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超声心动图评价移植心脏结构和功能改变的临床研究
Evaluation of Ventricular Geometry and Function Using Echocardiography in Postoperative Patients with Heart Transplantation
【作者】 覃小娟;
【导师】 谢明星;
【作者基本信息】 华中科技大学 , 影像医学与核医学, 2012, 博士
【摘要】 随着免疫抑制剂的应用和血管外科技术的不断进步,心脏移植已经成为终末期心衰患者最有效的治疗方法。心脏移植术后,大部分移植心脏能够恢复和维持正常的射血分数。但移植心脏在手术过程中经历了缺血、手术操作、再灌注等过程,术后可能会有排异、免疫损伤,长期应用免疫抑制剂引起的高血压等,这些因素都会损伤心肌,引起相应的功能改变。心脏移植术后患者,移植心脏的结构与功能参数改变是预测移植心脏预后的主要因素。超声心动图作为监测心脏形态结构和功能的首选检查手段,其不仅能够清晰观察移植心脏的解剖结构,而且还能评价其功能。二维斑点追踪技术(STI)是建立在高帧频动态二维灰阶超声图像基础上,通过实时跟踪完整心动周期过程中心肌组织的运动轨迹,然后通过工作站对整个心动周期的图像进行逐帧分析比较,最终反映出心室长轴和短轴方向的心肌收缩功能,具有无角度依赖性,可重复性好的优点。本研究的目的旨在应用常规二维超声和斑点追踪技术对移植心脏结构和功能进行检测,深入探讨心脏移植术后患者心脏结构和功能的改变,以期对移植术后患者心脏结构和功能改变提供更有价值的信息,进而为临床提供更大的帮助。本研究分为以下三部分:第一部分:二维超声心动图评价移植心脏左室质量变化34例健康自愿者及32例心脏移植患者行常规超声检查,其中心脏移植患者根据术后时间分为3组:A组(术后3月)、B组(术后6月)、C组(术后时间>12月)。测量所有研究对象的左室构型相关二维数据,计算左室质量,旨在观察移植术后不同移植心脏左室质量改变,并探讨引起左室质量增加的可能因素。结果:①与健康对照组相比,移植后各组左房增大、心率增快,且差异具有显著意义(P均<0.05),性别、BMI无显著性差异(P均>0.05);心脏移植各组间性别、年龄、BMI、LA均无显著差异(P均>0.05)。②左心室构型指标比较:心脏移植后各组与健康对照组间LVEDD无显著差异(P均>0.05)。IVST、PWT在心脏移植后各组的测值均较健康对照组大,差异均有统计学意义(P均<0.05),移植各组内部比较发现,C组的IVSTD、PWT较A组及B组均增厚(P均<0.05),但是A与B间差异不显著(P>0.05)。心脏移植后各组LVM均大于健康对照组(P均<0.05);移植术后各组间比较,移植后各组左心室质量随移植后时间呈增加趋势,B、C与A比,左心室质量显著增加(P分别=0.001,0.020),但C组与B间LVM差异无统计学意义(P=0.221)。③A组、B组及C组LVH发生率分别为20%、34.6%、54.2%,随术后时间延长而增加,但单因素分析提示左心室质量与术后时间之间无明显相关性(r=0.28),与高血压发生率关系密切。多因素分析提示,高血压及急性排异反应史是引起左心室肥大的危险因素。移植高血压组及急性排异史组的左心室质量明显高于非高血压及未发生急性排异反应组(P均<0.05)。术后1年后,患有高血压病的患者LVH发生的几率是没有高血压的5倍左右。第二部分:STI评价心脏移植术后长期存活患者左室整体收缩功能对心脏移植术后长期存活着(>1年)的24例患者(分为左室肥大组(n=13)与左室质量正常组(n=11))进行常规二维超声及彩色多普勒超声心动图检查,并获取胸骨旁左室乳头肌水平和短轴观,心尖四腔心观二维灰阶动态图像并储存,然后通过Qlab Analysis 7.1超声工作站进行脱机分析。比较左室整体纵向应变与应变率、环向应变与应变率,评价左室整体功能改变,并分析引起左室功能改变的可能因素。结果:①心脏移植术后两组患者进行移植时受体年龄、体重、肺动脉压力、左室射血分数、供体冷缺血时间、热缺血时间、主动脉阻断、供体年龄与体重均没有显著差异(P均>0.05)。②心脏移植后两组患者与正常对照组比较,年龄、身高、体重、性别间无显著差异(P均>0.05)。移植后两组患者的心率明显快于正常对照组(P均<0.05),但两组内差异不显著(P>0.05)。移植后两组与正常对照组比较,各组间左室射血分数差异不显著(P均>0.05)。与正常对照组比较,心脏移植术后二尖瓣口E/A比值明显大于正常对照组(P均<0.05),心脏移植后左室质量正常组大于左室质量肥大组,但是差异无统计学意义(P>0.05)。移植后两组的室间隔舒张末厚度、左室后壁舒张末厚度、左室质量明显大于正常对照组(P均<0.05),且移植后左室肥大组明显大于移植后左室质量正常组(P均<0.05)。移植后左室质量正常对照组和正常组相比较,左室舒张末内径无明显差异(P>0.05),但移植后左室肥大组左室舒张末内径大于左室质量正常组与正常对照组,差异具有显著意义(P均<0.05)。③与正常对照组相比较,移植后两组的GCS、GCSR、GRS、GRSR、GLS、GLSR均明显减低,差异具有统计学意义(P均<0.05),且移植后左室肥大组GCS、GCSR、GRS、GRSR、GLS、GLSR较移植后左室质量正常组进一步减低,差异具有统计学意义(P<0.05)。④GCS、GCSR、GRS、GRSR、GLS、GLSR与左室质量之间均存在线性相关,左室质量增加会导致GCS、GCSR、GRS、GRSR、GLS、GLSR值下降。⑤GCS、GCSR、GRS、GRSR、GLGLSR指标参数具有较高的可重复性与一致性。第三部分:STI评价心脏移植术后长期存活患者右室收缩功能以心脏移植术后超过1年的19例患者为研究对象,应用二维应变技术测量并记录右室游离壁及室间隔基底段、中间段、心尖段纵向收缩峰值应变及右室整体纵向收缩峰值应变(GLS),并分析术前影响GLS的因素、及术后预测GLS的相关指标。结果:①心脏移植组与正常对照组在年龄、性别、身高、体重等一般情况无差异(P均>0.05),但移植组心率明显快于正常对照组(P<0.05)。②移植组右房、右室均较正常对照组增大(P均<0.05),肺动脉内径及肺动脉瓣口收缩期血流峰速与正常对照组无显著差异(P均>0.05),心脏移植组三尖瓣口舒张早期与舒张晚期血流峰值速度比值较正常对照组大(P<0.05),右室面积缩小率、肺动脉瓣血流速度积分、右室游离壁侧三尖瓣环收缩期运动峰速较正常对照组小(P均>0.05)。心脏移植组三尖瓣返流发生率较正常对照组显著增高(P<0.05),返流压差较正常对照组稍高,但差异无显著意义(P>0.05)。③心脏移植组与正常组右室各节段纵向应变变化趋势一致,右室游离壁由基底向心尖逐渐减小,间隔由基底至心尖逐渐增大;基底段与心尖段游离壁侧纵向应变显著大于间隔(P均<0.05),但游离壁与间隔心尖段差异不显著(P>0.05)。心脏移植组右室游离壁基底段、中间隔、间隔基底段及右室整体纵向应变较正常对照组显著下降(P均<0.05),游离壁与间隔心尖段虽然也减低,但是差异无统计学意义(P均>0.05),间隔心尖段无明显差异(P>0.05)。④右室整体纵向应变与PVVTI、RVFAC、RV、Sm具有显著线性关系。⑤术前热缺血时间是影响右室整体独立危险因素(β0.515,P=0.001,R2=0.266);术后右室游离壁侧三尖瓣环收缩期运动峰速是右室整体纵向应变的独立预测因子(β-0.693,P<0.001),对右室整体纵向应变的预测值R2为0.48;术前热缺血时间与术后Sm一起对右室GLS%的预测值为0.5460(β1=0.275, P1=0.036;β2=-0.579, P2<0.001)。结论:通过以上观察和研究得到以下结论:①心脏移植术后患者左室发生重构,主要表现为左室质量增加,心室腔大小改变不明显。②移植后左室质量增加在术后早期即出现,随着术后时间越长,高血压发病率的增高,出现左室肥大的患者增加。高血压是引起术后左室肥大的主要原因之一。手术1年后,患有高血压病的患者发生LVH的几率是未患高血压病的5倍左右。急性排异反应也是引起术后左室重构的原因之一,发生过急性排异反应的患者左室质量增加更明显。③心脏移植术后长期存活患者,左室心肌收缩功能均有一定程度的受损,且左室肥大患者受损更严重。左室肥大会影响左室心肌功能,故移植后预防左室肥大可维持移植心脏收缩功能。④心脏移植术后长期存活患者,右室局部及整体收缩功能受损。右室功能损害与术后早期肺动脉高压无关,与术前热缺血时间关系明显。⑤超声技术作为心脏移植术后移植物形态和功能检测的常用工具,能对移植心脏形态、功能做出较为全面、准确的评价。
【Abstract】 Advances in immunosuppression and vascular surgical technique have allowed cardiac transplatation to be a viable and the most effective treatment for patients with end-stage heart failure. The vast majority of grafts can restore and maintain the normal ejection fraction after the transplantation. Heart graft has experienced the injury of ischemia-reperfusion, surgical trauma during the process of transplantation. Andrejection, immune injury, high blood pressure induced by long-term application of immunosuppressant may occur after surgery. These factors can lead to myocardial impairment and alterations of the cardiac function. Abnormal graft structure and function are the main predictive factors for the prognosis of patients after heart transplantation. Echocardiography is one of the best means in assessment of cardiac morphology and function, with which anatomical structure of the graft can be clearly observed, and the systolic function can be evaluated.Two-dimension speckle track imaging is based on two-dimensional gray scale ultrasound images and tracking of myocardial tissue space motion in real-time. The images which were obtained were analyzed and compared frame by frame in the work station, and parameters of left ventricular function, such as strain and strain rate in both short axis and long axis view, can be obtained. Two-dimension speckle track imaging has the benefit of no angular dependence, also not influencedby the swinging and stretching movement of the heart.In this study, we detected the structure and function of transplanted heart by usingconventional two-dimensional ultrasound and speckle tracking technique in order to explore the changes in cardiac structure and function of heart transplant patients after surgery.This article aimed to reveal the changes in structure and function ofgraft and to provide fundamental information for the treatment of such patients. The study was divided into three parts as followed:Part 1. Assessment of left ventricular mass in postoperative patients with heart transplantation by echocardiographyThe aim of this part was to observe the changes of LV structure over time in patient after HT, and toinvestigate the correlated factorsin LV remodeling. Conventional two-dimensional echocardiography was applied to scan 34 control healthy subjects and 32 patients with HT after 3months (A group),6 months (B group),>12 months (C group) of operation, and two dimensional parametersof the left ventricular were mearsured,andthe left ventricular mass was calculated.Results:①ompared with the control group, each group of HT had larger size of left atrium (LA), faster heart rate (HR) and older age(P<0.05). Body mass index (BMI), sex, left ventricular ejection fraction (LVEF) were similar in the two groups (P>0.05). Gender, age, BMI, LA, HR and LVEF had no significant differencesbetween each HT group (P>0.05).②ndicators of left ventricular geometry were different in each group:LVEDD had no significant difference between each group (P>0.05). IVST, PWT in each group of HT were larger than in control group, and in group C was larger than in group A and B (all P<0.05). However, there were no significant difference between group A and B (P>0.05). Value of LVM in HT groups were higher than in control group, and LVM was higher in group B and C than in group A (P<0.05). However, there were no statistically significant between group B and C (P>0.05).③Prevalence of LVH in group A, group B, group C was 20%、34.6%、54.2%, respectively, increased with the time after operation. But the univariate analysis indicated that there was no significant correlation between LVM and postoperative time (r=0.28, P>0.05). Instead, LVM was significantly related with the incidence of hypertension. In multivariate analysis, hypertension and acute rejection (AR) events were independent risk factors for the development ofLVH. Moreover, LVM in hypertension group of HT was higher than in non-hypertension group of HT (p<0.05), as well as of HT with AR.Part 2. Assessment of left ventricular global systolic function in long-term survival patients over HT operation by 2-dimensional speckle tracking echocardiographyIn this study,24 patientssurvived more than one year after heart transplantation were examined with two-dimensional echocardiography and Color Doppler Flow Imaging (CDFI). These patients weredivided into two groups:one group with left ventricular hypertrophy (LVH), another with normal left ventricular mass (LVM).The short axis view of the left ventricular on the level of papillary muscle and the apical four-chamber view were acquired and stored in dynamic mode, and then analyzed off-line in Qlab Analysis 7.1. We compared the global left ventricular longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), GLS rate (GLSR), GCS strain (GCSR) and GRS strain (GRSR) between the two groups. The global left ventricular function is evaluated, and the possible factorsare analyzed.Results:①There were no significant differences between the two groups in age, weight, pulmonary artery pressure, left ventricular ejection fraction, donor cold ischemia time, warm ischemia time, aortic cross-clamping, donor age and weight(P>0.05).②here are no significant differences betweenthe HT groups and thenormal control group in age, height, weight, gender and left ventricularejection (P>0.05). The heart rate of both HT groups is significantly faster thanthe normal control group (P<0.05), but the differences betweenthe two HTgroups are not significant (P>0.05). Compared with the normal controlgroup, theE/A ratios in the two HT groups weresignificantly greater than the normal control group (P<0.05), but thedifferences between the two groups were not significant (P>0.05). Theend-diastolic thickness of the interventricular septum and the left ventricular posterior wall inthe two groups is significantly greater than the normal controlgroup (P<0.05), and those in the LVH group weresignificantly greater than those in the group with normal LVM (P<0.05). The differences in left ventricular end diastolic diameter between thegroup of normal left ventricular mass and the normal control group wasnotsignificant (P<0.05), but it wassignificant between the LVH group and the normal control group (P<0.05).③Compared with the control group, in GCS, GLS,GRS, GCSR, GLSR, GRSR were significant lower in both HT groups (P<0.05). GCS, GLS, GRS, GCSR, GLSR, GRSR in the HT group with LVH was even lower than in the HT group with normal LVM (P<0.05).④There was a linear correlation between the increased LVM and the decreased GCS, GLS, GRS, GCSR, GLSR, GRSR..⑤There were high repeatability and consistency of these parameters:GCS, GLS, GRS, GCSR, GLSR, GRSR.Part 3. Assessment of right ventricular systolic function in hearttransplantation patients with late survival by 2-dimensional speckle tracking echocardiographyThe aim of this part was to assess RV regional and global function in asymptomatic HT patients by STI. 19 asymptomatic HT patients whose postoperative period is more than one year and 19 healthy controls were studied. RV longitudinal peak systolic strains were measured in the basal, mid and apical segmentsof RV free wall and interventricular septum (IVS) by STI from the apical 4-chamber view. RV global longitudinal peak systolic strain (GLS) was also measured. The preoperative factorsinfluencing GLS and the predictive factors of postoperative GLS were explored.Results:①There were no significantly difference in age, sex, height, weight between two groups (P>0.05). However, the heart rate in HT patients was faster than in control subjects (P<0.05).〤ompared with controls, the diameters of RA and RV were increased (P<0.05), Pulmonary artery diameter (PA) and the systolic peak velocity of PA were similar(P>0.05). The E/A value of tricuspid in HT patients were greater than in controls (P<0.05), but the RVFAC, PVVTI, Sm in HT patients were lower than in controls (P<0.05). The differential pressure of tricuspid regurgitation flow in HT patients were slightly higher than in control, without statistically significant (P>0.05).③Segmentalstrain of the HT patients and the controls had a same trend, gradually reduced from the basement to apexin RV free wall, and gradually increased from the basement to apexin interventricularseptum (IVS). The strain of the basal and middle segmentsin RV free wall were higher than in IVS (P<0.05), but the strain of apicalsegment between in RV free wall and in IVS had no significantly difference (P>0.05). Although The strain of basal segment in RV free wall and the strain of middle segment in IVS were lower in HT patients than in controls, it was not statistically significant (P>0.05), and there was no significant difference between the strain of apical segment in RV free wall in HT and in controls (P>0.05).@GLS of RV was correlated positively/inversely with these indicators:PVVTI、RV FAC、RV、Sm(r1=-0.451, P1=0.005; r2=-0.489, P2=0.002; r3=0.382, P3=0.018; r4=-0.693, P4<0.001).⑤reoperative warm ischemia time was the independent riskfactor of RV GLS (β=0.515, P=0.001, R2=0.266). Tricuspid valvular annular systolic peak velocity (Sm) after HT operation was the independent predictor for RV global strain and strain rate (/?=-0.693, P=0.000), withadjust R2=0.48. The conjointadjust R2value ofpreoperative warm ischemia time and postoperative Sm was 0.516 (β1=0.275, P1=0.036;β2=-0.579, P2=0.000).Conclusions:In this study, our conclusions are as follow:①The left ventricle in patients after heart transplantation wasreconstructed, mainly showed as the increase in left ventricular mass, and the changes in ventricular cavity size was not obvious.②Left ventricular mass increased in the early postoperative period after transplantation; the incidence of hypertension and left ventricular hypertrophyincreasedwith postoperation time. Hypertension was one of the main reasons for the development of postoperative left ventricular hypertrophy. Acute rejection was also one of the reasons for postoperative left ventricular remodeling, and the left ventricular mass increase was more obvious in patientswith acute rejection.③Left ventricular systolic function was impaired in heart transplant recipients with long-term survival and it was more serious in patients with leftventricular hypertrophy. Left ventricularhypertrophy can affect the left ventricular function. Therefore, prevention of left ventricular hypertrophy after operation can maintain the cantractilefunction of the transplantated heart.④Local and global right ventricular systolic function were impaired after hearttransplantation in patients with long-term survival. Right ventricular dysfunction was closely correlated with the preoperativewarmischemia time, rather than the early pulmonary hypertension.⑤As a commonly used tool for assessment of cardiac transplantation graft morphology and function, ultrasound technology can offera comprehensive and accurate evaluation on thegeometry and function of transplanted heart.