TAVI: The Real Deal? Marc Pelletier, MD Head, Department of Cardiac Surgery New Brunswick Heart Centre

TAVI: The Real Deal? Marc Pelletier, MD Head, Department of Cardiac Surgery New Brunswick Heart Centre

Disclosure St. Jude Medical: Consultant and Proctor Edwards Lifesciences: Proctor Medtronic: Research Grants Sorin: Consultant

Objectives Review current status and evolution of TAVI in Canada Understand the outcomes of TAVI in high risk patients Discuss the evaluation of potential TAVI candidates

Aortic Stenosis is Life-threatening and Progresses Rapidly Survival after onset of symptoms is 50% at two years and 20% at five years 1 Surgical intervention [for severe AS] should be performed promptly once even minor symptoms occur 2 1 S.J. Lester et al., The Natural History and Rate of Progression of Aortic Stenosis, Chest 1998. 2 C.M. Otto, Valve Disease: Timing of Aortic Valve Surgery, Heart 200 Chart: Ross J Jr, Braunwald E. Aortic Stenosis. Circulation. 1968;38(Suppl 1):61-7. 4

Aortic/Mitral Valve Surgery with/without other procedure 250 200 # cases 150 100 AVRpl MVRpr MVRpl 50 0 2005 2006 2007 2008 2009 2010 2011 2012

ACC/AHA INDICATORS FOR AVR Source: Robert O. Bonow et al. ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Valvular Heart Disease). JACC. 2006;e17-e26.

SURVIVAL BENEFIT IN SURGICALLY TREATED PATIENT COHORT % Survival 100 90 80 70 60 50 40 30 20 10 0 Patient survival 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Years AVR, no Sx AVR, Sx No AVR, no Sx No AVR, Sx Source: Morgan L. Brown et al. The benefits of early valve replacement in asymptomatic patients with severe aortic stenosis. J Thorac Cardiovasc Surg. 2008;135(2):308-315.

Many patients remain untreated EU United States Sources: 1) B J Bouma et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart. 1999;82:143-148. 2) Bernard Iung et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. Eur Heart J. 2003;24:1231-1243. 3) Patricia A. Pellikka et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circ. 2005;111:3290-3295. 4) Erik Charlson et al. Decision-Making and Outcomes in Severe Symptomatic Aortic Stenosis. J Heart Valve Dis. 2006;15:312-321. 5) Padmini Varadarajan et al. Clinical Profile and Natural History of 453 nonsurgically Managed Patients With Severe Aortic Stenosis. Ann Thorac Surg. 2006;82:2111-5. 6) David S. Bach et al. Unoperated Patients With Severe Aortic Stenosis. JACC. 2007;50:2018-2019. 7) Faud Jan et al. Unoperated Patients With Severe Symptomatic Aortic Stenosis. Circ.2009;120:S753. 8) Benjamin H. Freed et al. Reasons for Nonadherence to Guidelines for Aortic Valve Replacement in Patients With Severe Aortic Stenosis and Potential Solutions. AMJC. 2010;105:1339-1342.

How do you decide someone shouldn t have surgery??? 95 years old and Texas tough Courtesy Todd Dewey

It s not just about the STS risk score Same age (90) and predicted risk (12%) Frailty Index 7 (Severely frail) 1 (Very fit)

Evolution of AS surgery

Is TAVI better than medical therapy?

Rigorous Study Protocols and Management Two Individually Stratified and Powered Cohorts Symptomatic Severe Aortic Stenosis Yes ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened No Cohort A Total = 1,058 patients Cohort B N = 700 High Risk 2 Parallel Trials: Inoperable N = 358 Individually Powered ASSESSMENT: Transfemoral Access Yes No 1:1 Randomization Not In Study TAVI Transfemoral VS Standard Therapy (Usually BAV) Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)

20% Absolute Reduction in Mortality at 1 Year 100 All-Cause Mortality Standard Therapy Edwards THV All-Cause Mortality, % 80 60 40 20 0 at 1 yr = 20.0% NNT = 5.0 pts 50.7% 30.7% 0 6 12 18 24 Months HR [95% CI] = 0.55 [0.40, 0.74] P (log rank) <.001 Numbers at Risk Edwards THV 179 138 122 67 26 Standard Therapy 179 121 83 41 12

How does TAVI compare to surgery?

Rigorous Study Protocols and Management Two Individually Stratified and Powered Cohorts Symptomatic Severe Aortic Stenosis Yes ASSESSMENT: High-Risk AVR Candidate 3,105 Total Patients Screened No Cohort A Total = 1,058 patients Cohort B N = 700 High Risk 2 Parallel Trials: Inoperable N = 358 Individually Powered Yes ASSESSMENT: Transfemoral Access No ASSESSMENT: Transfemoral Access High-Risk TF High-Risk TA Yes No 1:1 Randomization 1:1 Randomization 1:1 Randomization Not In Study TAVI Transfemoral VS Surgical AVR TAVI Transapical VS Surgical AVR TAVI Transfemoral VS Standard Therapy (Usually BAV) Primary Endpoint: All-Cause Mortality (1 yr) (Non-inferiority) TA, transapical; TF, transfemoral; BAV, balloon aortic valvuloplasty. Primary Endpoint: All-Cause Mortality Over Length of Trial (Superiority) Co-Primary Endpoint: Composite of All-Cause Mortality and Repeat Hospitalization (Superiority)

Primary Endpoint: All-Cause Mortality at 1 Year 0.5 0.4 0.3 TAVR AVR HR [95% CI] = 0.93 [0.71, 1.22] P (log rank) = 0.62 26.8 0.2 24.2 0.1 0 0 6 12 18 24 No. at Risk Months TAVR AVR 348 298 260 147 67 351 252 236 139 65

PARTNER trial established: TAVI is better than medical therapy in HIGH risk (STS risk 11.2-12.1%) patients TAVI shows similar results to AVR in HIGH risk (STS risk 11.8%) patients TAVI is less invasive, recovery is easier Concerns with TAVI High rates of aortic insufficiency Vascular complications Unexpected complications (pacemaker, root rupture )

Corevalve PIVOTAL Trial

Baseline Demographics 21

Non-STS Co-Morbidity, Frailty, Disability 22

Primary Endpoint: 1 Year All-cause Mortality ACC 2014 Surgical Transcatheter 19.1% 14.2% 4.5% P = 0.04 for superiority 3.3% 23

Corevalve PIVIOTAL 2-Year All-cause Mortality

Corevalve PIVIOTAL 2-Year Stroke results 25

Other Endpoints 26

Echocardiographic Findings 27

PIVOTAL Trial First trial to demonstrate lower mortality and stroke with TAVI versus AVR Concerns with TAVI High rates of pacemaker Vascular complications

Current Advances Ability to accurately position valve Medtronic Evolut R St. Jude Portico Ability to diminish paravalvular leaks Smaller profile to deal with small and diseased femoral vessels

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

Characteristic, % or mean± SD N = 60 Age (years) 82.8 ± 6.1 Women 66.7 Body surface area (m 2 ) 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 68.3 Pre-existing permanent pacemaker 11.7

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 0.0 (0) 3.3 (2) All stroke 0.0 (0) 1.7 (1) Disabling 0.0 (0) 1.7 (1) Non-disabling 0.0 (0) 0.0 (0) Major vascular complications 8.3 (5) 8.3 (5) Life-threatening or disabling bleeding 5.0 (3) 8.4 (5) Embolization or migration 0.0 (0) 0.0 (0) Endocarditis 0.0 (0) 0.0 (0) Coronary obstruction 0.0 (0) 0.0 (0) Valve thrombosis 0.0 (0) 0.0 (0) Pacemaker* 11.7 (7) 13.4 (8) *Patients with a prior pacemaker included in the denominator.

NYHA Class Compared with Baseline, 74.9% Improved at 30 Days and 84.9% at 6 Months Percent of Patients 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 8.3% 60.0% 31.7% Baseline N=60 11.9% 11.3% 37.3% 50.8% 30 Days N=59 20.8% 67.9% 6 Months N=53 NYHA I NYHA II NYHA III NYHA IV CoreValve Evolut R CE Study 33

CoreValve Evolut R CE Study 34 Paravalvular Regurgitation Percent of Evaluable Echocardiograms 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 6.8% 3.4% 7.4% 57.6% 63.8% 35.6% 32.8% 24 H/ 7 Days N=59 30 Days N=58 35.2% 57.4% 6 Months N=54 None/Trace Mild Moderate Severe

Edwards SAPIEN 3 transcatheter heart valve 2 1 Outer Sealing Skirt Designed to minimise paravalvular leak 3 2 Frame Design Enhanced frame geometry for ultra-low delivery profile High radial strength for circularity and optimal haemodynamics Low frame height respects the cardiac anatomy 1 3 Proven Valve Tissue Optimised leaflet shape Utilises the same bovine pericardial tissue and processes as Edwards surgical valves Carpentier-Edwards ThermaFix* process for anti-calcification * No clinical data are available which evaluate the long-term impact of the Carpentier-Edwards ThermaFix process in patients

3.7% 2 4.5% 2 3.5% 2 2.1% 2 Impact of technology and procedure advancement on 30-day mortality rates (KM%) 20% 15% 10% 8.2% 1 6.3% 2 5% 1.6% 2 0% P1A (AVR) P1B (TF) P1A (TF) P2B (TF) P2B XT (TF) S3 EU (TF) S3HR (TF) 221 175 240 271 282 96 491 AVR SAPIEN Valve SAPIEN XT Valve SAPIEN 3 Valve 1. Kodali, S., Transfemoral AVR vs. Surgical Aortic Valve Replacement in High Risk Patients with Severe Aortic Stenosis: Results From The PARTNER Trial. Presented at TVT 2011, June 5, 2011; Vancouver, Canada. 2. Kodali, S., Clinical and Echocardiographic Outcomes at 30 Days with the SAPIEN 3 TAVR System in Inoperable, High-Risk and Intermediate-Risk AS Patients. Presented at ACC 2015, March 15, 2015; San Diego, California.

Unprecedented outcomes at 1 year with the SAPIEN 3 valve Paravalvular AR (Paired Analysis) Transfemoral Population None/Trace Mild Moderate Severe 100% 3.2% 3.2% 80% 28.6% 17.5% 60% 40% 68.2% 79.4% 20% 0% 30 Days 1 Year N = 63 N = 63 Incidence of Moderate/Severe Paravalvular AR Remained Low at 1 Year Data on file

Increase in 1 year survival rates from the SAPIEN valve to the SAPIEN 3 valve 1 Year KM All-Cause Mortality TF Population SOURCE SOURCE XT SAPIEN 3 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% 0 3 6 9 12 Months 91.6% 85.1% 80.1% Webb J., 1-Year Outcomes from The SAPIEN 3 Trial. Presented at EuroPCR 2015, May 19, 2015; Paris, France.

Ultra-low profile SAPIEN 3 system expands treatment possibilities while reducing complications Major Vascular Complications 15.9% 1 Reduction in Major Vascular Complications In Transfemoral Patients 11.3% 1 5.3% 2 4.2% 3 N = 271 N = 282 N = 491 N = 96 PARTNER II Trial Coh B SAPIEN Valve 23/26 mm PARTNER II Trial Coh B SAPIEN XT Valve 23/26 mm PARTNER II Trial SAPIEN 3 Valve 20/23/26/29 mm SAPIEN 3 Trial SAPIEN 3 Valve 23/26/29 mm Sheath Edwards RetroFlex 3 Introducer Sheath Set Edwards Expandable Introducer Sheath Set Edwards esheath Introducer Set Sheath Size 22 / 24F 16 / 18F 14 / 16F Minimum Vessel Access Diameter 7.0 / 8.0 mm 6.0 / 6.5 mm 5.5 / 6.0 mm 1. Data on file, Edwards Lifesciences 2. Kodali S., Clinical and Echocardiographic Outcomes at 30 Days with the SAPIEN 3 TAVR System in Inoperable, High-Risk and Intermediate-Risk AS Patients. Presented at ACC 2015, March 15, 2015; San Diego, California. 3. Webb J., Multicenter Evaluation of a Next-Generation Balloon-Expandable Transcatheter Aortic Valve. JACC, VOL.64,NO.21, pg.2238, 2014

Supported by unprecedented outcomes and real world results Edwards SAPIEN transcatheter heart valves are the most widely used transcatheter heart valves worldwide and consistently demonstrate clinical excellence in both trials and real-world experience*: Over 100,000 Patients Treated Worldwide Over 30,000 Patients Treated in Clinical Trials & Registries Treating Patients in Over 65 Countries *As of February 2015

Hospital to Hospital OPCC Dr. Paddock/ Dr. Pelletier Cath Severe Aortic Stenosis Acknowledge Referral Surgical Consult Consult Dr Paddock Dr Pelletier Coordinate Assessment Assessment Completed In Hospital or Hostel Local Review Health Canada Presentation Procedure Out of Province Reimbursement Approval

TAVI NB Heart Centre CANADA Special Access Program 2009 NBHC Oct 2015 Procedure Success 94% # of Patients (6 failed implants) 339 Transfemoral 169 Transapical 176 41 Alternative Access 96% 200 (6 failed implants) 152 5 Mean Age 81 ± 8 years Female 55% Procedural Outcomes (30 Day): 30 Day Mortality 10.4% Stroke 2.3% Myocardial Infarction (MI) Hemodialysis 1.2% 2.3% 81 years 51 % 2.0 % (4) 1.5 % (3) 1.5% (3) 0% Vascular Complications (Access-Related) 12.8% 1.0 % (2) 43

Final Thoughts TAVI IS the real deal Results of TAVI are consistent with Excellence in Hospital and Community Care Major technological advances in 13 years Next focus will be on trials for low risk patients TAVI as a day procedure is coming