曹 寅，黃 晶，鄒燕珂，廖晴瑤，熊 波，譚 杰

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

三維斑點(diǎn)追蹤成像左心室應(yīng)變指標(biāo)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(xué)附屬第二醫(yī)院心血管內(nèi)科，重慶 400010)

目的 采用Meta分析評(píng)估健康成人的三維斑點(diǎn)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(kù)中，檢索2016年8月1日前公開(kāi)發(fā)表的關(guān)于3D-STI評(píng)價(jià)左心功能的病例對(duì)照研究。按照納入和排除標(biāo)準(zhǔn)，對(duì)文獻(xiàn)進(jìn)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(jì)量，采用的統(tǒng)計(jì)分析軟件為STATA 12.0。結(jié)果 最終納入27項(xiàng)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(guò)Meta分析確定成人左心室應(yīng)變指標(biāo)的正常參考范圍，對(duì)采用3D-STI評(píng)價(jià)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(dǎo)意義。

三維斑點(diǎn)追蹤成像；心室，左；應(yīng)變；參考范圍

近年來(lái)，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(duì)疾病診治和預(yù)后至關(guān)重要。通過(guò)三維斑點(diǎn)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(zhǔn)確評(píng)估心肌功能[1]，可重復(fù)性較高[2-3]。目前臨床3D-STI已逐步用于左心室功能的評(píng)估[4-7]。但采用3D-STI評(píng)價(jià)成人左心室應(yīng)變指標(biāo)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(guò)對(duì)健康成人3D-STI左心室應(yīng)變指標(biāo)進(jìn)行Meta分析，獲得左心室應(yīng)變指標(biāo)的正常參考范圍，為3D-STI評(píng)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(xiàn)檢索 檢索Embase、Pubmed、Cochrane Library等數(shù)據(jù)庫(kù)于2016年8月1日前公開(kāi)發(fā)表的英文文獻(xiàn)。檢索詞為“three-dimensional speckle tracking”、“l(fā)eft ventricular”；對(duì)入選文獻(xiàn)的參考文獻(xiàn)進(jìn)行二次檢索。

1.2納入與排除標(biāo)準(zhǔn) 納入標(biāo)準(zhǔn)：公開(kāi)發(fā)表的英文文獻(xiàn)；采用3D-STI技術(shù)評(píng)價(jià)健康個(gè)體左心室功能的觀察性研究和對(duì)照組為健康人群的對(duì)照研究；包含左心室應(yīng)變指標(biāo)，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(biāo)準(zhǔn)：動(dòng)物和基礎(chǔ)實(shí)驗(yàn)研究；缺少左心室應(yīng)變指標(biāo)的研究；重復(fù)發(fā)表的文獻(xiàn)；綜述、文摘、讀者來(lái)信；編輯評(píng)論、會(huì)議論文；非英文文獻(xiàn)。

1.3文獻(xiàn)篩選及資料提取 根據(jù)納入和排除標(biāo)準(zhǔn)，由2名有經(jīng)驗(yàn)的工作者對(duì)符合標(biāo)準(zhǔn)的文獻(xiàn)進(jìn)行單獨(dú)篩選，并記錄基本資料和左心室應(yīng)變指標(biāo)，判斷不一致時(shí)經(jīng)協(xié)商解決。提取的基本資料包括第一作者、開(kāi)展研究的國(guó)家、發(fā)表年限、納入健康人群或正常對(duì)照組樣本數(shù)、健康人群或正常對(duì)照組人群的基本特征和3D-STI左心室應(yīng)變指標(biāo)(GLS、GRS、GCS、GAS)。

1.4統(tǒng)計(jì)學(xué)分析 采用STATA 12.0統(tǒng)計(jì)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(jì)量。通過(guò)I2和Q檢驗(yàn)對(duì)入選研究進(jìn)行異質(zhì)性檢驗(yàn)：當(dāng)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(jī)效應(yīng)模型分析。存在異質(zhì)性的研究，對(duì)可能造成異質(zhì)性的因素進(jìn)行亞組分析。以漏斗圖和Egger檢驗(yàn)評(píng)價(jià)發(fā)表偏倚；以排除單個(gè)研究后觀察結(jié)果有無(wú)顯著變化的方法判斷敏感度，評(píng)價(jià)研究成果的穩(wěn)定性。

2 結(jié)果

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

2.2納入文獻(xiàn)基本特征和質(zhì)量評(píng)價(jià) 入選的27篇文獻(xiàn)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(jiàn)表1。

2.3 納入文獻(xiàn)定量數(shù)據(jù)分析 27篇文獻(xiàn)測(cè)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(jiàn)圖1[WMD=17.80，95%CI(16.27,19.33)]。根據(jù)Egger檢驗(yàn)以及漏斗圖分布(圖2)，認(rèn)為GLS無(wú)發(fā)表偏倚(P=0.855)。

26篇文獻(xiàn)測(cè)量的GCS存在異質(zhì)性(I2=84.3%，P<0.01)，選擇隨機(jī)效應(yīng)模型分析，GCS參考范圍森林圖見(jiàn)圖3[WMD=24.73，95%CI(22.50,26.95)]。根據(jù)Egger檢驗(yàn)以及漏斗圖分布(圖4)，認(rèn)為GCS存在發(fā)表偏倚(P=0.022)。對(duì)不同設(shè)備廠家進(jìn)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(jī)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(xiàn)測(cè)量的GRS存在異質(zhì)性(I2=45.2%，P=0.009)，采用隨機(jī)效應(yīng)模型，GRS的WMD和95%CI為47.86和(39.52，56.19)，見(jiàn)圖5。根據(jù)Egger檢驗(yàn)及漏斗圖分布(圖6)，認(rèn)為GRS無(wú)發(fā)表偏倚(P=0.987)。對(duì)設(shè)備生產(chǎn)廠家進(jìn)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(jī)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(xiàn)測(cè)量的GAS存在異質(zhì)性(I2=57.3%，P=0.001)，選擇隨機(jī)效應(yīng)模型，GAS的WMD和95%CI為36.17和(34.08，38.26)，見(jiàn)圖7。根據(jù)Egger檢驗(yàn)結(jié)果以及漏斗圖兩側(cè)分布對(duì)稱(圖8)，認(rèn)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(jìn)行亞組分析，GE組(I2=35.4%，P=0.092)的異質(zhì)性較高，選擇隨機(jī)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(xiàn)對(duì)剩余文獻(xiàn)進(jìn)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(biāo)未發(fā)生明顯變化，提示入選的文獻(xiàn)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(zhǔn)確地對(duì)心臟功能進(jìn)行實(shí)時(shí)評(píng)估，提供更加準(zhǔn)確的結(jié)果[4-5,35]；相對(duì)于傳統(tǒng)檢查技術(shù)，3D-STI具有更高的效率和可重復(fù)性[6-7,35]。因其對(duì)心肌損傷早期變化和功能異常非常敏感，所以對(duì)于許多疾病初期階段心功能異常的診斷有重要意義。通過(guò)3D-STI技術(shù)可檢測(cè)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(duì)預(yù)后的評(píng)估也有重要價(jià)值[12]。目前，對(duì)心肌應(yīng)變參數(shù)正常范圍的研究缺乏統(tǒng)一標(biāo)準(zhǔn)，使該項(xiàng)技術(shù)的應(yīng)用受到一定限制[9-10,14,20,23,37]。本研究通過(guò)對(duì)納入的1 552名健康成年被試者的3D-STI檢查結(jié)果進(jìn)行分析，獲得了左心室整體應(yīng)變指標(biāo)的正常參考范圍。

本研究提示GLS相較于其他3個(gè)應(yīng)變指標(biāo)，具有更低的異質(zhì)性。研究[21]證明，對(duì)于原發(fā)性高血壓患者，GLS的降低發(fā)生在LVEF和其他指標(biāo)改變前，是一個(gè)非常敏感的指標(biāo)。可能由于GLS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?cè)缙凇９蕦?duì)于心肌梗死[35]、高血壓[21]、糖尿病[37-38]患者，GLS可作為一個(gè)心功能評(píng)估的敏感指標(biāo)。此外，作為一個(gè)新的左心室功能評(píng)價(jià)指標(biāo)，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(duì)左心室功能評(píng)價(jià)造成的干擾。研究[26]證實(shí)GAS與左心室射血分?jǐn)?shù)有很高相關(guān)性，且相較于其他3個(gè)指標(biāo)，GAS可更好地識(shí)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(biāo)[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(cè)儀器進(jìn)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(dǎo)致的誤差。GCS指標(biāo)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(lái)源于不同廠家對(duì)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(duì)英文數(shù)據(jù)庫(kù)進(jìn)行檢索，樣本量過(guò)??；除GLS外，GCS、GRS、GAS等參數(shù)存在異質(zhì)性；納入的12個(gè)亞洲國(guó)家研究中11個(gè)來(lái)自中國(guó)，還需考慮人種和地域因素可能導(dǎo)致測(cè)量結(jié)果的差異。

總之，本研究通過(guò)Meta分析，初步確定了成人左心室應(yīng)變指標(biāo)的正常參考范圍，對(duì)采用3D-STI評(píng)價(jià)心臟結(jié)構(gòu)和功能的改變具有一定的指導(dǎo)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(guó)家自然科學(xué)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(xué)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