1. Complex Coronary Cases Supported by: Abbott Vascular Boston Scientific Corporation Medtronic, Inc. Astrazeneca

2. Disclosures Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, AngioScore, The Medicines Company, Daiichi Sankyo, Inc. and Lilly USA, LLC Annapoorna S. Kini, MBBS, FACC Nothing to disclose Sameer Mehta, MBBS, FACC Consulting Fees – The Medicines Company American College of Cardiology Foundation staff involved with this case have nothing to disclose

3. Presentation: Patient with new onset cresendo angina and positive stress echo for infero-lateral ischemia underwent cardiac cath on June 26, 2013 which revealed 3 V CAD (60% prox LAD, 80% distal LCx and 100% distal RCA) and normal LV function; SYNTAX score 22. CABG was recommended but declined and pt underwent Resolute Integrity (3.5/30mm) DES PCI of distal LCx. Pt continued to have class II angina on MMT. Prior History: Hypertension, NIDDM, +F/H Medications: All once daily dosage Atenolol 50mg, Amlodipine 5mg, Aspirin 81mg, Prasugrel 5mg, Metformin XR 1000mg, Glimeperide 2mg, Omeprazole 20mg August 20th 2013 Case #14: SD, 62 yr M

4. Cardiac Cath 6/26/2013: Right Dominance 3 V CAD with LVEF 65% Left Main: No obstruction LAD: 60% prox LAD and 60% D1 non-bifurcation lesions LCx: 80% distal LCx, large vessel RCA: 80% mid and 100% distal RCA occlusion and distal vessel fills via bridge as well as retrograde collaterals Pt underwent successful DES PCI of distal LCx using 3.5/30mm Resolute Integrity DES. Pt did well but had class II angina despite MMT. Did not tolerate ISMN Plan Today: - PCI of distal RCA CTO using retrograde recanalization. Case# 14: cont…

5. Appropriateness Criteria for Coronary Revascularization

6. Issues Involving The Case Current status of CTO lesion success Retrograde recanalization approach

7. Issues Involving The Case Current status of CTO lesion success Retrograde recanalization approach

8. 1. CTO is present in 20-22% of cath cases but PCI is attempted only in 5-13% of these cases 2. From BARI trial (1994) to SYNTAX trial (2007), the single most common reason for a patient to be referred to surgery and not randomized was a CTO with low success rate of recanalization 3. Even in the recent era of increasing success rate of CTO recanalization (60-85%), the PCI success rate for CTO lesions in the SYNTAX trial was only 53% Chronic Total Occlusion (CTO) From Randomized Trials to Daily Practice

9. Current Perspective on Coronary CTO The Canadian Multicenter CTO Registry Management of CTO Registry Patients by Treating Center Fefer et al, J Am Coll Cardiol 2012;59:991

10. Anatomic Descriptors of Procedural Success In the current ERA; Severe calcification

11. Predictors of CTO Procedural Success Multivariate analysis from TOAST-GISE VariablesHazard Ratiop Length ≥15 vs. <8 mm3.90.028 Severe calcification3.50.023 Duration ≥ 180 days3.10.013 Multi-vessel disease2.30.009 Bridge collaterals present2.20.023 Stump morphology2.20.048 Olivari et al., J Am Cardiol Coll 2003;41:1672

12. Patel et al., JACC Cardiovasc Interv 2013;6:128 Incidence of Procedural Complications in Successful vs. Unsuccessful CTO PCI MACE (%)3.74.30.68 Death (%)0.41.5<0.0001 Emergent CABG (%)0.030.170.74 Stroke (%)0.070.40.04 MI (%)2.83.00.87 Q-wave MI (%)0.30.50.26 Coronary perforation (%)3.710.7<0.0001 Tamponade (%)0.01.7<0.0001 Vascular complication (%)1.70.90.20 Contrast nephropathy (%)5.04.60.86 SuccessfulUnsuccessful p value Complications

13. Patel et al., JACC Cardiovasc Interv 2013;6:128 Temporal Trends in Cumulative Angiographic Success Rates and Major Procedural Complication Rates 80% 0.5%

14. Meta-Analysis of CTO Outcomes Joyal et al., Am Heart J 2010;160:179. 13 Observational Studies, 7288 patients weighted averaged follow-up 6 years OR for Success vs. Failure 95% Clp Value Mortality0.560.43-0.72<0.001 MI0.740.44-1.250.26 Subsequent CABG0.220.17-0.27<0.001 Residual Angina0.450.30-0.670.001

15. All-Cause Mortality for Successful and Failed Groups of CTO Duration >3 Months Khan et al., Cath & Cardiovasc Intervn 2013;82:95

16. Residual SYNTAX Score: 1-Year Outcomes According to the rSS Généreux et al., JACC2012;59:2165 Death uTVR MACE MI Stent Thrombosis P = 0.006 P = 0.23 P =0.32 (%) P = 0.001 P = 0.007 rSS = 0 rSS = 0-2 rSS = 3-8 rSS = >8

17. PCI: Four-Year Clinical Outcomes in Patients by Complete vs. Incomplete Revascularization Patients (%) p=0.059 p=0.052 p=0.23 p=0.046 p=0.011 p=<0.001 Complete Revascularization (n=578) Incomplete Revascularization (n=510) Farooq et. al., J Am Coll Cardiol 2013;61:282

18. Total Charges, Payments and Direct Costs per Patient Undergoing CTO and Non-CTO PCI Karmpaliotis et al., Cath & Cardiovasc Interv 2013;82:1 Cost ( Dollars ) p=<0.001 p=0.58 CTO (n=154) Non-CTO (n=1,847)

19. Issues Involving The Case Current status of CTO lesion success Retrograde recanalization approach

20. Retrograde Wire Technique of CTO Recanalization

21. Retrograde Techniques for CTO Recanalization Typically reserved for LAD or RCA CTOs via septal collaterals; avoid using epicardial collaterals Four techniques: –Direct retrograde crossing –Kissing wire crossing –Controlled Antegrade and Retrograde Subintimal Tracking (CART); balloon dilatation or knuckle wire –Reverse CART

22. Retrograde Wire Technique for Chronic Total Occlusion Recanalization Four Patterns of Success in Retrograde CTO Recanalization Sumitsuji et al. J Am Coll Cardiol Intv 2011;4:941.

23. Increased Use of Retrograde Approach and Technical Success Rate Over Time Michael et al., Am J Cardiol 2013;112:488 % 2006 2007 2010 2009 2008 2011 30%

24. Karmpaliotis et al., JACC Cardio Interv 2012;5:1273 Summary of Published Retrograde CTO PCI Series StudyYearN Prior CABG % Septal Collateral Used % Reverse CART, % Technical Success % Major Complic % Flouroscopy Time, min, mean ± SD Contrast Use, ml mean ± SD Sianos200817510.979.4NR83.44.659 ± 29421 ± 167 Rathore200915717.867.5NR84.74.5NR Kimura200922417.679.014.092.41.873 ± 42457 ± 199 Tsuchikane20109310.882.860.998.90.060 ± 26256 ± 169 Morino20101369.663.9NR79.2NR US Registry201246250.071.041.081.42.661 ±345 ± 177

25. Retrograde PCI: 5 Steps Retrograde PCI for recanalization of CTOs has gained acceptance as a necessary technique to improve success The procedure involves five key steps: 1. Wiring of the collateral from the donor artery into the distal bed of the recipient artery, usually with the use of hydrophilic jacketed guidewires 2. Delivery of over-the-wire microcatheters especially Corsair channel dilator to allow an exchange for a CTO-specific guidewire 3. Crossing the total occlusion with the CTO guidewire and dilating the CTO with the retrograde small balloon (1.25-1.5/8-10mmsize) 4. Placing an antegrade guidewire into the distal bed through the recanalized CTO. Rarely exteriorization of the long retrograde guidewire (Viper wire 360cm) is needed to advance antegrade monorail or over-the-wire small balloon 5. Stenting the lesion over the antegrade guidewire

26. Retrograde Wire Technique for CTO Recanalization When to do Retrograde technique? - Minimum 200 CTO cases via antegrade technique - Dedicated setup, equipments and ability to handle compl. - Usually after failed antegrade (once or twice) approach - Ostial stump occlusion (RCA, LAD, LCx)

27. Procedural Steps of Current CTO-PCI Fundamental Wire Technique and Current Strategy for Chronic Total Occlusion PCI CTO - PCI Antegrade approach x2 Retrograde approach (ostial) IVUS guide re-entry Single Wire Technique Parallel Wire Technique Retrograde Wire Cross Kissing Wire Cross CART Reverse CART SuccessFailure Cotralateral Dual Injection

28. Take Home Message: Status of CTO lesion PCI and Retrograde recanalization approach Improvement in the procedural techniques and devices has resulted in increasing success of CTO PCI. A successful CTO PCI is associated with better long-term outcome, decreased cost & lower mortality. Technique of retrograde recanalization is gaining increasing momentum and adds to the already increasing technical success rates. Every advanced CTO PCI center should dedicated experienced operators for the retrograde approach.

29. Which one of the angiographic lesion morphology is associated with the highest rates of unsuccessful CTO recanalization : A. Blunt stump B. Side branch at the site of occlusion C. Short occlusion length D. Severe calcification E. Bridge collaterals Question # 1

30. A successful CTO recanalization is associated with following except : A. Lower MACE B. Lower mortality C. Lower stent thrombosis D. Lower incidence of long-term CABG E. Lower angina Question # 2

31. Following are the techniques for retrograde recanalization except : A. Kissing wire approach B. Retrograde wire cross C. Controlled antegrade and retrograde tracking (CART) D. Reverse CART E. Parallel wire technique Question # 3

32. Which one of the angiographic lesion morphology is associated with the highest rates of unsuccessful CTO recanalization : A. Blunt stump B. Side branch at the site of occlusion C. Short occlusion length D. Severe calcification E. Bridge collaterals Question # 1 The correct answer is D as of these unfavorable factors severe calcification still is associated with highest failure Olivari et al., J Am Cardiol Coll 2003;41:1672.

33. A successful CTO recanalization is associated with following except : A. Lower MACE B. Lower mortality C. Lower stent thrombosis D. Lower incidence of long-term CABG E. Lower angina Question # 2 The correct answer is C as stent thrombosis may even be higher in successful vs. unsuccessful CTO recanalization Joyal et al., Am Heart J 2010;160:179.

34. Following are the techniques for retrograde recanalization except : A. Kissing wire approach B. Retrograde wire cross C. Controlled antegrade and retrograde tracking (CART) D. Reverse CART E. Parallel wire technique Question # 3 The correct answer is E as all others are the techniques of retrograde CTO recanalization while the parallel wire technique is for antegrade recanalization Sumitsuji et al. J Am Coll Cardiol Intv 2011;4:941.