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急性心肌炎多模态影像学诊疗进展

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摘    要:急性心肌炎(AM)临床表现多变,早期明确诊断对临床决策与预后评估具有重要意义。作为无创诊断AM的主要工具,超声心动图、MRI及PET可从形态、功能及分子水平显示心肌损伤,在其风险分层和临床管理中发挥关键作用。本文就多模态影像学用于诊断与治疗AM进展进行综述。


关键词:心肌炎;超声心动描记术;磁共振成像;正电子发射断层显像;


Progresses of multimodal imaging for diagnosis and treatment of acute

myocarditis

ZHANG Yichan ZHANG Yanting HE Shukun

LIU Tianshu SHI Jiawei FU Yanan TAN

Yuting ZHANGLi XIE Mingxing WANG Jing

Department of Ultrasound Medicine Union Hospital, Tongji Medical College Huazhong

University of science and Technology Hubei Province Clinical Research Center for Medical

lmaging,Hubei Province Key Laboratory of Molecular Imaging


Abstract:The clinical manifestations of acute myocarditis(AM) are variable, and early diagnosis is of great significances for clinical decision-making and prognosis evaluation. Being the main noninvasive diagnostic tools for AM, echocardiography, MRI and PET can display myocardial damage at the morphological, functional and molecular levels, and play key roles in risk stratification and clinical management. The research progresses of multimodal imaging for diagnosis and treatment of AM were reviewed in this article.


Keyword:myocarditis; echocardiography; magnetic resonance imaging; positron-emission tomography;


心肌炎通常由感染、接触药物或有毒物质及异常免疫反应引起,可致心脏出现不同程度结构改变和功能障碍。急性心肌炎(acute myocarditis, AM)通常在1个月内发病,以心肌内炎性细胞浸润为组织学特征,临床表现差异较大,可无明显症状,也可出现轻微胸痛、严重心力衰竭甚至心源性休克[1]。针对AM目前尚无特异性疗法,早期确诊心肌受累对改善预后具有重要意义。心内膜心肌活检(endomyocardial biopsy, EMB)是诊断心肌炎的金标准,但敏感度较低、并发症较严重,且无法完全反映心肌炎症变化过程及心功能受损情况,临床应用受限[2]。超声心动图、心脏MR(cardiac MR, CMR)、PET可无创、准确量化心脏形态及功能变化,还可定性评估心肌组织的病理改变,明确心肌损伤部位、程度,是EMB的重要补充。本文就多模态影像学用于诊断与治疗AM研究进展进行综述。


1 诊断AM

AM病理改变缺乏特异性,间质性病变主要表现为心肌间质充血、水肿,心肌病变则主要表现为心肌细胞变性坏死、溶解。


1.1 心肌水肿充血

1.1.1 超声心动图

心肌水肿可致心脏形态结构和功能发生改变,主要包括左心室壁增厚、心腔扩大及心肌运动减弱。AM发病后1~3天,尤其暴发性心肌炎(fulminant myocarditis, FM),可出现一过性左心室壁厚度增加。既往研究[3]认为AM室壁增厚常表现为向心性肥厚,使舒张功能障碍和每搏输出量减少,可进一步演变为FM。AM所致心腔扩大与炎症累及心脏范围和严重程度有关,左、右心均可累及,以左心扩大更为多见,死于FM患者左心房前后径明显增加[4]。


心肌炎所致水肿通常不会导致整体心功能明显降低;斑点追踪超声心动图(speckle tracking echocardiography, STE)可识别局部水肿引起的亚临床收缩功能障碍。CHINALI等[5]回顾性分析33例经CMR证实的局灶性AM患儿,发现其左心室整体纵向应变(left ventricular global longitudinal strain, LVGLS)仍在正常范围内,但局部纵向应变已有所减低,左心室基底部下间隔、下壁、下侧壁局部纵向应变明显低于其他节段。与传统超声参数相比,心肌应变对心肌轻微损害更加敏感;左心室功能障碍严重程度与心肌应变所示水肿范围相关[6]。


1.1.2 心脏MR

根据路易斯湖标准(Lake Louise criteria, LLC),CMR诊断心肌炎需满足心肌水肿、充血和钆对比剂延迟强化(late gadolinium enhancement, LGE)中的任意2项,据此诊断准确率可达78%[7]。T2WI是检测急性心肌水肿的标准MR技术,加用黑血T2-短时间反转恢复(T2-weighted short tau inversion recovery, T2-STIR)序列可进一步提高水肿与正常心肌的对比度。mapping技术无需参考ROI即可量化疾病进展及其活动性,定量检测局限性及弥漫性心肌水肿,能够弥补常规T2-STIR的不足[8]。以990 ms 为T1 mapping的阈值诊断急性心肌水肿的敏感度和特异度均可达92%[9]。在急性炎症期,早期钆分布主要与组织血流和毛细血管通透性有关,因此早期钆摄取增加可反映AM心肌充血。一项研究[10]以早期增强T1 mapping(静脉注射0.15 mmol/kg体质量钆对比剂后2 min)为观察指标,所纳入45例疑似AM患者及19名健康对照者的早期T1中位缩短率分别为75%及65%,以早期T1缩短率≥70%诊断AM的敏感度为93%,特异度为100%,准确率为95%。


1.1.3 PET

OZAWA等[11]观察29例临床疑诊AM患者,18F-FDG PET所见左心室后壁活动性炎症与EMB结果的一致性极高。活化的巨噬细胞表面过度表达生长抑素受体(somatostatin receptor, SSTR)亚型1和2具有活性结合位点,可采用特定的SSTR靶向放射性示踪剂,如68Ga-DOTA-TATE或68Ga-DOTA-TOC,以直接识别活化的巨噬细胞,因此SSTR亚型2 PET成像可用于检测心血管炎症[12]。LAPA等[13]对AM患者行PET/CT SSTR靶向成像,结果显示受损心肌的68Ga-DOTA-TOC摄取量是未受损心肌的2倍。


1.2 心肌坏死、纤维瘢痕形成

LGE可反映心肌细胞坏死及纤维化,且出现LGE部位与巨噬细胞聚集及心肌细胞坏死灶分布相吻合。CMR定量T1 mapping及细胞外容积分数(extracellular volume fraction, ECV)可检测更为轻微、弥漫的纤维化,能较CMR常规功能指标更早地检出心肌重塑或组织损伤[14,15],且与LGE改变明显相关[16]。LURZ等[17]纳入129例经EMB证实的AM患者,观察CMR映射技术诊断早期心肌坏死的准确性;结果表明,初始T1 mapping及ECV诊断AM的效能均较传统LLC显著增高,其曲线下面积(area under the curve, AUC)分别为0.77、0.75 和0.52,且T1 mapping与ECV无明显差异。


CHINALI等[5]应用2D-STE观察AM患儿,发现随访期间部分患儿LVGLS仍明显受损,且相比该时段LVGLS恢复正常[(-21.8±2.1)%]者,LVGLS持续降低[(-18.1±1.7)%]患儿心肌纤维化发生率更高,提示AM不仅可致心肌水肿,还可引发心肌坏死,并致亚临床心功能不全。


2 监测AM治疗效果

FM常合并致命性心律失常和心源性休克,发生循环衰竭风险极高;静脉动脉体外膜肺氧合(venous artery extracorporeal membrane oxygenation, VA-ECMO)可显著提高FM致心源性休克患者的存活率[18]。欧洲心脏病学会专家共识[19]指出,所有心肌炎患者均应接受超声心动图随诊,超声心动图可床旁实时、动态监测心腔大小、容积及功能变化等参数,为调节流量与左心室压力平衡提供参考依据。左心室射血分数(left ventricular ejection fraction, LVEF)是判断VA-ECMO脱机的重要指标,可通过评估心脏收缩力恢复情况来决定是否脱机[20]。在心脏受累早期,3D-STE技术即可用于监测左心室收缩功能。DEGIOVANNI等[21]采用3D-STE连续检测57例AM患者住院期间左心室心肌分层应变,结果表明根据心外膜LVGLS>-18%可早期诊断LVEF保留的AM,且患者LVGLS变化符合AM早期心肌损伤的典型心外膜-心内膜模式,即心外膜最先受累、治疗过程中以心肌扩张为特征,并可据此与缺血性心肌病相鉴别(后者呈典型心内膜-心外膜模式),提示3D-STE可指导临床早期干预AM、提高评估病情的准确性。


CMR可定量监测疾病进展和活动性、评估抗炎治疗效果,从而监测炎症性疾病。LI等[22]发现,FM急性期初始T1值显著增高,至恢复期逐渐下降,提示初始T1值可作为评估疾病活动和进展的动态指标,以判断炎症进程。目前PET/CT评估心肌炎治疗效果的前瞻性随机研究较少。PET/CT显示1例女性嗜酸性粒细胞FM患者经类固醇冲击治疗后心肌18F-FDG摄取减少,提示PET/CT在监测治疗反应方面具有潜在应用价值[23]。


3 评估AM预后

3.1 LVEF

2020年AM管理专家共识[24]指出,超声心动图是影像学评估疑似AM患者心功能的重要方法。MERLO等[25]对淋巴细胞性AM患者行超声心动图随访,相比出院前LVEF正常的AM患者,LVEF降低患者1年后更易出现持续性左心功能不全,且2年后其心源性死亡及接受心脏移植率更高;LVEF<50%患者发生主要不良心血管事件(major adverse cardiovascular event, MACE)的风险较LVEF正常的AM患者增加4倍。一项基于CMR的研究[26]证实,根据左心室收缩功能可预测AM患者预后,如较低的LVEF与MACE相关,而较大的左心室舒张末期容积与随访期间LVEF改变有关。


3.2 右心室参数

右心室纵向应变(right ventricular longitudinal strain, RVLS)是评估心脏疾病患者预后的敏感参数[27]。LI等[28]对120例新型冠状病毒肺炎致AM患者行心脏2D-STE,发现RVLS、右心室面积变化分数及三尖瓣环收缩期位移均与死亡率相关,且RVLS可独立于左心室收缩功能指数预测死亡风险和不良结局,以-23%为最佳截断值,其预测敏感度达94.4%,特异度为64.7%。


一项多中心研究[29]对151例AM患者行CMR检查,观察右心室受累与MACE的相关性,发现共118例出现右心室心肌炎表现,并与心包受累(心包积液/心包炎)相关;随访4年(中位时间)后,21例出现MACE,以右心室受累者为主,且K-M生存分析曲线表明AM累及右心室患者的预后较累及左心室者更差;右心室及前间隔LGE是MACE的独立预测因子。


3.3 其他

另一项多中心研究[30]表明,出现LGE的具体部位与患者预后相关,如心肌前壁中间层LGE与MACE密切相关,前侧壁LGE则与MACE无明显相关,而心肌受累范围与预后无关。此外,随访期间临床恢复AM患者T2弛豫时间显著减低,但仍高于健康对照组[31]。


4 小结

多模态心脏影像学可在诊断AM与评估疗效方面发挥重要作用。随着心肌应变成像的普及,超声心动图成为辅助评估AM疗效与预后的重要工具,但其对于检测心室纤维化的价值仍待更多研究加以验证。目前已有动物研究[32]证实对比增强超声分子成像所示炎症细胞浸润或内皮激活与心肌纤维化发生、发展相关;以白细胞、CD4+淋巴细胞和P-选择素为靶点进行对比增强超声分子成像,根据所示炎症反应可预测纤维化发展;而靶向Th17淋巴细胞亚群可能获得反映心室重构的精确信息。未来或应侧重于更好地识别潜在心肌纤维化,并实现临床相关成像方式,为精准诊断AM提供更深层次的依据。


利于多参数CMR,特别是定量T1、T2 mapping技术,可精准评估心肌组织病理学改变,促进CMR标准化评估心肌炎患者心肌形态与功能。PET/CT检测潜在心肌炎症活动有其优越性,同步心脏PET/MR对评估AM具有补充价值,但其对于临床管理疑似心肌炎的价值有待继续观察。


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