曹 寅，黃 晶，鄒燕珂，廖晴瑤，熊 波，譚 杰

(重慶醫(yī)科大學附屬第二醫(yī)院心血管內(nèi)科，重慶 400010)

三維斑點追蹤成像左心室應(yīng)變指標正常參考范圍的Meta分析

曹 寅，黃 晶*，鄒燕珂，廖晴瑤，熊 波，譚 杰

(重慶醫(yī)科大學附屬第二醫(yī)院心血管內(nèi)科，重慶 400010)

目的 采用Meta分析評估健康成人的三維斑點追蹤成像(3D-STI)左心室整體縱向應(yīng)變(GLS)、整體環(huán)向應(yīng)變(GCS)、整體徑向應(yīng)變(GRS)、整體面積應(yīng)變(GAS)的正常參考范圍。方法 在Embase、Pubmed、Cochrane Library等英文資料庫中，檢索2016年8月1日前公開發(fā)表的關(guān)于3D-STI評價左心功能的病例對照研究。按照納入和排除標準，對文獻進行篩查和提取數(shù)據(jù)。以加權(quán)均數(shù)差(WMD)及95%可信區(qū)間(CI)作為合并統(tǒng)計量，采用的統(tǒng)計分析軟件為STATA 12.0。結(jié)果 最終納入27項研究，1 552名健康成年被試。GLS的WMD和95%CI為17.80、(16.27，19.33)，GCS的WMD和95%CI為24.73、(22.50，26.95)，GRS的WMD和95%CI為47.86、(39.52，56.19)， GAS的WMD和95%CI為36.17、(34.08，38.26)。結(jié)論 通過Meta分析確定成人左心室應(yīng)變指標的正常參考范圍，對采用3D-STI評價疾病狀態(tài)下心臟結(jié)構(gòu)和功能的變化具有一定的指導意義。

三維斑點追蹤成像；心室，左；應(yīng)變；參考范圍

近年來，心血管事件發(fā)生率顯著增加。早期發(fā)現(xiàn)左心室結(jié)構(gòu)重構(gòu)和功能異常對疾病診治和預(yù)后至關(guān)重要。通過三維斑點追蹤成像(three-dimensional speckle tracking imaging, 3D-STI)技術(shù)可敏感地獲得心肌應(yīng)變參數(shù)，準確評估心肌功能[1]，可重復性較高[2-3]。目前臨床3D-STI已逐步用于左心室功能的評估[4-7]。但采用3D-STI評價成人左心室應(yīng)變指標仍缺乏正常參考范圍，在一定程度上限制了該技術(shù)的應(yīng)用。本研究通過對健康成人3D-STI左心室應(yīng)變指標進行Meta分析，獲得左心室應(yīng)變指標的正常參考范圍，為3D-STI評估左心室功能變化提供參考依據(jù)。

1 資料與方法

1.1文獻檢索 檢索Embase、Pubmed、Cochrane Library等數(shù)據(jù)庫于2016年8月1日前公開發(fā)表的英文文獻。檢索詞為“three-dimensional speckle tracking”、“l(fā)eft ventricular”；對入選文獻的參考文獻進行二次檢索。

1.2納入與排除標準 納入標準：公開發(fā)表的英文文獻；采用3D-STI技術(shù)評價健康個體左心室功能的觀察性研究和對照組為健康人群的對照研究；包含左心室應(yīng)變指標，即整體縱向應(yīng)變(global longitudinal strain, GLS)、整體環(huán)向應(yīng)變(global circumferential strain, GCS)、整體徑向應(yīng)變(global radial strain, GRS)、整體面積應(yīng)變(global area strain, GAS)；被試者年齡>18歲。排除標準：動物和基礎(chǔ)實驗研究；缺少左心室應(yīng)變指標的研究；重復發(fā)表的文獻；綜述、文摘、讀者來信；編輯評論、會議論文；非英文文獻。

1.3文獻篩選及資料提取 根據(jù)納入和排除標準，由2名有經(jīng)驗的工作者對符合標準的文獻進行單獨篩選，并記錄基本資料和左心室應(yīng)變指標，判斷不一致時經(jīng)協(xié)商解決。提取的基本資料包括第一作者、開展研究的國家、發(fā)表年限、納入健康人群或正常對照組樣本數(shù)、健康人群或正常對照組人群的基本特征和3D-STI左心室應(yīng)變指標(GLS、GRS、GCS、GAS)。

1.4統(tǒng)計學分析 采用STATA 12.0統(tǒng)計分析軟件。以加權(quán)均數(shù)差(weighted mean difference, WMD)和95%可信區(qū)間(confidence interval, CI)為合并統(tǒng)計量。通過I2和Q檢驗對入選研究進行異質(zhì)性檢驗：當I2<50%且P≥0.1為不存在異質(zhì)性，采用固定效應(yīng)模型；反之采用隨機效應(yīng)模型分析。存在異質(zhì)性的研究，對可能造成異質(zhì)性的因素進行亞組分析。以漏斗圖和Egger檢驗評價發(fā)表偏倚；以排除單個研究后觀察結(jié)果有無顯著變化的方法判斷敏感度，評價研究成果的穩(wěn)定性。

2 結(jié)果

2.1文獻檢索及篩選結(jié)果 檢索數(shù)據(jù)庫初步獲得619條文獻，排除重復記錄的文獻328篇，排除綜述等非試驗性文獻和研究對象為非成年人的文獻254篇，進一步閱讀剩余74篇文獻，排除18篇無健康對照組的文獻，以及29篇缺少3D-STI整體應(yīng)變指標的文獻；最終納入27篇[8-34]。

2.2納入文獻基本特征和質(zhì)量評價 入選的27篇文獻中，共納入1 552名符合條件的健康成年被試者，27篇均包含GLS數(shù)據(jù)；26篇[8-29,31-34]包含1 522名健康被試者的GCS數(shù)據(jù)；24篇[8-9,11-29,32-34]包含1 473名健康被試者的GRS數(shù)據(jù)；18篇[8-9.11-15,17-19,21-22,26-29,32-33]包含983名健康被試者的GAS數(shù)據(jù)。納入研究的基本特征見表1。

2.3 納入文獻定量數(shù)據(jù)分析 27篇文獻測量GLS的異質(zhì)性較小(I2=0.0%，P=0.863)，選擇固定效應(yīng)模型分析，GLS參考范圍森林圖見圖1[WMD=17.80，95%CI(16.27,19.33)]。根據(jù)Egger檢驗以及漏斗圖分布(圖2)，認為GLS無發(fā)表偏倚(P=0.855)。

26篇文獻測量的GCS存在異質(zhì)性(I2=84.3%，P<0.01)，選擇隨機效應(yīng)模型分析，GCS參考范圍森林圖見圖3[WMD=24.73，95%CI(22.50,26.95)]。根據(jù)Egger檢驗以及漏斗圖分布(圖4)，認為GCS存在發(fā)表偏倚(P=0.022)。對不同設(shè)備廠家進行亞組分析，GE、Toshiba、Philips組的異質(zhì)性降低(I2=58.6%、74.8%、75.0%，P=0.002、0.001、0.007)，選擇隨機效應(yīng)模型分析；3組GCS的WMD和95%CI分別為20.07和(18.98，21.16)、20.46和(18.58，22.33)、25.19和(22.21，28.17)。

24篇文獻測量的GRS存在異質(zhì)性(I2=45.2%，P=0.009)，采用隨機效應(yīng)模型，GRS的WMD和95%CI為47.86和(39.52，56.19)，見圖5。根據(jù)Egger檢驗及漏斗圖分布(圖6)，認為GRS無發(fā)表偏倚(P=0.987)。對設(shè)備生產(chǎn)廠家進行亞組分析，GE組(I2=38.2%，P=0.066)及Philips組(I2=78.3%，P=0.010)存在異質(zhì)性，選擇隨機效應(yīng)模型分析，Toshiba組(I2=30.8%，P=0.204)異質(zhì)性減小，選擇固定效應(yīng)模型分析； GE組、Philips組、Toshiba組GRS的WMD和95%CI分別為46.84和(42.87,50.80)、44.73和(40.32,49.13)、42.81和(31.04,54.57)。

表1 納入研究的基本特征

注：Y：包含；N：不包含

18篇文獻測量的GAS存在異質(zhì)性(I2=57.3%，P=0.001)，選擇隨機效應(yīng)模型，GAS的WMD和95%CI為36.17和(34.08，38.26)，見圖7。根據(jù)Egger檢驗結(jié)果以及漏斗圖兩側(cè)分布對稱(圖8)，認為GAS不存在發(fā)表偏倚(P=0.771)。根據(jù)設(shè)備生產(chǎn)廠家進行亞組分析，GE組(I2=35.4%，P=0.092)的異質(zhì)性較高，選擇隨機效應(yīng)模型分析。Toshiba組(I2=47.5%，P=0.126)的異質(zhì)性較小，選擇固定效應(yīng)模型分析，GE組和Toshiba組GAS的WMD和95%CI分別為32.86和(30.92,34.79)、39.06和(35.59,42.52)。

2.4敏感度分析 剔除單篇納入文獻對剩余文獻進行敏感度分析，發(fā)現(xiàn)左心室應(yīng)變參數(shù)范圍的合并效應(yīng)指標未發(fā)生明顯變化，提示入選的文獻穩(wěn)定性好。

3 討論

3D-STI克服了傳統(tǒng)2D超聲技術(shù)的不足，可更準確地對心臟功能進行實時評估，提供更加準確的結(jié)果[4-5,35]；相對于傳統(tǒng)檢查技術(shù)，3D-STI具有更高的效率和可重復性[6-7,35]。因其對心肌損傷早期變化和功能異常非常敏感，所以對于許多疾病初期階段心功能異常的診斷有重要意義。通過3D-STI技術(shù)可檢測到高血壓早期患者左心室容量的增高[21]和肥胖人群左心室功能的早期改變[36]。此外，3D-STI對預(yù)后的評估也有重要價值[12]。目前，對心肌應(yīng)變參數(shù)正常范圍的研究缺乏統(tǒng)一標準，使該項技術(shù)的應(yīng)用受到一定限制[9-10,14,20,23,37]。本研究通過對納入的1 552名健康成年被試者的3D-STI檢查結(jié)果進行分析，獲得了左心室整體應(yīng)變指標的正常參考范圍。

本研究提示GLS相較于其他3個應(yīng)變指標，具有更低的異質(zhì)性。研究[21]證明，對于原發(fā)性高血壓患者，GLS的降低發(fā)生在LVEF和其他指標改變前，是一個非常敏感的指標?？赡苡捎贕LS受心內(nèi)膜縱向心肌狀態(tài)影響，而縱向心肌功能異常多出現(xiàn)在病變早期。故對于心肌梗死[35]、高血壓[21]、糖尿病[37-38]患者，GLS可作為一個心功能評估的敏感指標。此外，作為一個新的左心室功能評價指標，GAS結(jié)合了縱向應(yīng)變與環(huán)向應(yīng)變，可最大限度地降低追蹤誤差以及形變對左心室功能評價造成的干擾。研究[26]證實GAS與左心室射血分數(shù)有很高相關(guān)性，且相較于其他3個指標，GAS可更好地識別健康人群與早期心力衰竭患者的差異，可作為提示左心室收縮功能異常的可靠指標[21]。

圖1 GLS參考范圍森林圖 圖2 GLS發(fā)表偏倚漏斗圖 圖3 GCS參考范圍森林圖 圖4 GCS發(fā)表偏倚漏斗圖

圖5 GRS參考范圍森林圖 圖6 GRS發(fā)表偏倚漏斗圖 圖7 GAS參考范圍森林圖 圖8 GAS發(fā)表偏倚漏斗圖

GCS、GRS、GAS數(shù)據(jù)存在異質(zhì)性，且提示不同設(shè)備所獲得的3D-STI心肌應(yīng)變參數(shù)結(jié)果可能不具有可比性[21,34]，因此，本研究根據(jù)不同廠家(GE、Toshiba、Philips)檢測儀器進行亞組分析，結(jié)果顯示Toshiba組GRS和GAS的異質(zhì)性降低，可能因單一廠家分組，降低了因儀器不同而導致的誤差。GCS指標按廠家亞組分析中異質(zhì)性也有降低，但降低不明顯?？紤]儀器來源于不同廠家對異質(zhì)性有影響但可能不是最主要影響因素。

本研究的不足：僅對英文數(shù)據(jù)庫進行檢索，樣本量過小；除GLS外，GCS、GRS、GAS等參數(shù)存在異質(zhì)性；納入的12個亞洲國家研究中11個來自中國，還需考慮人種和地域因素可能導致測量結(jié)果的差異。

總之，本研究通過Meta分析，初步確定了成人左心室應(yīng)變指標的正常參考范圍，對采用3D-STI評價心臟結(jié)構(gòu)和功能的改變具有一定的指導意義。

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Reference range of left ventricular strain measured by three-dimensional speckle-tracking imaging:Meta analysis

CAOYin,HUANGJing*,ZOUYanke,LIAOQingyao,XIONGBo,TANJie

(DepartmentofCardiology,theSecondAffiliatedHospitalofChongqingMedicalUniversity,Chongqing400010,China)

Objective To obtain the normal reference ranges of global longitudinal strain (GLS), global circumferential strain (GCS), global area strain (GAS) and global radial strain (GRS) of left ventricular in normal adults by three-dimensional speckle tracking imaging (3D-STI) using Meta analysis. Methods Eligible trials which detected global strain of left ventricular in normal subject through 3D-STI were searched in Embase, Pubmed, Cochrane Library database. According to the heterogeneity, parameters of contained studies were analyzed the weighted mean difference (WMD) and 95% confidence interval (CI). The statistical software was STATA 12.0. Results Totally 1 552 healthy adults from 27 articles were included. Based on the Meta-analysis, the WMD and 95%CI of GLS were 17.80 and (16.27, 19.33), of GCS were 24.73 and (22.50, 26.95), of GRS were 47.86 and (39.52, 56.19), of GAS were 36.17 and (34.08, 38.26). Conclusion The Meta analysis defines reference range of strains obtained by 3D-STI in healthy adults. Using these parameters of 3D globe strains, a guidance of reference for patient's management and therapy selection may be provided.

Three-dimensional speckle tracking imaging; Ventricular, left; Strain; Reference ranges

國家自然科學基金(81370440)。

曹寅(1990—)，男，重慶人，在讀碩士，醫(yī)師。研究方向：心血管超聲。E-mail: 306127257@qq.com

黃晶，重慶醫(yī)科大學附屬第二醫(yī)院心血管內(nèi)科，400010。E-mail: huangjingcqmu@sohu.com

2017-01-19

2017-05-12

R3; R540.45

A

1672-8475(2017)07-0416-06

10.13929/j.1672-8475.201701030