Transcatheter Therapies for Mitral and

Tricuspid Regurgitation

Evolving Approaches Under Investigation

Josep Rodés-Cabau, MD

Quebec Heart & Lung Institute, Laval University

Quebec City, QC, Canada

Presenter Disclosure Information

Josep Rodés-Cabau, MD

Research Grants

Edward Lifesciences; Medtronic; St. Jude Medical; V-Wave

•Transcatheter edge-to-edge repair

•Transcatheter mitral annuloplasty

•Transcatheter mitral valve replacement

Transcatheter Therapies for MR

Transcatheter mitral annuloplasty

MITRALIGN System(Mitralign, Inc.)

CARDIOBAND System(Valtech)

ARTO System(MVRx)

CARILLON Mitral Contour System(Cardiac Dimensions)

Transcatheter mitral annuloplasty

MITRALIGN System(Mitralign, Inc.)

CARDIOBAND System(Valtech)

ARTO System(MVRx)

CARILLON Mitral Contour System(Cardiac Dimensions)

Transcatheter mitral annuloplasty

MITRALIGN System(Mitralign, Inc.)

CARDIOBAND System(Valtech)

ARTO System(MVRx)

CARILLON Mitral Contour System(Cardiac Dimensions)

Transcatheter mitral annuloplasty

MITRALIGN System(Mitralign, Inc.)

CARDIOBAND System(Valtech)

ARTO System(MVRx)

CARILLON Mitral Contour System(Cardiac Dimensions)

TMVR devices

TiaraNeovasc Inc.

TendyneAbbott Vascular

CardiAQEdwards Lifesciences

FortisEdwards Lifesciences

IntrepidMedtronic

HighLifeHighLife SAS

TMVR Devices Under Clinical Evaluation

CaissonCaisson Interventional

NCSI NaviGateNaviGate Cardiac

Structures Inc.

MValveMValve Technologies

Boston Scientific

TMVR Devices Under Pre-Clinical Evaluation

CardiovalveValtech HQ

CepheaCephea Valve Technologies

AccuFitSino Medical Science

Technology Inc.

Direct Flow MedicalDirect Flow Medical Inc.

SaturnHT Consultant

Valve shapeValve type Frame

TMVR Technologies Under Clinical Evaluation

Nitinol

Self-expandable

CardiAQ-

Edwards

Nitinol

Self-expandable

Neovasc

Tiara

Tendyne

Intrepid

TMVR

Fortisa

Caisson

Nitinol, double frame,

Self-expandable

Nitinol, double stent,

self-expandable

Nitinol

Self-expandable

Two components

(anchor and valve)

Nitinol, self-expandable

Leaflets

HighLife

TMVR

Two components (ring and valve)

Nitinol, self-expandable

Tri-leaflet

Bovine pericardium

Tri-leaflet

Bovine pericardium

Tri-leaflet

Porcine pericardium

Tri-leaflet

Bovine pericardium

Tri-leaflet

Bovine pericardium

Tri-leaflet

Porcine pericardium

Tri-leaflet

Bovine pericardium

Intra-annular

Supra-annular

Intra-annular

Intra-annular

Intra-annular

Supra-annular

-

Valve position

D-Shaped

Circular

D-Shaped (Outer stent)

Circular (Inner frame)

Circular

Circular

D-shaped

Circular

MValve system Dock system to be used with

commercially available valves

- --

NCSI

NaviGate

Mitral

Nitinol, self-expandable,

xenogeneic pericardium

Tri-leaflet -Circular

Anchoring mechanism

Fibrous trigone capture

with native leaflet

engagement

Mitral annulus capture

with native leaflet

engagement

Apical tether

Radial force and

subannular cleats

Native leaflet

engagement

External anchorMitral annulus capture

with engagement at sub-annular fibrous

groove External anchor

Valve-in-subannularmitral ring

External anchorMitral annulus

capture Annular winglets

Valve type Delivery system size

TMVR Technologies Under Clinical Evaluation

32 Fr

CardiAQ-

Edwards

33 Fr

Neovasc

Tiara

Tendyne

Intrepid

TMVR

Fortisa

Caisson

32 Fr

35 Fr

42 Fr

31 Fr

Recapture

HighLife TMVR NA

No

No

Fully recapturable system after complete

deployment

No

No

Fully recapturable

and retrievable

No

35mm and 40 mm

30 mm

NA (Multiple

configurations)

27 mm with 3 outer

stent sizes (43, 46,

and 50 mm)

29 mm

35mm – 40 mm

31 mm

Valve size(s)

MValve system 32 Fr Fully retrievable NA

NCSI NaviGate

Mitral

30 Fr NA 30/36; 30/40;

33/44

Two anterior and one posterior anchoring

structures

Supra-annular positionIntra-annular sealing skirt

Tappered Outflow

Single inner valve sizeMultiple outer frame

sizes

Dual stent designOuter provide fixation and

isolates the inner stent

-

SAM Management featureOne delivery catheter for each

system (anchor and valve)

NA

Additional features

Universal dock

system

NA

Access

Transapical

Transapical

Transeptal

Transapical

Transapical

Transapical

Transeptal

Transapical

(Transfemoral artery

for loop placement)

Transapical

Transapical,

transatrial or

transfemoral

TMVR – Initial Global Clinical Experience

Regueiro A, Granada J, Rodés-Cabau J. JACC, under review

Fortis Valve - Procedural Result

CardiAQ – TFQuebec Heart & Lung Institute

CardiAQ – TFQuebec Heart & Lung Institute

CardiAQ – TFQuebec Heart & Lung Institute

StudyValve type

Studydesign

Ongoing and Future Studies on TMVR for Treating MR

Prospective registry

CardiAQ-Edwards

Prospectriveregistry

CardiAQ-Edwards

NeovascTiara

Tendyne

Intrepid

Caisson

Prospective registryEFS Trial

Prospective registryEFS Trial

Prospective registryEFS Trial

Prospective registryEFS Trial

Estimated enrollment

MValve Prospective registryEFS Trial

200 patients

28 patients

30 patients

110 patients

10 patients

20 patients

30 patients

Freedom from major adverse cardiac and cerebrovascular events at 30 days per MVARC definition.Freedom from individual adverse events at 30 days

Safety assessed by freedom from device or procedure-related adverse events at 30 days

Safety assessed by freedom from device or procedure related adverse events at 30 daysPerformance assessed by freedom from device malfunction at 30 days

Adverse events associated with the delivery and/or implantation of the device at 30 days

Freedom from major adverse events including death, stroke, myocardial infarction and surgical reintervention through 30 days

Composite serious adverse cardiac events and stroke at 30 days

Primary outcome

RELIEF Trial (NCT02722551)

Early FeasibilityStudy

(NCT02718001)

TIARA-I (NCT02276547)

Early Feasibility Study of the TendyneMitral Valve System

(NCT02321514)

Twelve TranscatheterMitral Valve

Replacement Pilot Study (NCT02428010)

PRELUDE(NCT02768402)

DOCK 1(NCT0271991

2)

Freedom from all-cause mortality and major adverse events defined as disabling stroke, myocardial infarction, renal failure requiring dialysis, life-threatening bleeding, and cardiac surgical or transcatheter reintervention at 30 days

Challenges of Transcatheter Tricuspid Valve Therapies

Large tricuspid annulus size

Non-planar and elliptical annulus shape

Fragility of tricuspid anular tissue and narrower annular shelf in comparison to

mitral annulus

Non calcified annulus in secondary tricuspid regurgitation

Angulation in relation to superior and inferior vena cava

Trabeculated right ventricle, muscular bands and chordae tendinae

Thin right ventricular free wall

Proximity of AV-node and right His bundle branch

Proximity of the right coronary artery to annulus and risk of coronary injury

Risk of occlusion of coronary sinus, vena cava or outflow tract

Slow-flow in right ventricle

Patients with pacemaker or defibrillator leads

Rodés-Cabau et al. JACC 2016

Transcatheter Therapies for TR

Rodés-Cabau et al. JACC 2016

MitraClip Device for TR

Lesevic et al. Eur Heart J 2016

Tric Valve

Rodés-Cabau J, Hahn R, Latib A, Laule L, Lauten A, Maisano F, Schofer J, Campelo-Parada F, Puri R, Vahanian A. JACC 2015

A B

C

D

Sinus XL

stent

Edwards Sapien XT or Sapien 3 Valve

Rodés-Cabau J, Hahn R, Latib A, Laule L, Lauten A, Maisano F, Schofer J, Campelo-Parada F, Puri R, Vahanian A. JACC 2015

Device TricValve Sapien Valve Mitralign TriCinchN N=5 N=10 N=3 N=3

Baseline characteristics

Age, years (mean, SD) 78.6±4.4 68.5±6.7 83±6.5 NA

NYHA class ≥ III [n,( %)] 5 (100) 10 (100) 3 (100) 3 (100)

Signs of right heart failure [n,( %)] 5 (100) 10 (100) NA NA

Logistic Euroscore (mean, SD) 37.9±17.9 31.5±19.7 NA NA

Tricuspid regurgitation degree [n, (%)]

Mild

Moderate

Severe

0 (0)

0 (0)

5 (100)

0

0

10 (100)

0 (0)

1 (33)

2 (67)

NA

Procedural and 30-day data

Successful device implantation [n,( %)] (4, 80) 10 (100) 3 (100) 3 (100)

Tricuspid regurgitation degree [n,( %)]

at hospital discharge or 30 days

Mild

Moderate

Severe 5 (100) 10 (100)

1 (33)

0(0)

2 (67)

NA

Major periprocedural complications [n,( %)] 1 (20) 0 (0) NA NA

30-day mortality [n,( %)] 1 (20) 2 (20) NA 0

Follow-up data, n N=4 N=10 N=3 N=3

Follow-up time, months (mean, SD) 7.4±13.2 8.5±11.3 NA 6

NYHA class [n,( %)]

I-II

III-IV

2 (40)

0 (0)

6 (60)

4 (40)

NA 3 (100)

0 (0)

Improvement in right heart failure [n,( %)] 2 (40) 9 (90) NA 3 (100)

Tricuspid regurgitation degree [n,( %)]

Mild

Moderate

Severe 2 (40)

1 (10)

0 (0)

9 (90)

NA NA

Mortality [n,( %)] 4 (80) 9 (90) NA NA

Rodés-Cabau et al. JACC 2016

Transcatheter Therapies for Treating TR. Ongoing Studies.

Rodés-Cabau et al. Lancet 2016

Trialign Device (Mitralign Inc)

Schofer et al. JACC 2015

Overview– Safety and early performance study– Transcatheter Tricuspid Repair with Trialign System, Mitralign Inc.– 15 subjects at up to 6 investigational sites– Symptomatic functional tricuspid regurgitation, no left-side surgery

planned

Primary endpoint– Technical success at 30 days– Freedom from death with

• Successful access, delivery and retrieval of the device delivery system• Deployment and correct positioning of the intended device• No need for additional unplanned or emergency surgery or re-intervention

related to the device or access procedure

35

Hahn R. TCT 2016

36

Positive safety profile and implant success

Acute ProcedureImplant Success 100% (15/15)Unplanned intervention 7% (1/15)

• Intraprocedural stenting of RCA

30 Day Follow UpFreedom from death 100% (15/15)Correct Deployment/Implant Location 80% (12/15)

Major Adverse Events 0% (0/15)

‡ Change from baseline to 30 days computed on paired data.* p-value by paired t-test or Wilcoxon as appropriate

236.5

305.1

0

50

100

150

200

250

300

Baseline 30 D

p = 0.003

6 MWT m

49.6

18.8

0

10

20

30

40

50

Baseline 30 D

MLWHF

5041.7

5058.3

0

20

40

60

80

100

Baseline 30 D

I II III IV

NYHA Classification

p = 0.004 p < 0.001

%

%

%

%

%

%

∆ 62%∆ 22%

38

Per Protocol ‡ *

TriCinch Device (4Tech Cardio Ltd)

Latib et al. JACC Intv 2015

Vahanian A. TCT 2016

CARDIOBAND SYSTEM (VALTECH)

Cardioband IInitial Experience for Treating TR (n=5)

Tamarasso M. TCT 2016

Edwards FORMA Repair System

Overview

Spacer

• Positioned into the regurgitant

orifice

• Creates a platform for native

leaflet coaptation

• Preserves underlying structure

Rail

• Tracks Spacer into position

• Distally and proximally anchored

Spacer

Characteristic n=18

Age 76 ± 9.7

Female sex 13 (72)

NYHA Class III or IV 17 (94)

Exertional dyspnea 18 (100)

Pulmonary hypertension* 6 (33)

eGFR (ml/min) 45.4 ± 16.7

Atrial fibrillation 16 (89)

Coronary artery disease 10 (56)

Previous open heart surgery 13 (72)

COPD 5 (28)

Pacemaker/defibrillator 3 (17)

EuroScore II (%) 9 ± 5.7

Baseline Echocargiogram

LVEF (%) 56 ± 7.3

TR Grade Severe 17(94)

MR Grade ≥ 2 16 (89)

FORMA Compassionate UseBaseline

*Mean pulmonary artery pressure > 40 mmHg or Peak systolic pressure > 60 mmHg, or specific medical

treatment for pulmonary arterial hypertension

Values are mean ± SD or n (%)

Rodés-Cabau J. TCT 2016

FORMA Compassionate UseProcedural

n=18

Mortality 0 (0)

Successful device implantation* 16 (89)

FORMA Spacer Size Successfully Implanted

15mm

12mm

15 (83)

1 (6)

Conversion to open heart surgery due to cardiac

tamponade1 (6)

Device retrieval 1 (6)

Device dislocation 1 (6)

Ventricular arrhythmia 1 (6)

Procedure time (skin-to-skin, min) 129 ± 31

Fluroscopy time (min) 24.7 ± 7.3

Contrast media (ml) 65 ± 29

Intra-procedural TEE TR reduction ≥ grade 16 (89)

Hospital stay (median, IQR) 4 (2-5)

*A successful implantation of a FORMA Spacer resulting in an acute reduction of TR by at least 1 Values are mean ± SD or n (%)

FORMA Compassionate Use30-Day & 1-Year Follow Up

Clinical Outcomes 30 Day

(n = 18)

1 Year

(n=15)

Death 0 (0) 0 (0)

Rehospitalization for HF 0 (0) 1 (7)

Life threatening/Major bleeding 2 (11) 2 (13)

Major vascular complications 0 (0) 0 (0)

Acute kidney injury ≥ 2 0 (0) 1 (7)

Device thrombosis 0 (0) 1 (7)*

Pulmonary embolism 0 (0) 0 (0)

Stroke 0 (0) 0 (0)

New pacemaker 0 (0) 0 (0)

*Occurred in a patient with non-therapeutic INR levels, resolved with resumption of adequate anticoagulation

Values are mean ± SD or n (%)

FORMA Compassionate UsePaired Functional Outcomes at 1 Year Follow Up

1y

NYHA Grade

10

Baseline

IV

III

II

I

*2 patients have not reached 1Y; patients with device dislodgment

(1) or conversion to open heart surgery (1) not included

3

N = 14*

1 12

1

1

0

0

30-day

7

4

2

1

150

200

250

300

350

400

450

500

Baseline 1-year

Average

improvement

of 57m from

baseline to 1Y

6MWT (m)N = 6

50

60

70

80

90

100

Baseline 1-year

KCCQ ScoreAverage

improvement

18 points

N = 8

83 year-old patient, female sexMedical history

Hypertension, dyslipidemiaCOPDPrior CABG and mitral valve surgeryAtrial fibrillationLogEuroscore: 16.9

Severe TR, NYHA class III

Edwards Forma Repair. Case Example

Pre

6-Month Follow-Up

Baseline 30-day 6-month

NYHA class III II II

Weight 70 70 72

6MWT (m) 334 415 380

KCCQ 56.3 87.8 92.9

Furosemide dose (mg) 60 60 40

NT-proBNP (pg/mL) 3234 4009 3151

Creatinine (mmol/L) 93 72 74

Transcatheter Therapies for Treating TR. Ongoing Studies.

Rodés-Cabau et al. Lancet 2016

The SPACER TrialRepair of Tricuspid Valve Regurgitation using the Edwards TricuSPid

TrAnsCatheter REpaiR System

N= 78

Adult subjects with clinically significant, symptomatic,

tricuspid regurgitation who are at high surgical risk for

standard tricuspid repair or replacement as assessed by the

Heart Team

Primary Endpoint 30 daysAll-Cause Mortality

6 Month and 1, 2, 3, YearClinical and Imaging Echo FUP

1, 2 and 3 YearClinical and Imaging Echo FUP

Conclusions• Several transcatheter interventions (including multiple

mechanistic approaches) have recently emerged for the treatment of severe MR and TR in patients at high or prohibitive surgical risk

• Preliminary feasibility, safety and exploratory efficacyhave been promising with many devices

• Current data are restricted to observational studiesincluding a limited number of patients and follow-up; larger studies with a longer follow-up are warranted

• Proving the benefits of these transcatheter interventions may represent a major paradigm shift in the management of patients with severe MR/TR