心肌肌钙蛋白T基因突变在心肌病发病机制中的研究进展

肥厚型和扩张型心肌病中,基因缺陷分别占发病的50％和35％,其病理生理机制,主要包括肌小节蛋白基因突变引起的收缩力产生缺陷,细胞骨架蛋白基因突变引起的收缩力传递缺陷等。心肌肌钙蛋白T将肌钙蛋白C和肌钙蛋白I连接到肌动蛋白和原肌球蛋白上,在心肌细胞收缩和舒张过程中发挥重要作用。在肥厚型和扩张型心肌病中发现了多种心肌肌钙蛋白T的基因突变,围绕心肌肌钙蛋白T的研究有助于阐明心肌病的发病机制。本文总结了心肌肌钙蛋白T基因突变在心肌病发病机制中的研究情况。     

家族性扩张型心肌病的分子遗传研究进展

扩张型心肌病是一种以左心室和,或右心室扩大、心肌收缩功能受损为主要特征的心肌疾病,是除冠心病和高血压以外导致心力衰竭的主要病因之一。家族性扩张型心肌病约占扩张型心肌病的35％。目前为止,发现的和扩张型心肌病相关的基因突变主要是心肌蛋白基因突变和细胞骨架蛋白基因突变,此外还有线粒体DNA的突变和能量代谢相关的基因突变。本文对引起家族性扩张型心肌病的分子遗传进展进行了总结。     

儿童不明原因扩张型心肌病左室射血分数恢复的影响因素分析

目的:探讨儿童不明原因扩张型心肌病(DCM)左室射血分数(LVEF)恢复的影响因素。方法:回顾性分析2010年1月至2014年12月在我院住院治疗的不明原因DCM患儿的临床资料,对所有患者随访16月后,根据二维超声心动图(UCG)中LVEF值,分为LVEF恢复组、未恢复组和死亡组,比较各组之间各相关检测指标的差异。结果:大选194例患者男性113例。恢复组45例(23.20%),末恢复组65例(33.51%),死亡组84例(43.29%)。恢复组发病年龄≤2岁者患者比例明显高于未恢复组与死亡组(P均0.05)。初诊时,恢复组左室舒张末期内径(LVDD)明显小于未恢复组与死亡组AVEF明显高于未恢复组与死亡组(P均0.05)。恢复组二尖瓣轻度反流的患者明显多于未恢复组及死亡组(P均0.05)。恢复组室性心律失常者比例明显少于未恢复组及死亡组(P0.05)。恢复组患者无心肌延迟强化现象,末恢复组延迟强化占5.41%,死亡组占21.74%。恢复组LVEF恢复正常的中位时间8.0月,同时有LVDD恢复正常者11例。多因素分析发现年龄2.0岁(OR=17.064,95%C13.494-83.171,P=0.000)、心功能Ⅲ-Ⅳ级(OR=17.711,95%CI2.229-140.704,P=0.007)、MR中重度反流(OR=3.762,95%CI1.209-11.706,P=0.022)是LVEF不能恢复正常的独立危险因素。结论:年龄2.0岁、心功能Ⅲ-Ⅳ级、二尖瓣中重度反流是不利于儿童不明原因扩张型心肌病患儿LVEF恢复的独立危险因素。     

肥厚型心肌病的临床特征及治疗分析

目的:探讨肥厚型心肌病(hypertrophic cardiomyopathy,HCM)的临床特征及治疗方法.方法:回顾性分析我院2008年6月至2012年3月收治的85例经心脏超声或左室造影证实为肥厚型心肌病患者的临床特征及治疗方法和预后.结果:85例肥厚型心肌病患者的临床症状主要表现为胸闷、气短50例(58.8％);心前区疼痛21例(24.7％);心前区不适7例(8.2％);乏力2例(2.4％);心悸2例(2.4％);剑突下疼痛1例(1.2％);发现心电图异常前来就诊2例(2.4％).其中心尖肥厚型心肌病(apical hypertrophic cardiomyopathy)30例(35.3％);合并冠心病4例(血管狭窄小于70％)(4.8％)、心肌桥(myocardial bridge,MB)11例(12.9％)、冠状动脉粥样硬化症4例(4.8％)、冠状动脉粥样硬化症合并MB4例(4.8％)、冠心病合并MB3例(3.5％).67例患者服用β-受体阻滞剂(78.8％),4例患者同时服用β-受体阻滞剂及钙离子拮抗剂(4.8％),4例患者服用钙离子拮抗剂(4.8％),1例患者服用可达龙(1.2％),1例患者同时服用β-受体阻滞剂及可达龙(1.2％),8例患者因心率慢,未服用药物(9.6％).临床随访1～30(平均15.2±4.5)个月,临床症状均明显缓解.结论:HCM症状不典型,β-受体阻滞剂和钙离子拮抗剂在治疗肥厚型心肌病方面疗效肯定.     

基于Web of Science数据库扩张型心肌病研究的文献计量学分析

目的:对扩张型心肌病(Dilated Cardiomyopathy,DCM)的研究,目前仍是国际上对于原发性心肌病研究的热点问题。本文针对DCM相关领域的研究文献进行计量分析,从而进一步深入了解国际DCM研究进展,为该研究的相关领域提供参考。方法:基于(SCIE)引文数据库为检索对象,检索2003-2012年DCM的所有相关文献,分别对不同国家和地区、著者、机构、文献来源期刊及论文学科分布等进行统计分析。结果:共检索出DCM研究文献12728篇,研究论文发表共涉及了107个国家和地区,美国的发文数最多4500篇,占35.36%,其次为德国和日本。中国居第9位,504篇占总发文量的3.96%;主要刊登期刊涵盖了国际上心血管领域的15种知名期刊;研究热点涉及心血管系统及脏病学、分子生物学、基因遗传学等学科。结论:目前DCM研究仍是人们关注的一个热点,美国、德国、日本等发达国家在该领域的研究居领先水平,中国在这一领域也做出了贡献。与领先国家和机构相比,我国亟需进一步加强对DCM的研究。为我国进一步了解和深入研究DCM的方向提出参考。     

扩张型心肌病患者恶性室性心律失常与心率变异性关系分析

目的:了解扩张型心肌病患者恶性心律失常(MVA)与心率变异性(heart rate variability,HRV)的关系,探讨扩心病患者体内自主神经变化的临床意义。方法:选择扩心病患者48例作为研究对象,同时按照年龄配对,取48例正常者作为对照组,对其行24小时动态心电图检查,依据其是否出现恶性心律失常分为恶性室性心律失常(MVA+)组及单纯扩张型心肌病(MVA-)组,分析组间HRV的差异。结果:与对照组比较,单纯扩张型心肌病(MVA-)组HRV时域指标(SDNN、SDANN、RMSSD)均有降低(P<0.05)L与(MVA-)组相比,恶性室性心律失常(MVA+)组HRV相关指标进一步降低(P<0.05)。结论:自主神经功能异常是扩张型心肌病患者恶性心律失常的重要危险因子,可能可以用HRV预测其发生恶性心律失常危险性。     

心尖肥厚型心肌病的临床特征及治疗

目的:总结心尖肥厚型心肌病的临床特征及治疗方法.方法:回顾性分析我院2008年6月至2012年2月期间经心脏超声或左室造影证实的33例心尖肥厚型心肌病患者的临床特征及治疗情况.结果:患者的临床症状表现为以胸闷、气短为主者20例;心前区不适4例;心前区疼痛5例;乏力2例;心悸l例;发现心电图异常前来就诊l例.32例患者行左室造影诊断为心尖肥厚型心肌病.l例因肾功能不全,未行左室造影,但经心脏超声诊断为心尖肥厚型心肌病.27例患者服用β-受体阻滞剂,2例患者服用钙离子拮抗剂,4例患者因心率慢,未服用药物,临床随访1～36(平均16.7± 4.1)个月,临床症状均明显缓解.结论:β-受体阻滞剂和钙离子拮抗剂均适用于治疗心尖肥厚型心肌病.     

扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义

目的:探究扩张型心肌病慢性心力衰竭患者血浆脑利钠肽水平的临床意义。方法:收集2012年3月至2016年3月我院收治的90例扩张型心肌病慢性心力衰竭患者,将患者按照NYHA心功能分级分为A组(II级)20例、B组(III级)38例、C组(IV级)32例。比较各组患者的血浆脑力钠肽(BNP)以及超声心动图相关指标,包括左心室射血分数(LVEF)、左心房内径(LA)、左室舒张末期内径(LVEDD)以及左室收缩末期内径(LVESD),分析血浆BNP与NYHA分级和超声心动图相关指标的相关性,以及比较血浆BNP和LVEF在慢性心力衰竭病情程度中的能力。结果:C组患者的血浆BNP浓度显著高于A组和B组(P0.05),而B组患者的血浆BNP浓度显著高于A组,比较差异具有统计学意义(P0.05)。心脏超声检测发现,C组患者的LA显著高于A组(P0.05),而LVEF、LVEDD及LVESD比较差异无统计学意义(P0.05)。血浆BNP与NYHA分级呈正相关关系,但与LVEDD、LVESD、LVEF、LA无明显相关关系(P0.05)。血浆BNP对评价心力衰竭患者病情程度呈现出较强的能力(受试者工作特征曲线下面积=0.902,P0.001)。血浆BNP=523.5 pg/mL为中重度心力衰竭患者的诊断最佳值。LVEF对评价心力衰竭患者病情程度无明显能力(受试者工作特征曲线下面积=0.392,P=0.276)。结论:血浆BNP浓度对扩张型心肌病慢性心力衰竭患者的诊断、筛查以及心功能分级具有重要的临床意义。     

扩张型心肌病合并充血性心力衰竭的相关因素Logistic 分析

目的:寻找扩张型心肌病(DCM)合并充血性心力衰竭(CHF)的独立危险因素,为临床预防和治疗扩心病患者的病情提供依据。方法:选择我院收治的扩张型心肌病患者125例,按照NYHA分级分组,将心功能Ⅱ-Ⅳ级同时左心室射血分数(LVEF)<40%的患者91例定义为观察组;将心功能Ⅰ级同时左心室射血分数≥40%的患者34例定义为对照组。在比较两组临床资料的基础上,采用logistic多因素分析方法确立扩张型心肌病合并心力衰竭的独立危险因素。结果:单因素分析结果发现,观察组中的"房颤"及"脉压≥70mmHg"这两个参数比对照组的数量明显增多,差异有统计学意义(P<0.05)。logistic多因素分析发现"脉压≥70mmHg"、"房颤"是扩心病合并心力衰竭的独立危险因素。结论:"脉压≥70mmHg"、"房颤"是扩张型心肌病合并充血性心力衰竭的独立危险因素,需要在临床治疗扩心病患者时警惕这两项指标的异常。     

35 岁以下年轻乳腺癌患者的临床特征及预后因素分析

目的:探讨年轻乳腺癌患者的临床病理特点及影响其预后的相关因素。方法:选取潍坊市人民医院2005年11月至2011年11月收治的年龄不高于35岁的137例年轻乳腺癌患者的临床资料,其中共有116例入组,初步分析年轻乳腺癌患者的临床病理特征及对预后产生的影响。结果:116例患者中位随访时间为46.0个月。3年OS和PFS为94.6%和79.1%。单因素、多因素分析结果显示淋巴结转移情况和Ki67水平与预后的显著相关(P0.05),淋巴结转数目、Ki67水平与预后呈负相关。结论:年轻乳腺癌患者的生物学行为、病理及预后较为特殊。淋巴结转移情况、Ki67水平是影响预后的关键因素。     

中国人扩张型心肌病与受磷蛋白基因关系的研究

受磷蛋白（phospholamban）是心肌收缩的一个重要调节因子,可抑制心肌肌浆网钙ATPase的活性、降低其对钙的亲和力。正常情况下,受磷蛋白可被不同的蛋白激酶磷酸化从而解除其肌浆网钙ATPase的抑制作用。国外两个DCM家系研究发现受磷蛋白基因突变与DCM的发生有关,研究目的旨在探讨中国人群心肌特异性受磷蛋白基因突变与特发性扩张型心肌病发病的关系。收集60例确诊的特发性扩张型心肌病患者临床资料,采集血样本并分离白细胞和提取基因组DNA。应用PCR扩增肌特异性受磷蛋白基因片段,经测序检测基因突变的存在。结果显示60例扩张型心肌病人受磷蛋白基因开放阅读框未发现突变,仅有两例患者出现阅读框3′部分非翻译区分别离终止密码153和173位单个碱基T的缺失。两例患者终止密码后非翻译区单个碱基T的缺失据分析并无实际意义。因此我们认为绝大部分中国人扩张型心肌病的发病可能与受磷蛋白基因突变无关。Abstract: Phospholamban (PLB) is a prominent regulator of myocardial contractility and a reversible inhibitor of the cardiac sarcoplasmic reticulum Ca2+ ATPase activity. In normal cardiac muscles, phospholamban can be phosphorylated at distinct sites by various protein kinases and release its inhibition to sarcoplasmic reticulum Ca2+ ATPase. The studies of pedigrees have shown dilated cardiomyopathy (DCM) is related with mutation of PLB. The aim of present study is to investigate the relationship between mutation of PLB gene and DCM. Sixty patients with idiotic DCM were enrolled in present study. The clinical data were collected, including clinical symptoms, ECG and echocardiography. Peripheral blood samples of all these subjects were collected to extract genome DNA. The fragments of PLB gene were amplified by PCR and PCR fragment sequencing was performed to study weather mutation of phospholamban gene exists. phospholamban gene did not show any mutation in these patients. Most Chinese DCM patients may not be related with mutation of PLB gene.     

The Study of Cu and Zn Serum Levels in Idiopathic Dilated Cardiomyopathy (IDCMP) Patients and its Comparison with Healthy Volunteers

Changes in the cupper (Cu) and zinc (Zn) concentrations have been reported previously in idiopathic dilated cardiomyopathy (IDCMP). As a result of controversial results, the aim of this study was to compare the Zn and Cu concentrations and Zn/Cu ratio of IDCMP patients to healthy volunteers. In addition, the correlation of Cu and Zn levels with age has been evaluated. The study population consisted of 18 IDCMP patients and 27 healthy volunteers. IDCMP patients had normal angiography with echocardiography supporting cardiomyopathy without pericardial and valvular diseases. Exclusion criteria were renal or hepatic insufficiency, alcohol usage, and intake of supplements containing Cu or Zn within 1 week ago. Cu and Zn levels have been assayed with atomic absorption spectrophotometry. Statistical analysis was performed with SPSS 10 software with independent sample t test for comparing the level of Cu and Zn of IDCMP patients with normal subjects and Pearson correlation to determine the correlation between numeric data. P < 0.05 was considered as significant differences. There was a trend for a lower Zn level in IDCMP patients compared to healthy volunteers. (0.97 ± 0.25 mg/l vs. 1.12 ± 0.42 mg/l, respectively). The mean Cu levels of IDCMP and normal subjects were 1.33 ± 0.20 mg/l and 1.31 ± 0.23 mg/l, respectively. There was a significant difference in Zn/Cu ratio among patients based on the NYHA classification of heart failure (P = 0.003). Age was negatively correlated with Zn levels in IDCMP group (P = 0.037) and positively with Cu levels in healthy volunteers (P = 0.012). A lower Zn level in IDCMP patients compared to healthy volunteers and specially a significant difference in Zn/Cu ratio of patients based on their NYHA classification would suggest a critical role of zinc and Cu imbalance in development of IDCMP.     

药物性肝衰竭临床特点及预后有关因素分析

目的：探讨药物性肝衰竭的病因、临床特征及预后相关因素,提高对药物性肝衰竭的认识,减少不良事件发生的几率。方法：对2007年1月至2011年12月我院56例药物性肝衰竭患者进行回顾性分析,对患者用药情况、临床表现、肝衰竭的分型、并发症的发生、生化指标的特点及治疗与预后进行相关性分析。结果：导致肝衰竭前三位的药物分别是中药占30.3%、抗结核药占26.8%和非甾体类抗炎药占23.2%。发病时常见的临床表现为乏力64.2%、纳差60.7%、尿黄60.7%。并发症发生率最高的是感染73.2%、其次为肝性脑病66.1%、腹水64.3%。感染部位以腹腔最常见,占46.4%,其次为肺部41%。治愈好转者为18例（26.2%）,治疗无效者14例（25.0%）;死亡者为24例（42.9%）。从患者发病到死亡的中位时间为35天。治愈好转组的肝性脑病和消化道出血的发生率明显低于无效死亡组,激素治疗与好的预后密切相关（P〈0.05）。结论：药物性肝衰竭的主要致病药物有中药、抗结核药和解热镇痛药。患者的临床表现无明显特异性,肝性脑病和消化道出血一旦出现提示预后差。在疾病早期采用适当的激素治疗,可以明显改善肝衰竭患者的预后。     

血流向量图评价扩张性心肌病患者左室收缩功能的研究

目的：应用血流向量图（VFM）对扩张性心肌病（DCM）患者收缩期左室心腔血液流场变化情况进行检测,初步探讨VFM技术在评价DCM患者左心室收缩功能方面的临床价值。方法：选择临床诊断为DCM患者30例作为病例组,另选30例体检健康者作为对照组。在血流向量图条件下测量两组取样线上收缩期负向总流量（SystoleQ-,SQ-）在涡流条件下测量涡流的最大流量（Qmax）、半值面积（S）、涡流半径（r）以及涡流强度（Qmax／S）,并比较两组差异。应用Simpson双平面法获取左心室射血分数（EF）,并与SQ-、Qmax／S进行相关性分析。结果：两组比较病例组基底段、中间段、心尖段收缩期负向总流量SQ-、两组组内比较基底段、中间段、心尖段收缩期负向总流量SQ．均呈逐渐递减变化趋势（P均〈0．01）。收缩期涡流最大流量Qmax及涡流强度Qmax／S测值均低于对照组（P〈0．01）;收缩期涡流半值面积S、涡流半径r均大于对照组（P〈0．01）：Qmax／S与EF呈正相关,（r=0．78,P〈0．01）;结论：VFM技术可以定量分析DCM患者左室心腔内血流流场的变化情况,有望为临床提供一种较为准确检测DCM患者左心功能的新方法。     

Dilated Cardiomyopathy Mutations and Phosphorylation disrupt the Active Orientation of Cardiac Troponin C

Cardiac troponin (cTn) is made up of three subunits, cTnC, cTnI, and cTnT. The regulatory N-terminal domain of cTnC (cNTnC) controls cardiac muscle contraction in a calcium-dependent manner. We show that calcium-saturated cNTnC can adopt two different orientations, with the “active” orientation consistent with the 2020 cryo-EM structure of the activated cardiac thin filament by Yamada et al. Using solution NMR ¹⁵N R₂ relaxation analysis, we demonstrate that the two domains of cTnC tumble independently (average R₂ 10 s⁻¹), being connected by a flexible linker. However, upon addition of cTnI_1-77, the complex tumbles as a rigid unit (R₂ 30 s⁻¹). cTnI phosphomimetic mutants S22D/S23D, S41D/S43D and dilated cardiomyopathy- (DCM-)associated mutations cTnI K35Q, cTnC D75Y, and cTnC G159D destabilize the active orientation of cNTnC, with intermediate ¹⁵N R₂ rates (R₂ 17–23 s⁻¹). The active orientation of cNTnC is stabilized by the flexible tails of cTnI, cTnI_1-37 and cTnI_135-209. Surprisingly, when cTnC is incorporated into complexes lacking these tails (cTnC-cTnI_38-134, cTnC-cTnT_223-288, or cTnC-cTnI_38-134-cTnT_223-288), the cNTnC domain is still immobilized, revealing a new interaction between cNTnC and the IT-arm that stabilizes a “dormant” orientation. We propose that the calcium sensitivity of the cardiac troponin complex is regulated by an equilibrium between active and dormant orientations, which can be shifted through post-translational modifications or DCM-associated mutations.     

Dyssynchronous Ventricular Activation in Asymptomatic Wolff-Parkinson-White Syndrome: A Risk Factor for Development of Dilated Cardiomyopathy

A subset of children and adults with Wolff-Parkinson-White (WPW) syndrome develop dilated cardiomyopathy (DCM). Although DCM may occur in symptomatic WPW patients with sustained tachyarrhythmias, emerging evidence suggests that significant left ventricular dysfunction may arise in WPW in the absence of incessant tachyarrhythmias. An invariable electrophysiological feature in this non-tachyarrhythmia type of DCM is the presence of a right-sided septal or paraseptal accessory pathway. It is thought that premature ventricular activation over these accessory pathways induces septal wall motion abnormalities and ventricular dyssynchrony. LV dyssynchrony induces cellular and structural ventricular remodelling, which may have detrimental effects on cardiac performance. This review summarizes recent evidence for development of DCM in asymptomatic patients with WPW, discusses its pathogenesis, clinical presentation, management and treatment. The prognosis of accessory pathway-induced DCM is excellent. LV dysfunction reverses following catheter ablation of the accessory pathway, suggesting an association between DCM and ventricular preexcitation. Accessory pathway-induced DCM should be suspected in all patients presenting with heart failure and overt ventricular preexcitation, in whom no cause for their DCM can be found.