实时三平面应变率成像评价生理性与病理性左心室心肌肥

实时三平面应变率成像评价生理性与病理性左心室心肌肥 摘要 目的 应用实时三平面应变率成像检测原发性高血压与运动员生理性左心室肥厚左心房功能的不同。 方法 应用实时三平面显像技术在同一心动周期的同一时相上，同步显示受检者的心尖四腔心、心尖两腔心和心尖左心室长轴切面，测量左心房各壁收缩期应变率峰值、舒张早期应变率峰值、舒张晚期应变率峰值，并进行比较。 结果 高血压病患者左心房构型、功能变化是高血压病心肌损害的早期征象，应变率成像能敏感反映高血压病早期左心房功能的变化，生理性心肌肥厚是一种良性的反应，两者左心房功能的变化有显著差异 讨论 实时三平面应变率成像技术可以在三个切面上同时进行分析，节省了扫查时间，而且排除不同心动周期变异对左心房局部心肌节段定量分析的影响，使各节段心肌运动更具有可比性，从而能较全面、准确地评价原发性高血压与运动员生理性左心室肥厚左心房的收缩与舒张功能。 关键词 实时三平面应变率成像 生理性 左心室心肌肥厚 左心房 背景 实时三平面应变率成像技术是一种在同一心动周期的同一时相上，同步显示三个切面，直接定量评价局部心肌收缩功能的成像技术,反映单位心肌长度的速度梯度或者速度阶差的空间分布,只与相对速度有关,不受心脏整体运动和相邻节段牵拉的影响,能更真实地反映局部心肌的 功能状态 同[2、3][ 1 ] 。 研究表明，生理性与病理性左心室心肌肥厚的左心室功能不，作为心功能的一个重要方面、维持正常心脏功能有着十分重要意义的左心房，其功能常被忽视。运动员长期训练造成生理性左心室心肌肥厚，与原发性高血压性心脏病心肌肥厚预后不同，本研究通过对比运动员、高血压患者和正常人左心房应变率参数的差异,探讨应变率成像技术在评价生理性与病理性左心室肥厚左心房功能中的应用价值。 资料与方法 1(研究对象 选择心肌肥厚的职业运动员25例(运动员组)，男20例,女5例，年龄25,40岁，平均(31?6)岁，接受正规训练，职业运动年限大于8年,左心室质量指数(LVMI)男性大于134g/m，女性大于110g/m，排除有家族性高血压及肥厚型心肌病家族史。选择2008年1月至2008年8月我院门诊和住院的原发性高血压患者30例(髙血压组)，男 22例，女8 例，年龄 33,68岁，平均(49?6)岁。病例入选标准:?高血压诊断按照1999年世界卫生组织国际高血压学会标准，即收缩压?140mmHg(1mmHg,0.133kPa)和(或)舒张压?90mmHg;?左心室心肌肥厚，且心脏超声检查计算LVMI男性大于134 g/m , 女性大于110 g/m22[4]22 ;?无心律失常或心脏传导异常;?除外继发性高血压、肥厚性心肌病、糖尿病及其它心血管疾病;?超声图像质量理想。另外，选择与运动员组、髙血压组的年龄、性别和体表面积相匹配的健康志愿者30例(正常对照组)。 2(使用仪器 GE Vivid 7 型多功能彩色多普勒超声诊断仪，配有二维探头M3S，频率1.5,4.3MHz，三维探头V3，频率1.5,4.0MHz，可在实时三平面成像的基础上进行应变率成像并脱机定量分析;受检者左侧卧位，平稳呼吸，在呼气末屏气状态下采集超声图像，每个超声指标至少测量3个连续心动周期，取平均值;同步记录心电图。 3(研究方法 3.1 常规超声心动图 所有受检者均获得满意的二维超声图像后，于胸骨旁左心室长轴切面测量左心房前后径、左心室舒张和收缩末期内径、室间隔和左心室后壁舒张末期厚度，并计算左心室射血分数及左心室质量指数;心尖四腔切面测量左心房上下径和左心房横径，根据左心房容积公式计算左心房的容积(LAV),左心房容积=πD1D2D3 /6(D1、 D2 、D3分别为左心房前后径、左心房横径、左心房上下径)。脉冲多普勒模式下于心尖四腔切面测量舒张期二尖瓣口血流频谱，包括舒张早期峰值流速(E)、舒张晚期峰值流速(A)和E/A 比值。 3.2 实时三平面应变率显像 应用V3探头置于心尖部获得满意的二维超声图像后，记录心尖四腔切面图像，同时启动实时三平面显像技术，获得心尖四腔、心尖两腔和心尖左心室长轴三个切面，其原理是以一个二维标准切面为基准切面以空间 60?角的切割关系，获取与此基准切面互成60?角和120?角的2个切面，即可在同一心动周期的同一时相上，同步显示3个切面，然后启动应变率显像分析系统，将取样容积置于各节段的中间段，设置应变长度6mm ,取样区大小2mm×2mm ,系统将自动显示出该节段的应变率曲线，每个超声指标至少测量3个连续心动周期，取平 均值，然后脱机分析数据。实时三平面显示的左心房前壁、下 壁和后壁后，为了减少误差，尽量提高感兴趣区的图像质量，操作时尽可能的使多普勒声束平行于心房壁。左心房应变率常用指标:包括收缩期应变率峰值、舒张早期应变率峰值、舒张晚期应变率峰值，应变率单位为s- 1。 4(统计学分析 应用SPSS11.0统计学软件，计量资料以均数?标准差表示，组间变量比较采用单因素方差分析，P<0.01为差异有统计学意义。 结果 1(常规心脏超声参数:测量25例运动员、30例原发性髙血压及30例健康志愿者的左心房前后径、左心房上下径和左心房横径，左心室舒张末期内径、室间隔和左心室后壁舒张末期厚度，并计算左心房容积、左心室射血分数及左心室质量指数。对照组左心室质量指数的95%正常值范围上限，男性和女性分别为116g/m和105 g/m。正常对照组、运动员组与髙血压组三组间的性别构成、年龄、心率差异无统计学意义(P>0.05);运动员组与原发性髙血压组两组左心室质量指数男性和女性分别大于134g/m和110g/m;与正常对照组比较，运动员组与髙血压组两组左心房前后径、左心房上下径、左心房横径及左心房容积各项测值均增大，存在显著性差异(P<0.01)。 高血压组二尖瓣口血流频谱E/A 比值在小于1，运动员组与正常对照组均正常(表1)。 2(实时三平面应变率参数:测量所有受检者左心房前壁、下壁和后壁的收缩期应变率峰值、舒张早期应变率峰值、舒张晚期应变率峰值，结 果显示运动员组应变率峰值(图1)接近正常对照组(图2)，无统计学意义(P>0.05);与运动员组和正常对照组相比，髙血压组应变率峰值(图3)明显降低，存在显著性差异(P<0.01)(表2)。由于房间隔受右心大小、功能的影响，因此结果未做分析。研究过程中，我们发现高血压组左心房内径与正常对照无显著性差异的情况下,其应变率也是减低的。对左心房扩大的患者, 这种情况尤为明显。这意味着高血压性左心室心肌肥厚患者的左心房即使在常规的超声心动图上没有任何变化, 其左心房肌的变形能力也是减低的。相反，运动员组的应变率峰值与正常对照无显著性差异。 讨论 运动员心脏首先出现在1899年Henschen的报道，通过物理检查和叩诊描述心脏扩大。随着现代超声心动图和其它影像检查方法的到来，这些变化被进一步发现和证实，1975年，Morganroth等首次应用超声心动图发现运动员左心室壁增厚、重量增加与左室舒张末期容积增加。耐力训练导致耗氧量和清除量增加，心脏搏出量和输出量增加，外周血管阻力下降;但是，力量训练可引起心率、收缩压、舒张压增高，而心脏输出量和耗氧量没有增加。事实上，大多数运动都包括这两种训练，应该作为一个整体而不是分开来看，因此，本研究未做[5]2222 严格的划分。生理性与病理性左心室肥厚本质的不同在于前者具有功能良好与可逆性的特点，左心房各壁应变率峰值无变化，运动员心脏的变化在停止训练后会逐渐恢复原来的状况，心电图和超声心动图的改变慢慢消失，这也可以证实是生理性的左心室肥厚[6-8]，与高血压性心脏病预后不同，高血压性左心室肥厚并非是一种有益的代偿机制, 而可能是一种增 加心血管意外发病率和死亡率的独立危险因子 ;长期的运动训练导致心室结构改变，左心房内径增加、室壁增厚及左室重量增加，其增大程度与训练强度和持续时间有关[9-14][4] 。中国数据显示，近四成运动员心脏面积增大超过10%。心脏面积增大者以从事耐力训练项目者为多，增大程度多数不超过预测面积的30%。我国正常成人心脏容积的最大值为870 ml，而我国运动员为1209ml[15、16]。 左心房心肌分深浅两层，浅层为环绕心房的横行肌束，深层为左心房固有肌，主要有以下三个功能:1)储蓄功能;2)管道功能;3)助力泵功能:在心房收缩期作为主动射血泵增加左心室充盈。高血压性左心室肥厚患者其左心房管道功能减弱，储器功能增强，而在左心室肥厚之前，左心房助力泵功能已经开始增强，左心室肥厚时左心房助力泵功能增强尤为明显，心房构型及功能变化是高血压病心肌损害的早期征象，随着患者年龄的增大、病情的加重，左心房构型及功能变化更加明显。其病理基础是由于压力负荷增加而致心肌细胞体积增大，间质细胞增殖，纤维组织增生，引起心室顺应性减退;左心房压力升高，心房壁张力增加，导致心肌被拉长，左心房扩大，应变率峰值减低。 左心房功能的变化反映了左心房前、后负荷的状况，对维持正常的心脏功能有着十分重要的的意义[17、18 ] , 因而准确评价左心房的功能在临床上是十分必要的。目前，对左心房功能的评价主要有左心房面积、容积、直径及压力，这些研究主要从整体角度出发来评价左心房的功能。然而由于左心房形态的不规则, 以及心脏复杂运动的影响, 使对左心房功能的评价有许多局限性，主要是测量方法复杂, 并受到左心室功能的影响，应变 率成像技术克服了这些问题，为左心房的大小和功能的评价提供了定量分 析的手段。应用实时三平面应变率成像技术，可以同时在三个切面上进行 定量分析，节省了扫查时间，而且去除了不同心动周期变异对左心房局部 心肌节段定量分析的影响，使各节段心肌运动更具有可比性。 作为一种新的超声技术，应变率成像还存在一定的局限性，如噪声、 帧率、分辨率、入射角度等的影响。在我们的操作过程中，尽量降低误差， 因帧率对应变率的影响较大，要较为准确的测定收缩期峰值应变率，调节 帧率为 70,100帧/秒，舒张期应变率的测定需要120,150FPS的帧率; 为了减少入射角度的影响，操作时尽可能使多普勒声束平行于心房壁。此 外，在今后的研究中，我们将继续增加运动员组的样本量，并根据运 动类型的不同进行分类比较，也许能更加清楚、准确地阐明生理性与病理 性左心室肥厚左心房功能的变化。 Evaluation of left atrial function in physiological and pathological left ventricle myocardial hypertrophy by real time tri-plane三平面应变率 variability imaging Abstract Objective Detect the difference of left atrium function between left ventricular hypertrophy caused by primary hypertension and physiological left ventricular hypertrophy on athletes by left real time tri-plane三平面应变率 imaging. Method Apply real time tri-plane三平面imaging technique on the same phase of a same cardiac circle to synchronously demonstrate the cross section of cardiac apex 心尖四腔心 quadriloculare, cor biloculare and left ventricular long axis, measure the 应变率 peak values of each left atrial wall in systolic phase, in early stage of diastole and advanced stage of diastole, and make a comparison of these values. Results Alteration of configuration and function of left atrium on hypertension patients is the early stage signs of myocardial damage of hypertension. 应变率imaging could sensitively reflect left atrial function change in early stage of hypertension, while physiological myocardial hypertrophy is a benign reaction, left atrial function in which is significantly different from that in hypertension. Discussion Real time tri-plane三平面应变率 imaging technique could analyze simultaneously on three cross sections, which shortens scanning time and depletes the influence of variation of different cardiac cycles on quantitative analysis of local myocardial segments of left atrium, thereby improving the comparability of myocardial movement of different segments so that we could more comprehensively and accurately evaluate the systolic and diastolic function of left atrium in primary hypertension and physiological left ventricular hypertrophy in athletes. Key words real time tri-plane三平面应变率 imaging, physiological, left ventricle myocardial hypertrophy, left atrium Background Real time tri-plane三平面应变率imaging technique displays three cross sections synchronously at the same phase of same cardiac cycle and give direct quantitative evaluation on systolic function of local cardiac muscle, reflecting the spatial distribution of velocity gradient or shear rate of unit myocardial length, which is only related to relative velocity, insusceptible to the bodily movement of heart and the traction of neighboring segment, and therefore could more veritably reflect the functional status of local cardiac muscle[ 1 ]. Study shows that there are differences of left ventricular function in physiological and pathological left ventricle myocardial hypertrophy[ 2,3]. Nevertheless, the function of left atrium, which is an important part of heart function and plays a significant role in maintaining it, is often neglected. The physiological left ventricular hypertrophy on athletes has a different prognosis from that in myocardial hypertrophy of primary hypertensive cardiopathy; this study discusses the application value of应变率 imaging technique in evaluating left atrial function in physiological and pathological left ventricle myocardial hypertrophy by comparing the disparity of 应变率parameters of left atrium on athletes, hypertension patients and normal healthy people. Data and Method I. Subjects A total of 25 professional athletes (athletes group) with myocardial hypertrophy were chosen; among them there were 20 male, 5 female, aging from 25 to 40, with an average of(31?6)years old. All subjects received professional training and had been engaged in professional sports for over 8 years. Left ventricular mass index(LVMI)were above 134g/ m2 in male, and above 110g/ m2 in female; family history of hypertension and hypertrophic cardiomyopathy was excluded. Thirty patients with primary hypertension (hypertension group) who came to our clinic or were admitted in our hospital from January 2008 to August 2008 were chosen; among them there were 22 male, 8 female, aging from 33 to 68, with an average of(49?6)years old. The inclusion criteria were: i. The diagnosis of hypertension was in accordance with the criteria made in World health Organization’ International hypertension Conference, 1999, which is systolic pressure ?140mmHg (1mmHg,0.133kPa), and (or) diastolic pressure ?90mmHg;ii. Left ventricle myocardial hypertrophy with LVMI (calculated through cardiac ultrasonic examination) above 134g/ m2 for male, above 110g/ m2 for female[4]; iii. Without arrhythmia and cardiac conduction anomaly; iv. Secondary hypertension, hypertrophic cardiomyopathy, diabetes and other cardiovascular diseases were excluded; v. Good quality of sonograms. In addition, 30 healthy volunteers whose age, gender and surface area were in match with the athletes group and hypertension group were also chosen as control group. II. Equipments Duplex Color Doppler Ultrasonoscope GE Vivid 7, equipped with 2D detecting head M3S (frequency: 1.5,4.3MHz) and 3D detecting head V3 (frequency: 1.5,4.0MHz) could perform 应变率 imaging and offline quantitative analysis in addition to real time 三平面 imaging. The subject took left lateral position, breathing steadily, and ultrasound image was collected in end expiration when breath was held; at least 3 continuous cardiac cycles were measured by each ultrasound index and average value was calculated; electrocardiogram (ECG) was recorded simultaneously. III. Research method i. Routine ultrasonic cardiogram (UCG) After ideal 2D ultrasound images were taken from all subjects, anteroposterior diameter of left atrium, end diastolic and systolic diameter of left ventricle, end diastolic thickness of interventricular septum and left ventricular posterior wall were measured at the parasternal left ventricle long axis cross section, and left ventricular ejection fraction, as well as left ventricular mass index were calculated; the supra-inferior and transverse diameters of left atrium were measured at the cross sections of the four cavities in cardiac apex, and left atrial volume (LAV) was calculated according to LAV formula: LAV= πD1D2D3 /6(D1, D2, and D3 refer to the anteroposterior, transverse and supra-inferior diameters of left atrium respectively). Blood flow frequency spectrum at mitral orifice during diastolic phase, including flow rate peak value in early stage (E) and advanced stage (A) of diastole, as well as the ratio of E/A, were measured at the cross sections of the four cavities in cardiac apex under Pulse Doppler mode. ii. Real time 三平面应变率 imaging After obtaining ideal 2D ultrasound images by placing V3 detecting head on apex of heart, images of the cross sections of the four cavities in cardiac apex were recorded, and 三平 面 imaging technique was applied simultaneously to obtain the thee cross sections of four cavities of cardiac apex, two cavities of cardiac apex and cardiac apex-left ventricle long axis. The principle of it is to use a 2D standard cross section as model cross section and form an incision angle of 60?, thereby obtaining two cross sections that form an angle of 60? and 120? respectively with the model section, so that three cross sections could be displayed synchronously at the same phase of same cardiac cycle; then start the 应变率 imaging analytical system, place the sample volume into the central part of all segments, set straining length to 6mm, sampling area to 2mm×2mm; the system would demonstrate the应变率curve of this segment. Each ultrasound index measures at least three successive cardiac cycles; calculate the average value, then analyze the data off-line. After the anterior wall, superior wall and posterior wall of left atrium being displayed by real time三平面 imaging, the Doppler sound beam should be placed as parallel to the cardiac atrium wall as possible to reduce errors and increase the image quality of the interested region. Commonly used 应变率index of left atrium are : 应变率 peak value of systolic phase, 应变率peak value of early stage of diastole, 应变率peak value of advanced stage of diastole, the unit of which is s- 1. IV. Statistical analysis Statistic software SPSS11.0 was applied; measurement data was denoted by average ? standard deviation; mono-factor variance analysis was conducted to compare interblock variables; P<0.01 was regarded as difference and had statistical significance. Results I. Routine cardiac ultrasound parameter: Anteroposterior, supra-inferior and transverse diameter of left atrium, end diastolic and systolic diameter of left ventricle, end diastolic thickness of interventricular septum and left ventricular posterior wall were measured on 25 athletes, 30 primary hypertension patients and 30 healthy volunteers; left atrial volume (LAV), left ventricular ejection fraction and left ventricular mass index were calculated. Ninety five percent of LVMI in control group was stipulated as the top limit of normal value range, which was 116g/m2 for male, 105 g/m2 for female. The differences of gender composition, age and heart rate among the normal control group, athletes group and hypertension group were not statistically significant(P>0.05). LVMI in athletes group and hypertension group was above 134g/m2 for male, above110g/m2 for female; compared with control group, the anteroposterior, supra-inferior and transverse diameter of left atrium, as well as LAV were all increased in athlete group and hypertension group; there were significant differences (P<0.01). E/A ratio, the blood flow frequency spectrum at mitral orifice was below 1 in hypertension group, while the figure was normal in athlete group and control group (table 1). ii. Real time 三平面应变率parameter: 应变率 peak value of the front wall, inferior wall and posterior wall of left atrium in systolic phase, in early stage of diastole and in advanced stage of diastole were measured on all subjects. Results showed that the 应变率 peak value in athletes group (table 1) approximated that in control group (table 2) and was not statistically significant (P>0.05); compared with athletes group and control group, hypertension group had a clearly lowered应变率peak value (table 3) and there was significant difference (P<0.01) (table 2). We have not analyzed the results of the atrium septum because it is susceptible to the size and function status of right heart. During the study, we found that the 应变率 of left atrium in hypertension group was also lowered under the situation that inner diameter of left atrium was not significantly different from that in control group. This was especially obvious in patients with enlarged left atrium. The situation indicated that even if there was no any change of left atrium revealed in routine UCG in patients with hypertensive left ventricular myocardial hypertrophy, the deformation function of left atrial muscle was still reduced. On the contrary, the 应变率peak value in athletes had no significant difference compared with that of the control group. Discussion Reports of athlete’s heart first appeared in the work of Henschen[5], 1899, who described enlarged heart through physical examination and percussion. As the coming out of modern UCG and other imaging examining methods, these changes were further revealed and confirmed. In the year 1975, Morganroth and fellow researchers first found thickened left ventricular wall, increased weight and end diastolic volume of left ventricle in athletes by UCG. Endurance training causes increased oxygen consumption and clearance volume, stroke volume and output raising, peripheral vascular resistance decreasing; however, strength training could result in elevation of heart rate, systolic and diastolic pressure without increased output and oxygen consumption. In fact, most sports involve both endurance and strength training and there is no need to clearly divide them, therefore we did not separate sports into two types in this study. The essential difference between physiological and pathological left ventricular hypertrophy is that the former functions well and is reversible; there is no change in 应变 率peak values of the walls in left atrium. The change of athlete’s heart will recover after training is stopped; alteration of ECG and UCG disappears slowly, too, which also give evidence that this is physiological hypertrophy[6-8]. Having a different prognosis from physiological left ventricular hypertrophy, hypertensive hypertrophy is not a beneficial compensation mechanism, and rather, it could be an independent risk factor that increases the morbidity and mortality of cardiovascular accident [4]. Long term of endurance training causes structural change of ventricles, increased left atrium inner diameter, thickened ventricular wall and elevated left ventricle weight, the extent of these changes related to the intensity and duration of the training[9-14]. Statistics in china show that approximately forty percent of athletes’ heart has been enlarged by over 10%. Athletes with enlarged heart are more often seen among those engaged in endurance training, in most cases the enlarged area no more than 30% of the predicted area. In China, the maximum heart volume in normal healthy adults is 870ml, while the figure is 1209ml in athletes[15,16]. Left atrium myocardiums are distributed in two layers, the deep and the surface; the surface layer muscle is a transversal muscle bundle that encircles atrium, while the deep layer is inherent muscle in left atrium; they have three major functions, reservoir function, pipeline function, and assistant pump function (increasing left ventricular filling during atrial systole period as an active ejection pump). Patients with hypertensive left ventricular myocardial hypertrophy have weakened pipeline function of left atrium and strengthened reservoir function; the assistant pump function of left atrium has been enhanced before left ventricular hypertrophy appears, and the enhancement is especially significant after the hypertrophy appears. The configuration and function change of atrium is the early sign of hypertensive myocardial damage, and the change of left atrium gets more significant along with aging and aggravation of disease. The pathological fundament is, the increased pressure load causes volume enlargement of myocardial cells, proliferation of interstitial cells, as well as fibroplasia, which results in the decrease of ventricular compliance; the elevated left atrial pressure and tension of atrial wall induces the prolonging of myocardium, the enlargement of left atrium and the reduction of 应变率 peak value. Function change of left atrium indicates the preload and afterload of it and plays an important role in maintaining normal heart function[17,18], therefore, accurate evaluation of left atrium is clinically very necessary. At present, evaluation of left atrium mainly includes the area, volume, diameter and pressure of left atrium, which mainly based on the conception of entirety. However, because of the irregularity of the left atrium’s shape and the effect of the complicated movement of heart, the evaluation has many limits, the major problems of which are the complication of measurement and the influence of left ventricular function. Nevertheless, 应变率 imaging could overcome these problems and provide the method of quantitative analysis for the assessment of the size and function of left atrium. Real time tri-plane三平 面应变率 imaging technique could analyze simultaneously on three cross sections, which shortens scanning time and depletes the influence of variation of different cardiac circles on quantitative analysis of local myocardial segments in left atrium, thereby improving the comparability of myocardial movement of different segments. As a new technique of ultrasound, 应变率imaging has certain limits, for example, it could be affected by noise, frame rate, resolution, angle of incidence, etc. We have reduced errors as for as possible during our operative procedure; since frame rate has a big influence on 应变率, we adjusted frame rate to 70,100 frame/second to precisely measure the应变率in systolic phase, and to 120,150 frame/second in diastolic phase; we placed Doppler sound beam as parallel to cardiac atrium wall as possible, to decrease the influence of incidence angle. In addition, we will continuously increase the sample size of the athletes group in future studies and compare statistics of different types of sports, hopefully to disclose more distinctly and accurately the function change of left atrium in physiological and pathological left ventricle hypertrophy.