BRANCH Bare Metal BifuRcAtion SteNt Clinical Trial in Humans Early Clinical Experience by Raoul Bonan, MD On behalf of the BRANCH study investigators

Raoul Bonan, MD DISCLOSURES Consulting Fees Medtronic CardioVascular, Inc. Ownership Interest (Stocks, Stock Options or Other Ownership Interest) ReCor Medical I intend to reference unlabeled/ unapproved uses of drugs or devices in my presentation. I intend to reference Medtronic-Corevalve percutaneous aortic valve replacement Mitral Sonic from ProRhythm.

Current Approaches & Limitations Provisional Stenting: Alters stent structure, putting stresses on stent that were not intended PTCA in SB without scaffolding – same concerns as with balloon angioplasty Acute recoil Plaque shift Suppression of Neointimal hyperplasia T-Stenting: Gap at Ostium of side branch Lack of coverage at lesion site Crush: Overlapping / multiple layers of metal over Ostium and Carina Culotte and V/Y: False Carina, unnatural flow disturbance of metal sitting “naked” in the artery long-term Provisional Stenting “T-stenting” “Y” or “V” “V” 2 1 “Reverse-T” Culotte Stenting 1 2 Crush technique 2 1

Challenges Associated with Treating Coronary Bifurcation Lesion Simple Approaches Inconsistent coverage Ostial gap Imprecise recrossing struts Inadequate scaffolding of SB Complex Approaches Procedural complexity More metal Multiple layers of metal (crush, culotte) Difficulty re-accessing with repeat procedures

MDT Branch Bifurcation Stent Investigational Device Design Features Dual branch / Y – shaped Driver platform - 3 stents welded Dual balloon Sprinter technology Stepped balloon design to avoid proximal over-expansion Dual-wire delivery system with simultaneous inflation Single catheter / inflation lumen 7F Cobalt alloy Thin stent struts Modular architecture Flexibility, deliverability, conformability Ostial marker band No overlapping or gapping at the ostia or carina Crossing profile ~ 0.06” Side branch balloon Main branch balloon 4 mm 8 mm 7 mm 4 mm, 8Crown 7 mm, 12 Crown 8 mm, 10 Crown

Bifurcation Stent System BRANCH Study Design Single De Novo Bifurcation Lesions in Native Coronary Arteries with RVDs of Proximal Main Vessel: 3.8-4.3 mm Distal Main Branch: 3.0-3.5 mm Side Branch up to 2.5 mm Pre-dilatation required; Plavix ≥ 30 Days 60 patients 7 sites Bifurcation Stent System 30d 6mo 9mo 12mo Clinic Visit Contact Contact Contact Primary Endpoint: A composite of cardiac death, target vessel myocardial infarction (MI) and clinically driven target vessel revascularization (TVR) at 30 days Secondary Endpoints: Acute success (device, lesion, procedure) 4. Total index PCI procedure time Total fluoroscopy time 5. Composite of cardiac death, Total volume of contrast used MI and clinically driven TVR @ 6, 9 &12mo 6. TLR rate at 9 months

BRANCH Study Methods Baseline clinical and angiographic data One bifurcation lesion per subject Clinical follow-up at 30 days Subsequent follow up at 6, 9 and 12 months In the case of a failure to implant a trial stent subjects were included on an “Intent to Treat” basis through 30 d FU A total 60 patients received the bifurcation stent with each site having 1 run in patient per site (7)

BRANCH Investigators Robert Whitbourn Ian Meredith* Stephen Worthley Patients Robert Whitbourn St Vincent’s Hospital, Fitzroy, Melbourne 15 Ian Meredith* Monash Heart, Monas Medical Centre, Melbourne 12 Stephen Worthley Royal Adelaide Hospital, Adelaide Mark Webster Auckland City Hospital, Auckland , NZ 9 John Ormiston Mercy Hospital, Northshore, Auckland, NZ 4 1 *Principal Investigator

BRANCH Study Management QCA Core Lab Beth Israel, Boston, MA, USA Jeffrey J. Popma, MD IVUS Core Lab Cardiovascular Core Analysis Lab Stanford Interventional Cardiology, CA, USA Peter Fitzgerald, MD ECG Core Lab Harvard Clinical Research Institute, Boston, MA, USA Data Coordinating Center Medtronic Santa Rosa Clinical Events Committee/DSMB

BRANCH Inclusion/Exclusion Criteria Single de novo bifurcation lesion in a native coronary artery with a RVD of Proximal Main Vessel: 3.8 – 4.3 mm Distal Main Branch: 3.0 – 3.5 mm Side Branch: Up to 2.5 mm Target lesion lengths any combination of: ≤16 mm proximally from the carina in the proximal main vessel ≤16 mm distally from the carina in the distal main branch ≤12 mm from the carina in the side branch Exclusion: Acute MI within 72 hrs of the index procedure QWMI Non-Q wave MI CK ≥2X lab ULN with CK-MB > lab ULN History of stroke or TIA <6 mo LVEF <30% at most recent evaluation Participating in investigational drug / device study

BRANCH Inclusion Criteria 1,1,1 1,1,0 1,0,1 0,1,1 1,0,0 0,1,0 0,0,1 Must have a main vessel lesion ≥50%

BRANCH Demographics n = 53 n = 60 Age (yrs) 60 ± 12 61 ± 12 Male (%) 85 Hyperlipidemia (%) 83 Diabetes Mellitus (%) 26 25 Insulin Dependent (%) 9 8 Prior PCI (%) 55 52 Prior MI (%) 58 53 Stable Angina (%) 43 48 Unstable Angina (%) 16 Ejection Fraction (%) 58 ± 12 59 ± 12 # Diseased Vessels (n) Single 36 38 Double 51 50 Triple 13 12

BRANCH Pre Procedure Lesion Morphology Vessel Location – % (n) LAD 73.6 (39) LCX 15.1 (8) RCA 11.3 (6) Bifurcation Type – % (n) Medina Complex Bifurcation Type (1,1,1; 1,1,0; 1,0,1; 0,1,1) 71.7 (38) Medina Simple Bifurcation Type (1,0,0; 0,1,0; 0,0,1) 28.3 (15) Bifurcation Angle <45° 77.4 (41) ≥45° – <90° 22.6 (12) Group the 4 from the picture in slide 18 – show the true Medina types that are really requiring 2 stents

BRANCH Pre Procedure Bifurcation Morphology

BRANCH Pre Procedure Lesion and Procedure Characteristics Device and Procedure Characteristics Main Branch (average) Prox Main Branch Distal Main Branch Side Branch RVD (mm) 2.94 ± 0.38 3.34 ± 0.50 2.54 ± 0.34 2.32 ± 0.39 MLD (mm) 1.23 ± 0.42 1.41 ± 0.67 1.06 ± 0.44 1.29 ± 0.62 Lesion Length (mm) 13.68 ± 6.05 5.59 ± 3.91 8.08 ± 5.11 6.08 ± 3.92 % Stenosis 58.23 ± 12.60 57.67 ± 19.20 58.46 ± 16.08 44.45 ± 23.74 Pre dil (atm) 13.58 ± 3.34 11.90 ± 3.12 Stent Deployment (atm) 13.02 ± 2.06 12.46 ± 3.04 Post dil (atm) 15.95 ± 3.20 14.11 ± 2.71 Kissing Balloon Technique used 43.4% at pre dilatation and 74.% at post dilatation

BRANCH Patient Flowchart Patients Enrolled N = 60, 7 sites 1 run in per site allowed Evaluated n = 53 49/53 Lesion Success 47/53 Procedure Success 44/53 Device Success 53/53 Completed 30 day f/up

BRANCH Acute Success By Definition BRANCH defn Historical defn N = 53 N = 60 Lesion Success (%) 92.5 93.3 98.1 98.3 Device Success (%) 83.0 83.3 86.8 86.7 Procedure Success (%) 88.7 90.0 94.3 95.0 BRANCH Device success <30% residual in-segment %DS for all target lesion/s with assigned stent Lesion success <30% residual in-segment % DS for all target lesion/s with any percutaneous method Procedure success <30% residual in-segment % DS for all target lesions and without in-hospital death, MI or TLR HISTORICAL Device success <50% residual in-segment % DS for all target lesion/s using the assigned stent Lesion success <50% residual in-segment % DS for all target lesion/s with any percutaneous method Procedure success <50% residual in-segment % DS for all target lesions and no in-hospital death, MI or TLR

BRANCH Acute Success Main Branch/proximal (%DS) Main Branch/distal Side branch (% DS) Lesion Failure (pt 2000-09) 37.42 2.97 3.85 (pt 2001-06) 5.12 15.66 32.46 (pt 20902-04) 17.74 11.6 69.36 (pt 2002-06) 11.17 18.23 49.36 Stent also not implanted in 7/53 patients Lesion success 30% residual in-segment % DS for all target lesion/s with any percutaneous method

BRANCH Bifurcation

BRANCH Post Procedure Lesion Characteristics – QCA n= 53 Main Branch (average) Proximal Main Branch Distal Main Branch Side Branch RVD (mm) 3.00 ± 0.35 3.38 ± 0.47 2.62 ± 0.33 2.36 ± 0.35 MLD (mm) 2.66 ± 0.32 2.95 ± 0.40 2.38 ± 0.35 2.05 ± 0.41 % Stenosis 11.08 ± 4.46 12.43 ± 6.43 9.23 ± 6.24 13.01 ± 11.03

BRANCH Major Adverse Events All Patients In-Hospital n = 60 30 days Death (all) – % (n) Cardiac MI (all) – % (n) 3.3 (2) 3.4 (2) Q Wave Non Q wave Death (cardiac) + MI (all) – % (n) Stent Thrombosis (all) – % (n) 0-30 days TLR – % (n) TVR (non-TL) – % (n) TVR – % (n) MACE – % (n) TVF – % (n) 31.7% usage of IIb/IIIa inhibitors and 100% DAPT compliance.

BRANCH Major Secondary Endpoints – Summary Acute Success – % (n) Device Success 83.0 (44) Lesion Success 92.5 (49) Procedure Success 88.7 (47) Total Fluoroscopy Time (secs) 22.89 ± 10.55 Total Volume of Contrast Used (ml) 322.68 ± 87.84 Total Index PCI Procedure Time (mins) 70.85 ± 22.84

BRANCH Clinical Follow Up Events 43 yo M LAD/1st Diag Plaque disruption distal to the LAD stent lead to chest pain and CKMB elevation – Non–Q-Wave MI. Driver stent implanted 73 yo M Proximal LAD dissection treated with Driver stent. Protocol required CKMB assessment showed procedural elevation – Non–Q-Wave MI

BRANCH Summary and Conclusions In the majority of cases, bifurcation lesions can be treated with a simple approach using one DES with excellent clinical outcomes Provisional side branch stenting remains the most reasonable strategy When 2 stents are needed, the optimal approach is still a matter of debate but the use of the Medtronic Bifurcation stent appears to be safe and practical in a large number of bifurcation lesion types with a low peri-procedural and 30 day MACE

BRANCH Endpoint Definitions MACE All cause mortality, all MIs, TLR, Emergent CABG Myocardial Infarction CK ≥ 2X UPLN with the presence of an elevated CK-MB (any amount above the lab ULN) Device success <30% residual in-segment % DS for all target lesion/s with assigned stent Lesion success <30% residual in-segment % DS of all target lesion/s with any percutaneous method Procedure success <30% residual in-segment % DS for all target lesions & no in-hospital death, MI or TLR

BRANCH Procedure Information Summary of Stent Usage Stent Size 3025 34 Stent Size 3525 12 Main Branch Side Branch Additional Stents 32 20

BRANCH Acute Success Device Success (%) 83.0 Lesion Success (%) 92.5 Procedure Success (%) 88.7  Device success <30% residual in-segment percent diameter stenosis of all target lesion/s with assigned stent Lesion success <30% residual in-segment percent diameter stenosis of all target lesion/s with any percutaneous method Procedure success <30% residual in-segment percent diameter stenosis of all target lesions and no inhospital death, MI or TLR

BRANCH Post Procedure Lesion Characteristics IVUS n = 41 Proximal Main Branch (stent) Distal Main Branch (stent) Side Branch (stent) Length of Segment (mm) 4.87 ± 1.06 6.36 ± 1.87 3.50 ± 0.88 Luminal Diameter (mm) 3.65 ± 0.35 3.00 ± 0.27 2.62 ± 0.23 Lumen Area (mm2) 10.55 ± 2.07 7.05 ± 1.30 5.37 ± 1.00 Vessel Diameter (mm) 4.81 ± 0.49 4.00 ± 0.37 3.43 ± 0.43 Vessel Area (mm2) 18.31 ± 3.68 12.58 ± 2.40 9.30 ± 2.41 Plaque Area (mm2) 7.83 ± 2.12 5.60 ± 1.79 3.94 ± 1.63

BRANCH Major Adverse Events Protocol Followed In Hospital n = 53 30 days Death (all) – % (n) Cardiac MI (all) – % (n) 3.8 (2) Q Wave Non Q wave Death (cardiac) + MI (all) – % (n) Stent Thrombosis (all) – % (n) 0-30 days TLR – % (n) TVR (non-TL) – % (n) TVR – % (n) MACE – % (n) TVF – % (n) 34% usage of IIb/IIIa inhibitors and 100% DAPT compliance.

BRANCH Post Procedure Morphology – IVUS n=41 Main Branch Tissue Prolapse (%) 2.5 Incomplete Apposition (%) 5.0 Bifurcation 0.0 Incomplete Apposition 23.1 Side Branch 21.4