Clinic文库|冠脉生理学在ST段抬高型急性心肌梗死中的应用

作者:广东省人民医院心内科 周浪平、董豪坚
摘要

急性ST段抬高型心肌梗死(ST-segment elevation myocardial infarction,STEMI)是急诊介入手术的指征之一,由于急性期心肌、血管等病理生理学的特殊变化,导致冠脉生理学检查在该类患者中应用价值明显异于稳定期患者,然而随着对病理学、生理学等学科认识的深入,以及临床证据的增加,冠脉生理学检查在STEMI中非犯罪血管、甚至犯罪血管评估应用也逐渐增加,本文就STEMI中冠脉生理学评价应用的研究进展予以综述。

Abstract:Acute ST-segment elevation myocardial infarction is one of the indications of primary percutaneous coronary intervention. Due to the special pathophysiological changes of myocardia and vessels in the acute stage, the application value of coronary physiology examination in this kind of patients is obviously different from that in the stable stage. However, with the in-depth understanding of pathology, physiology and other disciplines, as well as the increase of clinical evidence, the application of coronary physiology examination in non-culprit artery assessment and even infarct-related artery assessment in STEMI is gradually increasing. This article reviews the research progress in the application of coronary physiological evaluation in STEMI.

关键词:ST段抬高型心肌梗死;经皮冠状动脉介入术;冠脉生理学

Key words: ST-segment elevation myocardial infarction; percutaneous coronary intervention; coronary physiology

作者:广东省人民医院心内科 董豪坚

实施经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)过程中,我们总会面临着两个问题:这个冠脉病变应当治疗吗?如果要治疗,那么应当如何治疗或如何获得最佳的结果?由于冠脉造影只能提供血管腔内的二维轮廓信息,以此来判断血管狭窄程度,而无法准确显示该处病变是否引起心肌缺血。因此在临床仅通过冠脉造影,难以很好地回答这两个问题。

冠脉生理学的提出,弥补了冠脉造影的不足,大大提高了PCI的准确性与有效性。冠脉生理学是基于冠脉造影之上血管功能评价的有益补充,目前临床常用的有冠状动脉定量血流分数测量(quantitative flow ratio,QFR)、血流储备分数(fractional flow reserve,FFR)、瞬时无波形比值(instantaneous wave-free ratio,IFR)、微循环阻力系数(index of microcirculatory resistance,IMR)和其他静息指数以及微血管评估[1]。冠脉生理学评估能很好地为冠心病病变血管提供参考,以此决定是否行PCI治疗,但是在STEMI中使用会受到限制。由于从一开始的心肌细胞缺血、坏死,再到内皮细胞功能失调引起血管舒缩功能受损,有害物质的释放和瘀滞,例如炎性细胞因子和活性氧,最终引起微血管阻塞(microvascular obstruction,MVO)和出血,因此在STEMI中应用冠脉生理学评估一直存在着争议。PCI可以让病变血管恢复冠脉血流,但同时也会引起缺血再灌注损伤。随着对病理学、生理学等学科认识的深入,以及临床研究证据的增加,冠脉生理学检查在STEMI应用逐渐增加,现予以综述。

1. 血流储备分数(FFR)

FFR基础是数学原理和丰富的临床数据,目前已成为评价稳定型冠心病(stable ischemic heart disease,SIHD)患者冠状动脉狭窄功能意义的参考标准[2]。FFR定义为存在狭窄病变的情况下,该冠状动脉所提供给心肌区域能获得的最大血流量与同一区域在正常情况下所能获得的最大血流量的比值[3]。FFR在不受血压、心率及心肌收缩力等情况的影响下,理论正常值为1.0。FFR值<0.75时,对冠状动脉阻塞性病变检测表现出较高的特异性和敏感性,确定病变诱发心肌缺血的特异性可达100%[4]。FFR可用于评价冠脉病变的生理功能、介入治疗的即刻效果及预后[5]。FFR最开始是用于稳定型心绞痛,后逐渐到不稳定型心绞痛、非ST段抬高型心肌梗死、STEMI的非犯罪血管,尽管已成为判定心外膜冠状动脉狭窄功能严重程度的金标准[6-8],但是在急性期STEMI的犯罪血管中却存在着争议。急性期STEMI行PPCI(primary percutaneous coronary intervention)时,由于犯罪血管(infarct-related artery, IRA)其特有的造影特点以及相符合的临床表现,我们很容易识别它。在这种特殊的情况下,不需要生理学指导来决定有无必要进行血运重建,而且由于显著的微血管功能失调(如MVO)和严重的低血压,FFR的检测会在IRA中受到影响[19]

目前超过50%的STEMI患者合并有多支血管病变(multivessel disease,MVD) [10]。在STEMI患者中应用FFR的临床证据较少,多数为非犯罪血管中的应用[10-17]。两个大型试验表明,在合并MVD的STEMI患者中,完全血运重建优于仅对IRA进行血运重建[12,18]。STEMI患者早期PCI术后进行完全血运重建,或者仅对IRA进行血运重建的临床试验,展示了在接受完全血运重建的大量STEMI患者中,心血管死亡和心肌梗死方面是有显著受益的[10]。这两个临床试验都描述了,相比较仅对犯罪病变进行血运重建,FFR引导下的完全血运重建的优越性[12,13]。在STEMI患者的急性期、亚急性期和术后6个月时,非犯罪血管的FFR没有统计学差异[14-15]。但是在Van der Hoeven等人的研究中,从急性期到术后30天的随访期,FFR呈现下降的趋势[16]。Choi等人观察到在非犯罪血管和SIHD中,FFR随病变严重程度的加重而降低的情况相似,这证明了在非犯罪血管中应用冠脉生理学的可行性与准确性[17]。上述实验研究了从STEMI急性期到术后随访,FFR在非犯罪血管中的应用,由于非犯罪血管相对于IRA,微循环功能的减退较不明显,FFR的应用受限也会相应减小,因此在非犯罪血管中应用冠脉生理学是可行的。

而对于犯罪血管中FFR的应用,目前普遍认为是不可靠的。远端栓塞、血管痉挛和炎症导致的MVO会导致最大充血减少,这可能会低估IRA的血流动力学严重程度,并错误地高估FFR。在IRA中,对腺苷的充血反应是减弱的,特别是在有MVO证据的患者中[19]。Cuculi等人评估了STEMI患者经历PCI后随着时间的冠脉生理学改变,表明在合并有MVO的IRA中,由于血管舒张功能减弱,会测量出明显偏高的FFR,而且在PCI术后6个月内呈现下降的趋势;在没有MVO的患者中,血管舒张功能相对保存完好,FFR的变化不明显,因此在STEMI急性期应用FFR的临床证据不足[9]

然而Stephen P. Hoole等人的研究表明[20],部分STEMI患者的IRA微循环功能在PPCI之前是相对保留的,这部分IRA的病变狭窄不会比IMR高的患者严重,仍能保持良好的充血反应。但是由于PPCI会造成微小斑块脱落至远端血管,即动脉粥样硬化斑块碎片的移位和远端栓塞,从而显著增加IMR,并使最终的FFR升高[21]。较轻的IRA病变所引起的微循环损伤较小,即较低的IMR,此时在PPCI时可以通过FFR更准确地评估病变程度,但是由于PPCI所导致的MVO可能会影响术后FFR的测量[20]。这是FFR应用于IRA的进一步探索。

2. 微循环阻力系数(IMR)

之所以在STEMI犯罪血管中应用FFR存在争议,是因为IRA本身微循环的问题,因此对这类患者的微循环评估是STEMI冠脉生理学目前的重点和热点。冠脉生理学可以在评估IRA下游的微血管功能中发挥重要作用,提供与预后相关的信息,并识别具有接收额外新型治疗资格的次优再灌注高风险的患者。IMR是一种有大量证据支持的压力线热稀释衍生指标,由于其能够在准确性和可行性之间提供合理的选择,因此是评估IRA微血管功能的首选指标[22]。在STEMI患者中,IMR≥40的临界值与预后不良和更广泛的心肌损伤有关[21]

PCI术后的IMR与微循环功能有关,可以体现MVO的严重程度[23]。同时PCI术后IMR≥40表明更高的心衰发病率和死亡率[24],而且IMR≥40可以作为预测MACE的指标[25]。在支架植入前进行IMR测量,可以判断是否需要对病变血管进行进一步处理[26]

保留的血管舒张功能反映了功能良好的冠脉微血管系统,这在STMEI患者PCI术后 6个月后是一项重要的心肌功能恢复的预测因素。阻力储备比被用来评估冠脉循环的血管舒张能力,是基线IMR和充血IMR的比值[27]。最近研究表明,阻力储备比对判断PCI术后的STEMI患者的预后有一定作用。术后阻力储备比<1.98的患者,通常在6个月时有更严重的MVO和更大的梗死面积,心脏功能也会更差[28]

目前有许多方法来缓解STEMI患者微循环功能障碍。STEMI患者PCI术后进行溶栓,这种治疗方法是有争议的。Sezer等人在41例PPCI术后STEMI患者中,应用了小剂量链激酶,根据降低的IMR和增加的冠脉血流储备,认为干预组比空白对照组有效[29]。在一项更大的研究中,相比较空白对照组,PCI术后接受了辅助性冠脉内链激酶的患者,有更小的梗死面积和更好的LVEF[30]。不同的是,McCartney等人发现在PPCI术后随机应用低剂量冠脉内阿替普酶的患者,通过心脏核磁共振检测出的MVO和对照组没有明显差异,并且两者呈现出相似的临床效应[31]。除了溶栓,还可以应用PiCSO装置,可以降低PCI术后6个月的IMR和梗死面积[25]

3. 瞬时无波形比值(IFR)

在ACC 2017上,DEFINE-FLAIR研究让IFR一炮而红:IFR不仅在指导冠脉血运重建方面与FFR效果一样,而且更为便宜、省时,且痛苦较小。IFR的定义是在舒张期无波形间期狭窄远端平均压力除以舒张期无波形间期平均动脉压,是一种评价冠状动脉狭窄程度的非腺苷依赖压力推导的新指数[32]。当非犯罪血管的FFR≤0.80时,IFR具有较高的准确性[14,33]。Thim等人认为,IFR应用时具有较高的特异度[34]。如果在STEMI患者研究中只用IFR进行非犯罪狭窄评估,有一种对病变严重程度高估的趋势。值得注意的是,在基线冠状动脉流量显著增加的不同临床环境中也观察到了类似的趋势[35,36]。IFR在急性冠脉综合征非犯罪血管中的诊断准确率与SIHD相当,而且会随着病变程度加重而降低[16,33]。在iSTEMI研究中,急性期和随访阶段IFR分类一致性一般(78%),比FFR的要低[34]。然而Van der Hoeven等人的研究中,IFR在急性期和术后30天随访中表现了与FFR相似的分类一致性(82.2%)[15]

总而言之,评估非犯罪血管的IFR并以此作为治疗依据,是有病理生理学的随机数据支持的。尽管目前有少量研究证明了IFR的优越性,但仍需要大量的临床研究,同时在理想状态下还需随机对照试验。

4. 定量血流分数(QFR)
QFR是一种新型的基于冠脉造影定量分析(quantitative coronary angiography,QCA)的诊断方法,不依赖于腺苷,不需要最大充血,也不需要使用压力线,可以在PCI时进行实时运算或延迟运算,指导医生在PCI期间进行急性完全血运重建或选择择期PCI[37-40]。FAVORⅡChina结果显示,QFR与FFR结果具有很高的相关性,而且在不同血管中的诊断准确度也很高,与QCA相比准确度更高[37]。在STEMI急性期和亚急性期非犯罪血管中,QFR展现了高度的重复性和预测异常FFR值的高度准确性,与随访时间没有相关性,特别是当QFR超出感受器工作特性(ROC)定义的灰..域(0.75–0.85)的时候[41]。当使用混合QFR-FFR方法时,仅在QFR处于灰..域才测量FFR,总体有96.7%的分类一致性,避免58.5%的患者在非犯罪血管中的进一步有创性诊断检查,QFR在预测非犯罪血管的异常FFR和IFR都具有良好的准确性[42]。Jiani Tang等人认为,在无MVO的STEMI患者中,通过QFR评估罪犯病变是可行的[43]。Nobuaki Suzuki等人的研究表明,当病变血管的QFR≤0.82时,患者更有可能发生不良心脑血管事件[44]。Spitaleri等人说明了QFR≤0.80且未经治疗的非犯罪病变的患者,有高概率发生临床不良事件[40]。尽管QCA评估急性期血管狭窄似乎比随访时更严重[45,46],但急性期QFR和术后随访时QFR有很高的分类一致性。Mejia-Renteria H等人认为,以FFR为参照的QFR诊断性能受到微循环功能的影响,这可能限制了QFR的使用[47]
使用QFR对非犯罪血管进行功能评估不会增加急诊手术的复杂性和时间框架,而且可以避免以后对非犯罪血管进行有创性或非侵入性的评估。无论QFR是在术中还是术后评估,急性期QFR都可能会减少对非犯罪血管进一步评估的需要,从而降低患者风险和医疗成本。因此QFR可能在简化急性冠脉综合征临床路径中发挥作用,但目前尚未深入研究QFR,需要更多的随机数据来探究其特点。

冠状动脉生理学为指导急性冠脉综合征患者的治疗提供了有用的信息。通常不需要对STEMI患者IRA进行功能评估。由于超过50%的STEMI患者微循环功能明显受损,降低了FFR和IFR在IRA中的价值;而IMR成为对STEMI患者不良事件或不良左心室重构,进行临床风险分层的重要工具。此外,越来越多的数据表明,IMR在识别心肌再灌注损伤方面具有潜在的作用。随着IFR和QFR的相继发明,冠脉生理学的评估越来越精准,然而,无论是IRA还是非犯罪血管,进行冠脉生理学评估的最佳策略(基于FFR、IFR、QFR)或评估的最佳时机仍尚未阐明,这将会成为未来的研究主题。


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