1、Acute Coronary Syndrome: From Pathophysiology to Management,安徽中医学院第一附属医院心内科 戴小华,New Terminology in ACS,ACS, acute coronary syndrome; MI, myocardial infarction; UA, unstable angina; NSTEMI, nonST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; PCI, percutan
2、eous coronary intervention. Cannon CP. J Thromb Thrombolysis. 1995;2:205-218.,STEMI,Clinical finding,EKG,Serum markers,Risk assessment,Non-cardiac chest pain,Stable angina,UA,NSTEMI,Negative,Positive,ST-T wave changes,ST elevation,Low probability,Medium-high risk,Thrombolysis Primary PCI,Aspirin + G
3、P IIb/IIIa inhibitor clopidogrel + heparin/ LMWH + anti-ischemic Rx Early invasive Rx,Discharge,Negative,Diagnostic rule out MI/ACS pathway,STEMI,Negative,Atypical pain,Low risk,Aspirin, heparin/low-molecular-weight heparin (LMWH) + clopidogrel Anti-ischemic Rx Early conservative therapy,Ongoing pai
4、n,DM=diabetes mellitus. Cannon, Braunwald. Heart Disease. 2001.,Rest pain, Post-MI, DM, Prior Aspirin,Exertional pain,The Spectrum of ACS,Normal,Fatty Streak,Fibrous Plaque,Occlusive Atherosclerotic Plaque,Plaque Rupture/ Fissure & Thrombosis,MI,Stroke,Critical Leg Ischemia,Clinically Silent,Coronar
5、y Death,Increasing Age,Effort Angina Claudication,Unstable Angina,Courtesy of P Ganz.,Atherosclerosis: A Progressive Process,Libby P. Lancet. 1996;348:S4-S7.,Media, T lymphocyte, Macrophage foam cell (tissue factor+), “Activated” intimal SMC (HLA-DR+), Normal medial SMC,Fibrous cap,Intima,Lipid core
6、,Lumen,The Anatomy of Atherosclerotic Plaque,Pathophysiology of ST-Elevation Myocardial Infarction,Results from stabilization of a platelet aggregate at site of plaque rupture by fibrin mesh,platelet,RBC,fibrin mesh,GP IIb-IIIa,Generally caused by a completely occlusive thrombus in a coronary artery
7、,CK- MB or Troponin,Troponin elevated or not,Adapted from Michael Davies,Adapted from Michael Davies,ACS without persistentST-segment elevation,ACS with persistentST-segment elevation,NSTE-ACS,STE-ACS,Inflammation,Atherosclerosis,Thrombosis,Thrombus,Quiescent,plaque,Platelets,and thrombin,Plaque rup
8、ture,Acute Coronary Syndromes Evolving Understanding of Pathophysiology,Thrombosis of a Disrupted Atheroma,Weakening of the fibrous cap Thrombogenicity of the lipid core,The signals that regulate these features of the plaque remain uncertain,Markers of Increased Risk in ACS,ST segment changes Serum
9、markers Necrosis Inflammation LV dysfunction Hemodynamic instability,TIMI Risk Score 7 Independent Predictors,Antman EM, et al. JAMA. 2002;284:835-842. Antman EM, et al. Circulation. 1999;100:1593-1601. Cohen M, et al. N Engl J Med. 1997;337:447-452.,Age 65 years 3 CAD risk factors (chol, FHx, HTN,
10、DM, smoking) Prior coronary stenosis 50% ASA in last 7 days 2 anginal events 24 hours ST deviation Elevated cardiac markers (CK-MB or troponin),Goals in ACS Management,Relieve symptoms Minimize loss of muscle Reduce mortality Treat specific complications,Therefore.,Reduce thrombus burden Limit throm
11、bus progression Prevent micro-embolization Promote healing and homeostasis of the injured vessel wall,ACS Treatment Strategies,Medical Theapy,Risk Modification,CABG,PCI,Antithrombotic therapy,Other medical therapy,ADP antagonists,Nitrates,BBs,STATINS,ACE-I,OTHERS,Reperfusion/Revascularization therap
12、y,Heparin,ASA,GPIIb/IIIas,Thrombosis,Inflammation,Mechanical options, 90% of “Normal” Arteries Have Significant Plaque Burden by IVUS,ACC/AHA Guideline Recommendations for Anti-thrombotic Therapy,Braunwald E, et al. J Am Coll Cardiol 2000;36:970-1062. www.acc.org 3/15/2002.,High Risk or Definite ACS
13、 With Cath and PCI,Likely/Definite ACS,Possible ACS,Aspirin,Systemic medical therapy to stabilize vulnerable plaque(s) Reduce thrombogenicity in blood (antiplatelets: aspirin, clopidogrel) Reduce plaque lipid content (lipid-lowering agents: statins) Decrease inflammation (statins, aspirin, clopidogr
14、el) Improve endothelial function (statins, ACE inhibitors) Increase plaque collagen content,Focal interventional treatment to stabilize ruptured plaque Fibrinolysis Percutaneous coronary intervention (PCI) with stenting,Ambrose J. Circulation. 2002;105:2000.,An Integrated Approach to Plaque Stabiliz
15、ation,fibrous cap,lumen,lipid core,tunica media,Non-occlusive lesion,Stenotic lesion, Potentially unstable (if cap thin) Little or no angiographic abnormality Greater lipid content “immature”, Often stable (if cap thick) Abnormal angiogram More fibrous “mature”,Libby, P. Nature-Medicine 1:17-18, 199
16、5,ANGIOGRAPHY DOES NOT PREDICT RISK OF PLAQUE RUPTURE,safe plaque,unsafe plaque,ANGIOGRAPHIC APPEARANCE,Nissen et al. In: Topol. Interventional Cardiology Update. 14;1995.,Angiographically Inapparent Atheroma,PTCA/stent,Fatal thrombus,Plaque Rupture: A common substrate for acute myocardial infarctio
17、n,Michael Davies Earling Falk Paris Constantinides,Non-vulnerable plaque with fibrous tissue that partially blocks blood flow, but is not likely to cause a clot or cardiac event,Vulnerable Plaque (TCFA) with lipid-rich core, thin fibrous cap, inflammation at margins,The “Vulnerable Plaque” Paradigm,
18、Serum Markers,total cholesterol LDL-cholesterol TC-HDL distribution HDL-2b: Inversely related for risk to coronary events APO-E Ox-LDL antibody Lp-PLA2, LDL phenotype A, B, or I, large particles: I-IIb, small particles: IIIa+ IIIb, IVb Antibody titers Chlamydia pneumonia, CMV, HSV1 and HSV2, mycopla
19、sma pneumonia, hepatitis A, pyloric helicobacter IL-1, IL-6, IL-18 TNF-alfa hs-CRP,Characteristics of plaques prone to rupture,Thin fibrous caps (50 mm) Lipid, macrophage-rich Smooth muscle cell poor,Davies MJ, Richardson PD, Woolf N, Katz DR, Mann J. Br Heart J 1993,Higher resolution IVUS（高频血管内超声 ）
20、 Optical coherence tomography（光学相干断层扫描 ） InfraRed Spectroscopy Thermal imaging Endovascular MRI Raman spectroscopy Pulse laser irradiation Fluorescence-mediated tomography (FMT),Future Technologies to predict “vulnerable” plaque,Morphology vs. Activity Imaging,Inactive and non-inflamed plaque,Active
21、 and inflamed plaque,IVUS VH,OCT,MRI,Morphology,Activity,Thermography, Spectroscopy, MRI with targeted CM,OCT Fibrocalcific Plaque,Yabushita et al., Circ, 2002,Oil-red-O (lipid),Lumen,Lumen,lumen,fibrous cap,Endovascular MRI,H & E,Yeghiazarians et al. 2002,Endovascular MRI correlates well with the h
22、istology of an advanced ex-vivo human iliac artery,Fluorescence-mediated Tomography: In vivo imaging of proteolytic activity in atherosclerosis,Chen et al. Circulation 2002;105:2766,Sudan IV,NIRF,Thermography: Inflammation is hot,Unstable angina DCA with abundant macrophages and lipids,Vulnerable pl
23、aques: Preventive Strategies,Systemic Cholesterol-lowering Anti-inflammatory agents Metalloproteinase inhibitionMechanical intervention Balloon Stent CABG,Energy Brachytherapy Photodynamic therapy,Vascular Damage,Inflammation,Myocyte Necrosis,Accelerated Atherosclerosis,Hemodynamic Stress,HbA1c Bloo
24、d glucose,CrCl Microalbuminuria,Troponin,BNP, NT-proBNP,hs-CRP, CD40L,Morrow DA, et al. Circulation. 2003;108:250-252.,Multimarker Strategy in ACS,ACC/AHA Guidelines for the Management of Patients With ST-Elevation Acute Myocardial Infarction- Focus Emergency Care,A Report of the American College of
25、 Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction),Available as full text or executive versions at http:/www.acc.org,Antman et al. JACC 2004;44:671-719.,AMI Stats,I
26、ncidence in the United States* Estimated 900,000 will suffer AMI this year 565,000 will be new attacks (avg. age- 65.8yrs/males, 70.4yrs/female) 300,000 will be recurrent attacks 42% of AMI pts will die within 1 year Approximately half of these deaths occur before reaching the emergency department M
27、ost cardiac deaths are the result of fatal arrhythmias Types of arrival/discharge AMIs* Upon arrival: STEMI on 1st ECG-26%; STEMI on 1st or subsequent ECG-35%; NSTEMI-65% Non-Q-wave: 75% Q-wave: 25%,*American Heart Association. Heart Disease June, 2004.,Hospital Admissions for ACS: UA/NSTEMI versus
28、STEMI,ACS,2.3 million hospital admissions ACS,UA/NSTEMI,1.43 million admissions per year,National Center for Health Statistics. 2001.,STEMI,829,000 admissions per year,Patients Transported by EMS After Calling 9-1-1,Onset of STEMI Symptoms,Call 911 Call Fast,9-1-1 EMS Dispatch,EMS on-scene Encourage
29、 12-lead ECG Consider prehospital fibrinolytic if capable and EMS-to-needle 30 min,EMS Triage Plan,Not PCI Capable Hospital,PCI Capable Hospital,Interhospital,Transfer,Hospital Fibrinolysis: Door-to-needle within30 min,EMS transport:EMS to Balloon within 90 min,Patient self-transport: Hospital Door-
30、to-Balloon within 90 min,EMS transport,EMS on scene,Within8 min,Dispatch,1 min,Patient,5 min after Symptom onset,Goals,Total ischemic time: Within 120 min*,* Golden hour = First 60 min,Adapted from Panel A Figure 1Antman et al. JACC 2004;44:676.,Adapted from Panel B Figure 1Antman et al. JACC 2004;4
31、4:676.,Fibrinolysis,Noninv. Risk Stratification,Late Hospital Care & Secondary Prevention,PCI or CABG,Primary PCI,Receiving Hospital,Not PCI Capable PCI Capable,Rescue,Ischemic driven,Early invasive strategy,+/- GP IIb/IIIa,Catheterization within 8 hours of last subcutaneous dose,UA/NSTEMI Identifie
32、d, LMWH,- GP IIb/IIIa,+ GP IIb/IIIa,Catheterization between 8-12 hours of last subcutaneous dose,No additional UFH or LMWH,Additional Enoxaparin 0.3 mg/kg IV bolus,Supplement with UFH 50 U/kg, aim for ACT 200-250,Supplement with UFH 60 U/kg, aim for ACT 250-300,Additional Enoxaparin 0.3-0.5 mg/kg IV
33、,Kereiakes DJ, et al. Am Heart J. 2002;144:615-624. (with permission),Expert Panel Consensus,Conclusions: ACS + Atherothrombosis,ACS is a manifestation of diffuse atherothrombosis Multiple plaques, inflammation, and thrombosis. Patients with ACS and post-PCI remain at increased risk for long-term is
34、chemic events. Management of ACS Focal Rx of ruptured culprit lesion (stents). Systemic Rx to prevent future ischemic events. Risk factor modification + 5 drugs for long-term medical therapy to treat: “Athero + thrombosis”Statins ASA ACE inhibitor Clopidogrel-blocker,Post MI/Angina,Other AtheroscleroticManifestations,Subclinical Atherosclerosis,Multiple Risk Factors,Low Risk,Secondary Prevention,Primary Prevention,Courtesy of CD Furberg.,Continuum of Patients at Risk for a CHD Event,
