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1、冠脉非阻塞性心肌梗死,BenQ Medical CenterJoshua.Zhang,1,Myocardial infarction with nonobstructive coronary arteries (MINOCA),80年前通过尸检首次详细记录了MINOCA。临床研究显示5% to 6% 的AMI-CAD为MINOCA。,Gross H, Steinberg WH. Myocardial infarction without significant lesions of coronary arteries. Arch Int Med (Chic). 1939;64:249267.P
2、asupathy S, Air T, Dreyer RP, Tavella R, Beltrame JF. Systematic review of patients presenting with suspected myocardial infarction and nonobstructive coronary arteries . 2015;131:861870. doi: 10.1161/CIRCULATIONAHA.114.011201,2,Epidemiology,MINOCA 患者通常较阻塞性 CAD 患者更年轻，男性略多于女性。MINOCA患者的心电图可以有或无 ST 段抬高
3、。在女性 STEMI 和 NSTEMI 患者中，发现非阻塞性 CAD 的几率相似；在男性 NSTEMI 患者中发现非阻塞性 CAD 的几率较低。MINOCA 患者血脂异常的发病率较阻塞性 CAD低。MINOCA 患者中传统冠心病危险因素如高血压、糖尿病、吸烟、 MI家族史不常见。,Barr PR, Harrison W, Smyth D, Flynn C, Lee M, Kerr AJ. Myocardial infarction without obstructive coronary artery disease is not a benign condition (ANZACS-QI 1
4、0). Heart Lung Circ. 2018;27:165174. doi: 10.1016/j.hlc.2017.02.023,3,Definition,2016ESC,2019AHA,4,Plaque DisruptionEpicardial Coronary VasospasmCoronary Microvascular DysfunctionCoronary Embolism/Thrombosis Spontaneous Coronary Artery Dissection Supply-Demand Mismatch,5,Plaque Disruption,动脉粥样斑块破裂是导
5、致冠脉非阻塞性心肌梗死的常见病因。通过IVUS发现约 40% 冠脉非阻塞性心肌梗死患者存在斑块破裂或斑块侵蚀，采用OCT等更高分辨率的影像学手段可能检测率更高。常发生于女性、吸烟者、单根血管病变 和几乎没有CAD危险因素的年轻患者。 对于可疑或确诊斑块破裂引起冠脉非阻塞性心肌梗死的患者，推荐双联抗血小板治疗 1 年，之后终身服用单一抗血小板药物，另外还推荐他汀治疗。,6,Epicardial Coronary Vasospasm,有研究显示，进行激发试验的MINOCA患者中，46%诊断为冠脉痉挛。亚洲人群的冠脉痉挛发病率远高于白种人。激发试验金标准方法：冠脉内注射高剂量乙酰胆碱。日本、韩临床应
6、用广泛，欧洲、美国应用受限。欧美不愿意常规应用激发试验的原因是1970s报道二氢麦角碱激发试验后导致的死亡。最近研究（n=80）显示，入院48小时内的激发试验是安全的，仅5%激发相关的心律失常，无主要不良事件。,Montone RA, Niccoli G, Fracassi F, Russo M, Gurgoglione F, Camm G, Lanza GA, Crea F. Patients with acute myocardial infarction and nonobstructive coronary arteries: safety and prognostic relevan
7、ce of invasive coronary provocative tests. Eur Heart J. 2018;39:9198. doi: 10.1093/eurheartj/ehx667Buxton A, Goldberg S, Hirshfeld JW, Wilson J, Mann T, Williams DO, Overlie P, Oliva P. Refractory ergonovine-induced coronary vasospasm: importance of intracoronary nitroglycerin. Am J Cardiol. 1980;46
8、:329334.,7,冠脉造影下观察到的自发痉挛,8,Therapies,Cornerstone therapy ：CCB顽固的冠脉痉挛性心绞痛：2种不同机制的CCB能够减轻症状。因为耐药问题，硝酸酯类药物长期获益并不明确。其他有效的药物：尼可地尔、西洛他唑。,Beltrame JF, Crea F, Kaski JC, Ogawa H, Ong P, Sechtem U, Shimokawa H, Bairey Merz CN; on behalf of the Coronary Vasomotion Disorders International Study Group (COVADIS)
9、. The who, what, why, when, how and where of vasospastic angina. Circ J. 2016;80:289298. doi: 10.1253/circj.CJ-15-1202 Slavich M, Patel RS. Coronary artery spasm: current knowledge and residual uncertainties. Int J Cardiol Heart Vasc. 2016;10:4753. doi: 10.1016/j.ijcha.2016.01.003,9,Coronary Microva
10、scular Dysfunction,the coronary microcirculation ：vessels 0.5 mm diameter.冠状动脉血管网包括心外膜下冠脉（500 um），前小动脉（100-50 um），小动脉（100 um）。临床冠脉造影只能显示5%的冠状动脉血管网。心外膜冠状动脉对冠状动脉循环阻力的贡献10%，而冠状动脉循环的阻力70%来自冠状动脉微血管（前小动脉与小动脉）；另20%来自毛细血管与静脉。好发于女性及心血管高危因素患者（如高龄、高血压、糖尿病、吸烟、血脂异常）。,10,11,standardized definition for microvascul
11、ar angina,ischemic chest discomfortnonobstructive coronary arteriesan impaired coronary flow,Ong P, Camici PG, Beltrame JF, Crea F, Shimokawa H, Sechtem U, Kaski JC, Bairey Merz CN; on behalf of the Coronary Vasomotion Disorders International Study Group (COVADIS). International standardization of d
12、iagnostic criteria for microvascular angina. Int J Cardiol. 2018;250:1620. doi: 10.1016/j.ijcard.2017.08.068,12,冠脉血流储备受损诊断符合以下任一条,腺苷激发后冠脉血流储备2.0；乙酰胆碱激发后胸部不适感和心电图缺血改变，而心外膜冠脉无痉挛；TIMI血流3级。,Ong P, Athanasiadis A, Borgulya G, Vokshi I, Bastiaenen R, Kubik S, Hill S, Schufele T, Mahrholdt H, Kaski JC, Sec
13、htem U. Clinical usefulness, angiographic characteristics, and safety evaluation of intracoronary acetylcholine provocation testing among 921 consecutive white patients with unobstructed coronary arteries. Circulation. 2014;129:17231730. doi: 10.1161/CIRCULATIONAHA.113.004096,13,Therapies,calcium ch
14、annel blockers and -blockers有效缓解症状。nitrates are less effective.几个小样本研究，非传统抗心绞痛药物：改善内皮功能（L-精氨酸、他汀、依那普利），冠脉微血管扩张剂（双嘧达莫、雷诺嗪），氨茶碱。山莨菪碱、前列地尔、尼可地尔。,14,Coronary Embolism/Thrombosis,冠脉血栓形成除了继发于斑块破坏或冠脉痉挛，也可能由遗传性或获得性血栓形成疾病引起，血栓形成倾向筛查研究显示 14% 冠脉非阻塞性心肌梗死患者存在遗传倾向。遗传性：factor V Leiden、Protein S and C deciencies获得性
15、：TTP、HIT、抗磷脂综合征、骨髓增殖异常冠脉栓塞则可能由于冠脉或系统性动脉血栓（房颤或瓣膜疾病引起）脱落导致，也可能因瓣膜赘生物、心脏肿瘤、瓣膜钙化及医源性空气栓塞等引起。,PasupathyS, Air T,DreyerRP,Tavella R,BeltrameJF.Systematicreview ofpatients presenting with suspected myocardial infarction and non-obstructive coronary arteries (MINOCA). Circulation 2015;131:861870.,15,Therapi
16、es,冠脉血栓/栓塞患者是否需要终生抗凝或抗血小板治疗尚需进一步研究。TTP：血浆置换、类固醇、利妥昔单抗 HIT ：避免再次使用肝素血液科专家会诊,16,Spontaneous Coronary Artery Dissection,SCAD常见于50岁的女性AMI。自发性冠脉夹层往往通过管腔阻塞导致急性心肌梗死，但冠脉造影有时未能显示管腔阻塞，因而被诊断为冠脉非阻塞性心肌梗死。冠脉内影像是诊断冠脉夹层的关键。目前冠脉内夹层原因尚未明确，可能与肌纤维发育不良相关。,Saw J, Humphries K, Aymong E, Sedlak T, Prakash R, Starovoytov A,
17、 Mancini GBJ. Spontaneous coronary artery dissection: clinical outcomes and risk of recurrence. J Am Coll Cardiol. 2017;70:11481158. doi: 10.1016/j.jacc.2017.06.053,17,18,Therapies,急性期，通常避免介入治疗，除非患者不稳定或出现STEMI并伴有完全闭塞的冠状动脉。大多数情况下，夹层段能自发愈合。介入治疗有夹层剥离扩大和壁内血肿风险。 治疗不明确，通常-blockers and aspirin，低危-blockers
18、。抗凝和双联抗血小板存在争议，理论上会增加夹层扩大和血肿风险。一些研究人员认为，一些SCAD患者的内膜撕裂可能是血栓形成前期，使用中等强度的P2Y12抑制剂，如氯吡格雷，可能是合理的。,Tweet MS, Eleid MF, Best PJ, Lennon RJ, Lerman A, Rihal CS, Holmes DR Jr, Hayes SN, Gulati R. Spontaneous coronary artery dissection: revascularization versus conservative therapy. Circ Cardiovasc Interv. 20
19、14;7:777786. doi: 10.1161/CIRCINTERVENTIONS.114.001659Saw J, Mancini GBJ, Humphries KH. Contemporary review on spontaneous coronary artery dissection published correction appears in J Am Coll Cardiol. 2016;68:1606. J Am Coll Cardiol. 2016;68:297312. doi: 10.1016/j.jacc.2016.05.034,19,Therapies,大多数夹层
20、冠脉并无动脉粥样硬化，他汀不被推荐。虽然并没有被长期研究证实，但一些专家仍建议自发夹层患者避免剧烈运动和怀孕。,Tweet MS, Hayes SN, Pitta SR, Simari RD, Lerman A, Lennon RJ, Gersh BJ, Khambatta S, Best PJ, Rihal CS, Gulati R. Clinical features, management, and prognosis of spontaneous coronary artery dissection. Circulation 2012;126:579588 .Alfonso F, Ba
21、stante T, Garca-Guimaraes M, Pozo E, Cuesta J, Rivero F, Benedicto A, Antua P, Alvarado T, Gulati R, Saw J. Spontaneous coronary artery dissection: new insights into diagnosis and treatment. Coron Artery Dis. 2016;27:696706. doi: 10.1097/MCA.0000000000000412,20,Supply-Demand Mismatch,第四版心肌梗死通用定义：2型心
22、肌梗死包括导致心肌灌注减少的因素，冠状动脉痉挛、冠状动脉微循环功能障碍（包括内皮功能异常、血管平滑肌功能异常和自主神经调节异常）、冠状动脉栓塞、冠状动脉夹层（伴或不伴壁内血肿）；供氧减少的因素，如严重的缓慢心律失常、呼吸衰竭、严重贫血、低血压/休克；耗氧量增加的因素，如持续快速心律失常、严重高血压等。治疗：病因的治疗和逆转。,Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD: the Executive Group on behalf of the Joint European Society o
23、f Cardiology (ESC)/American College of Cardiology (ACC)/American Heart Association (AHA)/World Heart Federation (WHF) Task Force for the Universal Definition of Myocardial Infarction. Fourth Universal Definition of Myocardial Infarction (2018). Circulation. 2018;138:e618e651. doi: 10.1161/CIR.000000
24、0000000617,21,PROGNOSIS,MINOCA患者的预后取决于潜在病因，目前正在积极研究中。大多数研究表明，MINOCA患者比AMI-CAD患者有更好的预后。另外一些研究表明MINOCA患者的1个月和1年死亡率与AMI-CAD患者相似，生活质量指标也相似。,Pasupathy S, Tavella R, Beltrame JF. The what, when, who, why, how and where of myocardial infarction with non-obstructive coronary arteries (MINOCA). Circ J. 2016;80:1116. doi: 10.1253/circj.CJ-15-1096Pasupathy S, Tavella R, Beltrame JF. The what, when, who, why, how and where of myocardial infarction with non-obstructive coronary arteries (MINOCA). Circ J. 2016;80:1116. doi: 10.1253/circj.CJ-15-1096,22,23,24,
