1. Francesco Liistro Cardiovascular Department, Arezzo, Italy Impact of Thrombus Aspiration on Myocardial Tissue Reperfusion and Left Ventricular Functional Recovery and Remodeling after Primary Angioplasty

2. BACKGROUND  Mounting interest has emerged regarding the role of distal embolization as a major determinant of impaired myocardial perfusion after primary PCI  Previous trials have shown the feasibility of thrombus aspiration during primary PCI and its impact on outcome  However, whether improvements in myocardial reperfusion with thrombus aspiration are directly connected to better follow-up left ventricular function and geometry, features which are strongly related to short and long-term mortality, has not been clarified so far

3. Single center, prospective, randomized study Consecutive patients with ST elevation acute MI Primary endpoint:  ST-segment elevation resolution (STR) Secondary endpoints:  TIMI Myocardial Perfusion Grade (TMPG)  TIMI grade flow  Corrected TIMI Frame Count (cTFC)  Contrast enhancement by intracoronary myocardial contrast echo (MCE)  Persistent ST-segment deviation  Time-course of wall motion score index, LV ejection fraction and volumes METHODS

4. Inclusion Criteria symptoms suggesting acute myocardial ischemia lasting more than 30’ onset of symptoms < 12 hours ST-segment elevation > 0.1 mV in two or more leads Exclusion criteria rescue PCI after thrombolysis absence of an optimal echocardiographic apical view life expectancy < 6 months METHODS

5. 111 Consecutive Patients with ST-segment elevation Myocardial Infarction within 12 hours of symptoms onset undergoing primary PCI Patients Randomization 1:1 PCI Standard PCI (n=56) EXPORT (Medtronic®) (n=55) Angioplasty:TIMI flow grade cTFC TIMI Myocardial Perfusion Grade Intracoronary MCE Evaluation of regional (WMSI) and global (EF) LV function and volumes (EDVI and ESVI) within 24 hours ECG (baseline, 90 min, 6 hours) Post-PCI Evaluation of regional (WMSI) and global (EF) LV function and volumes (EDVI and ESVI) Clinical follow-up for all patients 6-months Follow-Up TRIAL FLOW CHART

6. Control 56 patients N°(%) or M±SD Export 55 patients N°(%) or M±SD P value Male sex43 (77)43 (78)>0.9 Age65±1164±110.7 Current smoker36 (64)35(63)>0.9 Diabetes7(12)11(20)0.2 Family history of CAD13 (23)21 (38)0.1 Hypertension30 (53)33 (60)0.5 Hypercholesterolemia17(30)19(34)0.6 History of CAD2(4)4(8)0.1 Creatinine (mg/dL)1.0±0.20.9±0.10.2 Killip Class ≥ 34(8)2(4)0.1 Symptom-onset-to-balloon time (min)209±147189±1050.3 Symptoms-to-door time (min)141.6±140.1112.6±97.60.2 Door-to-balloon time (min)75.9±38.775.7±33>0.9 ST Segment elevation (mm)8.1±5.48.5±5.80.7 ST Segment Deviation (mm)11.6±7.912.7±7.80.5 Baseline clinical characteristics

7. Control 56 patients N°(%) or M±SD Export 55 patients N°(%) or M±SDP value Multivessel disease21(40)26(47)0.4 Infart Related Artery (IRA): LAD26 (46)21 (38)0.1 CX7(13)6(11)0.2 RCA23(41)28(51)0.1 Lesion length (mm)13.3±5.513.2±4.50.9 RVD (mm)2.97±0.442.97±0.380.9 Basal MLD (mm)0.03±0.140.01±0.060.2 Final MLD (mm)2.86±0.62.91±0.40.1 Baseline TIMI-0-143(76)38(69)0.4 Stented patients56(100)55(100)>0.9 Direct Stenting5(9)12(21)0.1 Complete revascularization35(62)29(53)0.3 Distal Embolization14(25)4(7)0.01 Final TIMI 346(82)53(96)0.02 Corrected TIMI Frame Count25.9±12.421.6±9.70.04 Angiographic no reflow10(18)2(4)0.02 Angiographic and Procedural Characteristics

8. Tissue level perfusion RESULTS Control Thrombus- Aspiration

9. Myocardial Contrast Echocardiography RESULTS Control Thrombus- Aspiration

10. Time Course of Changes in Left Ventricular Ejection Fraction in the two study groups RESULTS *P value according to repeated-measures ANOVA *p<0.0001

11. Time Course of Changes in Wall Motion Score Index in the two study groups RESULTS *P value according to repeated-measures ANOVA

12. Time Course of Changes in Left Ventricular End Diastolic Volume Index in the two study groups RESULTS *p=0.001 *P value according to repeated-measures ANOVA

13. Time Course of Changes in Left Ventricular End Sistolic Volume Index in the two study groups RESULTS *p<0.001 *P value according to repeated-measures ANOVA

14. 6-months clinical follow-up Control 56 patients N°(%) Export 55 patients N°(%)P value Cardiac Death01(2)0.5 Re-Myocardial Infarction3(5) >0.9 Stent Acute Thrombosis2(3.5)1(1.8)>0.9 Ischemia Driven TLR4(7) >0.9 MACE7(12)8(14)0.8 6-months re-admission for congestive HF3(5)00.2 RESULTS

15. Manual thrombus aspiration in the setting of primary PCI improves myocardial reperfusion as assessed by myocardial blush, myocardial contrast enhancement by intracoronary MCE and ST-segment resolution. The improvement in tissue-level perfusion is paralleled by a significant improvement in regional and global LV function and a significant reduction of LV remodeling at 6 months. This study provides the pathophysiological missing link between thrombus removal, tissue level perfusion, LV remodeling and clinical outcome. CONCLUSIONS