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心脏磁共振在急性心肌梗死预后评估中的应用

2017-01-13陆远龚艳君霍勇

中国介入心脏病学杂志 2017年4期
关键词:微血管左心室心肌梗死

陆远 龚艳君 霍勇



·综述·

心脏磁共振在急性心肌梗死预后评估中的应用

陆远 龚艳君 霍勇

心脏磁共振; 急性心肌梗死; 预后评估

急性心肌梗死(acute myocardial infarction,AMI)因其居高不下的发病率和死亡率[1],给人类健康造成了严重危害。随着近代医学的发展,临床上对AMI的诊疗已不再满足于单纯的定位诊断,而需要对梗死程度、心肌灌注和心脏功能做出精确测量,并对患者心室重构及远期预后做出精准评价。

近年来,心脏磁共振(cardiac magnetic resonance,CMR)成像技术飞速发展,不仅能够精准测量梗死程度、鉴别心肌水肿与坏死、识别微血管损伤,更能准确评价心脏整体及局部功能、定量检测心脏应变和心腔内血流。由于CMR可“一站式”地对心脏结构、功能、灌注及代谢进行全面而精准的评估,其在AMI疾病诊断、疗效预测、预后评估中的价值日益突出[2]。本文将重点综述CMR在AMI预后评价中的应用。

1 精准评估心肌活性

心肌活性即心肌的存活能力。存活心肌具有完整的细胞膜,代谢活动也依然存在,而坏死心肌的细胞膜完整性丧失,代谢活动也基本停止。通过延迟增强心脏磁共振扫描技术(late gadolinium-enhanced cardiac magnetic resonance, LGE-CMR),可以对存活心肌进行精准识别。胞外对比剂[如钆喷酸葡胺(Gd-DTPA)]经过静脉注入体内,并随血流分布至细胞外间隙。在有活性区域,细胞膜完整,对比剂无法进入细胞,随血流迅速排空,在延迟显像上呈低信号。而坏死心肌的胞膜完整性丧失,对比剂透入细胞发生滞留,故在延迟显像时呈高信号,即出现延迟增强[3]。基于此种原理,LGE-CMR可准确判断心肌细胞的活性,并进一步对心肌坏死区进行精准测量。

除了CMR,目前临床上可用于评估心肌活性的技术还包括超声心动图、单电子发射计算机断层显像术(single-photon emission computed tomography,SPECT)、正电子发射断层显像术(positron emission tomography,PET)等。然而,LGE-CMR因其与组织学极好的相关性(R=0.99)、更高的空间分辨率和更高的小梗死灶检出率而显示出了独特的优势[4-5]。

1.1 梗死程度及范围

LGE-CMR可对梗死程度和范围进行精准测量,甚至可检测到1 g以内的梗死灶[6]。梗死面积(infarct size,IS)、透壁程度(extent of transmurality,EOT)、梗死重量(infarct mass,IM)均是目前较常用的量化指标。

AMI急性期内测量梗死程度对患者预后评估有重要作用。多项研究对AMI患者随访发现,患者主要不良心血管事件(major adverse cardiac events,MACE;包括心源性死亡、再发心肌梗死、心力衰竭再次入院)的发生率与发病1周内的IS水平和EOT呈正相关。进一步的多因素分析提示,透壁梗死(梗死>50%室壁厚度)的节段数是MACE的独立预测因素[7-8]。在心肌17段划分模型中,透壁梗死的节段数每增加一段,发生MACE的风险增加38%(HR1.38,95%CI1.19~1.60,P<0.001)[8]。最近一项研究对27例患者随访3.5年也证实,AMI发生1周内行LGE-CMR检查,当IM>14 g时,发生MACE(死亡、再发心肌梗死、心绞痛或心力衰竭再次入院)的风险显著增高(HR20.9,95%CI1.8~256,P=0.02),ROC曲线结果提示IM>14 g是评估MACE发生风险的良好指标(曲线下面积0.719,灵敏度63%,特异度90%)[9]。

AMI慢性期LGE-CMR检测梗死程度同样对预测患者预后有较高的价值。一项研究对309例患者在心肌梗死3个月后通过LGE-CMR检测IS水平,并继续随访807 d,结果提示,IS水平较高的患者更容易发生MACE(死亡、再发心肌梗死、心力衰竭再次入院、非计划血运重建)。在矫正年龄、心率、左心室射血分数(left ventricular ejection fraction, LVEF)、肌钙蛋白峰值、左心室重量等指标后,IS水平依然是发生MACE的独立预测因素(HR1.13,95%CI1.05~1.21,P=0.001)[10]。在发病后不同的时间点,针对同一例AMI患者,使用细胞外非特异性对比剂Gd-DTPA行LGE-CMR所测的IS并非完全一致,而是随时间推移IS逐渐减小,其具体机制目前尚未完全阐明[11],可能与梗死核心边缘区细胞水肿导致细胞膜通透性改变、后期水肿消退有关。近年来,动物研究使用非卟啉类坏死亲和性对比剂(如ECⅢ-600)所测的IS未出现随时间而改变,并与组织病理学结果高度一致[12]。然而在进行预后评估时,无论是急性期(梗死1周内)还是慢性期(梗死3~6个月以后),LGE-CMR测得的梗死程度均是发生MACE的有效预测因素。

1.2 可挽救心肌指数

冠状动脉闭塞后,所支配的缺血区统称为危险区(area at risk,AAR)。其中缺血较严重的区域,心肌细胞坏死凋亡,发生不可逆损伤,称为梗死核心(myocardium infarction core,MIC)。而缺血相对较轻的区域,细胞仅表现为水肿等可逆性损伤,血管再通后损伤可逆转,称为可挽救区(salvageable zone,SZ)。

AAR内心肌缺血水肿、组织含水量增高,在T2加权像(T2-weighted image, T2WI)上呈高信号,这也成为准确评估AAR范围的经典手段[13-14]。随着近年来CMR的不断发展,新的扫描序列及成像技术,如T1值编码图(T1 mapping)和T2值编码图(T2 mapping),也在评估AAR的方面显现出潜在的价值[15-18]。

T2WI联合LGE-CMR,能够对AAR和SZ的范围进行精准测量,进而计算出可挽救心肌指数(myocardial salvage index,MSI)。MSI是SZ与AAR的比值(MSI=SZ/AAR),能够有效反映心肌损伤的可逆程度。与IS的绝对值相比,MSI代表可挽救心肌所占的比例,因此,能够更准确地反映病变严重程度,也使不同设备的扫描结果具备了可比性[19]。

目前,MSI被广泛应用于预测血管再通的疗效,而越来越多的研究也表明,MSI同样也是较好的预后评价指标。近期一项研究将208例AMI患者按照MSI水平分为高低两组并随访18.5个月,结果显示MSI较高的患者,MACE(死亡、再发心肌梗死、充血性心力衰竭)发生率和全因死亡率均明显低于MSI较低的患者。进一步矫正年龄、糖尿病、LVEF等因素后,MSI是AMI患者死亡的独立预测因素(HR0.93,95%CI0.91~0.96,P<0.01)[20]。在de Waha等[7]的研究中,MSI被证实同样也是MACE的独立预测因素(HR0.94,95%CI0.92~0.96,P<0.001),MSI越高,死亡风险越低。

T2WI图像中的AAR面积并非一成不变,而是随时间的延长呈双峰改变:AMI后AAR面积迅速增加,在24 h达到第一个高峰;随后AAR面积逐渐下降又再次升高,并在第7天达到第二个峰值[21-22]。对于这一现象目前尚无一致的解释。Fernández-Jiménez等[21]在动物模型中发现,梗死心肌的水肿程度也呈双峰改变,且与T2WI的信号变化时间完全吻合,因此认为T2WI信号的改变是由于心肌水肿的正常演变引起。但是Carrick等[22]却发现,T2WI的双峰改变只在合并心肌内出血(intramyocardial hemorrhage,IMH)的患者中才能观察到,因此他认为T2WI之所以呈现双峰改变是由于血红蛋白对信号的干扰引起。

2 准确识别微血管损伤

无论是药物溶栓、经皮介入还是手术治疗,及时开通梗死血管,重建冠状动脉血运,都是AMI治疗的关键策略。然而,“再灌注”本身又可诱发微血管损伤,加重局部病变。其中,微血管阻塞(microvascular obstruction,MVO)和IMH是最主要的微血管损伤表现。根据国际心肺血液协会(National Heart, Lung, and Blood Institute, NHLBI)缺血再灌注心肌保护共识,梗死后微血管损伤的治疗将是改善AMI预后的关键靶点[23]。

2.1 MVO

无复流现象(no reflow phenomenon),即罪犯血管开通后心肌灌注无显著改善的一种现象,组织学上主要表现为局部MVO[24]。MVO的具体机制目前仍不完全清楚,可能与血小板聚集、中性粒细胞黏附、毛细血管内红细胞淤积及局部组织水肿等因素有关[25]。

目前,CMR是评估MVO的有效检测手段。由于MVO,对比剂无法随血流分布到阻塞局部,因而在首过灌注显像(first-pass perfusion)时表现为灌注缺损,在LGE-CMR上表现为延迟强化区内的低信号无强化区[26-27]。尽管血管造影、超声心动图、核素扫描等技术也可对MVO进行识别,但CMR因其较高的空间分辨度和对比度、无电离辐射等优势而备受推崇[4]。

MVO的存在提示AMI患者的不良预后。Hombach等[28]对110例患者随访225 d后发现,存在MVO的患者,MACE和心室重构的发生率、死亡率均显著高于无MVO的患者。Bogaert等[29]和Regenfus等[30]也同样得出了类似的结论:存在MVO的患者更容易出现左心室不良重构和心血管不良事件,其心功能的恢复水平较差。van Kranenburg等[31]对8项临床研究的荟萃分析结果也证实MVO是AMI患者发生MACE(死亡、再发心肌梗死、心力衰竭再次入院、非计划性血运重建术)的独立预测因素(HR4.68,95%CI2.86~7.66,P<0.01)。

2.2 IMH

再灌注诱发微血管损伤,可表现为毛细血管屏障破坏、红细胞从毛细血管腔内溢出,发生IMH[32]。虽然IMH的机制仍未完全阐明,但与缺血-再灌注损伤密切相关[33]。IMH总是与再灌注伴随出现,若冠状动脉持续阻塞、不开通罪犯血管,则IMH将不会出现[34]。目前认为IMH的机制可能为:缺氧诱发内皮肿胀、细胞间连接受损,再灌注后损伤继续加重、基底膜降解、毛细血管的屏障作用消失,随后红细胞漏出到组织间隙,从而发生IMH[32]。漏出到组织间隙的氧合血红蛋白,依次代谢为去氧血红蛋白、高铁血红蛋白、含铁血黄素等降解产物。由于不同降解产物的顺磁性效应不同,在CMR图像上呈现的信号特点也不尽相同。T1、T2及T2*加权序列均可精准评估IMH,比较常使用的T2、T2*序列在心肌梗死后24 h以上表现为梗死区的低信号。CMR已经被认为是评价IMH的金标准[32]。

IMH的出现往往提示微血管的严重损伤,并与患者的长期预后密切相关。多项研究对AMI患者进行长期随访,结果均提示IMH与心室不良重构及心脏收缩功能密切相关[35-37]。另一项研究对304例AMI患者随访6个月发现,合并IMH的AMI患者,MACE(心源性死亡、再发心肌梗死、心力衰竭再次入院)发生率和死亡率都显著升高。更重要的是,在包含IMH、MSI、IS、MVO等多项CMR指标的多因素分析中,IMH是唯一能独立预测MACE的CMR测量指标(HR1.29,95%CI1.16~1.41,P<0.01)[38]。

3 全面评估心脏功能

心脏磁共振电影(cine cardiac magnetic resonance,cine-CMR)可通过连续扫描单层多相位图像,将其合成为心脏电影,来评估心脏功能。通过观察不同层面的电影图像,可以评价各心腔收缩及舒张运动、瓣膜功能,还可以精确测量收缩期及舒张期的室壁厚度、心腔大小、射血分数、射血量等心功能指标,准确评价心脏局部及整体的运动功能。CMR具有较高的时间、空间分辨率,能清晰显示心动周期中不同时相心内膜及心外膜的边界,而且还不易受到其他因素的干扰(如声窗对超声心动图的限制),因此成为评价局部运动最准确的技术之一。

3.1 左心室整体运动功能

LVEF是评价左心室整体运动功能的经典指标,临床上常用二维超声心动图进行测量。与超声心动图相比,cine-CMR对LVEF的测量不仅具有更好的客观性,还具有更高的准确性和重复性[39-40]。作为经典的心功能评价指标,心肌梗死后LVEF水平可以有效预测MACE (死亡、再发心肌梗死、心力衰竭再次入院、非计划性血运重建)的发生。一项研究对110例AMI患者随访225 d发现,死亡的患者LVEF基线水平(心肌梗死1周内检测)较存活患者更低,Cox回归分析提示基线LVEF水平是MACE发生的独立预测因素(P=0.0057)[28]。类似结论在多项临床研究中也得到证实[7,41-43]。2014年发表的一项系统评价同时纳入AMI患者及冠心病疑诊患者共计25 497例,多因素分析结果仍表明LVEF是MACE的独立预测因素[44]。除了LVEF,CMR也能够准确测定其他反映左心室运动功能的指标,如左心室收缩末期容积、左心室舒张末期容积及左心室重量指数等,这些CMR指标同样在多项研究中被证实与AMI患者的预后具有相关性[45-46]。

3.2 右心室整体运动功能

由于右心室特殊的结构和位置,准确测量右心室功能相对比较困难,因而针对右心室功能的研究数量远低于左心室。CMR同样也可以对右心室的结构及功能进行评估。Larose等[47]对147例患者的研究发现,在AMI后6.7年,CMR所测的右心室射血分数与患者随后17个月内的死亡率有良好的相关性。然而,Grothoff等[48]对421例患者随访20个月后却发现,右心室射血分数与MACE的发生并无独立相关性。由此看来,右心室功能与AMI患者预后的相关性还需要更多研究进一步探讨。

3.3 局部室壁运动

心脏具有极强的代偿能力,有时AMI发生后,整体的心功能指标可以不受影响,而仅表现为局部室壁运动的异常。因此,量化评估室壁运动,有助于精准把握心肌梗死对心脏运动功能的影响。CMR心肌标记(CMR tagging)通过无创地在心脏影像中添加放射状、平行状或栅格状标记线,可精确测量局部室壁运动的改变[49]。由于标记线的相对位置随室壁运动而发生改变,分析标记线的形变程度,即可得到局部室壁运动的各项参数。

目前,通过CMR评价局部室壁运动来评估预后的研究相对较少。El Aidi等[44]对56项临床研究进行系统评价,也未能确定室壁运动异常(wall motion abnormality, WMA)是否在AMI患者预后评价方面具有临床价值。该研究领域还需要更多研究进一步探索。

本文综述了目前CMR技术在AMI预后评估中的应用。CMR能够准确地对心肌活性、微血管损伤、心脏功能进行定量评估。CMR检测指标,如IS、透壁节段数、MSI等,均与患者的长期预后具有极好的相关性。而MVO及IMH也可被CMR准确识别,MVO和IMH的存在强烈提示严重的微血管损伤和不良生存预后。此外,CMR还能全面评价心脏的整体和局部运动功能,其中LVEF与预后良好相关,而局部运动功能在预后评价中的价值还有待更多的研究进行验证。与传统的超声心动图、SPECT、PET等技术相比,CMR除了更加客观、精准、全面,还具有“一站式”“无辐射”等特点,因此在临床应用中具有更大的优势。

近年来,CMR的发展突飞猛进,许多过去较难评估的参数,如心肌应变、心脏扭转等力学指标和血流速度、血液流向等腔内血流动力学特点,如今都可以通过心肌标记、相位对比、四维成像等一系列CMR技术进行无创、定量且准确的评估[50-54]。在心肌梗死后的修复过程中,梗死局部心肌和健康心肌的功能恢复遵循不同的特点[55],因而定量评价不同步心肌的运动,能更真实地反映梗死后心脏功能的改变。同时,精确评价心腔内血流的特点,也有助于进一步了解心肌收缩能力改变对心脏射血功能的影响。相比于传统的预后指标,心脏应变、腔内血流等参数更为精细和复杂,但却能为AMI评估预后提供细致而全面的参考信息。尽管目前有关心脏应变、腔内血流的预后研究还比较缺乏,但可以预见,通过全面分析心脏应变及血流特点,CMR将在AMI的预后评价中具有更广阔的应用前景。

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10.3969/j.issn.1004-8812.2017.04.007

100034 北京,北京大学第一医院心内科(陆远、龚艳君、霍勇);江苏徐州,徐州医科大学附属医院心内科(陆远)

霍勇,Email:huoyong@263.net.cn

R542.22

2016-11-28)

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