Progress in Transcatheter Mitral

Valve Replacement SOLACI 2017

Eduardo de Marchena, M.D., F.A.C.C., F.A.C.P., F.S.C.A.I.

Professor of Medicine & Surgery

Associate Dean for International Medicine

Program Director,

International Interventional Structural Heart Disease Fellowship

University of Miami Miller School of Medicine

Potential conflict of Interest

• Support for Educational Conference – Most Cardiovascular Corporations

• Active Sponsored Research Support – – Medtronic Other Conflicts:

1. Tendyne Medical Inc. - Co founder

2. Abbott Medical - Consultant

3. Intergene International LLC -Medical Advisory Board

4. Aegis Medical – Medical Advisory Board and stock holder

5. St. George Medical – consultant

6. Argo Medical – Investor/ Consultant

7. de Marchena Wellness - President

8. SwiftSynch – President

9. Vdyne – Advisory Board and investor

New Investigational Devices

******Not FDA or CE mark approved*******

4

Mirabel M, et al. Eur Heart J 2007;28:1358-1365

No surgery in 49%

Not all patients are good surgical candidates

396 patients in Europe with symptomatic severe MR (53% degenerative)

0

20

40

60

80

100

120

140

160Decision not tooperate

Decision tooperate

P<0.0001

63% 59% 67% 42%

15%

<50 50-60 60-70 70-80 >80

Stone ,G TVT2012

Prevalance of MR in US

de Marchena E, Badiye A, Robalino G, Junttila J, Atapattu S, Nakamura M,

De Canniere D, Salerno TJ Card Surg 2011;26:385-392

Carpentier’s functional classification.

Type I, normal leaflet motion;

Type II, increased leaflet motion (leaflet

prolapse);

Type IIIa restricted leaflet motion during

diastole and systole;

Type IIIb restricted leaflet motion predominantly

during systole.*

Mitral Valve Replacement

A Long Road

Anatomic Challenges

Pouch, A et al. Circulation

Mitral Valve Sizing

FMR/IMR Subjects

3D TEE

AP 33 - 40 mm

CC 40 - 44 mm

Topilsky, JAHA 2013; Khabbaz, ATS 2013; Kovalova, Echocardiography 2011

Mitral Annulus in the context of TMVI

Projected area

Leipsic J TVT 2014

Transcatheter Mitral Valve Implantation

(TMVI) Devices

Maisano EHJ 2015

CardiAQ Twelve Medtronic

Neovasc - Tiara

TMVR Candidates

Tendyne

Edwards Mitral Direct flow

Tendyne Valve

Tendyne Transcatheter Mitral Valve

Tendyne Device

• Tri-leaflet porcine pericardial valve

• Self-expanding nitinol double frame

• D-shaped outer frame, anterior cuff

• Large valve size matrix

• Single inner valve size

• Multiple outer frame sizes

• Large Effective Orifice Area (>3.0cm2)

• Transapical access, valve tethered to apex

• Adjustable tension provides valve stability

• Apical Pad assists in access closure

• Valve fully retrievable and repositionable

David WM Muller, MBBS, MD, TCT 2016

Animation Tendyne Valve

Site: Hospital Italiano;

Asuncion, Paraguay

Date: February & August, 2013

Team:

• Cardiac Surgery

• Georg Ludder

• Lucian Lozonski

• Adrian Ebner

• Santiago Gallo

• Interventional Cardiology

• Eduardo de Marchena

• Echocardiography

• Eduardo Alvarez

• James Berry

• Anesthesia

• Enrique Silva

• Technical assistant

• Dan Mans

• Bob Vidlund

• Zack Tegels

• Michael Evans

• Christian Marin y Kall

• Jeff Franco

Acute First in Man

Lutter G, Lozonshi Marin Y Kall C,… de Marchena E. J Am Coll Cardiol Intv. 2014;7(9):1077-1078

Tendyne Patient Number 1

• 57 y.o. man NYFC III from Myxomatous mitral valvular disease

• Echocardiographic findings • MR grade 4+ • Vena Contracta 8.0 mm • LA size 6.46 cm • Regurgitation fraction 35.4% • LV diastolic 51 mm; Systolic 35 mm • LVEF 59% • Carpentier class II with posterior leaflet prolapse

• STS mortality 7.1% and Mortality Morbidity 54.1%; Euroscore II - 8.8%. • Prolapse of posterior leaflet

22

Lutter G, Lozonshi Marin Y Kall C,… de Marchena E. J Am Coll Cardiol Intv. 2014;7(9):1077-1078

Baseline TEE patient 1

Lutter G, Lozonshi L,… de Marchena E. J Am Coll Cardiol Intv. 2014;7(9):1077-1078

Valve at annulus

Pre and Post Ventriculogram Patient 1

Transcardiac Echo of LV outflow post implantation Patient 1

3d short axis of valve

Lutter G, Lozonshi L,… de Marchena E. J Am Coll Cardiol Intv. 2014;7(9):1077-1078

David WM Muller, MBBS, MD, TCT 2016

David WM Muller, MBBS, MD, TCT 2016

Tendyne TMVI Trials

Compassionate Use (n=8)

• 3 sites

Global Feasibility Study (n=30)

• 8 sites, Australia, US and Norway

CE Mark Study/Expanded Feasibility Study (n=110)

• Up to 25 centers (10 US)

• Up to 40 US patients

Total experience to date:

• >50 cases, longest follow-up 2yrs

Tendyne TMVI Investigators

Global Feasibility Study (n=30)

• St Vincent’s Hospital, Sydney

• Abbott Northwestern, Minneapolis

• Prince Charles Hosp, Brisbane

• Baylor Heart and Vascular, Dallas

• Oslo University Hospital, Oslo

• Evanston Hospital, Chicago

• Cleveland Clinic, Cleveland

• Medstar Hospital, Washington DC

November 2014 – March 2016

Muller et al JACC In press

Tendyne GFS: Demographics (n=30)

Age at Baseline

Mean+SD 75.6+9.2 years

Range 55.1-91.4 years

Gender

Male 25 (83.3%)

Female 5 (16.7%)

NYHA Functional Class

II 14 (46.7%)

III 16 (53.3%)

IV 0 (0%)

STS Score (range) 7.3+5.7 (2-16 )

David WM Muller, MBBS, MD, TCT 2016

Tendyne GFS: Demographics

Co-morbidities N=30

Diabetes (all T2DM) 11 (36.7%)

Chronic lung disease/COPD 10 (33.3%)

Chronic kidney disease (eGFR<60) 17 (56.7%)

Prior CVA 2 (6.7%)

Prior thoracotomy

CABG 14 (46.7%)

Prior valve intervention/surgery 0 (0.0%)

Arrhythmia

Atrial fibrillation 17 (56.7%)

ICD/BiV PPM in situ 15 (50.0%)

David WM Muller, MBBS, MD, TCT 2016

Tendyne GFS: Patient Overview (n=30)

Baseline Mitral Valve pathology

Primary MR 3 (10%)

Secondary MR 23 (76.7%)

Mixed pathology 4 (13.3%)

Baseline LV function N=29

LVEF <30% 3 (10.3%)

LVEF 30-50% 14 (48.3%)

LVEF>50% 12 (41.4%)

David WM Muller, MBBS, MD, TCT 2016

GFS: Acute Outcomes

Outcome N=30

Death (all cause) 0 (0%)

CVA 0 (0%)

Major bleeding

Transfusion 3 (10%)

Device-related

Device embolization 0 (0%)

Cardiac perforation 0 (0%)

Paravalvular leak 1 (3.3%)

Device Retrieval

LVOT obstruction 1 (3.3%)

Did not properly seat - access issue 1 (3.3%)

David WM Muller, MBBS, MD, TCT 2016

Tendyne TMVI: D30 Outcomes

Outcome N=30

Death (all cause) 1 (3.3%)

Cardiac 0 (0%)

Non-cardiac 1 (3.3%)

CVA 0 (0%)

MV surgery 0 (0%)

Re-hospitalisation

Heart failure 4 (13.8%)

LVAD/transplant 0 (0%)

Other (ileus) 1 (3.3%)

Device-related

Hemolysis, transfusion 1 (3.3%)

Leaflet thrombosis 1 (3.3%)

David WM Muller, MBBS, MD, TCT 2016

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Baseline 30 days

Grade IV

Grade III

Grade II

Grade I

None

MR severity post-TMVI (n=30)

3.3

6.9

93.1

90.0

6.7* *No device in situ (n=2)

David WM Muller, MBBS, MD, TCT 2016

Functional capacity post-TMVI (n=30)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Baseline Day 30

NYHA Class

Class IV

Class III

Class II

Class I

7.1

46.7

53.3

25.0

50.0

17.9

p=0.03

David WM Muller, MBBS, MD, TCT 2016

Tendyne TMVI: D30 QOL Outcome

0

10

20

30

40

50

60

70

Baseline 30days

KCCQ score

p=0.0018

50.2

64.6

David WM Muller, MBBS, MD, TCT 2016

Baseline Day 30

90.1

72.1

p=0.0012

0

20

40

60

80

100

120

140

160

180

LV End-Diastolic Volume Index (mls/m2)

LV Volume post-TMVI (n=30)

David WM Muller, MBBS, MD, TCT 2016

Baseline Day 30

48.4 43.1

p=0.18

0

10

20

30

40

50

60

70

80

90

100

1 2

LV End-Systolic Volume Index (mls/m2)

LV Volume post-TMVI (n=30)

David WM Muller, MBBS, MD, TCT 2016

Baseline Day 30

47.1 41.3

p=0.043

LV Function post-TMVI (n=30)

0

10

20

30

40

50

60

70

1 2

LV Ejection Fraction (%)

David WM Muller, MBBS, MD, TCT 2016

Day 30 CT: systole

Circumferential apposition of atrial skirt

Seated well at annulus/atrioventricular junction

Tether perpendicular to plane of annulus

The Trans-catheter Mitral Valve Replacement era has begun!

• Early phase mayor questions:

– Case selection

– New designs to minimize LVOT obstruction

– Proper planning and imaging for technique

– Thrombosis and long term anticoagulation

– Can Transapical approach be replaced by antegrade approaches

– Longevity of valve

Thank You