1. Jie Qian National Heart Center & FuWai Hospitall FFR in Diffuse Multivessel Disease

2. Different Patients with the same symptom : angina IVUS –based or FFR –Based PCI ?Angio-based PCI

3. Why do we need functional evaluation ?  Limitations of coronary angiography  Limitations of noninvasive techniques  Cost issues ( Cost / Benefit )

4. Limitations of Angiography : “Lumengram”: Disconnection with function & physiology

5. FAME study: (dis)congruence between QCA and FFR Key paper: Tonino et al; JACC 2010; 55: 2816-2821

6. “I do not stent lesions of 50-70%” You are under-treating 40% of your patients “I always stent lesions of 50-70%” You are over-treating 60% of your patients “I only stent lesions > 70%” You are still over-treating 20% of your patients IVUS does not solve this problem ! (Key publication: Kang, Park, et al: Circulation Cardiov Interv 2011; 4: 65-71)

7. Limitations of noninvasive techniques  Often not performed  Can be inaccurate in multivessel disease  Generally “territory” specific, but not “vessel” specific  Can be “vessel” specific “ but not “lesion “ specific

8. Limitations of noninvasive techniques 143 patients with angiographically significant 3-vessel disease ( > 70% diameter stenosis) Tallium Scan Findings % Lima et al, J Am Cll Cardiol 2003; 42:63-70

9. Stress Rest Infero-lateral inducible ischemia 75 yrs male, Hyperlipidemia.Hypertension and diabetes Typical chest pain on exerction despite optimal medical therapy.

10. FFR= 0.82 Following stent implantation at prox LCX FFR= 0.72FFR= 0.97

11. Functional Evaluation is not mandatory for every patient :

12. Intermediate Lesion : Chest pain, without non invasive ischemic test Simple functional evaluation would provide better management …

13. The angio-guided approach : is it the optimal approach ?

14. Anatomic Scoring For Each Lesion Segment – Location – Length – Calcification – Tortuosity – Bifurcation – Diffuse Disease – Occlusion – Thrombus SYNTAX Score SYNTAX Score = 18 SYNTAX Score = 41

15. 0612 20 40 0 Months Since Allocation Cumulative Event Rate (%) TAXUS™ Express 2 ™ Stent (n=181) CABG (n=171) MACCE to 12 Months by SYNTAX Score™ Tercile Low Scores (0-22) 3VD Subset Calculated by core laboratory; ITT population P=0.66 * 17.3% 15.2% Event Rate ± 1.5 SE, * Fisher exact test Presenter: See Glossary

16. 0612 20 40 0 Months Since Allocation Cumulative Event Rate (%) TAXUS™ Express 2 ™ Stent (n=207) CABG (n=208) MACCE to 12 Months by SYNTAX Score™ Tercile Intermediate Scores (23-32) 3VD Subset P=0.02 * 18.6% 10.0% Calculated by core laboratory; ITT population Event Rate ± 1.5 SE, * Fisher exact test Presenter: See Glossary

17. 0612 20 40 0 Months Since Allocation Cumulative Event Rate (%) TAXUS™ Express 2 ™ Stent (n=155) CABG (n=166) MACCE to 12 Months by SYNTAX Score™ Tercile High Scores (  33) 3VD Subset P=0.002 * 21.5% 8.8% Calculated by core laboratory; ITT population Event Rate ± 1.5 SE, * Fisher exact test Presenter: See Glossary

18. 48% of patients received ≥5 stents Max # 14 stents! Stent Number and Length Higher in the SYNTAX Trial Patients (%) Total Number of Stents Implanted per Patient Multivessel disease: 96.2%* 3-vessel disease:90.8% Avg. stents per patient:4.6 ± 2.3 Avg. stented length:86.1 mm *3VD+LM/3VD+LM/2VD+LM/1VD

19. Linear Increase in MACCE by Number of Stentsin the SYNTAX Trial 12m MACCE in TAXUS Arm 12345678+ Number of Stents Implanted 12m MACCE Probability 12m MACCE Rate 4.6 Stents SYNTAX Average 17.8% 1.5 Stents “Typical” Real World Average 1 stent 5.6% Avg. in pts with 5-8+ stents in SYNTAX 19.6% 14325678

20. Functional SYNTAX Score 497 patients, FFR-guided arm of FAME Study 2-3 vessel disease Angio Syntax Score : Conventional fashion Functional ( FFR) Syntax Score : counting only the lesions with FFR < 0.80 Angio SYNTAX Functional ( FFR ) SYNTAX FFR reclassifies > 30% ! Fearon WF et al, TCT-MD 2011

21. Funtctional SYNTAX Score desciminates Risk of Death/MI and Risk of Total MACE Death / MI Total MACE Fearon WF et al, TCT-MD 2011

22. Is it safe to defer treatment ?

23. DEFER Study : 5-year Follow-up ( Death / MI )

24. MACE at 1 year % p<0.05 Chamuleau et al, AJC 2002;89:377-80 Risk of deferring PCI if FFR < 0.75

25. FFR-Guided PCI in Multivessel Disease 137 patients, non-randomized Wongpraparut et al, AJC 2005; 96:877-884

26. Angiography-guided PCI FFR-guided PCI Measure FFR in all indicated stenoses Stent all indicated stenoses Stent only those stenoses with FFR ≤ 0.80 Randomization Indicate all stenoses ≥ 50% considered for stenting Patient with stenoses ≥ 50% in at least 2 of the 3 major epicardial vessels 1-year follow-up FLOW CHART

27. FAME study: PRIMARY ENDPOINT Composite of death, myocardial infarction, or repeat revascularization (“MACE”) at 1 year

28. ANGIO-group N=496 FFR-group N=509 P-value Events at 1 year, No (%) Death, MI, CABG, or repeat-PCI91 (18.4)67 (13.2)0.02 Death15 (3.0)9 (1.8)0.19 Death or myocardial infarction55 (11.1)37 (7.3)0.04 CABG or repeat PCI47 (9.5)33 (6.5)0.08 Total no. of MACE 113760.02 Myocardial infarction, specified All myocardial infarctions43 (8.7)29 (5.7)0.07 Small periprocedural CK-MB 3-5 x N1612 Other infarctions (“late or large”) 2717 FAME study: Adverse Events at 1 year

29. FFR-guided 30 days 2.9% 90 days 3.8% 180 days 4.9% 360 days 5.3% Angio-guided absolute difference in MACE-free survival FAME study: Event-free Survival

30. Adverse Events at 2 Years Angio- Guided n = 496 FFR- Guided n = 509 P Value Total no. of MACE 139105 Individual Endpoints Death 19 (3.8)13 (2.6)0.25 Myocardial Infarction48 (9.7)31 (6.1)0.03 CABG or repeat PCI61 (12.3)53 (10.4)0.35 Composite Endpoints Death or Myocardial Infarction63 (12.7)43 (8.4)0.03 Death, MI, CABG, or re-PCI110 (22.2)90 (17.7)0.07

31. FAME study: 2-year Event-free Survival

33. Stent length / Number of stent & restenosis – stent thrombosis

34. % P<0.001 Stent Length is Independent Predictor of Restenosis. Lee CW et al. Am J Cardiol 2006;97:506-511 mm

35. Non-Q-Wave MI Data from DES studies suggest Non-Q-Wave MI rates increase as total stented length increases. TAXUS V Multiple stents 7.3 15 mm Mean Stent length ( mm) 65 mm Non Q wave MI 25mm 30mm40 mm TAXUS stent Cyphert stent

36. Full Metal Jacket. Ielasi, Colombo et al. Ital J Inv Cardiol 2009; 3 Suppl: 111 658 full metal jacket lesions (≥60mm) in 617 patients. 33% DM, 33 had prior PCI, 33% CTO. 39 months mean follow up (2 yr in 91% pts). Mortality 7.3% MI during follow up: 3.5% TLR: 23.4% Stent thrombosis (Def or Probable): 2.6% (10/17 while on DAP).

37. Longer Stents have more Thrombosis. Roy et al. AJC 2009; 803:801-5 Independent Predictors of Cumulative ST. ISRS (OR 2.7, p<0.001) Number of stents (OR 1.7, p<0.001) Clopridogrel Cessation (OR 1.7, p<0.001) Diabetes (OR 1.5, p 0.2) Renal Insufficiency (OR 1.4, p 0.4)

38.  Pressure wire assessment in MVD and diffuse disease is technically easy and offers more accurate functional evaluation of coronary stenoses.  Defering treatment of intermediate lesions when the FFR>0.80 seems safe and effective  Reducing the number and length of stents /vessel and or /patient is translated in less MACE on long term outcome Conclusions

39. THANKS!