Percutaneous Mitral Valve Therapies

1

Jeffrey J. Popma, MDDirector, Interventional Cardiology

Clinical ServicesBeth Israel Deaconess Medical Center

Associate Professor of MedicineHarvard Medical School

Boston, MA

Percutaneous Mitral Valve Therapies

2

Conflict of Interest StatementConflict of Interest Statement

Within the past 12 months, I have had a financial Within the past 12 months, I have had a financial interest/arrangement or affiliation with the interest/arrangement or affiliation with the organization(s) listed below.organization(s) listed below.

Physician NamePhysician Name Company/RelationshipCompany/Relationship

Jeffrey J. Popma, MD Research Grants: Cordis, Boston ScienJeffrey J. Popma, MD Research Grants: Cordis, Boston Scientific,tific,Medtronic, AbbottMedtronic, Abbott--Guidant, eV3, LabCoatGuidant, eV3, LabCoatMedical Advisory Board: Cordis, Boston Medical Advisory Board: Cordis, Boston Scientific, Abbot VascularScientific, Abbot Vascular

3

Transcatheter Mitral ValveTranscatheter Mitral Valve

Mitral Valve PathologyMitral Valve Therapies

Edge-edge repairChordal ShorteningCoronary Sinus AnnuloplastyDirect AnnuloplastyMV Replacement

4

Device Landscape 2011 Device Landscape 2011 Percutaneous MV RepairPercutaneous MV Repair

EdgeEdge--toto--edgeedge•• Evalve MitraClip*Evalve MitraClip*

DirectDirectAnnuloplastyAnnuloplasty

•• Mitralign Bident*Mitralign Bident*•• GDS Accucinch*GDS Accucinch*•• ReCor (US)*ReCor (US)*•• Quantum Cor (RF)Quantum Cor (RF)•• Valtech CardiobandValtech Cardioband•• Micardia enCorMicardia enCor

ChordalChordalShorteningShortening

•• CardiosolutionsCardiosolutions••MitraMitra--Spacer*Spacer*•• NeoChordNeoChord••Valtech VChordalValtech VChordal

Coronary sinusCoronary sinusAnnuloplastyAnnuloplasty

•• Cardiac Dimensions Carillon*Cardiac Dimensions Carillon*•• Edwards Monarch*Edwards Monarch*•• Viacor PTMA*Viacor PTMA*•• Cerclage annuloplastyCerclage annuloplasty

MV replacementMV replacement•• EndoValveEndoValve•• CardiAQCardiAQ•• Valtech CardiovalveValtech Cardiovalve•• ValveXchangeValveXchange

*In patients*In patients

5Adams et al. Eur Heart J 2010;31:1958-1967

+ ++ +++ ++++

FED FED+ Forme Fruste Barlow’s

Leaflet Tissue

First Question: Degenerative or Functional?First Question: Degenerative or Functional?

6

Second Question: What is the Surgical Second Question: What is the Surgical Risk (STS PROM)?Risk (STS PROM)?

FED FED+ Forme Fruste Barlow’s

Increasing Repair Difficulty

Adams et al. Eur Heart J 2010;31:1958-1967

7

Leaflet CoaptationLeaflet Coaptation–– EdgeEdge--toto--Edge RepairEdge Repair–– Alfieri StitchAlfieri Stitch

Annular ReshapingAnnular Reshaping–– CinchingCinching–– AnnuloplastyAnnuloplasty

Percutaneous Methods for Mitral Percutaneous Methods for Mitral Valve Repair Valve Repair Functional MRFunctional MR

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Percutaneous Mitral Valve RepairMitraClip® System

9

~3,135 patients at ~80 hospitals in EU

and 40 clinical trial sites in the U.S. have been treated with the MitraClip device

The MitraClip: Global ExperienceThe MitraClip: Global Experience(through 4/20/2011)(through 4/20/2011)

Finland

Austria

Italy

Spain

Morocco AlgeriaTunisia

LibyaEgypt

Turkey

Georgia

SyriaIraq

Iran

Kazakhstan

AzerbaijanArmenia

Saudi Arabia

Jordan

Lebanon

Israel

Cyprus

Sweden

Norway

Germany

France

Portugal

HungaryRomania

Bulgaria

Denmark

Poland

Belarus

UkraineCzech Rep.

Slovakia

Greece

Malta

Netherlands

Liechtenstein

SanMarino

Belgium

Ireland

SerbiaMontenegro

Albania

Moldova

Lithuania

Latvia

Estonia

Luxembourg

Andorra

Bosnia&

Herzegovina

CroatiaSlovenia

Switzerland

Macedonia

Iceland

Russia

RussiaUnited

Kingdom

0

0

500 Miles

500 KM

Study n

EVEREST I 55

EVEREST II Roll-in 60

EVEREST II HRR 78

EVEREST II Randomized 184

REALISM (Continued Access) 571

Commercial use (EU) 2187Source: Abbott VascularSource: Abbott Vascular

EVEREST II Randomized Clinical Trial279 Patients enrolled at 37 sites

Randomized 2:1

Echocardiography Core Lab and Clinical Follow-Up Baseline, 30 days, 6 months, 1 year, 18 months, and

annually through 5 years

Control GroupSurgical Repair or Replacement

N=95

Significant MR (3+-4+)73% DMR, 27% FMR

Specific anatomical criteria

Device GroupMitraClip System

N=184

Feldman T et al. NEJM 2011;364:1395Feldman T et al. NEJM 2011;364:1395--406406

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EVEREST II RCT: Patient FlowEVEREST II RCT: Patient Flow

Acute Procedural Success (APS) = MR ≤2+ at discharge

12 monthsn=134

98.5% Clinical Follow-up98% Echo Follow-up

12 months n=74

94% Clinical Follow-up92% Echo Follow-up

30 daysn=136

99% Clinical Follow-up

30 daysn=79

99% Clinical Follow-up

Acute Procedural SuccessAchieved

n=137 (77.0%)

Randomized, not treatedDevice, n=6

Control, n=15

Treatedn=178

Treatedn=80

(86% MV repair)

Device Groupn=184

Acute Procedural SuccessNot Achieved

n=41 (23.0%)**20 of 41 no implant

Surgical Groupn=95

Randomized Cohort n=279


28 had MV surgery28 had MV surgery

9 had MV surgery9 had MV surgery

37/178 total (20.8%)37/178 total (20.8%)

Per Protocol

121

0 0 Myocardial Infarction

2 (2.5%)0 Major Stroke

0 1 (0.7%)GI Complication Requiring Surgery

57.0%9.6%TOTAL % of Patients with MAEp<0.0001*

(95% CI 34.4%, 60.4%)

# Patients experiencing event

42 (53.2%)12 (8.8%)All Transfusions ≥2 units*

0 0 Septicemia

4 (5.1%)0 Ventilation >48 hrs

0 0 Renal Failure0 0 Deep Wound Infection

1 (1.3%)0Re-operation of Mitral Valve4 (5.1%)0 Urgent / Emergent CV Surgery

New Onset Permanent Atrial Fib

Death

Control Group(n=79)

Device Group(n=136)

2 (2.5%)0

0 0

30 Day MAE, non-hierarchical

*p<0.0001 if include Major Bleeding only

EVEREST II RCT: Primary Safety EndpointPer Protocol Cohort


13Ted Feldman, ACC 2011 Late Breaking Trial

EVEREST II: Mitral Regurgitation Grade Baseline, 1 and 2 Years (matched)

Intention to Treat

* Within group difference (p<0.05); † Between group difference at 1 year (p<0.05); ‡ Between group difference at 2 year (p<0.05)

0

20

40

60

80

100

Baseline 1 Year 2 Years

Perc

ent Pa

tient

s (%

) 1+

2+

4+

(N=122) (N=122) (N=122)

Percutaneous Surgery

3+

2+

4+3+

1+

2+

4+3+

0

20

40

60

80

100


Perc

ent Pa

tient

s (%

)

1+

2+

4+

(N=56) (N=56) (N=56)

3+

2+3+

0+

1+

2+

0+0+

**

**

‡†‡†


EVEREST II: LV Volumes Baseline, 1 and 2 Years (matched)

Intention to Treat

62 57 55 60 55 50

0

20

40

60

80

100

120

140

160

180

LVES

V (m

L)

Percutaneous N=117

157

133124

158

119110

0

20

40

60

80

100

120

140

160

180

LVED

V (m

L)

BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs Surgery N=55

BL 1 Yr 2 Yrs BL 1 Yr 2 Yrs Percutaneous

N=117 Surgery N=55

LV End Systolic Volume

* * *

* * *

* *

* * *

LV End Diastolic Volume

* Within group difference (p<0.05) † Between group difference at 1 year (p<0.05) ‡ Between group difference at 2 year (p<0.05)

† ‡ † ‡


EVEREST II: Kaplan-Meier Freedom from DeathIntention to Treat

163 133 52At Risk:

Surgery184 1530 Days 1yr

1666m 1.5yr 2yr 3yr

Percutaneous95 74 63 257178

0.0

0.2

0.4

0.6

0.8

1.0

0 180 360 540 720 900 1080

Days from Index Procedure

Free

dom

fro

m D

eath

PercutaneousSurgery

Surgery = 91.1%Percutaneous = 89.8%

p=0.78


p=0.95


EVEREST II: Landmark Analysis of Kaplan-Meier Freedom from MV Surgery (Percutaneous)/Re-operation (Surgery)

Intention to Treat

131 109 44At Risk:

Surgery124

1yr1386m 1.5yr 2yr 3yr

Percutaneous72 616977

1840 Days

95

0.0

0.2

0.4

0.6

0.8

1.0

0 180 360 540 720 900 1080

Days from Index Procedure

Free

dom

Fro

m S

urge

ry (

Dev

ice)

or

Reop

erat

ion

(Sur

gery

)


p=0.52


p=0.32


2424


EVEREST II: NYHA Functional Class

At Baseline, 1 and 2 Years (matched) Intention to Treat

* *


* †

* ‡ †

0

20

40

60

80

100

Baseline 1 Year 2 Years0

20

40

60

80

100


I

II

I

II

I

II

III

IV

I I I

II

II II

III III IV

(N=127) (N=127) (N=127) (N=56) (N=56) (N=56)

III

‡

Perc

ent

(%)

* Within group difference (p<0.05) † Between group difference at 1 year (p<0.05) ‡ Between group difference at 2 year (p<0.05)

18Ted Feldman, TCT 2010

EVEREST II RCT MitraClip ArmEVEREST II RCT MitraClip ArmMR Reduction by EtiologyMR Reduction by Etiology

0%

20%

40%

60%

80%

100%

Baseline 12 Months Baseline 12 Monthsn=135 n=87 n=49 n=32

3+/4+

1+

3+/4+

2+ 2+

2+

1+ 34.5%

11.5%

36.8%

17.2%

40.6%

12.5%

25.0%

21.9%3+/4+

DMR Cohort FMR Cohort

1+-2+

2+

1+-2+

3+/4+


0

40

80

120

160

Vol

um

e (m

l)

0

40

80

120

160

Vol

um

e (m

l)EVEREST II RCT MitraClip ArmEVEREST II RCT MitraClip ArmLeft Ventricular Function by EtiologyLeft Ventricular Function by Etiology

LV End Diastolic and End Systolic VolumesLV End Diastolic and End Systolic Volumes

LVEDVLVEDV LVESVLVESV

FMR CohortFMR Cohortn=30, matched datan=30, matched data

LVEDVLVEDV LVESVLVESV

BaselineBaseline 12 Months12 Months

p<0.0001p<0.0001

DMR Cohort DMR Cohort n=88, matched datan=88, matched data

p=0.002p=0.002

P=0.0002P=0.0002

p=0.04p=0.04


0

20

40

60

80

100

Perc

ent

Pati

ents

EVEREST II RCT MitraClip ArmEVEREST II RCT MitraClip ArmNYHA Functional Class by EtiologyNYHA Functional Class by Etiology

97.8%NYHA

Class I/II

96.7%NYHA

Class I/II

I

II

II

III

IVIV

III

II

I

II

I

BaselineBaseline BaselineBaseline12 months12 months 12 months12 months

p<0.0001p<0.0001 p<0.0001p<0.0001

DMR Cohort DMR Cohort n=93, matched datan=93, matched data

FMR CohortFMR Cohortn=31, matched datan=31, matched data

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EVEREST II High Surgical Risk CohortEnrollment

1 YearN = 133

1 YearN = 78

REALISM High Surgical Risk Trial^N = 294 Enrolled

EVEREST II High Surgical Risk CohortN = 372

EVEREST II High Surgical Risk CohortWith 1 Year Follow-Up

N = 211

EVEREST II High Surgical Risk Trial*N = 78 Enrolled

Ted Feldman. EuroPCR 2011

* EVEREST HR * EVEREST HR defined by predicted defined by predicted

surgical mortality surgical mortality ≥≥12% using STS risk 12% using STS risk calculator or surgeon calculator or surgeon

estimate from coestimate from co--morbuiditiesmorbuidities

^ ACCESS EU high ^ ACCESS EU high risk defined by risk defined by

EuroSCORE EuroSCORE ≥≥20% 20%

22Ted Feldman. EuroPCR 2011

EVEREST II High Surgical Risk Cohort Mitral Regurgitation Grade

Percutaneous Mitral Valve Therapies

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