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        房顫患者心外膜脂肪組織影像學(xué)評(píng)估的研究進(jìn)展

        2025-08-15 00:00:00楊新梅郭鈺史佳麗劉建莉
        關(guān)鍵詞:心動(dòng)圖心房影像學(xué)

        心房顫動(dòng)(atrialfibrillation,AF)是臨床最常見(jiàn)的心律失常之一,患病率 1.5%~2%[1-2] 。目前,AF的全球發(fā)病率與死亡率逐年增加,在我國(guó)的發(fā)病率也隨著人口老齡化而急劇增加,給社會(huì)及醫(yī)療系統(tǒng)造成嚴(yán)重的負(fù)擔(dān)[3]。心外膜脂肪組織(epicardial adi-posetissue,EAT)是介于心肌和心包膜臟層之間的內(nèi)臟脂肪組織,主要分布在房室溝和室間溝,非均勻地包繞在心肌組織及大血管周圍,部分延伸進(jìn)入心肌組織,與心肌共享微循環(huán),并由冠狀動(dòng)脈(冠脈)分支供血。EAT已被證實(shí)具有代謝活動(dòng),其分泌的生物活性物質(zhì)可通過(guò)旁分泌和自分泌途徑作用于冠脈和心肌組織[4-5],EAT的異常沉積可促進(jìn)心血管疾病的發(fā)生、發(fā)展。影像學(xué)檢查可評(píng)估EAT的厚度、脂肪衰減、體積及其炎癥活動(dòng)的發(fā)生等,在AF消融術(shù)前評(píng)估及術(shù)后復(fù)發(fā)的預(yù)測(cè)中起到一定協(xié)助作用。

        1 EAT在房顫發(fā)生中的作用

        研究表明,EAT與AF密切關(guān)聯(lián),其可通過(guò)多種機(jī)制促發(fā)心律失常,目前已被證實(shí)的機(jī)制包括炎癥、脂肪浸潤(rùn)、氧化應(yīng)激、心房纖維化和自主神經(jīng)系統(tǒng)刺激,這些因素直接或間接造成心房重構(gòu),增加AF的嚴(yán)重程度和持續(xù)性[6。全身炎癥和免疫性疾病會(huì)增加AF的發(fā)生風(fēng)險(xiǎn)[7-9],炎癥在AF的發(fā)生、發(fā)展中起著核心作用[10]。有學(xué)者在多個(gè)AF患者的心房標(biāo)本中發(fā)現(xiàn)鄰近心肌細(xì)胞的炎癥浸潤(rùn)、纖維化和壞死[]。與竇性心律患者相比,AF患者的促炎標(biāo)志物水平升高,其中C反應(yīng)蛋白(C-reactiveprotein,CRP)和白細(xì)胞介素(interleukin,IL)-6已被證實(shí)與AF的發(fā)展及復(fù)發(fā)相關(guān)[12-13]。另外,腫瘤壞死因子(tumor necrosisfactor,TNF)- ∝ 、轉(zhuǎn)化生長(zhǎng)因子(transforminggrowth factor,TGF)- β 和IL-6會(huì)促進(jìn)心房纖維化和電重構(gòu)[14]。EAT可通過(guò)脂肪細(xì)胞直接浸潤(rùn)心房的心肌細(xì)胞,脂肪異常沉積使得心肌細(xì)胞的同一性消失,導(dǎo)致電生理傳導(dǎo)異常,促發(fā) AF[15] 。有研究表明,與非皮下脂肪組織相比[16],內(nèi)臟脂肪的異常增多和沉積與AF相關(guān)性更大。EAT作為一種高代謝組織,在生理?xiàng)l件下可保護(hù)心臟及冠脈以減少機(jī)械變形,具有產(chǎn)熱功能,不僅提供心肌的主要能量來(lái)源一一游離脂肪酸,還可隔離循環(huán)游離脂肪酸,使其免受脂毒性[16-18]。此外,EAT釋放的脂肪細(xì)胞因子包括脂聯(lián)素、腎上腺髓質(zhì)素和網(wǎng)膜素,其通過(guò)抗氧化、抗炎和抗凋亡特性發(fā)揮作用19;與無(wú)AF患者相比,AF患者的EAT厚度、質(zhì)量和體積均有增加[20]。Wong等[21]的一項(xiàng)Meta分析表明,與腹部脂肪相比,EAT體積越大,與AF的相關(guān)性越高性,間接證明了EAT在AF中的潛在機(jī)制和臨床重要性。VanRosendael等22則提出了左心房(leftartial,LA)EAT的增加與持續(xù)性/永久性AF的高患病率相關(guān),持續(xù)性/永久性AF較竇率對(duì)照組的LAEAT更高。目前,EAT體積增加已被證明是AF后續(xù)發(fā)展的獨(dú)立預(yù)測(cè)指標(biāo)[23]。Huber等[24]通過(guò)LA增強(qiáng)-EAT(LAe-EAT)對(duì)比增強(qiáng)CT掃描與非對(duì)比CT掃描的EAT體積的比值,評(píng)估AF患者LAe-EAT與AF消融術(shù)后復(fù)發(fā)的關(guān)系,證明LAe-EAT與AF消融術(shù)后復(fù)發(fā)獨(dú)立相關(guān),可作為EAT代謝活動(dòng)的無(wú)創(chuàng)成像指標(biāo)。

        2EAT的影像學(xué)評(píng)估研究進(jìn)展

        2.1 超聲心動(dòng)圖評(píng)估

        EAT在超聲心動(dòng)圖上表現(xiàn)為位于心室壁之間的高回聲區(qū)域,主要集中在右心室游離壁周圍和壁心包周圍[25]。EAT厚度的測(cè)量通常選擇胸骨旁長(zhǎng)軸和短軸切面,這一位點(diǎn)的心外膜脂肪最高,能準(zhǔn)確評(píng)估右心室游離壁的EAT厚度[26],其正常值約 5mm 。超聲心動(dòng)圖除了評(píng)估EAT厚度,還可提供左室質(zhì)量、心臟收縮及舒張功能等心臟數(shù)據(jù)。且其對(duì)EAT厚度測(cè)量的可重復(fù)性較好[27],其中經(jīng)胸超聲心動(dòng)圖(transthoracic echocardiographic,TTE)具有便捷、便宜及操作方便等優(yōu)點(diǎn);而經(jīng)食管超聲心動(dòng)圖是一種半侵入性方法,主要用來(lái)評(píng)估左心耳的結(jié)構(gòu)及功能,其準(zhǔn)確性與操作者的技術(shù)水平有關(guān)。Gunturk等[28]研究表明,TTE測(cè)量的EAT厚度可預(yù)測(cè)術(shù)后新發(fā)AF,這也間接說(shuō)明EAT厚度與AF發(fā)展的風(fēng)險(xiǎn)增加有關(guān)。Yamaguchi等29在通過(guò)TTE測(cè)量EAT厚度的同時(shí),還檢測(cè)左心耳排空流速,首次證實(shí)了EAT厚度與左心耳排空流速呈顯著負(fù)相關(guān) (ρ=-0.56,Plt; 0.001),且血栓的發(fā)生均出現(xiàn)在厚EAT組,因此,采用EAT評(píng)估AF患者發(fā)生左心耳血栓的風(fēng)險(xiǎn)具有一定的潛在價(jià)值。超聲心動(dòng)圖在EAT評(píng)估中具有一定局限性:僅能評(píng)估EAT厚度,無(wú)法評(píng)估體積;結(jié)果易受操作者影響、有一定偏差;當(dāng)心房增大不對(duì)稱時(shí),會(huì)影響厚度的測(cè)量。

        2.2心臟CTA評(píng)估

        心臟CTA空間分辨率高,可提供心臟、主動(dòng)脈和外周血管的解剖信息,此外,在CT后處理工作站手動(dòng)勾畫EAT范圍,可實(shí)現(xiàn)半自動(dòng)測(cè)量,并根據(jù)勾畫范圍,對(duì)全心、LA及冠脈周圍EAT進(jìn)行測(cè)量。脂肪組織衰減值較低,易分辨,CT值通常選取 -190~ -30HU[30] ,通過(guò)對(duì)脂肪組織閾值的選擇,可得到EAT的體積及衰減值。研究證實(shí),EAT體積在AF的發(fā)生、發(fā)展及消融術(shù)后的復(fù)發(fā)中,均可作為獨(dú)立的預(yù)測(cè)因子[22-24]。EAT衰減值也可作為預(yù)測(cè)AF復(fù)發(fā)的影像學(xué)指標(biāo),但其可能因所用CT品牌、管電流、管電壓、對(duì)比劑、注射流率及閾值的不同而存在一定差異。Huber等[24]研究發(fā)現(xiàn),對(duì)比增強(qiáng)心臟CT掃描中較大的LAEAT離散度(反映EAT異質(zhì)性)與肺靜脈隔離術(shù)后AF復(fù)發(fā)獨(dú)立相關(guān)[31]。因此,將EAT指標(biāo)估計(jì)值添加到CT診斷報(bào)告中可為心血管疾病提供額外的風(fēng)險(xiǎn)評(píng)估,且不會(huì)增加患者的輻射暴露及負(fù)擔(dān)[32]。目前,心臟CTA作為AF患者影像學(xué)評(píng)估的第二選擇,可更全面地評(píng)估超聲心動(dòng)圖可能存在的LA血栓的漏診。對(duì)于植人左心耳封堵器或冠脈支架的患者,CT檢查時(shí)金屬偽影可能影響心臟評(píng)估的準(zhǔn)確性,而能譜CT作為一種新技術(shù),可顯著減少人工瓣膜或電極金屬造成的偽影[33],大大改善圖像質(zhì)量。但目前尚無(wú)能譜CT與EAT的相關(guān)研究。

        2.3 MRI評(píng)估

        心血管磁共振(cardiacmagneticresonance,CMR)空間分辨率高,可識(shí)別心房組織結(jié)構(gòu)的變化,且無(wú)CT相關(guān)的電離輻射危害[34],是目前識(shí)別脂肪組織的金標(biāo)準(zhǔn)。CMR常用的掃描序列包括黑血快速自旋回波 T1, 穩(wěn)態(tài)自由進(jìn)動(dòng)(steadystate freeprecession,SSFP)序列、3DDixon技術(shù)。其中,黑血快速自旋回波 T1 較易獲得,但掃描時(shí)間長(zhǎng),對(duì)患者要求高,且圖像質(zhì)量易受心率及場(chǎng)強(qiáng)影響。SSFP序列可清晰顯示EAT情況,但在有大量心包積液時(shí)應(yīng)用會(huì)受到一定限制,需與其他序列聯(lián)合以確定EAT邊界。3DDixon技術(shù)可在一次成像時(shí)間內(nèi)進(jìn)行多種組織成分成像[35]。Nakamori等[36]研究發(fā)現(xiàn),在3D Dixon掃描模式下,AF患者的LAEAT顯著增加,可為檢測(cè)LA結(jié)構(gòu)重塑之外的AF患者提供更多的影像信息。Henningsson等[37]研究發(fā)現(xiàn),與標(biāo)準(zhǔn)單相Dixon相比,CineDixon可用于量化EAT,更好地克服心臟、呼吸的運(yùn)動(dòng)偽影,提供更佳的圖像質(zhì)量。Chahine等[34研究證實(shí),在CMR定量下的EAT是AF患者消融術(shù)后復(fù)發(fā)獨(dú)立的預(yù)測(cè)指標(biāo)。盡管CMR發(fā)展極快,有很高的軟組織分辨率,但其掃描時(shí)間較超聲和CT長(zhǎng),且是幽閉恐懼癥患者的絕對(duì)禁忌,臨床應(yīng)用有一定限制。

        2.4 PET-CT評(píng)估

        氟-18-脫氧葡萄糖( 18F -flurodeoxyglucose, 18F? #FDG)PET-CT可檢測(cè)炎性病變的位置、活動(dòng)度及嚴(yán)重程度,在心血管炎性病變的診斷及療效評(píng)估中具有重要作用[38]。炎癥早期表現(xiàn)為組織充血、血管通透性增加和炎癥因子的釋放,促進(jìn) 18F -FDG輸送至病變部位;隨炎癥進(jìn)展,炎癥細(xì)胞中葡萄糖代謝不斷增加,進(jìn)而促使 18F -FDG攝取增強(qiáng)[39]。Mzaurek等[40]通過(guò) 18F -FDGPET-CT發(fā)現(xiàn)AF患者EAT最大標(biāo)準(zhǔn)攝取值(maximum standard uptake value, SUVmax )高于非AF對(duì)照組且差異有統(tǒng)計(jì)學(xué)意義,但該研究樣本量較?。?1例),且未調(diào)整BMI、左心房直徑等相關(guān)混雜因素。而王冰等[39]在校正高密度脂蛋白膽固醇、左室射血分?jǐn)?shù)、左心房直徑、EAT體積后,證實(shí)LAEAT炎癥活性與AF仍獨(dú)立相關(guān)是AF的影響因素;此外,研究還發(fā)現(xiàn)EAT炎癥活性增高( 與AF呈正相關(guān),AF發(fā)生的危險(xiǎn)程度隨EAT炎癥活性增高而升高,但此項(xiàng)研究缺乏病理金標(biāo)準(zhǔn)的對(duì)比。以上研究表明, 18F -FDGPET-CT可作為定量分析及動(dòng)態(tài)監(jiān)測(cè)AF患者炎癥活性的無(wú)創(chuàng)影像學(xué)指標(biāo),在AF的防治及抗炎療效評(píng)估中具有潛在的臨床價(jià)值和應(yīng)用前景。但目前因PET-CT費(fèi)用較高等, 18F -FDGPET-CT在AF中的應(yīng)用研究較少。

        2.5 人工智能技術(shù)評(píng)估

        隨著人工智能技術(shù)的快速發(fā)展,EAT的測(cè)量從半自動(dòng)技術(shù)發(fā)展到全自動(dòng)深度學(xué)習(xí)方法,除加快了分割時(shí)間,使EAT定量適合臨床實(shí)踐外,還提高了EAT體積測(cè)量的可重復(fù)性[32]。West等[41]基于心臟CTA提出了一種新的深度學(xué)習(xí)模型,證明EAT體積的評(píng)估可在不受其他危險(xiǎn)因素的影響下改善心血管和非心血管結(jié)局的風(fēng)險(xiǎn)評(píng)估,預(yù)測(cè)全因死亡率、非心源性死亡率、心肌梗死和卒中;另外其也證實(shí)了EAT體積是心臟術(shù)后AF的獨(dú)立危險(xiǎn)因子,但心臟術(shù)后的短期AF風(fēng)險(xiǎn)數(shù)據(jù)僅依賴于住院監(jiān)測(cè),缺少出院后的監(jiān)測(cè)隨訪,后續(xù)需更大樣本量的研究證實(shí)。Qu等[42]提出評(píng)估了基于深度學(xué)習(xí)的2D卷積神經(jīng)網(wǎng)絡(luò),并自動(dòng)量化了非對(duì)比CT數(shù)據(jù)的EAT體積,結(jié)果與手動(dòng)勾畫的體積一致,證明非對(duì)比CT測(cè)量EAT體積可行且具有臨床意義,未來(lái)或可整合到常規(guī)胸部CT中,用于預(yù)測(cè)AF。深度學(xué)習(xí)模型的應(yīng)用可減少人工誤差,提高效率,助力AF患者的并發(fā)癥預(yù)防和預(yù)后評(píng)估。

        目前,諸多研究證實(shí)了EAT與AF之間的相關(guān)性,并隨之衍生出了LAEAT、LAe-EAT等一系列影像學(xué)評(píng)估指標(biāo),其在AF的發(fā)生、發(fā)展、預(yù)后及消融術(shù)后的復(fù)發(fā)中,可作為獨(dú)立預(yù)測(cè)指標(biāo)。EAT有可能為臨床提供更多潛在的治療靶點(diǎn),而影像學(xué)技術(shù)的不斷革新也將更好地評(píng)估EAT。

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        (收稿日期 2024-07-18)

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