超声心动图三维斑点追踪技术诊断静息状态冠心病的价值

Incremental value of restingthree-dimensional speckle-tracking echocardiography in detecting coronaryartery disease

YOU‑JING SUN,FANG WANG, RUI‑SHENG ZHANG, HAI‑YAN WANG, CHEN‑GUANG YANG, JIE CAI, WEI‑ERZANG, MING‑ZHOU LI, XIN QI and JING LI, Beijing,China

超声心动图三维斑点追踪技术诊断静息状态冠心病的价值

报告人：赵小琪

Abstract

The aim of thepresent study was to investi­gate the incremental value of resting three-dimensionalspeckle-trackingechocardiography (3D-STE) in the detection of early‑stage left ventriculardysfunction in patients with coro­nary artery disease (CAD). A total of 110patients suspected of having CAD were recruited. All patients underwent 3D‑STEand coronary artery angiography (CAG). They were divided to a CAD group and anormal group according to the results of CAG. Using 3D‑STE software, the peakvalues of longitudinal strain (LS), circumferential strain (CS), radial strain(RS) and area strain (AS) and the time to peak value of these strains (T‑LS, T‑CS,T‑RS and T‑AS) were measured. A receiver operator characteristic curve (ROC)was used to analyze the sensitivity of these strains for the diagnosis of CAD.ROC analysis indicated that T‑LS and composite indices combining the peakstrain value and time to peak of LS, CS and AS have diagnostic value for theearly detection of CAD; the area under the curve (AUC) values were 0.667,0.692, 0.621 and 0.672 respectively (P<0.005). The composite index oflongitudinal strain demonstrated the highest diagnostic value for CAD with 62%sensitivity and 76% specificity. These results indicate that 3D-STE hasincremental value for the diagnosis of CAD in patients at rest.

摘要

本研究的目的是探讨超声心动图三维斑点追踪技术检测早期冠心病患者静息状态下左室功能不全的价值。研究对象是110例疑似冠心病的患者。所有受试者先行冠脉造影及三维超声心动图检查，根据冠脉造影检查结果分为冠心病组和正常对照组。应用三维斑点追踪技术软件获得左室各节段相应的应变的峰值(包括径向应变RS、圆周应变CS、纵向应变LS、面积应变AS)及相应的达峰时间(T-RS、T-CS、T—LS、T-AS)。应用ROC曲线分析上述各应变指标在冠心病诊断中的敏感性。ROC曲线分析结果表明纵向应变达峰时间及圆周应变CS、纵向应变LS、面积应变AS复合指标对早期冠心病有诊断价值。超声心动图三维斑点追踪技术(3D—STE)在冠心病诊断中诊断价值最大的为纵向应变复合指标LSI(LS达峰&LS达峰时间)，其敏感性为61．8%特异性为76．2％。从研究结果可以得出超声心动图三维斑点追踪技术(3D—STE)对静息状态下冠心病的诊断具有一定价值。

Introduction

Coronary arterydisease (CAD) is the most common cardio­vascular disease, and its incidenceincreases in the elderly (1). Early detection and intervention for leftventricular (LV) dysfunction are of great importance in patients with CAD (2).Echocardiography is noninvasive, inexpensive and convenient. The detection ofpatients with CAD by this method is likely to improve the benefit‑risk ratio inpatients.

During recentyears, strain and strain rate imaging echo­cardiography have emerged asvaluable tools that provide a comprehensive and reliable assessment ofmyocardial function. However, 2D‑STE has intrinsic limitations, such as longexamination times, a geometric assumption of LV morphology, and mistracking ifspeckles move out of the scanning plane.

three‑dimensionalspeckle‑tracking echocar­diography (3D‑STE) is free of geometric assumptionsand speckles moving out of the scanning plane. In the present study, the aimwas to investigate the incremental value of resting 3D‑STE in the detection ofLV dysfunction in patients with CAD and to identify sensitive indicators forthe detection of CAD.

冠心病是最常见的心脏疾病。老年发病率较高。对有左心功能不全的冠心病患者进行早发现、早干极其重要。超声心动是一种无创、经济、简便的检查方法。这种检查方法能最大程度提高患者的获益／风险比。

目前，应变(Strain，S)和应变率(Strain Rate，SR)成为较全面、可靠的评价心肌运动的重要指标。已经有研究证实了二维斑点追踪技术可以评价左室收缩功能。但二维‑STE具有局限性，如检查时间长，LV立体形态假设，及失追踪等。三维斑点追踪技术可以避免部分弊端。本研究的目的是探讨三维斑点追踪技术检测早期冠心病患者静息状态下左室功能不全的价值及确定诊断冠心病的敏感性指标

Patients and methods

Study population

Thestudy evaluated 110 patients (68 males; age, 63±9 years) who were suspected ofhaving CAD and who were referred for coronary artery angiography (CAG) atBeijing Hospital (Beijing, China) between June 2010 and August 2012.

Echocardiographicimage acquisition and analyses

Echocardiographicdata were acquired with a ultrasound system, which was equipped with a 2Dtransducer (frequency, 1‑5 MHz), 3D volume transducer, 3D speckle‑trackinganalysis software and a background processing workstation. Firstly, general 2Dultrasonic detectors were used to collect images of the para­sternal long axis,short axis and apical four‑chamber view. Secondly, following conversion to the3D volume transducer with an apical four‑chamber view, the pre‑4D mode wasselected to obtain a clear image of the LV endocardium. Then, as the full‑4Dmode was entered, the patient was asked to hold their breath at the end ofexpiration.

Thestored dynamic cardiac images were extracted in the off‑line state. Thisinvolved entering ‘3DT (three‑dimensional speckle tracking) mode’, adjustingthe baseline and angle, clearly displaying the image of the endocardium, mitralannulus and apex, and speckle assignment on plane A and plane B separately. Theinstrument then speckle‑tracked automatically when the ‘start’ button waspressed. The curve of the endocardium was drawn, and the software analyzed thedata and calculated the peak value strains (LS), (CS), (RS) (AS) of 16 sectionsof the left ventricle and the time to peak value of the strains.

Observational indices

Strainvalues and the time to peak value of the strain for 16 local myocardialsegments from the 3D‑STI were observed. The strain values were RS, CS, LS and AS.The time to peak values for the strains were (T‑RS), (T‑CS), (T‑LS) and (T‑AS).

Statistical analysis

The observation indices were numerical variable data. Afterestablishing the database, with the use of Excel (Microsoft Corporation,Redmond, WA, USA) and SPSS version 16.0, binary logistic regression analysisand receiver operator character­istic curves (ROCs) were used to analyze thesensitivity of the strains for the diagnosis of the CAD.

研究对象

2010年6月至2012年8月于卫生部北京医院心内科就诊疑似冠心病并拟行CAG术的患者1 10例，其中男性68例，女性42例，年龄(63．2±8．9)岁，身高(166．4±7．8)cm，体重(72．7±10．2)kg。排除标准：心律失常；陈旧心肌梗死病史、既往有PCI治疗史；心功能衰竭者；心肌病、严重瓣膜病、先心病史等其它心脏病变，三维图像质量差，无法进一步分析者

超声图像的获取及分析

研究仪器采用日本东芝Toshiba SSH一880H心血管专用彩色超声诊断仪，配有二维探头(频率为1-5MHz)和三维容积探头(频率-5MHz)及3DT三维斑点追踪分析软件和后台处理工作站。首先对所有受检者同步连接心电图，嘱受检者左侧卧位，使用常规二维探头(频率为l一5MHz)采集胸骨旁左室长轴、短轴、心尖四腔心、两腔心、三腔心等切面图像。(2)在心尖四腔心切面换用三维容积探头(探头频率卜5MHz)，选择pre一4D模式调整图像至左心室内膜显像清晰后，进入全容积(full一4D)模式，嘱受检者呼气末屏气，成像角度为(70—80。)×(70-80。)，采集并存储心脏三维全容积动态图。

脱机提取所存储的心脏三维全容积动态图，选择进入“3DT(三维斑点追踪)模式”，调整图像基线和角度，使心内膜、二尖瓣环及心尖部显像清晰，然后在A、B双平面分别对左、右二尖瓣环和心尖进行斑点标记，点击Start按钮仪器将自动进行超声回声斑点追踪，此时软件可描绘出心内膜曲线(见图1)，软件将自动分析并计算出左室心肌16个节段各段的应变指标的峰值及达峰时间。

观察指标

本研究选择观察的指标是由3D—STI技术得到的局部心肌各节段应变值和应变达峰时间。包括4项应变值：径向应变(RS)、圆周应变(CS)、纵向应变(LS)、面积应变(AS)；4项应变达峰时间：径向应变达峰时问(T—RS)、圆周应变达峰时问(T—CS)、纵向应变达峰时问(T-LS)、面积应变收缩期达峰时间(T-AS)。

统计分析

上述各观察指标均为计量资料，采用EXCEL和SPSS 16．0统计分析软件建立相应数据库并行统计学分析。计量资料用均数±标准差表示，多组间比较采用单因素方差分析，运用Logistic二元回归分析和ROC曲线对各指标诊断冠心病的敏感性进行分析。P〈O．05表示具有统计学差异。

Results

Resultsof CAG

According to the CAG results, of the 110 patients enrolled, 68 exhibitedCAD (levels 1-4), which were assigned to the CAD group. The other patients(level 0) were designated the non‑CAD group .

3D‑STE evaluation of LV local function in different gradedstenoses of coronary arteries. Generally, it was observed that the peak valueof strain of local segments of the left ventricle decreased as the stenosisdegree of the supplied vessel increased, the higher the degree of stenosis thelonger the time to the peak value. In addition, these relationships were mostevident at the highest graded degree of stenosis. For example, the peak valueof AS of certain segments supplied by the left circumflex (LCX) arteryexhibited a reduction in differently graded coronary stenosis groups. Thehigher the grade of stenosis the lower the peak value of AS . In addition, theT‑LS of certain segments supplied by the left anterior descending arteryascended in differently graded coronary stenosis groups .

ROCcurve and sensitive indicators

In this study, three kinds of ROC were generated. One was for thepeak strains RS, CS, LS and AS (Fig. 3), one was for the time to the peakstrain, which comprised T‑RS, T‑CS, T‑LS and T‑AS (Fig. 4), and the third wasfor the composite index. The composite indices were designated RS1, CS1, LS1and AS1

Through the ROC analysis, an area under the curve (AUC) wasdetermined for each index.

Analysis of the ROC curves and AUCs, revealed that each individualpeak value of strain, namely RS, CS, LS and AS, had no diagnostic value for theearly detection of CAD (P>0.05). Only T‑LS had statistical significance inthe diagnosis of CAD.

However, the composite index of peak strain and time to peakstrain had significantly higher sensitivity for the detection of CADand wasfound to have 62% sensitivity and 76% specificity for the detection of CAD.

Excellentdiagnostic value and individual prediction

Through the analysis of the ROC of LS1, it was determined that themaximum Youden index was 0.38 and the excellent diagnostic probability value (Pexce) of the LS1 was Pexce=0.615.Pexceis an ROC‑derived statistical index thatindicates the likelihood of a positive diagnosis.

Pindiis aprobability value that can be used to predict whether the individual patient islikely to have the disease or not, and can be compared with Pexce. For calculating PindiofLS1, this study established a binary logistic regression equation throughlogistic regression analysis.

冠脉造影结果

所有患者均行冠脉造影(CAG)术，造影结果68例为冠心病组，42例为正常对照组。根据冠脉造影显示的冠脉狭窄程度对病变冠脉进行分级：0级，冠脉狭窄率=O％，诊断为冠脉正常：然后以25、50、75分界分为冠脉微狭窄1；冠脉轻度狭窄2；冠脉中度狭窄3；冠脉重度狭窄4。当冠脉狭窄率≥50％，即狭窄程度≥3级，即可确诊为冠心病。本研究患者分为五组：左前降支病变(LAD)组87例，左回旋支病变(LCX)组59例；右冠状动脉病变(RCA)组67例。

三维斑点追踪技术对不同程度冠脉狭窄左室局部功能的评价。结果显示：病变血管所对应的部分室壁节段的应变峰值有随着狭窄程度的加重而减小的趋势，即狭窄成度越重，应变峰值越小：同样狭窄成度越重，病变血管所对应的部分室壁节段的应变达峰时间越长，尤其在重度狭窄组中尤为显著。

以LCX各节段的面积应变峰值为例说明，LCX病变组不同程度冠脉狭窄组间所供应室壁节段AS峰值比较，狭窄程度越重，面积应变的峰值越小。LAD病变组不同程度冠脉狭窄组间所供应室壁节段T—LS比较，狭窄程度越重，纵向应变达峰时间越长。

ROC曲线及敏感性指标

本研究中所做ROC曲线主要分为三部分：①所有应变峰值的ROC曲线；②所有应变达峰时间的ROC曲线；③各应变峰值和达峰时间组合的复合指标的ROC曲线。计算每个指标对应的曲线下面积。具体结果如下：通过上述ROC曲线和曲线下面积(可得出各应变峰值在冠心病诊断中均无统计学意义（P>O．05)；各应变达峰时间中仅纵向应变达峰时间(T—LS)在冠心病中诊断具有统计学意义(P：O．003)，曲线下面积(AUC)为0．667；而对于复合指标，对冠心病诊断的敏感性明显高于峰值或达峰时间单个指标，CS复合指标的AUC为0．621(P：O．034)，LS复合指标的AUC为0．692(P：O．001)，ASl的AUC为0．672(P=O．672)。3D-STE对诊断冠心病有统计学意义的各指标的诊断价值依次为：LSl>ASl>T—LS>CSl。LSl的诊断价值最高。

最佳诊断界值和个体预测

本研究对复合指标LSl进行ROC曲线分析，得出当Youden指数最大时(Youden=0．38)，所对应的最佳诊断界值概率值P=0．615，所对应敏感性为61．8％，特异性为76．2％。

个体预测概率值与最佳诊断界值概率值比较可以用来诊断是否患有冠心病。

将所有可能的切点作为阈值进行灵敏度和特异度计算后，以敏感性为纵坐标代表真阳性率，(1—特异性)为横坐标代表假阳性率，作图绘成ROC曲线。一般以Youden指数(约登指数)最大，即(灵敏度+特异度一1)达到最大所对应的值为最佳诊断界值。关于预测概率值的计算，需要首先建立Logistic回归方程。用SPSS的Binary Logistic方程对变量LS峰值和LS达峰时间进行Logistic回归分析，可得到两变量的回归系数，进而求得Logistic回归方程。然后将各变量值(LS峰值和LS达峰时间)代入上述方程，即可得出个体预测概率值P，与最佳诊断界值P=0．615进行比较，即可早期判断患者是否为冠心病。

Discussion

Speckle‑tracking strain imaging has been demonstrated to be anappropriate method for the examination of global and regional LV functionalproperties (15,16), which was confirmed in the present study. In this study, itwas found that changes in the peak value and time to peak value of certain strainsaccorded with the physiological characteristics of the left ventricle.Secondly,through the ROC analysis of each parameter measured by 3D‑STE。

By convention, myocardial deformation is divided into threedirections (17). LS and CS are considered to reflect the contraction oflongitudinally arranged endocardial fibers and circumferentially arrangedmidlayer fibers, respectively. In general, the longitudinally arrangedsubendocardial fibers are more vulnerable due to their direct exposure to theintraventricular blood pressure and the anatomy of the coro­nary circulation(18,19). As a result, longitudinal function is impaired first in many diseases,including CAD.

In the present study, it was demonstrated that resting 3D‑STE hadincremental value for the prompt detection of coronary lesions and a logisticregression equation was estab­lished。

In addition, an evaluation model may be established through theaddition of risk factors such as hyper­tension, diabetes, smoking andhyperlipidemia.

讨论

斑点追踪技术已被证实可以评价部分或整体心肌功能，本研究中也得到了证实。同时得出左室心肌应变峰值及应变达峰时间的分布特点与心脏运动的生理特性相符。

通过分析roc曲线获得最佳诊断指标LSI。

心脏正常心肌纤维呈三层分布。LS和CS可以反映心内膜下纵形心肌纤维、中层环形心肌纤维的收缩情况，通常情况下心内膜下纵向排列的心肌纤维由于直接接触心脏内血流压力及冠脉系统更易受损，所以，冠心病在内的很多心脏疾病中纵向功能最先受损。本研究证实3DSTE对静息状态冠心病有诊断价值，并建立了LOGISTIC回归方程。这为冠心病的诊疗带来更多有价值的信息。同时为以后更复杂的研究奠定了基础。