肥厚型心肌病患者肌钙蛋白T基因突变的研究

目的研究肥厚型心肌病（hypertrophiceardiomyopathy,HCM）患者肌钙蛋白T基因（TNNT2）基因突变的发生情况。方法对无血缘关系的102例HCM患者进行TNNT2基因突变筛查,其中家族性HCM患者与非家族性HCM患者各51例。结果家族性HCM患者发现TNNT2基因突变3例,其中1例14号外显子检出错义突变（编码区712位G-C）,GAA→CAA,编码谷氨酸变为谷氨酰胺;2例9号外显子检出同义突变（编码区348位C-T）,为ATC→ATT,均编码异亮氨酸;非家族性HCM患者未发现TNNT2基因突变。结论HCM患者TNNT2基因突变率较低。     

Cardiac troponin T mutations promote life-threatening arrhythmias

Mutations in contractile proteins in heart muscle can cause anatomical changes that result in cardiac arrhythmias and sudden cardiac death. However, a conundrum has existed because mutations in one such contractile protein, a so-called Ca²⁺ sensor troponin T (TnT), can promote ventricular rhythm disturbances even in the absence of hypertrophy or fibrosis. Thus, these mutations must enhance abnormal electrophysiological events via alternative means. In this issue of the JCI, Baudenbacher et al. report a novel mechanism to explain this puzzle (see the related article beginning on page 3893). They show that a selected TnT mutation in the adult mouse heart can markedly increase the sensitivity of cardiac muscle myofilaments to Ca²⁺ and enhance the susceptibility to arrhythmia, even in the absence of anatomical deformities. As these same mutations can cause some forms of arrhythmias in humans, these findings are of both basic and translational significance.     

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.     

Cardiac troponin T in diagnosis of acute myocardial infarction

Troponin T is a structurally bound protein found in striated muscle cells. We tested concentrations of its cardiac-specific isotype in peripheral venous blood samples serially drawn from 72 patients with confirmed myocardial infarction. Fifty-nine patients received thrombolytic treatment with intravenous streptokinase, urokinase, or recombinant tissue-type plasminogen activator; because of contraindications, the remaining 13 patients did not. Concentrations of troponin T in plasma, measured by an enzyme-linked immunosorbent assay, started increasing within a few hours after the onset of symptoms (median, 4 h; range, 1-10 h). The sensitivity of troponin T for detecting myocardial infarction was 100% from 10 to 120 h after the onset of symptoms; sensitivity on the seventh day after admission was 84%. Concentrations were increased for up to three weeks in some patients with late or high peak values. Successful reperfusion in Q-wave infarction obviously influences the release of troponin T into plasma, with all such cases showing peak values less than or equal to 26 h (median, 14 h) after the onset of symptoms. Troponin T concentrations in these patients returned to within the reference interval more rapidly than in nonreperfused subjects. In the 13 patients without fibrinolytic therapy, troponin T tended to peak approximately 48 h (median) after the onset of chest pain. Troponin T concentrations in patients for whom thrombolysis was unsuccessful resembled those in patients without fibrinolytic therapy. The specificity of the assay was 96% as tested in samples of 96 emergency-room patients. The reference interval (less than 0.5 micrograms/L) was established from samples of 100 healthy blood donors. Troponin T measurements are a specific and sensitive method for the early and late diagnosis of acute myocardial infarction and could, therefore, provide a new criterion in laboratory diagnosis of its occurrence.     

维持性血液透析患者血清肌钙蛋白T水平的相关影响因素分析

目的 研究维持性血液透析（maintenance hemodialysiS,MHD）患者血清心肌肌钙蛋白T（cardiac troponin T,cTnT）水平及其影响因素。方法 选取MHD治疗3个月以上的稳定患者,采用电化学发光法检测受试者血清cTnT。用Spearman相关和线性回归分析cTnT与其它指标之间的相关性。用受试者工作特征（receiver operating characteristic,ROC）曲线比较cTnT、氨基末端脑钠肽原（amino—terminal pro-brain natriuretic peptide,NT—proBNP）及高敏C反应蛋白（high sensitive C—reactive protein,hsCRP）与心血管疾病（cardiovascular disease,CVD）和左心室肥大的相关性。结果 123例MHD患者血清cTnT中位数为0．046（0．028～0．066）ng／ml。合并CVD的患者血清cTnT水平显著高于非CVD患者（0．062[0．044～0．083]ng／ml比0．031[0．020～0．046]ng／ml,P=-0．002）。糖尿病患者血清cTnT水平显著高于非糖尿病患者（0．061[0．042～0．102]ng／ml比0．044[0．025～0．064]ng／ml,P=0．003）。Spearman相关分析显示血清cTnT与年龄（ρ=0．309,P=0．002）、糖化白蛋白（ρ=0．192,P=0．040）、NT—proBNP（ρ=0．448,P〈0．001）、hsCRP（ρ=-0．335,P〈0．001）、颈动脉内膜中层厚度（ρ=0．315,P=0．004）及左心室质量指数（ρ=0．369,P〈0．001）呈正相关,与血清前白蛋白（ρ=-0．280,P=0．002）、高密度脂蛋白胆固醇（ρ=-0．201,P=0．047）呈负相关。线性回归分析显示年龄（β=0．204,P=0．043）、NT—proBNP（β=0．299,P=0．020）及左心室质量指数（β=0．345,P=0．003）与血清cTnT水平独立相关。ROC曲线分析显示cTnT水平与CVD的相关性高于NT—proBNP及hsCRP,与左心室肥大的相关性介于NT—proBNP与hsCRP之间。结论 MHD患者血清cTnT水平显著升高,cTnT水平升高与患者高龄、容量负荷、营养不良、微炎症状态、左心室肥大及伴发CVD相关。     

Cardiac troponin T circulates in the free, intact form in patients with kidney failure

BACKGROUND: The clinical significance of the increased concentrations of cardiac troponins observed in patients with end stage renal disease (ESRD) in the absence of an acute coronary syndrome (ACS) is controversial. One proposed explanation is that immunoreactive fragments of cardiac troponin T (cTnT) accumulate in ESRD. We used gel-filtration chromatography (GFC) to ascertain whether fragments of cTnT, which could cross-react in the commercial diagnostic immunoassay (Roche Diagnostics), were the cause of the increased cTnT in the serum of patients with ESRD. METHODS: We subjected sera from ESRD patients (n = 21) receiving dialysis and having increased cTnT concentrations to size-separation GFC. We detected cTnT in the chromatography fractions by use of the same antibodies used in the commercial assay for serum cTnT. RESULTS: In all patients, cTnT immunoreactivity eluted as a major, homogeneous peak in an identical position between the peaks of serum prolactin [relative molecular mass (Mr) 23,000] and albumin (Mr 67,000): the elution pattern of cTnT in samples obtained from ACS patients was identical to that of the ESRD patients. There was no evidence that low-molecular-mass (Mr < 23,000) cTnT fragments were the cause of the increased cTnT in the patients studied. CONCLUSIONS: The form of cTnT observed in the serum of patients with kidney failure and immunoreactive in the diagnostic assay is predominantly the free intact form, as in patients with ACS. Our data are consistent with the view that circulating cTnT in renal failure reflects cardiac pathology.     

Cardiac troponin T in the diagnosis of myocardial injury.

In the last several decades serum levels of cardiac enzymes and isoenzymes have become the final arbiters by which myocardial damage is diagnosed or excluded. Because conventionally used enzymes are neither perfectly sensitive nor specific, there is need for a new sensitive and cardiospecific marker of myocardial damage. Cardiac troponin T (TnT) is a contractile protein unique to cardiac muscle and can be differentiated by immunologic methods from its skeletal-muscle isoform. An enzyme immunoassay specific for cardiac TnT is now available in a commercial kit for routine use. The biggest advantage of this assay is its cardiospecificity. TnT measurements, however, are also highly sensitive in diagnosis of myocardial injury and accurately discern even small amounts of myocardial necrosis. TnT measurements are, therefore, particularly useful in patients with borderline CK-MB and in clinical settings in which traditional enzymes fail to diagnose myocardial damage efficiently because of lack of specificity--for example, perioperative myocardial infarction or blunt heart trauma. TnT release kinetics reveal characteristics of both soluble, cytoplasmic, and structurally bound molecules. It starts to increase a few hours after the onset of myocardial damage and remains increased for several days. TnT allows late diagnosis of myocardial infarction. The diagnostic efficiency remains at 98% until 6 d after the onset of infarct-related symptoms. TnT is also useful in monitoring the effectiveness of thrombolytic therapy in myocardial infarction patients. The ratio of peak TnT concentration on day 1 to TnT concentration at day 4 discriminates between patients with successful (greater than 1) and failed (less than or equal to 1) reperfusion. TnT measurements are very sensitive and specific for the early and late diagnosis of myocardial damage and could, therefore, provide a new criterion in laboratory diagnosis of the occurrence of myocardial damage.     

Cardiac troponin T for prediction of short- and long-term morbidity and mortality after elective open heart surgery

BACKGROUND: Increased cardiac troponins in blood are observed after virtually every open heart surgery, indicating perioperative myocardial cell injury. We sought to determine the optimum time point for blood sampling and the respective cutoff value of cardiac troponin T (cTnT) for risk assessment in patients undergoing cardiac surgery. METHODS: In a series of 204 patients undergoing scheduled open heart surgery, mainly for coronary artery bypass grafting (n = 132) or valve repair (n = 27), cTnT concentrations were measured before and 4 and 8 h after cross-clamping and then daily for 7 days. Individual risk was assessed by use of the Cleveland Clinic Foundation Risk score and intraoperative risk indicators such as duration of cardiopulmonary bypass, cross-clamping, and perioperative release of cardiac markers. Patients were followed for 28 months. RESULTS: Cardiac mortality, all-cause mortality rates, and rates of nonfatal acute myocardial infarction (AMI) at 28 months were 6.9%, 8.8%, and 6.8%, respectively. cTnT was higher in patients with Q-wave AMI or postoperative heart failure requiring inotropic support, and in nonsurvivors. The ROC curve revealed a cTnT > or = 0.46 microg/L at 48 h as the optimum discriminator for long-term cardiac mortality. Stepwise logistic regression identified higher Cleveland Clinic Risk Score [odds ratio (OR) = 2.6 per point], cross-clamp time >65 min (OR = 6.6), and cTnT (OR = 4.9) as significant and independent predictors of long-term cardiac mortality. CONCLUSIONS: A single postoperative cTnT measurement can be used to estimate myocardial cell injury that impacts long-term survival after open heart surgery. It adds independently to established risk indicators.     

Cardiac troponin elevations among critically ill patients

PURPOSE OF THE REVIEW: Elevated levels of cardiac troponins, indicative of the presence of cardiac injury, have been reported in critically ill patients. In this review, the incidence, significance, and clinical relevance of elevated troponin levels among this group of patients will be discussed. RECENT FINDINGS: It has been shown that elevated cardiac troponin levels can be present among critically ill septic patients without evidence of myocardial ischemia. Recent studies show that elevated troponin levels are also present in a diverse group of critically ill patients without sepsis or septic shock. In addition, several but not all studies show that the mortality rate of troponin-positive patients is significantly higher compared with troponin-negative patients. SUMMARY: Elevated troponin levels are not only present in patients suffering from acute coronary syndromes but can also be present in critically ill patients. Even minor elevations are specific for myocardial injury. However, every elevated troponin level in the critically ill patient should not be rigorously diagnosed or treated as a myocardial infarction.     

Cardiac troponin I and troponin T: recent players in the field of myocardial markers.

The troponin (Tn) complex consists of three subunits referred to as TnT, TnI and TnC. Myocardium contains TnT and TnI isoforms which are not present in skeletal muscles and which can be separated from the muscular isoforms by immunological techniques. Using commercially available immunoassays, clinical laboratories are able to determine cardiac TnT and TnI (cTnT and cTnI) quickly and reliably as classical cardiac markers. After acute myocardial infarction, cTnT and cTnI concentrations start to increase in serum in a rather similar way than CK-MB, but return to normal after longer periods of time (approximately one week). Because of their excellent cardiac specificity, Tn subunits appear ideally suited for the differential diagnosis of myocardial and muscular damage, for example in noncardiac surgery patients, in patients with muscular trauma or with chronic muscular diseases, or after intense physical exercise. cTnT and cTnI may also be used for detecting evidence of minor myocardial damage: therefore they have found new clinical applications, in particular risk stratification in patients with unstable angina. In spite of the possible reexpression of cTnT in human skeletal muscles, and of the lack of standardization of cTnI assays, Tn subunits are not far to meet the criteria of ideal markers for acute myocardial injury. Only an insufficient sensitivity in the first hours following the acute coronary syndroms requiries to maintain an early myocardial marker in the cardiac panel for routine laboratory testing.     

C-反应蛋白水平与血液透析患者贫血和促红细胞生成素抵抗的关系

目的探讨维持性血液透析患者C-反应蛋白(CRP)与贫血和促红细胞生成素(EPO)疗效的关系.方法 96例维持性血液透析患者于透析日空腹采血测定血红蛋白(Hb)、红细胞比积(Hct)、血清铁蛋白(SF)、转铁蛋白饱和度(TSAT)以及血浆白蛋白(Alb)、血脂、纤维蛋白原(Fib)和CRP,记录重组人红细胞生成素(rHuEPO)用量,以rHuEPO用量/Hct比值(EPO/Hct)作为EPO抵抗指标.结果 96例患者中57例(占59.4%)CRP升高(CRP增高组),39例(占40.6%)正常(CRP正常组),CRP增高组rHuEPO用量、EPO/Hct比值、Fib和CRP水平均高于CRP正常组,Hct、Hb、血浆白蛋白(Alb)低于CRP正常组;多因素逐步回归分析表明,影响EPO/Hct比值的因素有CRP、Alb和透析疗程(R2=0.388,P=0.039).结论微炎症反应在维持性血液透析患者中较为常见,C-反应蛋白升高是促红细胞生成素抵抗的独立影响因素.     

Circulating fetuin-A predicts early mortality in chronic hemodialysis patients

ObjectivesThe purpose of this study was to assess whether low serum levels of fetuin-A are potential biochemical predictor of early and/or late survival in chronic hemodialysis (HD) patients.Design and methodsWe measured serum levels of fetuin-A in 67 patients on chronic HD, and correlated it to 3, 12, and 24 months mortality.ResultsCumulative death rate was 7%, 19%, and 37% deaths at 3, 12, and 24 months. Serum fetuin-A was significantly lower in 3 months and 12 months non-survivals (p < 0.001), but not in 24 months non-survivals. Kaplan–Meier analyses based on fetuin-A tertiles showed statistically significantly increased probability of death up to 12 months of follow-up for decreasing fetuin-A concentrations (p < 0.008).ConclusionsFetuin-A as a circulating inhibitor of vascular calcification was significant predictor of early mortality in chronic HD patients but did not appear as a fair marker for later survival.     

Infective endocarditis in patients receiving long-term hemodialysis

OBJECTIVE: To ascertain the predominant characteristics of patients receiving long-term dialysis who develop infective endocarditis (IE). PATIENTS AND METHODS: We reviewed the records of all chronic hemodialysis patients who had IE at Mayo Clinic, Rochester, Minn, between 1983 and 1997. RESULTS: Twenty episodes of IE occurred in 17 patients. One patient had 3 episodes of IE, and 1 patient had 2 episodes of IE; each episode was caused by a different organism. The mean +/- SD age of our patients was 63 +/- 11 years; there were 13 males; 6 patients had diabetes mellitus; and the mean +/- SD duration of hemodialysis prior to IE was 24.2 +/- 20.5 months. This analysis included 10 episodes of IE (occurring in 9 patients) within the Mayo Clinic Dialysis System during which time 223,358 hemodialysis treatments were delivered, giving a rate of 10 IE episode per 223,336 hemodialysis treatments. Among all 20 IE episodes, there were 14 synthetic arteriovenous grafts, 4 permanent venous dialysis catheters, 2 temporary venous dialysis catheters, and 2 native arteriovenous fistulas (2 accesses in 2 patients), and access had been in place for a mean +/- SD of 15.9 +/- 18.6 months. The portal of infection was the hemodialysis access in 13 episodes of IE. The causative organisms for IE were Staphylococcus aureus in 8 cases, Enterococcus sp in 4 cases, viridans streptococcus in 3 cases, Staphylococcus epidermidis in 2 cases, and 1 case each of Streptococcus bovis, group G beta-hemolytic streptococcus, and Aspergillus sp. The mitral valve was involved in 9 cases, the aortic valve was involved in 5 cases, and the tricuspid and pulmonic valves were involved in 1 case each. Patient survival (after the first episode of IE) was 71% at 30 days; 53% at 60 days; and 35% at 1 year. Echocardiography was performed in 19 episodes of IE. The transthoracic echocardiogram was 62.5% sensitive and 40% specific for the presence of definite or probable vegetations. Univariate analysis for factors affecting 60-day survival show that presence of right-sided IE, vegetation size greater than 2.0 cm3, diagnosis of diabetes mellitus, and initial leukocyte count greater than 12.5 x 10(9)/L were poor prognostic factors. Aortic valve involvement carried a better prognosis. CONCLUSIONS: Infective endocarditis in hemodialysis patients is relatively infrequent but has a high mortality. Patients with synthetic intravascular dialysis angioaccess (synthetic grafts and venous catheters) are more likely to develop IE than patients with native arteriovenous fistulas. Transesophageal echocardiography is a preferred echocardiographic study for suspected cases of IE. Prolonged antibiotic therapy is needed for all patients, and close monitoring is needed for patients with right-sided IE, large vegetations, diabetes mellitus, and an elevated leukocyte count.     

长期维持性血液透析患者认知功能的探讨

目的探讨长期维持性血液透析患者认知功能的损害及其相关危险因素。方法选择解放军第101医院长期维持性血液透析,经门诊CT或MRI排除颅内器质性病变的患者,共42例为研究对象。解放军第101医院体检中心证实无颅内病灶的正常社区人群,共46例为对照组。2组进行记忆力、执行功能、信息处理速度、视空间能力、视觉结构能力及简易精神状态检查(mini-mental state examination,MMSE)等广泛的认知评估。结果校正了性别、年龄、受教育时间、吸烟、血压和血糖等因素后,病例组在听觉记忆能力、执行功能(包括控制能力、思维灵活性、概念的形成和转换能力及抽象推理能力)、信息处理速度和视觉结构能力等方面与对照组有显著差异(P<0.001)。而在视觉记忆方面(包括简化Rey复杂图形即刻记忆、长时延迟回忆、再认)、视空间2组患者表现无统计学差异(P=0.175,P=0.07,P=0.339;P=0.175)。多因素Logistic回归分析发现高血压、贫血是长期血液透析患者认知功能损害的独立危险因素(OR值分别为0.097,1.700)。结论长期维持性血液透析的患者存在广泛的认知功能损害,且与高血压、贫血密切相关。     

家族性肥厚型心肌病心肌肌钙蛋白T2基因突变特点:14例分析

目的:对14例家族性肥厚型心肌病患者第2～16号外显子进行扫描,试图发现在这一范围上有无基因突变位点。方法:选择2002-01/2006-12苏州大学附属第一人民医院心内科门诊及住院的肥厚型心肌病患者14例,年龄16～62岁。均符合WHO/ISFC1996年肥厚型心肌病诊断标准;汉族;无血缘关系;每例患者家族中至少两人发病;均对检测项目知情同意。对受试对象的聚合酶链反应扩增产物进行单链构象多态性分析,于肌钙蛋白T2基因第2～16外显子范围内寻找突变位点,并了解基因型明确的肥厚型心肌病患者的临床特点。之前,均已对该14例先证者的β-肌球蛋白重链基因3～26号外显子进行突变基因筛查,未见异常。结果:14例临床确诊的家族性肥厚型心肌病患者肌钙蛋白T2基因第2～16外显子,除10例患者106位密码子存在ATC-ATT多态性外,未发现基因位点的异常。结论:在中国汉族人群家族性肥厚型心肌病患者未发现肌钙蛋白T2基因突变类型。     

高敏心肌肌钙蛋白T水平与维持性血液透析患者心脏结构和功能的关系

目的 研究高敏心肌肌钙蛋白（hs-cTnT）与维持性血液透析（maintenance hemodialysis,MHD）患者心脏结构和功能的关系.方法 选择86例规律血液透析的慢性肾衰竭患者（每周3次,时间＞6月）,病情稳定,已排除近6个月内曾发生急性心肌梗死、急性心肌炎事件及肥厚性心肌病者,测定血清hs-cTnT、B型脑钠肽（BNP）、生化指标,同时应用心脏超声心动图测量左室射血分数（LVEF）、左室舒张末内径（LVDd）、室间隔厚度（IVST）、左心室后壁厚度（LVPWT）,计算左室心肌重量指数（LVMI）,分析hs-cTnT与心脏结构和功能指标间的关系.同时检测同期来院体检的60名健康体检者的hs-cTnT作对比分析.结果 维持性血液透析组hs-cTnT水平与健康对照组比较明显升高[（0.263±0.038） ng/ml比（0.016±0.008） ng/ml],差异有统计学意义（P＜0.05）,患者中hs-cTnT与BNP、LVMI及LVH呈正相关（P＜0.05）,与LVEF呈负相关（P =0.015）.结论 hs-cTnT的检测对维持性血液透析患者的早期心脏左室肥厚及收缩功能减退有预测作用.     

心肌肌钙蛋白T检测对维持性血透尿毒症患者心血管事件发生的临床意义

目的 探讨检测心肌肌钙蛋白T(cTnT)对维持性血透的尿毒症患者心血管事件发生的临床意义.方法 测定136例维持性血透尿毒症患者透析前、后的cTnT,每6个月测定cTnT 1次,随访3年,观察患者心血管事件及死亡事件发生情况,分析其与cTnT的关系.同时测定100名健康体检者的cTnT,并作对比分析.结果 维持性血透尿...