1 Jeffrey J. Popma, MD Professor of Medicine Harvard Medical School Director, Interventional Cardiology Beth Israel Deaconess Medical Center Boston, MA TAVR With the Medtronic TAVR System In Patients at Low Risk for Surgical Aortic Valve Replacement

2 Conflict of Interest Statement Over the past year, I have received the following: Institutional Grants: Medtronic, Boston Scientific, Abbott Vascular, Direct Flow, Cook Medical Advisory Board: Boston Scientific, Abbott Vascular, GE Healthcare, Covidien Non Vested Equity: Intelemage, Healthworks, Direct Flow Medical

3 Low Risk N=280 patients STS = 3.0% Thyregod et al JACC 2015;65:2184–94

4 Primary Objective To demonstrate that the safety and effectiveness of the Medtronic TAVR system is non-inferior to SAVR in patients with severe AS at low risk for SAVR Patients Subjects with severe AS with indication for SAVR with a bioprosthesis and predicted risk of mortality at 30 days < 3% Study Design Multi-center, prospective, randomized 1:1 randomization to either TAVR or SAVR Devices Investigational TAVR Arm Evolut R 23, 26, and 29 TAV with EnVeo R DCS CoreValve 31 mm TAV with AccuTrak DCS Control Arm Any commercially available bioprosthesis Number of Subjects 1256 subjects, inclusive of 400 subjects (200 Medtronic TAVR and 200 SAVR) in LTI sub-study ScopeUp to 80 sites Low Risk: Study Overview

5 4D CT for LTI 1:1 Randomization SAVR TAVR H eart Team Evaluation Two Cardiac Surgeons and One Interventional Cardiologist Low Surgical Risk (predicted mortality risk <3%) H eart Team Evaluation Two Cardiac Surgeons and One Interventional Cardiologist Low Surgical Risk (predicted mortality risk <3%) Leaflet sub- study N=200 Low Risk Patient Selection National Screening Committee One Cardiac Surgeons and One Interventional Cardiologist Confirm Low Risk for TAVR and SAVR National Screening Committee One Cardiac Surgeons and One Interventional Cardiologist Confirm Low Risk for TAVR and SAVR Leaflet sub- study N=200

6 Co-Principal Investigators Jeffrey J. PopmaJeffrey J. Popma Micheal J. ReardonMicheal J. Reardon Executive Committee Jeffrey J. PopmaJeffrey J. Popma Michael J. ReardonMichael J. Reardon G. Michael DeebG. Michael Deeb Stephen YakubovStephen Yakubov Screening Committee Jeffrey J. PopmaJeffrey J. Popma Micheal J. ReardonMicheal J. Reardon G. Michael DeebG. Michael Deeb Stephen YakubovStephen Yakubov Thomas GleasonThomas Gleason Echo Core Lab Mayo Clinic (J Oh) Clinical Events Committee Harvard Clinical Research Institute Data Safety Monitoring Committee Harvard Clinical Research Institute Core Pathology Lab CV Pathology (R Virmani) MDCT Core Lab (LTI Sub-study) St. Paul’s Hospital (J Leipsic, P Blanke) Low Risk: Study Administration

7 Low Risk: Safety and Effectiveness Endpoints Primary Endpoint All-cause mortality or disabling stroke at 2 years Secondary Safety Endpoints Composite of death, disabling stroke, life-threatening bleed, major vascular events, or AKI (II or III) at 30 days New permanent pacemaker implantation at 30 days Prosthetic valve endocarditis at one year Prosthetic valve thrombosis at one year All stroke (disabling and non-disabling) at one year Life-threatening bleeding at one year Valve-related dysfunction -> repeat procedure at one year Secondary Effectiveness Endpoints Valve-related dysfunction, defined as moderate or severe prosthetic valve stenosis, or moderate or severe prosthetic regurgitation at one year (per VARC II) Quality of Life (KCCQ) at one year Repeat hospitalization for aortic valve disease at one year Other Outcome Measures Device Success (VARC II) Hemodynamic performance metrics by echo through 10 years

8 Low Risk Inclusion Criteria: What’s New? < 3% heart team risk of mortality at 30 days Symptomatic severe aortic stenosis, defined as AVA ≤1.0 cm 2 (or AVAI ≤0.6 cm 2 /m 2 ), OR Mean gradient ≥40 mmHg, OR Max velocity ≥4.0 m/s Asymptomatic aortic stenosis – defined by an AVA ≤1.0 cm 2 (or AVAI ≤0.6 cm 2 /m 2 ), AND max velocity ≥ 5.0 m/s, OR AVA ≤1.0 cm 2 (or AVAI ≤ 0.6 cm 2 /m 2 ), AND mean gradient ≥40 mmHg, OR Max velocity ≥4.0 m/s AND positive ETT (limited exercise capacity, abnormal BP response, or arrhythmia) Indicated for SAVR with bioprosthesis

9 Low Risk: Exclusion Criteria: What’s New? Bicuspid aortic valve Multivessel CAD with Syntax score >22 and/or unprotected left main Acute MI ≤ 30 days prior to the procedure Severe MR or TR Moderate or severe mitral stenosis Aortic annulus 29 mm Prohibitive LVOT calcification

10 Low Risk Exclusion Criteria: What’s New? “Prohibitive” LVOT Calcification No Clinical Equipose with SAVR

11 Bicuspid Aortic Valve Excluded Low Risk Exclusion Criteria: What’s New?

12 What is the Same with the US IDE Trials? Best Practices CT based Sizing Optimal Aortography Post Procedural -Echo - Hemodynamics -Aortography Post dilation for AR Early Discharge First Patient Enrolled Pinnacle Health March 29, 2016

13 Why TAVR Might Win! TAVR had significantly better valve performance over SAVR at all follow-up visits (P<0.001) 13 Reardon JACC 2015 epub before print

14 Severe PPM = EOAi < 0.65 cm 2 /m 2 Zorn et al J Thorac Cardiovasc Surg 2015; epub before print US CoreValve High Risk Study

15 Zorn et al J Thorac Cardiovasc Surg 2015; epub before print The Truth: Severe PPM is Associated with A Higher Mortality Rate at One Year US CoreValve High Risk Study

16 Summary A randomized trial is justified but it has to be meticulously performed with contemporary best practices and technically proficient surgeons and interventionalists.