Complex Coronary Cases Supported by: Abbott Vascular Inc Boston Scientific Corp Terumo Vascular Corp Vascular Solutions Inc Cardiovascular Science Inc AstraZeneca Pharmaceuticals The Medicines Company Trireme Medical

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

July 21st 2015 Case #73: CW, 79 yrs M Presentation: Patient with hepatitis, cirrhosis and prior PCI of RCA, presented with new onset CCS Class III angina and dyspnea. A stress MPI revealed 2mm ST-seg depression but normal myocardial perfusion. A cardiac cath on June 12th 2015 revealed distal LM bifurcation with prox LAD and prox circumflex disease, LVEF 60% and SYNTAX score 26. Heart team discussion declined CABg due to cirrhosis. Pt continued to have class II symptoms on MMT. Prior History: Hypertension, Hyperlipidemia, Hepatitis and Cirrhosis Medications: All once daily dosage Lisinopril 10mg, Rosuvastatin 20mg, ASA 81mg, Prasugrel 5mg, Nebivolol 5mg, ISMN 60mg 3

Case# 73: cont… Cardiac Cath 6/12/2015: Right Dominance SYNTAX Score was : 26 Cardiac Cath 6/12/2015: Right Dominance dLM CAD with LVEF 60% LM: 80% distal obstruction, mild obstruction LAD: 80% prox LAD lesion, distal vessel is large with diffuse disease LCx: 60% prox LCx lesion, distal vessel is large OM1 RCA: mild diffuse disease, distal vessel is large with 30% disease in RPDA Plan Today: PCI of distal ULM bifurcation lesion with IVUS guidance 4

Appropriateness Criteria for Coronary Revascularization

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

Issues Involving The Case Role of Imaging in peri-procedural MI prediction Comparison of newer DES vs CABG in MV CAD

Issues Involving The Case Role of Imaging in peri-procedural MI prediction Comparison of newer DES vs CABG in MV CAD

Peri-procedural MI (PMI) - Occurs in 5-40% of PCI: Macro-size due to dissection, SBr occlusion or micro-size due to distal embolization, microvascular plugging, slow flow, spasm - Various definitions: Universal definition of PMI Type 4a: cTn > 5x of 99th percentile of URL or SCAI definition of PMI: CK-MB >10x ULN or cTn > 70x ULN. Associated with chest pain, EKG changes, angiographic complication and myocardial loss on imaging - PMIs are associated with ↑ future CV mortality and various approaches are used to reduce PMIs: pretreatment with oral antiplatelet therapy, high dose statin, GP IIb/IIIa inhibitors, DPD, preconditioning, BB

Imaging Parameters for Periprocedural MI Attenuated plaques by gray-scale intravascular ultrasound (IVUS) Necrotic core by radiofrequency IVUS (VH) Thin-capped fibroatheroma (TCFA) by optical coherence tomography (OCT) Large lipid core plaque by near-infrared spectroscopy (NIRS)

CANARY Trial: Patient Flow Diagram 709 consented patients All eligibility criteria met? No (n=624) PCI not done (n=317) Lesion exclusion (n=123) Other angiographic exclusion (n=128) Multi-lesion PCI (n=70) Physical discretion (n=50) Elevated biomarkers (n=32) Distal RVD too small for filter (n=17) Side branches present (n=12) Yes (n=85) Max LCBI 4mm ≥600 (n=31) Randomized 1:1 <600 (n=54) PCI with FilterWire EZ (n=14) PCI alone (n=17) PCI alone (n=54) In-hospital follow-up Stone, Kini et al., J Am Coll Cardiol Intv 2015;8:927

CANARY Trial: Procedural MI After Randomization PCI alone vs. PCI+FilterWire EZ PCI alone PCI +FilterWire EZ PCI alone (n=17) PCI +FilterWire EZ (n=14) p=0.58 Post-PCI biomarker elevation meeting Criteria (%) RR [95%CI] = 1.52 [0.50-4.60] p=0.69 p=0.66 p=>0.99 p=>0.99 4/17 5/14 troponin troponin troponin or troponin >1x ULN ≥5x ULN ≥10x ULN ≥70x ULN Peak troponin I or T or CK-MB ≥3x ULN Stone, Kini et al., J Am Coll Cardiol Intv 2015;8:927

CANARY Trial: Correlates of Periprocedural MI Stone, KIni et al., J Am Coll Cardiol Intv 2015;8:927

110 pts underwent OCT, IVUS and NIRS pre-PCI

Angiographic and Procedural Findings Kini, Sharma et al., J Am Coll Cardiol Intv 2015;8:937

OCT, IVUS and NIRS Findings Kini, Sharma et al., J Am Coll Cardiol Intv 2015;8:937

OCT, IVUS and NIRS Findings Kini, Sharma et al., J Am Coll Cardiol Intv 2015;8:937

Univariate and Multivariate Logistic Analysis for Predicting Periprocedural MI by OCT, IVUS, and NIRS Kini, Sharma et al., J Am Coll Cardiol Intv 2015;8:937

Multimodality Imaging of a Representative Case With Periprocedural MI Coronary angiography depicting significant stenosis in the LAD OCT image of thin cap fibroatheroma lesion fibrous cap thickness at thinnest portion is 60 µm (solid arrow) C, D – location of OCT/IVUS frames maxLCBI4 mm segment shown by arrows and white line Lipid arc is 159º (dashed semicircular arrow) NIRS indicates high probability of lipid-rich plaque IVUS showing plaque burden at the site of minimum lumen equal to 78% Kini, Sharma et al., J Am Coll Cardiol Intv 2015;8:937

LCBI and Plaque Burden in Stable CAD Dohi T, Maehara A, Moreno P, Kini A. EHJ Cardiov Img 2015:16:81

Issues Involving The Case Role of Imaging in peri-procedural MI prediction Comparison of newer DES vs CABG in MV CAD

MACCE to 5-Years Based on SYNTAX Score Tercile: 3 V CAD CABG TAXUS DES Death, MI or CVA 0-22 11.6 p=0.06 23-32 >33 18.8 8.4 18.2 21.1 10.5 p=0.004 p=0.006 171 155 166 181 208 207 Revascularization p=0.008 p=0.75 p=0.09 22.3 18.6 15.2 14.8 % % 12.4 11.4 171 181 208 207 166 155 0-22 23-32 >33 Mohr et al., Lancet 2013;381:629.

Cumulative Event Rate (%) Months Since Allocation SYNTAX Trial: MACCE to 5 Years by SYNTAX Score Tercile High Scores (33) TAXUS (N=290) CABG (N=315) CABG PCI P value Death 11.4% 19.2% 0.005 CVA 3.7% 3.5% 0.80 MI 3.9% 10.1% 0.004 Death, CVA or MI 17.1% 26.1% 0.007 Revasc 12.1% 30.9% <0.001 Overall 50 P<0.001 44.0% Cumulative Event Rate (%) 25 26.8% SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 57 12 24 36 48 60 Months Since Allocation Cumulative KM Event Rate ± 1.5 SE; log-rank P value Mohr et al., Lancet 2013;381:629.

FREEDOM Trial: Estimates of Key Outcomes at 5 Years after Randomization PCI (n=943) p=0.005 CABG (n=957) p=0.049 p=<0.001 p=0.12 % p=0.003 Primary Death MI Stroke CV Death Endpoint Farkouh et al., N Engl J Med 2012;367:2375 29

BEST Trial: Study Design Park et al., N Engl J Med 2015;372:2104

BEST Trial: KM Curves for the Primary Endpoint and the Major Secondary Endpoint Primary Composite Endpoint (Death, MI, TVR) Secondary Composite Endpoint (Death, MI, Stroke, rRevasc) 11% 7.9% Park et al., N Engl J Med 2015;372:2104

BEST Trial: Long-Term Clinical Endpoints After Randomization, According to Study Group PCI (n=438) CABG (n=442) p=0.04 p=0.003 % p=0.03 p=0.30 p=0.11 p=0.72 p=0.21 10 Endpoint Death MI Stroke Any revasc TVR Fatal death/MI/TVR bleeding Park et al., N Engl J Med 2015;372:2104

Study Population Bangalore et al., N Engl J Med 2015;372:1213

Risk of Primary and Secondary Outcomes in the Propensity-Score-Matched Cohort PCI (n=9223) CABG (n=9223) p=<0.001 % p=0.50 p=<0.001 p=<0.001 Death MI Stroke Revascularization Bangalore et al., N Engl J Med 2015;372:1213

Cumulative Risks of the Study Outcomes in the Matched Cohort Bangalore et al., N Engl J Med 2015;372:1213

EES vs CABG in Diabetic MV CAD: Short-Term Outcomes Within 30 Days Bangalore et al., Circ Cardiovasc Interv; ePub July 8, 2015

EES vs CABG in Diabetic MV CAD: Long-Term Outcomes Includes First 30 Days Death MI Bangalore et al., Circ Cardiovasc Interv; ePub July 8, 2015

EES vs CABG in Diabetic MV CAD: Long-Term Outcomes Includes First 30 Days Stroke Repeat Revascularization Bangalore et al., Circ Cardiovasc Interv; ePub July 8, 2015

EXCEL Trial (Evaluation of Xience Prime vs. CABG for Examination of LM Disease) LM disease (±1, 2 or 3 vessel disease) and a SYNTAX score of ≤32 Randomize 2600 pts Trial has finished enrollment After 1800 cases ABBOTT Vascular XIENCE Prime stent CABG The primary endpoint is the composite incidence of death, large MI or stroke at a median FU duration of 3 years, powered for sequential non-inferiority and superiority testing. The major secondary endpoint is the composite incidence of death, MI, stroke or unplanned repeat revascularization. All patients will be followed for 5 years total.

Take Home Message: Imaging for PMI prediction and newer DES vs Take Home Message: Imaging for PMI prediction and newer DES vs. CABG in MV CAD Multimodality invasive imaging can identify lesions likely to be associated with peri-procedure MI. OCT defined fibrous cap thickness followed by LCBI by NIRS and plaque volume by IVUS are important predictors. The use of strong antiplatelet therapy, GPI, statin and beta-blockers may be recommended to reduce PMI in these risk prone plaques on multimodality imaging (Filter DPD has no role) Recent randomized and registry data have shown that long-term death is not higher with newer DES (EES type) vs CABG in MV CAD including diabetics. Both MI and TVR is still higher with newer DES while stroke remains higher after CABG.

Question # 1 Following are the predictors of periprocedural MI on imaging except: High LCBI Lower lumen CSA on IVUS Thin cap on OCT Lower plaque burden Necrotic core on VH

Question # 2 Based on the multimodality imaging, which plaque characteristic has the highest OR for peri-procedural MI; Cap thickness on OCT LCBI on NIRS Plaque volume on IVUS Lumen CSA on IVUS Necrotic core on VH

Question # 3 In recent years, trials of newer DES vs CABG for MV CAD have shown the following except; A. Higher TVR with PCI B. Higher CVA with CABG C. Lower death rate with CABG D. Higher MI with PCI E. Higher death, MI and TVR with PCI

Question # 1 The correct answer is D Following are the predictors of periprocedural MI on imaging except: High LCBI Lower lumen CSA on IVUS Thin cap on OCT Lower plaque burden Necrotic core on VH The correct answer is D

Question # 2 The correct answer is A Based on the multimodality imaging, which plaque characteristic has the highest OR for peri-procedural MI; Cap thickness on OCT LCBI on NIRS Plaque volume on IVUS Lumen CSA on IVUS Necrotic core on VH The correct answer is A

Question # 3 The correct answer is C In recent years, trials of newer DES vs CABG for MV CAD have shown the following except; A. Higher TVR with PCI B. Higher CVA with CABG C. Lower death rate with CABG D. Higher MI with PCI E. Higher death, MI and TVR with PCI The correct answer is C