1. MUSTELA : A Prospective, Randomized Trial of Thrombectomy vs. no Thrombectomy in Patients with ST-Segment Elevation Myocardial Infarction and Thrombus-Rich Lesions Anna Sonia Petronio, MD Cardiothoracic and Vascular Department, University of Pisa

2. I, Anna Sonia Petronio, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. Vlaar P. et al, Lancet 2008; 371: 1915–20

4. TrialMBG ≥ 2TIMI 3No-reflow Slow flow MACEInfarct sizeSTRMVO AIMI jacc 2006 91.8% P=0.02 6.7% P=0.01 12.5% P=0.03 EMERALD Jama 2006 10.0% P=0.66 12.0% P=0.15 63.3% P=0.78 31.5% P=0.0005 DEAR-MI Jacc 2006 88% p=0.0001 89% P>0.20 3% P=0.04 68% p 0.05 EXPIRA Jacc 2009 88% p=0.001 64% p 0.001 JETSTENT Jacc 2010 80.6% P>0.20 11.2% p 0.011 11.8% P>0.20 85.8% p 0.043 VAMPIRE Jacc Card Int 2011 46.0% P=0.001 12% P=0.07 12.9% P=0.05

5. Study design First MI with high thrombotic burden Randomization 1:1 to thrombectomy (Rheolityc/Manual) Clopidogrel 600 mg oral load before PCI Abciximab administration during PCI Stratification for anterior wall MI

6. Cardiothoracic Dept, University of Pisa Cardiothoracic Dept, University of Pisa Cardiology Unit, Pisa General Hospital Cardiology Unit, Pisa General Hospital CathLabsCathLabs Monasterio Foundation- CNR, Pisa Monasterio Foundation- CNR, Pisa MRIMRI Monasterio Foundation-CNR, Massa Monasterio Foundation-CNR, Massa

7. STEMI with symptom onset <12 hours (ST elevation ≥ 2 mm in at least 2 contiguous leads or new LBB block) High thrombus burden (TIMI thrombus grade ≥3) at diagnostic angiography No contraindications to abciximab treatment Written informed consent

8. Previous MI in the same ventricular wall Recent PCI (<2 weeks) STEMI with cardiogenic shock Contraindications to abciximab Contraindications to MRI

9. 1.Infarct size at 3 months (assessed with delayed-enhancement MRI) 2.ST-segment elevation resolution >70% at 60 minutes after primary PCI

10. 1.Microvascular obstruction (3-month MRI) 2.Infarct transmurality (3-month MRI) 3.DysHomogeneous scar (3-month MRI) 4.Postprocedural TIMI flow grade 5.Postprocedural TIMI myocardial perfusion grade 6.MACE-free survival at 1 year

12. viable No-reflow Non viable

13. Voxel containining only scar tissue Voxel containing only viable myocites

14. Islands of viable myocardium with a scar core or diffuse small scars Voxel containing only viable myocites

15. Left ventricular mass 160 g Delayed enhancement by manual contour tracing 42 g (26%) Delayed enhancement by semi-automatic gray- scale analysis 33 g (20%)

16. Randomized (n=208) No aspiration (n=104) Aspiration (n=104) Rheolytic (n=54) No MRI (n=29) Dead (n=2) Refused MRI (n=25) Lost at f-up (n=1) Claustrofobia (n=1) 3-month MRI (n=41) 3-month MRI (n=41) 3-month MRI (n=75) Primary endpoint analysis (n=79) Primary endpoint analysis (n=75) 1-year follow-up n=68 Manual (n=50) No MRI (n=25) Dead (n=3) Refused MRI (n=21) Lost at f-up (n=1 ) 1-year follow-up n=73 1-year follow-up n=73 3-month MRI (n=38) 3-month MRI (n=38)

17. Control (N=104) Thrombectomy (N=104) P Age61.5±14.963.0±11.20.7 Male sex79 (76%)88 (88.4%)0.83 Diabetes21(20.4%)20 (19.2%)0.83 Hypertension49 (47.6%)54 (51.9%)0.53 Dyslipidemia45 (43.7%)54 (51.9%)0.23 Current smoker51 (49.5%)50 (48.1%)0.81 Renal failure5 (4.9%)3 (2.9%)0.46 Previous MI2 (1.9%)4 (3.8%)0.68

18. ControlThrombectomyp Pain–to-balloon time, m241±161260±1320.07 Max ST elevation, mm4.1±2.14.2±1.70.21 Total ST elevation, mm11.7±7.312.7±7.80.18 N° of leads with ST elevation4.3±1.54.6±1.70.34 Anterior wall MI48 (46.2%)49 (47.1%)0.89 Three-vessel disease9 (8.7%)14 (13.5%)0.27 Area at risk (angiography)23.5±8.424.9±8.90.19 Killip Class 39 (8.7%)4 (3.8%)0.10 LVEF, %46±1046±80.90

19. ControlThrombectomyP Thrombus Grade 315 (14.4%)7 (6.7%)0.07 415 (14.4%)12 (11.5%)0.50 574 (71.2%)85 (81.7%)0.07 Initial TIMI flow 0-181 (77.9%)95 (91.3%)0.007 26 (5.8%)5 (4.8%)0.70 317 (16.3%)4 (3.8%)0.002 Initial cTFC86±2895±170.004

20. ControlThrombectomyP Final TIMI flow 0-13 (2.9%) 0.68 216 (15.4%)7 (6.7%)0.04 385 (81.7%)94 (90.4%)0.07 Final cTFC28±2124±170.17 Final MBG 0-116 (15.4%)11 (10.6%)0.41 233 (31.7%)22 (13.5%)0.12 355 (52.9%)71 (68.3%)0.03 STE resolution >70%38 (37.3%)58 (57.4%)0.004 cTnI peak, ng/mL73±8252±620.37 CK-MB peak, mg/dL245±290292±21110.60

21. Control (N=75) Thrombectomy (N=79) P DE area, %19.3±10.620.4±10.50.54 DE area >20%41 (54.7%)44 (55.7%)0.90 Transmurality, %11.6±12.711.9±12.00.91 MVO14 (19.4%)4 (5.1%)0.01 Dyshomogeneous scar2 (2.7%)28 (35.4%)<0.0001 EDVi, mL/m 2 80±2082±240.79 Stroke Volume, mL/m 2 45±1245±110.80 LVEF, %59±1156±120.10

22. 98% successful delivery 98% successful delivery of thrombectomy catheters: – 98% Manual system – 100% Rheolytic system 1 crossover from Manual to Rheolytic system 1 crossover from Manual to Rheolytic system, which was successfully delivered to the culprit lesion No coronary complications No coronary complications associated with thrombectomy (0 dissections, 0 perforations) No prolonged asystole No prolonged asystole with Rheolytic system in RCAs (never placed temporary pacemaker before aspiration)

23. Procedural results Rheolytic (N=54) Manual (N=50) P Angiographic success51 (94.4%)39 (78.0%)0.02 Final TIMI flow 348 (88.9%)46 (92.0%)0.84 Final MBG 335 (64.8%)36 (72.0%)0.56 STE resolution >70%34 (63.0%)27 (54.0%)0.47 MRI results Rheolytic (N=41) Manual (N=38) P DE area, %17.5±9.621.3±11.30.10 DE area >20%21 (51.2%)23 (60.5%)0.40 Transmurality, %11.9±12.311.8±11.70.97 MVO3 (7.3%)1 (2.7%)0.62 Dyshomogeneous scar18 (43.9%)10 (27.0%)0.16

24. 92.3±2.8 93.9±2.4 P=0.57

25. Thrombectomy was not associated with a significant reduction in infarct size at 3-month MRI, even in a high-thrombus burden STEMI population However, thrombectomy was associated with a significantly higher rate of complete STE resolution, and of post-procedural myocardial perfusion grade 3, and with a lower rate of final TIMI 2 flow

26. Thrombectomy was associated with a different MRI pattern of myocardial scar at 3 months, with less microvascular obstruction and with areas of viable tissue interspersed with necrotic areas No significant difference was observed regarding 1-year freedom from MACEs Angiojet was superior to Export in terms of thrombus removal, but not regarding procedural and MRI results

27. The lack of benefit in terms of infarct size might be related to: little role of the prevention of thrombo- embolization during primary PCI in reducing final infarct size excellent myocardial referfusion in the standard PCI group (clopidogrel pre-load + abciximab) imbalance between groups, favoring standard PCI group (shorter pain-to-balloon time)