Transcatheter Options for MR

Howard C. Herrmann, MD, FACC, MSCAI

John Bryfogle Professor of Cardiovascular Medicine and SurgeryHealth System Director for Interventional Cardiology

Director, Cardiac Cath Labs, Hospital of the Univ of PA

Perelman School of Medicine University of Pennsylvania

Philadelphia

Disclosure Statement of Financial InterestWithin the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.

Discussion may include unapproved and off-label devices, procedures, and indications

Major Stock Shareholder/Equity

MicrointerventionalDevices

Consulting Fees/Honoraria

SiemensEdwards LifesciencesGlaxoSmithKlineMerck

Grant/Research Support

Abbott Vascular Edwards LifesciencesSt. Jude MedicalMedtronicGoreSiemens

Boston SciRegado BiosciCordisCardiokinetxUniv LavalMitraspan

Adapted from Herrmann and Maisano, Circulation 2014;130:1712-22

ANATOMIC TARGET DEVICE NAME MANUFACTURER STATUS

LEAFLET / CHORDAL MitraClip Abbott Vascular (IL) CE Mark, FDA approved

NeoChord NeoChord (MN) Phase 1 (OUS)

Mitra-Spacer Cardiosolutions (MA) Phase 1 (OUS)

MitraFlex TransCardiac Ther (GA) Preclinical

Middle Peak Medical Middle Peak Med (CA) Preclinical

Pascal Edwards Lifesciences Phase 1 (OUS)

INDIRECT ANNULOPLASTY Carillon XE2 Cardiac Dimensions (CA) CE Mark

ARTO system MVRx (CA) Phase 1 (OUS)

Cerclage NHLBI (MD) Phase 1 (OUS)

DIRECT/LV ANNULOPLASTY Perc Annulo System Mitralign (MA) Phase 1 (OUS)

Accucinch Ancora (CA) Phase 1 (OUS)

Boa RF QuantumCor (CA) Preclinical

Cardioband Valtech (Israel) Phase 1 (OUS)

Tasra MitraSpan (MA) Preclinical

Millipede Millipede (TX) Preclinical

HYBRID SURGICAL Adjustable Ring St Jude Med (MN) CE Mark

enCor Dynaplasty MiCardia (CA) CE Mark

Cardinal Valtech (Israel) CE Mark, Phase 1 (US)

LV REMODELING Basal annuloplasty Mardil (MN) Phase 1

Parachute CardioKinetix (CA) CE Mark, Phase III (US)

TMVR CardiAQ, Caisson Edwards, Caisson US EFS

MitraClip Catheter-Based Repair

18Investigational device limited by Federal (U.S.) law to investigational use only. PML02827 Rev. A 03/2010

0 20 40 60 80 100

EVEREST II RCT: Primary EndpointsPer Protocol Cohort

0 20 40 60

9.6%

Device Group, n=136

Control Group, n=79

57.0%

Met superiority hypothesisMet superiority hypothesis• Pre-specified margin = 6% • Observed difference = 47.4%• 97.5% LCB = 34.4%

72.4%

87.8%Control Group, n=74

Device Group, n=134

Met nonMet non--inferiority hypothesisinferiority hypothesis• Pre-specified margin = 31% • Observed difference = 15.4%• 95% UCB = 25.4%

SafetyMajor Adverse Events

30 days

EffectivenessClinical Success Rate*

12 months

LCB = lower confidence boundUCB = upper confidence bound

pSUP <0.0001 pNI =0.0012

* Freedom from the combined outcome of death, MV surgery or re-operation for MV dysfunction, MR >2+ at 12 months

55%

73%

ITT p=0.007

MitraClip vs Surgery 30 Day OutcomesSystematic Review of High Risk Pts (21 studies)

3.31.1

4.21.7 3

7

16.2

4.5

59

36.3

15

26

0

10

20

30

40

50

60

70

Death Stroke Bleeding ProlongedVent

ICU Days HospitalDays

MitraClipSurgery

Philip F et al, Cathet Cardiovasc Intervent 84:581, 2014

n=3198

n=3265

HPI • 90 yo• Progressive DOE (1/2 block, Class III-IV)• PH:

• COPD (50 pk-yr): FEV1 1.56 (111%), DLCO (50%)• PVD (AAA and carotid (>70% R))• DVD (cervical)• R diaph paralysis

• Echo: large P2 flail• STS risk for replacement = 16.5%

Images courtesy of Frank Silvestry, MD

Procedural Echo Guidance Must be Fully Integrated

• Transseptal puncture• Guide and delivery catheter insertion in LA• Alignment of the system axial to the valve plane

and over MR origin• Proper alignment of the Clip arms• Grasping of the leaflets• Release of the Clip• Steering system out of LA• Assessment of MR and leaflet insertion

Essential for:

Procedure

How are Patients with Isolated FMR Treated? Duke Databank: 1,538 pts with echocardiographic 3+ - 4+ FMR and LVEF ≥20% between 2000 and 2010 not undergoing CABG

Management:

11.4% 5.9% 8.4% 11.8% 18.4%

0%

25%

50%

75%

100%

All pts 20%-30% 30%-40% 40%-50% 50%-60%

Conservative management Isolated MV surgery

LVEFN=1538 N=440 N=298 N=313 N=479

8 other pts had LVEF >60%; none underwent MV surgery c/o Mitch Krucoff

2 Year F/U of 116 Repair PatientsJ Thoracic Cardiovasc Surg 2015;149:752

40%48%

HPI

• 74 yo

• CC: DOE, fatigue, CP (NYHA Class III)

• s/p CABG 1976• s/p re-do CABG 1991 • HTN, HL, PVD, AF, OSA, DM• VT s/p Biv ICD

Echocardiogram

Findings:

• Mod-severe MR (3+)

• VC 0.72, EROA 0.5, blunted to rev pul v flow

• 2-3 jets: largest medial to A2, smaller lateral to A2

• EF 30-35% (Inf AK, AS, AL, and apical HK)

• Normal RV, PASP 31 mmHg

• Dilated annulus with post leaflet tethering and anterior override

• Calcified aorta

• Pedicle RIMA crossing the midline

3D Echocardiogram

Procedure: Mitraclip X2

Follow up at 6 mos• No SOB limitation. Walks 1 ½ blocks to claudication• Has more energy• Class II• TTE: mild MR• Continues to do well (now at 15 mos)

EVEREST II REALISM High Risk by Etiology 25

Mitral Regurgitation SeverityEcho Core Lab Assessed

High Risk FMR(N=439)

High Risk DMR(N=189)

Paired Data (N=232) Paired Data (N=108)

N=survivors with paired data at 1 year; p-values for descriptive purposes only

4+4+

4+

4+

3+

3+

3+

3+

2+

2+

2+

2+

1+

1+ 1+

0+

0%

20%

40%

60%

80%

100%

Baseline 1 Year Baseline 1 Year

Patie

nts (

%)

83%

9%

83%

22%

p < 0.0001p < 0.0001

EVEREST II REALISM High Risk by Etiology 26

Hospitalizations for Heart Failure

0.67

0.460.56

0.120.0

0.2

0.4

0.6

0.8

1.0

1 Year Prior toMitraClip

1 Year Post-Discharge

1 Year Prior toMitraClip

1 Year Post-Discharge

HF

Hos

pita

lizat

ion

Rate

Per

Pa

tient

Yea

r

(N=189)

31% reductionp = 0.0002

(N=183)(N=439) (N=422)

79% reductionp < 0.0001

High Risk FMR(N=439)

High Risk DMR(N=189)

2710/17/2017

Edwards PASCAL Mitral Valve Repair System

Not approved for sale in any country. Edwards PASCAL is a trademark of Edwards Lifesciences.

Transseptal approach

Spacer is clasped between mitral valve leaflets

Independent leaflet clasping

Simple, intuitive delivery system

2810/17/2017

Edwards PASCAL Mitral Valve Repair System

2910/17/2017

Compassionate use of the PASCAL transcatheter mitral valve repair system for patients with severe mitral regurgitation: a multicentre, prospective, observational, first-in-man study

Fabien Praz, MD, Konstantinos Spargias, MD, Michael Chrissoheris, MD, Lutz Büllesfeld, MD, Prof Georg Nickenig, MD, Florian Deuschl, MD, Robert Schueler, MD, Neil P Fam, MD, Robert Moss, MD, Moody Makar, MD, Robert Boone, MD, Jeremy Edwards, MD, Aris Moschovitis, MD,

Saibal Kar, MD, Prof John Webb, MD, Ulrich Schäfer, MD, Prof Ted Feldman, MD, Prof Stephan Windecker, MD

The LancetVolume 390, Issue 10096, Pages 773-780 (August 2017)

DOI: 10.1016/S0140-6736(17)31600-8

3410/17/2017

Cardiac Dimensions CARILLON Device Implantable device

• Permanently placed into the coronary sinus

• Reduces annulus by traction• Restores valve leaflet closure

Status• 3 European Trials for safety and

efficacy resulted in CE Mark (Amadeus, TITAN, TITAN II)

• ~400 patients treated• Initial safety concerns mostly

resolved• Efficacy modest (~1 grade)• 3 new trials now enrolling

3510/17/2017

New Trials with Carillon

Reduce FMR Clinch US Pivotal

PI Sievert Schofer / HaudeVan Bardeleben

Kapadia / StarlingGillinov

Sites Europe/Australia Germany (3) 50 centers (US, Canada, Europe, Australia)

Inclusion FMR FMR Symptomatic FMR, 2-4+ MR

N 120 30 400

Randomization 3:1 1:1 2:1 (blinded)

1o Efficacy Endpoint

Regurg Volume 6 min walk distance Co-10 at 12 mos:Death, HF hosp, 6MWD

andRegurg Volume

Comparator Med manage Mitraclip with built in crossover for persistent

MR/Sx

GDMT

Confidential• Implant with no cinch • Implant with partial cinch • Completed Implant

AccuCinch®

Ventriculoplasty System

Confidential 42

U.S.Clinical Sites

St. LouisBarnes HospitalJohn Lasala, MD

New York CityColumbia UniversitySusheel Kodali MD/Marty Leon, MD

Salt Lake CityIntermountain Medical Center Brian Whisenant, MD

New York CityNYU Langone Medical CenterMathew Williams, MD

HoustonSt. Luke’s / Texas Heart InstituteGuilherme Silva, MD

LincolnNebraska HeartHosakote Nagaraj, MD

SeattleUniversity of WashingtonMark Reisman, MD

MinneapolisMinn. HeartPaul Sorajja, MD

Favorable FDA interactions

CMS reimbursement for IDE

8 centers15 patients

UW Medicine

Columbia University

St. Luke’s

NYU Langone

Intermountain Medical Center

Nebraska Heart

Barnes

Minn. Heart

• IDE EFS U.S.o 8 centerso 15 patients

• Cinch 2 EFS Europeo 10 centerso 27 patients

/

Update from European trial - 61 patients results

A single arm, multi-center, prospective study with intra-subject comparisons to evaluate the performance and safety of the Cardioband for repair of functional mitral regurgitation.

Courtesy of F. Maisano, MD

/

LIVE ADJUSTMENT OF ANNULAR SIZE TO OPTIMIZE COAPTATIONB

asel

ine

Fina

l siz

e Po

st

Adju

stm

ent

/

*Dr. Paul Grayburn – Baylor University

94% MR ≤ 2+at 12 Months

92% MR ≤ 2+at 24 Months

92% MR ≤ 2+at 6 Months

92% patients with MR ≤2+ At 24 Months By Core Lab*

87% MR ≤ 2+at 30 Days

3-4+

3-4+ 3-4+ 3-4+ 3-4+ 3-4+

2+

2+ 2+ 2+ 2+ 2+

0-1+ 0-1+ 0-1+ 0-1+ 0-1+

0%

20%

40%

60%

80%

100%

BaselineN=61

DischargeN=57

30 daysN=53

6 Months N=40 12 MonthsN=31

24 MonthsN=12

46

/

Annular Reconstruction by SignificantReduction in Septo Lateral (A-P) Dimension

30% average reduction in A-P

*P<0.01

20

25

30

35

40

Baseline Discharge

A-P

Dis

men

sion

[mm

]

37±4(29-46)

26±4(18-35)

17

22

27

32

37

42

47

Baseline Discharge

Sept

o La

tera

l Dim

ensi

on [m

m]

/

Functional Improvement at 12 Months

304

376

200225250275300325350375400

41

18

0

10

20

30

40

Baseline 12 MonthsBaseline 12 MonthsN = 24 N = 28

6MWTP<0.01Δ = 72

MLHFQ ScoreP<0.01Δ = -23

Met

ers

Wal

ked

MLH

FQ S

core

IV

III

III

II

II

I

0%

20%

40%

60%

80%

100%

Baseline 24 MonthsN = 34

79% N

1YHA

I/II

% o

f pop

ulat

ion

NYHA ClassP<0.01

48

ACTIVE pivotal trial imminent in the US

Considerations for Transcatheter Therapy of 2o MR

• Most patients don’t get surgery

• Surgical repair, when successful, has better LV remodeling than replacement, but has a high recurrence rate

• Transcatheter repair therapies are limited to certain anatomies and, though safer, generally less effective than surgery

• There is a need for a less invasive therapy than surgery that can improve symptoms better than medical management

Transcatheter MV Replacement:The Rationale:• Avoid risks and discomfort of surgery (CPB and

sternotomy/thoracotomy)• Avoid slower recovery of surgery• Must balance efficacy and safety (consider age,

frailty, co-morbidities, goals of care)• Results with transcatheter repair disappointing

(and sobering compared with TAVR)

The Hope for TMVR:• Feasibility demonstrated VIV, Phase 1• Better efficacy (more consistent MR reduction)• Less dependent on anatomy (more predictable

results)

1 Maisano and Herrmann, EHJ 20152 Herrmann and Chitwood, JACC 2017

Transcatheter Mitral Therapy at Penn