1、急性心肌梗死病理、病理生理及臨床,【急性心肌梗塞(AMI)】定 義,梗死：血管閉塞引起的組織壞死。 AMI是急性心肌缺血性壞死，大多是在冠狀動脈病變的基礎(chǔ)上發(fā)生冠狀動脈血供急劇減少或中斷，使相應的心肌嚴重而持久地急性缺血所致,Coronary Artery,Blood Clot (Thrombus),Unstable Plaque Rupture,Coronary Artery,Infarcted (dead) or injured (dying) tissue,Healthy Heart Muscle (Myocardium),Myocardial Infarction,原因通常是在冠狀動脈

2、粥樣硬化不穩(wěn)定斑塊病變的基礎(chǔ)上繼發(fā)血栓形成導致冠脈持續(xù)、完全阻塞,【急性心肌梗塞(AMI)】定 義,臨床診斷要求有病史和應用生化方法、心電圖和顯像方法的得到心肌壞死間接證據(jù)綜合評定 病理診斷要求有心肌細胞壞死的證據(jù)，壞死是缺血時間過長導致的。細胞壞死的特征性表現(xiàn)包括細胞凝固性壞死和（或）收縮帶的壞死，常伴有梗死灶周圍的斑片狀心肌細胞溶解區(qū)。,急性心肌梗死的新定義,（1）典型的心肌壞死生物標志物濃度升高（肌鈣蛋白）超過參考值上限（URL）99百分位值并有動態(tài)變化，同時伴有以下一項心肌缺血的證據(jù)： 缺血性癥狀 ECG提示新發(fā)的缺血性改變（新發(fā)的ST段變化或左束支傳導阻滯LBBB） 心電圖提示病理性

3、Q波形成 影像學證據(jù)提示新發(fā)的節(jié)段性室壁運動異?；虼婊钚募G失,新定義,；（2）突發(fā)的心源性死亡（包括心臟停搏），通常伴有 心肌缺血的癥狀 新發(fā)ECG缺血性改變或LBBB和（或） 經(jīng)冠狀動脈（冠脈）造影（或尸檢）證實的新發(fā)血栓證據(jù)，但死亡常常發(fā)生在獲取血標本或發(fā)現(xiàn)心肌酶學標志物升高之前；,新定義,（3）基線cTn水平正常者接受經(jīng)皮冠狀動脈介入治療（PCI）后，如果心臟標志物水平升高超過URL99百分位值，則提示圍手術(shù)期心肌壞死；如果心臟標志物水平超過URL99百分位值的3倍，則定義為與PCI相關(guān)的心肌梗死；,新定義,（4）基線cTn水平正常者接受冠狀動脈旁路移植術(shù)（CABG）后，如果心臟標志物

4、水平升高超過URL99百分位值，則提示圍手術(shù)期心肌壞死；如果心臟標志物水平超過URL99百分位值的5倍，同時伴有以下任何一項：新發(fā)的病理性Q波、新發(fā)的LBBB、冠脈造影證實新發(fā)橋血管或自身冠脈閉塞、新出現(xiàn)的存活心肌丟失的影像學證據(jù)，則定義為與CABG相關(guān)的心肌梗死；（5）病理檢查時發(fā)現(xiàn)急性心肌梗死。,心肌壞死生化標志物,新定義建議采用cTn，即在癥狀發(fā)生后24小時內(nèi)，cTn的峰值超過正常對照值的99百分位。因為cTnI或cTnT具有高度的心肌組織特異性和敏感性，即使心肌組織發(fā)生微小區(qū)域的壞死也能檢查到cTn的升高，因此是評價心肌壞死的首選標志物。如果沒有條件檢測cTn，也可以采用CK-MB m

5、ass作為最佳替換指標，診斷標準與cTn相同。由于CK廣泛分布于骨骼肌，缺乏特異性，因此不再推薦用于診斷心肌梗死。,在cTn升高但缺少心肌缺血臨床證據(jù)時，應尋找其他可能導致心肌壞死的病因，包括急性和慢性充血性心力衰竭、腎功能衰竭、快速性或緩慢性心律失常、急性神經(jīng)系統(tǒng)疾病、肺栓塞和肺動脈高壓、心臟挫傷/消融/起搏/復律、浸潤性心臟疾?。ㄈ绲矸蹣幼冃院陀财げ。?、炎性疾病（如心肌炎）、藥物毒性、主動脈夾層、肥厚型心肌病、甲狀腺功能減退、心尖球型綜合征、橫紋肌溶解伴心肌損傷、敗血癥等嚴重全身性疾病等。,按病因?qū)⑿募」Ｋ婪譃?型,1型：自發(fā)性心肌梗死，由于原發(fā)的冠狀動脈事件如斑塊破裂等引起的心肌缺血；

6、2型：心肌梗死繼發(fā)于心肌的供氧和耗氧不平衡所導致的心肌缺血，如冠狀動脈痙攣、貧血、冠狀動脈栓塞、心律失?；虻脱獕旱?； 3型：心源性猝死，有心肌缺血的癥狀和新出現(xiàn)的ST段抬高或新的LBBB，但未及采集血樣之前就死亡； 4型：與因缺血性冠脈事件而進行的PCI相關(guān)的心肌梗死；4a 4b 5型：與因缺血性冠脈事件而進行的CABG相關(guān)的心肌梗死。,60% Narrowing of Coronary Artery,痙攣Normal Coronary Artery Cross Section,Coronary Artery Thrombus,Source: University of Utah WebPat

7、h,The external anterior view of the heart shows a dark clot formation in this artery,陳舊性心肌梗死的定義標準為：（1）新出現(xiàn)的病理性Q波，伴或不伴癥狀；（2）影像學證據(jù)提示心肌變薄或瘢痕化，失去收縮力或無存活性；（3）病理檢查時發(fā)現(xiàn)已經(jīng)或正在愈合的心肌梗死。,【發(fā)病機理】,冠狀動脈粥樣硬化造成管腔狹窄和心肌供血不足，而側(cè)支循環(huán)尚未建立時，下列原因加重心肌缺血即可發(fā)生心肌梗塞。 一、 冠狀動脈完全閉塞 二、心排血量驟降 三、心肌需氧需血量猛增,一、冠狀動脈完全閉塞,1、病變血管粥樣斑塊內(nèi)或內(nèi)膜下出血， 2、血小

8、板聚集管腔內(nèi)血栓形成， 3、動脈持久性痙攣。,二、心排血量驟降,休克、脫水、出血、嚴重的心律失常或外科手術(shù)等引起心排出量驟降,三、心肌需氧需血量猛增,重度體力勞動、情緒激動或血壓劇升時，左心室負荷劇增，兒茶酚胺分泌增多，心肌需氧需血量增加。,誘因：,1、 飽餐（尤其是進食大量脂肪） 因餐后血脂增高，血液粘稠度也高，血小板粘附性增強，局部血流緩慢，血小板易于聚集以致血栓形成； 2、睡眠 迷走神經(jīng)張力增高，易引起冠狀動脈痙攣； 3、用力大便 增加心臟負荷。 心肌梗塞后發(fā)生的嚴重心律失常，休克或心力衰竭，均可使冠狀動脈灌流量進一步降低，心肌壞死范圍擴大。,【病理】,Coronary Artery W

9、ith Plaque and Thrombus Formation,A - Coronary Artery cross-section B - Lumen C - Fissured Plaque w/o Cap D - Acute thrombus,Source: Emergency Cardiovascular Care Library (CD-ROM), American Heart Association, Dallas 1997,Thrombus Causing MI,“Needle-Like” white spots are cholesterol crystals,Thrombus

10、 ocluding artery,Likely site of plaque rupture,高倍鏡下可見粥樣斑塊中有許多泡沫細胞（即吞噬大量脂質(zhì)的巨噬細胞）和膽固醇結(jié)晶。,動脈粥樣斑塊比右邊殘存的動脈中膜要厚?？梢姶罅酷槧畹哪懝檀冀Y(jié)晶（針狀空隙），左邊有新鮮出血，血栓可在這樣的斑塊頂部形成。,31,Myocardial Ischemia,Myocardial cell metabolic demands not met Time frame of coronary blockage: 10 seconds following coronary block Decreased strength

11、 of contractions Abnormal hemodynamics See a shift in metabolism, so within minutes: Anaerobic metabolism takes over Get build-up of lactic acid, which is toxic within the cell Electrolyte imbalances Loss of contractibility,32,20 minutes after blockage Myocytes are still viable, so If blood flow is

12、restored, and increased aerobic metabolism, and cell repair, Increased contractility About 30-45 minutes after blockage, if no relief Cardiac infarct 328:981-8.,Acute Right Ventricular Wall MIRight Sided Leads,七、生物標志物濃度的改變：,Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors.

13、Mayo Clinic Cardiology: Concise Textbook. 3rd ed. Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:77380. Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Figure 5.,Non ACS causes of Troponin Elevation,Trauma (including contusion; ablation; pacing; ICD firi

14、ngs, endomyocardial biopsy, cardiac surgery, after-interventional closure of ASDs) Congestive heart failure (acute and chronic) Aortic valve disease and HOCM with significant LVH Hypertension Hypotension, often with arrhythmias Noncardiac surgery Renal failure Critically ill patients, especially wit

15、h diabetes, respiratory failure Drug toxicity (eg, adriamycin, 5 FU, herceptin, snake venoms) Hypothyroidism Coronary vasospasm, including apical ballooning syndrome Inflammatory diseases (eg, myocarditis, Kawasaki disease, smallpox vaccination, Post-PCI Pulmonary embolism, severe pulmonary hyperten

16、sion Sepsis Burns, especially if TBSA greater than 30% Infiltrative diseases: amyloidosis, hemachromatosis, sarcoidosis, and scleroderma Acute neurologic disease, including CVA, subarchnoid bleeds Rhabdomyolysis with cardiac injury Transplant vasculopathy Vital exhaustion,Modified from Apple FS, et

17、al Heart J. 2002;144:981-986.,并發(fā)癥,Acute Myocardial InfarctionComplications,Death (18% within 1 hour, 36% within 24 hours) Non-fatal arrhythmia Acute left ventricular failure Cardiogenic shock Papillary muscle rupture and mitral regurgitation Myocardial rupture and tamponade Ventricular aneurysm and

18、thrombus,Acute MI: Acute Complications,Postinfarction VSD Free wall rupture Postinfarction ventricular aneurysm associated with ventricular tachyarrhythmias/CHF,Complications of MI,Cardiac Tamponade: Fluid between pericardium/myocardium Pericarditis: Inflammation of the pericardium Emboli: From eith

19、er MI thrombus or atrial clots formed with atrial pooling,Most Common Complications:,Congestive Heart Failure: 75% of MIs experience overt CHF Fluid backs up 25% of MIs experience “compensated” CHF reduced perfusion to “vital organs”? Dysrhythmias: The importance of ECG monitoring post-MI,Cyanosis (

20、blue fingernails 24: 2866.,目的,原則,如果開始PCI治療的時間要比開始藥物纖溶的時間延遲60分鐘以上，那么PCI治療可能并不能降低死亡率 及時采用合適的再灌注治療比選擇治療方式更重要,Ischemic Coronary Syndromes,“Ischemic and injured tissue have reduced blood flow but may be salvaged. The area of the Penumbra may be viable for several hours after onset of occlusion.” Source:

21、Emergency Cardiovascular Care Library (CD-ROM), American Heart Association, Dallas, 1997,Treatment of Acute MISummary,INFLUENCE OF TIME-TO-TREATMENT ON THE ODDS RATIO (OR) OF MORTALITY,Boersma et al. Lancet 1996; 348: 771775.,ABSOLUTE BENEFIT PER 1,000 TREATED PATIENTS,TREATMENT DELAY IN HOURS,0,3,6

22、,9,12,15,18,21,24,0,20,40,60,80,The “golden hour”: 65 lives are saved for every 1,000 patients treated when the treatment is initiated within the first hour of symptom onset!,IMPACT OF TIME-TO-TREATMENT AND 30-DAY MORTALITY PCI VS. THROMBOLYSIS,30-35-DAY MORTALITY (%),Thrombolysis,PCI,Cannon et al.

23、J Thromb Thrombol 1994; 1: 2734.Cannon et al. JAMA 2000; 283: 29412947. Huber et al. Eur Heart J 2005; 26: 10631074.,TIME FROM ONSET OF PAIN TO THERAPY IN HOURS,0,6,12,2,4,2,4,6,8,10,8,0,1,3,5,7,102,ESC STEMI GUIDELINES 2008: REPERFUSION STRATEGIES,Van de Werf et al. Eur Heart J 2008; 29: 2909-2945.

24、 .,Ambulance,First Medical Contact (FMC),PCI-capable hospital,Non-PCI-capable hospital,primary PCI,rescue PCI,angiography,Pre-, in-hospital fibrinolysis,2h,12h,24h,Time Limits,* Time FMC to first balloon inflation must be shorter than 90 min in patients presenting early ( 2 h after symptom onset), w

25、ith large amount of viable myocardium and low risk of bleeding.,#If PCI is not possible 2 h of FMC, start fibrinolytic therapy as soon as possible.,Not earlier than 3h after start fibrinolysis.,24/7 service,successful,failed,PCI 2h possible* PCI 2h not possible# .,Specifics of Early Hospital Care,An

26、ti-Ischemic Therapy Anti-Platelet Therapy Anticoagulant Therapy,Early Hospital CareAnti-Ischemic Therapy,Class I Bed/Chair rest and Telemetry Oxygen (maintain saturation 90%) Nitrates (SLx3 Oral/topical. IV for ongoing iscemia, heart failure, hypertension) Oral B-blockers in First 24-hours if no con

27、traindications. (IV B-blockers class IIa indication) Non-dihydropyridine Ca-channel blockers for those with contraindication fo B-blockers ACE inhibitors in first 24-hours for heart failure or EF40% (Class IIa for all other pts) (ARBs for those intolerant) Statins,Early Hospital CareAnti-Ischemic Therapy,Class III Nitrates if BP0.24 sec, 2nd or 3rd degree heart block, active asthma, or reactive airway disease NSAIDS and Cox-2 inhibitors,Early Hospital CareAnti-Platelet Therapy,Class I Aspirin (162-325 mg), non enteric coated Clopidogrel for th