Transcatheter Aortic Valve Implantation:

Current Clinical Update

Dr Martyn ThomasDirector of Cardiac Services

Guys and St Thomas NHS Foundation TrustA Member of Kings Health Partners

London

Available systems: Edwards (TA and TF) and Corevalve.

Current IndicationsThe Edwards SAPIEN transcatheter heart valve is indicated for use in patients with symptomatic aortic stenosis (aortic valve area <0.8 cm2) requiring aortic valve replacement who have high risk for operative mortality, or are “non-operable”, as determined by one of the following risk assessments:

1) Logistic EuroSCORE >20%or2) STS Score>10

Inclusion Criteria (from 18F safety & efficacy study)

1. Aortic valve area: < 1 cm2 (<0.6 cm2/m2)

2. Aortic valve annulus diameter: ≥ 20 mm and ≤ 27 mm

3. Ascending aorta: ≤ 43 mm

4. Iliac/femoral vessel diameter: ≥ 6 mmAND

5c. Age ≥ 65 yrs and 1-2 comorbidities

5b. Logistic ES ≥ 15% OR

5a. Age ≥ 75 yrs OR

Homograft – 1962

Porcine valve – 1965

Pericardial tissue valve – 1969

1960 20021970 2004

First CoreValve Transcatheter AVR by Retrograde ApproachLaborde, Lal, Grube – July 12, 2004

First PVT Transcatheter AVR by Antegrade ApproachAlain Cribier - 2002

Mechanical heart valve – 1962

Surgery

Transvascular

Aortic Valve Replacement

2006

First CoreValve PERCUTANEOUS AVRby Retrograde Approach – Oct 12, 2006Serruys, DeJaegere, Laborde

First Edwards/PVT Transapical Beating Heart AVRWebb, Lichtenstein – Nov 29, 2005

20012000

First PVT animalimplantationA. Cribier

First Corevalve animal implantation JC. Laborde

First-in-Man

RECAST REVIVE

REVIVE I REVIVAL I

Procedural success

in humans

Feasibility

REVIVE II REVIVAL II IDE TRAVERCE

PARTNER EU

Demonstrate “reasonable” safety

& effectiveness

Randomized Control

PARTNER IDE

Effectiveness vs. control (AVR &

medical therapy)

Post-Market

SOURCE

Evaluate transition to commercial use

Procedural success & clinical outcomes

Edwards SAPIEN™ THV Most recent clinical Results.

> 1500 Patients treated with Edwards Valve

*Implant success = Successful device delivery and deployment resulting in an AVA>0.9cm² with AI <2+

PARTNER EU TF: Procedure Outcomes

Ventricular embolization (n = 1)

Aortic embolization (n=1)23 mm SAPIEN valve

N=25

26 mm SAPIEN valve

N=27

Implant failures

n = 2

Patients Implanted

n = 54

Successful Implants*

n = 52

Patients Planned

n = 60Implant aborted

n = 6

Vascular access (n = 3)

Unsucessfull BAV (n=2)

Active endocarditis (n=1)

96.3%

THV Learning Curve Percent Successful Implant

80

85

90

95

100

%

PARTNER EU TFVascular Events

Event Total Days to Event

Phlebitis and Pulmonary Embolism 1 11

Iliac Artery Dissection 7 0

False Aneurysm 1 1

Wound dehiscence 1 4

Iliac Perforation 1 0

Groin Hematoma 2 0, 3

Iliac Occlusion 1 92

15%

Freedom from death at 6M = 90%

PARTNER EU TF: primary safety outcome.Freedom from death at 6 months.

PARTNER EU Transfemoral Survival (As Treated)

Data Extracted: 01SEP2008Time (months)

Pro

ba

bilty

(e

ve

nt

fre

e)

0 1 2 3 4 5 6

0.0

0.2

0.4

0.6

0.8

1.0

30D: 0.92Nrisk: 54

6M: 0.9Nrisk: 33

PARTNER EU TFFreedom from Stroke

PARTNER EU Transfemoral (As Treated) Freedom from Stroke

Data Extracted: 01SEP2008Time (months)

Pro

ba

bilty

(e

ve

nt

fre

e)

0 1 2 3 4 5 6

0.0

0.2

0.4

0.6

0.8

1.0

30D: 0.97Nrisk: 52

6M: 0.95Nrisk: 31

Freedom from Stroke at 6 Mo = 95%

NY

HA

Unknown

Exp/Withd

I

II

III

IV

Dead

Visit

Baseline(n= 54)

30 Day(n= 54)

3 Months(n= 54)

6 Months(n= 54)

13%

2%

15%

56%

15%

26%

31%

31%

4%

7%

22%

35%

31%

2%

9%

20%

41%

26%

4%

9%

PARTNER EU TF: Efficacy endpoints NYHA Class

Bubble Plot of Transvalvular Leak/Severity over Time

Transfemoral Only

Tra

nsv

alv

ula

r le

ak/

Se

veri

ty

0 (None)

+1 Trace

+2 Mild

+3 Moderate

Visit

Baseline(n= 18)

Discharge(n= 48)

30 Day(n= 36)

3 Months(n= 34)

6 Months(n= 34)

28%

22%

44%

6%

71%

23%

6%

69%

19%

11%

65%

26%

9%

74%

21%

3%

3%

PARTNER EU TF: Efficacy endpoints Paravalvular Leak

SOURCE Registry Post CE Mark Commercial Experience

Purpose Evaluate the transition to commercial clinical

use under controlled market release conditions with a prescribed training and proctor program

Objective Multicenter, observational collection of acute

and early (30d) procedural success and short term (1 yr)clinical performance outcomes

Procedural Success definition used by Sponsor to assess training success in new commercial sites

Defined as successful valve deployment and delivery system removal, AVA > 0.9 cm2 and AR ≤ 2.

The SOURCE Registry & SAPIEN™ THV Commercial Experience

Acute Procedural Success

Transfemoral Success 96.9%

(n=254)

Transapical Success 94.9%

(n=316)

Aborted Procedure 2.3%

Malposition 0.3%

Valve-in-Valve Bailout 0.7%

Pericardial Tamponade 0.7%

Coronary Interventions 0.7%

Vascular Complications 6.9% (19/273)

Intraprocedural Deaths 0.3% (1/273)

The SOURCE Registry Procedural Complications

Transfemoral

Complication Transapical(n = 295)

Aborted Procedure 1.0%

Malposition 0.7%

Valve-in-Valve Bailout 2.4%

Pericardial Tamponade 0.3%

Coronary Interventions 0.3%

Vascular Complications Access Injury Related to Closure Device Aortic Dissections/Perforations

1.0%0%0%

1.0%

Intraprocedural Deaths 1.7%

Hemodynamic Support 3.7%

The SOURCE Registry Procedural Complications

Transapical

*Population analyzed = Patients with Sapien in place and alive post-procedure (no conversion)

< 30 day TransfemoralSurvival*(n=204)

93.6%

NYHA(n=99)

Class I: 39.4% Class II: 50.5% Class III: 9.1% Class IV: 1.0%

MI(n=204)

1.0%

Stroke(n=204)

3.4%

Vascular Complications (n=204)

7.4%

The SOURCE Registry30 Day Results: Trans-femoral

*Population analyzed = Patients with Sapien in place and alive post-procedure (no conversion)

< 30 day TransapicalSurvival*(n=173)

89.6%

NYHA(n=55)

Class I: 38.2% Class II: 56.4% Class III: 5.5% Class IV: 0%

MI(n=173)

1.2%

Stroke(n=173)

0.6%

Vascular Complications (n=173)

0.6%

The SOURCE Registry (TA)30 Day Results

THV Learning Curve: TFPercent Successful Implant

80

85

90

95

100%

Pooled Transfemoral TAVIAll Cause Mortality

Months Post Procedure

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

0,8

0,9

1

0 2 4 6 8 10 12

Free

dom

fro

m D

eath

Revival

Canada

Revive

Partner

Source

90%93.6%

Generation 1

25FGeneration

221F

CoreValve Self-Expanding ReValving™ SystemTechnological Progress

Generation 3

18F

14 patients14 patients

65 patients**65 patients**

124 patients 124 patients

** including 10 in feasibility study and 2 ReDo

2004-2005

2004-2005

2005-2006

2005-2006

2006-2007

2006-2007 Apr Jun

AugOct

Dec Fe

bApr Ju

nAug

0

500

1000

1500

2000

2007 2008

> 1600 Cases

Post CE Mark Cumulative 18F ReValving PAVR Procedures

Updated 01-October-2008: ~100 sites in 20 countries

The CorevalveAortic Valve Replacement

Personnal contribution as ProctorBefore CE mark : N = 123Registry period : N = 495

Procedural Results

Series186%

88%

90%

92%

94%

96%

98%

100%

90.4%

94.4%

98.2%

Procedure Success

Series10

50

100

150

200

250

205.3

154.1

125.9

Procedure Mean Time ± SD

21F S&E

18F S&E

18F EE

Site reported data only in the case of registry & not monitored

PAVR Cases Post CE Mark

24

758

2106

457

1134

301

972

0

500

1000

1500

2000

25002

00

7-A

pr

Ma

y

Ju

n

Ju

l

Au

g

Se

p

Oc

t

No

v

De

c

20

08

-Jan

Fe

b

Ma

r

Ap

r

Ma

y

Ju

n

Ju

l

Au

g

Se

p

Oc

t

No

v

Total # of Cases

Total # of In-Training Cases

Total # of Certified Cases

Procedural Results

In-Training (N = 809)

Certified (N = 456)

Both(N = 1265)

25

97.5% 98.9% 98.0%

0%

20%

40%

60%

80%

100%

Procedural Success

130.9118.3

126.5

0

20

40

60

80

100

120

140

160

180

200

Procedure Mean Time SD (minutes)

Procedural Complications*

*Multiple events in same patients = data not cumulative

21F S&E Study

(N = 52)

18F S&E Study

(N = 124)

18F EE Registry

≤ 24-Hour Mortality 0.0% 3.2% 1.5%

Aortic dissection 9.6% 0.8% 0.4%

Major bleeding 13.5% 8.0% 2.3%

Cardiac tamponade 5.8%) 6.5% 2.3%

Conversion to surgery 5.8% 2.4% 0.6%

Access site complication 9.6% 4.8% 1.7%

Site reported data only in the case of registry & not monitored

≤ 30-Day Adverse Events*

* Multiple events in same patients = data not cumulative

† Includes 4 deaths where cause is not known

21F S&E Study

(N = 52)

18F S&E Study

(N = 124)

18F EE Registry

30-Day All Mortality 15.4% 14.5% 9.7%

Cardiac Deaths 7.7% 11.2% 4.9%†

Myocardial Infarction 3.8% 3.4% 0.7%

Major Arrhythmias 25.0% 18.5% 4.9%

Pacemaker 17.3% 25.8% 12.2%

Renal Failure 5.8% 4.8% 1.2%

Stroke 17.3% 6.5% 2.2%

TIA 0.0% 5.6% 0.3%

Structural Valve Dysfunction 0.0% 0.0% 0.0%

Valve Migration 0.0% 0.0% 0.0%

Site reported data only in the case of registry & not monitored

Paired NYHA Comparison Baseline to 30-Day Follow-up

28

74.9% 73.4% 74.3%

23.8% 25.2% 24.3%

1.3% 1.4% 1.3%0%

20%

40%

60%

80%

In-Training Certified Both

Improved (III-IV to I-II) Unchanged Worsened (I-II to III-IV)

Transfemoral approach362

Transapical * 5

Left Subclavian 26

Right Subclavian 1

Trans aorta * 2

Personnal contribution as ProctorRegistry period 04/01/08 - 30/09/08N = 397* Out of the Registry

PAVR by Femoral vs Subclavian Access

The PARTNER IDE TrialCo-principal Investigators:

Martin B. Leon, MD Interventional CardiologyCraig Smith, MD, Cardiac Surgeon

Columbia University

Population: High Risk/Non-Operable

Symptomatic, Critical Calcific Aortic Stenosis

No

Not in Study

No

VSTrans apical

AVR Control

1:1 Randomization

Cohort A TAPowered to be Pooled with TF

YesCohort B

NoASSESSMENT:

Operability

Cohort An= up to 690 pts

n=350 pts

Total n= 1040

ASSESSMENT: Transfemoral Access

Transfemoral

AVR Control VS

Yes

1:1 Randomization

Cohort A TFPowered

Independently

Primary Endpoint: All Cause Mortality(Non-inferiority)

Medical Management Control

ASSESSMENT: Transfemoral Access

VSTrans

femoral

1:1 Randomization

Yes

Primary Endpoint: All Cause Mortality(Superiority)

Two Trials: Individually Powered Cohorts(Cohorts A & B)

Conclusions (Personal)Primary success rate is improving and training can

“limit” the learning curve of a TAVI device.Patient selection remains a “learning” curve.

Technical success but a non-cardiac death at 1 year with not be cost effective.

The trans-apical approach is very simple BUT requires a minithoracotomy.

The transfemoral approach is technically more difficult but has advantages if the peripheral complication rate can be minimised.

This is a major technology breakthrough.............what, where, why and when remain the questions!!