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1、Acute Coronary Syndrome From Pathophysiology to Management STEMI Clinical finding EKG Serum markers Risk assessment Non cardiac chest pain Stable angina UANSTEMI NegativePositive ST T wave changes ST elevation Low probability Medium high risk Thrombolysis Primary PCI Aspirin GP IIb IIIa inhibitor cl
2、opidogrel 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 pain DM diabetes mellitus Cannon Bra
3、unwald Heart Disease 2001 Rest pain Post MI DM Prior Aspirin Exertional pain The Spectrum of ACS Inconsistent Approach to ACS nMultiplicity of interpretation of Clinical trials nProtocol variation nPropensity of PCI in clinical studies nPersonal preference of physicians nUnclear guidelines Inflammat
4、ionInflammationAtherosclerosisAtherosclerosis ThrombosisThrombosis Thrombus Quiescent plaque Platelets and thrombin Plaque rupture Acute Coronary Syndromes Evolving Understanding of Pathophysiology Relative Risk of Cardiovascular Events According to Several Biochemical Markers Relative Risk of Futur
5、e CV Events 01 02 04 06 0 Lipoprotein a LDL cholesterol Homocysteine Total cholesterol Apolipoprotein B TC HDL C ratio hs CRP hs CRP TC HDL C Ratio Adapted from Ridker PM et al N Engl J Med 2000 342 836 843 Thrombosis of a Disrupted Atheroma Weakening of the fibrous cap Thrombogenicity of the lipid
6、core The signals that regulate these features of the plaque remain uncertain Collagenase expression and circumferential stress in human coronary atheroma MMP 1 Lee RT et al Art Thromb Vasc Biol 1996 16 1070 Percentage Distribution of Coronary Atherosclerotic Plaque Ruptures Other Than the Culprit Le
7、sion of Ruptured Plaque Distinct From the Culprit Lesion Rioufol G et al Circulation 2002 106 804 8 0 1 2 3 4 5 Markers of Increased Risk in ACS nST segment changes nSerum markers nNecrosis nInflammation nLV dysfunction nHemodynamic instability 0 30 60 90 120 150 180 10 8 6 4 2 0 Days ST ACS T wave
8、inversion GUSTO IIb Study Correlation of 6 Month Mortality With Baseline ECG Findings in Patients With ACS Cumulative Mortality At 6 Months Savonitto S et al JAMA 1999 281 707 713 Copyrighted 1999 American Medical Association Association of Troponin Elevation with Risk of Mortality in ACS Mortality
9、at 42 Days 8311741481345067 Antman EM N Engl J Med 1996 335 12342 1349 x upper limit of normal Relationship Between Elevated CK MB and Mortality at 6 months Alexander JH et al Circulation 1999 Suppl 1 1 629 4 9 5 7 9 2 12 6 14 5 19 9 n 5 681 n 1 098 n 294 n 302 n 249 n 211 Normal 1 2 2 3 3 5 5 10 10
10、 CK MB levels during hospitalization TACTICS Outcome by Troponin Status and CAD on Cath at 6 months Tn neg No CAD Tn neg CAD Tn Pos No CAD Tn Pos CAD P value Death 01 72 24 1 0 082 Re MI 03 54 48 3 0 003 Death Re MI 05 05 511 2 0 001 ACS Hosp 2 27 014 611 4 0 005 All Cause 2 210 518 519 1 0 60 g L n
11、 377 Troponin T 0 60 0 59 g L n 367 Troponin T 10 mg L n 309 CRP 2 mg L n 314 P 001 P 29 Troponin I TnI C Reactive Protein CRP and B type Natriuretic Peptide BNP as Determinants of 30 Day Mortality in ACS Sabatine MS et al Circulation 2002 105 1760 1763 P 014P 0001 6715015578 30 Day Mortality Risk 5
12、0471732490 OPUS TIMI 16 1 1 8 3 5 6 0 1 2 3 4 5 6 0123 TACTICS TIMI 18 1 2 1 5 7 13 0 2 4 6 8 10 12 14 0123 No of Elevated BiomarkersNo of Elevated Biomarkers n 67n 150n 155 n 78 n 504 n 717 n 324 n 90 Inflammation in ACS Myeloperoxidase Circulation 2003 Inflammatory Marker Predicts Invasive Success
13、 in FRISC II Lindmark et al JAMA 2001 286 2107 13 Goals in ACS Management nRelieve symptoms nMinimize loss of muscle nReduce mortality nTreat specific complications Therefore nReduce thrombus burden nLimit thrombus progression nPrevent micro embolization nPromote healing and homeostasis of the injur
14、ed vessel wall Event incidence Day Cohen et al Am Heart J 2002 143 63 0 0 2 0 4 0 6 0 8 16111621 Recurrent angina MI Death Leading to urgent revascularization Peak Day 2 Peak Day 8 Peak Day 3 0 0 5 1 1 5 2 5 16111621 2 Day In Hospital Events in ACS ESSENCE TIMI 11b N 7 081 ACS Treatment Strategies M
15、edical Theapy Risk Modification CABG PCI Antithrombotic therapy Other medical therapy ADP antagonist s NitratesBBsSTATINSACE IOTHERS Reperfusion Revascularization therapy HeparinASAGPIIb IIIas FRISC II Investigators Lancet 1999 354 708 715 Cannon C et al N Engl J Med 2001 344 1879 1887 FRISC II TACT
16、ICS TIMI 18 DalteparinTirofiban Day 7 OR 0 59 P 0 033 Day 30 OR 0 51 P 0 002 0306090 Time days 120150180 0 00 0 02 0 04 0 06 0 08 0 10 0 12 0 14 Probability of Death MI Invasive Conservative Conservative Invasive UA NSTEMI Benefit of Early Invasive Strategy 0 14 0 12 0 10 0 08 0 06 0 04 0 02 0 0306090120150180 Time since start of open phase days Conservative tirofiban Early intervention tirofiban 6 month Death MI Re hospitalization 11 8 20 3 12 8 16 1 19 5 30 6 0 5 10 15 20 25 30 35 Low 0 2Inter
