H-FABP、cTnI及copeptin在老年急性非ST段抬高型心肌梗死患者早期诊断中的应用价值

目的:研究心肌型脂肪酸结合蛋白(H-FABP)、肌钙蛋白I(cTnI)及和肽素(copeptin)在老年急性非ST段抬高型心肌梗死患者早期诊断中的应用价值。方法:选取2016年2月-2018年2月我院收治的老年急性非ST段抬高型心肌梗死患者60例为研究对象,记为观察组。另取同期于我院接受治疗的心绞痛患者50例记为对照组。分别比较患者H-FABP与cTnI阳性、阴性分布情况以及copeptin表达水平。绘制受试者工作特征曲线(ROC),分析H-FABP、cTnI、copeptin以及三项联合检测老年急性非ST段抬高型心肌梗死的早期诊断价值。结果:观察组患者H-FABP与cTnI阳性人数占比均高于对照组(P0.05)。观察组患者copeptin表达水平高于对照组(P0.05)。H-FABP、cTnI及copeptin等3个指标均具有一定的早期诊断价值,H-FABP+cTnI+copeptin联合检测的敏感度和特异度更高,分别为86.46%和87.15%。结论:老年急性非ST段抬高型心肌梗死患者H-FABP、cTnI、copeptin表达较高,联合检查上述三项指标水平可提高临床诊断价值。     

Drastic Ca2+ sensitization of myofilament associated with a small structural change in troponin I in inherited restrictive cardiomyopathy

Six missense mutations in human cardiac troponin I (cTnI) were recently found to cause restrictive cardiomyopathy (RCM). We have bacterially expressed and purified these human cTnI mutants and examined their functional and structural consequences. Inserting the human cTnI into skinned cardiac muscle fibers showed that these mutations had much greater Ca2+-sensitizing effects on force generation than the cTnI mutations in hypertrophic cardiomyopathy (HCM). The mutation K178E in the second actin-tropomyosin (Tm) binding region showed a particularly potent Ca2+-sensitizing effect among the six RCM-causing mutations. Circular dichroism and nuclear magnetic resonance spectroscopy revealed that this mutation does not extensively affect the structure of the whole cTnI molecule, but induces an unexpectedly subtle change in the structure of a region around the mutated residue. The results indicate that the K178E mutation has a localized effect on a structure that is critical to the regulatory function of the second actin-Tm binding region of cTnI. The present study also suggests that both HCM and RCM involving cTnI mutations share a common feature of increased Ca2+ sensitivity of cardiac myofilament, but more severe change in Ca2+ sensitivity is associated with the clinical phenotype of RCM.     

Psychological distress and personality factors in takotsubo cardiomyopathy

Background

Takotsubo cardiomyopathy (TCC) is a transient condition characterised by severe left ventricular dysfunction combined with symptoms and signs mimicking myocardial infarction. Emotional triggers are common, but little is known about the psychological background characteristics of TCC. This study examined whether patients with TTC have higher levels of psychological distress (depressive symptoms, perceived stress, general anxiety), illness-related anxiety and distinct personality factors compared with healthy controls and patients with heart failure.

Methods and Results

Patients with TCC (N = 18; mean age 68.3 ± 11.7 years, 77.8?% women) and two comparison groups (healthy controls: N = 19, age 60.0 ± 7.6, 68.4?% women and patients with chronic heart failure: N = 19, age 68.8 ± 10.1, 68.4?% women) completed standardised questionnaires to measure depression (PHQ?9), perceived stress (PSS-10), general anxiety (GAD-7), illness-related anxiety (WI-7) and personality factors (NEO-FFI and DS-14). Psychological measures were obtained at 23 ± 18 months following the acute TTC event. Results showed that patients with TCC had higher levels of depressive symptoms (5.2 ± 5.2 vs. 2.5 ± 2.4, p = 0.039) and illness-related anxiety (2.1 ± 1.7 vs. 0.7 ± 1.3, p = 0.005) compared with healthy controls. Patients with TCC did not display significantly elevated perceived stress (p = 0.072) or general anxiety (p = 0.170). Regarding personality factors, levels of openness were lower in TCC compared with healthy controls (34.2 ± 4.3 vs. 38.2 ± 5.6, p = 0.021). No differences between TCC and heart failure patients were found regarding the psychological measures.

Conclusions

TCC is associated with higher levels of depressive symptoms, more illness-related anxiety and less openness compared with healthy controls. These data suggest that TCC is associated with adverse psychological factors that may persist well after the acute episode.

     

肌钙蛋白I和肌红蛋白在急性心肌梗死患者血清中的变化特点及其诊断价值

目的:探讨肌钙蛋白I、CKMB的即时检测技术在急诊科心肌梗死患者中的应用及其临床意义。方法:研究对象为2012年10月至2013年8月于我急诊科急诊的急性心肌梗死患者,按就诊时间分为对照组和实验组。对照组患者采用常规化验室检测肌钙蛋白I、CKMB,实验组采用急诊科即时检测方法检测肌钙蛋白I、CKMB。对比两组患者从就诊到确诊的时间、住院天数、治愈率、心功能不全发生率和死亡率。结果:实验组患者的确诊时间为(25.5±5.6)min,住院天数为(9.89±1.5)天,治愈率为80.8%,心功能不全发生率为15.4%。对照组患者的确诊时间为(66.8±10.0)min,住院天数为(12.6±2.5)天,治愈率为56.0%,心功能不全发生率为32.0%P均.0.05,有统计学意义。两组患者死亡率分别为12%和3.8%,无明显差异。结论:对心肌梗死患者采用肌钙蛋白I、CKMB的即时检测对于提高患者治愈率,减少确诊时间和住院时间,降低心功能不全发生率有很大帮助。     

Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs.

Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients > 70 years were classified as elderly. hs-cTnI was measured upon admission.

Results: Around 34.7% of 2903 patients were classified as elderly. Around 22.5% of elderly patients were finally diagnosed with AMI. Elderly patients had higher hs-cTnI levels at admission irrespective of the final diagnosis (p?<?0.001). According to the AUROC, hs-cTnI was a strong marker for detection of AMI in elderly patients. Application of the 99th percentile cutoffs showed a substantially lower specificity in elderly. By using optimized thresholds, specificity was improved to levels as in younger patients in both cohorts but accompanied with a decrease in sensitivity.

Conclusions: hs-cTnI levels have a lower specificity for detecting AMI in elderly patients. This lower specificity can be improved by using hs-cTnI thresholds optimized for elderly patients.     

A novel sandwich immunosensing method for measuring cardiac troponin I in sera

Common methods for monitoring human cardiac troponin I (cTn I) are based on using antibodies against cTn I labeled with horseradish peroxidase, radioactive isotopes, or other labels. In this study, a novel label-free sandwich immunosensing method for measuring cTn I was developed. Three monoclonal antibodies (mAbs 9F5, 2F11, and 8C12) against human cTn I were generated by the commonly used hybridoma technique and characterized by a surface plasmon resonance (SPR) biosensor. An optimal pair of mAbs for measuring human cTn I was selected, as both mAbs have high affinities for cTn I and do not compete against each other for cTn I binding. An optical immunosensor for measuring cTn I in sera based on SPR was developed by using avidin as an intermediate layer and biotinylated-2F11 as the capturing antibody. Two detection methods for cTn I with the immunosensor were performed: (1) the direct detection of cTn I with a detection range of 2.5 to 40 microg/L and (2) the sandwich immunosensing method. In the sandwich assay mode, the second antibody 9F5 biologically amplified the sensor response. As a result, the sandwich assay showed a sensitivity of 0.25 microg/L and a detection range of 0.5 to 20 microg/L with within-run variation of 4.9 to 6.7% and between-run variation of 5.2 to 8.4%. This method has greatly enhanced the sensitivity for detection compared to that previously reported in the literatures.     

Hypertrophic cardiomyopathy: two homozygous cases with "typical" hypertrophic cardiomyopathy and three new mutations in cases with progression to dilated cardiomyopathy

About 10% of cases of hypertrophic cardiomyopathy (HCM) evolve into dilated cardiomyopathy (DCM) with unknown causes. We studied 11 unrelated patients (pts) with HCM who progressed to DCM (group A) and 11 who showed "typical" HCM (group B). Mutational analysis of the beta-myosin heavy chain (MYH7), myosin-binding protein C (MYBPC3), and cardiac troponin T (TNNT2) genes demonstrated eight mutations affecting MYH7 or MYBPC3 gene, five of which were new mutations. In group A-pts, the first new mutation occurred in the myosin head-rod junction and the second occurred in the light chain-binding site. The third new mutation leads to a MYBPC3 lacking titin and myosin binding sites. In group B, two pts with severe HCM carried two homozygous MYBPC3 mutations and one with moderate hypertrophy was a compound heterozygous for MYBPC3 gene. We identified five unreported mutations, potentially "malignant" defects as for the associated phenotypes, but no specific mutations of HCM/DCM.     

Prognostic value of copeptin: one-year outcome in patients with traumatic brain injury

High plasma copeptin level has been associated with one-month mortality after traumatic brain injury. However, not much is known regarding its relation with long-term outcome. Thus, we investigated the ability of copeptin to predict 1-year outcome in patients with traumatic brain injury. One hundred and six healthy controls and 106 patients with acute severe traumatic brain injury were included. Plasma samples were obtained on admission. Its concentration was measured by enzyme-linked immunosorbent assay. Forty-eight patients (45.3%) suffered from unfavorable outcome (Glasgow Outcome Scale score of 1-3) and 31 patients (29.2%) died in 1 year after traumatic brain injury. Upon admission, plasma copeptin level in patients was substantially higher than that in healthy controls. A forward stepwise logistic regression selected plasma copeptin level as an independent predictor for 1-year unfavorable outcome and mortality of patients. A receiver operating characteristic curve analysis showed plasma copeptin level predicted 1-year unfavorable outcome and mortality obviously. The predictive value of the copeptin concentration was thus similar to that of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year. In a combined logistic-regression model, copeptin improved the area under curve of Glasgow Coma Scale score for the prediction of unfavorable outcome and mortality after 1 year, but the differences were not significant. Thus, copeptin level is a useful, complementary tool to predict functional outcome and mortality 1 year after traumatic brain injury.     

Recurrent and founder mutations in the Netherlands: mutation p.K217del in troponin T2, causing dilated cardiomyopathy

Background. About 30% of dilated cardiomyopathy (DCM) cases are familial. Mutations are mostly found in the genes encoding lamin A/C, beta-myosin heavy chain and the sarcomeric protein cardiac troponin-T (TNNT2). Mutations in TNNT2 are reported in approximately 3% of DCM patients. The overall phenotype caused by TNNT2 mutations is thought to be a fully penetrant, severe disease. This also seems to be true for a recurrent deletion in the TNNT2 gene; p.K217del (also known as p.K210del). Methods. We compared the phenotype of all Dutch patients identified as carrying the TNNT2 p.K217del mutation with those described in the literature. All index patients underwent cardiological evaluation. Family screening was done in all described families. Results. Six DCM patients carrying the TNNT2 p.K217del mutation were identified from four Dutch families. Mean age of disease manifestation was 33 years. Heart transplantation was required in three of them at ages 12, 18 and 19 years. These outcomes are comparable with those described in the literature. Conclusion. Carriers of the TNNT2 p.K217del mutation in our Dutch families, as well as in families described in the literature before, generally show a severe, early-onset form of DCM. (Neth Heart J 2010;18:478-85.)     

Genetic variation in exon 5 of troponin - I gene in hypertrophic cardiomyopathy cases

BACKGROUND:

Cardiomyopathies are a heterogeneous group of heart muscle disorders and are classified as 1) Hypertrophic Cardiomyopathy (HCM) 2) Dilated cardiomyopathy (DCM) 3) Restrictive cardiomyopathy (RCM) and 4) Arrhythmogenic right ventricular dysplasia (ARVD) as per WHO classification, of which HCM and DCM are common. HCM is a complex but relatively common form of inherited heart muscle disease with prevalence of 1 in 500 individuals and is commonly associated with sarcomeric gene mutations. Cardiac muscle troponin I (TNNI-3) is one such sarcomeric protein and is a subunit of the thin filament-associated troponin-tropomyosin complex involved in calcium regulation of skeletal and cardiac muscle contraction. Mutations in this gene were found to be associated with a history of sudden cardiac death in HCM patients.

AIM:

Therefore the present study aims to identify for mutations associated with troponin I gene in a set of HCM patients from Indian population.

MATERIALS AND METHODS:

Mutational analyses of 92 HCM cases were carried out following PCR based SSCP analysis.

RESULTS:

The study revealed band pattern variation in 3 cases from a group of 92 HCM patients. This band pattern variation, on sequencing revealed base changes, one at nt 2560 with G>T transversion in exon-5 region with a wobble and others at nt 2479 and nt 2478 with G>C and C>G transversions in the intronic region upstream of the exon 5 on sequencing. Further analysis showed that one of the probands showed apical form of hypertrophy, two others showing asymmetric septal hypertrophy. Two of these probands showed family history of the condition.

CONCLUSIONS:

Hence, the study supports earlier reports of involvement of TNNI-3 in the causation of apical and asymmetrical forms of hypertrophy.     

急诊超声心动图联合血清NT-proBNP、cTnI、CK-MB诊断急性心肌梗死的临床价值分析

摘要 目的：研究急诊超声心动图联合血清氨基末端脑钠肽前体（NT-proBNP）、肌钙蛋白（cTnI）和肌酸激酶同工酶（CK-MB）诊断急性心肌梗死（AMI）的临床价值。方法：将2019年12月至2020年6月期间我院收治的82例AMI患者纳入研究,记作病变组。另取同期于我院进行体检的健康者80例作为对照组。比较两组各项超声心动图指标水平,血清NT-proBNP、cTnI和CK-MB水平。分析超声心动图指标与血清NT-proBNP、cTnI和CK-MB的相关性。以受试者工作特征（ROC）曲线分析超声心动图联合血清NT-proBNP、cTnI和CK-MB水平诊断AMI的效能。结果：病变组左心室射血分数（LVEF）低于对照组,而左室舒张末期内径（LVEDD）高于对照组（P＜0.05）。病变组血清NT-proBNP、cTnI和CK-MB水平均高于对照组（P＜0.05）。Pearson检验显示LVEF与血清NT-proBNP、cTnI和CK-MB均呈负相关（r=-0.514、-0.578、-0.532,均P＜0.05）,LVEDD与血清NT-proBNP、cTnI和CK-MB均呈正相关（r=0.625、0.594、0.575,均P＜0.05）。超声心动图联合血清三项诊断AMI的曲线下面积、灵敏度以及特异度均高于超声心动图、血清三项单独诊断。结论：超声心动图联合血清NT-proBNP、cTnI和CK-MB诊断AMI的价值较高,具有一定的临床应用价值。     

Usefulness of copeptin as a potential biomarker in TBE

Objective: The aim of the study was to evaluate the usefulness of copeptin for differentiation of hyponatremia in the course of tick-borne encephalitis (TBE) and for being a prognostic marker of the severity of TBE.

Materials and methods: One hundred and fourteen patients with TBE were included in the study. The control group consisted of 62 patients diagnosed with viral meningitis.

Results: Copeptin concentration did not differ in patients with hyponatremia and normonatremia. Urinary sodium excretion to plasma copeptin (copeptin/UNa Secretion) ratio was significantly lower in Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion patients than in patients with hyponatremia of other origin. Mean copeptin concentration in TBE patients was higher than in control group (VM) patients. There were no differences between patients with severe and mild course of TBE.

Conclusions: Copeptin/UNa ratio may be used as a potential biomarker of SIADH in patients with TBE. Copeptin concentration is significantly higher in patients with TBE than in viral meningitis of other origin, especially in patients aged 18–34 and >49 years old. Copeptin does not differentiate TBE of mild and severe course.     

Phosphorylation of troponin I by protein kinase C: Mechanism of inhibition by calmodulin and troponin C

The mechanism by which calmodulin and troponin C influence phosphorylation of troponin I (TnI) by protein kinase C was investigated. The phosphorylation of TnI by protein kinase C requires the presence of acidic phospholipid, calcium and diacylglycerol. Light scattering intensity and fluorescence intensity experiments showed that TnI associated with the phospholipid membranes and caused extensive aggregation. In the presence of Ca²⁺, TnI-phospholipid interactions were prevented by approximately stoichiometric amounts of either troponin C or calmodulin. Troponin C was shown to completely inhibit phosphorylation of TnI by either protein kianse C or by phosphorylase b kinase. In contrast, calmodulin completely inhibited phosphorylation of TnI by protein kinase C, but had only little effect on TnI phosphorylation by phosphorylase b kinase. Inhibition by calmodulin did not appear to be due to interaction with PKC, since calmodulin mildly increased protein kinase C phosphorylation of histone III-S. The ratio of phosphoserine to phosphothreonine in protein kinase C-phosphorylated TnI remained approximately constant for reactions inhibited by up to 90% by clamodulin. TnI interactions with phospholipid and phosphorylation of TnI by PKC were also prevented by high salt concentrations. However, salt concentrations adequate to inhibit phosphorylation were sufficient to dissociate only TnI, but not protein kinase C from the membrane. These results suggest that the binding of TnI to phospholipid is required for phosphorylation by protein kinase C and that prevention of this binding by any means completely inhibited phosphorylation of TnI by protein kinase C.     

抗心肌肌钙蛋白T单抗杂交瘤细胞株的建立及鉴定

以牛心肌为原料,提取纯化得牛cTnT,并经特定处理,免疫BALB/C 小鼠,取其脾细胞与SP2/0 融合,获得两株抗cTnT 细胞3B2 和3D6 。Ig 亚类均是IgG1 。相加试验表明可识别不同表位,为建立测定cTnT方法奠定了基础。     

Acute myocardial infarction: Circadian, weekly, and seasonal patterns of occurrence

Convincing evidence has demonstrated that cardiovascular diseases do not occur randomly throughout the day, the week, or the year but show a well defined temporal organization. This article will review circadian, weekly, and seasonal patterns of occurrence of acute myocardial infarction, along with their underlying pathophysiological triggering factors.     

An analytical comparison of cobalt cardiomyopathy and idiopathic dilated cardiomyopathy

Toxic cardiomyopathy (TC) has a rapid clinical course and morphologically resembles idiopathic dilated cardiomyopathy (IDC). To further characterize TC, we used light microscopy to compare lesions caused by cobalt (Co) to those of IDC. Cobalt levels were also measured as a chemical marker to differentiate TC from IDC. We reviewed cases with TC and IDC and excluded all cases with chemotherapy-induced myopathy and catecholamine toxicity as well as cases with possible infectious, ischemic, or hypersensitivity-induced myopathies. We compared the light microscopic findings of 12 TC cases to 12 cases of IDC, and measured trace Co levels on digested heart tissue samples. The TC cases had prominent myofibrillar loss and atrophy; no cases had neutrophil infiltration or frank myocyte necrosis. In contrast, IDC had minimal myofibril loss and atrophy. Cobalt levels in the range of 0.6 to 5.45 μg/g of dry tissue were obtained for the TC cases, while IDC demonstrated Co levels of 0.01–0.2 μg/g. Distinction between TC and IDC is predominantly a function of myocyte change, with TC showing myofibrillar loss and atrophy in the absence of inflammatory infiltrates and fibrosis; IDC is predominantly associated with myocyte hypertrophy, atrophy, and fibrosis. The opinions or assertions expressed herein are the private views of the authors and are not to be construed as official or as representing the views of the Armed Forces Institute of Pathology, the Department of the Army or the Department of Defense.     

Cellular and molecular aspects of familial hypertrophic cardiomyopathy caused by mutations in the cardiac troponin I gene

Mutations in the cardiac troponin I (CTnI) gene occur in 5% of families with familial hypertrophic cardiomyopathy (FHC) and 20 mutations in this gene that cause FHC have now been described. The clinical manifestations of CTnI mutations that cause FHC are diverse, ranging from asymptomatic with high life expectancy to severe heart failure and sudden cardiac death. Most of these FHC mutations in CTnI result in cardiac hypertrophy unlike cardiac troponin T FHC mutations. All CTnI FHC mutations investigated in vitro affect the physiological function of CTnI, but other factors such as environmental or genetic factors (other genes that may affect the CTnI gene) are likely to be involved in influencing the severity of the phenotype produced by these mutations, since the distribution of hypertrophy among affected individuals varies within and between families. CTnI mutations mainly alter myocardial performance via changes in the Ca²⁺-sensitivity of force development and in some cases alter the muscle relaxation kinetics due to haemodynamic or physical obstructions of blood flow from the left ventricle. (Mol Cell Biochem 263: 99–114, 2004)     

结扎兔冠状动脉前降支与左室支的急性心肌梗塞比较

本文比较了结扎兔冠状动脉前降支（ＬＡＤ组）和左室支（ＬＶＡ组）两种方法建立的急性心肌梗塞模型。结果发现１：ＥＣＧ标测,三天内不同时间ＬＶＡ组∑△ＳＴ升高毫伏数均高于ＬＡＤ组（Ｐ＜０．０１或Ｐ＜０．０５）;２：Ｎ－ＢＴ染色,ＬＶＡ组心肌梗塞占心室重的百分率为１７．３％±０．５６％,而ＬＡＤ组为８．２％±２．４２％,两者相差非常显著（Ｐ＜０．０１）,证实了ＬＶＡ组心梗面积较ＬＡＤ组大且相对稳定。采用增强（Ｇｄ－ＤＴＰＡ）磁共振成像（ＭＲＩ）扫描发现ＬＶＡ组急性心梗范围在三天内基本稳定。作者认为,兔急性心梗模型采用结扎ＬＶＡ优于结扎ＬＡＤ。     

早期心肌缺血与梗死后肌钙蛋白和肌红蛋白的观察

目的：观察早期心肌缺血（可疑）与梗死心肌细胞内肌钙蛋白（CTnT）、肌红蛋白（Mb）的变化情况.方法：应用H.E染色和免疫组织化学技术分别对6例正常心肌、11例早期心肌缺血（可疑）及9例梗死的心肌细胞内肌钙蛋白、肌红蛋白进行观察.结果：H.E染色正常组心肌未见异常;早期（可疑）心肌缺血组未见明显心肌梗死病灶;心肌梗死组见心肌梗死病灶.CTnT和Mb的免疫组织化学染色和图像分析显示,CTnT和Mb在正常组心肌的表达量明显高于早期（可疑）心肌缺血组和心肌梗死组（p＜0.05）.结论：CTnT、Mb免疫组织化学染色可用于早期（可疑）心肌缺血和心肌梗死的诊断.     

血清CREG蛋白在急性心肌梗死早期的表达研究

目的：探讨血清中CREG蛋白在急性心肌梗死发作早期的表达情况,尝试为临床心肌缺血的极早期诊断提供一种新的血清标志分子。方法：在2010年6月至2010年11月期间,入选在沈阳军区总医院心内科住院治疗的急性ST段抬高型心肌梗死患者50例及非AMI对照50例,于AMI组胸痛发作后的不同时间点采血测定CK、CK—MB、LDH和cTnT,同时应用Westem blot技术测定血清中CREG蛋白的含量,并与对照组比较。结果：AMI组发病72小时内的血清中CREG蛋白表达均较对照组有不同程度的增高（P〈0．05）。胸痛开始2h内,AMI组血清中CREG的含量即明显增高,其在2h、4h及6h的含量显著高于对照组（P〈0．001）。在胸痛已经发作2小时内,两组间血清cTnT、CK、CK-MB及LDH水平比较无统计学意义（P〉0．05）。结论：CREG在AMI患者血清中的表达增高．其在血清中表达时间早于cTNT及CK-MB。