1. Effect of Intracoronary Streptokinase Administered Immediately after Primary PCI on Left Ventricular Infarct Size, Volume and Function (J Am Coll Cardiol 2009;54:1065–71) Murat Sezer, Arif Cimen, Emre Aslanger, Ali Elitok, Berrin Umman, Zehra Buğra, Ebru Yormaz, Cüneyt Türkmen, Isık Adalet, Yılmaz Nişancı, Sabahattin Umman Istanbul University, Istanbul Faculty of Medicine, Department of Cardiology

2. It has been previously shown that, complementary intracoronary streptokinase (250 kU) infusion immediately after primary PCI significantly improves microvascular perfusion. It has been previously shown that, complementary intracoronary streptokinase (250 kU) infusion immediately after primary PCI significantly improves microvascular perfusion. Sezer et al, et al. NEJM 2007; 356(18): 1823-1834 The purpose of this study is to investigate the reflections of the improvement in microvascular perfusion provided The purpose of this study is to investigate the reflections of the improvement in microvascular perfusion provided by complementary intracoronary streptokinase (ICSK) on late-phase infarct size and left ventricular volumes and functions. Background: Objective:

3. Patients and Randomization Immediately after diagnostic angiography eligible patients (n =95) were randomized to ICSK group (n=51)Control group (n=44) (Primary PCI + 250 kU intracoronary streptokinase) (primary PCI) (Primary PCI + 250 kU intracoronary streptokinase) (primary PCI) All patients recieved: All patients recieved: - 300 mg of aspirin, - A loading dose of 600 mg of clopidogrel, - Intracoronary unfractioned heparin at a dose of 100 U/kg during the procedure, - Tirofiban as a bolus of 0.1 μg/kg in 3 minutes followed by continuous infusion of 0.15 μg/kg/min for 12 hours, and - Low molecular weight heparin initiated four to five hours after primary PCI and continued for at least 48 hours

4. All patients underwent intracoronary hemodynamic measurement and angiographic analysis two days after primary PCI to evaluate microvascular function ST segment resolution Diastolic deceleration time Echocardiographic assessment of left ventricular volumes and function Coronary flow reserve Index of microvascular resistance Myocardial blush grades Corrected TIMI frame count Assesing microvascular perfusion and LV volumes in early phase of STEMI Control angiography (TIMI frame count, Myocardial blush grade) Infarct size measurement (SPECT), Echocardiographic assessment of left ventricular volumes and function Long term assesments (at 6 months) Transthoracic echocardiography, 2 days after AMI Second angiography and intracoronary hemodynamic measurements 2 days after AMI. Study Design

5. Thermodilution-derived Coronary Flow Reserve (CFR)* Thermodilution-derived Coronary Flow Reserve (CFR)* = Resting mean transit time / hyperemic mean transit time = Resting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486 Index of Microvascular Resistance (IMR)**: Index of Microvascular Resistance (IMR)**: = Distal coronary pressure x hyperemic mean transit time **Fearon WF. et al.. Circulation. 2003;107:3129-3132 Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Thermodilution-derived Coronary Flow Reserve (CFR)* Thermodilution-derived Coronary Flow Reserve (CFR)* = Resting mean transit time / hyperemic mean transit time = Resting mean transit time / hyperemic mean transit time *Pijls NHJ et al.. Circulation 2002;105:2482-2486 Index of Microvascular Resistance (IMR)**: Index of Microvascular Resistance (IMR)**: = Distal coronary pressure x hyperemic mean transit time **Fearon WF. et al.. Circulation. 2003;107:3129-3132 Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Coronary Wedge Pressure (CWP) and Pressure-derived Collateral Flow Index (CFIp): = CWP/Pa Microvascular Perfusion Indices:

6. Primary End Point: Long-term (6 months) infarct size (by SPECT) Secondary End Points: Long- term (6 months) left ventricular volumes and ejection fraction, Major adverse cardiac events (reinfarction, revascularization, death)

7. RESULTS

8. Comparison of the invasive and noninvasive measures of microvascular perfusion. MeasureMultivariateLAD Subgroup ICSK GroupControl Group p ICSK (N:27)Control (N:24) p IMR At 2nd day (U)20.2 (14.3 to 26.2)34.2 (27.9 to 40.4)<0.00118.2 + 6.4(24) 33.7 + 11.1<0.001 CFR At 2nd Day2.5 (2.1 to 3.0)1.7 (1.3 to 2.1)<0.0012.4 + 0.91.6 + 0.5<0.001 CTFC, mean IA Primary PCI32.4 (27.8 to 37.0)32.4 (27.5 to 37.3)0.99731.7 + 10.433.7 + 8.80.451 At 2nd Day20.7 (17.1 to 24.3)29.2 (25.3 to 33.1)<0.00121.4 + 7.031.0 + 7.4<0.001 At 6th Months21.5 (16.7 + 26.3)27.8 (22.6 + 33.0)0.00120.7 + 7.030.2 + 9.70.001 DDT in the LAD (msec) at 2nd day 732 (429 to 1035)399 (91 to 706)0.002(23) 811 + 270(21) 489 + 3580.002 STR 90 minutes after primary PCI 81.3 (65.7 to 96.9)74.9 (59.0 to 90.8)0.28358.3+30.754.5 + 21.60.613 Comparison of ICSK and Control groups with regard to microvascular functions: IMR= Index of microvascular resistance, CFR: Coronary flow reserve, DDT: Diastolic deceleration time, STR: ST resolution, CTFC: Corrected TIMI frame count

9. Left Ventricular Volumes and Ejection Fraction at 2 Days and 6 Months and Infarct Size at 6 Months. MeasureMultivariate Analysis ICSK GroupControl GroupP Value Mean (95% CI) End-systolic volume (ml) 2 days after primary PCI47.1 (37.2 to 57.2)58.0 (47.4 to 68.7)0.077 6 mo after primary PCI41.1 (26.4 to 55.8)60.9 (45.1 to 76.8)0.009 End-diastolic volume (ml) 2 days after primary PCI101.1 (86.9 to 115.3)110.9 (95.9 to 125.9)0.101 6 mo after primary PCI95.5 (74.5 to 116.5)118.3 (95.6 to 141.0)0.006 Left ventricular ejection fraction (%) 2 days after primary PCI53.5 (49.0 to 58.1)50.3 (45.5 to 55.1)0.097 6 mo after primary PCI57.2 (51.4 to 63.0)51.8 (47.6 to 58.1)0.018 Infarct size at 6 months (%)22.7 (15.0 to 30.4)32.9 (24.9 to 41.0)0.003 Plus–minus values are means ± SD. ICSK denotes intracoronary streptokinase, CI confidence interval, PCI percutaneous coronary intervention. Infarct size was determined by single-photon-emission computed tomography

11. Conclusion Low-dose ICSK administered immediately after primary PCI improves microvascular perfusion, decreases long-term infarct size and improves LV volumes and function. Low-dose ICSK administered immediately after primary PCI improves microvascular perfusion, decreases long-term infarct size and improves LV volumes and function. These positive effects on main determinants promise parallel changes in long term clinical outcomes. These positive effects on main determinants promise parallel changes in long term clinical outcomes.