TRANS-CATHETER MITRAL VALVE INTERVENTION

THE NEXT INTERVENTIONAL REVOLUTION?

Juan F. Granada, MD Executive Director and Chief Scientific Officer

CRF-Skirball Center for Innovation Columbia University Medical Center, New York

DISCLOSURE STATEMENT OF FINANCIAL INTEREST

Within the past 12 months, I or my spouse/partner have had a financial

interest/arrangement or affiliation with the organization(s) listed below:

Grant/Research Support: Abbott Vascular, Amaranth Medical, Angiometrix,

AstraZeneca, Bioventrix, Boston Scientific, Caliber Therapeutics, Cardia, Cardiac

Implants, Cagent, Cardiovascular Systems Inc., Cardiosolutions, Celladon,

Cephea, Circulite/Heartware, ControlRad, Corindus Vascular Robotics, CR

Bard/Lutonix, DC Devices, Direct Flow Medical, Draper, Edwards LifeSciences,

Fulgur Medical, Guided Delivery Systems, Intact Vascular, Lutonix, Marvel

Medical, Medtronic, Mercator, MedAlliance, Meril Life Sciences, Microvention,

MicroInterventional Systems, Mitralign, Neovasc, Nitiloop, Nitinotes, Orbus

Neich Medical, REVA Medical, Siemens, Sonivie, Spectranetics, Svelte, Stentys,

Surmodics, Thoratec, UniQure, Volcano, WL Gore, Zenvalve

Equity Position/Consulting: Cephea

As AV disease worsens overtime annular size and configuration remain relatively stable even in the presence of low EF

Mild Moderate Severe

AS PROGRESSION= STENOSIS AND CALCIFICATION

DEPENDS ON DISEASE SUBSTRATE + GEOMETRICAL DISTORTION

+

MR PROGRESSION= ANNULAR AND VENTRICULAR DILATATION

As MV disease worsens overtime it induces changes in the sub-valvular apparatus and other surrounding tissues (atrium, etc.)

It is challenging to develop an “universal device concept” tailored to target all

potential anatomical variations seen in all MR types and patient risk profiles

SURGICAL OPTIONS FOR THE TREATMENT OF MITRAL REGURGITATION: REPAIR VS. REPLACEMENT

Transcatheter MV Intervention: Device Landscape 2017

Coronary sinus annuloplasty • Cardiac Dimensions Carillon**

• Cerclage annuloplasty

Edge-to-edge • MitraClip***

• Pascal* • MitraFlex

Direct annuloplasty • Mitralign TAMR**

• Valtech Cardioband** • GDS Accucinch* • Millipede IRIS* • MVRx ARTO* • Mardil BACE*

• Mitraspan TASRA* • Valcare Amend* • Micardia enCor*

• Cardiac Implants RDS • QuantumCor (RF)

• Valfix

MV replacement (cont) • MitralHeal

• HT Consultant Saturn • Lutter valve

• Transcatheter Technologies Tresillo • Venus • Verso

• Transmural Systems • 4C

Other approaches • NeoChord DS 1000** • Harpoon neochords*

• Babic chords* • Middle Peak Medical*

• St. Jude leaflet plication* • Cardiosolutions Mitra-Spacer*

• Mitralix* • Valtech Vchordal

• Coramaze Mitramaze

MV replacement • Edwards CardiAQ*

• Edwards Fortis* • Neovasc Tiara*

• Abbott Tendyne* • Medtronic Intrepid*

• HighLife* • MValve* • Caisson* • Cephea

• NCSI NaviGate • St. Jude

• Micro Interventional • Valtech CardioValve

• ValveXchange • MitrAssist

• Braile Quattuor • Direct Flow

• Sinomed Accufit • Corona MVR w/Amend ring

*In patients *CE mark *FDA approved

• Safe, highly successful delivery rate

• Especially good for A2 or P2 disease

• It limits the possibility of re-intervention

EDGE-TO-EDGE MV REPAIR: MITRACLIP

Treating Centers 800

Patients (clinical & commercial) >40,000

Implant Rate 97%

Functional MR 64%

Degenerative MR 22%

Mixed 14%

Table courtesy of M. Leon

CE MARK DEVICES FOR TRANS-CATHETER MITRAL VALVE REPAIR

MitraClip Evalve-Abbott

2008

CARILLON Mitral Contour System

Cardiac Dimensions 2009

Enhanced CARILLON Mitral Contour System

Cardiac Dimensions 2011

NeoChord 2012

Edwards Cardioband

2015

Mitralign 2016

Courtesy of Feldman von Bardeleben (Modified)

Abbott MitraClip NT

2016

CATHETER-BASED REPAIR OF POSTERIOR LEAFLET PROLAPSE (MITRAL-BUTTERFLY)

Werner Mohl MD, TCT 2016

• Very safe implantation

– 92.8% procedural success

– Procedural success is implantation with on table reduction of MR to moderate or less

– In-hospital mortality: 2.7%

• At 1yr: 6.1% had a re-intervention with a clip

• At 1yr: 2.1% required surgery

• At 1yr: 25.9% mortality rate

– Residual MR was an independent predictor of mortality

Paul Sorajja. ACC.17

LESSONS LEARNED FROM MITRA-CLIP POTENTIAL PITFALSS OF TRANS-CATHETER

MITRAL VALVE REPAIR

• Agnostic to etiology of MR • Ease of implantation • Reliable elimination of MR • Less recurrence of MR

POTENTIAL ADVANTAGES

DESIGN GOALS

• Eliminate MR

• Ease of delivery

• Leaflets preservation

• Minimize LVOT obstruction

• No paravalvular leak

• Leafleft durability

THE VALUE PROPOSITION OF TRANS-CATHETER MITRAL VALVE REPLACEMENT THERAPIES

MECHANISM OF ANCHORING AND DEVICE SAFETY

2nd Patient FORTIS Case

Blank P. J Am Coll Cardiol Img. 2015;8(10):1191-1208

DYNAMIC ANNULAR DEFORMATION AND TRANS-CATHETER VALVE IMPLANT

COMPRESSION AND PVL

POTENTIAL FOR LVOT OBSTRUCTION: IMPACT ON PATIENT SELECTION

Bla

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20

16

TMVR DEVICES IN DEVELOPMENT (N=33)

• Edwards CardiAQ*

• Edwards Fortis*

• Neovasc Tiara*

• Abbott Tendyne*

• Medtronic Intrepid*

• HighLife*

• MValve*

• Cephea

• NCSI NaviGate

• St. Jude

• Micro Interventional

• Valtech CardioValve

• MitralHeal

• HT Consultant Saturn

• Lutter valve

• Tresillo

• Venus

• Verso

• Transmural Systems

• MitrAssist

• Braile Quattuor

• Caisson

• Direct Flow

• Sinomed Accufit

TRANS-APICAL VALVE DELIVERY (TIARA, NEOVASC)

TIARA TMVR (NEOVASC) 26 Patients Enrolled

CardiAQ TMVR (EDWARDS™) 13 Patients Enrolled

MEDTRONIC INTREPID TMVR 44 Patients Enrolled

TENDYNE TMVR (ABBOTT) 83 Patients Enrolled

180 cases done to date (5/2017) including ALL systems using the

trans-apical approach

CAISSON TMVR (TRANS-SEPTAL) 6 Patients Enrolled (5/2017)

Positioning + Partial Deployment Ventricular Disk Deployment

Full Device Deployment

CEPHEA TMVR DELIVERY (TRANS-SEPTAL) Annular Engagement

Post-Deployment Echo Post-Deployment

FIH Compassionate Use TS CardiAQ (6/12/2012)

TA Tiara (1/30/2014) TA FORTIS (3/2014)

TA Tendyne (10/2014) TA 2nd Gen CardiAQ (5/13/2015)

TMVR DEVELOPMENT TIMELINES

FIH Compassionate Use Cribier et al. 4/16/2002

Inoperable High Risk PARTNER Trial 2007 Started

FDA Approved 2011

Intermediate Risk PARTNER IIa

12-2011 to 11-2013

Low Risk PARTNER III

2016

General Patient Adoption 2020?

14

Yea

rs

TAVR DEVELOPMENT TIMELINES

5-Y

ears

CONCLUSIONS • TC-MVR is today one of the most exciting and potentially promising fields

in cardiovascular medicine

• Unlike TAVR, specific device attributes will greatly influence clinical use, outcomes and physician adoption

• The successful development of this field depends on a proper, thoughtful and step-wise validation approach including:

– Clear definition of the target/disease population (risk-benefit-response)

– Development of accurate predictive models of device failure

– Refinement of imaging tools and co-registration algorithms

– “Re-design” of the heart-team approach

• Meaningful lessons learned from early FIH studies are already the basis of future technological improvements and trial design strategies in this exciting field