【作者】 袁建松；

【导师】 乔树宾； 张岩； 田月琴； 尤士杰； 吕秀章；

【作者基本信息】 中国协和医科大学 ， 心血管内科， 2007， 博士

【摘要】 目的研究中国人家族性肥厚型心肌病（HCM）的致病基因突变位点，分析基因型与临床表型的相互关系。方法对3个家族性HCM的先证者进行β-肌球蛋白重链基因（β-MHC）扫描，聚合酶链反应（PCR）扩增其功能区外显子片段，双脱氧末端终止法测序。对阳性测序结果者进行家系中其他成员筛查，并分析患者临床表型特点。结果在其中1个家系发现Val606Met杂合突变，而正常对照组同一位置未见异常，属于在我国HCM家系中首次发现。结论MYH7基因16号外显子Val606Met错义突变为我国家族性HCM的致病基因之一。其临床表型的异质性提示多因素参与了HCM的发生及外显。目的评价室间隔化学消融术治疗肥厚梗阻型心肌病在术后急性期和远期的效果方法对72例确诊肥厚梗阻型心肌病患者进行经皮室间隔化学消融术治疗（PTSMA），术前、术后急性期、术后远期进行超声心动观察。结果59例患者介入治疗成功，成功率为81．9％。术前超声观察室间隔平均厚度22．40±5．02mm，LVOTPG 97．88±40．91mmHg，术后急性期（3-7天）室间隔平均厚度20．73±4．53mm，与术前比变薄，p<0．05；LVOTPG 50．96±37．92mmHg，较术前明显降低，p<0．001。术后远期（6个月）室间隔平均厚度16．48±4．42mm，与术前比变薄，p<0．05；LVOTPG 41．35±29．97mmHg，较术前明显降低，p<0．001。结论经皮室间隔化学消融术（PTSMA）治疗肥厚梗阻型心肌病，在急性期和术后远期可使室间隔平均厚度降低，收缩期左室流出道压力阶差显著下降。目的1．评价多巴酚丁胺激发试验在肥厚型心肌病激发试验的安全性及有效性。2．比较潜在型肥厚梗阻型较静息型肥厚梗阻型心肌病患者临床特点。方法对22例确诊肥厚型心肌病患者（LVOTPG正常或轻度增加）进行多巴酚丁胺激发试验，并对其临床特点与57例静息型肥厚梗阻型患者相比较。结果16例（72．72％）患者达到阳性标准；6例（27．27％）患者虽达到阴性标准，但LVOTPG也有显著升高。潜在型较静息型肥厚梗阻型心肌病两类患者多数指标类似，但SAM现象发生率低，MaronⅡ型占50％。结论1．在肥厚型心肌病激发试验中，小剂量多巴酚丁胺负荷超声是一较为安全、敏感性高的方法。2．潜在型较静息型肥厚梗阻型心肌病患者，SAM现象发生率低，MaronⅡ型占优势。目的：应用多普勒组织成像脉冲速度模式测量室间隔、后壁和二尖瓣环各点速度，以评价肥厚梗阻型心肌病患者在PTSMA前后左室收缩舒张功能的改变。材料和方法：在PTSMA术前和术后急性期对肥厚梗阻型心肌患者分别测量室间隔、后壁和二尖瓣环各点收缩期和舒张期早期和舒张晚期峰值速度。结果：肥厚型心肌病患者术后急性期室间隔、后壁和二尖瓣环各点收缩期、舒张期早期峰值速度均较术前减低，有显著性差异。舒张晚期峰值也较术前减低，大部分有显著性差异。结论：肥厚型心肌病患者PTSMA术后急性期左室长轴收缩功能及主动松弛功能较术前减低。目的使用对比增强MRI评价HOCM患者PTSMA消融范围及影响因素方法对我院30例确诊肥厚梗阻型心肌病患者进行经皮室间隔化学消融术治疗（PTSMA），并于术前、术后急性期（3-7天）进行MRI观察，分别进行常规扫描和电影序列各室壁与心腔结构，观察消融区域，以及消融范围与其它因素的关系。结果术后急性期所有患者延迟扫描可见室间隔有不同程度高密度区，平均消融重量35．1±18．04g，消融重量与酒精用量正相关（r=0．608，p=0．036）结论使用对比增强MRI可准确描述消融范围，消融范围主要与酒精用量正相关。目的了解HOCM患者行PTSMA前、后心肌灌注和心肌代谢的变化。方法对31例HOCM患者进行了在PTSMA术前⁹⁹Tc^m MIBI灌注显像和¹⁸F-FDG代谢显像，其中15例进行术后急性期⁹⁹Tc^mMIBI灌注显像和¹⁸F-FDG代谢显像复查，以半定量记分法评价各室壁节段灌注和代谢变化情况。结果在⁹⁹Tc^m-MIBI SPECT灌注显像，28例（90．3％）HOCM患者PTSMA术前室间隔放射性浓聚，PTSMA术后12例HOCM患者（80％）室间隔灌注有不同程度的减低，¹⁸F-FDG代谢显像在PTSMA术前17例（54．83％）表现代谢异常，术后5例（33．3％）代谢异常降低，以间隔后段最为明显。结论⁹⁹Tc m-MIBI SPECT灌注显像可作为评价PTSMA术后效果的重要手段。¹⁸F-FDG代谢显像有重要的参考价值。目的评价HOCM患者PTSMA前后自主神经系统的功能。方法72例确诊肥厚梗阻型心肌病患者进行经皮室间隔化学消融术治疗（PTSMA），并于术前、术后急性期（3-7天）、术后6个月进行Holter检查和超声心动图观察。对照组62例进行1次检查，病例组在PTSMA术前及术后3-7天、术后6个月以上各进行1次检查，对SDNN、SDNN指数、pNN50、RMSSD等指标进行测定，并分别记录白天（5：00-23：00）与夜间（23：00-5：00）数值。结果HOCM患者HRV较正常人降低明显，在PTSMA术后急性期有进一步的降低，在PTSMA术后远期，HOCM患者的HRV指标近似术前甚至有所提高室间隔厚度、LVOTPG与心率变异度各指标无明确相关关系。结论心率变异度在HOCM患者HRV各时域指标对PTSMA有一定预测价值，本研究未显示HRV与HOCM各项指标如LVOTPG室间隔厚度有相关关系。更多还原

【Abstract】 Objective To study the disease-causing gene mutation in Chinese with hypertrophic cardiomyopathy（HCM）, and to analyze the correlation between the genotype and phenotype. Methods Samples of peripheral blood were collected from three Chinese families with HCM in whose families at least two HCM patients existed. The exons in the functional regions of the beta myosin heavy chain gene（MYH7） were amplified with PCR and the products were sequenced. Results A Val606Met missen mutation was identified in the exon 16 of MYH7 gene in a Chinese family . One hundred and twenty patients as controls were normal in the genetic test. Conclusion The Val606Met missen mutation may be a benign mutation in Chinese HCM. In one family, the identical mutation has different phenotypes and prognoses. The heterogeneity of phenotype suggests that multiple factors might be involved in the pathogenesis. Object: Gauging the acute effect of Percutaneous transluminal septal myocardial ablation （PTSMA） as a treatment for hypertrophic obstructive cardiomyopathy （HOCM）.Methods: PTSMA was performed in seventy -two patients with symptomatic HOCM. All patients had echocardiography performed before the procedure, three to seven days and six months after the procedure.Results: Procedure success was achieved in forty-one patients, success rate was 81.9%.The average left ventricular outflow tract （LVOT） gradient was 97.88±40.91 mmHg before the procedure, 50.96±37.92mmHg three to seven days post-PTSMA （p<0.001） and 41.35±29.97mmHg six month post-PTSMA（p<0.001）. The thickness0 of inter ventricular septum （IVS） was 22.96±5.15 mm before the procedure, 20.73±4.53mm three to seven days post-PTSMA （p < 0.05） and 16.48±4.42mm six month post-PTSMA（p<0.05）. The incidence of right bundle branch block development post-PTSMA was 19.4% （>48hour） , and one patient（1.38%） had complete heart block. Two patients died.Conclusions: PTSMA is an effective non-surgical procedure for symptomatic patients with HOCM because of its low risk and its significant hemodynamic and echocardiographic improvement. Objects 1.To evaluate the safety and efficiency of the dobutamine stressechocardiography in the patients with hypertrophic cardiomyopathy. 2.To estimate thedifference between provokable obstruction and resting obstruction.Methods Echocardiogarphy-Doppler ultrasound measurements in twenty-two patientswith HCM（LVOTPG<50mmHg at rest） studied at rest and at the end point ofdobutamine stress.Fifty-seven patients with HCM（LVOTPG>50mmHg at rest）werealso studied at rest.Results Sixteen patients had positive result at the end point of dobutamine stress.Themain difference between the provokable obstruction and resting obstruction was thatin provokable obstruction patients,the SAM positive patients were fewer and theproportion of MaronⅡpatients was 50%.Conclusions Dobutamine stress echocardiography was a safe and sensitive way for the patients with hypertrophic cardiomyopathy. In provokable obstruction patients,the SAM positive patients are fewer and the proportion of MaronⅡpatients was higher. Objective To evaluate the left ventricular function in patients with hypertrophic obstructive cardiomyopathy（HOCM） before and after the PTSMA procedure. Methods The velocity of mitral annulus was measured by Doppler tissue pulsed wave mode. Doppler tissue imaging（DTI）Was obtained from the apical window at 4-chamber,2-chamber, and long apical views to measure Ea, Aa, Sa,respectively. The DTI data of HOCM patients before the PTSMA procedure were compared with the data after the PTSMA procedure. Results There were differences in systolic myocardial velocities of mitral annulus（Sa） ,early diastolic myocardial velocities of mitral annulus（Ea） and late diastolic myocardial velocities of mitral annulus（Aa） before the PTSMA and after the PTSMA . Sa and Ea were higher before than those after the procedure. Conclusions Relaxation and systolic function of the left ventricle decrease in patients with HOCM who underwent PTSMA after several days. Objective To evaluate myocardial infarction induced by percutaneous transluminal septal myocardial ablation （PTSMA） in symptomatic patients with hypertrophic obstructive cardiomyopathy using contrast-enhanced （CE） magnetic resonance imaging （MRI）.Methods Cine and CE MRI were performed before and three to seven days after PTSMA in thirty patients. Results Three to seven days after PTSMA, regional hyper enhancement was visualized in the basal interventricular septum in all patients. Mean infarction size was 35.1±18.04g. Volume of ethanol administered correlated well with infarction size（r=0.608, p=0.036） and peak creatine phosphokinase-MB （r=0.762 p=0.01）. Conclusions Contrast-enhanced MRI can evaluate the size and location of septal myocardial infarction induced by PTSMA precisely. Infarction size correlated well with ethanol volume. Object: To evaluate myocardial perfusion and metabolism functions influenced byPTSMA.Methods: ⁹⁹Tc^mMIBI and ¹⁸F-FDG Images were performed in 31HCM patientsbefore and in 14 patients 3-7days after PTSMA. Analysis the images in different LVsegments by using scores.Results: In ⁹⁹Tc ^m MIBI images, uptake decreased at the septal regions in most of theHCM patients after PTSMA, ¹⁸F- FDG Images also showed decreased uptake at theseptal regions in most of the HCM patients after PTSMA.Conclusions: ⁹⁹Tc ^mMIBI images might be an important method to evaluate PTSMAresults, ¹⁸F-FDG images showed important value as reference. Object Assess the autonomic function in hypertrophic Obstructive cardiomyopathy（HOCM） patients who underwent PTSMA through heart rate variability （HRV）.Methods HRV were performed in Seventy-two HOCM patients before PTSMA,three to seven days and 6 month after PTSMA. Six-two volunteers also underwentHRV test as controls. Time domain variables were obtained at daytime and nightrespectively.Results HRV was shown to be lower in HOCM patients before PTSMA, and becameeven lower three to seven days after PTSMA. Six month after PTSMA ,HRV inHOCM patients seemed recovered, analysis showed no difference between HOCMpatients and controls.Conclusions HRV showed its value on gauging autonomic stimulatic function in HCM patients who underwent PTSMA; no correlation was found between HRV and LVOTPG.更多还原