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

Does IVUS improve PCI Outcomes StudyHelpfulNo SIPSX CRUISEX Choi et alX AVIDX CENICX Gaster et alX RESISTX TULIPX OPTICUSX

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: 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 P=0.004 Non IVUS Cohort IVUS Cohort

Park SJ et al., JACC 2005;45: Comparison of BMS (IVUS 75%) and DES (IVUS 86%) MACE Free Survival (%) Months SES group BMS group 81.4 ± 3.7% 98.0 ± 1.4% IVUS in LMCA Stenting

Event-free Survival (%) Time (days) 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

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

Park SJ Circ Cardiovasc Interv 2009;2: DeathDeath or MI Patients at risk IVUS-guidance Angiography-guidance Angiography-guidance IVUS-guidance P= % ( %) 6.0% ( %) Cumulative Mortality (%) Days Patients at risk IVUS-guidance Angiography-guidance Angiography-guidance IVUS-guidance P= % ( %) 22.7% ( %) 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

Park SJ Circ Cardiovasc Interv 2009;2: TVRDeath/MI/TVR Patients at risk IVUS-guidance Angiography-guidance Angiography-guidance IVUS-guidance P= % ( %) 8.8% ( %) Cumulative Incidence of TVR (%) Days Patients at risk IVUS-guidance Angiography-guidance P= 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

IVUS Guidance in DES for LMCA Stenosis Cumulative Mortality (%) Patients at risk IVUS-guidance Angiography-guidance Months % 16.0% P=0.048 Angiography-guidance IVUS-guidance 3 year mortality (K-M) in 145 propensity matched pairs

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

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

IVUS and Left Main Disease IVUS MLD (mm) QCA MLD (mm) r= IVUS ref (mm) QCA Ref. (mm) 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 p=0.106 AS Abizaid et al JACC 1999;34: MACE IVUS MLD (mm) 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

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

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. ACCi Assessment of Intermediate LMCA Lesions by IVUS Survival in Revascularized and Deferred Patients

Time Defer (medical therapy) with MLA ≥6mm 2 (n=179) Survival free of Cardiac Death P= 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

The Assessment of LMCA Shortfalls of Luminology for Even Experienced Clinicians

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): 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%

The Grey Zone of FFR De Bruyne B et al. Circulation 2001;104: FFR 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

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

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< Max Calcium Arc (°)78 ± ± 101< Eccentric plaque (%) Lesion length (mm)2.3 ± ± Remodeling index0.87 ± ± Bifurcation vs Ostium: more calcium and plaque, longer, and more positive remodeling Distribution of atherosclerosis in LMCA: Ostium vs Bifurcation

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

Impact of IVUS on TVR after LMCA Stenting Kang SJ et al., 2011;107: 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

Ostial Left Main Stenosis

A B A B

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