Davos 2011 - Percutaneous mitral interventions. where we ...assets.escardio.org/.../other2011/davos/vahanian_mitral-intervention… · Coronary artery disease 47.0 46.3 >0.99 Myocardial

Percutaneous mitral interventions:

where are we, where do we go?

Alec Vahanian, FESC, FRCP (Edin.)

Bichat Hospital, Paris, France

Percutaneous Mitral Commissurotomy:

The gold standard?

Percutaneous Mitral Commissurotomy

Surgical Commissurotomy

(K. Inoue, 1984) (D.Harken, 1948)

Bouleti C, Iung B, Himbert D, Brochet E,

Messika-Zeitoun D, Garbarz E, Cormier B,

Michel PL, Luxereau P, Vahanian A.

Bichat Hospital, Tenon Hospital, AP-HP, Paris, France

Twenty-Year Results of Percutaneous

Mitral Commissurotomy in a Series of

1024 Patients.

(ESC Annual congress 2010)

Immediate Results

Adverse events

- In-hospital death: 4 patients (0.4%)

- Embolism with sequelae: 3 patients (0.3%)

- Mitral regurgitation ≥ 3/4: 35 patients (3.4%)

Valve function

Valve area Mean gradient

0

0,5

1

1,5

2

Planimetry Doppler0

2

4

6

8

10

12

Mean Gradient

Before PMC

After PMC

cm² mmHg

20-Year Results

Survival without Surgery or Re-PMC, and in NYHA class I or II

n= 912 836 752 651 553 483 424 353 222 105 43

n= 1024 867 768 665 563 492 433 361 227 108 45

n= 112 31 16 14

32.3±2.5%

29.4±2.0%

12.1±3.1%

YEARS

(%)

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18 20

Good immediate results (n=912) All patients (n=1024) Poor immediate results (n=112)

The Role of Percutaneous

Valve Interventions

0%

20%

40%

60%

80%

100%

AS AR MS MR

Percut. Int.

Valve Repair

Bioprosthesis

Mech Prosthesis

Homograft

Autograft

N = 512 119 112 155

(Iung. Eur Heart J 2003;24:1231)

Current percutaneous techniques

Future directions

Conclusion

Percutaneous Treatment of

Mitral Regurgitation

Transcatheter Mitral Valve Therapies

Above water

MitraClip

Coronary Sinus

Annuloplasty devices

Still under the waterline

Direct Annuloplasty

Mitral Valve Replacement

…..

Edge to Edge Percutaneous Repair

Edge-to-Edge Technique

Clinical Experience

Data as of 9/10/2010.

.

Study Population n

EVEREST I (Feasibility)* Non-randomized 55

EVEREST II* Pre-randomization 60

EVEREST II High Risk Registry 78

EVEREST II (Pivotal) Randomized patients 279

REALISM (Continued Access) Patients 408

EUROPE Commercial Patients 1109

Total1,894 MitraClip

+ 95 surgery

EVEREST II Randomised Clinical Trial

Study Design

279 Patients enrolled at 37 sites

Randomised 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+)Specific Anatomical Criteria

Device GroupMitraClip System

n=184

EVEREST II Randomised Clinical Trial

Key Inclusion/Exclusion Criteria

Inclusion

Candidate for MV Surgery

Moderate to severe (3+) or

severe (4+) MR

• Symptomatic

– >25% EF & LVESD

≤55mm

• Asymptomatic with one or

more of the following

– LVEF 25-60%

– LVESD ≥40mm

– New onset atrial

fibrillation

– Pulmonary hypertension

Exclusion

AMI within 12 weeks

Need for other cardiac surgery

Renal insufficiency

• Creatinine >2.5mg/dl

Endocarditis

Rheumatic heart disease

MV anatomical exclusions

• Mitral valve area <4.0cm2

• Leaflet flail width (≥15mm) and

gap (≥10mm)

• Leaflet tethering/coaptation

depth (>11mm) and length

(<2mm)

Device (%)

n=184

Control (%)

n=95 P

Age (mean) 67.3 years 65.7 years 0.32

Male 62.5 66.3 0.60

Congestive heart failure 90.8 77.9 <0.01

Coronary artery disease 47.0 46.3 >0.99

Myocardial infarction 21.9 21.3 >0.99

Angina 31.9 22.2 0.12

Atrial fibrillation 33.7 39.3 0.42

Cerebrovascular disease 7.6 5.3 0.62

Peripheral vascular disease 6.5 11.6 0.17

Cardiomyopathy 17.9 14.7 0.61

Hypercholesterolemia 61.0 62.8 0.80

Hypertension 72.3 78.9 0.25

Moderate to severe renal disease 3.3 2.1 0.72

Diabetes 7.6 10.5 0.50

Previous cardiovascular surgery 22.3 18.9 0.54

MR Severity: 3+ to 4+ 95.7 92.6 0.48

MR Etiology: Degenerative / Functional 73 / 27 73 / 27 0.81

EVEREST II RCT

Baseline Demographics & Co-morbidities

EVEREST II RCT: Patient Flow

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

12 months

n=13498.5% Clinical Follow-up

98% Echo Follow-up

12 months

n=7494% Clinical Follow-up92% Echo Follow-up

30 days

n=13699% Clinical Follow-up

30 days

n=7999% Clinical Follow-up

Acute Procedural SuccessAchieved

n=137 (77%)

Randomized, not treatedDevice, n=6

Control, n=15

Treatedn=178

Treatedn=80

(86% MV repair)

Device Groupn=184

Acute Procedural SuccessNot Achieved

n=41**20 of 41 no implant

Control Groupn=95

Randomised Cohort n=279

Intent to Treat Cohort

1616

EII RCT: Safety & Effectiveness Endpoints

Intention to Treat Cohort

Met superiority hypothesis• Pre-specified margin =2%• Observed difference = 34.2%

Met non-inferiority hypothesis• Pre-specified margin = 25% • Observed difference = 7.3%

30 Day Modified MAE II*

Intent to Treat, Hierarchical EventsSafety endpoint met with a wide margin

0

10

20

30

40

50

Device Control

30 D

ay

Modifie

d M

AE I

I (%

)

Major Bleeding Complication*

GI Complication

New Onset Atrial Fibrillation

Ventilation >48hrs

Urgent CV Surgery

Stroke

Death5.0%

30.9%

*Major bleeding requiring transfusion ≥ 4U or surgical intervention Based on STS reporting of RBC transfusions

p<0.0001

Device Control

Primary Effectiveness Endpoint

Components

12 Month Endpoint

Components

% Patients experiencing event

Device Group

(n=134)

Control Group

(n=74)p-value

Death 4.5% 6.8% 0.5260

MV Surgery or

Re-operation for MV

dysfunction

6.7% 2.7% 0.3344

MR>2+ 16.4% 2.7% 0.0026

Total 27.6% 12.2%

Difference Device-Control 15.4%

(90% two-sided Conf Int: 5.4%, 25.4%)

0

20

40

60

80

100

Baseline 12 Months

Perc

ent Patients

0

20

40

60

80

100

Baseline 12 Months

MR Reduction

Baseline vs 12 Months, Per ProtocolSurgery more often achieves lower degree of residual MR

p<0.0001

1+

1+-2+

2+

4+

(n=119) (n=119)

Device Control

3+

2+

4+

3+

1+

1+-2+

2+

4+

(n=67) (n=67)

3+

2+

3+

0+1+-2+ 7.7% (1/13)

Replacement

13.4%

36.1%

11.8%

33.6%

16.0%

17.4%

58.2%

8.7%

3.0%

18.4% (7/38) Replacement

2.5%

p-value compares the distribution of MR grade in device with the distribution of MR grade in control at 12 months (Fishers’ Exact test)

3,6 3,53,3 3,3

0

1

2

3

4

5

65,55,1

5,4

4,8

0

1

2

3

4

5

6

Dim

ensi

on (

mm

)

Baseline

12 Months

Device(n=122)

Control(n=66)

LV Dimensions

Baseline vs 12 Months, Per Protocol, Matched Cases

p<0.0001 p<0.0001

Device(n=120)

Control(n=66)

p=0.0564 p=0.4785

End Diastolic Dimension (LVIDd) End Systolic Dimension (LVIDs)

*p=0.0030

p-value compares baseline to 12 month measurements within device and control* p-value compares change from baseline to 12 months between device and control

*p=0.4070

NYHA Functional Class

Baseline vs 12 Months, Per Protocol, Matched Cases

0

20

40

60

80

100

Perc

ent

Patients

97.6%NYHA

Class I/II

87.9%NYHA

Class I/II

n=124 n=66

I

II

III

I

II

III

IVIV

III

II

I

II

I

Device Control

Baseline Baseline12 months 12 months

p<0.0001 p<0.0001

*p=0.0162

p-value compares the distribution of NYHA class at baseline to the distribution at 12 months within device and control*p-value compares the distribution of NYHA class in device to the distribution in control at 12 months (Fishers’ Exact test)

European Experience

*Data as of 8/31/2010. Source: EU Case Observation Reports

N = 1060 Total Patients

4

10 912

7

1614

19

26 25

3028

35 35

47

53 54

70

7880

87

112

97

112

0

20

40

60

80

100

120

Sep

08

Oct Nov Dec Jan

09

Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan

10

Feb Mar Apr May Jun Jul Aug

Co

un

t

# of Patients Treated

# of Sites

# of Sites Treating Patients

European Experience

Overall Results

Patients Treated 1060

Hospitals/Sites 56

Etiology: FMR/DMR/Mixed (%) 64%/29%/8%

Average Device Time (hr:min) 1:51

Clip Implant Rate (%) 96%

1 Clip/2 Clip/3 Clip/4 Clip(%) 67%/30%/2%/<1%

Site Reported MR Reduction (%) 98%

Clip Embolization (%) 0.01%

(Maisano,TCT 2010)

(Alfieri et al. J Thorac Cardiovasc Surg 2001;122:674-81)

Potential Limitations of Percutaneous

Edge to Edge technique

Lack of annuloplasty

(De Bonis et al. Circulation 2005;112:I-402) (Bhudia. Ann Thoracic Surgery

2004;77:1598-606)


Edge to Edge technique

Controversial Surgical Results

(N=31) (N=230)

http://ats.ctsnetjournals.org/content/vol77/issue5/images/large/14804.1598.gr2.jpeg

Management of Symptomatic Severe

Chronic Organic Mitral Regurgitation

LVEF > 30%

NoYes

Valve repair is likelyand low comorbidity

NoYes

* valve replacement can be considered in selected patients

Surgery (repair whenever

possible) Medical therapy*

Transplantation

Refractory to medical therapy

Yes No

Medical therapy

Severe symptomatic organic MR

(ESC Guidelines, Eur Heart J 2007;28:230-68)

A role for E to E?

Potential Candidates for Percutaneous

E to E Technique in Organic MR

After assessment by the ‘Team’

Severe MR

Absence of anatomic contraindication according to EVEREST

criteria

Symptomatic

Life expectancy >1year

Contraindication for surgery, or high risk for surgery

AND/OR

History of thoracic irradiation

Patent coronary bypass

Severe calcification of mitral annulus

Previous aortic valve replacement

Indications for Surgery in

Ischaemic / Functional MR

Chronic Ischemic MR Class

Patients with severe MR, LV EF > 30% undergoing CABG I C

Patients with moderate MR undergoing CABG if repair is

feasible

IIa C

Symptomatic patients with severe MR, LV EF < 30% and

option for revascularization

IIa C

Patients with severe MR, LVEF > 30%, no option for

revascularization, refractory to medical therapy, and low

comorbidity

IIb C

Functional MR : surgery can be considered only in selected

patients with severe symptoms despite optimal medical therapy

(ESC Guidelines, Eur Heart J 2007;28:230-68)

A role for E to E?

Patients at Increased Risk for

Mitral Valve Repair in CHF

Presence of >4 of the following:

LV end diastolic Diam. >80mm

Peak Vo2<13ml/kg/mn

Resting BP<80mmHg

Atrial fibrillation

Heart failure duration >8years

Exercise-induced increase

in systolic BP<10%

Six-mn walk <350m

Previous cardiac surgery

BUN>100mg/dl

Cachexia

(Mehta. J Am Coll Cardiol 2005;45:388-90)

Need for a team discussion with HF specialists and transplant team to discuss indications of E to E or LV assist as a destination therapy or transplant

Coronary Sinus Annuloplasty

The Devices

The Edwards MONARC

system*

The CARILLON device

The PTMA Implant

System*

* abandoned

Distal AnchorProximal Anchor

Bridge

Elongated bridge at implant Foreshortened state at ~6 weeks

Prosthetic Ring Annuloplasty

Technique

EVOLUTION I Study Overview

INCLUSION

Functional mitral valve regurgitation: dilated or ischemic cardiomyopathy

MR grade 2+ to 4+ on a scale of 4+

Coronary Sinus Dimensions Target Area is ≥ 14 cm

and ≤ 18 cm in length, Distal section of Target

Area, the AIV is ≥ 3 mm in diameter

EXCLUSION

Organic mitral regurgitation

Ischemia requiring cardiac revascularisation within 3 months prior to or planned after the implant procedure

Implanted cardiac defibrillator (ICD) or pacing leads within the coronary sinus

Ejection Fraction < 25%

Moderate to severe mitral annulus calcification

Monarc* Carillon † Viacor ‡

n= 72 48 27

Success implantation (%) 82 63 48

In-hospital death (%) 0 2 0

Myocardial infarction (%) 4 6 0

Tamponade (%) 3 6 4

Dissection of coron. sinus (%) 0 6 NA

* JACC Intervention, in press

† Circulation 2009;120:326-33

‡ Circ Cardiovasc Intervention 2009;2:277-84

Percutaneous Mitral Annuloplasty

Feasibility / Safety at 30 Day

Percutaneous Mitral Annuloplasty

Six Minute Walk Test

307

387403

100

200

300

400

500

Me

ters

n=30 n=28 n=23

304

400

100

200

300

400

500

349 351

100

200

300

400

500

Implanted Patients (N=32))

Non-Implanted Patients (N=14)

P<0.001

NS

P<0.001

Implanted Patients

Baseline 1 Month 6 Months

AMADEUS™ TITAN™(Interim)

(Courtesy J Schofer)

Mitral valve

Tricuspid

valve

Coronary

sinus



Monarc*

n=27

Carillon†

n=23

Viacor‡

n=9

Pre 3 yr Pre 6 Mo. Pre Post

Reduction MR

≥1/4 (%)

- 59 - NA - 22

ERO ( cm²) 0.22 0.15 0.25 0.17 NA NA

Rvol (ml) 32 23 35 24 NA NA

* JACC Intervention in press

† Circulation 2009;120:326-33

‡ Circ Cardiovasc Intervention 2009;2:277-84



Limited Efficacy

50 PatientsBaseline & 90-Day Angio

35 PatientsNo Coronary

Vessel Changes

15 Patients (30%)Coronary

Vessel Changes

( 3MI’s (1death))

9 PatientsBridge

Compression

5 Patients Anchor

Compression

1 PatientAnchor & Bridge

Compression

5 Faulty devices4 Device separation

1 Device slippage

• Monarc

• Carillon6 cases (12%) of coronary compression (device recaptured)

(Schofer et al. Circulation 2009;120:326-33)



Coronary Compression

Surgery of Ischaemic MR CABG

With or Without Valve Repair

2 groups of patients with ischaemic MR 3/4 matched according to a propensity score

54 had isolated CABG54 had CABG + valve repair

No significant difference in survival and NYHA class III-IV during F.U.

(Mihajlevic. J Am Coll Cardiol 2007;49:2191-201)

Current percutaneous techniques

Future directions

Conclusion



« Valve in a Valve »

(Courtesy D Himbert)

(De Weger et al. Eur J Cardio-thorac Surg. 2010)

« Valve in a Ring »

Biventricular pacing leadsEdge-to-Edge repair

Combining Coronary Sinus Annuloplasty

and Other Procedures

Transcatheter Mitral Valve Therapies

Above water

MitraClip


devices

Still under the waterline

Direct Annuloplasty

Mitral Valve Replacement

…..

Lenox HillHeart and VascularInstituteOf New York


• Transcatheter apically-anchored balloon

• Phase 1 clinical

• Target: FMR

• Everest II completed

• Pending FDA approval

• Target: OMR and FMR


• Nitinol rods of

variable length and

diameter

• Active fixation

• Distributed

anatomical bending

• Recapturable

/removable

• Abandoned

• Anchors connected

by elongated wire

with springs

• Reinforcement

against myocardial

stretch – aids diastolic

filling and systolic

contraction

• Pre-clinicals

• Small metal links

connected by 2

flexible cables

• Removable

• Pre-clinicals


• HIFU on a non-occlusive balloon

• Change in collagen ⇒ shrinkage

• Successful FIM study


• Retro-aortic approach

• Sub-annular placement of self-expanding anchors

encasing a cinching cable along the posterior annulus

• In clinical trials

Cinching cable

P1

P3

P2


• Transseptal ring secured from trigone-to-

trigone with miniature anchors

• Adjustable



• Transpericardial (mini-thoracotomy)

• Adjustable over time

• Impacts annular and subannular

• Approximation of both papillary

muscles

• Preclinical


• Nitinol frame

• Bovine pericardium

• PTFE membrane

• Transapical

• Repositionable

• Nitinol frame

• Proprietary pericardium

• Annular anchoring without relying

on radial force

• Transseptal

• Nitinol frame

• Refocused on direct transatrial

delivery

Transcatheter valve interventions are

the natural evolution of mitral valve

surgery

Most surgical procedures can be delivered through a catheter

Image guidance will enable feasibility and safety

Physiologic fine tuning will enhance therapeutic benefit

New concepts could expand current indications

The Future of

Cardiac Surgery:

The Times, They

Are a Changin’

ATS

2005;79:1470-

1472

• The current results obtained with E to E technique suggest

that it may be useful in selected high risk patients.

• The results with coronary sinus annuloplasty are

disappointing

• In the future combination of techniques and evaluation of

new devices aimed at reproducing surgical techniques is

expected

• Results should be carefully evaluated in comparison to

surgery and contemporary medical treatment



Remember…..

Documents

Davos 2011 - Percutaneous mitral interventions. where we ...assets.escardio.org/.../other2011/davos/vahanian_mitral-intervention… · Coronary artery disease 47.0 46.3 >0.99 Myocardial