1. Coronary stenting: the appropriate use of FFR Morton J. Kern, MD Professor of Medicine Chief of Cardiology LBVA Associate Chief Cardiology University California Irvine Orange, California

2. To treat or not to treat? Is this lesion producing Ischemia? Is PCI appropriate for situation?

3. The rationale for using coronary physiology is the inability of the 2D images of angiogram to accurately depict the 3D lesion characteristics limiting flow. 75% Dia 20% Dia

4. Uncertainty in Critical Angiographic Based Decisions Intermediate Stenosis, no evidence ischemia Left Main Stenosis Multivessel CAD Serial Lesions Ostial and Branch Disease

5. Aortic, Pa Coronary, Pd FFR= Pd/Pa = 65/90 = 0.72 Measurement of FFR correlates to the results of stress testing and ischemia out of the lab. FFR is a ‘stress test’ for that artery in the lab at time of cath. Adenosine Resting pressures

6. 5 Steps to Accurate FFR 1.Zero guide and wire on table to atmosphere 2.Insert wire into guide and match wire/guide pressures in aorta 3.Cross lesion 2-3cm distal 4.Turn on IV adenosine 2-4 minutes 5.Confirm accuracy with pressure pull back

7. Rely on FFR Avoid pitfalls of pressure and FFR Technical loose connections loose connections Improper zero Improper zero Calibration offset Calibration offsetAnatomic Extreme tortuosity Extreme tortuosity Inability to wire vesselInability to wire vessel SpasmSpasmMechanical Wire/artery impact Pharmacologic Inadequate hyperemiaInadequate hyperemia Hemodynamic Artifacts: Damped pressure waveforms. Damped pressure waveforms. Guide obstruction Guide obstruction Contrast media Contrast media Very small guide (<5F) Very small guide (<5F) Pressure signal drift Pressure signal drift Side holes and ostial ‘pseudostenosis’ Side holes and ostial ‘pseudostenosis’

8. Rely on FFR Effect of Wire Introducer

9. Rely on FFR – No Guide Catheter Side Holes or Damping From Nico Pijls

10. Notch No notch Rely on FFR – Avoid Signal Drift Drift Drift True Gradient

11. Distal wave form is one key to drift Severe stenosis filters high frequency components – No dichrotic notch Notch No notch

12. IV vs IC Pharmacologic Hyperemic agents

13. Ref Diam (mm) % Stenosis for an Cross Sectional Area of 4 mm² < 4 mm² = significant stenosis ? 02550 2 3 4 5 Q: Why can we not use IVUS/OCT for functional assessment? A: A single cross-sectional area does not mean the same thing everywhere.

14. Single anatomic parameters do not predict FFR with confidence IVUS v FFR

15. When can you NOT rely on FFR? False Negative FFR 1.Pressure Damping 2.No hyperemia - wrong drug, not mixed not delivered (IV?) or side holes 3.STEMI, culprit. STEMI – non-culprit OK 4. LM + LAD when FFRepicardial <0.6 5. Serial lesion FFR of individual lesion (only gradient useful) False Positive FFR 1. Technical errors (Pressure signal drift,zero, etc.)

16. ApplicationFFR Ischemia detection, >15 studiesPos <0.75 Neg >0.80 Deferred angioplasty, >8 studies (Key Study: Defer) >0.75 Multivessel FFR guided PCI, LM, Ostial, Jailed Side Branch (Key Study: FAME I, II) (Key Study: Hamilos for LM) (Key Study: Koo BW et al) >0.80 Endpoint of stenting *(IVUS better post stent) >0.94* Coronary Physiologic (FFR) Criteria and Clinical Outcome Studies

17. 62 yo Man, RCA stent occl 2yr ago with return of CP LAD FFR=0.86, 0.87 Now 1V CAD and new approach

18. DEFER Study – 5 year data JACC 2007;49:2105

19. RW. 59 yo man with Angina, inferior perf defect 3V CAD – CABG vs PCI? FFR=0.71 2 Questions How Accurate is Stress Test? If PCI needed, FFR directed?

20. JACC 2010;56:177

21. FAME study: Death and MI after 2 Years 10 0 5 2 year 12.7 8.4 % FFR-guided Angio-guided P= 0.03 9.5 6.1 2 year (exclusion of small periprocedural infarction) Tonino et al, NEJM 2009, Pijls et al, JACC 2010 Death or MI MI

22. Incremental QALY FFR Guidance Improves Outcomes FFR Guidance Saves Resources Incremental Cost [$] DES CABG ROTO BMS Balloon Economic Evaluation of FFR-guided PCI in pts with MVD. Fearon WF et al. Circ 2010;122:25450-2550

23. FAME: Angiography vs FFR Tonino, P. A. L. et al. J Am Coll Cardiol 2010;55:2816-2821 Angiographic 3- or 2-Vessel Disease does NOT equal Physiologic 3- or 2V CAD 3V CAD Angio = 14% physiol 2V CAD Angio= 43% physiol

24. FAME II – Ischemia directed PCI+OMT vs OMT alone Stable patients scheduled for 1, 2 or 3 vessel DES stenting FFR in all target lesions When all FFR >0.80 OMT At least 1 stenosis with FFR ≤ 0.80 Randomisation 1:1 PCI + OMT OMT Follow-up after 1, 6 months, 1, 2, 3, 4, and 5 years Randomised Trial Registry 24 50% randomly assigned to FU

25. 25 Rate of Any Revascularisation 131884140 3541111REGISTRY:OMT only 3522561441411401391142518 RCT:PCI+OMT 339238123119115112832010 8RCT:OMT only No. at risk Months after randomisation 0 10 20 30 40 50 60 01234567891012 RCT:PCI+OMT vs. REGISTRY:OMT, p=0.54 RCT:OMT vs. RCT:PCI+OMT = 12.1% vs. 1.7% HR (95% CI): 7.63 (3.24-18.0); logrank p<.0001 Cumulative incidence (%) FAME II

26. 71 yo Man with typical angina, pos stress, CAD risk factors What’s your best approach?

27. FFR CFX FFR CFX=0.88

29. LAD Xience 3.5x18. 2 nd LAD lesion? All done? ? FFR = 0.68

30. Physiologic Guidance 1. Appropriate need for Stents 2. Objective info re ischemia 3. Eliminates operator uncertainty

31. Chest pain, No objective evidence ischemia FFR Asymptomatic Patients

32. Revascularization Approaches per AUC FFR reduces uncertainty and documents appropriateness 2v CAD with prox LAD 3v CAD Isolated LM LM and other CAD

33. Class IIa Guidelines - ACC/ AHA/ SCAI Class IA Guidelines - ESC The Mandate for Physiologic Guidance arises from a decade of outcomes studies and is supported by guidelines