1. STOPAMI 1 & 2 Predictive Factors and Impact of No-Reflow After Primary Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction Gjin Ndrepepa, Klaus Tiroch, Dritan Keta, Massimiliano Fusaro, Melchior Seyfarth, Jürgen Pache, Julinda Mehilli, Albert Schömig, Adnan Kastrati Deutsches Herzzentrum München, Technische Universität, Munich, Germany 1

2. STOPAMI 1 & 2 Objectives of the Study The Relationship Between No-reflow and Myocardial Salvage Quantified by Scintigraphic Studies Before and after Primary PCI Predictive Factors of No-reflow after Primary PCI The Persistence or Resolution of No-reflow in the 6-month Angiography The Impact of No-reflow on the Left Ventricular Function at 6 Months and One-year Mortality 2

3. STOPAMI 1 & 2 Methods Baseline Tc-sestamibi Scintigraphy Primary Percutaneous Coronary Intervention (PCI) Tc-sestamibi Scintigraphy 7-14 Days After PCI 6-Month Coronary Angiography One-year Follow-up 1140 Patients with Acute ST-Segment Elevation Myocardial Infarction (STEMI) 3

4. STOPAMI 1 & 2 Diagnosis of No-reflow and Outcomes Diagnosis: 1.Angiographic Evidence of Re-opening of Occluded Coronary Artery with no Evidence of Flow-limiting Residual Stenosis. 2.Angiographic Documentation of TIMI Flow Grade ≤ 2, at Least 10 Minutes after the End of PCI Procedure Outcomes: Primary Outcome: One-year Mortality Secondary Outcomes: - Amount of Myocardial Salvage - Predictive factors of No-reflow - Left Ventricular Ejection Fraction at 6 Months after Primary PCI 4

5. STOPAMI 1 & 2 Scintigraphic Parameters I nitial Area at Risk: Perfusion Defect in the Baseline Scintigraphy (% of the Left Ventricle) Infarct Size: Perfusion Defect in the 7-14 Days Scintigraphy (% of the Left Ventricle) Absolute Salvage: Initial Area at Risk Minus Infarct Size (% of the Left Ventricle) Salvage index: Initial Area at Risk Minus Infarct Size Divided by Initial Area at Risk (Proportion of Salvaged Initial Area at Risk). 5

6. STOPAMI 1 & 2 Differences in Baseline Characteristics 6

7. STOPAMI 1 & 2 Angiographic Data Type of intervention 0.96 Stenting 88 (81.5) 843 (81.7) Balloon angioplasty 20 (18.5) 189 (18.3) Pre-procedural abciximab therapy 84 (77.8) 800 (77.5) 0.95 Data are median [25th; 75th percentiles] or number of patients (%) 7

8. STOPAMI 1 & 2 Scintigraphic Data VariableNo-reflow (n =108) Reflow (n =1032) P value Initial Area at Risk (% of LV)26.0 [18.5; 52.5] 24.0 [14.0; 40.0] 0.008 Infarct Size at 7-14 days (% of LV)18.9 [10.3; 33.8] 9.1 [3.0; 20.9] <0.001 Absolute Salvage (% of LV)9.8 [5.3; 16.3] 12.0 [5.0; 21.0] 0.04 Salvage Index0.34 [0.15; 0.49] 0.55 [0.29; 0.81] <0.001 Data Are Median [Interquartile Range] 8

9. STOPAMI 1 & 2 Salvage Index 0 10 20 30 40 50 60 0 10 20 30 40 50 60 % of Left Ventricle P=0.008 No-reflow Reflow P<0.001 No-reflow Reflow Initial Area at Risk Final Infarct Size 9

10. STOPAMI 1 & 2 Salvage Index 0 0.2 0.4 0.6 0.8 1.0 Reflow (TIMI Grade 3) No-reflow (TIMI Grade ≤2) Salvage index P<0.001 Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. 10

11. STOPAMI 1 & 2 Predictors of No-reflow Variable Unadjusted Odds Ratio [95% Confidence Interval] Adjusted Odds Ratio [95% Confidence Interval] Previous myocardial infarction 1.71 [1.02-2.88]2.17 [1.18-3.99] C-reactive protein (for 1mg/L increase) 1.02 [1.01-1.03]1.02 [1.01-1.04] Baseline TIMI flow grade (for 1 grade decrease) 1.98 [1.52-2.57]2.02 [1.47-2.76] Initial area at Risk (for 5% of the LV increase) 1.10 [1.04-1.16]1.07 [1.01-1.13] 11

12. STOPAMI 1 & 2 No-reflow (TIMI 0-2) (n =76) Reflow (TIMI 3) (n = 867) TIMI Flow Grade in the 6-Month Angiography Suboptimal Flow (TIMI 0-2) (n =121) Normal Flow (TIMI 3) (n = 822) 761 (87.8%) 61 (80.3%) 106 (12.2%) 15 (19.7%) Post-primary PCI TIMI Flow Grade Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. Time-course of TIMI Flow 12

13. STOPAMI 1 & 2 Left ventricular Ejection Fraction at 6 Months After PCI Reflow No-reflow 0 2 3 4 5  EF at 6 months P=0.005 -15 -10 0 5 15  EF at 6 months Resolution of No-reflow Persistence of No-reflow P=0.002 % 1 10 -5 Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. 13

14. STOPAMI 1 & 2 One-year Survival 100 70 75 80 85 90 95 0123456789101112 Months Numbers at Risk No-reflow Reflow 10895 90888786 10321003990976 959 943 929 Probability of survival (%) Hazard Ratio = 3.35, 95 CI 1.97-5.69; P<0.001 Reflow (5.5%) No-reflow (16.7%) Ndrepepa et al. Circ Cardiovasc Interv. 2010;3-27-33. 14

15. STOPAMI 1 & 2 Predictors of One-Year Mortality 15

16. STOPAMI 1 & 2 Main Findings and Conclusions No-Reflow after Primary PCI is Associated with Considerable Reduction of the Myocardial Salvage, Worse Left Ventricular Function and Increased One-Year Mortality Independent Predictors of No-reflow were: - Absence of Residual Blood Flow in the Infarct-Related Artery - Large Infarct Size - Previous Myocardial Infarction - Elevated Level of C-reactive Protein Normalization of Blood Flow Occurs in 80% of Patients 6 Months After Primary PCI Resolution of Blood Flow is Associated with Significantly Better Left Ventricular Function Compared with Persistence of No-reflow 6 Months after Primary PCI 16