连锁分析血管紧张素转换酶基因插入/缺失多态性和血管紧张素原 M235T基因多态性与肥厚型心肌病的关系

目的 连锁分析中国人群血管紧张素转换酶（ACE）基因插入／缺失多态性及血管紧张素原（AGT）M235T基因多态性与肥厚型心肌病（HCM）发病的关系。方法 对63例HCM患分别用PCR法检测ACE基因插入／缺失和AGT M235T基因多态性。结果 HCM患中ACE DD＋AGT TT基因型的比数比高于单基因型,其心脏事件发生率高于其他基因型组合和AGT TT型。结论 同时具有ACE DD＋AGT TT基因型,较单基因型发生HCM的风险率显增高;同时具有ACE DD＋AGT TT基因型的HCM患发生心脏事件的危险更大。     

血管紧张素原基因M235T多态性与肥厚型心肌病及高血压性心肌肥厚的关系

血管紧张素原 (AGT)基因的多态性与心血管疾病的关系日益引起重视。在中国人群中 ,高血压性心肌肥厚 (HCH)和肥厚型心肌病 (HCM)在AGT基因多态性方面有何异同的研究尚少 ,本研究旨在探讨AGT基因M2 35T多态性与HCM及HCH的关系。1.资料与方法 :( 1)研究对象 :HCM组 ,40例 ,汉族 ,男2 2例、女 18例 ,平均年龄 ( 5 3 4± 19 8)岁 ,诊断符合临床和超声心动图标准 ,除外家族性遗传及高血压病、瓣膜病、先天心脏病等所致心肌肥厚 ;HCH组 ,5 0例 ,汉族 ,男 2 8例、女2 2例 ,平均年龄 ( 6 0 8± 14 5 )岁 ,高血压诊断标准符合 1978年WH…     

血管紧张素原基因多态性与心血管疾病

血管紧张素原(AGT)基因的多态性与心血管病的研究很多,但二者的关系复杂且不同的研究所得结果也不一致。本文综述了AGT基因的多态性与肥厚型心肌病、二尖瓣脱垂、心房颤动、高血压病及冠心病关系的研究概况。     

血管紧张素原基因M235T多态性与胃癌的相关性

目的 探讨血管紧张素原(AGT)基因M235T多态性与中国人群胃癌易感性的关系.方法 采用聚合酶链反应-限制性片段长度多态性方法检测168例胃癌组和211例健康对照组AGT基因M235T多态性.结果 胃癌组与对照组AGT基因M235T基因型和等位基因分布差异不显著(P＞0.05).根据临床病理特征进行分层分析,发现低分化胃癌患者中TT基因型频率明显高于高中分化胃癌患者(P=0.021)；AGT M235T多态性与胃癌临床分期及转移状态之间无显著差异(P＞0.05).结论 ACT M235T多态性与中国人群胃癌分化程度等临床病理特征密切相关.     

血管紧张素原基因多态性与高血压关系的研究

目的研究中国人血管紧张素原基因多态性与原发性高血压的关系。方法应用聚合酶链反应对天津地区１１２例正常人及１３１例高血压患者ＡＧＴ基因２３５位点限制酶切片段长度多态性进行检测。结果ＡＧＴ基因２３５位点有三种基因型为ＴＴ、ＴＣ、ＣＣ，其中ＣＣ基因型与高血压发病相关，高血压组Ｃ基因频率高于对照组（Ｐ＝０．０３２）。结论ＣＣ基因型与Ｃ等位基因可作为高血压易感性的指标     

血管紧张素原基因和血管紧张素转换酶基因多态性与高血压

目的　研究中国人群中血管紧张素原 (AGT)基因单核苷酸多态性 (SNP)及血管紧张素转换酶 (ACE)基因插入 /缺失多态与高血压病的关系。方法　在 3 4 5例高血压病患者与 2 0 6名血压正常人中采用PCR RFLP法检测AGT基因A 2 0C ,A 6G和M 2 3 5T的多态性 ,用PCR法检测ACE基因 16内含子Alu片段插入 /缺失多态 ,同时用EM算法进行两位点连锁不平衡分析。结果　在M 2 3 5T和A 2 0C ,M 2 3 5T和A 6G ,A 2 0C和A 6G位点观察到了连锁不平衡 (P <10 - 4)。病例 对照检验显示T2 3 5等位基因频率在高血压组中高于对照组 ,且高血压病患者中ACE (DD +ID) +AGT TT2 3 5基因型频率高于对照组。结论　受检人群中AGT基因各多态频率处于两两连锁不平衡 ,但AGT基因即T2 3 5位点以隐性作用方式与高血压关联 ,T2 3 5等位基因与ACE D等位基因在高血压病发生中具协同作用     

血管紧张素转化酶基因缺失多态性与肥厚型心肌病的关系

为探讨血管紧张素转化酶（ＡＣＥ）基因缺失／插入多态性与肥厚型心肌病（ＨＣＭ）发病的关系，对３５例ＨＣＭ患者进行了检测。结果证实ＡＣＥ基因缺失多态性与ＨＣＭ发病相关，并进一步发现前者还与左心室重量指数相关，为临床运用ＡＣＥ抑制剂治疗ＨＣＭ提供依据。     

血管紧张素原基因启动子区域单核苷酸多态性与心肌梗死的相关性

为研究血管紧张素原基因启动子区域 - 2 17、- 2 0位和 - 6位上的三种单核苷酸多态性与心肌梗死的相关性 ,采用多重SnaPshot反应 ,在中国南方汉人群中 ,对 2 16例心肌梗死患者和 185名健康对照者进行G 2 17A ,A 2 0C和G 6A多态基因分型。结果发现 ,G 2 17A多态AA、AG和GG基因型分布和A、G等位基因频率在心肌梗死组与对照组之间相比有显著性差异 (分别为 10、77、12 9比 8、37、14 0 ,P =0 .0 0 2 ;2 2 .4 5 %、77.5 5 %比 14 .32 %、85 .6 8% ,P=0 .0 0 3)。G 6A多态AA、AG和GG基因型分布在心肌梗死组和对照组之间亦有显著性差异 (分别为 14 7、6 4、5比12 7、4 4、14 ,P =0 .0 2 9) ,但A、G等位基因频率在两组间无显著性差异 (P =0 .394 )。A 2 0C多态CC、AC和AA基因型分布在两组间有差异 (分别为 6、5 1、15 9比 2、6 1、12 2 ) ,但无统计学意义 (P =0 .0 6 7) ,C、A等位基因频率在两组间亦无显著性差异 (P >0 .0 5 )。Logistic回归分析发现 ,年龄 (P =0 .0 0 1)、收缩压 (P =0 .0 13)和血浆甘油三酯浓度 (P =0 .0 10 )是该人群发生心肌梗死的独立危险因素 ,而高密度脂蛋白胆固醇 (P =0 .0 18)是一种保护因素。结果提示 ,在中国南方汉人群中 ,血管紧张素原基因G 2 17A和G 6A多态可能与心肌梗死的发生     

血管紧张素原基因多态性与慢性心力衰竭的相关性研究

目的探讨血管紧张素原基因(AGT)多态性与慢性心力衰竭(CHF)发病的关系。方法应用聚合酶链反应-限制性片段长度多态性技术检测2004年4月至2005年12月珠海市3家医院的111例CHF患者和110名健康对照者的AGT基因M235T多态性并进行统计学比较。结果共检测出3种AGT基因型,分别为MM型、MT型和TT型。CHF患者TT基因型频率高于对照组,在老年病例与对照组间,差异具有统计学意义(P=0.042)。与非TT型者相比,老年TT型者发生CHF的相对风险率为3.367。结论AGT基因M235T多态性与CHF的发生相关,TT基因型可能是该地区老年人群CHF发病的遗传危险因素。     

血管紧张素原基因M235T多态性与心血管疾病

近年来,越来越多的研究结果表明血管紧张素原基因M235T多态性与心血管疾病密切相关,通过对二者关系的研究,我们可以从分子水平上探讨心血管疾病的病因,从而为心血管疾病的防治提供新的思路。现对这一研究现状作一综述。     

Long‐term outcomes for different surgical strategies to treat left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Aims

Surgical intervention is used to treat dynamic left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy. This study assesses the effect of different surgical strategies on long‐term mortality and morbidity.

Methods and results

In total, 347 patients underwent surgical intervention for LVOTO (1988–2015). Group A (n = 272) underwent septal myectomy; Group B (n = 33), septal myectomy and mitral valve (MV) repair; Group C (n = 22), myectomy and MV replacement; and Group D (n = 20), MV replacement alone. Median follow‐up was 5.2 years (interquartile range 1.9–7.9). The mean resting LVOT gradient improved post‐operatively from 71.9 ± 39.6 mmHg to 13.4 ± 18.5 mmHg (P < 0.05). Overall, 72.4% of patients improved by >1 New York Heart Association (NYHA) class; 58.9% of patients undergoing MV replacement alone did not improve their NYHA class. There were 5 perioperative deaths and 20 late deaths (>30 days). Survival rates at 1, 5 and 10 years respectively were 98.4, 96.9, 91.9% in Group A; 97.0, 92.4, 61.6% in Group B; 100.0, 100.0, 55.6% in Group C; and 94.7, 85.3, 85.3% in Group D (log‐rank, P < 0.05). Long‐term (>30 days) complications included atrial fibrillation (29.6%), transient ischaemic attack/stroke (2.4%) and heart failure hospitalisation (3.2%). There were 16 repeat surgical interventions at 3.0 years.

Conclusion

Septal myectomy is a safe procedure resulting in symptomatic improvement in the majority of patients. The annual incidence of non‐fatal disease‐related complications after surgical treatment of LVOTO is relatively high. Patients who underwent MV replacements had poorer outcomes with less symptomatic benefit in spite of a similar reduction in LVOT gradients.

     

Mitral valve remodeling in the development of obstructive hypertrophic cardiomyopathy

Approximately 2/3 of patients with hypertrophic cardiomyopathy (HCM) have significant left ventricular outflow tract obstruction (LVOTO), which is caused by the interaction mitral valve apparatus and the hypertrophied septum. The contribution of mitral valve remodeling to the development of obstruction over time has never been described. We analyzed retrospectively 40 patients with HCM and no baseline obstruction followed up for a median of 2179 days. At follow up, 13 patients developed significant LVOTO. Patients who developed LVOTO had longer posterior leaflets and longer anterior leaflet residual length.     

Pharmacological treatment of hypertrophic cardiomyopathy: current practice and novel perspectives

Hypertrophic cardiomyopathy (HCM) is entering a phase of intense translational research that holds promise for major advances in disease‐specific pharmacological therapy. For over 50 years, however, HCM has largely remained an orphan disease, and patients are still treated with old drugs developed for other conditions. While judicious use of the available armamentarium may control the clinical manifestations of HCM in most patients, specific experience is required in challenging situations, including deciding when not to treat. The present review revisits the time‐honoured therapies available for HCM, in a practical perspective reflecting real‐world scenarios. Specific agents are presented with doses, titration strategies, pros and cons. Peculiar HCM dilemmas such as treatment of dynamic outflow obstruction, heart failure caused by end‐stage progression and prevention of atrial fibrillation and ventricular arrhythmias are assessed. In the near future, the field of HCM drug therapy will rapidly expand, based on ongoing efforts. Approaches such as myocardial metabolic modulation, late sodium current inhibition and allosteric myosin inhibition have moved from pre‐clinical to clinical research, and reflect a surge of scientific as well as economic interest by academia and industry alike. These exciting developments, and their implications for future research, are discussed.     

Long term exercise capacity in patients with hypertrophic cardiomyopathy treated with percutaneous transluminal septal myocardial ablation

BACKGROUND: In hypertrophic obstructive cardiomyopathy, percutaneous transluminal septal myocardial ablation (PTSMA) improves functional capacity in the short term. However, long term functional capacity is unknown. AIM: To assess the long term exercise capacity of patients with hypertrophic obstructive cardiomyopathy undergoing PTSMA. METHODS: Twenty three patients (56.5% male, mean age 44.5+/-13.6 years) who underwent PTSMA were included. All patients had also undergone a symptom limited cardiopulmonary exercise treadmill test before the procedure, then after 3 months (early follow-up) and after a mean 7.2+/-1.0 years (long term follow-up). RESULTS: Before PTSMA, mean maximal pressure gradient in the left outflow tract (LVOTGmax) was 82+/-29 mmHg, 17 patients had NYHA functional class> or = III and peak oxygen uptake (pVO2) was 18+/-4 ml/kg/min. PTSMA led to a reduction in mean LVOTGmax (to 29+/-19 mmHg, p<.0001), improvement of heart failure symptoms (NYHA> or =III in 1 patient, p<.0001) and an increase of pVO2 (to 22+/-6 ml/kg/min, p=.0002) at short term. LVOTGmax, functional class and pVO2 did not change significantly during long term follow-up compared to early follow-up. However, there was a continuous improvement in percentage predicted pVO2 over time. CONCLUSIONS: In patients with hypertrophic obstructive cardiomyopathy and symptoms of heart failure, PTSMA leads to stable long term improvement of objectively measured exercise capacity.     

A novel approach in the use of radiofrequency catheter ablation of septal hypertrophy in hypertrophic obstructive cardiomyopathy

ObjectiveAlcohol septal ablation (ASA) is a therapeutic alternative to surgical myectomy in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, the anatomical variability of the septal branch, risk of complete heart block, and late onset ventricular arrhythmias are limitations to its therapeutic usage. There is recent interest in the use of radiofrequency catheter ablation (RFCA) as a therapeutic option in HOCM. We aimed to assess the safety and efficacy of RFCA in the treatment of symptomatic HOCM.MethodsSeven patients with symptomatic HOCM (mean age 43.7 ± 15.6 years, five males), and significant left ventricular outflow tract (LVOT) gradient despite optimal drug therapy, underwent ablation of the hypertrophied interventricular septum. These patients had unfavorable anatomy for ASA. Ablation was performed under 3D electro-anatomical system guidance using an open irrigated tip catheter. The region of maximal LV septal bulge as seen on intracardiac echocardiography was targeted. Patients were followed up at 1, 6, and 12 months post-procedure.ResultsThe mean baseline LVOT gradient by Doppler echocardiography was 81 ± 14.8 mm of Hg which reduced to 48.5 ± 22.6 (p = 0.0004), 49.8 ± 19.3 (p = 0.0004), and 42.8 ± 26.1 mm of Hg (p = 0.05) at 1, 6, and 12 months respectively. Symptoms improved at least by one NYHA class in all but one patient. One patient developed transient pulmonary edema post-RFA. There were no other complications.ConclusionRFCA of the hypertrophied septum causes sustained reduction in the LVOT gradient and symptomatic improvement among patients with HOCM. Electroanatomical mapping helps to perform the procedure safely.     

Hypertrophic cardiomyopathy in 2013: Current speculations and future perspectives

Hypertrophic cardiomyopathy (HCM), the most variable cardiac disease in terms of phenotypic presentation and clinical outcome, represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance. To date, more than 1400 mutations of myofilament proteins associated with the disease have been identified, most of them “private” ones. This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations. Additionally, topics pertaining to patients’ everyday lives, such as sudden cardiac death (SCD) risk stratification and prevention, along with disease prognosis, are grossly related to the genetic variation of HCM. This review incorporates contemporary research findings and addresses major aspects of HCM, including preclinical diagnosis, genetic analysis, left ventricular outflow tract obstruction and SCD. More specifically, the spectrum of genetic analysis, the selection of the best method for obstruction alleviation and the need for a unique and accurate factor for SCD risk stratification are only some of the controversial HCM issues discussed. Additionally, future perspectives concerning HCM and myocardial ischemia, as well as atrial fibrillation, are discussed. Rather than enumerating clinical studies and guidelines, challenging problems concerning the disease are critically appraised by this review, highlighting current speculations and recommending future directions.     

肥厚型梗阻性心肌病患者行左心室流出道疏通术的麻醉管理

目的:总结肥厚型梗阻性心肌病(HOCM)患者行左心室流出道疏通术的麻醉管理经验。方法:70例HOCM患者在全身麻醉体外循环下行左心室流出道疏通术,麻醉诱导和麻醉维持采用咪达唑仑、丙泊酚、异氟烷、芬太尼和哌库溴铵,术中持续监测ECG、HR、脉搏血氧饱和度(SPO2)、有创动脉血压(IBP)、中心静脉压(CVP)、心输出量(CO)、心脏排血指数(CI)、外周血管阻力(SVR)、肺血管阻力(PVR)及平均肺动脉压(MPAP)。术中部分患者使用艾司洛尔、去氧肾上腺素及地尔硫卓等维持血液动力学平稳。结果:术中血液动力学平稳,无严重心律失常发生,全组均顺利完成手术。结论:麻醉管理的关键在于①以适度的麻醉深度避免抑制心肌收缩力;②维持正常的心率和血压,酌情使用增强心肌收缩力的药物;③维持好前后负荷,避免使用血管扩张药;     

氨基末端B型脑钠肽前体与非梗阻性肥厚型心肌病患者左心室舒张功能的相关性研究

目的探讨血浆氨基末端B型脑钠肽前体(NT-proBNP)水平与非梗阻性肥厚型心肌病(HNCM)患者左心室舒张功能的关系。方法选择46例HNCM患者,20名健康体检者作为对照组,电化学发光法检测两组血浆NT-proBNP水平,超声心动图、组织多普勒显像(TDI)检测室间隔厚度、射血分数和反映左心室舒张功能的参数。结果HNCM组患者平均NT-proBNP血浆水平明显高于对照组(P<0.001);NT-proBNP血浆水平与以下左心室舒张功能参数均呈正相关:二尖瓣室间隔侧舒张早期最大运动速度e(r=0.74,P<0.001)、e与二尖瓣室间隔侧舒张晚期最大运动速度a比值e/a(r=0.69,P<0.001)、心房收缩开始至左室流出道内心室收缩期前流速开始的间期A-Ar(r=0.63,P=0.029)、Tei指数(r=0.63,P<0.001)、肺静脉频谱收缩期肺静脉血流速度S与舒张期肺静脉血流速度D的比值S/D(r=0.62,P<0.001)、等容舒张时间(IVRT)(r=0.56,P<0.001)、二尖瓣血流频谱舒张早期充盈峰值速度E(r=0.54,P<0.001)、a(r=0.53,P<0.001)、二尖瓣血流频谱舒张晚期充盈峰值流速A(r=0.36,P=0.02)、E/A(r=0.47,P<0.001)。多因素Logistic回归分析显示,e/a、S/D是NT-proBNP血浆水平的独立影响因素。结论NT-proBNP血浆水平与超声心动图左心室舒张功能参数间存在明显的正相关性,可以作为评价HNCM患者左心室舒张功能不全的客观指标。     

WJC 6~th Anniversary Special Issues(3):Cardiomyopathy Hypertrophic cardiomyopathy in 2013:Current speculations and future perspectives

Hypertrophic cardiomyopathy(HCM),the most variable cardiac disease in terms of phenotypic presentation and clinical outcome,represents the most common inherited cardiomyopathic process with an autosomal dominant trait of inheritance.To date,more than 1400 mutations of myofilament proteins associated with the disease have been identified,most of them "private" ones.This striking allelic and locus heterogeneity of the disease certainly complicates the establishment of phenotype-genotype correlations.Additionally,topics pertaining to patients' everyday lives,such as sudden cardiac death(SCD)risk stratification and prevention,along with disease prognosis,are grossly related to the genetic variation of HCM.This review incorporates contemporary research findings and addresses major aspects of HCM,including preclinical diagnosis,genetic analysis,left ventricular outflow tract obstruction and SCD.More specifically,the spectrum of genetic analysis,the selection of the best method for obstruction alleviation and the need for a unique and accuratefactor for SCD risk stratification are only some of the controversial HCM issues discussed.Additionally,future perspectives concerning HCM and myocardial ischemia,as well as atrial fibrillation,are discussed.Rather than enumerating clinical studies and guidelines,challenging problems concerning the disease are critically appraised by this review,highlighting current speculations and recommending future directions.