Complex Coronary Cases Supported by: Abbott Vascular Inc Boston Scientific Corp Terumo Vascular Corp Vascular Solutions Inc Cardiovascular Science Inc AstraZeneca Pharmaceuticals

Disclosures Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, AngioScore, DSI/Lilly Inc., ABIOMED, CSI Annapoorna S. Kini, MBBS, FACC Nothing to disclose Sameer Mehta, MBBS, FACC Consulting Fees – The Medicines Company

January 20th 2015 Case #67: CG, 83 yrs F Presentation: Patient with cresendo angina CCS Class III and dyspnea on minimal exertion for last 2 weeks. Pt has known moderate ULM+ 2V CAD on cath in 2009 and being managed medically after declining CABG and remained stable until few weeks ago. A Cardiac cath done on 1/12/2015 revealed distal ULM bifurcation disease with normal LVEF and normal right heart pressures. Heart team consultation took place and pt elected for PCI Prior History: Hypertension, Hyperlipidemia, PUD, H/o DVT Medications: All once daily dosage Atenolol 50mg, Amlodipine 10mg, Simvastatin 40mg, ASA 81mg, Fenofibrate 48mg, Ranolazine 1000mg, Esomeprazole 40mg 3

Case# 67: cont… Cardiac Cath 1/12/2015: Right Dominance LM+2 V CAD with LVEF 60% RCA: mild diffuse disease, large size LM: 70% calcific bifurcation disease LAD: 60-70% heavily calcified ostial LAD, large size, mild diffuse D1 LCx: 80% heavily calcified prox LCx lesion, large size vessel SYNTAX Score was : 24 Plan Today: PCI of calcified distal LM lesion involving OCT, Rotational atherectomy and planned 2 Stent approach. 4

Appropriateness Criteria for Coronary Revascularization

Appropriate Mode of Revascularization for Multi-vessel and LM CAD CABG PCI Two-vessel CAD with proximal LAD stenosis A Three Vessel CAD with low CAD burden (i.e., three focal stenosis, low SYNTAX score) Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, presence of CTO, or high SYNTAX score >32) U Isolated left main stenosis Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33) Left main stenosis and additional CAD with intermediate to high CAD burden (i.e., three vessel involvement, presence of CTO, or high SYNTAX score >32) I 6

Issues Involving The Case Update on Unprotected Left Main (ULM) PCI Risk of Non-cardiac Surgery after Coronary Stenting

Issues Involving The Case Update on Unprotected Left Main (ULM) PCI Risk of Non-cardiac Surgery after Coronary Stenting

LMCA Stenosis Location LCX About two third of LMCA Lesions include distal bifurcation; 1/3rd are ostial/shaft lesions 66% Bifurcation LMCA 26% Ostium 8% Body-Shaft LAD

SYNTAX Trial: 5-Year Outcomes in Pts with LM Disease Treated with PCI or CABG CABG (n=348) TAXUS (n=357) p=<0.001 % p=0.53 p=0.03 p=0.03 Mohr et al., Lancet 2013;381:629

Cumulative Event Curves for MACCE by Baseline SYNTAX Score Tercile Overall Cohort Left Main Coronary Disease Subgroup Three-Vessel Disease Subgroup Mohr et al., Lancet 2013;381:629

SYNTAX Score-ll Eight Predictors Anatomical SYNTAX Score Age Creatinine clearance Left ventricular ejection fraction (LVEF) Presence of unprotected left main coronary artery (ULMCA) disease Peripheral vascular disease (PVD) Female Sex Chronic obstructive pulmonary disease (COPD) Farooq et al., Lancet 2013;381:639

All other interaction P values <0.10 SYNTAX Score II: Designed to Objectively Discriminate Between CABG and PCI Interactions All other interaction P values <0.10 2 CrCl Syntax score Age LVEF 1 Pint = 0.30 Log HR -1 PCI PCI PCI PCI CABG CABG CABG CABG -2 20 40 60 60 70 80 90 30 60 90 120 10 20 30 40 50 60 Log HR 2 1 -1 -2 PVD 3VD vs LM Gender COPD Pint = 1.0 PCI PCI PCI PCI CABG CABG CABG CABG 3VD LMS F M No Yes No Yes Farooq V et al. Lancet 2013;381:639.

Event Rates Stratified by the SYNTAX Score-ll Through 5 Years All-cause death MI Ischemic-driven TVR Xu et al., J Am coll Cardiol Intv 2014;7:1128

MACCE Rates Stratified by the SYNTAX Score-ll Through 5 Years Xu et al., J Am coll Cardiol Intv 2014;7:1128

Bifurcation Angle (BA) Analysis 2-D Single-Plane Angiographic Images LM bifurcation in LAO caudal view LM bifurcation in RAO caudal view New BA parameter: Systolic-diastolic range (SDR) defined as absolute difference between diastolic & systolic distal BA values (<10 vs >100) 3-D Reconstructed Image Proximal BA defined between the LM stem and LCx; distal BA defined between LAD and LCx Post PCI, proximal BA is enlarged, the distal BA gets narrower Girasis et al., J Am Coll Cardiol 2010;3:41

Impact of PCI Diastolic Distal Bifurcation Angle (BA) on 5-Year MACCE All-cause death, CVA, MI and Repeat Revascularization MACCE at 5 yrs – pre-PCI distal BA Pts with 1 stent in LMCA bifurcation (n=75) MACCE at 5 yrs – pre-PCI distal BA Pts with ≥2 stents in LMCA bifurcation (n=110) Girasis et al., J Am Coll Cardiol Intv 2013;6:1250

Impact of Post-PCI Systolic-Diastolic Range (SDR) of the Distal BA on 5-Year MACCE All-cause death, CVA, MI and Repeat Revascularization MACCE at 5 yrs – post-PCI BA SDR Pts with 1 stent in LMCA bifurcation (n=75) MACCE at 5 yrs – post-PCI BA SDR Pts with ≥2 stents in LMCA bifurcation (n=110) Girasis et al., J Am Coll Cardiol Intv 2013;6:1250

DELTA Registry: Cumulative Incidence of MACCE at Follow-up of 5 Yrs PCI Overall (n=1874) CABG Overall (n=900) % Chieffo et al., J Am Coll Cardiol Intev 2012;5:718

DELTA Registry: Study Population Flow Chart Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

DELTA Registry: Cumulative Incidence of MACCE at 5 Yrs in Ostial/mid Shaft LM Lesions PCI group (n=482) - 1 DES P= 0.06 CABG group (n=374) % P= NS P= 0.009 P= NS P= NS Naganuma et al., J Am Coll Cardiol Intev 2014;7:354

Proposed Approach to LM PCI Single Stent Crossover DK Crush II T stenting SKS/V stent Culotte stent Single Stent Crossover Sign LCX 50% Insign or small LCX Small LM 4 mm Large LM

Bifurcation Left Main Stenting An approach for bifurcational lesions when using 2 stents as planned strategy Bifurcational lesion with short disease proximal to the bifurcation or very short left main and each branch is large size Bifurcational lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 900 angle Bifurcational lesion with main branch disease extending proximal to the bifurcation and side branch which has origin with about 600 angle DK/MINI Crush SKS/V-STENT T-STENT

DKCRUSH III Study: Clinical Follow-up at 12 Months DK Group (n=210) p=0.001 Culotte Group (n=209) p=0.02 % p=0.38 p=1.00 p=0.62 Chen et al., JACC 2013;61:1482

Method of Revascularization of Multi-vessel and LM Coronary Artery disease CABG PCI Two-vessel CAD with proximal LAD stenosis A Three Vessel CAD with low CAD burden (i.e., three focal stenosis, low SYNTAX score) Three-vessel CAD with intermediate to high CAD burden (i.e., multiple diffuse lesions, presence of CTO, or high SYNTAX score >32)/DM U/I Isolated left main stenosis U Left main stenosis and additional CAD with low CAD burden (i.e., one to two vessel additional involvement, low SYNTAX score <33) Left main stenosis and additional CAD with intermediate to high CAD burden (i.e., three vessel involvement, presence of CTO, or high SYNTAX score >32) I 29

Indication for CABG vs PCI in Stable CAD with LMCA Involvement American and European Guidelines

Completed Randomized Studies Evaluating Unprotected Left Main Revascularization with PCI vs CABG Noble Excel N patients, sites 1200; 26 European sites 1900; 126 sites in 17 countries DES BES Biomatrix® EES, Xience, V/Prime® LM location Ostial, shaft, or bifurcation LM severity Angio DS >50% or FFR ≤0.80 Angio DS ≥70% or ≥50% - <70% + either FFR ≤0.80 or IVUS MLA ≤6.0 mm2 or extensive ischemia Other anatomic inclusion criteria ≤3 additional non-complex lesions (excludes length >25 mm, CTO, 2-stent bifurcation, calcified or tortuous vessels) SYNTAX Score ≤32 Primary endpoint Death, CVA, non-index MI, revascularization Death, CVA, MI Timing of primary EP 2 years Median 3 years Duration of follow-up 5 years 5 year Completed

Issues Involving The Case Update on Unprotected Left Main (ULM) PCI Risk of Non-cardiac Surgery after Coronary Stenting

Risk of MACE Following Non-Cardiac Surgery in Patients with Coronary Stents Time Between Stent and Surgery Associated with MACE at 24 Months (N=124,844) p = <0.001 % Hawn et al., JAMA 2013;310:1462

61,770 matched pts at VA centers who underwent stenting were compared in gps; who underwent non-cardiac surgery vs who did not undergo surgery in 1:2 ratio

Cumulative Incidence of Adverse Cardiac Events Following Coronary Stent Placement Holcomb et al., J Am Coll Cardiol 2014;64:2730

Adverse Cardiac Events and All-Cause Mortality at 30-Days Post-Operative Time Interval: Surgical vs Nonsurgical Cohort Event All-Patients (N=16,770) Stent/Surg (N=20,590) Stent Only (N=41,180) p Overall Risk Difference, % (95% CI) Composite MACE 2.3 3.1 1.9 <0.001 1.3 (1.0 to 1.5) MI 1.6 2.5 1.1 1.4 (1.2 to 1.7) Revascularization 1.0 0.37 0.1 (-0.1 to 0.3) Al-cause mortality 0.7 1.4 0.4 1.0 (0.9 to 1.2) Holcomb et al., J Am Coll Cardiol 2014;64:2730

Outcomes and Risk Differences in Surgical vs Nonsurgical Cohorts 30-Day Adverse Cardiac Event Rates (Surgical and Nonsurgical Cohorts) Rates for Surgical and Nonsurgical Cohorts Immediately Post-Stent Holcomb et al., J Am Coll Cardiol 2014;64:2730

Incremental Risk of Non-Cardiac Surgery <6 Weeks (n=3222) 6 Weeks to 6 Months (n=13,419) >6 Months to 24 Months (n=45,129) % Composite cardiac MI Revascularization All-cause mortality Holcomb et al., J Am Coll Cardiol 2014;64:2730

∆Risk Difference for Adverse Cardiac Events in the Stent/Surgery Group Holcomb et al., J Am Coll Cardiol 2014;64:2730

Risk Difference in Adverse CE 30 Days Following Surgery for Pts with Coronary Stents Holcomb et al., J Am Coll Cardiol 2014;64:2730

After DAPT Interruption Xience V USA Registry: Late ST Rates (30 D – 1 Year) After DAPT Interruption Overall Standard (Low) Risk Subsequent Late ST (ARC Def/Prob) (%) 0.49 0.37 0.26 0.16 13/3500 2/1272 2/435 0/157 1/378 0/147 0/292 0/120 No Interruption Interruption After 30 Days Interruption After 90 Days Interruption After 180 Days Krucoff, Hermiller, Sharma et al. JACC Intervent 2011;4:1298.

Stepwise Approach to Perioperative Cardiac Assessment for CAD Fleisher et al., J Am Coll Cardiol 2014;64:2373

Summary of Recommendations for Supplemental Perioperative Evaluation Fleisher et al., J Am Coll Cardiol 2014;64:2373

Summary of Recommendations for Perioperative Therapy Fleisher et al., J Am Coll Cardiol 2014;64:2373

Algorithm for Antiplatelet Management in Patients with PCI and Non-Cardiac Surgery DES: 6 mths Fleisher et al., J Am Coll Cardiol 2014;64:2373

Clinical Outcomes With Short (≤6 Months) vs Standard (At Least 12 Months) DAPT Stefanini et al., J Am Coll Cardiol 2014;64:953

Take Home Message: Updates on ULM PCI and Risk of Non-cardiac surgery after stenting Recent data support use of PCI in low-to-moderately complex ULM lesions with outcomes similar to CABG especially ostial/shaft lesions. In more complex lesions (Syntax score >32), CABG remains the standard choice. Results of completed EXCEL trial will have the final answer on this issue. ?BA prediction Risk of non-cardiac surgery after stenting is highest in first 6 week period and then continue to decline overtime with significant reduction after 6 months. Hence unless really urgent, non-cardiac surgery should be deferred after 6 months post stenting.

Question # 1 In which SYNTAX score group of LM disease, CABG was superior to PCI at 5 years with lower MACCE: SYNTAX score <23 SYNTAX score >23 SYNTAX score 23-32 SYNTAX score >32 All SYNTAX groups

Question # 2 Which ULM pt will be Class III indication for PCI as per ACC Guidelines: Isolated ULM lesion with SYNTAX score 32 ULM lesion with 2 V CAD and SYNTAX score 33 and low surgical risk ULM lesion with 2 V CAD and SYNTAX score 33 and high surgical risk ULM lesion with 3 V CAD and SYNTAX score 22 ULM lesion with 1 CTO and SYNTAX score 31

Question # 3 Recent data have suggested deferring non-cardiac surgery post stenting for……….. months to significantly reduce cardiac events: A. 1.5 months B. 3 months C. 6 months D. 12 months E. >12 months

Question # 1 The correct answer is D In which SYNTAX score group of LM disease, CABG was superior to PCI at 5 years with lower MACCE: SYNTAX score <23 SYNTAX score >23 SYNTAX score 23-32 SYNTAX score >32 All SYNTAX groups The correct answer is D

Question # 2 The correct answer is B Which ULM pt will be Class III indication for PCI as per ACC Guidelines: Isolated ULM lesion with SYNTAX score 32 ULM lesion with 2 V CAD and SYNTAX score 33 and low surgical risk ULM lesion with 2 V CAD and SYNTAX score 33 and high surgical risk ULM lesion with 3 V CAD and SYNTAX score 22 ULM lesion with 1 CTO and SYNTAX score 31 The correct answer is B

Question # 3 The correct answer is C Recent data have suggested deferring non-cardiac surgery post stenting for……….. months to significantly reduce cardiac events: A. 1.5 months B. 3 months C. 6 months D. 12 months E. >12 months The correct answer is C