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Antithrombotic TherapyStable AnginaUnstable AnginaNon Q-wave MIThrombolysis Primary PCIQ-wave MIMinutes- hoursDays- weeksSTEMIUA/NSTEMIAtherothrombosisNew termOld termPlaque RuptureNew Terminology in ACSACS, acute coronary syndrome; MI, myocardial infarction; UA, unstable angina; NSTEMI, nonST-segment elevation myocardial infarction; STEMI, ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention. Cannon CP. J Thromb Thrombolysis. 1995;2:205-218.STEMIClinical findingEKGSerum markersRisk assessmentNon-cardiac chest painStable anginaUANSTEMINegativePositiveST-T wave changesST elevationLow probabilityMedium-high riskThrombolysis Primary PCIAspirin + GP IIb/IIIa inhibitor clopidogrel + heparin/ LMWH + anti-ischemic Rx Early invasive RxDischargeNegativeDiagnostic rule out MI/ACS pathwaySTEMINegativeAtypical painLow riskAspirin, heparin/low-molecular- weight heparin (LMWH) + clopidogrel Anti-ischemic Rx Early conservative therapyOngoing painDM=diabetes mellitus. Cannon, Braunwald. Heart Disease. 2001.Rest pain, Post-MI, DM, Prior AspirinExertional painThe Spectrum of ACSNormalNormalFatty StreakFibrous PlaqueOcclusive Atherosclerotic PlaquePlaque Rupture/ Fissure 348:S4-S7. MediaT lymphocyte Macrophage foam cell (tissue factor+) “Activated” intimal SMC (HLA-DR+) Normal medial SMCFibrous capIntimaLipid coreLumenThe Anatomy of Atherosclerotic PlaquePathophysiology of ST-Elevation Myocardial InfarctionResults from stabilization of a platelet aggregate at site of plaque rupture by fibrin meshplateletRBCfibrin meshGP IIb-IIIaGenerally caused by a completely occlusive thrombus in a coronary arteryCK- MB or TroponinTroponin elevated or notAdapted from Michael DaviesAdapted from Michael DaviesACS without persistentST-segment elevationACS with persistentST-segment elevationNSTE-ACSSTE-ACSInflammationInflammationAtherosclerosisAtherosclerosisThrombosisThrombosisThrombusQuiescent plaquePlatelets and thrombinPlaque ruptureAcute Coronary Syndromes Evolving Understanding of PathophysiologyThrombosis of a Disrupted AtheromaWeakening of the fibrous capThrombogenicity of the lipid coreThe signals that regulate these features of the plaque remain uncertainMarkers of Increased Risk in ACSnST segment changesnSerum markersnNecrosisnInflammationnLV dysfunctionnHemodynamic instabilityTIMI Risk Score 7 Independent PredictorsAntman 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;337:447-452.1.Age 65 years 2.3 CAD risk factors (chol, FHx, HTN, DM, smoking) 3.Prior coronary stenosis 50% 4.ASA in last 7 days 5.2 anginal events 24 hours 6.ST deviation 7.Elevated cardiac markers (CK-MB or troponin)Goals in ACS ManagementnRelieve symptomsnMinimize loss of musclenReduce mortalitynTreat specific complicationsTherefore.nReduce thrombus burdennLimit thrombus progressionnPrevent micro-embolizationnPromote healing and homeostasis of the injured vessel wallACS Treatment StrategiesMedical TheapyRisk ModificationCABG PCIAntithrombotic therapyOther medical therapyADP antagonist sNitratesBBsSTATINSACE-IOTHERSReperfusion/Revascularization therapyHeparinASAGPIIb/IIIasThrombosisInflammationStentsStents or Bypass or Bypass insertioninsertionXMechanical options 90% of 90% of “Normal” “Normal” Arteries Arteries Have Have Significant Significant Plaque Plaque Burden by Burden by IVUSIVUSACC/AHA Guideline Recommendations for Anti-thrombotic TherapyBraunwald E, et al. J Am Coll Cardiol 2000;36:970-1062. www.acc.org 3/15/2002.High Risk or Definite ACS With Cath and PCILikely/Definite ACSPossible ACSAspirin + IV heparin/LMWH* + IV platelet GP IIb/IIIa antagonistclopidogrelAspirin + SQ LMWH* or IV UFHclopidogrelAspirinSystemic 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, clopidogrel) Improve endothelial function (statins, ACE inhibitors) Increase plaque collagen contentFocal interventional treatment to stabilize ruptured plaque Fibrinolysis Percutaneous coronary intervention (PCI) with stenting Ambrose J. Circulation. 2002;105:2000.An Integrated Approach to Plaque Stabilizationfibrous caplumenlipid coretunica mediaNon-occlusive lesionStenotic 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, 1995ANGIOGRAPHY DOES NOT PREDICT RISK OF PLAQUE RUPTUREsafe plaqueunsafe plaqueANGIOGRAPHIC APPEARANCENissen et al. In: Topol. Interventional Cardiology Update. 14;1995.Angiographically Inapparent AtheromaPTCA/stentPTCA/stentFatal thrombusPlaque Rupture: A comm