10 mins. Martin B. Leon, MD. Columbia University Medical Center Cardiovascular Research Foundation New York City

Transcription

1 10 mins Martin B. Leon, MD Columbia University Medical Center Cardiovascular Research Foundation New York City Tuesday, November 1, 2016

2 Disclosure Statement of Financial Interest TCT 2016 Washington, DC; Oct 29 Nov 2, 2016 Martin B. Leon, MD Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation / Financial Relationship Company Grant / Research Support Abbott, Boston Scientific, Edwards Lifescience, Medtronic, St. Jude Medical Consulting Fees / Honoraria Abbott, Boston Scientific Shareholder / Equity Claret, Cathworks, Elixir, GDS, Medinol, Mitralign, Valve Medical

3 Estimated Global TAVR Procedure Growth SOURCE: Credit Suisse TAVI Comment January 8, ASP assumption for 2024 and 2025 based on analyst model. Revenue split assumption in 2025 is 45% U.S., 35% EU, 10% Japan, 10% ROW In the next 10 years, TAVR growth will increase X4!

4 TAVR Journey The relentless evolution of TAVR clinical growth has been driven by: the multi-disciplinary heart team commitment to evidence-based medicine rapid technology enhancement simplification of the procedure striking reduction in complications

5 noun / ac. ces. so. ry something that can be added to something else in order to make it more useful, attractive, or effective Merriam Webster Dictionary

6 Categories Balloon aortic valvuloplasty devices or novel aortic valve remodeling technologies Neuroprotection (stroke prevention) devices Large hole vascular closure devices Dedicated guide wires Large bore vascular sheaths Novel imaging modalities (echo/ct, fusion, etc.)

7 Background & General Concepts The TAVR accessory devices (technologies) are designed to either simplify the procedure (e.g. dedicated guide wires and sheaths), improve procedural safety by reducing complications (e.g. neuroprotection and large hole closure), or improve procedural efficacy (e.g. BAV devices and adjunctive imaging modalities), or some combination of the above Sometimes difficult to isolate the safety and efficacy of accessory devices in the setting of a dominant primary therapy (TAVR); generally lower assessment standards required with frequent use of surrogate endpoints

8 Background & General Concepts Since the primary therapy is TAVR, the pre-clinical and clinical assessment standards of these new technologies must be calibrated for each device (or category) according to (1) predicate technology, (2) presumed or proven safety profile, and (3) intended use of the device (IFU claims ) TAVR accessory devices are a wastebasket

9 Balloon Aortic Valvuloplasty (1) V8 Balloon TRUE Balloon CardioSculpt Locks into annulus for stability (doesn t need PM) Hyperextends leaflets safely Good for post-dilation Kevlar composite materials Non-compliant and rupture resistant (precise sizing) Good for post-dilation Scoring elements improve stability (doesn t need PM) Enhance valuloplasty effect

10 Balloon Aortic Valvuloplasty (2) TRUE Flow Balloon Perfusion balloon valvuloplasty system 8 balloon chambers linked by a fiber-based shell; continuous flow during dilatation Improved stability (doesn t need PM), maintained hemodynamics, and allows prolonged inflation times

11 Aortic Valve Remodeling (1) Leaflex AVRT Mechanical shock waves fracture leaflet calcium and improve leaflet mobility 13 Fr catheter Non-occlusive (no PM) Can be used as (1) stand-alone, (2) bridge to TAVR/SAVR or (3) preparation for TAVR (esp. bicuspid valves) diamond stabilizer

12 Aortic Valve Remodeling (2) Lithoplasty for Aortic Leaflet Restoration Electro-hydraulic lithotripsy in a balloon; microsecond bubble expansion and collapse travels thru balloon and disrupts calcium Supra-vavular approach Procedural hemodynamic stability; no need for PM Trans-femoral access Preparation for TAVR preparation or stand-alone therapy

13 BAV & Valve Remodeling Difficult to demonstrate specific clinical benefits, but these new BAV devices have been safe in clinical settings, so the regulatory assessment standards have been very reasonable; no significant clinical trials required, but should monitor outcomes carefully New BAV Devices Valve Remodeling Technologies Safety and efficacy still unknown (potential for calcium fragmentation resulting in embolization or increased AR); clinical trials needed (observational registries) to assess clinical safety and hemodynamic benefits (improvement in AVA cw standard BAV)

14 Neuroprotection Due to the high-frequency of strokes in early TAVR studies, the profound clinical impact of strokes (on both mortality and QOL), and the almost uniform appearance of perfusion abnormalities on neuroimaging studies, the use (need) of neuroprotection using filters/deflectors during TAVR remains important and controversial. Recently, stroke frequency after TAVR has declined (rates similar to surgery) making studies attempting to assess neuroprotection devices based on clinical outcomes difficult; thus, the use of surrogate and composite endpoints in current clinical trials. Embolic debris frequently found

15 Claret Sentinel Cerebral Protection System (CPS) Dual, independent filter (proximal and distal) cerebral embolic Proximal protection Filter device with visible embolic debris (Innominate capture and Artery) removal 9 15 mm The 3rd generation CE-marked embolic protection device Universal size and shape Deflectable compound curve sheath facilitates cannulation of LCC Distal Filter (LCC Artery) mm Right transradial 6F sheath access using a standard guidewire Filters are out of the way of TAVI delivery catheter and accessories during the TAVI procedure

16 CLEAN-TAVI: A randomized trial (n=100) with Claret filters during TAVR Lesion Number per Patient Total Lesion Volume per Patient Claret Montage Cerebral Protection System significantly reduced new cerebral lesion number and volume at 7 days, as measured by DW-MRI Haussig S, Linke A et al, JAMA 2016, 316:

17 SENTINEL Study Design (TAVR RCT) US Co-PIs: Samir Kapadia Susheel Kodali German Co-PI: Axel Linke Population: Subjects with severe AS with clinical indications for TAVR with the Edwards Sapien THV/XT/S3 or Medtronic CoreValve/Evolut-R N=296 subjects randomized 1:1:1 at sites in the U.S and Germany. SAFETY ARM TAVR with Sentinel TEST ARM TAVR with Sentinel RCT CONTROL ARM TAVR only Histopathology Safety Follow-up Safety Follow-up MRI Assessments Neurological and Neurocognitive Tests Primary (superiority) Efficacy Endpoint: Reduction in median total new lesion volume assessed by 3T DW-MR by baseline subtraction (3-7 days) Primary (non-inferiority) Safety Endpoint: Occurrence of all MACCE at 30 days

18 The Triguard Cerebral Protection Device Single-wire nitinol frame and mesh filter (pore size 130μm) designed to deflect cerebral emboli during TAVR while allowing maximal blood flow Positioned across all 3 cerebral vessels and maintained by a stabilizer in the innominate Delivered via 9 Fr sheath from the femoral artery

19 REFLECT US IDE Trial Design Subjects with AS undergoing TAVI N=285 Roll-In N 90 2:1 Randomization TriGuard Embolic Protection n=190 Safety Combined safety endpoint (VARC- 2) at 30 days TriGuard vs. Performance Goal Unprotected TAVI n=95 Efficacy Hierarchical composite efficacy endpoint (Finkelstein-Schoenfeld): o Death or stroke (30 d) o NIHSS or MoCA worsening (inhospital) o Total lesion volume by DW-MRI (post-procedure) TriGuard vs. Control PIs: Baumbach, Lansky, Makar, Moses

20 Neuroprotection Transcatheter neuroprotection during TAVR is still a high-interest controversial subject Thusfar, catheter-based filters/deflectors appear reasonably safe (? resource consumption and cost) Demonstration of efficacy is challenging and current assessment standards, including RCTs using surrogate or composite endpoints are appropriate Embolic debris frequently found

21 Large-Hole Vascular Closure With early TAVR systems, significant vascular complications were frequent ( 15%) and were associated with increased mortality Recently, with lower profile TAVR devices and improved vascular management strategies, there has been a dramatic reduction in vascular complications (< 5%), but there still is considerable time, planning, effort, and expense required to achieve optimal large hole vascular access and closure Prostar Proglide Current suture-based closure devices

22 Large Hole Vascular Closure (novel technologies) Conforming absorbable patch-graft Vivasure PerQseal tether Nitinol frame Sealing membrane (absorbable) Inseal Vascular Closure Device

23 Large Hole Vascular Closure (novel technologies) MANTA Collagen seal with footplate and footplate (14 and 18 Fr) losure Large hole vascular closure is an integral component of the transfemoral TAVR procedure Safety concerns are moderate early and late requiring reasonable demonstration of device performance in observational registries with day clinical follow-up

24 Dedicated Guide Wires Major Characteristics Confida Pre-shaped distal curve (excellent shape retention) Improved shaft stiffness Customized for specific TAVR systems Safari

25 Dedicated Guide Wires Often undervalued but a meaningful accessory device which facilitates TAVR by providing a stable rail with less ventricular ectopy, and likely, reduces LV perforations Since only minor safety concerns, assessment standards have been appropriately adjusted to expedite clinical availability; no significant clinical trials required but clinical performance should be carefully monitored

26 Dedicated Pacing Lead Standard Connector Pins Handle Delivery System 6F Shapeable Lead Body FDA 510(k) approval Bipolar Pacing on Electrodes October 25, 2016 Soft atraumatic tip Lead-positioning Balloon Soft Tip Orientation Marker Stabilizers for secure fixation Stabilizers

27 Large Bore Vascular Sheaths Expandable and In-Line Sheaths (to effectively reduce transfemoral entry profiles) Solopath Expandable from 12 Fr to 18 Fr e-sheath

28 Large Bore Vascular Sheaths Expandable and In-Line Sheaths (to effectively reduce transfemoral entry profiles) In-line Sheath Due to favorable safety profiles, significant clinical trials aren t necessary, but clinical performance should be carefully monitored!

29 Novel Imaging Systems Multi-modality Imaging is the RULE Angio CTA Patient Follow-up Patient Screening, Procedural Planning TTE TEE + 3D Intraprocedural Guidance

30 EchoNavigator Co-registration for fusion imaging 3D Marker 2D Marker Annotation marker is transferred to the fluoroscopic space and will remain accurate regardless of TEE probe position or registration

31 Novel Imaging Systems Trans-septal Puncture Trans-septal Puncture Trans-septal Puncture

32 Novel Imaging Systems MitraClip

33 Novel Imaging Systems Paravalvular Regurgitation

34 Novel Imaging Systems LAA Imaging for Watchman

35 Novel Imaging Systems TAVR Guidance (?)

36 Novel Imaging Systems Patient Follow-up Intraprocedural Guidance Patient Screening, Procedural Planning Modern multi-modality imaging systems are rapidly evolving for use in structural procedures. Apart from standard regulatory approvals, specific oversight and assessment isn t required and should be left to the physician scientists and operators to determine use patterns.

37 Categories Balloon aortic valvuloplasty devices or novel aortic valve remodeling technologies Neuroprotection Clinical need, (stroke value, prevention) safety, and devices Large assessment hole vascular standards closure devices vary among Dedicated guide the device wires categories. Large bore vascular sheaths Novel imaging modalities (echo/ct, fusion, etc.)

38 Categories Balloon aortic valvuloplasty devices or novel aortic valve remodeling technologies Neuroprotection (stroke prevention) devices Large hole vascular closure devices Dedicated guide wires Large bore vascular sheaths Novel imaging modalities (echo/ct, fusion, etc.)