TAVR. Global and US Data. Pichard, L. Satler, R Waksman, I Ben-Dor, N Bernardo, P Corso, S Boyce, S Goldstein, H Cooper, Z Wang, F Asch, J Weidel, T. Weddington, G Weissman, G Weigold, T Fuisz, S Minha, Marco Magalhaes, P Okubagzi, J Lindsay, A. Taylor Medstar Washington Hospital Center. Washington, DC Snowmass, March 2014

Conflict of Interest for A Pichard Proctor for Edwards Lifesciences.

Edwards CENTERA Valve Self Expanding Balloon Expandable Edwards SAPIEN 3 Valve Self Expanding Edwards CENTERA Valve Designed to further reduce PV leaks. TF delivery through a 14 Fr eSheath. Dramatically reduced TA profile: 18 F. Discrete valve anchors in the annulus. Edwards’ bovine pericardial tissue leaflets. Motorized delivery system for stable deployment and single operator use. Repositionable & pre-loaded. Delivered through a 14 Fr eSheath. Discrete valve anchors in the annulus. Edwards’ bovine pericardial tissue leaflets. CE Approved Binder et al. JACC Interv 2013;6:301

Multiple Options for Vascular Access carotid subclavian/ axillary direct aortic Transeptal transapical IVC to Aorta Entry Common Iliac RPA transfemoral

Implants by Access Site Europe 2010 to 2012 Subcl Trans Aortic

US TVT Registry. Mack et al. JAMA 2013;310: 2069-77 Trans-femoral: 64% Trans Apical 29% Trans Aortic 4% Percutaneous Access: 36%

Propensity-Matched Comparison of Outcomes after TA vs. TF (501 patient pairs). Prolonged LOS Hospital death Renal failure Bleeding More likely after TF More likely after TA Pacemaker Stroke Shorter LOS .05 .2 .5 1 2 5 20 Odds Ratio Eugene Blackstone, TCT 2013

Procedural Factors. 23 TAVR Centers in 8 European Countries Hybrid room: 12% TAVR in the Cath Lab: 96% Cardiac surgeon participate in the procedure: 83% CPB machine in Cath lab: 48% TEE used routinely: 70% General anesthesia: 61% Percutaneous Access: 70%

US TVT Registry. Mack et al. JAMA 2013;310: 2069-77 Hybrid OR: 57% Hybrid Cath Lab: 28% Cath Lab 14% Cardio pulmonary bypass: 4% Conscious Sedation: 2% Percutaneous Access: 36% Cross Over to Open Heart surgery: 1%

Procedural Success. CoreValve EU Registries. Ruiz, TVT 2012 Key Message: There was a consistently high (more than 97%) procedural success rate across all CoreValve® System studies. Success of the CoreValve® System implantation procedure means the correct implantation and normal functioning of the prosthesis (evaluated by angiography and echocardiogram) of the valve. Procedural Success. CoreValve EU Registries. Ruiz, TVT 2012

France TAVI 2013. 30 day Results. 41 centres 64% of 3707 TAVI Success rate: 94.1% Death (%) 6.6 Annulus Rupture(%) 0.4 Valve migration(%) 1.3 Coronary obstruction(%) Tamponade(%) 1.2 Surgery(%) 0.6 Stroke with sequelae (%) 2 Vascular complication(%) Pacemaker (%) Edw: 8.1/ MCV: 21 Bataille et al.

Worldwide TAVI Distribution 2012-2013 Rest of the World United States Western Europe Courtesy of BIBA Medtech

11 European Countries Registry TAVI: 2007 to 2012 Registry data

TAVI Centres Registry data

TAVI Implants per Annum Registry data

BIBA Marketing

Annual Implants each Country

National Reimbursement Systems 2012-2013

Implants in Europe 2009-2013

Cumulative implants in Europe 2009-2013

Projected TAVR Heart Teams By Region Highly dependent on reimbursement, continued procedural success.

Courtesy of Patrick Serruys

Trends in TAVI. France 2010 2011 2013 N= 1555 2364 3707 Age(yr) 82±7 83± 7 83 ± 9 LES (%) 23 ± 14 21 ± 14 19 ± 13 General Anesthesia(%) 73 66 62 TA (%) 19 17 7 Length of stay (d) 12 11

Number of AVR’s in Europe Before and After TAVI 1.2% 6.5% 13% 20% SAVR 49459 73000 # of procedures 2007 2008 2009 2010

Germany :TAVI – a Game Changer in AVR konventionell Katheterbasiert % Patients undergoing conventional AVR vs TAVI (Quelle: DGTHG Statistik 2010)

All Aortic Valve Interventions in patients aged 80 or over 1055 2035 2006 2007 2008 2009 2010 UK SATIRE Registry. Moat et al.

All Surgical Aortic Valve Interventions (AVR + AVR & CABG) 6217 7252 2006 2007 2008 2009 2010 7548 UK SATIRE Registry. Moat et al.

250

Source: STS/ACC TVT Registry data warehouse 7/1/2012-6/30/2013

New Trials/Registries UK Satire (TAVR vs SAVR). NORDIC Trial (Corevalve vs AVR). Activation Trial (PCI or not in TAVI with CAD). Simplify TAVI (BAV pre vs no BAV). CHOICE (CoreValve vs Edwards) Clean TAVI, Sentinel is US (Claret device). TAO EmbolX (EmbolX cerebral protection). Cooling and Brain Oxygenation (Rhino-chill device). BRAVO 2/3 (Bivalirudine). AUREA (DAPT vs Oral Anticoagulation)

Learning Curve Partner I. 2621 patients TA TF TF p for trend<0.001

Learning Curve Partner I. 2621 patients Successful device deployment. TA TF TA p for trend<0.05 TF p for trend<0.05 The first metric was device success (successful delivery of one valve, successful retrieval of catheter, resulting in area>0.9, <+3AR). TA had higher success rate but both procedures have demonstrates a trend toward improvement over time. Asymptote at around 40-50 cases Asymptote at around 40-50 cases

Learning Curve 2621 patients in Partner 1 Major Bleeding Vasc Complic. TA TF P<0.34 Although TA is a real surgical procedure, the rates of bleeding did not change of the cases performed which signifies the fact the surgeons know what they’re doing…. On the other hand, the introduction of large bore sheaths for the interventionalist was initially associated with high rates of bleeding events decreasing over time. This trend was significant P<0.04 P<0.004 P<0.04

The Association of Transcatheter Aortic Valve Replacement (TAVR) Availability, Surgical AVR Case Volume, and In-hospital Mortality in the United States A Report from the STS National Database and the STS/ACC TVT Registry J. Matthew Brennan, MD, MPH Assistant Professor of Medicine Interventional Cardiology Duke University Medical Center J. Matthew Brennan, Fred Edwards, Sarah Milford-Beland, John Carroll, Fred Grover, Ralph Brindis, Dave Shahian, Murat Tuczu, Sean O’Brien, Cynthia Shewan, Kathleen Hewitt, Eric Peterson, James Gammie, John Rumsfeld, David Holmes, Michael Mack On Behalf of the TVT Registry Participants Primary STS Discussant: Joseph E. Bavaria, M.D.

Overall AVR & SAVR volumes are increasing Greatest gains seen among lowest risk & TAVR cohorts

TAVR Centers (n=230) ‘No TAVR’ Centers (n=571) Largest gains in surgical AVR volume have been at TAVR centers (although, ‘no TAVR’ centers have also seen modest gain in surgical AVR volume)

Surgical AVR Risk 2008 – 2009 2010 – 2011Q2 2011Q3 – 2013Q2 Low Falling observed & adjusted inhospital mortality over past 5 years Greatest absolute gains in ‘high risk’ surgical cohort Surgical AVR Risk 2008 – 2009 2010 – 2011Q2 2011Q3 – 2013Q2 Low 0.60 (0.53, 0.68) 0.56 (0.49, 0.65) 0.50 (0.44, 0.57) Intermediate 0.76 (0.68, 0.85) 0.66 (0.58, 0.76) 0.62 (0.55, 0.70) High 0.86 (0.78, 0.94) 0.74 (0.66, 0.82) 0.62 (0.55, 0.69) *o:e Ratio calculated using STS PROM calibrated for yr2007 *p<0.0001 across intervals

Low Risk AVR High Risk (S+T) AVR Separation in o:e among high risk patients– improving faster at TAVR centers This increased separation is not seen in low risk patients. May be effect of ‘heart team’ or ‘technology availability’– or, both. *o:e Ratio calculated using STS PROM calibrated for yr2007

Surgical AVR- STS Database 2006-2010 n=100,031 Mean 2.9% PARTNER 2A SURTAVI PARTNER 1 Corevalve US Risk of Mortality

Survival Data Partner Trials and Corevalve Extreme risk have proven Survival Benefit. We are learning on who not to do TAVR, “Cohort C”.

Long Term Outcomes of TAVI Rodes-Cabau et al. JACC 2012;60:1864-75 CHF 15.1% Sudden Death 2.6% MI 3.9% Endocarditis 0.7% MVR 0.7% 339 patients, 52% TA, 3.5 years median f/u Pulmonary 26.9% Kidney Failure 7.9% Stroke 5.9% Major Bleeding 4.6% Cancer 5.3% Other 8.6%

Mortality and STS Score (ITT) (Society Thoracic Surgery Score) Standard Rx TAVR STS <5 STS 5-14.9 STS ≥15 Death Incidence (%) Months Months Months Numbers at Risk 28 26 25 24 16 12 8 7 6 5 108 80 76 67 52 119 84 59 42 29 43 32 23 19 15 47 29 14 8

Inoperable Patients, Partner 1B. Makkar et al. JACC 2014;63:901-11 Standard Therapy Clin. Inoperable Techn. Inoperable

Technical Inoperability Partner Trial. Makkar et al Technical Inoperability Partner Trial. Makkar et al. JACC 2014;63:901-911 85 (23%) of 369 patients

Clinically Inoperable. Partner 1B. Makkar et al. JACC 2014;63:901-11 284 of 369 patients

ESC/EACTS Guidelines - 2012 Class I: Inoperable Heart Team required On-site cardiac surgery Class IIa: High-risk for surgery. Heart team decides. USA: Same as Partner 1 Trial Inclusion Criteria.

USA Requirements for TAVR Program. AATS, ACCF, SCAI, STS Consensus Interventional Cardiology Hospital: 1,000 caths/400 PCIs per year Operators: 100 structural procedures lifetime or 30 L-sided structural procedures per year (60% should be BAV). Surgery Hospital: 50 AVR per year, of which > 10 high-risk (STS ≥ 6%) Operators: 100 AVR career, of which at least 10 are high-risk (STS ≥ 6%) or 25 AVR per year or 50 AVR in 2 years (at least 20 in the last year before initiating TAVR) This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 49

TVT U.S. National Registry Comprehensive prospective observational database (7-page). FU includes 30-days, 1-year (incl. QOL measures). TVT Registry entry linked to reimbursement. This is the Bulleted List slide. To create this particular slide, click the NEW SLIDE button on your toolbar and choose the BULLETED LIST format. (Top row, second from left) The Sub-Heading and footnote will not appear when you insert a new slide. If you need either one, copy and paste it from the sample slide. If you choose not to use a Sub-Heading, let us know when you hand in your presentation for clean-up and we’ll adjust where the bullets begin on your master page. Also, be sure to insert the presentation title onto the BULLETED LIST MASTER as follows: Choose View / Master / Slide Master from your menu. Select the text at the bottom of the slide and type in a short version of your presentation title. Click the SLIDE VIEW button in the lower left hand part of your screen to return to the slide show. (Small white rectangle) 50

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