应变/应变率成像定量分析肥厚型心肌病患者左室功能的临床研究
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摘要
研究背景肥厚型心肌病是一种主要由10个编码心肌细胞肌小节蛋白的基因突变而引起的常染色体显性遗传性疾病。在无明显阻力及容量负荷增加的情况下,发生心肌肥厚,临床表现为晕厥、胸闷、胸痛、心律失常和猝死。但有些患者出现严重临床事件前可能并未出现症状,因而早期诊断显得尤为重要。传统的超声心动图可提供诊断肥厚型心肌病的形态学和血流动力学信息,室间隔及左室壁不均匀性增厚为最常见表现。然而,文献报道有13%~31%肥厚型心肌病患者可表现为均匀性左室肥厚,而与高血压性左室肥厚难以区分。有4%~47%的高血压性左室肥厚可表现为非均匀性左室肥厚。因此,鉴别某些肥厚型心肌病和高血压性左室肥厚成为该领域的研究热点和难点。对于肥厚型心肌病常用药物为倍他乐克,但其并不能在宏观上逆转肥厚的心肌,传统的超声心动图不能较好的评价其疗效,其有效性不很确切。因此,有必要对肥厚型心肌病患者倍他乐克治疗前后左室功能的变化进行评价。应变及应变率显像技术是新近发展的组织多普勒新技术,其时间分辨率高,能够同时定量分析多节段心肌运动,已有许多研究证实应变、应变率技术可定量研究局域左室心肌收缩、舒张功能,其测定的心肌的运动能够准确的反应心肌本身的收缩舒张特性而不受周围组织牵拉的影响。
     目的本研究运用应变/应变率成像技术研究肥厚型心肌病患者、高血压患者左室功能,旨在探讨以下问题:(1)评价应变/应变率成像技术在肥厚型心肌病和高血压患者左室功能研究中的应用价值;(2)肥厚型心肌病患者左室心肌舒缩功能的改变;(3)评价各种类型的肥厚型心肌病左室舒缩功能的改变的差异;(4)评价应变/应变率成像对心尖部肥厚型心肌病的诊断价值;(5)评价肥厚型心肌病患者局部心肌收缩功能改变与室壁厚度的相关性;(6)利用应变/应变率成像技术评价倍他乐克对肥厚型心肌病患者的疗效。
     材料与方法
     1选择受试者130例,分为以下三组:
     (1)对照组:共27例,均为健康查体者和健康志愿者,经详细询问问病史和体格检查、12导联常规心电图或24小时动态心电图检查、常规超声心动图检查、血液生化检查、肝肾功能检查等均无异常发现,排除肥厚型心肌病、高血压病、糖尿病、冠心病、肾病、及心律失常、心力衰竭病史和高血压家族史,系统检查排除器质性心脏病。其中男16例,女11例,年龄24—58岁,平均44±12岁。
     (2)肥厚型心肌病(HCM)组:共69例,均为肥厚型心肌病患者。均符合1996年WHO/IFS肥厚型心肌病的诊断标准,即经二维超声心动图测量显示以室间隔中上部肥厚为主,肥厚>15mm;左室后壁、下壁、前壁、后壁无增厚或轻度增厚,室间隔与后壁厚度之比>1.3:1,仅表现为局限于左室乳头肌水平以下的心尖部肥厚者立为心尖部肥厚型心肌病。其中男48例,女21例,年龄14—63岁,平均41±12岁。病史0—96月。根据不同的研究目的应用不同的分组标准对本组受试者进行分组:根据左室流出道的压力阶差,将本组非心尖部肥厚型心肌病受试者分为梗阻性肥厚型心肌病和非梗阻性肥厚型心肌病两组:
     ①梗阻性肥厚型心肌病(HOCM)组:通过超声心动图检查,左室流出道压力阶差≥20mmHg。共23例,其中男16例,女7例,年龄25—57岁,平均40±11岁,病史0—60月;
     ②非梗阻性肥厚型心肌病(HNCM)组:通过超声心动图检查,左室流出道压力阶差<20mmHg。共35例,其中男24例,女11例,年龄14—63岁,平均43±17岁,病史0—96月;
     ③心尖部肥厚型心肌病(APH)组:局限于左室乳头肌水平以下的心尖部肥厚者为心尖部肥厚型心肌病,共11例,其中男8例,女3例,年龄22—61岁,平均41±14岁,病史3—84月;
     为评价倍他乐克对肥厚型心肌病患者的疗效,选取肥厚型心肌病患者中心率未达标(即心率大于60次/分)者共21例,其中男13例,女8例,年龄22—63岁,平均41±15岁,在常规给予拜阿斯匹林、ACEI和合心爽的基础加用倍他乐克缓释片47.5mg治疗一月后复查超声,运用应变/应变率显像评价治疗前后左室舒缩功能的变化。
     (3)高血压组:共34例,均为高血压病患者。均符合2003年WHO/ISH高血压病诊断标准,即未服抗高血压药情况下,收缩压≥140mmHg和(或)舒张压≥90mmHg,经体格检查及相应的实验室检查排除继发性高血压。其中男21例,女性13例,年龄31—67岁,平均44±13岁,病史0—156月;
     2、仪器设备:采用美国通用电气公司生产的GE Vivid7型彩色多普勒超声显像仪,经胸探头频率1—3MHz,该机配有M型超声、二维超声、脉冲波多普勒和连续波多普勒及彩色多普勒血流显像五种基本功能,具有实时心肌组织多普勒显像、组织追踪显像及应变和应变率显像等先进的超声技术,并配有Q-analyze软件可对心肌各节段进行应变和应变率定量分析。
     3、研究方法:所有研究对象均进行经胸M型超声、二维超声、频谱多普勒及应变/应变率成像技术检查。应用经胸M型超声、二维超声测量主动脉内径、左房及左室的内径和各左室壁厚度;应用频谱多普勒测量二尖瓣血流频谱、左室舒张早期与舒张晚期的峰值流速及比值;应用频谱多普勒测量肺静脉瓣口收缩期S波与舒张早期D波的峰值流速及比值;应用应变/应变率成像技术测量左室各个壁的收缩期峰值应变εet、收缩期SRs、舒张早期SRe、舒张晚期SRa峰值应变率。
     所有的计量资料均以(?)±SD表示,计数资料的比较采用x~2,两组间参数比较采用两组独立样本资料的t检验,多组间参数比较采用ANOVA,组间两两比较采用LSD—t检验,变量间做Pearson直线相关分析。所有的数据分析都采用统计学软件包SPSS13.0进行,当P<0.05时具有统计学意义。
     结果:
     1、与正常对照组左室结构和功能相比:HCM组左房内径、室间隔和左室后壁厚度、左室射血分数、左心室重量均明显高于正常对照组(P<0.01),E/A、S/D均明显低于正常对照组(P<0.01);高血压组左房内径、室间隔和左室后壁厚度均明显高于正常对照组(P<0.01),左心室重量均高于正常对照组(P<0.05),E/A、S/D明显低于正常对照组(P<0.01);HCM组左房内径、室间隔和左室后壁厚度、左室射血分数、左心室重量均明显高于高血压组(P<0.01);
     2、HCM各组间左室结构和功能比较:梗阻性HCM组室间隔厚度、左心室重量、主动脉瓣口血流速度明显高于非梗阻性HCM组(P<0.01),左室后壁厚度,高于非梗阻性HCM组(P<0.05);心尖部HCM组室间隔厚度、左心室重量、主动脉瓣口血流速度明显低于梗阻性HCM组(P<0.01),左室后壁厚度低于梗阻性HCM组(P<0.05);心尖部HCM组与非梗阻性HCM组各指标差别无统计学意义;
     3、心尖部HCM组和正常对照组左室结构和功能指标:APH患者的左房内径、室间隔和左室后壁厚度、左室射血分数、左心室重量均明显高于正常对照组(P<0.05或P<0.01),E/A、S/D均明显低于正常对照组(P<0.05或P<0.01);
     4、与正常对照组应变、应变率的比较:HCM组各节段的εet、SRs、SRe、SRa值均显著低于正常对照组(P<0.05或P<0.01);高血压组各节段的εet,基底部、中间部和心尖部的SRe,中间部的SRs均显著低于正常对照组(P<0.05或P<0.01),心尖部的SRa高于正常对照组(P<0.05),余指标未见显著统计学差异;HCM组各节段的εet、SRs、SRe、SRa值均显著低于高血压组(P<0.05或P<0.01);
     5、HCM各组间应变、应变率指标差异:非梗阻性HCM、梗阻性HCM基底部和中间部εet、SRs、SRe显著低于心尖部HCM组(P<0.05或P<0.01),SRa较心尖部HCM减低但无统计学意义;非梗阻性HCM、梗阻性HCM心尖部εet显著高于心尖部HCM组(P<0.01),SRs、SRe、SRa高于心尖部HCM组,但无统计学差异;非梗阻性HCM组和梗阻性HCM组比较各节段的应变、应变率均无统计学差异(P>0.05);
     6、心尖部HCM组和正常对照组应变、应变率的比较:APH患者中间部和心尖部的εet、心尖部的SRs和各节段的SRe、SRa均低于正常对照组(P<0.01),差异具有统计学意义;
     7、室壁厚度与收缩期峰值应变的相关性分析:收缩期峰值应变(绝对值)与室壁厚度相关系数r=-0.783,P<0.001,呈高度负相关;
     8、心率未达标的HCM患者给予倍他乐克缓释片47.5mg治疗一个月,治疗前后左室功能指标、应变和应变率指标变化:治疗前后EF略降低,E/A、S/D比值升高,但无统计学意义;εet、SRs、SRe治疗后增加但无显著差异(P>0.05),SRa治疗后增加(P<0.05),有显著的差异。
     结论:
     1、应变及应变率成像技术可以敏感检测肥厚型心肌病左室沿长轴方向局部心肌收缩及舒张功能的异常,该技术可作为评价心肌肥厚病变早期病理及功能异常的首选方法;
     2、应变/应变率显像能够很好的区分肥厚型心肌病患者和高血压患者,早期作出确切的诊断;
     3、应变/应变率显像可以用于心尖部肥厚型心肌病的诊断;
     4、肥厚型心肌病患者的左室收缩功能的降低与心肌肥厚的程度密切负相关;
     5、肥厚型心肌病患者左室的舒缩功能均降低;给予倍他乐克治疗后左室舒张功能得到改善;
     6、应变及应变率成像技术不受心室梗阻动力的影响,且相对不受心脏整体运动和局部牵拉影响,在评价局部心肌功能方面具有广阔的临床应用前景。
Background:HCM is a autosomal dominant inherited disease which is caused by the genic mutation of ten proteinum encoding the cadiocyte sarcomere.The myocardium pachynsis happens without the obvious increasing of volume load and pressure load,and its manifestation is apopsychia,chest distress,chest pain,arrhythmia and sudden death.But some patients may have the serious consequence without the clinical symptom,the pristine diagnosis is very important.The traditional ultrasonic cardiogram can offer the morphologic and hemodynamic information to diagnose HCM,the most common manifestation is the inhomogeneous pachynsis of interventricular septum and left ventricular wall.Hypertensive left ventricular hypertrophy(H-LVH)has a history of hypertension,and its main manifestation is the homogeneous pachynsis of left ventricular wall,so it is not too difficult to diagnose the typical cases.But some literatures pointed that thirteen to thirty-one percents patients of HCM have the manifestation of the homogeneous pachynsis of the left ventricular wall,and four to tourty-seven percents patients of H-LVH have the manifestation of the inhomogeneous pachynsis of the left ventricular wall.So the appreciation of the HCM and H-LVH is always the hot spot and the difficult spot in this sphere. Betaloc is the most common drug for HCM,but it can not reverse the myocardial pachynsis in macroscopy,and the traditional ultrasonic cardiogram can not evaluate the therapeutic effectively,it does not have a certain effective power.So it is necessary to carry out a systematic research for the alteration of the left ventricular function in these diseases. The technique of straining/strain rate image formation,which is developed recently is about organizational Doppler,has a high timeresolution, and it can quantitive analyze the movement of multi-segmented myocardium simultaneouly.Many researches have confirmed that this technique can investigate the contractile function and the diastolic function of the partial left ventricular myocardium quantitatively,and the movement of the myocardium which is determined by that technique can reflect the contractile character and the diastolic character of the myocardium without the influence of the peripheral organizational attraction.
     Purpose:In this research,we use the technique of straining/strain rate image formation to study the alteration of the left ventricular function in the patients of HCM and H-LVH in order to discuss these problems:(1) The alteration of the contractile function and the diastolic function in the patients of HCM;(2)to evaluate the value of the technique of straining/strain rate image formation in studying the left ventricular function in the patients who have the pachyntic left ventricle;(3)to evaluate the disparity of the alteration of the contractile function and the diastolic function in all kinds of the HCM patients;(4)to evaluate the value of the straining/strain rate image formation to analyze the APH;(5) the correlation between the alteration of the contractile function and the diastolic function in the patients of the partial myocardium and the thickness of the ventricular wall;(6)using the technique of straining/strain rate image formation to evaluate the therapeutic effect of Betaloc to patients with HCM.
     Subjects and methods:
     1 A total of 130 consecutive subjects were separated into 3 groups:
     (1)The control group consisted of 27 subjects(16 males and 11 females, age 24-62 years,averaged 44±12 years)without hypertrophic cardiomyopathy,coronary artery disease,nephrosis,hypertension,or diabetes mellitus who had no abnormal findings on physical/blood-biochemistry examination or abnormalities on electrocardiographic or conventional echocardiographic examinations.All subjects of this group do not have the history of heart failure or the history of hypertension.
     (2)A total of 69 patients(48 males and 21 females,age 14-63 years, average 41±12 years,case history 0-96 months)whose the cardiac muscle thickness met the criteria for the diagnosis of hypertrophic cardiomyopathy established by WHO/IFS were admitted to the hypertrophic cardiomyopathy group,hypertrophic cardiomyopathy was defined as the thickness of middle and superior parts of interventricular septum>15mm measured by two dimensional echocardiography; posterior wall,inferior wall,anterior wall and lateral wall of left ventricle are thickening lightly or no thickening;the ratio of the thickness of interventricular septum:the thickness of posterior left ventricular wall>1.3:1;the one which had apical hypertrophy appearance merely was defined as apical hypertrophy cardiomyopathy.According to different study objectives,the subjects of this group were divided with different standards:According to pressure gradient of left ventricle outflow tract, this group was divided into obstructive hypertrophic cardiomyopathy group and non-obstructive hypertrophic cardiomyopathy group:
     ①Obstructive hypertrophic cardiomyopathy group:left ventricle outflow tract pressure≥20mmHg.23 subjects totally in this group,16 males and 7 females,age25-57 years,average 40±11years,case history0-60 months;
     ②Non-obstructive hypertrophic cardiomyopathy group:left ventricle outflow tract pressure<20mmHg.35 subjects totally in this group, 24 males and 11 females,age 14-63 years,average 43±17 years, case history 0-96months;
     ③Apical hypertrophy cardiomyopathy group:The apical hypertrophy is limited under the level of the left ventricular columna papillares.11 subjects totally in this group,8 males and 3 females,age 22-61 years,average 41±14 years,case history 3-84 months;
     In order to estimate the curative effect of Betaloc,21 HCM patients whose heart rate is above 60pm/min,are chosen and offered Betaloc and followed up one month.
     (3)A total of 34 patients(21 males and 13 females,age 31-67 years, average44±13years,case history 0-156months)whose blood pressure met the criteria for the diagnosis of hypertension established by WHO/ISH were admitted to the hypertension group.Hypertension was defined as a blood pressure of at least 140/90mmHg or the use of anti-hypertension medications.Patients with secondary hypertension were excluded by physical and laboratory examinations.
     2.Methods:inter-and intra-group comparisons were performed with a one-way ANOVA test and post-hoc LSD-t test respectively.Univariate correlation was assessed by Pearson correlation coefficient.Significantly correlated parameters were subjected to linear regression ananlysis.For all statistical procedures,SPSS statistical analysis software was used.A p value<0.05 was considered statistically significant.
     Results:
     1.Compared with the control group about the left ventricular structure and function,the numerical values of the left ventricular inner diameter、the thickness of the interventricular septum and the left ventricular posterior wall、the EF of the left ventricle、the weight of the left ventricle of the HCM group are more than those in the control group significantly (P<0.01),and the numerical values of the E/A、S/D are less than those in the control group significantly(P<0.01);the numerical values of the left ventricular inner diameter、the thickness of the interventricular septum and the left ventricular posterior wall of the hypertension group are more than those in the control group significantly(P<0.01),the numerical values of the weight of the left ventricle are more than those in the control group(P<0.05),and the numerical values of the E/A、S/D are less than those in the control group significantly(P<0.01);the numerical values of the left ventricular inner diameter、the thickness of the interventricular septum and the left ventricular posterior wall、the EF of the left ventricle、the weight of the left ventricle of the HCM group are more than those in the hypertension group significantly(P<0.01);
     2.The result of the comparison about the left ventricular structure and function among the different HCM groups is that,the numerical values of the thickness of the interventricular septum、the weight of the left ventricle、the blood flow rate of the debouch of the aortic valve of the HCM group with obstruction are more than the HCM group without obstruction significantly(P<0.01),and the thickness of the left ventricular posterior wall are bigger(P<0.05);the numerical values of the thickness of the interventricular septum、the weight of the left ventricle、the blood flow rate of the debouch of the aortic valve of the HCM group which has the apical hypertrophy are less than the HCM group with obstruction significantly(P<0.01),and the numerical values of the thickness of the left ventricular posterior wall are less than that(P<0.05);all the other indexes of the HCM group which has the apical hypertrophy and the HCM group with obstruction have no statistical variance;
     3.Compared with the control group about the left ventricular structure and function,the numerical values of the left ventricular inner diameter、the thickness of the interventricular septum and the left ventricular posterior wall、the EF of the left ventricle、the weight of the left ventricle of the apical hypertrophic cardiomyopathy are more than those in the control group significantly(P<0.05),and the numerical values of the E/A、S/D are less than those in the control group significantly(P<0.05);
     4.Compared with the control group about the straining/strain rate,the numerical values of all segmentedεet、SRs、SRe、Sra of the HCM group are less than those in the control group significantly(P<0.05or P<0.01);the numerical values of all segmentedεet、SRe of basilar part、intermediate part and Apex of heart are less than those in the control group significantly(P<0.05or P<0.01),the SRa of Apex of heart is higher than those in the control group(P<0.05),and the others have no statistical variance;the numerical values of all segmentedεet、SRs、SRe、Sra of the HCM group are less than those in the hypertension group significantly(P<0.05or P<0.01);
     5.The variance of indexes about the straining/strain rate among the different groups:the numerical values ofεet、SRs、SRe of the basilar part and intermediate part of the HCM group with obstruction or not are less than the HCM group which have the apical hypertrophy significantly(P<0.05or P<0.01),SRa is lower but it has no statistical variance;εet of the HCM group with obstruction or not is higher than the HCM group which has the apical hypertrophy significantly(P<0.01),the numerical values of SRs、SRe、SRa are more than the HCM group which has the apical hypertrophy but they have no statistical variance;the comparison of all segemented straining/strain rate between the HCM group with obstruction and the group without obstruction has no statistical variance(P>0.05);
     6.Compared with the control group about the straining/strain rate,the numerical values ofεet、SRs of the intermediate and apex part are lower than those in the control group(P<0.05),the numerical values of all segmented SRe、Sra of the HCM group are less than those in the control group significantly(P<0.05or P<0.01);
     7.The correlation between the thickness of the ventricular wall and the straining of the systolic peak:the correlation coefficient of the the thickness of the ventricular wall and the straining of the systolic peak(absolute value)r=-0.783,presenting a high negative correlation.
     8.The alteration of the indexes about the function of the left ventricle and the straining/strain rate in the HCM patients between pre-treatment and after one-month-treatment:no significant alteration of the indexes about the left ventricular structure and function,the increasing ofεet after-treatment is statistical singificant(P<0.05), the increasing of SRs、SRe、SRa is not statistical significant.
     Conclusions:
     1.The technique of straining/strain rate image formation can detect the abnormality of the contractile function and the diastolic function by the the aspect of left ventriculate image formatr long axis sensitively,it can be the first choice to estimate the pristine myocardial pathological change and the disfunction.
     2.The technique of straining/strain rate image formation can discriminate the HCM patients and the HP patients great to give the early diagnosis exactly.
     3.The technique of straining/strain rate image formation can be used to diagnose the apical hypertrophic cardiomyopathy.
     4.The decrease of the left ventricular contractile function are relative to the thickness of the myocardial hypertrophy.
     5.The contractile function and the diastolic function of the left ventricle are depressing in the HCM patients,but the diastolic function can be improved after the treatment of Betaloc.
     6.The technique of straining/strain rate image formation is not effected by the motivation of the ventricular obstruction,and it is not effected by the integrity movement and the partial tensile force relatively.It has a wide perspective of clinical application in evaluating the function of the partial myocardium.
引文
1. Shapiro, L.M. and W.J. McKenna, Distribution of left ventricular hypertrophy in hypertrophic cardiomyopathy: a two-dimensional echocardiographic study. J Am Coll Cardiol, 1983. 2(3): p. 437-44.
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