1. IVUS Use during Left Main PCI improve Immediate and Long Term Outcome Where is the Evidence? E Murat Tuzcu, MD, FACC Professor of Medicine Vice Chairman Department of Cardiovascular Medicine Cleveland Clinic

2. Does IVUS improve PCI Outcomes 1990 -2000 StudyHelpfulNo SIPSX CRUISEX Choi et alX AVIDX CENICX Gaster et alX RESISTX TULIPX OPTICUSX

3. Role of IVUS in Stenting in the DES Era Intravascular IVUS-guided DES Placement Associated with Reduced Incidence of Recurrent Clinical Events B. Claessen et al., JACC 2010;56:41 1504 pts, IVUS guidance in 632 (42%), F/U 2 yrs CRF and Amsterdam Multivariate Analysis for Predicting Death/MI IVUS guidance Age CHF Renal impairment Time in Years 00.51.01.52.0 0 3 6 9 12 15 P=0.004 Non IVUS Cohort IVUS Cohort

4. Park SJ et al., JACC 2005;45:351-356 Comparison of BMS (IVUS 75%) and DES (IVUS 86%) 70 60 0 MACE Free Survival (%) Months 024681012 100 90 80 SES group BMS group 81.4 ± 3.7% 98.0 ± 1.4% IVUS in LMCA Stenting

5. 1.0.5 0.0 Event-free Survival (%) Time (days) 02004006008001000 Distal LM Non-Distal LM IVUS (n=14) No IVUS (n=12) No IVUS (n=22) IVUS (n=10) Agostoni et al AJC 2005;95:644-7 IVUS Guidance in DES for LMCA Stenosis Event Free Survival in 24 IVUS+ and 34 IVUS- Patients

6. 975 elective BMS or DES for unprotected LMCA stenosis975 elective BMS or DES for unprotected LMCA stenosis IVUS (756), angiography (219) guidance by operator discretionIVUS (756), angiography (219) guidance by operator discretion Angiography group was older and sickerAngiography group was older and sicker 201 propensity-score matching pairs (DES + BMS)201 propensity-score matching pairs (DES + BMS) 145 propensity-score matching pairs of DES patients145 propensity-score matching pairs of DES patients MAIN COMPARE REGISTRY

7. Park SJ Circ Cardiovasc Interv 2009;2:167-177 DeathDeath or MI Patients at risk IVUS-guidance20119414388 Angiography-guidance20119113864 01803605407209001000 Angiography-guidance IVUS-guidance P=0.063 40 30 20 10 0 13.6% (8.0-19.24%) 6.0% (2.6-9.4%) Cumulative Mortality (%) Days Patients at risk IVUS-guidance20117813182 Angiography-guidance20117512867 01803605407209001000 Angiography-guidance IVUS-guidance P=0.078 40 30 20 10 0 13.9% (9.1-18.8%) 22.7% (16.2-29.2%) Cumulative Incidence of Death or MI (%) Days IVUS Guidance in Stenting for LMCA Stenosis 3 year death and MI (K-M) in 201 propensity matched pairs

8. Park SJ Circ Cardiovasc Interv 2009;2:167-177 TVRDeath/MI/TVR Patients at risk IVUS-guidance20117612518 Angiography-guidance20117912970 01803605407209001080 Angiography-guidance IVUS-guidance P=0.056 40 30 20 10 0 11.9% (7.3-16.5%) 8.8% (4.6-12.9%) Cumulative Incidence of TVR (%) Days Patients at risk IVUS-guidance20116411574 Angiography-guidance20116812964 01803605407209001000 P=0.274 40 30 20 10 0 Cumulative Incidence of Death, MI or TVR (%) Months Angiography-guidance IVUS-guidance 28.0% 22.2% IVUS Guidance in DES for LMCA Stenosis 3 year TVR and MACE (K-M) in 201 propensity matched pairs

9. IVUS Guidance in DES for LMCA Stenosis Cumulative Mortality (%) Patients at risk IVUS-guidance1451409837 Angiography-guidance1451378829 Months 0 10 20 30 40 01803605407209001080 4.4% 16.0% P=0.048 Angiography-guidance IVUS-guidance 3 year mortality (K-M) in 145 propensity matched pairs

10. Differences in Patient Outcomes for LMCA PCI Thoraxcenter vs. Asan Medical Center: Impact of Baseline Characteristics on Outcomes of DES Age 65, LVEF 45% Euroscore 4.3, IVUS 32%, SYNTAX score 39 STEMI 23%, Shock 9% Age 61, LVEF 59% Euroscore 3.3, IVUS 89% 32%, SYNTAX score 39 STEMI 0%, Shock 0% All Cause Mortality 35% versus, 6% Onuma et al. JACC Int, 2010Park DW et al., JACC, 2010

11. Left Main Coronary Artery (LMCA) Disease T o treat or not to treat? That is the question.

12. IVUS and Left Main Disease IVUS MLD (mm) QCA MLD (mm) r=0.364 0 1 2 3 4 5 6 7 0123456 7 IVUS ref (mm) QCA Ref. (mm) 0 1 2 3 4 5 6 7 8 012345678 r=0.495 Independent predictors of MACE DM (P=0.004) Any untreated lesion >50% (p=0.04) IVUS MLD (P=0.005) IVUS DS QCA DS 0 20 40 60 80 100 020406080100 p=0.106 AS Abizaid et al JACC 1999;34:707-15 MACE IVUS MLD (mm) 1.42.23.03.84.65.4 1.82.63.44.25.05.8 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 DM and  1 untreated vessel with DS  50% DM and no untreated vessels No DM and  1 untreated vessel with DS  50% No DM and no untreated vessels 122 patients with moderate LMCA disease, f/u 1 year

13. Assessment of Intermediate LMCA Lesions by IVUS 354 Patients MLA ≥6.0 mm 2 (N=186) MLA <6.0 mm 2 (N=168) 7 revascularized16 not revascularized No LMCA revascularization (n=179, 96%) LMCA revascularization (n=152, 90%) 56% PCI of other vessels 55% CABG 45% PCI (+ other vessels in 62%) LITRO Study – 22 Spanish Centers De La Torre Hernandez et al. ACCi2 2010

14. Survival free of cardiac death, MI and any revascularization P=0.22 Defer (n=179) Revascularization (n=152) Survival free of cardiac death P=0.20DeferRevascularization De La Torre Hernandez et al. ACCi2 2010 Assessment of Intermediate LMCA Lesions by IVUS Survival in Revascularized and Deferred Patients

15. Time Defer (medical therapy) with MLA ≥6mm 2 (n=179) 100 80 60 40 20 0 Survival free of Cardiac Death P=0.02 0100200300400500600700 Defer (medical therapy) with MLA <6mm 2 (n=160) Assessment of Intermediate LMCA Lesions by IVUS LITRO Study – Survival in Medically Treated Patients De La Torre Hernandez et al. ACCi2 2010

16. The Assessment of LMCA Shortfalls of Luminology for Even Experienced Clinicians

17. Agreement or Disagreement on Stenosis Severity Visual Assessment%(absolute #) Reviewer Anscorrect 53%27/51 sincorrect22%11/51 uunsure25%13/51 Reviewer Bnscorrect49%25/51 sincorrect39%20/51 uunsure12%6/51 Reviewer Cnscorrect51%26/51 sincorrect49%25/51 uunsure-0/51 Reviewer Cnscorrect45%23/51 sincorrect33%17/51 uunsure22%11/51 Lindstaedt M et al. Int J Cardiol. 2007;120(2):254-261 Reviewer Assessment Results 51 intermediate LMT assessed by angiography and FFR 4 experienced interventional cardiologist correctly classified lesion severity in 50% of patients. 4 experienced interventional cardiologist correctly classified lesion severity in 50% of patients. Interobserver variability was large resulting in unanimous correct classification in only 29% Interobserver variability was large resulting in unanimous correct classification in only 29%

18. The Grey Zone of FFR De Bruyne B et al. Circulation 2001;104:157-162 0.20.30.40.50.60.70.80.91.0 FFR 100 80 60 40 20 0 Sensitivity Specificity FFR = 0.75 Specificity Sensitivity 0.80 FFR Caveats Other coronary stenosis Other coronary stenosis Distal LMCA stenosis Distal LMCA stenosis Variability of hyperemic response Variability of hyperemic response

19. IVUS shows us so much more! Courtesy of G Mintz (modified) Vessel size Vessel size Remodeling Remodeling Length Length Calcification Calcification Ostium Ostium Bifurcation Bifurcation

20. Morphological Assessment of LMCA by IVUS Maehara A et al., AJC 2001;88:1-4 OstiumBifurcationp value n=32n=55 Plaque burden (%)62 ± 1580 ± 9<0.0001 Max Calcium Arc (°)78 ± 65195 ± 101<0.0001 Eccentric plaque (%)97760.01 Lesion length (mm)2.3 ± 2.44.5 ± 2.70.001 Remodeling index0.87 ± 0.191.01 ± 0.210.005 Bifurcation vs Ostium: more calcium and plaque, longer, and more positive remodeling Distribution of atherosclerosis in LMCA: Ostium vs Bifurcation

21. 0% 100% Medina 1,1,1 (n=21) Medina 1,1,0 (n=9) Medina 1,0,1 (n=6) Medina 0,1,1 (n=11) Medina 1,0,0 (n=7) Medina 0,1,0 (n=14) Medina 0,0,1 (n=12) Medina 0,0,0 (n=60) All lesions (n=80) Others Oviedo et al. Circ Cardiovasc Interv. 2010;3:105-12

22. Impact of IVUS on TVR after LMCA Stenting Kang SJ et al., 2011;107:367-373 168 patients with distal LMCA stenosis w/ 42 mo F/U Pre-PCI MLA at POC was predictor of MACE. Pre-PCI MLA at POC was predictor of MACE. MLA at POC determined final stent size MLA at POC determined final stent size POC: Polygon of confluance

23. Ostial Left Main Stenosis

24. A B A B

25. Why IVUS is Important in LMCA Intervention IVUS improves our understanding of the pathology better and helps to plan the strategy of PCIIVUS improves our understanding of the pathology better and helps to plan the strategy of PCI Determination of the extent and distribution of atheroma in distal LMT, ostial LAD and Cx Determination of the extent and distribution of atheroma in distal LMT, ostial LAD and Cx Location and involvement of the ostium of LMCALocation and involvement of the ostium of LMCA True vessel size of LMCATrue vessel size of LMCA True vessel size of LAD and CxTrue vessel size of LAD and Cx Optimize stent expansion particularly at the osteaOptimize stent expansion particularly at the ostea Ensure coverage of the LMCA-ostium when necessaryEnsure coverage of the LMCA-ostium when necessary Identify and treat complicationsIdentify and treat complications