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, 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: Presented on 2/26/2013 with vague chest pain with nonspecific pre- cordial T wave changes associated with variable dyspnea. Stress test suggested but declined and underwent cath revealing one vessel CTO (mLAD) with LVEF 56%. No PCI done as was inappropriate; not on any anti-ischemic meds and no documented ischemia. Pt was placed on Metoprolol XL 25mg and Amlodipine 5mg daily. A F/U stress MPI revealed moderate size large antero- lateral and apical ischemia. Still has residual class I-II angina. Prior History: Hyperlipidemia, NIDDM, Ex-smoker, +F/H, H/o RA Medications: All once daily dosage Aspirin 81mg, Metoprolol XL 25mg, Amlodipine 5mg, Metformin XL 1000mg, Rosuvastatin 20mg, Methotrexate, Sulfasalazine April 16th 2013 Case #10: SA, 53 yr M

4. Cardiac Cath 2/26/2013: Right Dominance 1 Vessel CAD with LVEF 56% (minimal apical hypokinesis) Left Main: Short LAD: 100% lesion in mid and distal fills via RCA and bridge collaterals, 90% D1 LCx: Non-obstructive RCA: No obstruction Plan Today: - PCI of CTO mid LAD via antegrade or retrograde approach Case# 10: cont… SYNTAX score 19.5

5. Appropriateness Criteria for Coronary Revascularization

6. Issues Involving The Case Predictors of CTO lesion success Correlation of IVUS, OCT and FFR

7. CHRONIC TOTAL OCCLUSION

8. Anatomic Descriptors of Procedural Success

9. Predictors of Procedural Success Multivariate analysis from TOAST-GISE VariablesHazard Ratiop Length ≥15 vs. <8 mm3.90.028 Moderate to 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

10. 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

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

12. Predictors of Reocclusion After Successful Drug-Eluting Stent-Supported Percutaneous Coronary Intervention of Chronic Total Occlusion: Florence CTO PCI Registry Valenti et al., J Am Coll Cardiol 2013;61:545

13. Successful CTO PCI (%) 1-Year clinical outcome MACE16.0 Cardiac death3.2 Myocardial Infarction0.9 CABG0.0 CTO vessel repeat PCI12.8 First-generation PES and SES14.1 EES10.5 STAR32.3 Definite stent thrombosis0.4 Angiographic outcome (n=616); 82% In-segment restenosis or reocclusion20 Reocclusion rate7.5 First-generation PES and SES10.1* EES3.0 STAR57.0 CTO PCI Registry: Clinical and Angiographic Outcomes First-Generation DES vs. Second-Generation EES (N= 802) Valenti et al., J Am Coll Cardiol 2013;61:545 * p = 0.001

14. Valenti et al., J Am Coll Cardiol 2013;61:545 CTO PCI Outcomes: Predictors of Clinical and Angiographic Outcome Clinical OutcomeHR95% CIp Value Cardiac death Age >75 yrs4.642.19-9.83<0.001 LVEF <40%7.252.77-19<0.001 LAD-CTO2.391.13-4.330.020 Completeness of revascularization0.480.24-0.950.037 MACE Age >75 yrs1.641.17-2.310.004 STAR technique2.261.21-4.220.010 LVEF <40%1.471.06-20.60.023 LAD-CTO1.421.02-2.010.046 Angiographic OutcomeOR Reocclusion STAR technique29.5011.9-73.2<0.001 EES0.220.09-0.540.001 Non-occlusive restenosis RCA-CTO1.641.02-2.620.040

15. Valenti et al., J Am Coll Cardiol 2013;61:545 CTO PCI Outcomes: 3 Years MACE Free Survival Based on the Technique P = 0.014 nonSTAR STAR

16. Whitlow et al., JACC Cardio Interv 2012;5:393 CrossBoss Crossing Catheter Stingray Re-Entry Balloon Catheter and Guidewire Use of Novel Crossing and Re-Entry System in Coronary CTOs Failing Standard Crossing Techniques

17. CTO Dissection/Re-entry Strategies CTO dissection/re-entry strategies Antegrade Retrograde DissectionRe-entry Knucle wire CrossBoss STAR Contrast- guided STAR mini-STAR LAST Stingray Knucle wire CART Reverse Cart Dissection Re-entry

18. Issues Involving The Case Predictors of CTO lesion success Correlation of IVUS, OCT and FFR

19. Schematic representation of various functional hemodynamic measurements Microvasculature OCT Criteria for significant stenosis: IVUS = <4mm2 FFR = <0.8 OCT = ? Microvasculature

20. FIRST Study: Fractional Flow Reserve and Intravascular Ultrasound Relationship Study 10 US/European centers enrolled 350 pts (367 lesions) with intermediate angiographic lesions (40-80%) and underwent IVUS, VH and FFR Waksman et al., JACC 2013;61:917

21. FIRST Study Scatterplots of IVUS MLA and FFR Correlation: Infarct of Vessel Size (RVD) Waksman et al., JACC 2013;61:917 All Vessels 3.07 mm 2 RVD <3.0mm RVD 3-3.5mm RVD >3.5mm 2.68 mm 2 3.16 mm 2 3.74 mm 2

22. FIRST Study: Diagnostic Accuracy of IVUS MLA in Prediction of Functionally Significant Stenosis and by RVD Waksman et al., JACC 2013;61:917 % sensitivity specifity ppv npv

23. Waksman et al., JACC 2013;61:917 FIRST Study: Scatterplots of IVUS and FFR All lesions that underwent PCI with FFR of 0.8, MLA of 3.07 mm 2 All lesions that did not undergo PCI with FFR of 0.8 and MLA of 3.07 mm 2

24. OCT vs IVUS Assessment of Native Coronary Artery Disease Bezzera et al., JACC Cardiovasc Interv 2013;6:228 p=0.294 p=<0.001 p=0.226 IVUS (56) FD-OCT (56)

25. OCT vs. IVUS Assessment of Stented Vessels Post PCI and at Follow Up Bezzera et al., JACC Cardiovasc Interv 2013;6:228

26. Morris et al., JACC Cardiovasc Interv 2013;6:149 VIRTU-1 Study: Example of vFFR in a Left Anterior Descending Artery

28. DeFACTO Study: Computation of FFR CT

29. DeFACTO Study: Discrimination

30. DeFACTO Study: Per-Patient Diagnostic Performance for Intermediate Stenoses by CT (30-70%)

31. Take Home Message: Predictors of CTO success and Correlation of various non-invasive studies In the current era of CTO recanalization, angiographic predictors of failure are few, important being heavy Ca++. Subintimal tracking is associated with high reocclusion rates and hence should be avoided. Unsuccessful recanalization is still associated with higher MACE rates Recent data suggest IVUS lumen CSA of 3.1mm2 to correlate with FFR of <0.8 and is dependent on RVD. OCT provides on an average 1mm smaller lumen area compared to IVUS & hence OCT criteria for hemodynamic significant lesion may be different then IVUS

32. Following are the predictors of successful recanalization of the CTO lesions except : A. Tapered end B. Heavy calcification C. No bridge collaterals D. Short occlusion (8-15mm) Question # 1

33. A recent multicenter registry showed current success of CTO to be : A. <50% B. 50-70% C. 71-85% D. >85% Question # 2

34. Following observation about FFR and IVUS correlation was noted in the FIRST study : A. There is a fixed relationship with RVD and FFR of <0.8 B. There is a good correlation of IVUS MLD and FFR C. FFR cutoff of 0.8 will lead to less PCI vs. IVUS MLD cutoff D. VH parameters on IVUS correlate well with FFR of <0.8 Question # 3

35. Following are the predictors of successful recanalization of the CTO lesions except : A. Tapered end B. Heavy calcification C. No bridge collaterals D. Short occlusion (8-15mm) Question # 1 The correct answer is B. Heavily calcified lesions are associated with lower success of CTO recanalization Olivari et al., J Am Cardiol Coll 2003;41:1672

36. A recent multicenter registry showed current success of CTO to be : A. <50% B. 50-70% C. 71-85% D. >85% Question # 2 The correct answer is C. Recent multicenter CTO registry demonstrated increasing success of CTO recanalization over the years with latest being over 80% Patel et al., JACC Cardiovasc Interv 2013;6:128

37. Following observation about FFR and IVUS correlation was noted in the FIRST study : A. There is a fixed relationship with RVD and FFR of <0.8 B. There is a good correlation of IVUS MLD and FFR C. FFR cutoff of 0.8 will lead to less PCI vs. IVUS MLD cutoff D. VH parameters on IVUS correlate well with FFR of <0.8 Question # 3 The correct answer is C. FIRST study showed that FFR and IVUS MLD has poor correlation and is dependent on RVD. FFR cutoff of 0.8 will lead to less PCI compared to any IVUS MLD cutoff even of 3.1mm2 Waksman et al., JACC 2013;61:917