not acute infarction. Significant differences were apparent between traditional CK-MB results and cTnI measurements. Using total CK elevation as a prerequisite for subsequent CK-MB measurement may limit the clinical sensitivity of this enzyme marker for detecting subacute ischemic damage to the myocardium. Elevated total CK and CK-MB isoenzyme without corresponding elevations in cTnI, on the other hand, may reflect changes in enzyme elimination kinetics due to renal failure, or cross-reactivity of the cTnI assay with non-cardiac antigens.     

Analysis of CK-MB using immunoinhibition method]

The significance of creatine kinase (CK) in the diagnosis of acute myocardial infarction was evaluated. The serum level of CK-MB, a CK isozyme was determined by the immunoinhibition method. The CK-MB activity could be determined by the immunoinhibition method in a short time with an autoanalyzer, suggesting that the immunoinhibition technique is adequate as a method of emergency examination. The immunoinhibition method has the disadvantage of error induction because of contamination with CK-BB, CKm and macro-CK by this method. Thus, CK-MB activity should be determined in parallel with total CK activity. When a significant contribution from CK-BB is suspected, its presence should be confirmed by other methods. The present results suggest that the efficiency of coronary artery reperfusion therapy can be evaluated earlier by determination of CK-MB activity than by that of total CK activity.     

心肌肌钙蛋白在急性冠状动脉综合征诊断中的应用

为探讨心肌型肌酸激酶同工酶(CK-MB)与心肌肌钙蛋白T(cTnT)在诊断急性冠状动脉综合征(ACAS)时的相互关系,本文选择了157例疑似ACAS患者的血液标本,同时进行了CK-MB和cTnT的测定.结果表明:CK-MB与cTnT的相符率达82.1%(129/157).CK-MB对ACAS的敏感性为76.8%(43/56),特异性为78.2%(43/55);cTnT对ACAS的敏感性为94.6%(53/56),特异性为100%(43/43).cTnT与CK-MB在诊断ACAS的敏感性和特异性上,有显著差别(P《0.005).结论:cTnT取代CK-MB成为检测ACAS的新指标是可行的.     

Clinical evaluation of the new creatine kinase MB reagent kit "L-System CK-MB MtO"

The creatine kinase MB (CK-MB) activity assay, which is based on the immunoinhibition method, has long been used in the diagnosis of acute myocardial infarction (AMI) because of its good cost-performance ratio and simplicity. However, the immunoinhibition method can not differentiate between CK-MB and MtCK, and therefore, CK-MB activity determined using this method is higher than the actual value in the sample which MtCK appears; this may lead to the misdiagnosis of AMI. We, therefore, evaluated the analytical and clinical performance of a new CK-MB reagent kit "L-System CK-MB MtO," which can inhibit MtCK. The kit yielded good precision and linearity and no interference from hemolysis, bilirubin or chyle. A good correlation was observed between the values determined using this kit and those determined using the conventional kit for samples of patients with acute coronary syndromes. However, differences were observed in the CK-MB values determined for samples from patients with malignancy. CK isoenzyme analysis indicated that MtCK was present in all these samples. The new method permits the accurate estimation of CK-MB activity in samples of patients with high serum levels of MtCK activity and indicates that the conventional method has a high false-positive rate for CK-MB activity. CK-MB activity in the serum of healthy individuals measured using the new and the conventional kits was 1.9-9.5 U/l and 4.5-15.3 U/l, respectively. The new kit, enables accurate estimation of CK-MB activity and is, therefore, more useful than the conventional kit in the diagnosis of acute coronary syndromes.     

心肌酶谱、BNP、MYO及cTnⅠ联合检测诊断急性心梗的价值

目的 分析心肌酶谱[肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）、谷草转氨酶（AST）、α-羟丁酸脱氢酶（α-HBD）、肌酸激酶（CK）]、血浆脑钠肽（BNP）、肌红蛋白（MYO）及肌钙蛋白（cTnⅠ）联合检测诊断急性心梗（AMI）的价值。方法 选取2017年6月~2019年5月于我院治疗的急性胸痛患者82例,将其分为非AMI组（42例）和AMI组（40例）。检测并观察两组心肌酶谱、BNP、MYO及cTnⅠ水平,计算各指标单项及联合诊断AMI的敏感度、特异度。结果 AMI组心肌酶谱、MYO、BNP、cTnⅠ水平均高于非AMI组,差异有统计学意义（P＜0.05）;心肌酶谱+MYO+BNP+cTnⅠ诊断AMI的敏感度（97.50%）高于各单项指标（72.50%、70.00%、80.00%、77.50%）,诊断特异度（92.86%）高于MYO（66.67%）,差异有统计学意义（P＜0.05）。结论 心肌酶谱、cTnⅠ、MYO、BNP联合检测有助于提升AMI诊断准确率,可为临床诊断及尽早开展治疗提供参考依据。     

Signs and symptoms in diagnosing acute myocardial infarction and acute coronary syndrome: a diagnostic meta-analysis.

BACKGROUND: Prompt diagnosis of acute myocardial infarction or acute coronary syndrome is very important. AIM: A systematic review was conducted to determine the accuracy of 10 important signs and symptoms in selected and non-selected patients. DESIGN OF STUDY: Diagnostic meta-analysis. METHOD: Using MEDLINE, CINAHL, EMBASE, tracing references, and by contacting experts, studies were sought out that described one of the 10 signs and symptoms on one or both conditions. Studies were excluded if they were not based on original data. Validity was assessed using QUADAS and all data were pooled using a random effects model. RESULTS: Sixteen of the 28 included studies were about patients who were non-selected. In this group, absence of chest-wall tenderness on palpation had a pooled sensitivity of 92% (95% confidence interval [CI] = 86 to 96) for acute myocardial infarction and 94% (95% CI = 91 to 96) for acute coronary syndrome. Oppressive pain followed with a pooled sensitivity of 60% (95% CI = 55 to 66) for acute myocardial infarction. Sweating had the highest pooled positive likelihood ratio (LR+), namely 2.92 (95% CI = 1.97 to 4.23) for acute myocardial infarction. The other pooled LR+ fluctuated between 1.05 and 1.49. Negative LRs (LR-) varied between 0.98 and 0.23. Absence of chest-wall tenderness on palpation had a LR- of 0.23 (95% CI = 0.18 to 0.29). CONCLUSIONS: Based on this meta-analysis it was not possible to define an important role for signs and symptoms in the diagnosis of acute myocardial infarction or acute coronary syndrome. Only chest-wall tenderness on palpation largely ruled out acute myocardial infarction or acute coronary syndrome in low-prevalence settings.     

冠脉介入治疗对冠心病急性心肌梗死患者 心肌损伤及心室重塑的影响

目的 观察冠脉介入治疗对冠心病急性心肌梗死患者心肌损伤及心室重塑的影响。方法 选取我院自2017年9月~12月收治的64例冠心病急性心肌梗死患者作为观察对象,随机分为研究组33例和对照组31例。对照组给予吸氧、镇静、对症治疗,并给予氯吡格雷+阿司匹林口服,研究组在此基础上进行冠脉介入治疗,对比两组CK、CK-MB、BNP及LVEF、LFESV、LVEDV变化情况。结果 在治疗3 d、7 d后,研究组BNP水平均低于对照组,差异有统计学意义（P＜0.05）。研究组CK峰值、CK-MB峰值与对照组比较,差异无统计学意义（P＞0.05）,但研究组CK峰值、CK-MB峰值出现时间均短于对照组,差异有统计学意义（P＜0.05）。治疗7 d后,两组患者LVEF均升高,LFESV、LVEDV均降低,且研究组LVEF高于对照组,LFESV、LVEDV低于对照组,差异均有统计学意义（P＜0.05）。结论 冠脉介入治疗冠心病急性心肌梗死患者可降低患者BNP水平,改善患者心肌损伤,促进心室重塑,具有较高的应用价值。     

A computer protocol to predict myocardial infarction in emergency department patients with chest pain

To achieve more appropriate triage to the coronary care unit of patients presenting with acute chest pain, we used clinical data on 1379 patients at two hospitals to construct a simple computer protocol to predict the presence of myocardial infarction. When we tested this protocol prospectively in 4770 patients at two university hospitals and four community hospitals, the computer-derived protocol had a significantly higher specificity (74 vs. 71 percent) in predicting the absence of infarction than physicians deciding whether to admit patients to the coronary care unit, and it had a similar sensitivity in detecting the presence of infarction (88.0 vs. 87.8 percent). Decisions based solely on the computer protocol would have reduced the admission of patients without infarction to the coronary care unit by 11.5 percent without adversely affecting the admission of patients in whom emergent complications developed that required intensive care. Although this protocol should not be used to override careful clinical judgment in individual cases, the computer protocol for the most part yields accurate estimates of the probability of myocardial infarction. Decisions about admission to the coronary care unit based on the protocol would have been as effective as those actually made by the unaided physicians who cared for the patients, and less costly. Whether physicians who are aided by the protocol perform better than unaided physicians cannot be determined without further study.     

Cardiac isoenzyme methodology and the diagnosis of acute myocardial infarction

In view of rapidly evolving technology, a thorough appreciation of the subtle nuances of isoenzyme analysis is mandatory in the selection of appropriate methods. The effectiveness of a given laboratory in diagnosing and monitoring ischemic heart disease is related to the sensitivity and specificity of the methods employed. The occurrence of variants of creatine kinase will decrease the specificity of some isoenzyme methods. This study compares the sensitivity and efficiency of four methods for CK-MB and two methods for LD isoenzymes currently available to the laboratory community. The significance of isoenzyme patterns in confirming myocardial infarction was compared with other cardiac diagnostic parameters to determine the most effective laboratory methods. The selection of methods for measurement of cardiac isoenzymes will determine the effectiveness of the laboratory in the diagnosis of myocardial infarction.     

急性心肌梗死患者务清肌钙蛋白T和C反应蛋白变化及其意义

目的：评价血汪肌钙蛋白T（TnT）和C反应蛋白（CRP）在急性心肌梗死（AMI）和不稳定型心绞痛（UAP）的早期诊断及预后评价。方法：分析了AMI48例，UAP45例及健康对照36人血清CRP、TnT、肌酸激酶（CK）和同工酶（CK－MB）水平，并对结果行配对χ^2检验。结果：AMI组入院时血清CRP和TnT阳性率分别为81．3％和97．9％，均明显高于同时间CK和CK－MB的阳性率（p均＜0．01）；UAP组血清CRP、TnT、CK及CK－MB阳性率分别为42．2％、13．3％、11．1％及6．7％。健康对照组36例四项指标均无1例阳性。结论：TnT和CRP在早期辅助诊断AMI和评估UAP患者预后中有应用价值，CK、CK－MB和CRP、TnT联合测定可以提高对AMI诊断的准确性。     

生化标志物的检测对判定急性心肌梗死溶栓后冠脉再通的临床价值

目的研究检测生化标志物血清肌红蛋白（MYO）、肌钙蛋白I（cTnI）、肌酸激酶同工酶（CK—MB）和C-反应蛋白（CRP）对急性心肌梗死溶栓冠脉再通的早期诊断价值。方法MYO、cTnI、CK—MB使用酶联免疫分析法、CRP使用激光散射比浊法测定127例急性心肌梗死患者溶栓治疗前后MYO、cTnI、CK-MB和CRP浓度和时间的变化,分析急性心肌梗死患者溶栓再通组（83例）和溶栓未通组（44例）上述指标的连续、动态演变。结果急性心肌梗死溶栓再通组MYO、cTnI、CK—MB和CRP达到峰值浓度的时间较未通组明显提前（P〈0．01）。其中MYO较cTnI、CK-MB和CRP峰值时间出现更早,分别为（6．1±2．4）h、（13．8±3．5）h、（14．4±3．8）h和（25．2±5．7）h（P〈0．01）;再通组MYO和CRP峰值浓度明显高于未通组（P〈0．01）;MYO、cTnI、CK—MB和CRP对判断冠脉再通的敏感性、特异性、预测值差异无统计学意义（P〉0．05）。结论血清MYO、cTnI、CK-MB和CRP可以较好地预测急性心肌梗死患者溶栓再通,其中MYO较cTnI、CK—MB和CRP能更早期判断冠状动脉是否再灌注;CRP对溶栓后冠脉再通的判断也有积极的参考意义。     

Timed sequential analysis of creatine kinase in the diagnosis of myocardial infarction in patients over 65 years of age.

AIM--To assess the value of timed sequential analysis of creatine kinase (CK) activity for the early diagnosis of acute myocardial infarction (AMI) in patients over 65 years of age. METHOD--Samples were collected on admission and eight to 12 hours later from 156 patients over 65 years of age. Routine cardiac enzyme activities were determined and serial electrocardiograms (ECGs) recorded. The predictive value of timed samples for CK activity, standard cardiac enzyme activities, and ECGs was compared with the final diagnosis on discharge. RESULTS--Forty one patients had a discharge diagnosis of AMI, 83 of angina pectoris, and the remaining 32 patients had other diagnoses. Electrocardiograms had a sensitivity of 55% and a specificity of 96%, giving a predictive value of 86% for a negative and 84% for a positive ECG. Standard cardiac enzymes had a predictive value of 99% for a negative result but only 68% for a positive result. The logarithm of the rate of change of CK activity had a predictive value of 97% for a negative result and 95% for a positive result. CONCLUSION--This study has shown that slope analysis of CK activity can be used for the early diagnosis of AMI in patients over 65 years of age, and that this was not affected by the presence of possible confounding diagnoses.     

Positive troponin T without cardiac involvement in inclusion body myositis

Cardiac troponin T (cTnT) is considered as a specific marker for acute myocardial infarction. Here, we present a case with elevated cTnT, determined by a third-generation assay, without signs of a myocardial lesion. Routine investigation of a 66-year-old female patient with indolent B-cell lymphoma revealed increased serum levels of creatine kinase (CK), MB fraction of CK (CK-MB), and cTnT, although she did not complain of cardiac symptoms. Electrocardiographic monitoring, echocardiography, magnetic resonance computed angiography, and percutaneous coronary angiography excluded myocardial damage. However, the close follow-up showed a steady increase of CK-MB and cTnT levels and gradual development of weakness in both thighs. A biopsy of the right quadriceps muscle led to the diagnosis of inclusion body myositis. In contrast to cTnT, cardiac troponin I could not be detected retrospectively in any of her serum samples. These results demonstrate for the first time that cTnT is elevated in patients with inclusion body myositis.