Predicting the Future for Transcatheter Valve Therapies: New Devices and Expanded Clinical Indications Martin B. Leon, MD Columbia University Medical

Transcription

1 Predicting the Future for Transcatheter Valve Therapies: New Devices and Expanded Clinical Indications Martin B. Leon, MD Columbia University Medical Center Cardiovascular Research Foundation New York City

2 Presenter Disclosure Information for TCTAP 2010; April 27-30, 2010 Martin B. Leon, M.D. NON-PAID Consultant: Edwards Lifesciences, Medtronic

3 TAVI in 2005 Rules of Engagement Surgery TAVI

4 Transcatheter AVI (TAVI) Predicting the Future

5 TAVI: The Future New Devices Expanded Clinical Indications

6 TAVI: The Future New Devices Expanded Clinical Indications

7 Early Catheter-Based AV Designs The Davis valve (1965) The Andersen valve (1992)

8 TAVI Technologies Current Generation Devices Edwards Lifesciences Medtronic CoreValve

9 TAVI Technologies Current Generation Devices Edwards Aortic Bioprosthesis Balloon expandable stainless steel bioprosthesis Equine Bovine pericardial valve Sheathed (RetroFlex) with tip deflection Antegrade, retrograde, or trans-apical apical approach CoreValve Revalving TM System Self-expanding expanding nitinol cage bioprosthesis Porcine pericardial valve Sheathed system (low profile = 18 Fr) Retrograde (femoral + subclavian) approach

10 The Current Generation Edwards SAPIEN THV Bovine Tissue ThermaFix Treatment Pericardial Mapping Leaflet Deflection Proprietary Processing Untreated Equine Tissue ] Edwards-SAPIEN THV New Skirt Height Current Skirt Height [ Cribier-Edwards THV

11 Edwards Flex Cath Delivery System Evolution Retroflex 3 Retroflex 2 Retroflex Delivery Catheter

12 Edwards Sapien XT THV Cobolt Frame & New Leaflet Geometry Tissue Attachment Leaflet Matching & ThermaFix Partially Closed Design Sapien XT Finite Element Analysis

13 Sapien XT + NovaFlex Delivery System 18 Fr profile

14 Transcatheter AVI Transapical Access Route Transfemoral Transapical

15 CoreValve Self-Expanding HIGHER PART: low radial force area axes the system and increases quality of anchoring Bioprosthesis MIDDLE PART: functional valve area with three leaflets and constrained to avoid coronaries (convexo- concave) avoids need for rotational positioning LOWER PART: high radial force of the frame pushes aside the native calcified leaflets for secure anchoring and avoids recoil and para- valvular leaks A porcine pericardial tissue valve fixed to the frame with PTFE sutures

16 GEN1 8mm CoreValve ReValving System Delivery Catheter Evolution GEN2 7mm GEN3 6mm (18 Fr) 12 Fr shaft

17 CoreValve ReValving TM System 18 Fr Delivery System Loading/Release Handle 12F Shaft Over-the-wire compatible 18F Capsule

18 TAVI Technologies Access Possibilities Edwards Aortic Bioprosthesis Trans-Arterial: femoral (percutaneous), iliac (surgical), abdominal Ao (surgical), subclavian-axillary axillary (surgical), thoracic Ao (surgical) Trans-Apical (surgical) CoreValve Revalving TM System Trans-Arterial: femoral (percutaneous), subclavian-axillary axillary (surgical), thoracic Ao (surgical)

19 Trans-axillaryaxillary (subclavian) TAVI (CoreValve) 18Fr sheath (± graft) Surgical exposure

20 TAVI Technologies Lower profile devices What is Needed 18 Fr (ultimately Fr) Expanded range of valve sizes accommodate annulus diameters from mm Dedicated delivery systems user-friendly, sheath-based with soft tapered nosecone,? tip deflection Improved circumferential annulus fixation reduced para-valvular AR

21 TAVI Technologies Long-term durability of valve and platform year valve and sustained mechanical integrity of platform Optimal positioning before/during deployment (improved placement position) advanced imaging What is Needed localization and stabilizing features? retrievable and repositionable Embolic protection devices prevent embolic strokes

22 TAVI Technologies What is Needed Dedicated accessory devices specialized sheaths, guidewires, valvuloplasty balloons, indeflators, etc. Improved vascular closure methodologies large hole closure devices

23 Direct Flow Sadra AorTx Jena Valve HLT New TAVI Technologies ABPS PercValve EndoTech Ventor Embracer Symetis

24 Sadra Lotus Valve System Adaptive Seal Self-expanding expanding nitinol platform External polyurethane conforming membrane

25 Sadra Lotus Valve System Can be fully retracted and repositioned

26 Sadra Lotus Valve System Simplified Attachment Current 15 finger design New 3 finger design

27 Non-metallic Percutaneous Direct Flow Aortic Valve Tri-leaflet Valve constructed of Bovine Pericardium Aortic and Ventricular Rings - Inflate independently so device can be repositioned - Deflatable so that device can be fully retrieved Multilumen Slightly Tapered, Conformable Polyester Fabric Cuff Position Fill Lumens (PFLs) -Used to position/reposition valve -Complete Inflation Media Exchange

28 Direct Flow Medical New 18F Design Improved Coronary Clearance and Opening Force 3 sizes matching valvuloplasty balloons 22F Design 18F Design

29 Paieon THV Imaging System Device on target

30 Ventor Embracer Transapical Aortic Valve Diverging Outlet Prevents turbulence Pressure recovery Optimal hemodynamics Throat at native orifice No aggressive predilatation required Avoids pushing the native leaflets against the coronary ostia Subvalvular Inlet Physiologic flow entry Seals off sub-annular zone (limits PVL)

31 TAVI Technologies Need for embolic protection 32 pts with TAVI; Diffusion-Weighted MRI at baseline, post- procedure, 3 mos 22 balloon-expandable and 10 self-expanding expanding THV devices New foci of restricted perfusion in 27/32 pts (84%) Lesions usually multiple and both hemispheres (embolic) No impairment of neuro-cognitive function nor clinical neurologic events assoc with MRI defects 80% of MRI defects resolved at 3 mos imaging study

32 TAVI in Evolution Cerebral Embolic Protection SMT Embrella Deflectors and Filters Claret

33 Embrella: Embolic Protection (intra-cardiac and valve procedures)

34 Cerebral Embolic Protection Claret Filter in Innominate Filter in Left Carotid

35 Percutaneous Closure 10 Fr Prostar device

36 CoreValve F 1st Gen CoreValve - Surgical access and closure - Cardiopulmonary bypass - General anesthesia CoreValve F 3rd Gen CoreValve - Percutaneous access and closure - No hemodynamic support - Conscious sedation PCI like Procedure!

37 TAVI: The Future New Devices Expanded Clinical Indications

38 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

39 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

40 At Least 30% of Patients with Severe Symptomatic AS are Untreated! Severe Symptomatic Aortic Stenosis Percent of Cardiology Patients Treated AVR No AVR 100% 90% 80% 70% 60% 50% 40% 30% 20% Under-treatment especially prevalent among patients managed by Primary Care physicians 10% 0% Bouma 1999 Iung* 2004 Pellikka 2005 Charlson 2006 Bach Spokane (prelim) Vannan (Pub. Pending) 1. Bouma B J et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82: Iung B et al. A prospective survey of patients with valvular heart disease in Europe: The Euro Heart Survey on Valvular Heart Disease. European Heart Journal 2003;24: (*includes both Aortic Stenosis and Mitral Regurgitation patients) 3. Pellikka, Sarano et al. Outcome of 622 Adults with Asymptomatic, Hemodynamically Significant Aortic Stenosis During Prolonged Follow-Up. Circulation Charlson E et al. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis2006;15:

41 TAVI Patient Selection Includes Careful Frailty Assessment Patient A vs. Patient B Same age and predicted risk One passes the eyeball test one does not Frailty is being studied systematically as part of the PARTNER U.S. IDE study Photos courtesy of Michael J. Mack, MD Medical City Dallas

42 Severe AS without AVR Bach DS, et al. Circ Cardiovasc Qual Outcomes. 2009;2:

43 Severe AS without AVR Non-operative operative Patients with Severe AS by Site Percent (%) Unoperated Unoperated symptomatic Unoperated symptomatic risk<avr median 0 Total University VA Private

44 SOURCE Registry EuroSCORE as Predictor of 30-day Mortality ROC Curves TA ROC TF ROC Sensitivity EuroSCORE = 25 EuroSCORE = 35 EuroSCORE = 30 EuroSCORE = 20 C statistic: TF = 0.64 TA = Specificity Courtersy of Martyn Thomas

45 Correlation Between STS and Logistic EuroSCORE in High Risk AS Patients STS Score (%) R 2 = Logistic EuroSCORE (%) * Data from patients enrolled in REVIVAL II and PARTNER EU studies

46 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

47 Many Presumed Asymptomatic Patients May Not Be Percent of Asymptomatic Patients with Positive Exercise Test Genuinely Asymptomatic Tested Symptomatic Amato 2001 Das 2005 Amato MCM et al. Heart 2001;86: ; 386; Das P et al. European Heart Journal 2005;26:

48 TAVI in 2010 Asymptomatic Severe AS Rosenheck R, et al. Circulation 2010;121:151-6

49 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

50 Aortic Stenosis in the Community Low gradients and AS severity % patients with AVG < 40 mmhg AVA > 1.5 AVA AVA < 1.0 Sarano et al; TCT09

51 Low Flow/Low Gradient AS Two Distinct Entities! 1. Low EF - may be pseudo severe AS or true anatomic severe AS 2. Normal EF paradoxical low flow 2 ry valvulo-arterial arterial impedance mismatch Both syndromes require further diagnostic assessment and both have important prognostic and therapeutic implications

52 544 consecutive pts with at least mod AS (jet velocity 2.5 m/s) and no symptoms at baseline primary endpoint = overall mortality regardless of therapy (incl AVR); 4-year actuarial FU 4-yr survival significantly (p < 0.001) lower in patients with baseline Zva 4.5 mm Hg.ml - 1.m 2 Hachichi Z, Dumesnil JG, Pibarot P. J Am Coll Cardiol 2009;54:

53 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

54 Number of Aortic Valve Procedures STS Database Cumulative Over Last 10 Years Cumulative Count 120, , ,000 90,000 80,000 70,000 60,000 50,000 40,000 30,000 20,000 10, AV Replace AV Replace + CAB AV Replace + MV Replace

55 Unadjusted Aortic Valve Operative Mortality STS Database Yearly Over Last 10 Years Percent of Patients 12% 11% 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% 0% AV Replace AV Replace + CAB AV Replace + MV Replace

56 Ann Thorac Surg 2009; 88: 23-42, 43-62

57 Complications of AVR Pts STS Database (2002-6) Mort CVA RF Vent DSWI Reop Comp Isolated AVR AVR + CABG Average Ann Thorac Surg 2009; 88: 23-42, 43-62

58 Dallas Cardiac Surgery Database Aortic Valve Surgery N = 41,023 total cardiac surgery cases Mortality (%) AVR Isolated AVR + CABG AVR After CABG Source: Courtesy of Michael Mack

59 Operative Mortality of AVR After CABG? CABG + AVR for CAD + mild/mod AS Mortality (%) n=2,416 age > 75yrs STS St. Lukes TX Mayo

60 Combined CAD and AS Integrating modern PCI (hybrid approaches) In high surgical risk or inoperable pts, pre-treatment with PCI may defer AVR (esp. in mod AS pts) or reduce subsequent risk of surgical AVR In pts with AS + CAD Ø pre-treatment with PCI may reduce risk of AVR + CABG Ø PCI + TAVI (? staged) may reduce risk of AVR + CABG

61 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

62 Currently, treating highest risk decile (top 10% risk strata) next target should be top 33% risk strata. Ø Ø Ø Still older pts estimated mean age ~80 yrs Disproportionate % pts with concomitant CAD both requiring CAD treatment and after previous CABG (? TAVI + PCI strategies) Approximate STS 5 For the time being, should avoid Ø Younger pts, esp. with bicuspid valve disease + dilated Ao Ø Ø TAVI Medium Risk AS Target Population Asymptomatic AS Low flow low gradient AS

63 Achieve 30-day mortality with TAVI ~ 4-5%, in these more standard risk AS pts. Ø Ø Requires intense training effort and commitment to a multi-disciplinary valve therapy center concept Restrict access to no more than 25% of currently practicing interventionalists Reduce current TAVI related complications. Ø Ø TAVI Medium Risk AS TAVI Goals Improve precision and consistency of THV positioning (adjunctive imaging) Reduce para-valvular leak (THV sizing, technique, and other device adjustments)

64 Ø Ø Ø Reduce peri-procedural procedural strokes (e.g. embolic protection devices) Reduce vascular complications (case selection and lower profile - < 20 Fr TAVI systems) Other pacemaker requirements, chronic kidney injury, CA access and obstruction Stress lesser-invasive procedural considerations. Ø Ø Ø TAVI Medium Risk AS TAVI Goals Conscious sedation (whenever possible) Access closure (totally percutaneous procedure) Reduced LOS and ICU time, reduced ventilatory requirements, rapid ambulation and return to daily activities

65 Insist on adequate valve/support structure DURABILITY ( 10 years for these standard risk pts) Ø Ø Careful annual echo follow-up Valve-in-valve may be mitigating factor Demand rigorous clinical trial methodologies Ø Ø TAVI Medium Risk AS TAVI Goals Standard endpoint definitions (VARC) Randomized trials for most important subsets (incl. standard risk pts vs. surgical AVR)

66 TAVI in 2010 Expanded Clinical indications Untreated Severe AS (+ symptoms) Asymptomatic Severe AS Low Flow Low Gradient AS AS + CAD Medium (normal) Risk AS Bioprosthetic Valve Failure

67 Transcatheter AVI Endless Possibilities! Trans-apicalapical AVR Trans-apicalapical MVR (valve-in-valve) Edwards-Sapien Courtesy of Dr. John Webb

68 TAVI in 2010 Bioprosthetic Valve Failure Webb JG, et al. Circulation 2010;121:151-6 Aortic (n=10), mitral (n=7), pulmonary (n=6), and tricuspid (n=1)

69 Transcatheter AVI My Rosey Prophecy Surgery The PAST In the next 5-10 years, most patients with severe AS requiring AVR will be treated using transcatheter lesser-invasive modalities! TAVR The Future

70 TAVI in 2010 Rules of Engagement TAVI surgery

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