Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy

BACKGROUND: Because of controversial earlier studies, the purpose of this study was to provide novel experimental and additional clinical data regarding the possible reexpression of cardiac troponin T (cTnT) in regenerating skeletal muscle in Duchenne muscular dystrophy (DMD). METHODS: Plasma from 14 patients (mean age, 7.5 years; range, 5.7-19.4 years) with DMD was investigated for creatine kinase (CK), the CK MB isoenzyme (CKMB), cTnT and cardiac troponin I (cTnI), and myoglobin. cTnT concentrations were measured by an ELISA (second-generation assay; Roche) using the ES 300 Analyzer. cTnI, myoglobin, and CKMB were measured by an ELISA using the ACCESS System (Beckman Diagnostics). Troponin isoform expression was studied by Western blot analysis in remnants of skeletal muscle biopsies of three patients with DMD and in an animal model of DMD (mdx mice; n = 6). RESULTS: There was no relation of cTnT and cTnI to clinical evidence for cardiac failure. cTnI concentrations remained below the upper reference limit in all patients. cTnT was increased (median, 0.11 microg/L; range, 0.06-0.16 microg/L) in 50% of patients. The only significant correlation was found for CK (median, 3938 U/L; range, 2763-5030 U/L) with age (median, 7.5 years; range, 6.8-10.9 years; r = -0.762; P = 0.042). Western blot analysis of human or mouse homogenized muscle specimens showed no evidence for cardiac TnT and cTnI expression, despite strong signals for skeletal muscle troponin isoforms. CONCLUSIONS: We found no evidence for cTnT reexpression in human early-stage DMD and in mdx mouse skeletal muscle biopsies. Discrepancies of cTnT and cTnI in plasma samples of DMD patients were found, but neither cTnT nor cTnI plasma concentrations were related with other clinical evidence for cardiac involvement.     

Cardiac troponin and beta-type myosin heavy chain concentrations in patients with polymyositis or dermatomyositis

Cardiac troponin T (cTnT), cardiac troponin I (cTnI), myosin heavy chains (MHC), myoglobin, creatine kinase (CK), and creatine kinase isoenzyme MB (CKMB), were measured in blood samples from 39 polymyositis (PM) or dermatomyositis (DM) patients without clinical evidence for cardiac involvement to evaluate their clinical usefulness in this patient population. MHC, myoglobin, and CKMB were frequently elevated and correlated with each other and with disease severity. Undetectable cTnI in all but one patient indicated that MHC was released from skeletal muscle, thereby providing the first laboratory evidence of frequent slow-twitch muscle fibre-necrosis in patients with PM or DM. CKMB was elevated in 51%, cTnT in 41%, and cTnI in only 2.5% of patients. cTnI did not correlate with other markers or with disease severity scores. The close correlations found between cTnT and skeletal muscle damage markers and the relationship between cTnT with disease severity without clinical evidence for myocardial damage suggest a release of cTnT from skeletal muscle. The relationship of cTnT with disease severity indicates a possible role of the marker for risk stratification. However, the prognostic values of cardiac troponins and other muscle damage markers in PM/DM patients remain to be compared in prospective outcome trials.     

Tissue specificity of cardiac troponin I, cardiac troponin T and creatine kinase-MB.

The purpose of the paper is to review the tissue specificity of creatine kinase (CK)-MB, cardiac troponin I (cTnI), and cardiac troponin T (cTnT) in human and animal heart and skeletal muscle. Alterations are described which demonstrate that CK-MB is expressed in human skeletal muscle, and is not 100% specific for the heart. cTnI has been shown to be 100% specific for the heart. While cTnT isoforms are expressed in injured skeletal muscle, they are not detected by the diagnostic assays used in clinical practice. Therefore, cTnI or cTnT challenge CK-MB as the new standards for detection of myocardial injury.     

Cardiac troponin elevations in chronic renal failure: prevalence and clinical significance

OBJECTIVES: The aim of the study was investigate the prevalence of abnormal values of cardiac troponin T (cTnT) and cardiac troponin I (cTnI) in patients with chronic renal failure (CRF) and their clinical significance. DESIGN AND METHODS: We investigated the concentrations of cTnT and cTnI in 49 CRF patients without heart disease or diabetes. Cardiac TnT values were measured with a second generation immunoassay and cTnI with two immunoassays with different analytical sensitivity. All CRF patients underwent regular clinical follow-up over a 18-month period. RESULTS: No patients with CRF had elevated values of cTnI when measured with one assay and only 2 patients displayed minimally elevated values with the second assay. In contrast, 23 CRF patients (47%) displayed cTnT concentrations elevated above the upper reference limit. The elevated cTnT values observed were below the values detected in acute myocardial infarction and were not associated with adverse cardiac events during follow-up. CONCLUSIONS: Mildly elevated cTnT concentrations are common in patients with CRF and do not appear to be associated with adverse coronary events.     

Comparison of cardiac troponin T and troponin I assays--implications of analytical and biochemical differences on clinical performance

The usefulness of cardiac troponins for detection of myocardial cell necrosis and risk stratification has been established beyond doubt. Cardiac troponin testing is a key diagnostic element for the diagnosis and management of patients with acute coronary syndromes without ST segment elevation and is increasingly used in non-coronary diseases to indicate prognostically important cardiac damage. Given the biochemical and analytical differences of cTnT and cTnI there is ongoing controversy regarding the comparability and clinical performance of cTnT and cTnI. cTnT and cTnI are both expressed in cardiomyocytes but differ with respect to biochemical and analytical characteristics. While minor differences of analytical precision or biochemical properties are not relevant for diagnosis and management of patients with acute coronary syndromes and most diseases with non-coronary related elevations of cardiac troponins, these differences may be amplified in patients with chronic renal failure. In fact, recent studies in patients with end-stage renal disease under chronic hemodialysis have readdressed the issue whether cTnT and cTnI are really comparable. The present review will provide a state-of-the-art overview on the performance of cardiac troponins in acute coronary disease and other clinical conditions.     

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers

OBJECTIVE: Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. MATERIAL AND METHODS: We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H-FABP) in 23 patients admitted with acute ST-segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24 h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2 h after admission. RESULTS: From 30 min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H-FABP (p<0.05). CONCLUSIONS: The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.     

血清心肌肌钙蛋白对心肌损伤的临床诊断价值

目的　探讨定量分析肌钙蛋白T(cTnT)、肌钙蛋白I(cTnI)对心肌损伤程度评价的临床意义。方法　对80例心肌梗死患[急性心肌梗死(AMI)50例、陈旧性心肌梗死(OMI)30例]、100例心脏手术患、60例非心脏手术患和20例健康人进行了血清cTnT、cTnI、肌酸激酶同工酶(CK—MB)和肌酸激酶(CK)检测。结果　(1)血清cTnT、cTnI、CK—MB和CK检测心肌损伤的敏感度和特异性分别为cTnT(72.4％，100.0％)、cTnI(81.8％，100.0％)，CK—MB(54.6％，87.5％)和CK(64.8％，62.2％)。(2)AMI和心脏手术组cTnT、cTnI、CK—MB和CK四项指标浓度均显高于正常对照组(P＜0.01)。(3)急性心肌梗死组、心脏手术组3h内cTnT和cTnI阳性检出率分别为(50％，56％)和(44％，45％)，明显高于CK—MB(24％，22％)和CK(20％，28％)；急性心肌梗死组、心脏手术组5d后cTnT和cTnI阳性检出率为(70％，66％)和(66％，61％)，而CK—MB仅为(4％，6％)，CK仅为(8％，10％)。结论　血清cTnT、cTnI能确切反映急性心肌梗死、心脏手术等心肌损伤程度，具有较宽的诊断窗口时间，是心肌损伤较敏感和特异的血清标志物。     

心肌肌钙蛋白Ⅰ和肌钙蛋白T对急性缺血性心脏病预后相关性分析

目的探讨心肌肌钙蛋白I(cTnI)和肌钙蛋白T(cTnT)对急性缺血性心脏病转归的影响。方法对就诊的急性缺血性心脏病患者定性测定入院时及距胸痛发作间隔10h的cTnI和定量测定相同时点的cTnT。同时随访患者发病后1、3、6、12个月的疾病转归,以心绞痛、心肌梗死、心力衰竭、心源性猝死为终点评价指标。结果cTnI或cTnT异常患者与正常者相比较,不稳定型心绞痛、心肌梗死、心力衰竭、心源性猝死的发生率具有显著性差异(P<0.01)。cTnI或cTnT异常与终点事件(不稳定型心绞痛、心肌梗死、心力衰竭、心源性心源性猝死)发生率呈正相关。结论cTnI或cTnT对急性心肌梗死,尤其是微小心肌坏死诊断具有高度的敏感性和特异性,并与急性缺血性心脏病的预后密切相关。     

心肌肌钙蛋白I、肌钙蛋白T、肌酸激酶同工酶MB早期诊断 急性心肌梗死敏感性及特异性比较分析

目的 探讨心肌肌钙蛋白Ⅰ（cTnI)、 肌钙蛋白T（cTnT)、 肌酸激酶同工酶MB（CK－MB）早期诊断急性心肌梗死的临床应用价值。方法 对60例急性心肌梗死（AMI）和40例不稳定型心绞痛（UA）患者的同一血样标本检测cTnI、cTnT、CK－MB3项指标,分别进行两组间比较,并对 AMI组和UA组各指标作对比分析。结果 cTnI、cTnT早期诊断急性心肌梗死灵敏度高于CK－MB,阳性率分别为63.3%、46.7%、18.3％,P＜0.01;cTnI和cTnT无显著差别,P＞0.05;cTnI、cTnT、CK－MB特异性相当。结论 心肌肌钙蛋白I和肌钙蛋白T对于AMI的早期诊断具有较高灵敏度和较强特异性,是心肌损伤特异笥标志物,cTnI检测方便、快捷、准确,具有较好的临床价值。     

Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology

BACKGROUND: Spurious increases in serum troponins, especially troponin T, have been reported in patients with and without acute myocardial syndromes. METHODS: We studied 78 autopsied patients without clinical myocardial infarction (MI) and correlated histologic cardiac findings with antemortem serum creatine kinase (CK), its MB isoenzyme (CK-MB), cardiac troponin I (cTnI), and cardiac troponin T (cTnT). RESULTS: There was no significant myocardial pathology in 15 patients. Cardiac pathologies were in five groups: scarring from previous MI or patchy ventricular fibrosis (n = 9), recent MI (n = 27), healing MI (n = 7), degenerative myocyte changes consistent with congestive heart failure (CHF; n = 12), and other cardiac pathologies (n = 8). The median concentrations in the five groups were not significantly different for either CK or CK-MB. Compared with the no-pathology group, only the MI group was significantly different for cTnI, and the MI and other pathology groups were significantly different for cTnT. For patients with MI, 22%, 19%, 48%, and 65% had increased CK, CK-MB, cTnI, and cTnT, respectively; for CHF and other cardiac pathologies combined, the percentages were 28%, 17%, 22%, and 50%. For patients with increased cTnI, 72% and 28% had MI and other myocardial pathologies, respectively; patients with increased cTnT had 64% and 36%, respectively. Patients without myocardial pathology had no increases in CK-MB, cTnI, or cTnT. CONCLUSIONS: All patients with increased serum CK-MB, cTnI, and cTnT had significant cardiac histologic changes. The second-generation cTnT assay appears to be a more sensitive indicator of MI and other myocardial pathologies than the cTnI assay used in this study.     

Cardiac troponin T and I in end-stage renal failure

BACKGROUND: In patients suffering from end-stage renal failure, cardiac troponin T (cTnT) and I (cTnI) may be increased in serum without other signs of acute myocardial damage. Whether these increases are specific to myocardial injury or nonspecific is not completely clear. METHODS: We investigated time courses of cTnT and cTnI over 1 year and the clinical outcome over 2 years in 59 patients with end-stage renal failure undergoing chronic hemodialysis. At the start of the study, we divided the patients into two groups, group 1, without history of cardiac failure, and group 2, with history of cardiac failure, and looked for differences between the groups in later adverse outcome. cTnT was measured using the Enzymun((R)) troponin T assay on an ES 700 analyzer (Roche). cTnI was measured on a Stratus((R)) II analyzer (Dade Behring). Creatinine and blood urea nitrogen were measured on a Vitros((R)) 950 IRC (Ortho). RESULTS: Dialysis acutely increased cTnT (P: <0.01) and decreased cTnI (P: <0.001) regardless of the dialysis membrane used. Although statistically not significant, cTnT but not cTnI was increased more frequently in group 2 than in group 1, in some cases over the whole study period. Five patients (8.5%) died of cardiac complications within 2 years; all of them had mostly increased cTnT and, in one or more samples, increased cTnI. CONCLUSIONS: Dialysis alters measured cTnT and cTnI concentrations in serum. In patients suffering from end-stage renal failure, sporadic or persistently increased cTnT and cTnI appear to predict cardiac complications. Because of the effects of the dialysis procedure on troponin values, we recommend that blood be collected before dialysis.     

Effect of denervation on the content of cardiac troponin-T and cardiac troponin-I in rat skeletal muscle

Abnormal rhabdomyocyte expression of cardiac troponin-T (cTnT) was thought to interfere with the cTnT assay. cTnT isoforms have been shown to be transiently expressed in skeletal muscle during development and in response to muscle denervation. The effect of denervation and aging on cTnT and cardiac troponin-I (cTnI) content in fast and slow rat skeletal muscles was assessed quantitatively. Sections of the tibial nerve were transected from one hind limb of both young (n=12) and old (n=12) rats. Animals were sacrificed at 1, 2, and 4 weeks after the operation, and the extensor digitorum longus (EDL) and the soleus were removed from both the denervated and the contralateral control limb. There was no significant difference in cTnI content between the fast EDL and slow soleus muscles. The cTnT content was significantly higher in the soleus than the EDL muscle (p<0.001). These data, combined with data on other models in the literature, indicate that re-expression of cTnT and cTnI isoforms in adult skeletal muscle is unlikely and does not interfere with cTnT assays for assessment of cardiac damage.     

Improved assay of cardiac troponin I is more sensitive than other assays of necrosis markers

Objective. Highly sensitive and specific assays of cardiac troponins I and T are the preferred biomarkers in diagnosing myocardial infarction (MI). Assays of cardiac troponin I (cTnI) have been improved with the addition of antibodies against the cTnI molecule and may have increased sensitivity. We hypothesized that a cTnI assay with modern antibody configuration will exhibit equal or better sensitivity in the setting of acute MI compared to cTnT and other markers of myocardial necrosis. Material and methods. We investigated release kinetics of cTnI (Abbott ADV, Abbott Diagnostics), cTnT (Roche Diagnostics), CKMBmass, myoglobin and heart fatty acid binding protein (H‐FABP) in 23 patients admitted with acute ST‐segment elevation MI undergoing primary percutaneous coronary intervention. Calibrators for the Abbott ADV cTnI assay are traceable to the United States National Institute of Standards and Technology (NIST) reference material for cTnI. Eleven blood samples were drawn from each patient in the period from admission to 24?h. Biomarkers of necrosis showed marked increases in relative concentrations, especially within the first 2?h after admission. Results. From 30?min after admission onwards, cTnI exhibited significantly higher relative concentrations compared to cTnT, CKMBmass, Myoglobin and H‐FABP (p<0.05). Conclusions. The NIST standardized Abbott TnI ADV assay appears to be more sensitive than cTnT and other biomarkers in the early phase of MI.     

Clinical performance of a new point-of-care cardiac troponin I assay compared to three laboratory troponin assays

BackgroundStudies of cardiac markers in diagnosing acute myocardial infarction (AMI) have mostly been performed using central laboratory platforms. The AQT90 FLEX TnI (troponin I) assay is designed for quantitative point of care testing (POCT). This study evaluated clinical performance in diagnosing AMI of the AQT90 FLEX TnI POCT assay compared with central laboratory troponin assays.MethodsThe study included 458 chest pain patients. Blood samples were obtained on admission and after 6–9 h. Blood was analyzed using the following assays: AQT90 FLEX TnI, Access AccuTnI, Abbott AxSYM ADV, Roche cTnT, Roche CKMBmass. Patients were diagnosed with AMI according to the new universal definition of AMI.ResultsThe performance of the AQT90 FLEX TnI assay on admission was equivalent to the Abbott AxSYM ADV cTnI but inferior to the AccuTnI. After 6–9 h both laboratory based assays were superior. The AQT90 FLEX TnI had a negative predictive value (NPV) of 90 and 96% (admission; 6–9 h). No statistical differences were seen in receiver operating characteristics analysis.ConclusionsThe AQT90 FLEX TnI POCT assay was marginally inferior to the two laboratory based assays of cTnI in diagnosing AMI. A high (NPV) may make this assay suitable as a rule out marker.     

心肌肌钙蛋白I和T联合检测在病毒性心肌炎诊断中的应用

目的探讨肌钙蛋I（cTnI）和肌钙蛋白T（cTnT）在病毒性心肌炎（VMC）的诊断及病情观察方面的价值。方法对79例VMC患者进行入院后1、2、3周及2个月cTnT和心肌酶谱的动态监测；cTnT、cTnI与心电图（ECG）及病程关系的研究。结果急性VMC患者在各检测期内血清cTnT的阳性率（73．41％）和cTnI的阳性率（67．08％）显著高于心肌酶谱各项目（P〈0．05）：肌酸激酶47．4d％、肌酸激酶同工酶51．28％、天冬氨酸氨基转移酶42．31％、乳酸脱氢酶42．31％、α-羟丁酸脱氢酶44．87％。cTnT和cTnI阳性组ECG正常率（5．26％、9．62％）明显低于阴性组（71．43％、57．69％）（P〈0．05）。结论在VMC的诊断中，cTnT和cTnI可取代传统的心肌酶谱测定作为判断急性心肌炎的指标；同时cTnT和cTnI在VMC病情进展的观察中也具有重要意义。     

Analytical and diagnostic performance of troponin assays in patients suspicious for acute coronary syndromes

BACKGROUND: The controversy whether there is a clinically significant difference between troponin T (cTnT) and troponin I (cTnI) in regard to predictive value and cardiac specificity is still ongoing. METHODS: We evaluated enzyme-linked immunosorbent assay systems for cTnI and cTnT in patients with acute coronary syndromes and multiple control groups to define threshold values for risk stratification and compare their predictive value. RESULTS: In 312 patients with noncardiac chest pain, cTnI levels were below the detection limit of 0.2 microg/L and cTnT levels were 0.011 [0.010-0. 013] microg/L. In patients with end-stage renal failure (n = 26) and acute (n = 38) or chronic (n = 16) skeletal muscle damage, median concentrations were 0.20 [0.20-0.35], below the detection limit, and 0.20 [0.20-0.25] for cTnI, and 0.04 [0.01-0.10], 0.011 [0.005-0.025], and 0.032 [0.009-0.054] microg/L for cTnT. In patients with acute coronary syndromes (n = 1130), maximized prognostic value for 30-day outcome (death, infarction) was observed at a threshold level of 1.0 microg/L for cTnI (29.0% positive) and at 0.06 microg/L for cTnT (35. 0% positive). Significant differences in the area-under-the-curve values were observed between cTnI and cTnT (0.685 vs. 0.802; p = 0. 005). For both markers, the area-under-the-curve values did not increase with the second (within 24 h after enrollment) or third (48 h) blood draw. CTnI showed a less strong association with 30-day outcome than cTnT. When cTnI was put in a logistic multiple-regression model first, cTnT did add significant information. CONCLUSION: By using the defined threshold values and the employed test systems, single testing for cTnI and cTnT within 12 h after symptom onset was appropriate for risk stratification. Despite the lower cardiac specificity for cTnT, it appears to have a stronger association with the patients' outcome, whereas, as previously shown, the ability to identify patients who benefit from treatment with a GP IIb/IIIa receptor antagonist is similar.     

The specificity of biochemical markers of cardiac damage: a problem solved.

This paper reviews the tissue specificity of cardiac troponin I (cTnl), cardiac troponin T (cTnT) and creatine kinase (CK) MB in human and animal heart and skeletal muscles. Studies reveal that CK-MB can be expressed up to 20% of total CK activity in human skeletal muscle; and therefore is not 100% specific for the heart. One cTnl isoform has been described and shown to be 100% specific for the heart. While one to four cTnT isoforms are expressed in diseased and regenerating human skeletal muscle, these isoforms are not the same as the cTnT isoforms expressed in the human heart and are not detected by the cTnT diagnostic assays used in clinical practice. Representative cases are described demonstrating the role of monitoring cardiac troponins in blood for differentiating false positive CK-MB increases due to skeletal muscle injury. Further, sufficient reactivity and tissue specificity of cTnl and cTnT assays are demonstrated for use as markers of myocardial injury in laboratory animals. Monitoring cTnl and cTnT concentrations in the circulation appears poised as the new standards for detection of myocardial injury.     

肌钙蛋白Ⅰ与CK-MB联合检测对急性心肌梗死的诊断价值

目的探讨肌钙蛋白I(cTnI)与CK-MB联合检测对急性心肌梗死(AM I)的临床诊断价值。方法采用罗氏电发光2010自动生化分析仪和日立7180生化分析仪,测定62例AM I患者、50例健康体检者血清的cTnI、肌酸激酶(CK)和CK-MB,并对结果进行统计学分析。结果AM I组血清cTnI、CK和CK-MB高于正常对照组(P<0.01)。cTnI与CK-MB联合检测阳性率为96.7%,高于前三者,且动态检测对早期AM I敏感性更高、阳性持续时间更长。结论肌钙蛋白I与CK-MB联合检测能提高早期急性心肌梗死的检出率,具有更宽的诊断时间窗。     

肌钙蛋白I和T测定对急性心肌梗塞的诊断意义

目的探讨肌钙蛋白I（cTnI）和肌钙蛋白T（cTnT）测定对急性心肌梗塞（AMI）的诊断价值。方法对52例AMI患者采用免疫层析法进行检测cTnI和cTnT,以对照区和检测区均有显色带者为阳性,并作灵敏度和特异性的比较。结果以胸痛0～3h、4～6h两个时段观察其灵敏度,cTnI为56.7%和96.1%;cT-nT为50.0%和92.3%。特异性cTnI为100%和96.2%;cTnT为100%和91.6%。cTnI灵敏度高于cTnT,特异性cTnI与cTnT之间无显著性差异。结论对AMI急性胸痛患者可同时进行cTnI和cTnT检测,有利于AMI的诊断和治疗。