Beyond TIMI 3 Flow CTFC < 14 CTFC > % (n=41) (n = 18/640) (n =35/563) 2.8% p= “TIMI 4” Flow TIMI 3 Flow 14 < CTFC < % % Risk of In Hospital Mortality Gibson, Circulation 1999; 99: Hyperemic Flow Reproducibility: r = 0.97 between readers Accuracy: r=0.88 vs Doppler velocity Reproducibility: r = 0.97 between readers Accuracy: r=0.88 vs Doppler velocity

TIMI Myocardial Perfusion (TMP) Grades 6.2% 4.4% 2.0% n = 203 n = 46 n = 434 TMP Grade 3 p = 0.05 Mortality (%) n = % Gibson et al, Circulation 2000 Normal ground glass appearance of blush Dye mildly persistent at end of washout Normal ground glass appearance of blush Dye mildly persistent at end of washout Dye strongly persistent at end of washout Gone by next injection Dye strongly persistent at end of washout Gone by next injection Stain present Blush persists on next injection Stain present Blush persists on next injection No or minimal blush TMP Grade 2 TMP Grade 1 TMP Grade 0

Not All TIMI Grade 3 Flow is Created Equally: Myocardial Perfusion Grade 3 Myocardial Perfusion Grade 3 Myocardial Perfusion Grade 2 Myocardial Perfusion Grade 2 Myocardial Perfusion Grades 0/1 Myocardial Perfusion Grades 0/1 N = 136 N = 34 N = % 2.9% 5.4% % Mortality P = Gibson CM, et al. Circulation. 2000;101: Among Patients. With Successful Lysis, There is a 7 Fold Range in Mortality

TIMI 10 B: Independent Predictors of 2 Year Mortality TIMI Grade 3 FlowRR 0.61, p=0.047 TIMI Myocardial BlushRR 0.50, p = TIMI Grade 3 FlowRR 0.61, p=0.047 TIMI Myocardial BlushRR 0.50, p = In a MV model correcting for : Performance of PCI Age Gender Pulse Anterior MI In a MV model correcting for : Performance of PCI Age Gender Pulse Anterior MI Pre-PCI Epicardial and Myocardial Flow Are Independently Associated with 2 Year Mortality Gibson et al, Circulation 2002

p< /1 2 n=690 n=55 n=32 0/1 n=236 2 n=393 3 n=148 TIMI Flow GradesMyocardial Blush Grades Survival Time (days) p< van ‘t Hof AWJet al. Circulation 1998; 97: Myocardial Reperfusion Score Zwolle Myocardial Blush Grades (n=777)

A Comparison of TMPP and Zwolle System TIMI Epicardial Flow Grade TIMI Myocardial Perfusion Grade Zwolle System Grade 0No flow Grade 1Penetrates but does not perfuse Dye penetrates but is stuck in muscle Very Pale Grade 2Slow flow in artery Slow flow in muscle Less Pale Grade 3Normal flow in artery Normal flow in muscle

A Comparison of TMPG and Zwolle System TIMI Myocardial Perfusion Grade Zwolle System Grade 0No flow Grade 1Dye penetrates but is stuck in muscle Very Pale Grade 2Slow flow in muscle Less Pale Grade 3Normal flow in muscle

A Comparison of TMPP and Zwolle System TIMI Myocardial Perfusion Grade Zwolle System Grade 0 or 1No flow = Grade 2 or 3Normal or near normal =

Myocardial Perfusion After Primary PCI is Strongest Predictor of Mortality /1 n=236 2 n=393 3 n=148 Myocardial Blush Grades Time (days) /1 100 Cumulative Survival (%) Final Blush Score (patients with final TIMI grade 3 flow) Blush 1-Year Mortality 3 2 0/1 6.8% 13.2% 18.3% P=0.004 RR*95% CIP MBG 0 and 1 vs 2 and to MVD 2 and 3 vs to LAD vs non-LAD MI to TIMI flow before: 0 to 2 vs to Independent Angiographic Variables as Risk Factors of Long-Term Mortality in Patients With TIMI Grade 3 flow After Angioplasty MBG 0/1 (n=100) MBG 2 (n=74) MBG 3 (n=79)P Death at 30 days 26.0%9.9%3.9%<0.001 Death at 1 year 35.1%13.4%9.4%<0.001 Death during F/U 39.0%18.3%12.4%<0.001 Relation of Myocardial Perfusion Grade to Mortality  2 of 3 pts have a closed muscle after 1 0 PCI  Mortality goes up 3 fold  2 of 3 pts have a closed muscle after 1 0 PCI  Mortality goes up 3 fold Stone GW, et al. J Am Coll Cardiol. 2002;39: Haagar PK, et al. J Am Coll Cardiol. 2003;41: Henriques JP, et al. Circulation. 2003;107: van ‘t Hof AWJet al. Circulation 1998; 97:

Peak Myocardial Brightness, Circumference and Circumference Growth in Culprit and Non-culprit Arteries in Acute MI and in Normal Patients p < Normal Non-culprit AMI DSA Peak Gray Scale Culprit AMI p = NS p < p = NS p < (cm/sec) p = 0.02 Peak Circumference Peak Circumference Growth (cm) n=65 n=290 n=161 n=88 n=377 n=187 n=85 n=305 n=182 Murphy SA, Am J Cardiol 2003

Early Impaired Myocardial Perfusion is Associated with Larger SPECT Infarct Size Patients with a closed myocardium (TMPG 0/1) and patients without complete ST resolution (<70%) had larger infarcts. In a multivariate model, both impaired TMPG and incomplete ST resolution were independently associated with larger infarct size Patients with a closed myocardium (TMPG 0/1) and patients without complete ST resolution (<70%) had larger infarcts. In a multivariate model, both impaired TMPG and incomplete ST resolution were independently associated with larger infarct size n=209 n=111 p<0.001 Median = 13 TMPG ST Resolution p=0.004 Res <70% Res >70% TMPG 0/1 TMPG 2/3 n=108 n=113 Median = 7 Median = 6 Median = 14 % SPECT Infarct Size Circulation 2002

Reduction in Plaque Volume (mm 3 ) TMPG 3 Mortality 0% TMPG 3 Mortality 0% TMPG 0-2 Mortality 22% TMPG 0-2 Mortality 22% P=0.077 for mortality P=0.077 for mortality P= Greater Reduction in Plaque Area on IVUS is Associated with Impaired TIMI Myocardial Perfusion Grades (TMPG 0-2) in STEMI Kotani J,Mintz GS,Pregowski J et al for Wash Hosp Ctr, Am J Cardiol 2003; 92:728–732. N=17 N=18 Multivariate analysis indicated that the strongest predictor of a closed myocardium (TMPG 0-2) after primary PCI was a greater reduction in plaque volume on IVUS

FilterWire-Ex as an Adjunct to Primary PCI Corrected TIMI Frame Count p=0.005 Corrected TIMI Frame Count p=0.005 TIMI Frame Count Myocardial Blush Grade 3 p=0.006 Myocardial Blush Grade 3 p=0.006 Circulation 2003; 108: Design: Compared use of the FilterWire-Ex (FW) distal embolic protection device as an adjunct to primary PCI (n=53) vs matched control (n=53) in patients with acute MI. Results FW successfully positioned in 89% patients without complication FW use remained only independent predictor of ST-segment resolution (OR 0.18, 95% CI , p=0.003) and myocardial blush grade 3 (OR 0.33, 95% CI , p=0.01) All 13 filters that underwent histological analysis contained multiple embolic debris No difference in 30 day MACE rates (5% for FW vs 11% for controls, p=0.488) Design: Compared use of the FilterWire-Ex (FW) distal embolic protection device as an adjunct to primary PCI (n=53) vs matched control (n=53) in patients with acute MI. Results FW successfully positioned in 89% patients without complication FW use remained only independent predictor of ST-segment resolution (OR 0.18, 95% CI , p=0.003) and myocardial blush grade 3 (OR 0.33, 95% CI , p=0.01) All 13 filters that underwent histological analysis contained multiple embolic debris No difference in 30 day MACE rates (5% for FW vs 11% for controls, p=0.488) Filter Wire Control % ST-segment Resolution p=0.006 ST-segment Resolution p=0.006 %

Coronary Flow Reserve Antithrombin + Eptifibatide Antithrombin + Eptifibatide N=27 N=16 P=0.02 Gray per sec P=0.05 N=27 N=18 Coronary Flow Reserve Rate of Increase in DSA Brightness (Gray /sec) Rate of Increase in DSA Brightness (Gray /sec) Circumference (cm) N=24 N= P=0.18 Rate of Growth in Blush Circumference (cm / sec) Rate of Growth in Blush Circumference (cm / sec) ESPRIT Substudy: Results All Patients Have TIMI Grade 3 Flow at Completion of Stenting & Antithrombin Treatment Antithrombin + Eptifibatide Antithrombin + Eptifibatide Antithrombin + Eptifibatide Antithrombin + Eptifibatide Gibson CM et al, Am J Cardiol 2001;87(11):

TMPG and Maximum CK-MB 24 Hours Post-stent Maximum CK-MB >2x ULN (%) 41.2% p = /2414/34 4.2% All Patients Have TIMI 3 Flow at Completion of Stenting Gibson CM et al, Am Heart J Jan;143(1): Stain Slow Pale Normal

TMPG Post-stent and Composite Events by 48 Hrs & 1 Yr Composite Event (%) 1 Year Death, MI, Urgent TVR p = % 4.2% 1/24 11/34 All Patients Have TIMI 3 Flow at Completion of Stenting Stain Slow Pale Normal Gibson CM et al, Am Heart J Jan;143(1):

A Decline in TMPG after Stenting is Associated with Larger Infarct Sizes Ricciardi, Gibson et al, CCD 2004 All patients had normal epicardial TIMI Grade 3 Flow before PCI 12 of 14 patients had normal TMPG 3 before PCI Only 7 of 14 had normal TMPG 3 after PCI All patients had normal epicardial TIMI Grade 3 Flow before PCI 12 of 14 patients had normal TMPG 3 before PCI Only 7 of 14 had normal TMPG 3 after PCI CK-MB p=0.01 HE mass p=0.04 No Yes Decline in post-stent TMPG HE mass (gm) CK-MB (ng/dL) = = Ramondo et al,Catheter Cardiovasc Interv 2004;61:222–226.

Tn I (ng / mL) tn T (ng / mL) TMPG 0/1 TMPG 2/3 P=0.006 P=0.007 TMPG 2/3 TMPG 0/1 Peak [tnT] and [tnI] by TIMI Myocardial Perfusion Grade (TMPG) status Circulation 2002;106:

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

Troponin T & Angiographic Findings % Stenosis % Vessel Occlusion % Normal TMPG 3 % Thrombus tnT + tnT - P=0.021 P= 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

Event Free Survival is Associated with Tissue Level Perfusion in UA / Non Q Wave MI: TACTICS – TIMI 18 Circulation 2002;106: 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 Stain Slow Pale Normal N = 253 % TMPG 3 P = “Upstream” Duration (> median) “Upstream” Duration (> median) 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 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 Gibson CM, AHA 2001

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