Prognostic value of N-terminal pro B-type natriuretic peptide and troponin Ⅰ in children with dengue shock syndrome

Objective:To investigate the contribution of N-terminal pro B-type natriuretic peptide(NT-pro BNP)and troponin Ⅰ to mortality in children with dengue shock syndrome.Methods:A longitudinal study was conducted on children with dengue shock syndrome in a hospital in southern Vietnam.Detailed clinical histories,physical examinations,and laboratory parameters,including NT-pro BNP and troponin Ⅰ,were recorded.A comparison between survival and non-survival was carried out to identify factors influencing mortality.Results:A total of 107 patients with a median age of 9 years were included in the study.Among them,63.6%(68/107)presented with compensated shock,36.4%(39/107)had hypotensive shock,23.4%(25/107)required mechanical ventilation,and 12.1%(13/107)died.The NT-pro BNP levels were 3.9 pmol/L(IQR:1.9,10.3)and 15.2 pmol/L(5.8,46.3),while the median high sensitivity troponin Ⅰ levels were 20 pg/L(6,95)and 62 pg/L(12,325)at the first and second measurements,respectively.The mortality group exhibited higher rates of hypotensive shock,prolonged shock,lactate levels,liver damage,NT-pro BNP,and troponin Ⅰ levels.Hypotensive shock(OR 12.96,95%CI 2.70-62.30,P=0.004),prolonged shock(OR 39.40,95%CI 6.68-232.70,P<0.001),AST>1000 IU/L(OR 9.50,95%CI 2.63-34.34,P=0.041),and NT-pro BNP>7 pmol/L(OR 44.40,95%CI 5.44-362.20,P=0.001)were identified as predictive factors for mortality in dengue shock syndrome.Conclusions:The NT-pro BNP level could serve as a potential biomarker for predicting mortality in children with dengue shock syndrome.

Computed tomography coronary angiography after excluding myocardial infarction:high-sensitivity troponin versus risk score-guided approach

BACKGROUND:Patients with suspected acute coronary syndrome (ACS) in whom myocardial infarction has been ruled out are still at risk of having obstructive coronary artery disease (CAD).This rate is higher among patients with intermediate high-sensitivity troponin I (hsTnI) concentrations (5 ng/L to 99th percentile) than low concentrations (<5 ng/L).Therefore,an intermediate concentration has been suggested as a candidate for downstream investigation with computed tomography coronary angiography(CTCA).We tried to compare the HEART score-guided vs.hsTnI-guided approach for identifying obstructive CAD.METHODS:From a prospective cohort study of patients presenting to the emergency department with suspected ACS,433 patients without elevated hsTnI who also underwent CTCA were selected and analyzed.The performances of hsTnI concentration and HEART score were compared using sensitivity,specificity,positive predictive value (PPV),and negative predictive value (NPV).RESULTS:Overall,120 (27.7%) patients had obstructive CAD.Patients with intermediate hsTnI concentrations were more likely to have obstructive CAD than those with low hsTnI concentrations(40.0%vs.18.1%);patients with non-low-risk HEART scores (≥4 points) were also more likely to have obstructive CAD than those with low-risk scores (0 to 3 points)(41.0%vs.7.6%).The HEART score had higher sensitivity and NPV for detecting obstructive CAD in each classification than hsTnI concentration (sensitivity:89.2%vs.63.3%;NPV:92.4%vs.81.9%,respectively).CONCLUSION:After excluding myocardial infarction in patients with suspected ACS,adding the HEART score for selecting candidates for CTCA could improve patient risk stratification more accurately than relying on hsTnI concentration.

Remdesivir, dexamethasone and angiotensin-converting enzyme inhibitors use and mortality outcomes in COVID-19 patients with concomitant troponin elevation

BACKGROUND There are indications that viral myocarditis,demand ischemia,and renin-angio-tensin-aldosterone system pathway activation play essential roles in troponin elevation in coronavirus disease 2019(COVID-19)patients.Antiviral medications and steroids are used to treat viral myocarditis,but their effect in patients with elevated troponin,possibly from myocarditis,has not been studied.AIM To evaluate the effect of dexamethasone,remdesivir,and angiotensin-converting enzyme(ACE)inhibitors(ACEI)on mortality in COVID-19 patients with elevated troponin.METHODS Our retrospective observational study involved 1788 COVID-19 patients at seven hospitals in Southern California,United States.We did a backward selection Cox multivariate regression analysis to determine predictors of mortality in our study population.Additionally,we did a Kaplan Meier survival analysis in the subset of patients with elevated troponin,comparing survival in patients that received dexamethasone,remdesivir,and ACEI with those that did not.RESULTS The mean age was 66 years(range 20-110),troponin elevation was noted in 11.5%of the patients,and 29.9%expired.The patients'age[hazard ratio(HR)=1.02,P<0.001],intensive care unit admission(HR=5.07,P<0.001),and ventilator use(HR=0.68,P=0.02)were significantly associated with mortality.In the subset of patients with elevated troponin,there was no statistically significant difference in survival in those that received remdesivir(0.07),dexamethasone(P=0.63),or ACEI(P=0.8)and those that did not.CONCLUSION Although elevated troponin in COVID-19 patients has been associated with viral myocarditis and ACE II receptors,conventional viral myocarditis treatment,including antiviral and steroids,and ACEI did not show any effect on mortality in these patients.

Role of NT-proBNP and Troponin I in Assessing the Severity of Pulmonary Embolism

Introduction: Pulmonary embolism is a diagnostic and therapeutic emergency that can be life-threatening. Its mortality is largely attributable to severe forms classically defined by clinical and morphological criteria. The aim of this study is to establish the role of two cardiac biomarkers (NT-proBNP and troponin) in assessing the severity of pulmonary embolism. Patients and Methods: We conducted a descriptive and analytical cross-sectional study. Data collection was retrospective over the period from January 1, 2011 to December 31, 2021. All patients hospitalized for pulmonary embolism in two cardiology referral clinics in Cotonou (Atinkanmey Polyclinic and CICA Clinic) were included. Results: The hospital prevalence of pulmonary embolism was 9.08%. The mean age was 52.6 years, with extremes of 18 and 92 years. The sex ratio was 0.73. Pulmonary embolism was severe according to hemodynamic, morphological and sPESI criteria in 12%, 24% and 39% of cases respectively, and mortality was 61.53%. Mean NT-ProBNP and troponin I levels were significantly higher in patients with severe criteria than in those without. NT-proBNP and troponin had good specificity for predicting cardiovascular arrest (99% and 90%), shock (100% and 98%), and hypotension (99% and 96%). NT-proBNP has the best positive predictive values in relation to the occurrence of shock (100%) and right ventricular dilatation (93%). The best correlation coefficient was obtained between right ventricular dilatation and NT-proBNP (0.78). Conclusion: NT-proBNP and troponin I are good biomarkers for predicting the severity of pulmonary embolism and allowing therapeutic adaptation when they are elevated.

电刺激和延迟冷却对宰后牛肉肌原纤维Troponin-T降解的影响

为了探讨牛肉嫩化的机理,选择24头24月龄,体重约500kg杂交牛(鲁西黄牛×西门塔尔)随机分成4组,在宰前或宰后分别进行以下4种处理:常规预冷组,延迟冷却组,电刺激处理组,电刺激和延迟冷却处理组。用SDS-PAGE和蛋白免疫印迹的方法比较分析了4种处理牛肉成熟1,3,7,10d其肌原纤维骨架蛋白Troponin-T的降解情况。结果表明:与常规冷却组相比,电刺激处理在1、3、7d时显著加快了Troponin-T的降解,而10d时差异不显著;延迟冷却处理在1、3d时显著加快了Troponin-T的降解,而7、10d时差异不显著;1、3d时延迟冷却对Troponin-T的降解影响比电刺激显著,而7、10d时则是电刺激比较显著;电刺激和延迟冷却处理的结合对Troponin-T降解的影响比电刺激处理组、延迟冷却处理组显著。综上可见,延迟冷却、电刺激无论在速度和数量上显著加快了Troponin-T的降解,加快了牛肉成熟,缩短了成熟时间,且二者有协同作用。

虾过敏原Troponin C(Pen m6)的克隆表达、免疫学鉴定及生物信息学分析

目的对斑节对虾(Penaeus monodon)第6组过敏原(Pen m6),肌钙蛋白C(Troponin C)进行克隆表达、免疫学鉴定并研究其生物学意义。方法提取斑节对虾总RNA;根据Gen Bank:HM034316.1设计引物及构建表达载体PET-24a-Pen m6;转化至大肠杆菌BL21(DE3)进行表达;纯化后的重组Pen m6用Western bolt来鉴定免疫学特性;用生物信息学相关工具对Pen m6进行同源性分析,并预测其蛋白质的结构和功能。结果克隆出斑节对虾Pen m6基因开放阅读框453 bp,编码150个氨基酸。重组Pen m6蛋白呈可溶性,分子量约35kDa,能够与斑节对虾过敏患者血清IgE结合。斑节对虾与凡纳滨对虾亲缘关系比较近,其中斑节对虾Pen m6蛋白与凡纳滨对虾Troponin C1(gb|AET36896.1|)同源性为98%。理化性质预测Pen m6蛋白质不稳定。蛋白质结构预测结果显示Pen m6的结构主要以α螺旋组成。T细胞抗原表位预测得到4个肽序列(15~23、35~43、91~99、112~120)。B细胞抗原表位预测得到4个肽序列(7~16、21~30、28~37、58~67)。结论克隆的重组斑节对虾Pen m6蛋白具有良好的免疫原性,为进一步研究斑节对虾过敏原的结构成分及其理化性质奠定理论基础。

人Troponin I的表达载体构建诱导表达和纯化及活性测定

以人肝脏cDNA文库为模板,通过PCR方法扩增出Tropon in基因,将其克隆到pCR-TOPO质粒中,构建表达质粒pET-22 b(+)-TnI,转化大肠杆菌BL 21(DE 3)-RPX并进行诱导表达,表达的目的蛋白占菌体总蛋白的20%以上并主要以可溶形式存在。建立了Tropon in I的非亲和色谱纯化工艺,纯化后蛋白产量约为20 mg/L,纯度在90%以上。体外活性实验表明重组蛋白具有良好的抗血管生成。

血清Troponin I,CK-MBmass,Myoglobin在急性心肌梗塞诊断中的应用评价

为了解CTnI，CK－MBmass和Mb指标对急性心肌梗塞（AMI）早期诊断、后期监测及预后判断的临床意义，采用微粒子化学发光法，对20例AMI患者、24例不稳定心绞痛（UA）患者、17例骨骼肌损伤（SM）患者和19例健康者（对照组）进行血清CTnI，CK－MBmass和Mb的测定，并对AMI患者胸病发生3～5小时，8～14小时，20～24小时，72小时和7天共五个时段进行了测定。结果：AMI患者发病早期CTnI，CK－MBmass和Mb的阳性检出率分别为65％，70％，70％，CTnI在UA患者组和SM患者组中未检出。CTnI，CK－MBmass和Mb测定值含量在AMI组中明显高于UA组和SM组，AMI患者组CTnI分别是UA组和SM组的84倍和91.63倍，CK－Mbmass分别是该二组的8．82倍和4．67倍，Mb分别是该二组的11．57倍和2．25倍，AMI组与UA组和SM组比较，有显著性差异（P＜0．001）。AMI患者组中该三项指标的动态测定显示，在疾病发生早期（3～5小时）时，CTnI，CK－MBmass和Mb都有显著性升高，随时间延长而逐渐升高，高峰值期均在8～14小时段，72小时时Mb已基本回到正常。7天时血清中仍有CTnI的持续存在，但CK－MBmass已接近正常。以上显示，CTnI，CK－MBmass和Mb在早期诊断AMI时，都具有较高的敏感性，CTnI在AMI患者中的阳性检出率具有心肌特异性。

Diagnostic and prognostic value of minor elevated cardiac troponin levels for percutaneous coronary intervention-related myocardial injury:a prospective,single-center and double-blind study

Cardiac troponin-I （cTnI） and -T （cTnT） are sensitive and specific markers of myocardial injury. However, the role of increased cTnI and cTnT in percutaneous coronary intervention （PCI）-related myocardial injury remains controversial. In this prospective, single-center and double-blind study, we aimed to determine the diagnostic and prognostic value of cTnI as well as cTnT （cTns） in PCI-related myocardial injury in a Chinese population. A total of 1,008 patients with stable angina pectoris and non-ST-segment elevation acute coronary syndrome were recruited. The levels of cTnI and cTnT were examined before and after PCI. All patients were followed up for 26± 9 months to observe the incidence of major adverse cardiac events （MACEs）. Our results showed that post- PCI cTnI and/or cTnT levels were increased to more than the 99^th percentile upper reference limit （URL） in 133 （13.2%） patients, among which 22 （2.2%） were more than 5 × 99^th percentile URL. By univariate analysis, an elevation in cTns after PCI was not an independent predictor of increased MACEs, HR 1.35 （P = 0.33, 95% CI： 0.74-2.46）. In conclusion, our data demonstrate that the incidence of PCI-related myocardial injury is not common in a Chinese population and minor elevated cTns levels may not be a sensitive prognostic marker for MACEs.

Association between preoperative high sensitive troponin I levels and cardiovascular events after hip fracture surgery in the elderly

Objective Cardiovascular complications contribute to postoperative morbidity and mortality in elderly hip fracture patients. Limited data are available regarding which preoperative risk factors predict cardiovascular course following hip fracture surgery （HFS）. We used high sensitive troponin I （hs-TnI） assays and clinical parameters to identify preoperative risk factors associated with major adverse cardiac events （MACE） in elderly hip frac^u＇e patients. Method From August 2014 to November 2016, 575 patients with hip fracture were enrolled in a retrospective, single-center registry. A total of 262 of these patients underwent HFS and hs-TnI assays. MACE was defined as postoperative all-cause deaths, heart failure （HF）, new-onset atrial fibrillation （AF）, myocardial infarction （MI） and cardiovascular re-hospitalization that occurred within 90 days postoperative. Results Of 262 HFS patients, MACE developed following HFS in 65 （24.8%）. Patients with MACE were older and had higher rates of renal insufficiency, coronary artery disease, prior HF, low left ventricular ejection fraction and use of beta blockers; higher levels of hs-Tnl and N-terminal pro-brain natriuretic peptide （NT-proBNP） and higher revised cardiac risk index. A preoperative hs-TnI≥ 6.5 ng/L was associated with high risk of postoperative HF, new-onset AF and MACE. In multivariable analysis, pre-operative independent predictors for MACE were age 〉 80 years [adjusted hazard ratio （HR）： 1.79, 95% confident interval （CI）： 1.03-3.13, P = 0.04], left ventricular ejection fraction （LVEF） 〈 50% （adjusted HR： 3.17, 95% CI： 1.47-5.82, P 〈 0.01） and hs-TnI 〉 6.5 ng/L （adjusted HR： 3.75, 95% CI： 2.09~5.17, P 〈 0.01）. Conclusion In elderly patients with hip fracture who undergo HFS, a preoperative assessment of hs-TnI may help the risk refinement of cardiovascular complications.

Preparation of Anti-cardiac Troponin I Monoclonal Antibodies and Their Characterization with Surface Plasmon Resonance Biosensor

Cardiac troponin I(cTnI) was separated and purified from human left ventricular tissue by affinity chromatographic method and used to immunize Balb/c mice by intraperitoneal injection and four hybridoma cell lines, which secreted monoclonal antibody(mAb) against human cTnI, were obtained by cell fusion, identification and cloning twice. Three mAbs(9F5, 2F11, 8C12) were produced from the ascites of Balb/c mice injected intraperitoneally the hybridoma cells and characterized by means of a surface plasmon resonance(SPR) biosensor. An optimal and specific sensing membrane for troponin I was prepared with staphylococcal protein A(SPA) as the intermediate layer and mAb against human cTnI as the capture antibody. On the basis of the sensing membrane, two modes of operation of the SPR biosensor were developed, i.e ., a direct detection of antigen antibody affinity and a sandwich assay. In the sandwich assay detection mode, the mAbs competition was measured by monitoring whether the secondary antibody had been attached to the cTnI already captured by the first antibody on the sensor surface. The SPR biosensor was shown to be able to directly detect the antigen antibody affinity and the order of the affinity was found to be 9F5>2F11>8C12. In the sandwich detection mode, it was found that the different epitopes on the cTnI molecules were recognized by the three mAbs respectively, but the asymmetrical competition was shown between 2F11 and 8C12 and no competition was found between 9F5 and 2F11 or 8c12. Based on these results, a double monoclonal sandwich immunoassay for cTnI was developed by using the optimal antibody pair of 9F5 and 2F11 and the SPR biosensor with SPA substrate membrane, which showed an excellent sensitivity of 0.8 μg/L for both the buffer and the serum samples compared with the direct detection of cTnI for the buffer with the lowest detection limit of 4 μg/L and conventional ELISA with the sensitivity of 1.9 μg/L.

The combination of creatine kinase-myocardial band isoenzyme and point-of-care cardiac troponin/contemporary cardiac troponin for the early diagnosis of acute myocardial infarction

BACKGROUND:The early diagnosis of acute myocardial infarction(AMI)remains challenging,especially for institutions without the high-sensitive cardiac troponin(hs-c Tn)assay.Herein,we aim to assess the value of creatine kinase-myocardial band isoenzyme(CK-MB)combined with different cardiac troponin(c Tn)assays in AMI diagnosis.METHODS:This multicenter,observational study included 3,706 patients with acute chest pain from September 1,2015,to September 30,2017.We classified the participants into three groups according to the c Tn assays:the point-of-care c Tn(POC-c Tn)group,the contemporary c Tn(c-c Tn)group,and hs-c Tn group.The diagnostic value was quantified using sensitivity and the area under the curve(AUC).RESULTS:Compared to the single POC-c Tn/c-c Tn assays,combining CK-MB and POC-c Tn/c-c Tn increased the diagnostic sensitivity of AMI(56.1%vs.63.9%,P<0.001;82.7%vs.84.3%,P=0.025).In contrast,combining CK-MB and hs-c Tn did not change the sensitivity compared with hs-c Tn alone(95.0%vs.95.0%,P>0.999).In the subgroup analysis,the sensitivity of combining CKMB and c-c Tn increased with time from symptom onset<6 h compared with c-c Tn alone(72.8%vs.75.0%,P=0.046),while the sensitivity did not increase with time from symptom onset>6 h(97.5%vs.98.3%,P=0.317).The AUC of the combination of CK-MB and POC-c Tn significantly increased compared to the single POC-c Tn assay(0.776 vs.0.750,P=0.002).The AUC of the combined CKMB and c-c Tn/hs-c Tn assays did not significantly decrease compared with that of the single c-c Tn/hs-c Tn assays within 6 h.CONCLUSIONS:The combination of CK-MB and POC-c Tn or c-c Tn may be valuable for the early diagnosis of AMI,especially when hs-c Tn is not available.

High-sensitivity cardiac troponins in everyday clinical practice

High-sensitivity cardiac troponin(hs-cTn) assays are increasingly being used in many countries worldwide,however,a generally accepted definition of high-sen-sitivity is still pending.These assays enable cTn mea-surement with a high degree of analytical sensitivity with a low analytical imprecision at the low measuring range of cTn assays(coefficient of variation of < 10% at the 99th percentile upper reference limit).One of the most important advantages of these new assays is that they allow novel,more rapid approaches to rule in or rule out acute coronary syndromes(ACSs) than with previous cTn assay generations which are still more commonly used in practice worldwide.hs-cTn is also more sensitive for the detection of myocardial damage unrelated to acute myocardial ischemia.Therefore,the increase in early diagnostic sensitivity of hs-cTn assays for ACS comes at the cost of a reduced ACS specificity,because more patients with other causes of acute or chronic myocardial injury without overt myocardial isch-emia are detected than with previous cTn assays.As hs-cTn assays are increasingly being adopted in clinical practice and more hs-cTn assays are being developed,this review attempts to synthesize the available clinical data to make recommendations for their everyday clini-cal routine use.

Comparison of plasma microRNA-1 and cardiac troponin T in early diagnosis of patients with acute myocardial infarction

BACKGROUND:Early reperfusion can effectively treat acute myocardial infarction(AMI) and reduce the mortality signif icantly. This study aimed to compare the role of plasma microRNA-1(miR-1) and cardiac troponin T(cTnT) in early diagnosis of AMI patients.METHODS:From May 2011 to May 2012,plasma samples were collected from 56 AMI patients and 28 non-AMI controls. The expression of plasma miR-1 was measured by quantitative reverse transcription-polymerase chain reaction(qRT-PCR),and the level of plasma cTnT was measured using electrochemiluminescence-based methods on an Elecsys 2010 Immunoassay Analyzer. SPSS 16.0 was used for the statistical analysis of the results. Data were expressed as mean±standard deviation unless otherwise described. The differences about clinical characteristics between the AMI patients and controls were tested using Student's t test or Fisher's exact test. The Mann-Whitney U test was conducted to compare the expression of microRNAs between the AMI patients and controls. MicroRNAs expression between different intervals of the AMI patients was compared using Wilcoxon's signed-rank test. The receiver operating characteristic(ROC) curve was established to discriminate the AMI patients from the controls.RESULTS:In the present study,the expression of plasma miR-1 was signifi cantly increased in the AMI patients compared with the healthy controls(P<0.01). The plasma miR-1 in the AMI patients decreased to the normal level at 14 days(P>0.05). The expression of plasma miR-1 was not related to the clinical characteristics of the study population(P>0.05). ROC curve analyses demonstrated that miR-1 was specifi c and sensitive for the early diagnosis of AMI,but not superior to cTnT.CONCLUSION:Plasma miR-1 could be used in the early diagnosis of AMI,but it is similar to cTnT.

Characteristics of elevated cardiac troponin I in patients with acute ischemic stroke

Objective To study prognostic characteristics of cardiac troponin I （cTnI） elevation in acute ischemic stroke. Methods We retrospectively studied patients （n = 248） with acute ischemic stroke, acute ST-segment elevation myocardial infarction, and acute non-ST-elevation myocardial infarction who were treated between January 2013 and October 2015. Baseline demographic data and changes in cTnI levels among these three groups were compared. Patients with acute ischemic stroke were assigned to either the cTnI elevation group （cTnI 〉 0.034 ng/mL） or the no cTnI elevation group （cTnI ≤ 0.034 ng/mL）. Logistic regression analysis was used to identify risk factors associated with elevated serum cTnI in patients with acute ischemic stroke. Moreover, the duration of hospital stay and incidence of major cardiovascular outcomes were compared in patients with acute ischemic stroke, with or without elevated cTnI. Results In this study population of patients with acute ischemic stroke （n = 178）, acute ST-segment elevation myocardial infarction （n = 35）, and acute non-ST-elevation myocardial infarction （n = 35）, patients with acute ischemic stroke with elevated cTnI comprised 18.54% of subjects. Patients with elevated cTnI were older and more likely to have a history of hypertension. In addition, these patients had higher levels of inflammatory markers, reduced renal functions, increased D-dimer levels, higher NIH stroke scores, and lower left ventricular ejection fractions. Logistic regression analysis showed that both percentage of neutrophil and NIH stroke scores were elevated; estimated glomerular filtration rate and left ventricular ejection fraction were decreased in patients with acute ischemic stroke who had elevated cTnI, and they had more frequent major cardiovascular events during hospital stay. Conclusion Elevated cTnI detected in patients with acute ischemic stroke, indicated a greater likelihood of poor short-term prognosis during hospital stay.

A MXene-functionalized paper-based electrochemical immunosensor for label-free detection of cardiac troponin I

Convenient,rapid,and accurate detection of cardiac troponin I(cTnI)is crucial in early diagnosis of acute myocardial infarction(AMI).A paper-based electrochemical immunosensor is a promising choice in this field,because of the flexibility,porosity,and cost-efficacy of the paper.However,paper is poor in electronic conductivity and surface functionality.Herein,we report a paper-based electrochemical immunosensor for the label-free detection of cTnI with the working electrode modified by MXene(Ti_(3)C_(2))nanosheets.In order to immobilize the bio-receptor(anti-cTnI)on the MXene-modified working electrode,the MXene nanosheets were functionalized by aminosilane,and the functionalized MXene was immobilized onto the surface of the working electrode through Nafion.The large surface area of the MXene nanosheets facilitates the immobilization of antibodies,and the excellent conductivity facilitates the electron transfer between the electrochemical species and the underlying electrode surface.As a result,the paper-based immunosensor could detect cTnI within a wide range of 5-100 ng/mL with a detection limit of 0.58 ng/mL.The immunosensor also shows outstanding selectivity and good repeatability.Our MXene-modified paper-based electrochemical immunosensor enables fast and sensitive detection of cTnI,which may be used in real-time and cost-efficient monitoring of AMI diseases in clinics.

Restrictive Cardiomyopathy Resulting from a Troponin Ⅰ Type 3 Mutation in a Chinese Family

Objective To identify the pathogenic variant responsible for restrictive cardiomyopathy （RCM） in aChinese family.Methods Next generation sequencing was used for detecting the mutation and results verified bysequencing. We used restriction enzyme digestion to test the mutation in the family members and 200 unrelatednormal subjects without any cardiac inherited diseases when the mutation was identified.Results Five individuals died from cardiac diseases, two of whom suffered from sudden cardiacdeath. Two individuals have suffered from chronic cardiac disorders. Mutation analysis revealed a novelmissense mutation in exon 7 of troponin I type 3 （TNNI3）, resulting in substitution of serine （S） withproline （P） at amino acid position 150, which cosegregated with the disease in the family, which is predictedto be probably damaging using PolyPhen-2. The mutation was not detected in the 200 unrelated subjectswe tested.Conclusion Using next generation sequencing, which has very recently been shown to be successfulin identifying novel causative mutations of rare Mendelian disorders, we found a novel mutation of TNNI3 in aChinese family with RCM.

Prognostic value of high-sensitivity cardiac troponin T in patients with en-domyocardial-biopsy proven cardiac amyloidosis

Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis （CA）, and to determine predictive value of high-sensitivity cardiac troponin T （hs-cTnT） in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age （56 ±12 years vs. 50 ±15 years, P=0.022）, higher incidences of heart failure （36.92%vs. 16.22%, P=0.041）, pericardial effusion （60.00%vs. 35.14%, P=0.023）, greater thickness of interventricular septum （IVS） （15 ±4 mm vs. 13 ±4 mm, P=0.034）, higher level of hs-cTnT （0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001） and higher NT-proBNP （N-terminal pro-B-type natriuretic pep-tide） levels （11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006）. At multivariate Cox regression analysis, heart failure （HR：1.78, 95%CI：1.09-2.92, P=0.021）, greater wall thickness of IVS （HR：1.44, 95%CI：1.04-3.01, P=0.0375） and higher hs-cTnT level （HR：6.16, 95%CI：2.20-17.24, P=0.001） at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.

Physician-level variation in the diagnosis of myocardial infarction and the use of angiography among veterans with elevated troponin

Background:Cardiac troponin assays have improved the ability to detect myocardial damage.However,ascertaining whether troponin elevation is due to myocardial infarction(MI) or secondary to another process can be challenging.Our aim is to evaluate provider-level variation in the diagnosis of MI and the use of invasive coronary angiography(ICA) among patients with undifferentiated elevations in cardiac troponin.Methods:We analyzed data from all patients with elevated troponin levels in a single Veterans Affairs(VA) Medical Center between 2006 and 2007.One of several cardiologists prospectively evaluated each patient's presentation and course of care.We compared the frequency of MI diagnosis and ICA use between physicians using univariate odds ratios(OR).Results:Among 761 patients,34.0% were diagnosed with MI and 25.9% underwent ICA.The unadjusted rates of MI(23.9% to 56.7%,P=0.02) and ICA(17.3% to 73.3%,P<0.001) differed between physicians.Comparing the patient cohorts for each physician,baseline characteristics were similar except for chest pain.In multivariate regression,factors associated with the use of cardiac ICA included an abnormal electrocardiograph(ECG)(OR=1.89,P=0.014),level of troponin(OR=1.71,P=0.004),chest pain(OR=8.60,P<0.001),and care by non-VA physicians(OR=4.45,P=0.006).One physician had a lower ICA use(OR=0.56,P=0.017).In multivariate regression of MI,no physician-level variation was observed.Conclusion:Among patients with elevated troponin,the likelihood of being diagnosed with MI and undergoing ICA is dependent on their clinical presentation.After adjustment,physician-level variation in care was observed for the use of ICA,but not for the diagnosis of MI.