Complex Coronary Cases Supported by: Abbott Vascular Boston Scientific Corporation Medtronic, Inc. AstraZeneca St Jude’s Medical Abiomed Vascular solution CSI Inc.

Disclosures Samin K. Sharma, MBBS, FACC Speaker’s Bureau – Boston Scientific Corporation, Abbott Vascular Inc, AngioScore, Daiichi Sankyo Inc, Abiomed, CSI Annapoorna S. Kini, MBBS, FACC Nothing to disclose Sameer Mehta, MBBS, FACC Consulting Fees – The Medicines Company American College of Cardiology Foundation staff involved with this case have nothing to disclose

Feb 18th 2014 Case #20: CS, 82 yrs M Presentation: Patient presented with new onset exertional dyspnea and negative stress MPI, but coronary CTA revealed extensive calcific three vessel CAD. A cardiac cath on Jan 10th 2014 revealed complex calcific 3 V CAD with normal lV function (SYNTAX score 36). Heart team discussion took place and CABG was recommended but declined by the pt and family. Pt was placed on MMT. Prior History: Hypertension, Hyperlipidemia, prior CVA in 2001 with no deficit Medications: All once daily dosage Metoprolol XL 25mg, ISMN 60mg, ASA 81mg, Atorvastatin 20mg, Valsartan 80mg 3

Case# 20: cont… SYNTAX score 36 Cardiac Cath 01/10/2014: Right Dominance 3 V CAD with LVEF 60% Left Main: no obstruction LAD: 80% calcified lesions in prox and mid LAD, 90% D1/D2 LCx: multiple 80-90% lesions in prox, OM1/OM2 and LPL RCA: 90% calcified lesion in prox with moderate diffuse disease in large vessel and 80% diffuse RPDA lesion CABG was recommended after Heart team discussion and pt declined and went home on MMT to think over about CABG. Pt continued to have DOE symptoms <1block (CCS class III). Plan Today: - PCI of calcific RCA as 1st part of staged multi-vessel PCI SYNTAX score 36 4

Appropriateness Criteria for Coronary Revascularization

Issues Involving The Case Status of Trans Radial Intervention (TRI-PCI) Role of Kissing Balloon Inflation (KBI) in PCI

Issues Involving The Case Status of Trans Radial Intervention (TRI-PCI) Role of Kissing Balloon Inflation (KBI) in PCI

Adoption of Radial Access in PCI in US Trend in the Use of r-PCI Over Time in the Overall & Key Subgroups All Patients 20 18 16 14 12 10 8 6 4 2 16.1% % Radial Overall % Radial PCI 2007 - Qtr 2007 - Qtr 2008 - Qtr 2008 - Qtr 2009 - Qtr 2009 - Qtr 2010 - Qtr 2010 - Qtr 2011 - Qtr 2011 - Qtr 2012 - Qtr 2012 - Qtr Men and Women Pts with Stable angina, NSTE ACS, STEMI 20 18 16 14 12 10 8 6 4 2 20 18 16 14 12 10 8 6 4 2 Female Male UA/NSTEMI STEMI Stable Angina % Radial % Radial 2007 - Qtr 2007 - Qtr 2008 - Qtr 2008 - Qtr 2009 - Qtr 2009 - Qtr 2010 - Qtr 2010 - Qtr 2011 - Qtr 2011 - Qtr 2012 - Qtr 2012 - Qtr 2007 - Qtr 2007 - Qtr 2008 - Qtr 2008 - Qtr 2009 - Qtr 2009 - Qtr 2010 - Qtr 2010 - Qtr 2011 - Qtr 2011 - Qtr 2012 - Qtr 2012 - Qtr Feldman et al., Circulation 2013;127:2295

Adoption of Radial Access in PCI Unadjusted Rates of the Primary Outcomes of r-PCI and f-PCI r-PCI f-PCI % Feldman et al., Circulation 2013;127:2295

Adoption of Radial Access in PCI Unadjusted and Adjusted Association Between r-PCI and Primary Outcomes (f-PCI as Reference) Unadjusted Adjusted Odds Ratio Outcome OR (95% CI) p Value C Index Procedural Success 1.24 (1.17-1.33) <0.001 1.13 (1.06-1.20) 0.651 Any bleeding compl 0.42 (0.40-0.45) 0.51 (0.49-0.54) 0.774 Any vasc compl 0.36 (0.28-0.45) 0.39 (0.31-0.50) 0.672 Feldman et al., Circulation 2013;127:2295

Radial Access in STEMI PCI Temporal Trend in Use of TRI for STEMI PCI from 2007 to 2011 Baklanov et al., JACC 2013;61:420

Radial Access in STEMI PCI Procedural Characteristics in Patients with STEMI Treated with Radial and Femoral Access PCI Baklanov et al., JACC 2013;61:420

Radial Access in STEMI PCI In-Hospital Outcomes of TRI in STEMI Baklanov et al., JACC 2013;61:420

SAFE-PCI for Women: Objective To Determine the Efficacy and Feasibility of Transradial PCI in Women

SAFE-PCI for Women Trial: Study Design Female patient undergoing PCI or cardiac cath w/poss. PCI Radial Femoral N=3000 pts randomized for 1800 PCI pts Patent hemostasis required Vascular closure devices allowed Best background medical therapy Bivalirudin, P2Y12 inhibitors 2b3a at investigator’s discretion Primary Efficacy Endpoint (72 hrs or hospital discharge): BARC Types 2, 3, or 5 bleeding or Vascular Complications requiring intervention Primary Feasibility Endpoint: Access site crossover Secondary endpoints: Procedure duration, total radiation dose, total contrast volume, 30-day death/vascular complications/unplanned revas. Rao et al, TCT 2013

SAFE-PCI for Women: Endpoint Definitions Primary Efficacy Endpoint Primary Feasibility Endpoint BARC Bleeding Type 2: Overt, actionable bleeding not meeting criteria for type 3, 4, or 5 bleeding Type 3: Overt bleeding with hgb drop ≥ 3 g/dL (corrected for transfusion) Transfusion with overt bleeding cardiac tamponade bleeding requiring surgical intervention or intravenous vasoactive drugs intraocular bleeding or ICH Type 5: Fatal bleeding Vascular complications requiring intervention AV fistula Pseudoaneurysm Arterial access site occlusion Access site crossover Inability to complete the procedure from the assigned access site CEC Adjudication of all suspected bleeding or vascular complication events Rao et al, TCT 2013

SAFE-PCI for Women Trial: Methods Workflow Randomization Demographics Medical Hx Procedural data Autopopulate Unique pages for trial Analytic Database Rao et al, TCT 2013

SAFE-PCI for Women Trial: Conduct After 1120 women had been randomized, routine review of trial endpoints by DSMB Primary efficacy event rate markedly lower than expected Trial unlikely to show a difference at the planned sample size Recommended termination of the trial No harm noted in either the radial or femoral groups Steering committee voted to continue study until enrollment in a quality-of-life sub-study was complete (N=300) Rao et al, TCT 2013

SAFE-PCI for Women Trial: Final Recruitment 1787 women randomized At 60 US sites 893 women assigned to Radial 894 women assigned to Femoral ITT: Primary 72 hr or discharge endpoints 891 women 345 underwent PCI 884 women Secondary 30-day endpoints 290 PCI pts 292 PCI pts 96.7% of sites enrolled ≥ 1 patient 70.9% of sites enrolled ≥ 10 patients Rao et al, TCT 2013

SAFE-PCI for Women Trial: Baseline Characteristics Total Randomized Cohort Radial (N=893) Femoral (N=894) Median age, yrs 63.4 (55.1, 72.2) 63.9 (55.7, 72.0) Median BMI, kg/m2 30.5 (26.1, 35.1) 30.8 (26.5, 35.8) Current or Recent smoker 27.2% 24.2% HTN 79.5% 79.9 Prior MI 17.9% 19.6% Prior CABG 4.5% 6.4% Dialysis 0.3% PAD 5.7% 6.0% Diabetes 35.2% 35.0% CAD presentation Non-ACS NSTEACS STEMI 46.8% 52.7% 0.4% 43.5% 56.3% 0.2% Rao et al, TCT 2013

SAFE-PCI for Women Trial: Primary Efficacy and Feasibility Endpoints Total Randomized Cohort Radial (n=893) Radial (N=893) Femoral (N=894) OR (95% CI) P BARC 2, 3, 5 bleeding or Vasc Complications 0.6% 1.7% 0.3 (0.1-0.9) 0.03 Access site crossover 6.7% 1.9% 3.7 (2.1-6.4) <0.001 Femoral (n=894) p=<0.001 % p=0.03 BARC bleeding Access site or vasc compl crossover Most common reason for needing to convert from radial to femoral access to complete the procedure was radial artery spasm (43.6% of crossovers) Only one patient did not have the procedure successfully completed – was randomized to femoral Rao et al, TCT 2013

SAFE-PCI for Women Trial: Primary Efficacy and Feasibility Endpoints PCI Cohort Radial (n=345) Radial (N=345) Femoral (N=346) OR (95% CI) P BARC 2, 3, 5 bleeding or Vasc Complications 1.2% 2.9% 0.4 (0.1-1.3) 0.12 Access site crossover 6.1% 1.7% 3.6 (1.5-9.2) 0.006 Femoral (n=346) p=0.006 % p=0.12 BARC bleeding Access site or vasc compl crossover Most common reason for needing to convert from radial to femoral access to complete the procedure was radial artery spasm (42.9% of crossovers) Interactions not significant for ACS vs. Non-ACS, tertiles of site radial volume, or PCI vs. no PCI Rao et al, TCT 2013

SAFE-PCI for Women Trial: Secondary Endpoints PCI Cohort Radial (N=290) Femoral (N=291) P Procedure duration (min) 51.6 ± 32.3 49.9 ± 30.5 0.46 Total radiation dose (mGy) 1604 ± 1394 1472 ± 1274 0.26 Total contrast volume (mL) 152.7 ± 76.9 165.6 ± 82.7 0.03 30-day death, vascular complications, or unplanned revasc 5.2% 3.4% Patient prefers assigned access site for next procedure 71.9% 23.5% 0.01 Rao et al, TCT 2013

SAFE-PCI for Women Trial: Conclusions The SAFE-PCI for Women Trial represents several “firsts” The first randomized trial comparing interventional strategies in women The first multicenter randomized trial comparing radial with femoral access in the United States The first registry-based randomized trial in the United States In this trial that did not reach its planned enrollment due to early termination, radial access Did not significantly reduce bleeding or vascular complications in the subgroup of women undergoing PCI Did significantly reduce bleeding or vascular complications in the larger sample size of all women undergoing cardiac catheterization or PCI Was preferred over femoral approach by the majority of women undergoing PCI Increased the need for conversion to femoral access in ~6% of cases Rao et al, TCT 2013

RADIAL-CABG Trial: Patient Screening & Enrollment Screened n=237 109 patients were not included for the following reasons: Abnormal Allen’s test, n=29 Participation in other trials, n=33 Known severe peripheral vascular disease, n=18 CTO interventions, n=17 Known occluded grafts, n=4 Declined participation, n=6 Elevated INR, n=2 Randomized n=128 Transfemoral approach n=64 Transradial approach n=64 Had diagnostic cath only (n=34) Had diagnostic cath + PCI (n=29) Had PCI only (n=1) Crossover TR access (n=0) Hand diagnostic cath only (n=40) Had diagnostic cath + PCI (n=23) Had PCI only (n=1) Crossover to TF access (n=1) Michael et al., JACC Cardiovasc Interv 2013;6:1138

RADIAL-CABG Trial: Procedural Outcomes and Resource Use in Patients Undergoing Diagnostic Coronary Angiography Michael et al., JACC Cardiovasc Interv 2013;6:1138

RADIAL-CABG Trial: Procedural Outcomes and Resource Use in Patients Undergoing Coronary Intervention Michael et al., JACC Cardiovasc Interv 2013;6:1138

RADIAL-CABG Trial: Patients’ Access Preference for Future Catheterization TR Group TF Group Others in Radial group: Lower adhoc PCI Higher access crossover 17% Similar vascular complications p=<0.001 % Michael et al., JACC Cardiovasc Interv 2013;6:1138

Status of Trans-Radial PCI: Recommendations STEMI ACS ↓MACE + ↓Bleeding - High risk of bleeding - Overweight - PAD - ? Women - ? Routine Benefit in ↓ Bleeding or Vascular Compl CABG pt Radial spasms/AV fistula Aortic Arch anomaly No Benefit or harm Increasing TRI Volume

Issues Involving The Case Status of Trans Radial Intervention (TRI-PCI) Role of Kissing Balloon Inflation (KBI) in PCI

Kissing Balloon Inflation Rules Guiding the Choice of the Balloon Diameters for Kissing Balloon Inflation Squeglia and Chevalier, JACC Cardiovasc Interv 2012;5:803

Kissing Balloon Inflation Summary of Clinical Trials Assessing the Clinical Utility of KB Inflation in PCI Study N (KB vs Non-KB) % F/U Cardiac Death (KB vs Non-KB) % MI TLR MACE ST (KB vs Npn-KB) THUEBIS 56 vs 54 6 mos 0 vs 3.7 3.6 vs 1.9 17.9 vs 14.8 23.2 vs 24.1 Nordic III 238 vs 239 0.8 vs 0 0.4 vs 1.3 1.3 vs 1.7 2.1 vs 2.5 0.4 vs 0.4 CORPAL Kiss 124 vs120 12 mos 0.8 vs 1.7 3.2 vs 1.7 4.0 vs 1.7 9.0 vs 6.0 0.8 vs 0.8 Squeglia and Chevalier, JACC Cardiovasc Interv 2012;5:803

Outcome of Kissing Balloon Inflation in Single Stent Strategy in Randomized Trials KB Inflation Non-KB Inflation P =NS in all % TLR MACE ST TLR MACE ST TLR MACE ST THUEBIS Study (n=110) Nordic III Study (n=477) CORPAL Kiss Study (n=224) Squeglia and Chevalier, JACC Cardiovasc Interv 2012;5:803

Stent Deformation caused by PTCA via MV Stent: Rationale for final Kissing Balloon Inflation (KBI) Provisional T-Stent

Kissing Balloon Inflation Influence of Main Vessel Stent Cell Rewiring on Stent Deformation Following Kissing Balloon Better scaffolding pushes the struts inward towards the main vessel lumen Bench testing showing wire crossing through strut closest to the carina Squeglia and Chevalier, JACC Cardiovasc Interv 2012;5:803

Provisional SB Stenting Proximal Optimization Technique (POT) Inflating a short, bigger balloon just proximal to the carina Good proximal stent apposition Restoring the normal carina configuration

Optimization of Stent Result Choose the stent diameter related to the size of the distal main vessel The proximal part of the stent is then post-dilated (Proximal Optimization Technique (POT) - Optimize stent apposition in the proximal MV - Facilitates a “distal’ cross as opposed to a proximal one to improve a scaffolding of the ostium of the side branch

Contemporary Bifurcation Intervention Contemporary provisional Side Branch Stenting Facilitates distal MV stent strut wire passage during guide wire exchange POT performed by post-dilating MV stent prox to carina Short NC balloon sized for prox MV reference diameter Creation of stent scaffold at ostium of SB following KBI Mylotte et al., Cath and Cardiovasc Interv 2013;82:E437

Kissing Balloon or Sequential Dilation of the Side Branch and Main Vessel for Provisional Stenting of Bifurcations Flow Chart and Representative Planar Radiographic Images Post-Dilation in Bifurcation Stenting Foin et al., JACC Interven 2012;5:47. 44

Kissing Balloon or Sequential Dilation of the Side Branch and Main Vessel for Provisional Stenting of Bifurcations Post-Dilation in Bifurcation Stenting Finite Element Analysis in the Model Bifurcation Foin et al., JACC Interven 2012;5:47. 45

Post-Dilation in Bifurcation Stenting Kissing Balloon or Sequential Dilation of the Side Branch and Main Vessel for Provisional Stenting of Bifurcations Post-Dilation in Bifurcation Stenting Ostial Stenosis and Strut Malapposition Measured in the Bifurcation and Proximal Stent Edge Foin et al., JACC Interven 2012;5:47. 46

Diameter Stenosis after Main Vessel Stenting, % Functional Assessment of Jailed Side Branches in Coronary Bifurcation lesions Using FFR Diameter Stenosis after Main Vessel Stenting, % Ahn et al., JACC 2012;5:155

OPTIMIZING TECHNIQUE of BIFURCATION STENTING: Indications for KBI Sidebranch compromise; decrease flow, FFR <0.8 PTCA of SBr via stent struts 2 stent strategy Downstream lesion for future need of PCI

Take Home Message Status of Transradial PCI & Role of Kissing Balloon Inflation Transradial PCI use is on gradual rise in the US with latest reports being in high teens. TRI is trended with lower bleeding & vascular complications but significantly higher access site crossover to trans-femoral approach. In STEMI pts, TRI has shown to be especially beneficial by reducing bleeding and perhaps mortality Few randomized trials have shown the futility of routine kissing balloon inflation in bifurcation lesions. If SBr PTCA is required after main vessel stenting, then KBI is routinely recommended. Sequential balloon inflation rather then KBI has shown promising results. Final KBI is essential in bifurcation lesions requiring 2-stent approach

Question # 1 For the SAFE-PCI trial, following statement is correct for the radial approach : Higher crossover to femoral approach Lower cross over to femoral approach Lower fluoroscopy duration Significantly lower bleeding/vascular complications in all pts Significantly lower mortality

Question # 2 What percent of pts usually cross over to femoral approach from radial approach in the trials of TRI PCI ? <5% 5-10% >10-15% >15-20% >20%

Question # 3 Following statement is true for routine kissing balloon inflation in the treatment of bifurcation lesions: A. KBI reduces TLR B. KBI reduces stent thrombosis C. KBI reduces peri-procedure MI D. KBI reduces overall MACE E. KBI is not beneficial routinely

Question # 1 For the SAFE-PCI trial, following statement is correct for the radial approach : Higher crossover to femoral approach Lower cross over to femoral approach Lower fluoroscopy duration Significantly lower bleeding/vascular complications in all pts Significantly lower mortality The correct answer is A as SAFE-PCI trial showed about 6% crossover to femoral approach in the radial group while other parameters were not significantly different

Question # 2 What percent of pts usually cross over to femoral approach from radial approach in the trials of TRI PCI ? <5% 5-10% >10-15% >15-20% >20% The correct answer is B as SAFE-PCI and other trials comparing TRI vs. TFI have shown about 6-8% crossover to femoral approach in the radial group.

Question # 3 Following statement is true for routine kissing balloon inflation (KBI) versus no-KBI in the treatment of bifurcation lesions: A. KBI reduces TLR B. KBI reduces stent thrombosis C. KBI reduces peri-procedure MI D. KBI reduces overall MACE E. KBI is not beneficial routinely The correct answer is E as 3 randomized trials have shown no benefit of routine KBI vs. no-KBI in treatment of bifurcation lesions.