TAVR Emerging Technologies New Valves and Adjunctive Equipment

TAVR: Emerging Technologies, New Valves and Adjunctive Equipment Jeffrey J. Popma, MD Director, Interventional Cardiology Clinical Services Beth Israel Deaconess Medical Center Associate Professor of Medicine Harvard Medical School Boston, MA 1

Jeffrey J. Popma, MD §Contracted Research / Grant Support: §Abbott Vascular §Abiomed, Inc. §Atrium Medical Corporation §Boston Scientific Corporation §Cordis Corporation §IDEV Technologies, Inc. §Medtronic, Inc.

§Consulting Fees: §Abbott Vascular §Boston Scientific Corporation My presentation will include off label discussions: Percutaneous aortic valves

Core. Valve® Percutaneous Aortic Valve Outflow Orientation Low Radial Force 1. Sits in ascending aorta 2. Orientation during deployment Constrained Portion Valve Function High Hoop Strength Inflow Portion Sealing High Radial Force 1. Supra-annular leaflet function 2. Designed to avoid coronaries 1. Intra-annular anchoring 2. Mitigates paravalvular aortic regurgitation Available Valve Sizes: 23 mm, 26 mm, 29 mm, 31 mm Annular Sizes: 18 mm 29 mm 5

Design Features to Reduce Leaflet Stresses • Areas of high stress can induce collagen degeneration that could lead to tearing and valve failure over time 1 • Valve designs that reduce leaflet stresses are likely to have better durability 2 Commissure Pad Leaflet Geometry Supra-Annular Valve Location Valve Height 1. Schoen Frederick J. Cardiac Valve Prostheses: Pathological and Bioengineering Considerations. J Cardiac Surg. 1987; 2: 65 -108. 2. Sun W. , Li K. , Sirois E. Simulated elliptical bioprosthetic valve deformation: Implications for asymmetric transcatheter valve deployment. J Biomech. 2010; 43: 3085 -3090. 6

Majority of US Core. Valve Implants in Hybrid ORs 7

Core. Valve US Trial: Current Status Core. Valve U. S. Pivotal Trial d te t le en p m llm 12 o o 0 C nr 2 E an J “Extreme Risk” (Up to 687) “High Risk” N=790 Iliofemoral access ? No Core. Valve Observational Up to 200 Randomization 1: 1* Yes Core. Valve Single Arm N=487 Core. Valve N=395 SAVR N=395 8

Direct Aortic – Median Hemisternotomy BIDMC last Tuesday 83 year old man NYHA Class III Porcelain Aorta Annular Size 27. 4 mm Unsuitable iliofemoral access Operative Plan: RFA for 6 Fr Pigtail Temporary Pacemaker FRV Median Hemisternotomy 31 mm Core. Valve 9

Direct Aortic – Median Hemisternotomy Two Heart Surgeons – Two Interventionalists – Cardiac Anesthesia 10

Direct Aortic – Median Hemisternotomy Marker Clip 11

Direct Aortic – Median Hemisternotomy 12

Direct Aortic – Median Hemisternotomy 13

Direct Aortic – Median Hemisternotomy 14

Direct Aortic – Median Hemisternotomy Overnight CV-ICU Ambulating Next Day Home on POD #4 15

TAVR – What We Have Learned • Embolic strokes have become a major concern following TAVR --- new technology will focus on reducing the occurrence of neurologic events after the procedure • Vascular complications and closure devices • New TAVR devices - Repositionable and Retrieval - Reducing peri-valvular regurgitation - New Transapical devices 16

Stroke Following s. AVR and TAVR Etiology of Strokes • During TAVR: TCD has shown that the majority of procedural embolic events occurred during BAV, manipulation of catheters across the aortic valve, and valve implantation. • During AVR, TCD evidence of emboli during insertion of an aortic cannula at the start of CPB and after declamping the aorta • Late embolic events post-AVR are presumably caused by debris from the prosthesis and atrial fibrillation Daneault J Am Coll Cardiol 2011; 58: 2143– 50 17

Stroke Following TAVR (range 0 -6. 7%) Daneault J Am Coll Cardiol 2011; 58: 2143– 50 18

Source for Emboli After TAVR Grube ISET Miami 2012 19

Source for Emboli in TAVI: Aortic Atheroma 268 of 3404 CABG patients (8%) had atheroma (≥ 5 mm) defined by epi-aortic ultrasound 15. 3% of group had intraoperative stroke Stern et al. American Heart Journal Oct. 1999. 20

How do we detect events? DW-MRI Grube ISET Miami 2012 Transcranial Doppler 21

Cerebral Ischemia After TAVI New Lesions % Lesion Volume mm 3 Kahlert PK et al. Circulation 2010; 121: 870 -878 22

When Do the TCD Events Occur? Kahlert et al, AHA 2010 23

Neurological Events in the Partner A Trial 30 Day Events: TAVR: 1 year Events: TAVR: 8. 3% Major Stroke (30 days): TAVR: 3. 8% 5. 5% SAVR: : 2. 4% SAVR: 4. 3% p = 0. 04 SAVR: 2. 1% p = 0. 20 TAVR: 5. 1% SAVR: 2. 4% TAVR: 16% p = 0. 04 SAVR: 6% Major Stroke (1 year): p = 0. 07 Minor Stroke: Of these events occurred within 10 days (periprocedural): TAVR: 53% SAVR: Smith C et al. N Engl J Med 2011; 364: 2187 -98 47% 24

Timing of Neurological Events AATS May, 2011 D. Craig Miller , M. D. 0 -2 days 3 -5 days 6 -10 days 11 -30 days Smith C et al. N Engl J Med 2011; 364: 2187 -98 31 -364 days 1 -2 years TAVR AVR TAVR AVR TAVR >53% Periprocedural 2 -3 years 25

PARTNER A: Early hazard of neurologic event %/mo TAVR AATS May, 2011 D. Craig Miller , M. D. AVR Months after Procedure Smith C et al. N Engl J Med 2011; 364: 2187 -98 26

Cerebral Protection Devices SMT - Deflector • Clinical Phase • 9 F Transfemoral delivery Claret Medical - Dual Filter (Montage) • Clinical Phase • 6 F Transradial or brachial delivery Edwards/Embrella - Deflector • Clinical Phase • 6 F Transradial or brachial delivery Grube ISET Miami 2012 27

Claret Dual Filter “Montage” 2 nd Generation Grube ISET Miami 2012 28

Variety of Emboli Captured and Removed Embolic Material Grube ISET Miami 2012 29

Embrella Embolic Deflector® • Porous membrane designed to deflect embolic debris • Nitinol® Frame & Shaft • Hydrophillic Coating with antithrombogenitc properties • 3 Radiopaque Markers • Suture; Monofilament Nylon Grube ISET Miami 2012 30

Edwards-Embrella Deflector Grube ISET Miami 2012 31

Embrella: Embolic Protection Coverage Grube ISET Miami 2012 32

Average # of TCD HITS/Subject 55% decrease in TCD HITS • Embrella 12 TAVI, 1 BAV • No Embrella 9 TAVI 841 P = 0. 016 379 Embrella Protection Grube ISET Miami 2012 No Protection 33

TAVR – What We Have Learned • Embolic strokes have become a major concern following TAVR --- new technology will focus on reducing the occurrence of neurologic events after the procedure • Vascular complications and closure devices • New TAVR devices - Repositionable and Retrieval - Reducing peri-valvular regurgitation - New Transapical devices Grube ISET Miami 2012 34

Vascular Complications • Bleeding • Vessel obstruction • (Vessel rupture) Grube ISET Miami 2012 35

Closure System Landscape Grube ISET Miami 2012 36

In. Seal Intravascular Closure Device Acute Tether (biodegradable) Sealing membrane (biodegradable) Grube ISET Miami 2012 After biodegradation Nitinol frame 37

TAVR – What We Have Learned • Embolic strokes have become a major concern following TAVR --- new technology will focus on reducing the occurrence of neurologic events after the procedure • Vascular complications and closure devices • New TAVR devices - Repositionable and Retrieval - Reducing peri-valvular regurgitation - New Transapical devices Grube ISET Miami 2012 38

New TAVI valves: The Future Today Tomorrow Next Gen. Medtronic Core. Valve Boston Sci. Lotus™ HLT Saint Jude Portico™ Direct Flow Edwards Sapien XT Medtronic Core. Valve Medtronic Engager Edwards Sapien XT Grube ISET Miami 2012 Jena. Valve Symetis ACCURATE 39

Sadra Lotus™ Valve Concept • Braided nitinol stent structure • Radial expansion as it shortens § Enables a more flexible delivery system § Enables device repositioning or retrieval § Provides significant radial strength • Nitinol Frame designed for retrieval and repositioning • Adaptive Seal to conform to irregular anatomical surfaces, and to minimize perivalvula leaks • Locking Mechanism • Bovine Pericardium Proven material 40

Direct Flow Medical Position & Fill Lumens Aortic Ring • Design Features – Delivery System • Polymer nylon sleeve • Multilumen catheter 3 position and fill lumen 1 guide wire lumen • Flexible nose cone – Non-metallic delivery system and valve Ventricular Ring • Flexible and trackable – Precise positioning Guidewire Lumen – Retrievable with deflation and withdrawl into retrieval basket Grube ISET Miami 2012 41

DFM Aortic Valve Aortic Insufficiency - PV Leaks Conformable cuff design and precise positioning maximizes sealing to prevent PV leaks Grube ISET Miami 2012 42

Direct Flow Medical 2 sizes matching valvuloplasty balloons 22 F Design Grube ISET Miami 2012 18 F Design 43

St Jude Medical (Portico Transcatheter Heart Valve) • Nitinol self expanding stent • Open stent cell allows access to coronaries and low crimp profile • Bovine and porcine pericardial valve (Linx™ anticalcification technology*) • Low placement of leaflets/cuff within stent frame allows for minimal protrusion into the LVOT • 23 mm Size • First Human Implant June 7 th, 2011 Grube ISET Miami 2012 44

Jena Valve • Self-expanding nitinol stent with flexible stent posts • Porcine root valve • Sizes 23, 25, 27 • 32 F introducer sheath for TA N = 10 No Death or Stroke Grube ISET Miami 2012 45

TAVR – What We Have Learned • Most “High Risk” “High Gain Procedure • Present focus in clinical trials will be on stroke detection and prevention cerebroprotection devices will provide only part of the answer • Better imaging (CTA, intraprocedural echocardiography) will help reduce perivalvular regurgitation and vascular complications • Dedicated vascular closure devices in development • New TAVR designs (TF and TA) will also help reduce procedural complications 46