Association of Troponin Elevation with Risk of Mortality in Acute Coronary Syndromes Mortality at 42 Days 831 174 148 134 50 67  % A study by Antman and colleagues published in the New England Journal of Medicine shows increasing mortality rates with greater levels of cardiac troponin I elevations. These results demonstrate the high risk of patients with elevated levels of cardiac troponin I and indicate that patients with this finding should be treated immediately to avoid progression of MI. Antman EM. N Engl J Med 1996; 335: 12342-1349.

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

The Presence of A Stained or Closed Muscle on Diagnostic Cath Circulation 2002;106:202-207

Troponin T & Angiographic Findings % 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

Peak [tnT] and [tnI] by TIMI Myocardial Perfusion Grade (TMPG) status tn T (ng / mL) Tn I (ng / mL) TMPG 2/3 TMPG 0/1 TMPG 2/3 TMPG 0/1 Circulation 2002;106:202-207

Troponin Elevations on Admission are Associated with Tissue Level Perfusion Following PCI: TACTICS TIMI 18 p=0.004 p=0.013 % TMPG 0/1 % TMPG 0/1 Circulation 2002;106:202-207

Event Free Survival is Associated with Tissue Level Perfusion in UA / Non Q Wave MI: TACTICS – TIMI 18 P = 0.018 % TMPG 3 TMPG 2/3 Pre or Post-PCI Slow Normal N = 253 N = 253 p=0.026 “Upstream” Duration (> median) TMPG 0/1 Pre & Post PCI Event Free Survival Gibson. Am J Cardiol. 2004; 94:492-4 Stain Pale Lecture Notes Event free survival (death or MI) through 6 months of follow-up, stratified by TMPG flow. The presence of TMPG 0/1 flow prior to and following successful PCI was associated with higher rates of death or MI through to 6 months compared to patients without TMPG 0/1 flow prior to and following PCI. Reference: Wong GC, Morrow DA, Murphy SA, Kraimer N, Pai R, James D, Robertson DH, Demopoulos LA, DiBattiste PM, Cannon CP, Gibson CM. Elevations in troponin T and I are associated with abnormal tissue level perfusion: A TACTICS-TIMI 18 substudy. Circulation 2002, in press. Impaired tissue perfusion on diagnostic cath is associated with Tn + and adverse outcomes Earlier upstream initiation of GPIIbIIIa inhibition is associated with improved tisse perfusion om diagnostic cath Days Circulation 2002;106:202-207

Thrombus Is Less Common and Flow Is Better With Upstream GP IIb/IIIa Use Overall Odds Ratio: 0.77 P=0.022 20 40 60 80 100 20 40 60 80 100 Fresh occlusion TIMI Flow Medium or large thrombus Grade 3 % Patients Grade 2 Possible or small thrombus Grade 1 Grade 0 No thrombus An angiographic substudy of the Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial assessed the relationship between the use of the GP IIb/IIIa inhibitor tirofiban and the presence of thrombus in a culprit artery in patients with unstable angina or non–Q-wave MI. After mandatory infusion of study drug for 48 hours, patients were taken to the cardiac catheterization laboratory. The combination of tirofiban and heparin was associated with a reduction in the intracoronary thrombus burden of the culprit lesion as determined by thrombus grading, with fewer fresh occlusions and fewer medium or large thrombi. In addition, absence of thrombus was more frequently noted. Further, the perfusion grade based on TIMI perfusion criteria was significantly better with the addition of tirofiban. The overall severity of the obstruction was also significantly decreased, but as expected, the severity of the underlying plaque was similar in both groups. Heparin Alone Tirofiban + Heparin Heparin Alone Tirofiban + Heparin Zhao et al. Circulation. 1999;100:1609-1615. Zhao, XQ, Theroux P, Snapinn SM, Sax FL, for the PRISM-PLUS Investigators. Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Angiographic results from the PRISM-PLUS trial (Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Angina and Symptoms.) Circulation. 1999;100:1609-1615.

Patients With Event (%) Long-Term Benefit of Upstream Therapy in Reducing Thrombus and Improving TIMI 3 Flow Events at 30 Days 5 15 10 20 25 30 5 15 10 20 25 30 Thrombus TIMI 0-2 (n=298) No thrombus TIMI 3 (n=1095) 20% Patients With Event (%) 12% 10% 9% 7.4% 5.5% The variables of thrombus and TIMI flow grade were correlated to outcomes at 30 days. Persistence of the thrombus was associated with a 2.1-fold increase in the composite endpoint of death, MI, or refractory ischemia at 30 days. This also increased the risk of each component of the composite endpoint 2-fold or more, which was statistically significant at all levels. Further, suboptimal TIMI flow, grades 0-2, defined a population with a 1.7-fold increase in risk for the composite endpoint at 30 days and also significantly increased the risk for refractory ischemia. Composite MI/Death Refract Isch Composite MI/Death Refract Isch Hazard ratio P value 1.72 <0.001 1.44 0.08 1.68 0.02 1.72 <0.001 1.44 0.08 1.68 0.02 Zhao et al. Circulation. 1999;100:1609-1615. Zhao XQ, Théroux P, Snapinn SM, Sax FL, for the PRISM-PLUS Investigators. Intracoronary thrombus and platelet glycoprotein IIb/IIIa receptor blockade with tirofiban in unstable angina or non-Q-wave myocardial infarction. Circulation. 1999;100:1609-1615.

GP IIb-IIIa Inhibitor > 24 Hrs. GP IIb-IIIa Inhibitor < 24 Hrs. NRMI also shows that early GP IIb-IIIa inhibitor therapy reduces in-hospital mortality 5.3 % * P < 0.001 n = 32,710 8.5 % In-hospital Death 3.2 % GP IIb-IIIa Inhibitor > 24 Hrs. GP IIb-IIIa Inhibitor < 24 Hrs. * Unadjusted for risk. Peterson E. Presented at ACC. March 2002.