EdgeToEdge Mitral Leaflet Repair with Mitral Clip Technology

Edge-To-Edge Mitral Leaflet Repair with Mitral Clip Technology Update James Hermiller, MD, FACC, FSCAI St Vincent Medical Group St Vincent Heart Center of Indianapolis, IN

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship • Grant/Research Support Company • Edwards, Medtronic, Abbott, BSC • Consulting Fees/Honoraria • Edwards, Medtronic, Abbott, BSC

Outline • Introduction • Real-World Results • Randomized Trial Status • Technology Update • Summary/Conclusions

MITRACLIP THERAPY CURRENT GLOBAL ADOPTION (>40, 000 Pts. ) Treating Centers Patients Implant Rate 1 Functional MR 2 Degenerative MR 2, 3 Mixed 1. 2. 3. 734 >40, 000 97% 64% 22% 14% First-time procedures only. Includes commercial patients, ACCESS I and ACCESS II patients OUS Commercial Experience Etiology not inclusive of U. S. cases as of 14/04/2014 Data As of July 31, 2016. Source: Data on file at Abbott Vascula

Mitra. Clip Therapy Worldwide Commercial Implant Etiology >40, 000 Patients Mixed 13% DMR 22% Implant Rate: 97% Data as of February 6, 2015. Source: Abbott Vascular FMR 65%

Outline • Introduction • Real-World Results • Randomized Trial Status • Technology Update • Summary/Conclusions

Mitral Valve Disease Etiology Ailawadi G, TCT 2016 TVT Update Etiology - % of pts with: 2014 2015 (n=1, 023) (n=3, 362) Degenerative Mitral Regurgitation (DMR) only 79. 7% 75. 5% Functional Mitral Regurgitation (FMR) only 10. 0% 8. 8% Mixed (both FMR and DMR) 6. 2% 10. 1% Neither DMR and FMR 4. 2% 5. 6% Source: STS/ACC TVT Registry Data Mart 3, 362 pt records from 2014 -15, as of 4 -24 -16

Leaflet Clip – Procedure Details Ailawadi G, TCT 2016 TVT Update Count of Leaflet Clips (used during the procedure) 2014 2015 1 Leaflet Clip 51. 8% 54. 3% 2 Leaflet Clips 39. 8% 38. 4% >=3 Leaflet Clips 7. 0% 6. 9% Source: STS/ACC TVT Registry Data Mart 3, 362 pt records from 2014 -15, as of 4 -24 -16

Leaflet Clip Procedures Outcomes & Adverse Events at Discharge Post Procedure Events (at discharge) 2014 2015 (n=1, 023) (n=3, 362) 0% 0. 1% Acute Kidney Injury (stage 3) 1. 2% 0. 8% Bleeding (major) 1. 3% Bleeding (life threatening) 1. 1% Major Vascular Complication 0. 2% 0. 3% Myocardial Infarction Source: STS/ACC TVT Registry Data Mart 3, 362 pt records from 2014 -15, as of 4 -24 -16 Ailawadi G, TCT 2016 TVT Update

Leaflet Clip Procedures Ailawadi G, TCT 2016 TVT Update At discharge 2014 2015 (n=1, 023) (n=3, 362) Mitral Regurgitation (<=2+) 92. 0% MV Mean Gradient <=8 mm. Hg 92. 3% 93. 8% Single Leaflet Device Attachment 1. 2% 1. 6% MV Re-intervention 0. 4% 0. 9% ASD requiring closure 1. 6% Source: STS/ACC TVT Registry Data Mart 3, 362 pt records from 2014 -15, as of 4 -24 -16

Mortality Source: STS/ACC TVT Registry Database 3, 657 pt records from 2014 -15, as of 10 -12 -16. 30 day endpoint among records with 30 day follow-up status not missing Ailawadi G, TCT 2016 TVT Update

Leaflet Clip Procedures - NYHA Source: STS/ACC TVT Registry Data Mart 2, 339 pt records from 2015, as of 4 -24 -16 Ailawadi G, TCT 2016 TVT Update

Leaflet Clip Procedures – Initial 1 Year Outcomes 2013 q 4 -2014 q 3 Mortality 20. 6% Atrial Fib 2. 8% Stroke (any) 2. 4% Re-intervention 3. 0% HF Re-admission 10. 0% MR (3 -4+) 12. 1% MV mean gradient <=8 mm Hg 94. 3% TCT 2015 Source: STS/ACC TVT Registry Data Mart 462 pt records (376 w/complete f-u, 190 with echo data) from 2013 q 4 -2014 q 3, as of 4 -24 -16 Ailawadi G, TCT 2016 TVT Update

European Heart J. 2016: 37; 703 -7012 Success rate Mitra. Clip improved 77% to 97% in predominantly FMR-treated EU registries Surgical reoperation dropped 21% EVEREST 2009 to 0. 9 to 2. 3% EU/GER

Outline • Introduction • Real-World Results • Randomized Trial Status • Technology Update • Summary/Conclusions

Mitra. Clip RCTs in Functional MR • 5 trials randomizing ~1656 patients with heart failure and secondary (functional) MR to Mitra. Clip vs. GDMT or MV Surgery • As of Feb 13 th, 2017, ~1, 021 patients have been randomized: - COAPT – 514/610 (84%) - MITRA-FR – 288/288 (100%) - RESHAPE-HF-2 – 182/380 (48%) - MATTERHORN – 37/210 (18%) - EVOLVE-HF – 0/168 (0%)

COAPT: Trial design ~564 patients enrolled at up to 84 US sites Significant FMR (≥ 3+ by core lab) Not appropriate for mitral valve surgery (local heart team) Specific anatomical criteria Randomize 1: 1 Mitra. Clip N=210 Feb 13 th, 2017 Randomized Control group 514 Patients at. Standard of care N=210 84 Sites Clinical and TTE follow-up: 1, 6, 12, 18, 24, 36, 48, 60 months PIs: Michael Mack and Gregg W. Stone Sponsor: Abbott Vascular

CEC-Adjudicated Safety Outcomes Event 30 days (n=50) 1 year (n=47) Death 0% (0) 15. 5% (7)* 14. 0% (10) 54. 9% (51) Heart failure hospitalization (1˚ effectiveness endpoint) 12. 0% (7) 29. 1% (26) Other CV Hospitalization 2. 0% (1) 11. 5% (8) Non-CV Hospitalization 4. 0% (2) 32. 8% (17) 8. 0% (5) 10. 6% (7) 4. 0% (2) Stroke 0% (0) 2. 5% (1) MV replacement due to Mitra. Clip device or procedure 0% (0) Endocarditis requiring surgery 0% (0) Echo core lab confirmed MS requiring surgery 0% (0) 4. 0% (2) Single leaflet device attachment (SLDA) 0% (0) Device embolization 0% (0) Myocardial infarction† 2. 0% (1) 4. 6% (2) Major bleeding† 4. 0% (2) 10. 4% (15) Hospitalization, any Adverse event, any 1˚ safety endpoint composite Non-elective CV surgery for device-related complication *6 cardiovascular, 1 non-cardiovascular. †CEC adjudicated through 30 days; site reported thereafter. Rates are KM estimates % (n events).

Hospitalizations for Heart Failure Annualized Rate ~21% Reduction p = 0. 32 1. 00 ~43% Reduction p = 0. 04 ~61% Reduction p = 0. 005 HF Hospitalization Rate Per Patient-Year All 1 -year visit/death 0. 80 1 -year visit/death 1 -year visit 0. 60 0. 40 0. 84 ± 0. 13 0. 66 ± 0. 13 0. 20 0. 48 ± 0. 11 0. 33 ± 0. 10 0. 00 1 Year Prior to Mitra. Clip Treatment. N=50 (Site-Reported) 1 Year Post Mitra. Clip Treatment. N=43⁺ Treatment. N=43** Treatment. N=36 (CEC-Adjudicated) +Deaths (CEC-Adjudicated) treated as HF hospitalizations **Death treated as a censoring event (HF hospitalizations counted up until time of death)

Outline • Introduction • Real-World Results • Randomized Trial Status • Technology Update • Summary/Conclusions

Decade of Mitra. Clip

Change is Here!!!!!!!

Next Generation Mitra. Clip NT • Improved Ability to Capture Leaflets & Maintaining Leaflet Capture • Improved Steering and Clip Retraction 2016 Mitra. Clip Next-Gen • Ergonomic Single Operator System • Intuitive Procedure 2017

Mitra. Clip NT Product Enhancements Grasping Enhancements üGripper material change to nitinol to increase gripper drop angle to >120º üGreater mitral leaflet engagement to avoid losing grasp

Mitra. Clip NT Gripper Enhancement

Mitra. Clip NT Steering Enhancements üLess anterior movement upon steering towards valve üSelf aligning clip upon retraction into Guide

Mitra. Clip NT

Next Gen Mitra. Clip System Improve Usability Simplify procedure • Provide intuitive controls • Single operator system • Reduce number of steps ü Reliable delivery catheter movement ü Controlled stabilizer movements ü Platform Technology ü Technology can be used to deliver future therapies in adjacent and new spaces

Beyond Next Gen: Longer Arms LA pressure monitoring

Outline • Introduction • Real-World Results • Randomized Trial Status • Technology Update • Summary/Conclusions

Summary and Conclusions • Worldwide > 40, 000 patients treated with Mitra. Clip – 70% FMR, 20% DMR, 10% Mixed • Procedural success Mitra. Clip high and improving – Safety profile remains favorable • Randomized trials in FMR subset progressing • Technology enhancements – Mitra. Clip NT - Improved grasping and steering – Next. Gen - Simpler and more effective system control

Thanks for your attention!