Dye strongly persistent Other Angiographic Efficacy Endpoint: 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 6.2% 5.1% Mortality (%) p = 0.05 4.4% Lecture Notes: While the TIMI flow grades and the TIMI frame count assess flow in the epicardial arteries, the TIMI Myocardial Perfusion Grades (TMPG) assesses flow at the tissue level. Views are chosen to minimize superimposition of non-infarcted territories in the assessment of the culprit artery’s TMP Grade. The duration of cinefilming should be equal to or exceed 3 cardiac cycles in the washout phase to assess the washout of the myocardial blush. Care should be taken not to mistake filling of the venous system such as the great cardiac vein as blush. Blush is assessed during the same phase of the cardiac cycle as it may be less intense during diastole. TIMI Myocardial Perfusion Grade 0: Failure of dye to enter the microvasculature. Either minimal or no ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit artery indicating lack of tissue level perfusion. TIMI Myocardial Perfusion Grade 1: Dye slowly enters but fails to exit the microvasculature. There is the ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit lesion that fails to clear from the microvasculature, and dye staining is present on the next injection (approximately 30 seconds between injections). TIMI Myocardial Perfusion Grade 2: Delayed entry and exit of dye from the microvasculature. There is the ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit lesion that is strongly persistent at the end of the washout phase (i.e. dye is strongly persistent after 3 cardiac cycles of the washout phase and either does not or only minimally diminishes in intensity during washout). TIMI Myocardial Perfusion Grade 3: Normal entry and exit of dye from the microvasculature. There is the ground glass appearance (“blush”) or opacification of the myocardium in the distribution of the culprit lesion that clears normally, and is either gone or only mildly/moderately persistent at the end of the washout phase (i.e. dye is gone or is mildly/moderately persistent after 3 cardiac cycles of the washout phase and noticeably diminishes in intensity during the washout phase), similar to that in an uninvolved artery. Blush that is of only mild intensity throughout the washout phase but fades minimally is also classified as grade 3. References: Gibson CM, et al. Circulation. 2000;101:125-130 2.0% n = 203 n = 46 n = 79 n = 434 Gibson et al, Circulation 2000 Neumann F-J, Blasini R, Schmitt C, et al. Effect of glycoprotein IIb/IIIa receptor blockade on recovery of coronary flow and left ventricular function after the placement of coronary-artery stents in acute myocardial infarction. Circulation. 1998;98:2695-2701.

Not All TIMI Grade 3 Flow is Created Equally: Among Patients. With Successful Lysis, There is a 7 Fold Range in Mortality P = 0.007 5.4% 2.9% % Mortality 0.7% Lecture Notes This slide illustrates that not all TIMI Grade 3 flow is created equally. Every patient shown here had successful reperfusion with TIMI Grade 3 Flow. However, if the myocardium was occluded (TMPG Grades 0/1 on the right), the mortality remained elevated at 5.4%. It is not until both the epicardial artery and the myocardium are open (TMPG 3 shown on the far left), that the mortality was lowest in acute MI, below 1%. References: Gibson CM, et al. Circulation. 2000;101:125-130 N = 278 N = 136 N = 34 Myocardial Perfusion Grade 3 Myocardial Perfusion Grade 2 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 Lecture Notes While 90 minute TIMI Flow Grades (TFG), Corrected TIMI Frame Counts (CTFC) and TIMI Myocardial Perfusion Grades (TMPG) have been associated with 30 day outcomes, we hypothesized that these indices would be related to long term outcomes following thrombolytic administration. As a substudy of the TIMI 10B trial (tPA vs TNK), 49 centers carried out 2 year follow-up. TIMI Grade 2/3 Flow (Cox Hazard Ratio, HR = 0.41, p=0.001), reduced CTFCs (faster flow, p=0.02) and an open microvasculature (TMPG 2/3) (HR = 0.51, p=0.038) were all associated with improved 2 year survival. Rescue percutaneous coronary intervention (PCI) of closed arteries (TFG 0/1) at 90 minutes was associated with reduced mortality (p=0.03) and mortality trended lower with adjunctive PCI of open (TFG 2/3) arteries (p=0.11). In a multivariate model correcting for previously identified correlates of mortality (age, gender, pulse, LAD infarction, and any PCI during initial hospitalization), patency (TFG 2/3) (HR=0.32, p<0.001), CTFC (p=0.01) and TMPG 2/3 remained associated with reduced mortality (HR=0.46, p=0.02). Both improved epicardial flow (TFG 2/3 and low CTFCs) and tissue level perfusion (TMPG 2/3) at 90 minutes after thrombolytic administration are independently associated with improved 2 year survival, suggesting complementary mechanisms of improved long-term survival. While rescue PCI reduced long-term mortality, improved microvascular perfusion (TMPG 2/3) before PCI was also related to improved mortality independent of epicardial blood flow and the performance of rescue or adjunctive PCI. Further prospective trials are warranted to re-examine the benefit of early PCI with thrombolysis. 1. Gibson CM, Cannon CP, Murphy SA, Marble SJ, Barron HV, Braunwald E for the TIMI Study Group. Relationship of the TIMI Myocardial Perfusion Grades, TIMI Flow Grades and TIMI Frame Count to Long Term Outcomes Following Thrombolytic Administration. Circulation, 2002, in press. Gibson et al, Circulation 2002

Myocardial Perfusion After Primary PCI is Strongest Predictor of Mortality Myocardial Blush Grades 100 90 360 900 1440 2250 2790 3 n=148 2 95 n=393 3 0/1 90 n=236 Cumulative Survival (%) Final Blush Score (patients with final TIMI grade 3 flow) 2 85 Time (days) van ‘t Hof AWJet al. Circulation 1998; 97:2302-6. Blush 1-Year Mortality 0/1 3 6.8% 80 Relation of Myocardial Perfusion Grade to Mortality 2 13.2% P=0.004 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% Death during F/U 39.0% 18.3% 12.4% 0/1 18.3% 75 2 4 6 8 10 12 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 Haagar PK, et al. J Am Coll Cardiol. 2003;41:532-538 2 of 3 pts have a closed muscle after 10 PCI Mortality goes up 3 fold Henriques JP, et al. Circulation. 2003;107:2115-2119.

Myocardial Blush and Mortality: CADILLAC Results Costantini, J Am Coll Cardiol 2004;44:305–12

Independent Contribution of Myocardial Blush and ST Resolution to Survival The myocardial blush and ST resolution following primary PCI are independently related to long term survival in acute myocardial infarction Hagger et al, J Am Coll Cardiol, 2003

Further Risk Stratification Provided by the TMPG among Patients with TIMI 3 Flow or TIMI 2/3 flow Martinez-Rios MA, Am J Cardiol 2004;93:280–287.

Combining TIMI Flow and Perfusion Grades Martinez-Rios MA, Am J Cardiol 2004;93:280–287.