陳亞磊,賀毅,米宏志,楊婭,宋現(xiàn)濤
· 綜述 ·
冠狀動(dòng)脈慢性完全閉塞病變開(kāi)通價(jià)值的研究進(jìn)展
陳亞磊1,賀毅2,米宏志2,楊婭3,宋現(xiàn)濤1
冠狀動(dòng)脈慢性完全閉塞病變(CTO)指冠狀動(dòng)脈完全閉塞超過(guò)3個(gè)月、TIMI血流0級(jí)的病變,發(fā)生率約占冠狀動(dòng)脈造影確診為冠狀動(dòng)脈粥樣硬化性心臟病(冠心病)患者的20%~30%[1],僅8%~15%的患者接受經(jīng)皮冠狀動(dòng)脈介入治療(PCI)。CTO發(fā)病率和接受PCI的比例呈明顯反差,一方面是CTO治療難度大,成功率低,術(shù)后并發(fā)癥發(fā)生率高。研究報(bào)道在技術(shù)成熟的診療中心或豐富經(jīng)驗(yàn)的介入專(zhuān)家,CTO患者PCI的成功率可達(dá)82.9%~87.5%[2]。另一方面是患者獲益程度有爭(zhēng)議,但大多數(shù)觀察性及回顧性研究顯示開(kāi)通CTO可減少不良心血管事件發(fā)生率。近期一篇Meta分析表明,與優(yōu)化藥物治療組(OMT)比較,有存活心肌的缺血性心臟病經(jīng)血運(yùn)重建后其遠(yuǎn)期死亡率降低,無(wú)存活心肌的患者接受血運(yùn)重建后其遠(yuǎn)期死亡率無(wú)明顯差異[3]。存活心肌是CTO再血管化治療的基礎(chǔ),術(shù)前評(píng)估CTO患者存活心肌已逐漸得到國(guó)內(nèi)外專(zhuān)家的認(rèn)可,識(shí)別存活心肌對(duì)CTO病變治療策略的選擇具有重要指導(dǎo)意義[4],但目前尚需大規(guī)模隨機(jī)對(duì)照實(shí)驗(yàn)論證存活心肌數(shù)量多少時(shí)有利于改善預(yù)后。目前評(píng)估存活心肌方法有正電子發(fā)射計(jì)算機(jī)斷層掃描(PET)、單光子發(fā)射計(jì)算機(jī)斷層掃描(SPECT)及超聲心動(dòng)圖等。CTO開(kāi)通前采用冠狀動(dòng)脈計(jì)算機(jī)斷層掃描(CCTA)評(píng)估閉塞部位特征,有利于術(shù)者選擇治療策略以及提高手術(shù)的成功率。本文針對(duì)有助于評(píng)估CTO病變開(kāi)通價(jià)值技術(shù)手段作一簡(jiǎn)要綜述。
臨床經(jīng)驗(yàn)表明閉塞時(shí)間超過(guò)3個(gè)月的冠狀動(dòng)脈介入成功率較低,因此更傾向?qū)?個(gè)月以上的病變稱(chēng)為慢性閉塞病變。臨床上根據(jù)既往是否存在急性冠脈綜合征,是否有典型心絞痛癥狀及既往冠狀動(dòng)脈造影結(jié)果等判斷閉塞時(shí)間[5]。CTO是一個(gè)慢性進(jìn)行性演變過(guò)程,其管腔內(nèi)充積著不同程度的粥樣硬化斑塊和陳舊性血栓,常伴纖維化、鈣化,導(dǎo)致管腔完全性阻塞,由于病變兩端或近端形成致密較硬的纖維帽,導(dǎo)致導(dǎo)絲及球囊難以通過(guò),這是CTO介入治療成功率較低的病理基礎(chǔ)。但CTO多數(shù)存在側(cè)支循環(huán),側(cè)支循環(huán)供應(yīng)區(qū)域心肌處于低代謝、低灌注的冬眠狀態(tài),冬眠心肌是存活心肌一種。如果能及時(shí)恢復(fù)心肌的供氧平衡,冬眠心肌的功能就可得到部分或全部恢復(fù),這是CTO介入治療有助于恢復(fù)心臟功能及改善預(yù)后的病理基礎(chǔ)[6]。
2.1 臨床獲益 研究表明:對(duì)于有癥狀的CTO患者,接受介入治療可以緩解心絞痛發(fā)作次數(shù)、改善左室功能、提高生活質(zhì)量,Grantham等[7]證實(shí)了這一點(diǎn)。Jeong Hoon等[8]以CTO患者為研究對(duì)象,根據(jù)最初的治療策略分為將PCI組(n=883)與OMT組(n=664),通過(guò)平均隨訪45.8個(gè)月發(fā)現(xiàn),PCI組患者的全因死亡率明顯低于OMT組,遠(yuǎn)期預(yù)后優(yōu)于OMT組。Romain等[9]以老年CTO患者作為研究對(duì)象,發(fā)現(xiàn)其PCI的成功率與年輕人相似,通過(guò)隨訪20個(gè)月發(fā)現(xiàn),老年CTO患者接受PCI治療后再發(fā)心肌梗死顯著低于PCI失敗組,同時(shí)提高了無(wú)心血管不良事件生存率。Yamamoto等[10]通過(guò)對(duì)1524例CTO患者隨訪研究發(fā)現(xiàn),1192例PCI成功組患者3年內(nèi)接受減少冠狀動(dòng)脈旁路移植術(shù)(CABG)比例顯著少于失敗組,再次接受血運(yùn)重建比例少于PCI失敗組,但兩組患者心源性死亡率及全因死亡率無(wú)顯著差別,這與既往研究不同。多項(xiàng)研究證實(shí)CTO行血運(yùn)重建后可以改善心功能,提高生活質(zhì)量,減少CABG手術(shù)次數(shù),其開(kāi)通價(jià)值也得到越來(lái)越多的臨床醫(yī)生的重視和認(rèn)可。
2.2 存活心肌 存活心肌指心肌細(xì)胞應(yīng)對(duì)低灌注等病理環(huán)境下的自我保護(hù)防御性機(jī)制,表現(xiàn)形式有兩種,即頓抑心肌和冬眠心肌,冬眠心肌細(xì)胞血流灌注減低,收縮功能障礙,但細(xì)胞膜完整,心肌代謝仍存在,具有潛在的收縮儲(chǔ)備功能。支配存活心肌區(qū)域血管開(kāi)通后,有益于改善節(jié)段性室壁運(yùn)動(dòng)異常和提高左心室功能[11]。部分研究發(fā)現(xiàn)CTO患者經(jīng)成功血運(yùn)重建后其左心室射血分?jǐn)?shù)較術(shù)前有所提高,存在存活心肌的患者尤為顯著[12]。當(dāng)CTO患者血管支配范圍有大量存活心肌時(shí),開(kāi)通CTO可影響長(zhǎng)期預(yù)后。研究發(fā)現(xiàn):當(dāng)冠心病患者無(wú)存活心肌時(shí),無(wú)論是否接受血運(yùn)重建其遠(yuǎn)期生存率無(wú)明顯差異[13]。臨床確實(shí)存在缺血證據(jù),血管解剖條件合適,由經(jīng)驗(yàn)豐富的術(shù)者(成功率>80%)開(kāi)通CTO是合理的,2011年ACC/AHA對(duì)于CTO介入治療指南與2012年中國(guó)CTO介入治療指南均為Ⅱa類(lèi)推薦(B級(jí)證據(jù)),ESC對(duì)于CTO介入治療指南為Ⅱb類(lèi)推薦(C級(jí)證據(jù))[14,15]。
3.1 PET PET通過(guò)比較心肌代謝顯像與血流灌注是否匹配來(lái)評(píng)估存活心肌,是檢測(cè)存活心肌的“金標(biāo)準(zhǔn)”,目前常用18F標(biāo)記的氟代脫氧葡萄糖(18F-FDG)心肌代謝顯像。當(dāng)心肌灌注節(jié)段性降低時(shí),PET心肌代謝顯像FDG 攝取正?;蛳鄬?duì)增加,說(shuō)明該節(jié)段心肌灌注與代謝顯像不匹配,表明該節(jié)段心肌細(xì)胞處于缺血但存活狀態(tài);相反,若相應(yīng)節(jié)段 FDG攝取減低,則心肌灌注與代謝顯像匹配,標(biāo)志著該節(jié)段心肌細(xì)胞不存活。賈志新等[16]對(duì)20例陳舊性心肌梗死患者PCI術(shù)前行13N-NH3、18F- FDG-PET心肌灌注/代謝顯像預(yù)測(cè)存活心肌,隨訪3~6個(gè)月結(jié)果顯示,術(shù)前13N-NH3、18F-FDG-PET判定為存活心肌患者介入治療后85.7%的心肌節(jié)段血流灌注及代謝恢復(fù)正常,而治療前判定為無(wú)存活的心肌節(jié)段僅3.3%的心肌節(jié)段血流灌注及代謝恢復(fù)正常。有研究表明,當(dāng)18F-FDG-PET檢測(cè)存活心肌大于7%的患者行介入治療不僅可降低死亡率,還降低再發(fā)心肌梗死事件以及減少心源性因素住院率[17]。由于CTO病變慢性形成過(guò)程以及其側(cè)支循環(huán)的形成,血流供應(yīng)區(qū)域存在存活心肌對(duì)心功能及預(yù)后的改善有明顯意義。Ling等[18]采用靜息銣-82(Rb-82)和F-18-FDG心肌代謝灌注PET顯像預(yù)測(cè)疤痕心肌、缺血心肌及冬眠心肌,表明當(dāng)存活心肌超過(guò)10%時(shí),冠心病患者接受血運(yùn)重建的遠(yuǎn)期生存率優(yōu)于單純藥物治療。
3.2 SPECT SPECT顯像是一種重要的評(píng)價(jià)存活心肌的方法,準(zhǔn)確率不及PET,但其應(yīng)用普及率高于PET,是性?xún)r(jià)比較高的一種替代方法。目前研究認(rèn)為18F-FDG-SPECT復(fù)合線路檢測(cè)存活心肌提供的數(shù)據(jù)與18F-FDG-PET相似,18F-FDG-PET檢測(cè)組織全部為存活心肌中,SPECT檢測(cè)存活心肌占88%[19]。18F-FDG-SPECT檢測(cè)存活心肌的準(zhǔn)確性與PET相似,費(fèi)用相對(duì)低,臨床應(yīng)用價(jià)值大。一項(xiàng)關(guān)于SPECT與PET對(duì)比評(píng)估冠心病患者存活心肌的差別薈萃分析表明,SPECT檢測(cè)存活心肌的敏感性和特異性分別可達(dá)59%~95%和79%~100%,與PET檢測(cè)存活心肌符合率可達(dá)76%~100%[20]。其缺點(diǎn)是空間分辨率低,對(duì)心外膜下存活心肌和心內(nèi)膜下心肌梗死心肌特異性差,但可滿(mǎn)足臨床基本要求,對(duì)心肌缺血范圍及存活心肌判斷精確性差以及較長(zhǎng)時(shí)間的射線暴露[21]。
3.3 CMR CMR空間分辨率高,清晰顯示心外膜和心內(nèi)膜的邊界,準(zhǔn)確評(píng)估心臟射血分?jǐn)?shù)及容積,是評(píng)價(jià)心臟功能的金標(biāo)準(zhǔn),近年來(lái)研究發(fā)現(xiàn)其在評(píng)價(jià)冠心病患者存活心肌方面具有較高價(jià)值[22]。與正常心肌細(xì)胞相比,代謝減低的心肌細(xì)胞,細(xì)胞間隙增大,對(duì)比劑排泄延遲及滯留增加,出現(xiàn)延時(shí)強(qiáng)化。釓對(duì)比劑延遲增強(qiáng)核磁共振(LGE-MRI)可評(píng)估缺血性心臟病的瘢痕組織,識(shí)別小范圍的心內(nèi)膜下心肌梗死時(shí),比SPECT有更高的敏感度(92% vs. 28%)[23],LGE-MRI通過(guò)評(píng)估心肌梗死部位透壁程度與再血管化治療后局部心臟收縮功能改善有明顯相關(guān)性,當(dāng)透壁程度>75%時(shí),僅4%患者局部收縮功能得到改善,當(dāng)透壁程度小于50%時(shí),絕大部分心肌節(jié)段功能可恢復(fù)。研究表明[24],對(duì)于評(píng)價(jià)無(wú)存活心肌的心肌節(jié)段血運(yùn)重建后心肌收縮功能的恢復(fù),CMR優(yōu)于PET/SPECT,對(duì)于冠心病患者接受血運(yùn)重建是否獲益方面,CMR更具優(yōu)勢(shì)。延遲增強(qiáng)心臟核磁共振(DECMR)能夠精確區(qū)分正常心肌和壞死心肌、纖維化心肌,與組織病理學(xué)結(jié)果有較高的一致性,對(duì)篩選接受血管化治療無(wú)明顯獲益的CTO患者有一定指導(dǎo)作用,能有效預(yù)估接受血運(yùn)重建患者整體及局部的心功能改善。
3.4 超聲心動(dòng)圖 超聲心動(dòng)圖對(duì)存活心肌的檢測(cè)主要依賴(lài)于其收縮儲(chǔ)備能力的評(píng)估及室壁運(yùn)動(dòng)異常的判斷,其中,小劑量多巴酚丁胺單用及其合用硝酸酯負(fù)荷超聲心動(dòng)圖是檢測(cè)存活心肌的可靠方法。楊躍進(jìn)等[25]以冠心病合并嚴(yán)重左心室收縮功能障礙患者為研究對(duì)象,對(duì)比多巴酚丁胺10 μg /(kg·min)二維超聲與99mTc-甲氧基異丁腈(MIBI)/18F-脫氧葡萄糖(FDP)雙核素同時(shí)采集法(DISA)SPECT心肌顯像,DISA SPECT的敏感性高,特異性偏低,準(zhǔn)確性較好;小劑量的10 μg二維超聲檢測(cè)效果與之相當(dāng),特異性還較DISA SPECT更高。Baer等[26]研究顯示,以18F-FDG PET為標(biāo)準(zhǔn),小劑量多巴酚丁胺負(fù)荷超聲心動(dòng)圖(LDDSE)檢測(cè)存活心肌陽(yáng)性預(yù)測(cè)值是67%,陰性預(yù)測(cè)值78%,LDDSE和18F-FDG PET 檢測(cè)存活心肌的敏感性分別是86%和92%,特異性是88%和69%。運(yùn)用多巴酚丁胺負(fù)荷超聲心動(dòng)圖組織速度成像技術(shù)結(jié)合斑點(diǎn)追蹤顯像技術(shù)可更準(zhǔn)確的評(píng)估缺血性心臟病的心肌活性[27]。由于傳統(tǒng)二維超聲心動(dòng)圖受檢查醫(yī)生的主觀控制及經(jīng)驗(yàn)等因素影響,對(duì)室壁運(yùn)動(dòng)觀察存在主觀性,同時(shí)判斷指標(biāo)非定量化,限制了其的臨床使用。
與冠狀動(dòng)脈造影相比,CCTA可以精確評(píng)估冠狀動(dòng)脈鈣化程度,測(cè)定閉塞段長(zhǎng)度及是否為多部位閉塞、閉塞斷端纖維帽的形狀等影響CTO介入治療成功率的因素,術(shù)前通過(guò)CCTA評(píng)估閉塞病變部位,對(duì)其預(yù)測(cè)其開(kāi)通可能起至關(guān)重要的作用。研究表明:術(shù)前CCTA評(píng)估冠狀動(dòng)脈血管負(fù)性重構(gòu)以及閉塞病變長(zhǎng)度>31.89 mm是CTO順行介入治療的主要危險(xiǎn)因素,假設(shè)排除以上三種影響因素,CTO順行開(kāi)通成功率可達(dá)98.0%[28]。血管的負(fù)性重構(gòu)是長(zhǎng)時(shí)間閉塞病變的主要特征,也是導(dǎo)致CTO介入治療失敗的主要影響因素[29],但傳統(tǒng)的冠狀動(dòng)脈造影無(wú)法識(shí)別負(fù)性重構(gòu),從而影響CTO介入治療的成功率。術(shù)前CCTA評(píng)估閉塞病變的鈣化、閉塞長(zhǎng)度,閉塞部位近端及遠(yuǎn)端殘端形態(tài)、側(cè)支循環(huán)將有利于提高手術(shù)的成功率[30]。近期一項(xiàng)關(guān)于CCTA預(yù)測(cè)CTO患者接受血運(yùn)重建難度分級(jí)的多中心、回顧性研究發(fā)現(xiàn):CCTA測(cè)定數(shù)據(jù)病變部位多節(jié)段閉塞、鈍性殘端、閉塞部位成角,嚴(yán)重鈣化和閉塞時(shí)間長(zhǎng)短以及閉塞部位既往是否PCI是預(yù)測(cè)導(dǎo)絲30 min通過(guò)閉塞病變的獨(dú)立危險(xiǎn)因素,危險(xiǎn)因素越多,CTO病的開(kāi)通成功率越低,術(shù)前評(píng)估CTO病變,無(wú)上述危險(xiǎn)因素時(shí),30 min內(nèi)導(dǎo)絲通過(guò)閉塞病變的成功率可達(dá)95%,當(dāng)危險(xiǎn)因素≥3個(gè),30 min內(nèi)導(dǎo)絲通過(guò)閉塞病變的成功率≤24%[31]。研究表明,CCTA是一種評(píng)價(jià)閉塞病變的非侵入性工具,有助于術(shù)前評(píng)估CTO開(kāi)通難度分級(jí),有效預(yù)測(cè)CTO開(kāi)通成功與否以及減少開(kāi)通所需時(shí)間。
介入治療是目前開(kāi)通CTO的主要治療手段之一。術(shù)前評(píng)估CTO患者的存活心肌,選擇能獲益的患者接受介入治療。對(duì)于無(wú)存活心肌患者不推薦血運(yùn)重建治療。PET是評(píng)價(jià)存活心肌的金標(biāo)準(zhǔn),但其應(yīng)用率較低限制其價(jià)值,SPECT可作為在某些方面替代PET評(píng)估存活心肌。藥物負(fù)荷超聲心動(dòng)圖應(yīng)用過(guò)程有再次誘發(fā)心肌缺血的風(fēng)險(xiǎn),但在缺乏其他評(píng)價(jià)存活心肌手段地區(qū),其應(yīng)用廣泛及方便。CMR不僅可評(píng)估存活心肌,還可識(shí)別疤痕心肌,心肌纖維化及評(píng)估心臟功能,精確區(qū)分心內(nèi)膜下存活心肌。其次CCTA評(píng)估病變特征,合理全面評(píng)估CTO患者局部病變特征及介入治療價(jià)值,有助于指導(dǎo)選擇治療策略及提高開(kāi)通成功率。綜上所述,術(shù)前合理選擇評(píng)價(jià)手段評(píng)估CTO患者存活心肌情況,對(duì)于適合血運(yùn)重建患者術(shù)前采用CCTA評(píng)估閉塞病變部位的特征,預(yù)測(cè)其開(kāi)通價(jià)值,有助于手術(shù)方式選擇及提高成功率。
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本文編輯:阮燕萍
R543.4
A
1674-4055(2016)11-1391-03
北京市科技計(jì)劃課題(Z161100000516139)
1100029 北京,首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院北京市心肺血管疾病研究所心內(nèi)科一病房;2100029 北京,首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院北京市心肺血管疾病研究所影像醫(yī)學(xué)與核醫(yī)學(xué)科;3100029 北京,首都醫(yī)科大學(xué)附屬北京安貞醫(yī)院北京市心肺血管疾病研究所超聲心動(dòng)圖室
宋現(xiàn)濤,E-mail:songxiantao@medmail.com.cn
10.3969/j.issn.1674-4055.2016.11.31