1. Clinical Trial Results. org C. Michael Gibson, M.S., M.D. Director TIMI Data Coordinating Center Invasive Cardiologist Beth Israel Deaconess Medical Center & Chief of Clinical Research Associate Professor of Medicine, Harvard Medical School The Pathophysiology of Myocardial Perfusion

2. Clinical Trial Results. org Closed Muscle on Angiogram During Life Closed Muscle on Angiogram After Death Erling Falk et al. Circulation 1985; 71: 699-708 Closed Muscle in Life and Death Gibson CM, 2006

3. Clinical Trial Results. org Pathophysiology of Downstream Microvascular Obstruction Platelet / fibrin aggregates (micro embolii) Platelet / fibrin aggregates (micro embolii) Swelling and edema of endothelial and myocardial cells Swelling and edema of endothelial and myocardial cells Neutrophil plugging Neutrophil plugging Capillary leak Capillary leak

4. Clinical Trial Results. org 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 = 79 5.1% 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

5. Clinical Trial Results. org The Goal is to Restore Both Normal Epicardial & Normal Myocardial Blood Flow 3.7% n = 487 n = 328 Epicardial TIMI Grade 3 Flow Epicardial TIMI Grade 2 / 1 / 0 Flow Myocardial Perfusion Grade 3 Myocardial Perfusion Grade 3 p = 0.05 2.9% n = 136 5.4% n = 279 7.5% n = 64 4.7% n = 226 5 way p = 0.007 Mortality (%) n = 34 0.7% Myocardial Perfusion Grade 2 Myocardial Perfusion Grade 2 Myocardial Perfusion Grades 0/1 Myocardial Perfusion Grades 0/1 Myocardial Perfusion Grade 3 Myocardial Perfusion Grade 3 Myocardial Perfusion Grades 2/1/0 Myocardial Perfusion Grades 2/1/0 7.0% Gibson et al, Circulation 2000

6. Clinical Trial Results. org Myocardial Perfusion & Mortality: 8 Years of Follow-Up 90 360 900 1440 2250 2790 0/1 n=236 2 n=393 3 n=148 Time (days) van ‘t Hof AWJet al. Circulation 1998; 97:2302-6. Survival  Majority of patients have TIMI Grade 3 flow in epicardial artery after primary PCI However  2 of 3 pts have a cosed muscle after 0 primary PCI  Majority of patients have TIMI Grade 3 flow in epicardial artery after primary PCI However  2 of 3 pts have a cosed muscle after 0 primary PCI

7. Clinical Trial Results. org Two Chamber View Abn TMPG = 8 X Risk Of HE (p = 0.02) Circulation. 2006;114:662-669.

8. Clinical Trial Results. org MRI Hyperenhancement and Troponin Release After PCI 37% of patients had tn elevation after PCI, all had hyperenhancement on MRI 37% of patients had tn elevation after PCI, all had hyperenhancement on MRI 63% had no tn elevation and none of these pts had hyperenhancement on MRI 63% had no tn elevation and none of these pts had hyperenhancement on MRI Tn elevation was proportional to grams of MRI enhancement Tn elevation was proportional to grams of MRI enhancement Loss of myocardium was 5% of muscle mass Loss of myocardium was 5% of muscle mass Selvanayagam, Circulation. 2005;111:1027-1032.

9. Clinical Trial Results. org Early Impaired Myocardial Perfusion is Associated with Larger SPECT Infarct Size & Poorer Salvage Median = 7 p=0.004 TMPG 2/3 TMPG 0/1 n=108 n=113 Median = 13 % SPECT Infarct Size Angeja et al; Circulation 2002 In a multivariate model, TMPG 2/3 remained independently associated with a higher salvage index (p=0.001) Dibra et al, JACC 2003:41: 925-929

10. Clinical Trial Results. org Poorer TMPG is Associated with Higher Coronary Wedge Pressure (Pressure Distal to Stenosis) and Higher Pulmonary Capillary Wedge Pressure Coronary Wedge Pressure Closed TMPG 0/1 Closed TMPG 0/1 Open TMPG 2/3 Open TMPG 2/3 28 mm Hg 9 mm Hg K P Balachandran et al; Heart. 2004;90: 1450-1454. p=0.001 Closed TMPG 0/1 Closed TMPG 0/1 Open TMPG 2/3 Open TMPG 2/3 p=0.02 % with PA wedge > 18 mm Hg 56% 44% Kirtane AJ et al; J Thromb Thrombolysis.2004;17:177-84

11. Clinical Trial Results. org Wire Passage in STEMI Can Be Associated with Staining (TMPG 1) Gibson 2004