Beyond TIMI 3 Flow 5 10 15 Risk

Beyond TIMI 3 Flow 5 10 15 % Risk of In Hospital Mortality 0 21 Reproducibility: r = 0. 97 between readers Accuracy: r=0. 88 vs Doppler velocity 6. 2% p= 0. 003 2. 8% 0. 0% (n=41) CTFC < 14 (n = 18/640) (n =35/563) 14 < CTFC < 40 CTFC > 40 “TIMI 4” Flow TIMI 3 Flow Hyperemic Flow Gibson, Circulation 1999; 99: 1945 -1950

Mortality (%) TIMI Myocardial Perfusion (TMP) Grades TMP Grade 3 TMP Grade 2 TMP Grade 1 TMP Grade 0 Normal ground glass appearance of blush Dye mildly persistent at end of washout Dye strongly persistent at end of washout Gone by next injection Stain present Blush persists on next injection No or minimal blush p = 0. 05 4. 4% 6. 2% 5. 1% 2. 0% n = 203 n = 46 n = 79 n = 434 Gibson et al, Circulation 2000

Not All TIMI Grade 3 Flow is Created Equally: Among Patients. With Successful Lysis, There is a 7 Fold Range in Mortality % Mortality P = 0. 007 5. 4% 2. 9% 0. 7% N = 136 N = 34 Myocardial Perfusion Grade 3 Myocardial Perfusion Grade 2 N = 278 Myocardial Perfusion Grades 0/1 Gibson CM, et al. Circulation. 2000; 101: 125 -130.

TIMI 10 B: Independent Predictors of 2 Year Mortality Pre-PCI Epicardial and Myocardial Flow Are Independently Associated with 2 Year Mortality • TIMI Grade 3 Flow RR 0. 61, p=0. 047 • TIMI Myocardial Blush RR 0. 50, p = 0. 038 In a MV model correcting for : Performance of PCI Age Gender Pulse Anterior MI Gibson et al, Circulation 2002

Myocardial Reperfusion Score Zwolle Myocardial Blush Grades (n=777) TIMI Flow Grades Myocardial Blush Grades Survival 1. 0 n=690 0. 9 0. 8 3 n=55 2 0. 7 n=148 n=393 p<0. 0001 3 2 n=236 p<0. 0001 n=32 0. 6 0. 5 0/1 90 360 900 1440 2250 2790 Time (days) van ‘t Hof AWJet al. Circulation 1998; 97: 2302 -6.

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

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

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

Myocardial Perfusion After Primary PCI is Strongest Predictor of Mortality Cumulative Survival (%) 95 3 90 2 85 Blush 1 -Year Mortality 3 2 0/1 80 75 0 2 6. 8% 13. 2% 18. 3% 4 0/1 P=0. 004 6 8 10 12 Final Blush Score (patients with final TIMI grade 3 flow) 100 Stone GW, et al. J Am Coll Cardiol. 2002; 39: 591 -597. Independent Angiographic Variables as Risk Factors of Long-Term Mortality in Patients With TIMI Grade 3 flow After Angioplasty RR* 95% CI P MBG 0 and 1 vs 2 and 3 2. 9 1. 4 to 5. 8 0. 003 MVD 2 and 3 vs 1 2. 3 1. 1 to 4. 7 0. 02 LAD vs non-LAD MI 2. 2 1. 1 to 4. 4 0. 03 TIMI flow before: 0 to 2 vs 3 1. 8 0. 5 to 6. 1 0. 31 Henriques JP, et al. Circulation. 2003; 107: 2115 -2119. Myocardial Blush Grades 3 2 0/1 90 360 900 1440 Time (days) n=148 n=393 n=236 2250 2790 van ‘t Hof AWJet al. Circulation 1998; 97: 2302 -6. Relation of Myocardial Perfusion Grade to Mortality Death at 30 days Death at 1 year Death during F/U MBG 0/1 (n=100) 26. 0% MBG 2 (n=74) 9. 9% MBG 3 (n=79) 3. 9% P <0. 001 35. 1% 13. 4% 9. 4% <0. 001 39. 0% 18. 3% 12. 4% <0. 001 Haagar PK, et al. J Am Coll Cardiol. 2003; 41: 532 -538 § 2 of 3 pts have a closed muscle after 1 PCI 0 § Mortality goes up 3 fold

Peak Myocardial Brightness, Circumference and Circumference Growth in Culprit and Non-culprit Arteries in Acute MI and in Normal Patients Culprit AMI Non-culprit AMI Normal p < 0. 0001 p = 0. 02 (cm) (cm/sec) p = NS n=65 n=290 n=161 n=88 n=377 n=187 DSA Peak Gray Scale Peak Circumference n=85 n=305 n=182 Peak Circumference Growth Murphy SA, Am J Cardiol 2003

Early Impaired Myocardial Perfusion is Associated with Larger SPECT Infarct Size p=0. 004 % SPECT Infarct Size Median = 13 p<0. 001 Median = 14 Median = 7 Median = 6 n=108 TMPG 0/1 n=113 TMPG 2/3 TMPG n=209 n=111 Res <70% Res >70% 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 ST Resolution Circulation 2002

Reduction in Plaque Volume (mm 3) Greater Reduction in Plaque Area on IVUS is Associated with Impaired TIMI Myocardial Perfusion Grades (TMPG 0 -2) in STEMI TMPG 3 TMPG 0 -2 Mortality 0% Mortality 22% P=0. 077 for mortality 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 P=0. 0039 N=17 Kotani J, Mintz GS, Pregowski J et al for Wash Hosp Ctr, Am J Cardiol 2003; 92: 728– 732.

Myocardial Blush Grade 3 p=0. 005 p=0. 006 Filter Wire ST-segment Resolution p=0. 006 % Corrected TIMI Frame Count % TIMI Frame Count Filter. Wire-Ex as an Adjunct to Primary PCI Design: Compared use of the Filter. Wire-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 0. 060. 56, p=0. 003) and myocardial blush grade 3 (OR 0. 33, 95% CI 0. 13 -0. 81, 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) Control Circulation 2003; 108: 171 -176

ESPRIT Substudy: Results All Patients Have TIMI Grade 3 Flow at Completion of Stenting & Antithrombin Treatment Coronary Flow Reserve Rate of Increase in DSA Rate of Growth in Brightness (Gray /sec) Blush Circumference 1. 78 + 0. 95 (cm / sec) 7. 30 + 8. 13 1. 28 + 0. 4 N=27 Antithrombin Circumference (cm) P=0. 05 Gray per sec Coronary Flow Reserve P=0. 02 N=16 Antithrombin + Eptifibatide 3. 97 + 2. 46 N=27 Antithrombin N=18 Antithrombin + Eptifibatide P=0. 18 8. 5 + 4. 0 7. 2+ 3. 2 N=32 Antithrombin N=24 Antithrombin + Eptifibatide Gibson CM et al, Am J Cardiol 2001; 87(11): 1293 -5.

TMPG and Maximum CK-MB 24 Hours Post-stent All Patients Have TIMI 3 Flow at Completion of Stenting Maximum CK-MB >2 x ULN (%) p = 0. 002 41. 2% Slow Stain 4. 2% 1/24 Normal 14/34 Pale Gibson CM et al, Am Heart J. 2002 Jan; 143(1): 106 -110.

TMPG Post-stent and Composite Events by 48 Hrs & 1 Yr All Patients Have TIMI 3 Flow at Completion of Stenting 1 Year Death, MI, Urgent TVR 32. 4% Composite Event (%) p = 0. 01 Slow Stain 4. 2% 1/24 Normal 11/34 Pale Gibson CM et al, Am Heart J. 2002 Jan; 143(1): 106 -110.

A Decline in TMPG after Stenting is Associated with Larger Infarct Sizes = CK-MB p=0. 01 HE mass p=0. 04 4 40 3 30 2 20 1 10 0 0 No HE mass (gm) CK-MB (ng/d. L) 50 Ramondo et al, Catheter Cardiovasc Interv 2004; 61: 222– 226. 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 Yes Decline in post-stent TMPG Ricciardi, Gibson et al, CCD 2004

Peak [tn. T] and [tn. I] by TIMI Myocardial Perfusion Grade (TMPG) status P=0. 007 tn T (ng / m. L) Tn I (ng / m. L) P=0. 006 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. 013 % TMPG 0/1 p=0. 004 Circulation 2002; 106: 202 -207

Troponin T & Angiographic Findings P=0. 021 tn. T - tn. T + P=0. 0003 tn. T - tn. T + % Normal TMPG 3 % Vessel Occlusion % Stenosis % Thrombus P=0. 007 P=0. 03 tn. T - tn. T + Even when epicardial TIMI flow grade and the presence of thrombus were adjusted for, the presence of a closed microvasculature was independently associated with tn. T 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 Event Free Survival TMPG 2/3 Pre or Post-PCI p=0. 026 % TMPG 3 P = 0. 018 Slow Normal N = 253 “Upstream” Duration TMPG 0/1 Pre & (> median) Post PCI Stain Pale Gibson CM, AHA 2001 • Impaired tissue perfusion on diagnostic cath is associated with Tn + and adverse outcomes Days Circulation 2002; 106: 202 -207 • Earlier upstream initiation of GPIIb. IIIa inhibition is associated with improved tisse perfusion om diagnostic cath

Troponin Elevations on Admission are Associated with Tissue Level Perfusion Following PCI: TACTICS TIMI 18 p=0. 013 % TMPG 0/1 p=0. 004 Circulation 2002