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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. GUSTO 2B: ST Depression A High-Risk Patient Population. ST . P 0.001. ST . T-wave inversion. CM Gibson 2002.
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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
GUSTO 2B: ST DepressionA High-Risk Patient Population ST P 0.001 ST T-wave inversion CM Gibson 2002
Unstable Angina: Platelet Plugging of the Capillaries “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.” From: Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death Davies MJ, Circulation 1986
UA / Non STEMI versus STEMIMechanisms of Long Term Outcomes Necrosis by closed Muscle ST Arrhythmias CHF Death Necrosis by closed Artery ST CM Gibson 2002
Correlation Between Elevated Cardiac Enzymes at Presentation and Long-term Mortality % mortality at 1 year + Cardiac Troponin T at Baseline(n=559) 14.1% P<0.0001 – Cardiac Troponin T at Baseline(n=474) 4.5% Newby LK et al. Circulation. 1998; 98: 1853-1859.
% % % Mortality at 42 Days % % % 831 174 148 134 50 67 Association of Troponin Elevation with Risk of Mortality in Acute Coronary Syndromes
Audience Poll • What is a powerful angiographic predictor of the patient’s troponin status? Circulation 2002;106:202-207
Answer: 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
Tissue Perfusion Predicts Troponin Release P=0.021 P=0.007 P=0.0003 P=0.03 % Normal TMPG 3 % Thrombus % Stenosis % Vessel Occlusion tnT - tnT + tnT - tnT + tnT - tnT + tnT - tnT + 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
Event Free Survival is Associated with Tissue Level Perfusion in UA / Non Q Wave MI: TACTICS – TIMI 18 TMPG 2/3 Pre or Post-PCI Log rank p=0.026 TMPG 0/1 Pre & Post PCI Event Free Survival Days Circulation 2002;106:202-207
TMPG and Maximum CK-MB 24 Hours Post-stent All Patients Have TIMI 3 Flow at Completion of Stenting p = 0.002 41.2% Maximum CK-MB >2x ULN (%) 4.2% 1/24 14/34 Gibson, Am Heart J 2002
The Time Dependent Open Artery and Open Microvascular Hypothesis Plaque rupture/erosion/fissure Occlusive STEMI Non – Occlusive UA / NSTEMI Platelet thrombus Vasoconstriction Embolization TIMI 2 Flow Inflammation TIMI 0 Flow Edema Impaired tissue level perfusion Time Dependent Necrosis GP 2b3a Antithrombin + GP 2b3a + Troponin / CK Arrhythmias / CHF CM Gibson 2002 Death
Conclusions: • The source of Tn and CK is the muscle • Tn positive: Poorer muscle perfusion before PCI1 • CK positive: Poorer muscle perfusion post PCI2 • Poorer TMPG before PCI: worse outcomes at 6 months in TACTICS1 • Poorer TMPF after PCI: worse outcomes at one year in ESPRIT2 2. Gibson, Am Heart J 2002 1. Circulation 2002;106:202-207