1. Presentation: Presented with progressive dyspnea on exertion and cresendo angina CCS Class III, presented on 10/14/2011 and cath revealed mild pulm HTn, minimal AS, II V CAD (RCA and calcified LAD/D1/D2 bifurcation) and LVEF 25%. Pt underwent DES (Promus 3.0/15mm) PCI of RCA. Still continues to have Class II angina and mild DOE Prior History: Hyperlipidemia, Hypertension, Diet controlled DM, Medications: All once daily dosage ASA 81mg, Carvedilol CR 10mg, Amlodipine 5mg, Simvastatin 40mg Lisinopril 10mg, Spironolactone 25mg, added Clopidogrel 75mg November 15 th 2011 Case #15: BS, 72 yr F

2. Cardiac Cath 10/14/2011: Syntax score 21 2 Vessel CAD with LVEF 25% Left Main: No obstruction LAD: 80% proximal and 50% mid calcified bifurcation lesions with 70% lesions in D1 and D2 LCx: mild diffuse disease RCA: 95% prox lesion with large distal vessel Subsequent Course: -Pt underwent DES (Promus 3/15mm) of RCA on 10/14/2011; since then still continues to have exertional symptoms Plan Today: - PCI of LAD/D1/D2 calcified bifurcation lesion with Impella assist Case# 15: cont…

3. Appropriateness Criteria for Coronary Revascularization

4. Impella use in pts with aortic valve disease Technical Pearls and Issues With the Case by Dr Kini Inability to fully dilate lesion or full stent expansion vessel due to calcification Bifurcation lesion intervention with a plan to ‘keep artery open’ (KAO of SBr) at end of PCI

5. Issues Involving The Case Hemodynamic support in high risk PCI On-treatment platelet reactivity (OTR) & outcomes

6. Issues Involving The Case Hemodynamic support in high risk PCI On-treatment platelet reactivity (OTR) & outcomes

7. Percutaneous LV Assist Devices IABP PTVA: TandemHeart IMPELLA: Recovers 2.5

8. IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP AMI Randomized Trial Inclusion Criteria Anterior STEMI 2 mm in 2 contiguous leads or at least 4 mm in the anterior leads Planned Primary PCI within 6 hr Anterior STEMI Without Shock IABP prior to PCI Standard of Care Primary PCI alone At least 12 hours of IABP post PCI Routine Post PCI care Cardiac MRI performed day 3-5 post PCI Primary Endpoint: Infarct Size on CMR 1.All Patients with CMR data 2.Patients with Prox LAD occlusion TIMI 0/1 flow Clinical Events – 6 months Randomize Open Label (n ~ 300 ) Patel et al. JAMA 2011;306:1329

9. All IABP+PCI PCI Alone P (N=337) (N=161) (N=176)Value Primary endpoint Infarct size (% LV), modified ITT all patients with CMR data 0.060 N 275 133 142 Mean 39.8 42.1 37.5 Median 38.8 42.8 36.2 Infarct size (%LV), modified ITT patients prox. LAD and TIMI flow 0/1 0.110 N 192 93 99 Mean 44.4 46.7 42.3 Median 42.1 45.1 38.6 Patel et al. JAMA 2011;306:1329 IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP AMI Randomized Trial

10. IABP+PCI (N=161) PCI Alone (N=176) P Value Death, % 1.9*4.0*0.26* Stroke, % 1.90.60.35 Major bleed per GUSTO 1 definition or transfusion, % 3.11.70.49 Vascular complications, (n) % 7 (4.3)2 (1.1)0.09 Major limb ischemia requiring operative intervention (n) 00 Distal embolization (n) 00 Major dissection (n) 20 Pseudoaneurysm or AV fistula (n) 32 Hematoma > 5 cm (n) 30 30-day Clinical Events * From KM curves and log-rank test. Patel et al. JAMA 2011;306:1329 IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP AMI Randomized Trial

11. (%) Death Death/recurrent MI/ Death/Shock/ new or worsening CHF new or worsening CHF IABP+PCI (N=161) PCI Alone (N=176) P = 0.12 P = 0.15 P = 0.03 Patel et al. JAMA 2011;306:1329 IABP and infarct size in patients with acute anterior MI infarction without shock: CRISP AMI- 6 Month F/U

13. PROTECT II: Procedural Differences Procedural CharacteristicsIABP(N=223)Impella(N=224)p-value Use of Heparin82.4%93.5% <.001 GP IIb/IIIa Inhibitors26.1%13.5% 0.001 Total Contrast Media (cc)241±114267±142 0.037 Rotational Atherectomy (RA)9.5%14.9% 0.088 Median # of RA Passes/lesion (IQ range) 1 (1-2)3 (2-5) 0.001 Median # of RA passes/pt (IQ range) 2.0 (2.0-4.0)5.0 (3.5-8.5) 0.004 Median RA time/lesion (IQ range sec) 40 (20-47)60 (40-97) 0.005 RA of Left Main Artery3.1%8.0% 0.024 % of SVG Treatment or RA use17.5%25.4% 0.041 Total Support Time (hour)8.2±21.11.9±2.7 <.001 Discharge from Cath Lab on device37.7%5.7% <.001

15. PROTECT II MACCE Per Protocol Population, n=426 Log rank test, p=0.04 Death, Stroke, MI, Repeat revasc. IABP IMPELLA

17. PROTECT II 90-day Outcome (PP) HRPCI w/o Atherectomy (N=371, 88%) Death Death MI (>3x ULN) MI (>3x ULN) Stroke/TIA Stroke/TIA Repeat Revascularization Vascular Complication Acute Renal Dysfunction Severe Hypotension Severe Hypotension CPR / VT CPR / VT Aortic Insufficiency Aortic Insufficiency Angio Failure Angio Failure 11.6% 14.9% 1.1% 6.6% 2.8% 7.7% 9.4% 12.7% 0.0% 4.4% 8.9% 17.4% 2.6% 10.5% 3.7% 11.6% 12.1% 10.0% 0.0% 2.1% Composite IMPELLAIABP 12.5% 37.5% 3.1% 3.1% 0.0% 21.9% 18.8% 9.4% 0.0% 0.0% 10.0% 10.0% 0.0% 30.0% 5.0% 10.0% 20.0% 15.0% 0.0% 0.0% HRPCI with Atherectomy (N=52, 12%) 35.9%51.1%(p=0.003) IMPELLAIABP 68.8%55.0%(p=0.316) (p=0.006) (p=0.03) (p=0.399) (p=0.522) (p=0.280) (p=0.181) (p=0.616) (p=0.211) (p=0.400) (p=0.411) (p=0.208) (p=0.784) (p=0.425) (p=0.202) (p=0.271) (p=0.911) (p=0.537)

18. PROTECT II: Critical Look at 90 day Outcomes Repeat Revascularization (PP) (90 day Per Protocol, N=425) O’Neill et al, TCT 2011 IABP IMPELLA

19. $173,402 IABP Impella $172,583 Protect II Economic Study: Total Hospital Charges Per Patient at 90 Days (N=427)

20. PROTECT II: Critical Look at 90 day Outcomes Cost-Effectiveness of Impella vs. IABP O’Neill et al, TCT 2011

21. PROTECT II: Critical Look at 90 day Outcomes O’Neill et al, TCT 2011 Comparative Cost-Effectiveness Studies

22. Class I: 5.2.3 Cardiogenic Shock: Recommendation: “A hemodynamic support device is recommended for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacological therapy (384,424–427). (Level of Evidence: B).” This classification includes the statement: “Refractory cardiogenic shock unresponsive to revascularization may necessitate institution of more intensive cardiac support with a ventricular assist device or other hemodynamic support devices to allow for myocardial recovery or subsequent cardiac transplantation in suitable patients.” Class II b: 5.6 Percutaneous Hemodynamic Support Devices: Recommendation: “Elective insertion of an appropriate hemodynamic support device as an adjunct to PCI may be reasonable in carefully selected high-risk patients (Level of Evidence: C).” ACCF/AHA/SCAI 2011 Guidelines for Percutaneous Coronary Intervention Incorporates IMPELLA Support

23. LVEF + Lesion Complexity: LV Support during High-Risk PCI LVEF >35% LVEF 20-35% LVEF <20% Simple PCI Complex PCI No support IABP Impella/ PTVA Simple or Complex: Inoperable cases IABP Impella Simple PCI Complex PCI: High Syntax score >32/STS >5 Extensive revasc.

24. Issues Involving The Case Hemodynamic support in high risk PCI On-treatment platelet reactivity (OTR) & outcomes

25. Price et al., Circulation 2011;124:1132 % Standard Dose Clopidogrel (N=1013) High Dose Clopidogrel (N= 1011) Platelet Reactivity & PCI: Update from GRAVITAS Trial Impact of On-treatment Reactivity (OTR) at 30 days P =0.20 % < 230> 230 < 230 PRU< 208 PRU P <0.01 P <0.001 P =0.02 < 208 >208 % Primary endpoints

26. ADAPT–DES Assessment of Dual AntiPlatelet Therapy with Drug-Eluting Stents A large Scale, Prospective, Multicenter Registry Examining the Relationship Between Platelet Responsiveness and Stent Thrombosis After DES Implantation Gregg W. Stone, MD Columbia University Medical Center New York- Presbyterian Hospital Cardiovascular Research Foundation

27. ADAPT–DES Stone et al, TCT 2011 PCI with >1 non-investigational DES Successful and uncomplicated (IVUS/VH substudy;Up to 3000 pts. enrolled) Clinical FU at 30 days, 1 year and 2 years Angio core lab assessment all STs w/1:2 matching controls Up to 11,000 pts. prospectively enrolled No clinical or anatomic exclusion criteria 11 sites in US and Germany Assessment of Dual Antiplatelet Drug Eluting Stents Assess platelet function after adequate DAPT loading and GPI washout: Accumetrics Verify Now Aspirin, Verify Now P2Y12, and Verify Now IIb/IIIa assays

28. Stone et al, TCT 2011

29. + + ++ + + + ++ +

33. Conclusions and Implications of Platelet OTR Data suggests that agents which more effectively inhibit ADP-induced platelet activation should reduce 30-day stent thrombosis when applied to large patient populations (underlying the positive findings of TRITION-TIMI 38 and PLAT0) However, the modest sensitivity and specificity of platelet function testing, coupled with the low prevalence of events, implies that testing of platelet ADP antagonist responsiveness is unlikely to provide useful information to guide clinical decision-making in most indidual patients for the prevention of stent thrombosis at 30 days; New PRU cutoff is <208 which predicts outcomes post PCI

34. Take Home Messages: High Risk PCI with Support and Platelet Reactivity Impella assist device use has shown to be safe and beneficial in high risk complex PCI achieving extensive and full revascularization Platelet reactivity testing on treatment may be indicated in pts with ACS and new PRU cutoff is <208