Disclosures. During the past 12 months, I have received research grants, advisory boards, consultation fees/honoraria, and/or travel expenses from:

Transcription

1 Update on Transcatheter Aortic Valve Replacement Vinod H. Thourani, MD Associate Professor of Cardiothoracic Surgery Associate Director, Structural Heart Center Associate Director, CTS Clinical Research Unit Associate Director, CT Surgery Residency Program Emory University School of Medicine American Association for Thoracic Surgery April 28, 2012

2 Disclosures During the past 12 months, I have received research grants, advisory boards, consultation fees/honoraria, and/or travel expenses from: Edwards LifeSciences: Emory Co-PI, National Steering and Publications Committee St Jude Medical DirectFlow Sorin Medical Co-Founder and IP (via Emory University): Apica Cardiovascular Some of the products are investigational and/or not FDAapproved or available for sale in the US (Corevalve, Sapien non- TF, DirectFlow, Portico, Apica). Some products have only been tested in non-humans

3 Current- Transcatheter Aortic Devices Edwards Sapien Medtronic Corevalve Future- St. Jude Portico Sadra Direct Flow Symetis Medtronic Engager (Ventor) JenaValve

4 TAVR: Transfemoral (TF) and Transapical (TA) Transfemoral Transapical

5

6 Number of T-AVR and S-AVR in Europe TAVI SAVR # of procedures

7 Tests to Assist in Decision Making n TTE/TEE (3D echo beneficial in some) n Determine accurate annulus sizing n Cardiac Catheterization within past 6 months n Iliac vessel angiogram CT SCAN n n Chest/abd/pelvis/through the mid thigh with 1.5 mm cuts and 3D reconstruction n Without contrast in those with creatinine > 1.5 n Evaluate the ascending aorta for calcification n Evaluate femoral and iliac arteries for calcification n Pulmonary function tests n Carotid duplex

8 TTE/TEE Measurements Annular diameter: 18-21mm Use 23mm Valve Annular diameter: > mm Use 26mm Valve

9 CT Imaging for TAVR

10 Potential Transapical Patient

11 CT Imaging for TAVR

12 Our First Patient at Emory: 2007

13 The Patient Population with AS 74 yo primary AVR 90 yo redo AVR

14 Outline Background Preoperative Assessment Intraoperative Technical Aspects Postoperative Complications Outcomes

15 Innovative Catheter Tip Design Sapien XT/Novaflex New shorter softer tip New balloon Processing for Smooth transition To valve RF3 NF - Original NF - Original NF - Improved

16 TAVI Approaches Transfemoral +++ Less invasive Percutaneous Local anesthesia Delivery more difficult than TA More stroke? Delivery profile matters Not for all patients

17 Access/Closure Preclosure with 2-3 Proglides

18 Retroperitoneal Iliac Exposure

19 Transapical AVR

20 Transapical AVR

21 Transapical AVR

22 Medtronic CoreValve Available in Europe: > 3000 cases CoreValve ReValving System Self Expandable Nitinol Frame Porcine Pericardium Size: 26 and 29 mm CE Mark in Europe 18F sheath NOT retrievable Porcine

23 CoreValve Bioprosthesis: Two Sizes Small Large Height Outflow 55 mm 53 mm 40 mm 43 mm Constrained 22 mm 24 mm Inflow Accomodates Annulus of: 26 mm 29 mm 20 mm to 23 mm 23 mm to 27 mm

24 CoreValve Delivery Step 1

25 CoreValve Delivery Step 2

26 CoreValve Delivery Step 3

27 CoreValve Delivery Completed

28 Procedural Success. Corevalve. 100% 96.8% 98.1% 97.0% 98.0% 98.7% 99.0% 98.1% Perc cent of Patients (%) 80% 60% 40% 20% 83.1% * 0% 18 Fr S&E 1 ANZ 2 Spain 3 French 4 Belgian 5 Germany 6 UK 7 Italian 8 N = 126 N = 62 N = 108 N = 78 N = 141 N = 588 N = 460 N = 772 Procedure Success is not defined consistently across all studies. * Technical Success is reported here. 1. Medtronic Data on File. COR : 18 Fr Safety & Efficacy Study Re-Analysis, August 14, Meredith IT. A Snapshot from the Ongoing Australia-New Zealand Medtronic CoreValve Registry. Transcatheter Cardiovascular Therapeutics 2009, September 21-25, San Francisco, CA. 3. Avanzas P, Munoz-Garcia AJ, Segura J, et al. Percutaneous implantation of the CoreValve self-expanding aortic valve prosthesis in patients with severe aortic stenosis: early experience in Spain. Rev Esp Cardiol. 2010;63: Eltchaninoff. French Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 5. Bosmans. Belgian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 6. Zahn. German Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 7. Ludman. UK Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France. 8. Petronio. Italian Registry, TAVI Facts, Figures and National Registries. EuroPCR 2010, Paris, France.

29 CoreValve Pacemaker Rates (high, but vary by center) 60% Weighted Average 28.5% Percent of Patients (%) 50% 40% 30% 20% 10% 31.3% 40% 35.2% 26.9% 23% 42.5% 26% 18.5% 0% 18 Fr S&E 1 ANZ 2 N = 125 N = 118 Spain 3 N = 108 French 4 N = 66 Belgian 5 N = 119 German 6 N = 588 UK 7 N = 460 Italian 8 N = 772

30 CoreValve US Pivotal Trial Design 40 Sites in the US National Co-PIs: Jeff Popma, MD David Adams, MD Medtronic CoreValve U.S. Pivotal Trial No Extreme Risk Patient Group Iliofemoral access? High Risk Patient Group 790 Randomization 1:1 Up to 100 Yes * 395 CoreValve Observational CoreValve Single Arm CoreValve SAVR Alternative Access *Includes iliofemoral and alternative access patients Note: 3 roll-in patients per study site equates to a maximum of 1,497 patients enrolled

31 Complications Severe transvalvular or paravalvular AR Major bleeding Aortic rupture or dissection Coronary artery obstruction Severe MR Arrhythmias/Bradycardia Pericardial effusion VSD Valve misdeployment

32 Aortic Dissection H.S., 83 y, male Successful CoreValve implantation Collapsed on ICU on 1st POP day Resuscitation unsuccessful Autopsy performed Aortic wall perforation Courtesy of R. Langer, et al, Munich

33 Ventricular Deployment

34 Valve Positioning Software

35 Left Main Occlusion

36 LV Bleeding

37 Transapical Closure Devices In Development Apica Entourage CardioClose MID Permaseal Novogate SpirX Closure Cardiapex

38 Iliac Rupture

39 All Cause Mortality: TF vs Med Tx (PARTNER 1B) Freedom fro om Death (%) at 1 yr = 20.0% NNT = 5.0 pts 69.3% 49.3% Standard Rx TAVI Months Numbers at Risk TAVI Standard Rx

40 Neuro events at 30D & 1Y: PARTNER 1B Major Stroke All Stroke or TIA per cent P = 0.06 P = 0.18 P = P = Days 1 Year TAVR (n=179) Standard Rx (n=179)

41 Major Vascular Complications: PARTNER 1B 16.8% 30 Days p < % 1 Year P< % 2.2% TAVR n=30 Std Tx n=2 TAVR n=31 Std Tx n=4

42 PARTNER 1A: 2 YEAR Kodali, NEJM, 2012

43 PARTNER 1A: 2 YEAR Kodali, NEJM, 2012

44 PARTNER 1A: 2 YEAR Kodali, NEJM, 2012

45 DW-MRI after TAVI Valve New lesions Strokes Ghanem CoreValve 73% 10% Knipp SAPIEN 58% 4% Kahlert Both 84% 0% Astarci Both 91% 0% Rodes, Webb SAPIEN 68% 3.3%

46 Embrella Deflector Radial access Canadian/German feasibility study SHEF Deflector Femoral access German feasibility study Claret Dual carotid filter German feasibility study

47 PV Aortic Regurgitation: PARTNER 1A 100 P < P < P < Patien nts % TAVR AVR TAVR AVR TAVR AVR 30 Days 6 Months 1 Year None Trace Mild Moderate Severe

48 PARTNER 1A: 2 YEAR Kodali, NEJM, 2012

49 Additional Experience Through Non-Randomized Continued Access # of Patients Enrolled May 2007 Dewey, STS, 2012 Randomized Clinical Trial PMA-TA = 104 AVR = 103 April 2008 Sep 2009 PMA Continued Access Period NRCA-TA = 843 Sep 21, 2011 PMA Data Lock

50 Clinical Outcomes at 30 Days and 1 Year (AT) All percents are KM estimates. 30 Days 1 Year Outcome PMA-TA (n = 104) AVR (n = 92) NRCA-TA (n = 822) PMA-TA (n = 104) AVR (n = 92) NRCA-TA (n = 822) All-Cause Mortality pts. (%) 9 (8.7%) 7 (7.6%) 66 (8.2%) 30 (29.1%) 23 (25.3%) 148 (23.6%) Stroke pts. (%) 7 (7.0%) 5 (5.5%) 16 (2.0%) 10 (10.8%) 6 (7.0%) 22 (3.7%) Death or Stroke pts. (%) 16 (15.4%) 11 (12.0%) 80 (9.9%) 36 (34.8%) 27 (29.7%) 163 (25.7%) Note: p-values between NRCA-TA vs PMA-TA and NRCA-TA vs AVR are all not significant. Dewey, STS, 2012

51 All-Cause Mortality (AT) 40% AVR All-Cause Mortality 30% 20% 10% PMA-TA NRCA-TA at 1 yr: AVR - PMA-TA = 3.8% AVR - NRCA-TA = +1.7% 0% No. at Risk Months Post Procedure 29.1% 25.3% 23.6% PMA-TA - NRCA-TA = +5.5% AVR PMA-TA NRCA-TA

52 Stroke (AT) St troke 40% 30% 20% AVR PMA-TA NRCA-TA at 1 yr: AVR - PMA-TA = 3.8% AVR - NRCA-TA = +3.3% PMA-TA - NRCA-TA = +7.1% 10% 10.8.% 7.0% 0% No. at Risk Months Post Procedure AVR PMA-TA NRCA-TA %

53 Conclusions Additional experience in The PARTNER Trial NRCA-TA (n=843) further supports transapical as a safe and effective treatment option for high risk patients not eligible for transfemoral access: Mortality: PMA-TA 29.1%, AVR 25.3% NRCA-TA 23.6% Stroke: PMA-TA 10.8% AVR 7.0% NRCA-TA 3.7%

54 Self expanding stent designed to be: Fully re-sheathable Repositionable* (antegrade and retrograde) at the implant site Retrieveable TF and TA St. Jude Medical Portico Transcatheter Valve Program Bovine and porcine pericardial valve with Linx anti-calcification technology Cuff tissue and stent geometry designed to minimize PV leak Leaflet/cuff position within the frame, and stent length, designed for minimal protrusion into LVOT, potentially minimizing conduction system and mitral valve apparatus interference

55 Portico First-in-Human Deployment: Vancouver

56 First-in-Human Deployment

57 Direct Flow Medical: Valve Concept Aortic Ring Positioning Wires Ventricular Ring Check Valves Investigational device not for sale in or outside the United States

58 FIM 18F DFM Valve: Final angiogram (after polymer exchange) Investigational device not for sale in or outside the United States

59 Access For TAVI Subclavian Minimally Diseased Vessel Less Invasive Than TA Local Anesthesia Possible Crosses Arch But Less Traumatic? Direct Access To Valve Direct Aortic Most Direct Access Less Invasive Than TA Surgeons More Comfortable With Access

60 The Future: Valve-in-Valve Deployment

61 The Future: TAo Deployment

62 Two T-AVRs in One Patient.. Trans-apicalapical AVR Trans-apicalapical MVR (valve-in-valve) Sapien Courtesy of Dr. John Webb

63 The Creep for TAVR 25 th percentile =STS th percentile = STS 8% PARTNER II SUR TAVI

64 The PARTNER II Study Design Symptomatic Severe Aortic Stenosis ASSESSMENT: Operability Total = 2000 patients n= 2000 Operable 2 Parallel Trials: Inoperable Individually Powered Inoperable n=500 ASSESSMENT: Transfemoral Access ASSESSMENT: Transfemoral Access Transfemoral Transapical 1:1 Randomization tavr Trans femoral VS Surgical AVR 1:1 Randomization tavr Trans apical VS Surgical AVR tavr SAPIEN 1:1 Randomization VS tavr SAPIEN XT Nested Registry Transapical Primary Endpoint: All Cause Mortality, Major Stroke Primary Endpoint: All Cause Mortality, Major Stroke and Rehospitalization

65 Integral Components Qualified multi-disciplinary team Surgeon Open surgical AVR experience (especially in high risk AVR patients) Catheter-based experience Interventional cardiologist (skilled in structural heart disease) Experienced surgical OR team Experienced transcatheter OR team Vascular surgeon accessible for aorto-iliac disease complications Perfusionist and CPB circuitry present in the OR Fixed-imagining fluoroscopic capability Minimum requirements for sterile OR environment Discuss and prepare for all catastrophic events with specific roles for each member of the team.

66 Conclusions n TAVR is here!!! ARE WE READY???? n Results are superior to medical tx and comparable to open surgery n The patient population who does not benefit from TAVR needs to be further refined n Techniques to prevent embolization (via imaging), vascular complications (via sizing), paravalvular leaks (via imaging), and stroke (via catching of emboli) need to be further refined n Success can only be achieved with a collaborative and dedicated team

67 The Team: Cardiologist and Cardiac Surgeon

68 Thanks Vinod H. Thourani, MD

69

70 CoreValve US Pivotal Trial Design 40 Sites in the US National Co-PIs: Jeff Popma, MD David Adams, MD Medtronic CoreValve U.S. Pivotal Trial No Extreme Risk Patient Group Iliofemoral access? High Risk Patient Group 790 Randomization 1:1 Up to 100 Yes * 395 CoreValve Observational CoreValve Single Arm CoreValve SAVR Alternative Access *Includes iliofemoral and alternative access patients Note: 3 roll-in patients per study site equates to a maximum of 1,497 patients enrolled

71 Impact of TAVR at Emory AVR TAVR