沈珠军ACS诊治及进展沧州

ACS诊治及其进展,,北京协和医院 心内科 沈珠军,提纲,诊断: STEMI & NSTEMI,UAP再血管化治疗: PCI & Thrombolytic therapy药物治疗：抗血小板和抗凝治疗及其他合并症及并发症治疗,Acute Coronary SyndromeUnstable Inflammed Plaque Thrombosis plus plaque limiting Flow “ Active Volcano”,Stable AnginaCalcified PlaquePlaque Limiting Flow (Dormant Volcano),急性冠脉综合症(ACS),血管腔,心电图,心肌酶谱,预后严重性,诊断,CK MB 或肌钙蛋白,ST段抬高心梗,猝死,肌钙蛋白升高或不升高,不稳定心绞痛，非ST段抬高心梗,进展为ST段抬高心梗,血管完全闭塞,血管未完全闭塞,ST段持续抬高的急性冠脉综合征,非ST段持续抬高的急性冠脉综合征,James Herrick 1912:First description ofCoronary Thrombosisas cause of Acute Myocardial Infarct (AMI),Renthrop 1982:Demonstration of Coronary thrombus in patients with STEMI undergoing selective coronary angiography,OCCLUSIVE ACTIVATED PLAQUE,Plaque with Thrombus,FreshThrombus,Thrombus (Platelet & Thrombin) is ACS Culprit,“Man lives with Atherosclerosis, dies with thrombosis”. Anonymous German,急性心肌梗死诊断标准ESC2012指南,急性心肌梗死诊断三要素,症状:Symptom心电图:ECG or EKG心肌酶:Enzyme,症状,部位时间程度药物缓解情况,心电图:非ST段抬高心肌缺梗死,ST Depression NSTEMI,T wave inversion NSTEMI,Early Repolarization,Brugada Syndrome,Anterior AMI,Prinzmetal Angina,Pericarditis,Acute Inf. AMI,ST 段抬高心肌梗死,非心肌梗死的 ST 抬高,AMI的血清心肌标记物及其检测时间,项目 肌红蛋白 cTnI cTnT CK CK-MB AST出现时间（h） 1-2 2-4 2-4 6 3-4 6-12100%敏感时间（h）4-8 8-12 8-12 8-12峰值时间（h） 4-8 10-24 10-24 24 10-24 24-48持续时间（d） 0.5-1 5-10 5-14 3-4 2-4 3-5,新型心肌酶标志物的检测,在欧洲和北美，每年有1500-2000万人因为急性胸痛至急诊室就诊，2/3的患者被除外急性冠脉综合征,急性心梗患者再血管化治疗的获益主要取决于起病后数小时内的早期诊断,European Heart Journal (2014) 35, 552556,急性心梗的诊断依赖于心肌标志物的快速检测,Translational Research 2012;159:252264,Translational Research 2012;159:252264,Cardiac troponin： Conventional cTn I and T High-sensitivity cTn,Low Sensitivity,European Heart Journal (2014) 35, 552556,More preciseug/l ng/lhs-cTnT, Roche in 2010hs-cTnI, Abbott in 2013,Iatrogenic pitfall,European Heart Journal (2014) 35, 552556,Copeptin（和肽素）the c-terminal part of the vasopressin prohormonequantify the individual endogenous stress levelappears to be identified early after symptom onsetideal marker to compensate for the sensitivity deficit of conventional cTn assays in early presenters,J Am Coll Cardiol 2013;62:15060,J Am Coll Cardiol 2013;62:15060,J Am Coll Cardiol 2013;62:15060,Heart type fatty acid binding protein（H-FABP） low molecular weight protein released early in myocardial infarction （before necrosis） reaching peak levels at 56 h returning to normal levels within 36 h higher content in cardiac cells lower plasma value of HFABP,Biosensors and Bioelectronics 43 (2013) 400411,MiRNAs： Short non-coding RNA molecules involved in post-transcriptional gene regulation Cardiac miRNAs are markedly dysregulated in MI Levels of circulating miRNAs after AMI are induced by myocardial injury and parallel the extent of the myocardial damage measured by cTn levels,Biomarkers, 2013; 18(7): 547558,European Heart Journal (2010) 31, 659666,STEMI,时间就是心肌,前壁心梗，LAD血栓,STEMI的时间延误情况,ESC Guideline (2012),AHA2013,AMI24小时内院前及院内处理流程ESC指南2012,Summary of 23 Randomized Trials (n=7739),p=0.0003,p0.0001,p=0.0004,p0.0001OR=0.57,Keeley & Grines Lancet 2003,PCI,Lytic,Risk ReductionDeath28%Death/MI/CVA43%,Primary PCI: The Preferred Reperfusion Strategy,Evidence to support Transfer to PCI Centers from Hospitals without PCI facilities for STEMI ACS,再灌注治疗策略推荐,院前溶栓 for Early ( 2 Hour) STEMI,STEMI的溶栓治疗,适应症： 典型胸痛持续30分钟以上 相邻两个导联ST段抬高 （胸导 0.2mv,肢导 0.1mv）或提示AMI伴左束支传导阻滞 发病12小时以内，年龄75岁,STEMI溶栓禁忌证,溶栓药物进展,溶栓药物比较,注：a.体重60kg，剂量为30mg；每增加10kg，剂量增加5mg；直至体重90kg，最大剂量为50mg.,冠状动脉再通指征直接指征 (90min冠造),TIMI分级 0 级：无再灌注或闭塞远端无血流级：造影剂部分通过闭塞部位，但梗塞区供血冠状动脉充盈不完全级：部分再灌注或造影剂能完全充盈冠状动脉远端，但造影剂进入及清除速度慢级：完全再灌注，造影剂能在冠状动脉内完全迅速充盈及清除“IV级”：心肌完全再灌注，造影剂在心肌内很快清除达到级或级为血管再通,冠状动脉再通指征间接指征,在溶栓开始后2h内，ECG抬高最显著的导联的ST段迅速回降50%2h内胸痛基本消失2h内再灌注心律失常(加速性室性自主心律, 房室或束支传导阻滞突然改善或消失,下壁MI者出现一过性窦缓,窦房阻滞或伴低血压)血清CK-MB高峰前移到14h内, CK前移到16h内 符合4项中2项或以上者为再通, 但第2和第3两项组合不能判定为再通,Non-STEMI ACS,危险分层，早期干预,NSTEMI - PURSUIT SCORE,最为简单的TIMI评分,Non-STE ACS 介入治疗的益处,在高危病人减少死亡率 在大部分病人减少心绞痛，减少住院 缩短住院时间，减少花费,心肌梗死热点研究,1CvLPRIT ESC 2014 hotline; 2ATLANTIC ESC 2014 hotline; 3FAMOUS-NSTEMI ESC 2014 hotline; 4NOMI ESC 2014 hotline;5MITOCARE ESC 2014 hotline;,doi:10.1093/eurheartj/ehu338,doi:10.1093/eurheartj/ehu338,Activation,TXA2,ActivatedPlatelet,COX,Degranulation,Gp IIb/IIIafibrinogenreceptor,to neighboringplatelet,Mehta SR. J Am Coll Cardiol.,AZD 6140 Cangrelor Prasugrel,抗血小板治疗指南最近推荐,抗血小板治疗常用药物及剂量推荐,新型抗血小板药物的使用,Expert Rev.Clin.Pharmacol 7(4):507-221,61,两组均包含阿司匹林.*1年时的NNT.,随机后时间（月）,0,2,4,6,8,10,12,12,11,10,9,8,7,6,5,4,3,2,1,0,13,累积发生率 (K-M%),11.7,氯吡格雷,9.8,替格瑞洛,ARR=0.6%RRR=12%P=0.045HR: 0.88 (95% CI, 0.771.00),030 天,4.8,5.4,氯吡格雷,替格瑞洛,ARR=1.9%RRR=16%NNT=54*P208)患者(%),Parodi G, presented in 2014 ESC,ATLANTIC研究,N Engl J Med 2014；37:1016-27,ATLANTIC研究探索STEMI患者PCI术前抗栓治疗的时机,导管室 DOOR,PCI,症状发作,R,替格瑞洛 180 mg,医疗接触,安慰剂,替格瑞洛 180 mg,安慰剂,LD1,LD2后12小时,开始维持剂量,替格瑞洛90 mg BID,鞘管插入,PCI术前,冠脉造影,LD2,双盲期,30天积极治疗期,7天随访,院前,导管室,拟行PCI的STEMI 患者N=1770,手术结束,诊断,PCI术后1小时,ECG,Montalescot G, et al. Am Heart J 2013;165:515-22,替格瑞洛可用于院前或院内，不增加出血风险,吗啡未治疗者ST段回落未达70%的风险显著降低,主要终点：组间无差异,P=NS,P=NS,P=NS,P=NS,患者百分比(%),OR(95% CI),终点事件率院前 院内,OR(95% CI),组间P值,90.8%82.8%,88.8%88.4%,1.493(0.954, 2.331)0.632(0.423, 0.943),0.005,0.5,1.0,2.0,院前更好,院内更好,使用吗啡未使用吗啡,Montalescot G et al. N Engl J Med September 1, 2014 Epub ahead of print; DOI: 10.1056/NEJMoa1407024,院前 vs 院内提前31分钟使用替格瑞洛降低了术后24小时和30天支架血栓,81%p=0.02,替格瑞洛院前,替格瑞洛院内,24 hP=0.008,30 天P=0.02,Time (days),Montalescot G et al. N Engl J Med September 1, 2014 Epub ahead of print; DOI: 10.1056/NEJMoa1407024,替格瑞洛与氯吡格雷的成本效益比,Scandinavian Cardiovascular Journal, 2014; 48: 138147,普拉格雷（Prasugrel）,Wiviott S, Braunwald E, et al. N Engl J Med 2007;357:20012015.,TIMI38,Cangrelor（坎格雷洛）： Cangrelor, like ticagrelor, is an allosteric inhibitor of the P2Y12 receptor with a half-life of 35 min. It is administered as an intravenous infusion and normal platelet function is restored within 1 h of cessation.,CHAMPION-PCI,N Engl J Med 2009;361:2318-29.,CHAMPION-PCI,N Engl J Med 2009;361:2318-29.,N Engl J Med 2009;361:2318-29.,CHAMPION-PLATFORM,N Engl J Med 2009;361:2330-41.,N Engl J Med 2009;361:2330-41.,CHAMPION-PHOEMIX,Enrolled patients with Stable Angina/NSTE-ACS/STEMI Indicated for PCI (N=11,145),1:1 Randomization,MITT CANGRELOR(N=5472),MITT CLOPIDOGREL(N=5470),48 hour follow-up(N=5470),48 hour follow-up(N=5469),30 day follow-up(N=5462),30 day follow-up (N=5457),PCI,PCI,N Engl J Med 2013;368:1303-13,CHAMPION-PHOEMIX,1. The logistic model was adjusted for baseline status and clopidogrel dose. P value of 0.006 shown on the KM curve is log rank p value.,at ,N Engl J Med 2013;368:1303-13,Log Rank P Value = 0.006,Event Rate (%),Bhatt DL, Stone GW, Mahaffey KW, et al. Harrington RA. NEJM 2013 at ,CHAMPION-PHEOMIX,N Engl J Med 2013;368:1303-13,Log Rank P Value = 0.01,Event Rate (%),CHAMPION-PHEOMIX,Bhatt DL, Stone GW, Mahaffey KW, et al. Harrington RA. NEJM 2013 at ,Bhatt DL, Stone GW, Mahaffey KW, et al. Harrington RA. NEJM 2013 at ,CHAMPION-PHEOMIX,N Engl J Med 2013;368:1303-13,5.0,1.0,0.2,Subgroups: Death/MI/IDR/ST at 48 Hours,Cangrelor Better,Clopidogrel Better,N Engl J Med 2013;368:1303-13,N Engl J Med 2013;368:1303-13,3. GPI的使用现状,Intracoronary abciximab in STEMI,JAMA .2012;307(17):1817-26,Intracoronary abciximab in STEMI,JAMA .2012;307(17):1817-26,JAMA .2012;307(17):1817-26,GP IIb/IIIa拮抗剂,I,2014 ESC/EACTS血运重建指南,Windecker S, et al. Eur Heart J 2014; doi: 10.1093/eurheartj/ehu278,血小板糖蛋白IIb/IIIa受体拮抗剂,常用药物：阿昔单抗、依替巴肽和替罗非班最主要的风险：出血并发症一般高危患者才可以联合三重抗血小板治疗阿昔单抗仅用于准备PCI的患者选择性策略：根据患者的血栓负荷和是否已经进行了充分的氯吡格雷负荷剂量和时间来决定是否应用血小板糖蛋白IIb/IIIa受体拮抗剂。,AMI的抗凝治疗,抗凝治疗指南最近推荐,抗凝治疗常用药物及剂量推荐,磺达肝癸钠OASIS 5,Yusuf S, Mehta SR, et al. N Engl J Med 2006;354: 14641476.,磺达肝癸钠OASIS 6,新型抗凝药物,Expert Rev.Clin.Pharmacol 7(4):507-221,2010 ESC/EACTS血运重建指南,2012 ESC STEMI指南,2014 ESC/EACTS血运重建指南,1. Wijns W, et al. Eur Heart J 2010; 31(20):2501-55.2. Steg PG, et al. Eur Heart J. 2012 ; 33(20):2569-619. 3. Windecker S, et al. Eur Heart J 2014; doi: 10.1093/eurheartj/ehu278,比伐卢定推荐级别下降,HORIZONS AMI,Stone GW et al. N Engl J Med 2008;358(21):22182230,比伐卢定可显著减少30天 净临床不良事件,比伐卢定可显著降低30天的心血管死亡和全因死亡,EUROMAX研究比伐卢定及早用于急诊PCI转运患者的疗效,主要终点: 30天时的死亡和非CABG相关主要出血,主要终点事件%,8.5%,P=0.001,5.1%,天,Steg PG et al. N Engl J Med. 2013;369:2207-2217,HEAT PPCI研究比较直接PCI患者应用肝素与比伐卢定的抗栓治疗疗效,主要安全性终点：3-5级主要出血(BARC定义),主要疗效终点28天内全因死亡率、脑血管突发事件、心肌再梗、非计划内的靶血管再次血运重建的复合事件,Shahzad, Adeel, et al. The Lancet (2014).,MACE：,肝素用于PPCI的主要疗效优于比伐卢定；不增加出血并发症；显著节约药物成本,Lancet 2014；384:599-606,Meta-analysis of Bivalirudin,Lancet 2014；384:599-606,Meta-analysis of Bivalirudin,Lancet 2014；384:599-606,Meta-analysis of Bivalirudin,Lancet 2014；384:599-606,Meta-analysis of Bivalirudin,Meta-analysis of NOAC,European Heart Journal 2013 34:1670-80,Meta-analysis of NOAC,European Heart Journal 2013 34:1670-80,Meta-analysis of NOAC,European Heart Journal 2013 34:1670-80,Meta-analysis of NOAC,European Heart Journal 2013 34:1670-80,需要OAC的三联抗栓治疗推荐,