1. Unstable Angina: Embolism Can Occur Prior to PCI Thrombus in proximal RCA Stain of muscle before injection begins: TIMI Myocardial perfusion grade 1 CM Gibson 2002

2. T-wave inversion ST  ST  GUSTO 2B: ST Depression A High-Risk Patient Population P  0.001 CM Gibson 2002

3. Unstable Angina: Platelet Plugging of the Capillaries From: Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death Davies MJ, Circulation 1986 “The results support the view that platelet aggregates in the myocardium represent an embolic phenomenon and are a potential cause of unstable angina. The association of myocardial necrosis with such emboli could precipitate sudden death from ventricular fibrillation.”

4. ST  ST  UA / Non STEMI versus STEMI Mechanisms of Long Term Outcomes Necrosis by closed Muscle Necrosis by closed Muscle Necrosis by closed Artery Necrosis by closed Artery Arrhythmias CHF Arrhythmias CHF Death CM Gibson 2002

5. Correlation Between Elevated Cardiac Enzymes at Presentation and Long-term Mortality + Cardiac Troponin T at Baseline (n=559) 14.1% 4.5% – Cardiac Troponin T at Baseline (n=474) % mortality at 1 year Newby LK et al. Circulation. 1998; 98: 1853-1859. P<0.0001

6. Association of Troponin Elevation with Risk of Mortality in Acute Coronary Syndromes Mortality at 42 Days 831 174 148 134 50 67   % % % % % % % % % % % %

7. Audience Poll What is a powerful angiographic predictor of the patient’s troponin status? Circulation 2002;106:202-207

8. Even when epicardial TIMI flow grade and the presence of thrombus were adjusted for, the presence of a closed microvasculature was independently associated with tnT elevation in a multivariate model (O.R. 1.79, p=0.017). Circulation 2002;106:202-207 Answer:

9. Tissue Perfusion Predicts Troponin Release % Stenosis % Vessel Occlusion % Normal TMPG 3 % Thrombus tnT + tnT - P=0.021 P=0.0003 P=0.03 P=0.007 Even when epicardial TIMI flow grade and the presence of thrombus were adjusted for, the presence of a closed microvasculature was independently associated with tnT elevation in a multivariate model (O.R. 1.79, p=0.017). Circulation 2002;106:202-207

10. Event Free Survival is Associated with Tissue Level Perfusion in UA / Non Q Wave MI: TACTICS – TIMI 18 Circulation 2002;106:202-207 Log rank p=0.026 Days Event Free Survival TMPG 0/1 Pre & Post PCI TMPG 0/1 Pre & Post PCI TMPG 2/3 Pre or Post-PCI

11. TMPG and Maximum CK-MB 24 Hours Post-stent Maximum CK-MB >2x ULN (%) 41.2% p = 0.002 1/2414/34 4.2% All Patients Have TIMI 3 Flow at Completion of Stenting Gibson, Am Heart J 2002

12. The Time Dependent Open Artery and Open Microvascular Hypothesis Plaque rupture/erosion/fissure Platelet thrombus EmbolizationEmbolization Time Dependent Necrosis TIMI 2 Flow VasoconstrictionVasoconstriction Impaired tissue level perfusion Arrhythmias / CHF EdemaEdema InflammationInflammation TIMI 0 Flow Non – Occlusive UA / NSTEMI Non – Occlusive UA / NSTEMI Occlusive STEMI Occlusive STEMI + Troponin / CK Death CM Gibson 2002 GP 2b3a Antithrombin + GP 2b3a GP 2b3a Antithrombin + GP 2b3a

13. Conclusions:Conclusions: The source of Tn and CK is the muscle Tn positive: Poorer muscle perfusion before PCI 1 CK positive: Poorer muscle perfusion post PCI 2 Poorer TMPG before PCI: worse outcomes at 6 months in TACTICS 1 Poorer TMPF after PCI: worse outcomes at one year in ESPRIT 2 The source of Tn and CK is the muscle Tn positive: Poorer muscle perfusion before PCI 1 CK positive: Poorer muscle perfusion post PCI 2 Poorer TMPG before PCI: worse outcomes at 6 months in TACTICS 1 Poorer TMPF after PCI: worse outcomes at one year in ESPRIT 2 2. Gibson, Am Heart J 2002 1. Circulation 2002;106:202-207