IVUS Use during Left Main PCI improve Immediate and Long Term Outcome Where is the Evidence?

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 Study Helpful No SIPS X CRUISE X Choi et al X AVID X CENIC X Gaster et al X RESIST X TULIP X OPTICUS X

3. Role of IVUS in Stenting in the DES Era Intravascular IVUS-guided DES Placement Associated with Reduced Incidence of Recurrent Clinical Events 1504 pts, IVUS guidance in 632 (42%), F/U 2 yrs CRF and Amsterdam 15 Non IVUS Cohort IVUS Cohort Multivariate Analysis for Predicting Death/MI IVUS guidance Age CHF Renal impairment 12 P=0.004 9 6 3 0 0 0.5 1.0 1.5 2.0 Time in Years B. Claessen et al., JACC 2010;56:41

4. IVUS in LMCA Stenting Comparison of BMS (IVUS 75%) and DES (IVUS 86%) MACE Free Survival (%) 100 98.0 ± 1.4% 90 80 81.4 ± 3.7% 70 SES group BMS group 60 0 0 2 4 6 8 10 12 Months Park SJ et al., JACC 2005;45:351-356

5. IVUS Guidance in DES for LMCA Stenosis Event Free Survival in 24 IVUS+ and 34 IVUS- Patients Event-free Survival (%) 1.0 IVUS (n=14) No IVUS (n=12) No IVUS (n=22) IVUS (n=10) .5 Distal LM Non-Distal LM 0.0 0 200 400 600 800 1000 Time (days) Agostoni et al AJC 2005;95:644-7

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

7. IVUS Guidance in Stenting for LMCA Stenosis 3 year death and MI (K-M) in 201 propensity matched pairs Death Death or MI Cumulative Incidence of Death or MI (%) Cumulative Mortality (%) 40 40 Angiography-guidance IVUS-guidance Angiography-guidance IVUS-guidance 30 30 P=0.078 22.7% (16.2-29.2%) P=0.063 20 20 13.6% (8.0-19.24%) 13.9% (9.1-18.8%) 10 10 6.0% (2.6-9.4%) 0 0 0 180 360 540 720 900 1000 0 180 360 540 720 900 1000 Days Days Patients at risk Patients at risk IVUS-guidance 201 178 131 82 Angiography-guidance 201 175 128 67 IVUS-guidance 201 194 143 88 Angiography-guidance 201 191 138 64 Park SJ Circ Cardiovasc Interv 2009;2:167-177

8. IVUS Guidance in DES for LMCA Stenosis 3 year TVR and MACE (K-M) in 201 propensity matched pairs TVR Death/MI/TVR Cumulative Incidence of Death, MI or TVR (%) Cumulative Incidence of TVR (%) 40 40 Angiography-guidance IVUS-guidance Angiography-guidance IVUS-guidance 30 30 28.0% P=0.274 P=0.056 22.2% 20 20 11.9% (7.3-16.5%) 10 10 8.8% (4.6-12.9%) 0 0 0 180 360 540 720 900 1000 0 180 360 540 720 900 1080 Patients at risk Months Patients at risk Days IVUS-guidance 201 176 125 18 Angiography-guidance 201 179 129 70 IVUS-guidance 201 164 115 74 Angiography-guidance 201 168 129 64 Park SJ Circ Cardiovasc Interv 2009;2:167-177

9. IVUS Guidance in DES for LMCA Stenosis 3 year mortality (K-M) in 145 propensity matched pairs Cumulative Mortality (%) 40 Angiography-guidance IVUS-guidance 30 P=0.048 20 16.0% 10 4.4% 0 0 180 360 540 720 900 1080 Months Patients at risk IVUS-guidance 145 140 98 37 Angiography-guidance 145 137 88 29

10. Differences in Patient Outcomes for LMCA PCI Thoraxcenter vs. Asan Medical Center: Impact of BaselineCharacteristics 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, 2010 Park DW et al., JACC, 2010

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

12. IVUS and Left Main Disease 122 patients with moderate LMCA disease, f/u 1 year MACE 7 8 7 1.0 6 DM and 1 untreated vessel with DS 50% 6 5 0.9 5 4 IVUS MLD (mm) IVUS ref (mm) 4 0.8 3 3 DM and no untreated vessels 2 0.7 2 1 r=0.364 r=0.495 1 0.6 0 0 0 1 2 3 4 5 6 7 No DM and 1 untreated vessel with DS 50% 0 1 2 3 4 5 6 7 8 0.5 QCA MLD (mm) QCA Ref. (mm) 0.4 Independent predictors of MACE DM (P=0.004) Any untreated lesion >50% (p=0.04) IVUS MLD (P=0.005) 100 0.3 p=0.106 80 0.2 60 0.1 IVUS DS 40 0.0 No DM and no untreated vessels 20 1.4 2.2 3.0 3.8 4.6 5.4 1.8 2.6 3.4 4.2 5.0 5.8 0 IVUS MLD (mm) 0 20 40 60 80 100 QCA DS AS Abizaid et al JACC 1999;34:707-15

13. Assessment of Intermediate LMCA Lesions by IVUS LITRO Study – 22 Spanish Centers 354 Patients MLA ≥6.0 mm2 (N=186) MLA <6.0 mm2 (N=168) 7 revascularized 16 not revascularized No LMCA revascularization (n=179, 96%) LMCA revascularization (n=152, 90%) 55% CABG 45% PCI (+ other vessels in 62%) 56% PCI of other vessels De La Torre Hernandez et al. ACCi2 2010

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

15. Assessment of Intermediate LMCA Lesions by IVUS LITRO Study – Survival in Medically Treated Patients 100 80 60 40 Defer (medical therapy) with MLA ≥6mm2 (n=179) Defer (medical therapy) with MLA <6mm2 (n=160) 20 Survival free of Cardiac Death P=0.02 0 0 100 200 300 400 500 600 700 Time 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 51 intermediate LMT assessed by angiography and FFR Visual Assessment % (absolute #) Reviewer A ns correct 53% 27/51 s incorrect 22% 11/51 u unsure 25% 13/51 Reviewer B ns correct 49% 25/51 s incorrect 39% 20/51 u unsure 12% 6/51 Reviewer C ns correct 51% 26/51 s incorrect 49% 25/51 u unsure - 0/51 Reviewer C ns correct 45% 23/51 s incorrect 33% 17/51 u unsure 22% 11/51 Reviewer Assessment Results • 4 experienced interventional cardiologist correctly classified lesion severity in 50% of patients. • Interobserver variability was large resulting in unanimous correct classification in only 29% Lindstaedt M et al. Int J Cardiol. 2007;120(2):254-261

18. The Grey Zone of FFR FFR Caveats • Other coronary stenosis • Distal LMCA stenosis • Variability of hyperemic response Sensitivity 100 Specificity 80 60 40 Sensitivity Specificity 20 0 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0 0.80 FFR = 0.75 FFR De Bruyne B et al. Circulation 2001;104:157-162

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

20. Morphological Assessment of LMCA by IVUS Distribution of atherosclerosis in LMCA: Ostiumvs Bifurcation Ostium Bifurcation p value n=32 n=55 Plaque burden (%) 62 ± 15 80 ± 9 <0.0001 Max Calcium Arc (°) 78 ± 65 195 ± 101 <0.0001 Eccentric plaque (%) 97 76 0.01 Lesion length (mm) 2.3 ± 2.4 4.5 ± 2.7 0.001 Remodeling index 0.87 ± 0.19 1.01 ± 0.21 0.005 Bifurcation vs Ostium: more calcium and plaque, longer, and more positive remodeling Maehara A et al., AJC 2001;88:1-4

21. Others All lesions (n=80) 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) 0% 100% Oviedo et al. Circ Cardiovasc Interv. 2010;3:105-12

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

23. Ostial Left Main Stenosis

24. Ostial Left Main Stenosis B B A A

25. Why IVUS is Important in LMCA Intervention • IVUS 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 • Location and involvement of the ostium of LMCA • True vessel size of LMCA • True vessel size of LAD and Cx • Optimize stent expansion particularly at the ostea • Ensure coverage of the LMCA-ostium when necessary • Identify and treat complications