無創(chuàng)血流儲備分數(shù)測定對冠心病患者心肌缺血功能評估的臨床進展

胡文超，曹豐

(解放軍總醫(yī)院心血管內(nèi)科，北京 100853)

以往的研究表明，冠狀動脈重度狹窄往往預(yù)示著心肌缺血存在。然而，隨著研究的深入，人們逐漸發(fā)現(xiàn)冠狀動脈狹窄嚴重程度與心肌缺血并不完全相關(guān)。有研究顯示，在經(jīng)冠狀動脈CT血管造影(coronary computed tomographic angiography，CCTA)或侵入性冠狀動脈造影(invasive coronary angiography，ICA)檢查提示狹窄程度≥50%的阻塞性病變中，僅有約一半的病變導(dǎo)致了真正的心肌缺血[1,2]；另一方面，狹窄程度≤50%的非阻塞性病變也可能會引起心肌缺血[3-5]，提示冠狀動脈解剖學(xué)狹窄并不一定代表功能性的心肌缺血。

冠狀動脈血流儲備分數(shù)(fractional flow reserve，F(xiàn)FR)概念的提出為冠狀動脈狹窄的功能學(xué)評估開辟了新紀元，目前已成為診斷冠狀動脈狹窄病變引起血流動力學(xué)異常的“金標準”[6,7]。FFR是指存在冠狀動脈狹窄病變的情況下，該冠狀動脈所供應(yīng)區(qū)域心肌能獲得的最大血流量與該區(qū)域理論上正常情況下能獲得的最大血流量之比[8,9]。目前研究人員認為，引起冠狀動脈血流動力學(xué)異常的FFR值在0.75～0.80之間[10-12]。FFR值<0.75的冠狀動脈狹窄病變往往表現(xiàn)出心肌缺血的征象，而FFR值>0.80的病變則極少出現(xiàn)可誘導(dǎo)的心肌缺血征象[13,14]。

然而，F(xiàn)FR測定需要使用壓力測定導(dǎo)絲，具有有創(chuàng)性、手術(shù)費用高、風(fēng)險較高及輻射量大等缺點，因而不能成為診斷心肌缺血的常規(guī)檢測。近年來，隨著計算機流體動力學(xué)(computational fluid dynamics，CFD)技術(shù)的發(fā)展，衍生出了一種基于CCTA的無創(chuàng)性FFR(fractional flow reserve derived from coronary computed tomographic angiography，F(xiàn)FRCT)測定技術(shù)，相比經(jīng)導(dǎo)管的有創(chuàng)FFR測定，F(xiàn)FRCT測定具有無創(chuàng)、經(jīng)濟、低風(fēng)險、低輻射等優(yōu)點。本文就FFRCT的基本概念、原理、臨床研究進展、優(yōu)缺點及應(yīng)用前景作一綜述。

1 概念及原理

1.1 概念

基于冠狀動脈CTA圖像，采用CFD的方法模擬冠狀動脈狹窄在靜息及藥物負荷狀態(tài)下的血流動力學(xué)狀態(tài)，通過該無創(chuàng)方法計算出的FFR值即為FFRCT。

1.2 原理

隨著CFD技術(shù)的發(fā)展，計算機可以通過CCTA數(shù)據(jù)模擬出冠狀動脈的解剖模型和血液流體動力學(xué)模型。基于圖像的血流模型的發(fā)展，使得在真實患者的特定模型中分割建立搏動的冠狀動脈血流和壓力模型成為可能；而且通過該模型，我們可以模擬出冠狀動脈樹的入口、出口邊界條件，并能模擬出注射腺苷后的最大充血狀態(tài)。根據(jù)既往研究，冠狀動脈內(nèi)血流狀態(tài)遵循流體動力學(xué)物理規(guī)律，因此可以根據(jù)計算機建立的冠狀動脈樹模型和獲取的邊界條件，計算整個冠狀動脈樹的流體控制方程。最后，創(chuàng)建一個可以顯示冠狀動脈血液流速及壓力的三維冠狀動脈樹模型，計算出各個點的FFR值[15]。

2 臨床研究及進展

盡管FFRCT技術(shù)日益完善，臨床應(yīng)用前景良好，但是仍需在嚴格的臨床試驗中以有創(chuàng)FFR為“金標準”，對其臨床有效性進行評估。無論是從目前著名的多中心大型臨床研究，還是近期的一些單中心研究來看，F(xiàn)FRCT在識別心肌缺血方面均顯示出良好的診斷性能。

2.1 多中心臨床研究

關(guān)于FFRCT，目前國際上著名的多中心大型前瞻性臨床研究包括DISCOVER-FLOW 研究[16]、DeFACTO 研究[17,18]、NXT 研究[19]，以及PLATFORM研究[20]。其中前三者均以有創(chuàng)FFR為參考標準，是評價FFRCT診斷價值的臨床研究；后者則是首次評估FFRCT檢查指導(dǎo)臨床決策的準確性和臨床預(yù)后效果的隊列研究。

DISCOVER-FLOW研究、DeFACTO研究和NXT研究納入的研究對象主要是臨床確診或疑診的成年冠狀動脈疾病(coronary artery disease，CAD)患者，并在60 d內(nèi)先后進行了CCTA、ICA和FFR檢查。研究結(jié)果顯示，無論是以靶血管、還是以患者為研究對象進行分析，F(xiàn)FRCT檢查結(jié)果與FFR結(jié)果均呈現(xiàn)出良好的正相關(guān)性，且在診斷敏感性、特異性、陽性預(yù)測值、陰性預(yù)測值和準確性方面，F(xiàn)FRCT較CCTA均有明顯提升；從各個研究的受試者工作特征(receiver operating characteristic，ROC)曲線分析來看，F(xiàn)FRCT的曲線下面積(area under the curve，AUC)均顯示出其在識別患者缺血方面良好的診斷性能(表1)。值得一提的是，NXT研究納入了更多的中度病變患者，使用了更加自動化的軟件版本，并且嚴格按照指南加強了β-受體阻滯劑以及硝酸鹽類藥物的使用[21,22]，這表明FFRCT檢查在中度CAD患者中的應(yīng)用前景也良好。另外，NXT研究中的一項亞組分析表明[23]，兩種檢查技術(shù)具有高度的可重復(fù)性。

PLATFORM研究是首次評估FFRCT臨床應(yīng)用效果的連續(xù)性隊列研究。研究結(jié)果顯示，在由FFRCT指導(dǎo)的原計劃行ICA的受試者中，有61%避免了有創(chuàng)檢查，且取消ICA的受試者在1年隨訪中沒有遭遇不良事件[24]。此外，使用CCTA聯(lián)合FFRCT的診斷策略使得通過ICA檢查顯示非梗阻性疾病的發(fā)病率減少了83%，且該策略在減少醫(yī)療保健成本的同時能夠提高患者生活質(zhì)量[20,24,25]。

2.2 近期的單中心臨床研究

傳統(tǒng)的FFRCT操作及計算需要復(fù)雜地幾何建模和高強度地血流分析計算過程，這往往需要由與患者進行CCTA檢查地點異地的超級計算機來完成。近期，伴隨著一種新型的、計算強度較低的冠狀動脈降階模型出現(xiàn)，使得計算機斷層掃描血流儲備分數(shù)(computed tomography fractional flow reserve，CT-FFR)值的計算在現(xiàn)場即可實現(xiàn)。目前，已經(jīng)有一些研究者通過單中心臨床研究[26-29]，驗證了使用該新型方法進行現(xiàn)場CT-FFR操作的準確性和可靠性。從這些研究結(jié)果中可以看出，這種新型算法在顯著提高CT-FFR計算效率的同時，仍然保持了其在識別心肌缺血病變方面良好的診斷性能(表2)。

3 優(yōu)缺點

由于FFRCT值是在基于CCTA圖像的基礎(chǔ)上運用CFD方法分析計算出來的，所以FFRCT不僅具有CCTA無創(chuàng)、安全、快速、經(jīng)濟等優(yōu)點，而且FFRCT可提供整個冠狀動脈生理功能學(xué)方面的信息。從上述多中心和單中心臨床研究中也可以發(fā)現(xiàn)，F(xiàn)FRCT與FFR有高度相關(guān)性，在識別心肌缺血病變方面有較高的準確性。

表1 著名的FFRCT多中心臨床研究

FFRCT: fractional flow reserve derived from coronary computed tomographic angiography; CCTA: coronary computed tomographic angiography; ICA: invasive coronary angiography; PPV: positive predictive value; NPV: negative predictive value; AUC: area under the curve; CI: confidence interval

表2 現(xiàn)場CT-FFR的單中心臨床研究

CT-FFR: computed tomography fractional flow reserve; CCTA: coronary computed tomography angiography; ICA: invasive coronary angiography; QCA: quantitative coronary angiography; PPV: positive predictive value; NPV: negative predictive value; AUC: area under the curve; CI: confidence interval

FFRCT技術(shù)本身也存在一定的局限性。(1)高質(zhì)量的CCTA圖像數(shù)據(jù)是獲得準確FFRCT值的關(guān)鍵，圖像質(zhì)量的好壞程度直接影響FFRCT值的準確性[30,31]。(2)過高的冠狀動脈鈣化積分(coronary artery calcium score，CACS)也會降低FFRCT的準確性[32]。(3)如今FFRCT技術(shù)尚未常規(guī)應(yīng)用于臨床實踐。(4)對于FFR值在“灰度值(0.75～0.80)”范圍內(nèi)的患者，F(xiàn)FRCT的診斷性能欠佳[33]。(5)在微循環(huán)障礙的患者中，通過FFRCT計算往往會錯誤地估計病變遠端的實際FFR值[15]。

4 應(yīng)用前景

較之核素心肌顯像等其他無創(chuàng)性心肌缺血評估方法[34]，F(xiàn)FRCT有著其不可比擬的優(yōu)勢。盡管目前FFRCT在診斷急性冠脈綜合征(acute coronary syndrome,ACS)、冠狀動脈旁路移植(coronary artery bypass graft,CABG)術(shù)后、經(jīng)皮冠狀動脈介入(percutaneous coronary intervention,PCI)術(shù)后的應(yīng)用情況仍然是未知的，相信隨著CFD技術(shù)的發(fā)展，通過計算機模擬PCI術(shù)后或CABG術(shù)后患者的血流模型終將成為可能。Chinnaiyan等[35]發(fā)起了一項國際性多中心前瞻性臨床研究(Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care，ADVANCE)，該研究計劃自2015年7月起累計納入5000例穩(wěn)定型心絞痛患者，預(yù)計2021年完成，旨在確定FFRCT/CCTA聯(lián)合診斷策略能否顯著改變穩(wěn)定型心絞痛患者的管理方案。

諸如外周動脈、腦動脈、腎動脈等其他血管也有使用FFRCT技術(shù)評估血流動力學(xué)生理功能狀態(tài)的可能性[15]。相信隨著FFRCT技術(shù)的日趨成熟和標準化，再加上充分的臨床研究證據(jù)，應(yīng)用FFRCT技術(shù)指導(dǎo)臨床醫(yī)師選擇相應(yīng)管理策略指日可待[36]。

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