【作者】 崔洁；

【导师】 葛均波； 舒先红；

【作者基本信息】 复旦大学 ， 心血管内科学， 2007， 博士

【摘要】 第一部分实时三维超声心动图定量评价左室容积及收缩功能的临床研究研究目的：1．研究在机QLAB 4.0软件的三维双平面法和脱机Tomtec 4D LV-Analysis软件的三维6平面法两种测量方法定量评价左室容积及整体收缩功能的准确性。2．观察QLAB三维双平面法和Tomtec三维6平面法在正常人和心衰患者中定量评价左室节段容积—时间变化的异同。探讨更适合于评价左室收缩同步性的三维超声心动图方法。资料和方法：1．心功能不全患者20例，其中男性14例（70％），年龄46～77岁，平均61.4±10.1岁。应用Philips SONOS 7500超声诊断仪进行二维及三维检查，并脱机应用Tomtec软件进行三维左室容积和收缩功能定量分析。测量结果与^99mTc-MIBI核素心血池显像检查结果进行比较。2．心功能不全患者20例，其中男性12例（60％），年龄48～70岁，平均58.2±11.3岁；正常人20例，其中男性12例（60％），年龄44～68岁，平均56.9±8.7岁。应用Philips IE33超声诊断仪进行二维及三维超声心动图检查，在机应用QLAB 4.0软件进行三维左室整体及节段性容积和收缩功能定量分析，并脱机应用Tomtec软件进行定量分析。结果：1．在心功能不全患者中，Tomtec软件脱机测量的三维6平面法与核素法测定的LVEDV、LVESV以及LVEF均无统计学差异（P＞0.05）且测量结果高度相关（P＜0.01）。二维Simpson法测量左室容积低于核素法（P＜0.05），但二维LVEF高于核素法LVEF（单侧检验，P＜0.01）。2．在机应用QLAB软件三维双平面法和脱机应用Tomtec软件三维6平面法测定的左室容积以及LVEF均无统计学差异（P＞0.05）且测量结果相关性好（r=0.6847，P＜0.01）。而在机测量时间更短，仅需2min。3．QLAB和Tomtec软件测量患者的左室基底段和中间段各节段EDV、ESV和节段EF均无统计学差异（P＞0.05）。但无论在正常人组或心衰组，Tomtec软件测得左室各节段达到最小容积时间的标准差和最大差值（Tmsv-SD％和Tmsv-Dif％）均明显大于QLAB软件测量值（P＜0.01）。同一软件测量结果相比，Tomtec软件测得心衰组Tmsv-SD％和Tmsv-Dif％均大于正常人组测量值（P＜0.05），而应用QLAB软件测量结果在两组间无统计学差异（P＞0.05）。结论：1．在心功能不全患者中，Tomtec三维6平面法测量左室容积和功能的准确性与核素法无统计学差异且高度相关，优于二维Simpson法。2．在机QLAB三维双平面法与Tomtec三维6平面法测量左室整体容积结果无统计学差异且高度相关，但用时明显缩短，可以快速测量左室三维LVEF，满足临床准确评价左室整体收缩功能的需要。3．Tomtec 4D LV-Analysis CRT软件测定的左室各节段Tmsv-SD％和Tmsv-Dif％在正常人和心衰患者存在显著差异，能够较敏感的检出心衰患者存在左室机械收缩不同步。而QLAB 4.0软件测定的Tmsv-SD％和Tmsv-Dif％在正常人和心衰患者无明显差别，不能敏感的识别心衰患者的左室机械收缩不同步情况。因此在目前实时三维超声心动图容积分析软件中，脱机定量测量能更敏感的评价左室收缩同步性。第二部分实时三维超声心动图评价正常人左室节段性收缩同步性的临床研究背景：实时三维超声心动图是一种准确的定量评价左室整体和节段收缩活动的技术，目前其临床应用在国内外均处于初步阶段，尚无测量各节段收缩同步性的公认指标及在正常人中的参考值范围。研究目的：探讨实时三维超声心动图定量测量正常人左室节段性收缩同步性的适宜指标及其正常参考值。资料与方法：接受健康体检成年人共59例，男性31例，女性28例，年龄18-76岁，平均43.3±21.7岁。应用Philip SONOS 7500超声仪或IE33超声仪行实时三维超声心动图检查，应用Tomtec软件脱机定量测量左室舒张末期容积、收缩末期容积，并计算三维LVEF和描记左室整体及各节段容积—时间曲线，左室收缩同步性分析指标包括：各节段容积达到最小值的时间（time to minimal segmental volume，Tmsv）及其所占心动周期的百分率（Tmsv％）、节段Tmsv的标准差（Tmsv-SD）占心动周期的百分率（Tmsv-SD％）、节段Tmsv之间的最大差值（Tmsv-Dif，ms）占心动周期的百分率（Tmsv-Dif％）。对左室16节段，基底段及中间段共12节段、基底段6节段和中间段6节段分别计算其Tmsv-SD％及Tmsv-Dif％。两名观察者分别独立对10例受检者的实时三维超声心动图原始资料进行两次重复脱机分析观察其重复性。结果：1．正常人Tmsv-SD％分别为：16节段4.25％±1.02％、12节段4.36％±1.19％、基底段4.51％±1.42％、中间段4.19％±1.37％，Tmsv-Dif％分别为：16节段14.79％±3.48％、12节段15.50％±11.79％、基底段14.60％±3.62％、中间段11.70％±3.57％。且与QRS时限、LVEF及左室容积等因素无统计学相关（P＞0.05）。2．正常人中各节段达到最小容积时间较一致，各节段Tmsv％无统计学差异（P＞0.05）。按照室壁分布，达到最小容积最早的节段最少见为后壁，而最晚的节段常见为前间隔。按照左室各水平节段分布，达到最小容积最早的节段多为中间段，最晚的节段多为基底段。3．两位观察者内重复测量和观察者间重复测量结果均无统计学差异（P＞0.05）。结论：1．正常人的左室各节段Tmsv-SD％和Tmsv-Dif％均较小，且与QRS时限、LVEF及左室容积等因素无关，各参数在同一观察者内以及不同观察者间多次测量结果较稳定，可作为评价左室机械收缩同步性的指标。2．正常人左室各节段心肌达到最小容积时间一致，各节段Tmsv早晚顺序存在一定特征。第三部分实时三维超声心动图评价心力衰竭及室内传导阻滞患者左室收缩同步性的临床研究目的：探讨实时三维超声心动图在不同类型心力衰竭患者及传导阻滞患者中定量测量左室收缩同步性的价值。方法：研究对象分为：A组：无明显器质性心脏病的室内传导阻滞组（单纯宽QRS组）32例A-L亚组：完全性左束支传导阻滞亚组（单纯CLBBB组）17例A-R亚组：完全性右束支传导阻滞合并左前分支传导阻滞亚组10例A-O亚组：其他室内传导阻滞亚组5例B组：窄QRS波合并左室收缩功能不全组（单纯心衰组）44例B-I亚组：缺血性心肌病亚组17例B-NI亚组：非缺血性心肌病亚组27例（扩张型心肌病20例，高血压心脏病7例）C组：宽QRS波合并左室收缩功能不全组（宽QRS合并心衰组）40例C组患者根据传导阻滞类型分为：C-L亚组：完全性左束支传导阻滞亚组12例C-NL亚组：其他类型室内传导阻滞亚组28例C组患者根据病因类型分为：C-I亚组：缺血性心肌病亚组18例C-NI亚组：非缺血性心肌病亚组22例对三组患者进行二维及三维超声心动图测量左室各节段Tmsv-SD％和Tmsv-Dif％，分析不同类型患者左室各节段Tmsv顺序特征及Tmsv-SD％、Tmsv-Dif％测量结果的特点，及各指标与QRS时限、三维LVEF的关系。结果：（一）无明显器质性心脏病的室内传导阻滞组（A组）1．A组患者的左室容积、二维LVEF与正常人无统计学差异（P＞0.05）。A-L亚组患者的二维LVEF和A组的三维LVEF低于正常人（P＜0.05）。2．A组患者Tmsv-SD％和Tmsv-Dif％明显高于正常人（P＜0.01），其中A-L亚组的16节段、12节段及中间段Tmsv-Dif％大于A组的平均水平（P＜0.05）。3．A-L亚组中Tmsv最早的壁段多为前壁及后间隔；Tmsv最迟的壁段以后壁较多。Tmsv最迟位于前间隔及下壁的患者，其3D-EF相对较低，Tmsv-SD％和Tmsv-Dif％相对较大。4．A-R亚组中Tmsv最早的壁段一般为下壁；而Tmsv最迟的壁段分布较平均，其中前间隔或前壁最迟Tmsv患者的3D-EF略低。在QRS相对较窄患者，其Tmsv最早与最迟节段较临近。（二）QRS时限正常的左室收缩功能不全组（B组）1．B组患者除左室容积明显大于正常人，2DEF及3DEF均明显低于正常人（P＜0.01）外，QRS时限高于正常人组（P＜0.01）。B组Tmsv-SD％和Tmsv-Dif％明显高于正常人（均为P＜0.01）。其中两不同病因亚组的各指标无统计学差异（P＞0.05）。2．B组患者中，Tmsv最早的壁段以侧壁和后壁较少见；而Tmsv最晚的壁段以下壁和后壁较少见。Tmsv最早为侧壁的患者的LVEF较低且Tmsv-SD％和Tmsv-Dif％较大；Tmsv最早为后壁或最晚为下壁的患者的QRS相对较窄且Tmsv-SD％和Tmsv-Dif％较小；Tmsv最早为后间隔和前壁的患者的LVEF较高。3．B-I亚组患者中，后壁最少成为Tmsv最早或最迟壁段；其次侧壁较少见。前间隔Tmsv最早患者的Tmsv-SD％和Tmsv-Dif％较小；前间隔Tmsv最晚患者的左室各节段Tmsv-SD％及Tmsv-Dif％均较大。（三）宽QRS合并左室收缩功能不全组（C组）1．C组患者的QRS时限明显大于正常人（P＜0.01）及A组（P＜0.05）。3D-EDV和3D-ESV明显大于正常人和B组（均为P＜0.01）。2D-EF和3D-EF明显低于正常人（均为P＜0.01），但与B组无统计学差异（均为P＞0.05）。2．C组患者的Tmsv-SD％和Tmsv-Dif％大于其他各组（除C组中间段Tmsv-Dif％与B组无统计学差异外），左室16节段、12节段及基底段的Tmsv-SD％和Tmsv-Dif％均与3D-EF呈线形相关。3．C组患者中，Tmsv最迟为侧壁患者不同步情况最显著，其三维EF较低下，QRS更宽大畸形。Tmsv最早位于室间隔的患者，其收缩同步性明显低于其他类型患者。其中以Tmsv最早位于后间隔的患者更显著，Tmsv最迟位于前间隔的患者，其3D-EF相对较低且不同步程度较明显，其次在Tmsv最迟为后间隔的患者，不同步程度也比较明显。4．C-L亚组患者除基底段和中间段Tmsv-Dif％外，其余收缩同步性参数均明显高于其他类型的传导阻滞患者（P＜0.01）。其中后间隔Tmsv最早患者以及后壁、下壁Tmsv最迟患者的QRS较宽且3D-EF较低，Tmsv-SD％或Tmsv-Dif％相对较大。前间隔Tmsv最迟患者Tmsv-SD％或Tmsv-Dif％也较大。5．C-I亚组最早Tmsv的壁段主要为室间隔而无一例为侧壁或者后壁，最迟Tmsv的壁段以下壁最多见。Tmsv最早为前间隔者的Tmsv-SD％及Tmsv-Dif％较大；而Tmsv最迟为后间隔患者的Tmsv-SD％或Tmsv-Dif％均较大。（四）在CLBBB伴随或不伴心力衰竭患者中，左室收缩同步性与3D-EF存在明显线性相关，但与QRS时限不存在线性相关（P＞0.05）。（五）在所有心衰患者中，QRS时限与LVEF存在负相关，相关系数r=-0.4249，（P=0.0003）。左室16节段、12节段及基底段收缩同步性与LVEF及QRS时限也分别存在中等程度负相关。而多因素回归分析显示，在所有心衰患者中，三维LVEF是左室收缩同步性的独立预测因素，但QRS时限不是LVEF的独立预测因素。结论：（一）无明显器质性心脏病的室内传导阻滞组（A组）1．孤立的室内传导阻滞患者往往合并亚临床心功能损害，出现较明显的左室节段性收缩时程异常和收缩不同步。其不同步特征与传导阻滞类型相关。2．孤立CLBBB患者收缩不同步较正常人和其他类型室内传导阻滞患者更严重，其后间隔与前间隔Tmsv明显不一致，Tmsv最迟节段的位置与其电活动、心功能和收缩同步性均存在一定关联。3．孤立CRBBB合并LAH患者的收缩不同步顺序与电激动顺序相似。（二） QRS时限正常的左室收缩功能不全组（B组）1．窄QRS的心衰患者也存在较明显的收缩不同步，其不同步程度与LVEF减退程度相关。2．缺血性心肌病亚组患者的前间隔收缩时程与患者的Tmsv-SD％和Tmsv-Dif％有关，前间隔Tmsv可能是提示缺血性心肌病心衰患者左室收缩不同步程度的标志之一。3．心衰患者中最早Tmsv为侧壁者，LVEF较低且收缩同步性较差，提示Tmsv最早为侧壁可能是左室收缩功能明显不协调的标志之一。（三）宽QRS合并左室收缩功能不全组1．对所有心衰患者进行多因素回归分析，只有3D-EF是左室收缩同步性的独立预测因素。2．在CLBBB合并心衰患者中，多数患者后间隔、前间隔和前壁Tmsv最早，而下壁、后壁及侧壁Tmsv最晚。Tmsv最迟为侧壁患者不同步情况最显著，其EF较低下，QRS也更宽大畸形。3．心衰患者如存在后间隔Tmsv最早以及前间隔Tmsv最迟，往往提示患者存在弥漫而严重的左室收缩不同步。4．缺血性心肌病心衰患者室间隔常表现为Tmsv最早或者最迟节段，后壁较少表现为Tmsv最早或者最迟的节段，可能与血供异常范围有关。更多还原

【Abstract】 Clinical Studies of Left Ventricular Systolic Function and Mechanical SynchronyUsing Real-Time Three-Dimensional EchocardiographyPartⅠMethodological Study Of Real Time Three-DimensionalEchocardiography In Assessing Global And Segmental Left Ventricular SystolicFunctionBackground:Recent developments with high resolution real time three-dimensionalechocardiography (RT3DE) facilitate the acquisiton of high quality images and theanalysis of global and segmental volume-time curves (VTCs).ObjectiveTo evaluate (1) the accuracy of left ventricular (LV) volume quantification usingoffline three dimensional system compared with radionuclide ventriculography inheart failure (HF), and (2) to evaluate the feasibility of direct evaluation of global andsegmental left ventricular volume by biplane method using online three-dimensionalsystem in HF, and (3) to compare the sensitivity of detecting LV systolic asynchronyby online and offline three dimensional systems.Methods and Results:Twenty HF patients underwent RT3DE, offline quantification of global LVvolume and LVEF were compared with radionuclide ventriculography. The LVvolume and LVEF were of no difference between RT3DE and radionuclide results (P> 0．05) with moderate correlation (r = 0．6847, P < 0．01) , despite the relativeinaccuracy of 2D echocardiography results (2D-EF 37．73%±7．27%, LVEF byradionuclide ventriculography 31．34±7．81, P < 0．01) . Then online(QLab 4．0) andoffline (Tomtec LV analysis CRT 1．0) quantification of global and segmental LVsystolic function were used in 20 HF patients and 20 normal subjects, the end systolictime reaching minimal segmental volume (Tmsv) for 16 segments were obtained bythe two 3D analysis system. Compared with offline multiplane 3D methods, online3DBiplane methods could rapidly quantify LV global volume and LVEF as well asoffline 3D methods in both HF patients and normal subjects (P > 0．05) . By offline 3Dsystem, the standard deviation of Tmsv (Tmsv-SD% ) and the difference between the latest Tmsv and the earliest Tmsv (Tmsv-Dif%) were higher in HF patients(for 16segments: Tmsv-SD% 6．44±3．55, Tmsv-Dif% 22．8±14．1) than normal subjects(for 16 segments: Tmsv-SD% 4．41±0．99, Tmsv-Dif% 14．97±3．44, P < 0．05) ,however, by the online QLab system, the Tmsv-SD% and Tmsv-Dif% are of nodifference in HF patients(for 17 segments: Tmsv-SD% 1．10±0．34, Tmsv-Dif% 3．91±1．01) and normal subjects (for 17 segments: Tmsv-SD% 0．83±0．22, Tmsv-Dif%2．57±0．51, P>0．05) .ConclusionBoth online and offline 3D methods could accurately evaluate LV volume andLVEF in HF patients, in which online method was more rapidly. But only offlineRT3DE system could sensitively detect the segmental LV systolic asynchrony in heartfailure patients over normal subjects. PartⅡAssessment of Left Ventricular Systolic Function and MechanicalSynchronicity in Normal Subjects Using Real Time Three DimensionalEchocardiographyBackground:Real time three-dimensional echocardiography ( RT3DE) is a novel techniquecurrently being investigated in the evaluation of left ventricular contraction patternsby analyzing global and segmental volume-time curves (VTCs). However, thephysiological time course curves of normal subjects have not been studied yet.ObjectiveTo explore the normal LV segmental volume-time changes by RT3DE over thecardiac cycle, and to get the range of Tmsv-SD% and Tmsv-Dif% in normal subjects.MethodsFifty-nine healthy subjects underwent RT3DE and the data were analyzed offlineby two independent observer. Tmsv-SD% and Tmsv-Dif% were evlatuated for all 16segments, 12 segments not including the apex, basal 6 segments and middle 6segments.ResultsTmsv% in all 16 segments were of no difference within normal subjects(16-segment Tmsv-SD% 4．25%±1．02%, Tmsv-Dif%4．79%±3．48%; 12-segmentTmsv-SD% 4．36%±1．19%,Tmsv-Dif%; basal-6-segment Tmsv-SD%4．51 %±1．42% 15．50 %±11．79 % , Tmsv-Dif% 14．60 %±3．62 % ; middle-6-segmentTmsv-SD%4．19%±1．37%, Tmsv-Dif% 11．70%±3．57%). The result of Tmsv-SD%and Tmsv-Dif % were comparable both for Interobserver and intraobservermeasurements.ConclusionThe segmental systolic motion are synchronous in normal subjects , Tmsv-SD%,Tmsv-Dif% results are low and stable in normal subjects. PartⅢAssessment Of Left Ventricular Systolic Function And MechanicalAsynchrony In Heart Failure And Ventricular Conduction Disturbances UsingReal Time Three Dimensional Echocardiography: a clinical studyBackground:Left ventricular mechanical dyssynchrony is frequently observed in chronic heartfailure patients. Volume-time curves determined by real time three-dimensionalechocardiography could be used to identify geometric and time-course changes of leftventricular segments in selected patients underwent CRT therapy. However, thepathological changes of time-course curves in isolated ventricular conductiondisturbances and in heart failure population have not been studied yet.ObjectiveTo evaluate the LV systolic asynchrony in isolated ventricular conductiondisturbances, as well as in heart failures patients with or without ventricularconduction disturbances.Methods116 patients underwent RT3DE, including 32 isolated ventricular conductiondisturbances patients (GROUP A, 17 with CLBBB, 10 with CRBBB+LAH, 5 others),44 heart failure patients with narrow QRS complex (GROUP B, 17 with ischemiccardiomyopathy, 20 with dilated cardiomyopathy and 7 with hypertension), and 40heart failure with ventricular conduction disturbances (12 CLBBB /28 non-CLBBB,18 ischemic/ 22 non-ischemic cardiomyopathy). The Tmsv-SD% and Tmsv-Dif%were compared among different groups and subgroups, and the relationship ofsegmental Tmsv% with 3D-EF, QRS interval, type of ventricular conductiondisturbances and heart diseases were evaluated within and among groupsResults1．Patients with isolated wide QRS complex have higherTmsv-SD%, higher Tmsv-Dif% and lower 3DEF(P <0．05) , especially inisolated CLBBB patients(16 segmental Tmsv-SD% 4．90±1．89 P < 0．01,Tmsv-Dif% 17．2±6．3, P< 0．01) .2．In most isolated CLBBB patients, the earliest Tmsv were found in anterior wall and post interventricular septum. Relative Lower LVEF,shorter QRS interval and worse asynchrony were found in patients withmost delayed Tmsv located in the inferior or posterior wall comparedwith those located in the anterior interventricular septum (IVS).3．In HF patients with CLBBB, Tmsv-SD% and Tmsv-Dií% werehigher than other subgroup. In all CLBBB patients, a liner correlationwas found between 3D-EF and LV systolic asynchrony determined byTmsv-SD% and Tmsv-Dif%(16 segmental Tmsv-SD% 7．47±3．85, P <0．001, Tmsv-Dif% 26．17±16．37, P < 0．01) .4．HF patients with narrow or wide QRS complex, have higherTmsv-SD% and Tmsv-Dif% than normal subjects. (16 segmentalTmsv-SD% r =-0．6216 P < 0．001, Tmsv-Dif% r =-0．5077 , P < 0．01)5．In all HF patients, a liner correlation was found between 3D-EFand LV systolic asynchrony determined by Tmsv-SD% and Tmsv-Dif%.By multiple regression analysis, LVEF determined by RT3DE was theonly independent factor of LV systolic asynchrony. (16 segmentalTmsv-SD% r =-0．4913, P < 0．0, Tmsv-Dif% r =-0．4819, P < 0．0)6．Different shapes of volume-time curves were found betweenanterior and posterior IVS, with various relationship with QRS interval,3D-EF and LV synchronicity, which indicated different role of segmentmovement between the two adjacent segments.7．In ischemic HF subgroups, the most delayed Tmsv in theposterior wall indicated a relative preserved LVEF and less obvious LVasynchrony.ConclusionLV mechanical asynchrony could be detected by RT3DE in either HF orventricular conduction disturbances patients, which were more severe in HF patientswith wide QRS complex. LVEF determined by RT3DE was the only independentfactor of LV systolic asynchrony. The reduced cardiac function and abnormalventricular conduction patterns may support a possible cause-and-effect relationshipbetween ventricular conduction disturbances and HF.更多还原