6-Month Outcomes Following Transcatheter Aortic Valve Implantation With a Novel Repositionable Self-Expanding Bioprosthesis Ian T. Meredith, MBBS, PhD, MonashHeart and University, Melbourne, Australia Antony S. Walton, MBBS, Epworth Hospital, Melbourne, Australia Stephen J. Brecker, MBBS, MD, St. Georges Hospital, London, United Kingdom Sanjeevan Pasupati, MBChB, Waikato Hospital, Hamilton, New Zealand Daniel J. Blackman, MD, Leeds General Infirmary, Leeds, United Kingdom Ganesh Manoharan, MBBCh, MD, Royal Victoria Hospital, Belfast, United Kingdom

Potential Conflicts of Interest Speaker's name: Ian T. Meredith  I have the following potential conflicts of interest to report: Consultant: Medtronic and Boston Scientific Medtronic is the sponsor of the CoreValve Evolut R CE Study; and performed all statistical analyses and assisted in the graphical display of the data.

Background Transcatheter aortic valve implantation (TAVI) is a viable option for the treatment of symptomatic severe aortic stenosis for patients who are at extreme- or high-risk for open heart surgery. Recent technological advancements have aimed at reducing implant profile and improving valve implantability to ensure optimal valve positioning. Optimal positioning may be associated with less paravalvular leak and lower new pacemaker rates. We evaluated outcomes following TAVI with a new and fully repositionable CoreValve Evolut R 14F-equivalent self-expanding TAV through 6 months. MDT Confidential

Transcatheter Valve (26, 29 mm) Catheter Delivery System Evolut R System Transcatheter Valve (26, 29 mm) Supra-annular design, optimized sealing Catheter Delivery System 14Fr-equivalent profile Loading System MDT Confidential

Evolut R Valve Details Redesigned Outflow Enhanced Sealing Reduced height (~10mm), reshaped for improved fit, especially in angulated anatomy 45 mm Enhanced Sealing Optimized Oversizing Consistent Radial Force Extended Sealing Skirt* 13 mm 4 mm 6 mm *Measurements provided are approximate and do not include paddles/frame loops. Images may not be to scale and are for illustration purposes only. CoreValve Evolut R CE Study 5

Study Overview Objective To evaluate the safety and clinical performance of the CoreValve Evolut R System (26 mm, 29 mm) in symptomatic extreme- or high-risk patients (Heart Team assessment) with symptomatic aortic stenosis Design Prospective, non-randomized, multicentre, observational study Follow-up at early post-procedure (24h–7 days), 30 days, 6 months, 1 and 2 years post TAVI Multislice CT of the peripheral vascular and aortic annulus 100% source data monitored Endpoints Safety: All-cause mortality and the rate of any stroke at 30 days Clinical Performance: Device success per Valve Academic Research Consortium (VARC-2) and the % of patients with > mild aortic regurgitation at early post procedure (24h–7d) Core Labs Echocardiography (Mayo Clinic, Rochester, MN) Adjudication Clinical endpoints reported per VARC-2* Compliance 98.3% of patients completed 30-day follow-up and 100% completed 6- month follow-up *Kappetein AP, et al. Eur Heart J 2012; 33: 2403-18. CoreValve Evolut R CE Study 6

Investigational Sites Belfast Leeds Melbourne (2) London Hamilton

Patients Characteristic, % or mean± SD N = 60 Age (years) 82.8 ± 6.1 Women 66.7 Body surface area (m2) 1.7 ± 0.2 Society of Thoracic Surgeons Predicted Risk of Mortality (%) 7.0 ± 3.7 Logistic EuroSCORE I (%) 20.5 ± 12.5 New York Heart Association class III or IV 68.3 Previous CABG 28.3 Any chronic lung disease 43.3 Diabetes 26.7 Peripheral vascular disease 16.7 Atrial fibrillation / atrial flutter 36.7 Frailty Pre-existing permanent pacemaker 11.7

Procedure Variable, % N = 60 General anaesthesia 63.3 Access Approach Iliofemoral 98.3 Direct aortic 1.7 Pre TAVI balloon aortic valvuloplasty performed 96.7 Valve Size Implanted 26 mm 31.7 29 mm 68.3 Post TAVI balloon dilatation performed 21.7 Permanent pacemaker implantation 11.7

Clinical Performance Variable, % (no./total no.) N = 60 Absence of procedural mortality 100.0 (60/60) Correct positioning of 1 valve in proper location 98.3 (59/60) Mean gradient < 20 mm Hg or peak velocity < 3 m/sec Absence of moderate or severe regurgitation 93.3 (56/60) Absence of patient prosthesis mismatch* 83.6 (46/55) VARC-2 device success 78.6 (44/56) *Effective orifice area could not be determined in 5 patients to calculate patient prosthesis mismatch.

Repositioning Successfully used 22 times in 15 patients (25%): 10 Resheaths among 7 patients 12 Full recaptures among 10 patients No full retrievals Valve Too Deep Recapture Begins Partially Recaptured Valve Fully Captured

Effective Orifice Area, cm2 Haemodynamics Effective Orifice Area, cm2 Mean Gradient, mm Hg Gradient 60 57 52 EOA 56 55 54 50 CoreValve Evolut R CE Study 12

NYHA Class Compared with Baseline, 74.9% Improved at 30 Days and 84.9% at 6 Months Percent of Patients CoreValve Evolut R CE Study 13

Safety Event, K-M rates (no. of patients) 30 Days N=60 6 Months N=60 All-cause mortality 0.0 (0) 5.0 (3) Cardiovascular 3.3 (2) All stroke 1.7 (1) Disabling Non-disabling Major vascular complications 8.3 (5) Life-threatening or disabling bleeding 8.4 (5) Embolization or migration Endocarditis Coronary obstruction Valve thrombosis Pacemaker* 11.7 (7) 13.4 (8) *Patients with a prior pacemaker included in the denominator. MDT Confidential

Paravalvular Regurgitation Percent of Evaluable Echocardiograms CoreValve Evolut R CE Study 15

Implant Depth by Pacemaker Implantation Mean Implant Depth Patients with a pacemaker 8.1 ± 3.5 mm (non-coronary cusp) Patients with NO pacemaker 3.3 ± 2.5 mm (non-coronary cusp) Difference (P<0.001) = non-coronary cusp (NCC) = left coronary cusp (LCC) = annular plane Patients with Pacemaker (8) MDT Confidential

Summary & Conclusions The ability to reposition the Evolut R TAV resulted in a low pacemaker rate and low incidence of PVL Forward flow haemodynamics were excellent with single-digit mean gradients No evidence of valve dysfunction Improved and sustained symptom reduction CoreValve Evolut R CE Study 17