THE COREVALVE ReValving SYSTEM LEADING THE WAY TO PERCUTANEOUS AORTIC VALVE REPLACEMENT Laborde JC,MD Chief Physician Proctor, January 28, 2009 * CoreValve

THE COREVALVE ReValving SYSTEM LEADING THE WAY TO

PERCUTANEOUS AORTIC VALVE REPLACEMENT

Laborde JC ,MD Chief Physician Proctor, January 28, 2009

* CoreValve® and REVALVING® System are registered trademarks of CoreValve Inc, USA

Questions to IndustryQuestions to Industry


MY CONFLICTS OF INTEREST AREAffiliation/Financial Relationship Company

Grant/Research Support n/a

Consulting Fees/Honoraria CoreValve, Stentys, Triplelay

Major Stock Shareholder/Equity CoreValve, Stentys, Triplelay

Royalty Income Devax

Ownership/Founder n/a

Intellectual Property Rights Stentys, Triplelay, Devax

Other Financial Benefit n/a

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 ReplacementAortic 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

• Specifically designed for Specifically designed for transcatheter deliverytranscatheter delivery

• Single layer porcine pericardiumSingle layer porcine pericardium

• Tri-leaflet configurationTri-leaflet configuration

• Tissue valve sutured to frameTissue valve sutured to frame

• Standard tissue fixation techniquesStandard tissue fixation techniques

• 200M cycle AWT testing completed200M cycle AWT testing completed

• Supra-annular valve function

• Intra-annular implantation and sealing skirt

Porcine Pericardial Tissue ValvePorcine Pericardial Tissue Valve

Valve implantationValve implantation

Blood flowBlood flowdistributiondistribution

duringduringimplantationimplantation

1.1.

2.2. 3.3.

44..

No Ventricular SupportNo Rapid pacing

25F catheter : 8 mm

21F catheter : 7 mm

18F catheter : 6 mm

Pre-closing with 10 F Prostar True percutaneous approach

CoreValve CoreValve ReValving System System Technology EvolutionTechnology Evolution

2004

2005

2006


SizeSize 18French/6mm : smallest in the clinicPure percutaneous (femoral) Accommodates subclavian and direct

aorta access techniquesLocal anesthesia possible<2 hour procedure door to doorNo ECC, no accelerated pacing, no

obstruction of the aortic orifice

CoreValve PAVR ReValving System Basic Characteristics

FunctionFunction Hemodynamics > surgical tissue valves

DurabilityDurability Durability in vitro > surgical tissue valves

TissueTissue Porcine pericardium Widely availableAvoids BSE


CoreValve PAVR ReValving System Advanced Characteristics

Repositioning capabilityRepositioning capability NOT a one-shot manipulation During (stepwise) deployment Distally before annulus contact Proximally until frame release Proximally after frame release

Reposition of the valve

At 2/3 of implantation

CoreValve CoreValve ReValving System System

Reposition of the valveAfter implantation



CoreValve PAVR ReValving System Advanced Characteristics

Repositioning capabilityRepositioning capability NOT a one-shot manipulation During (stepwise) deployment Distally before annulus contact Proximally until frame release Proximally after frame release

Retrieval capabilityRetrieval capability Any time before frame release Requires use of new device

Retrieval of the valve

At 2/3 of implantation


Current & Future UK accounts

UNITED KINGDOM

1. London - Brompton Hospital2. London - St. Georges Hospital3. Leicester - Glenfield Hospital4. Bristol - Bristol Royal Infirmary5. Brighton - Brighton/Sussex University Hospital6. Manchester - Wynthenshaw Hospital7. Belfast - Royal Victoria Hospital8. Leeds - Leeds General Infirmary9. Glasgow - Glasgow Western Infirmary10. Wolverhampton - Newcross hospital11. Blackpool- Victoria Hospital

225 Pts225 Pts

Updated Jan 2009Updated Jan 2009

PAVR Cases Post CE Mark

758

2106

457

1134

301

972

0

500

1000

1500

2000

2500 Total # of Cases

Total # of In -Training Cases

Total # of Certified Cases

Updated Dec 2008Updated Dec 2008

18F Expanded Evaluation Registry Cases with 30-Day Follow-up by Case Type

Site Reported and Non-Adjudicated

1265 Cases “captured” and follow-up status received1265 Cases “captured” and follow-up status received

In-TrainingRegistry

809 64 %

« solo » centersRegistry

456 36 %

Updated Dec 2008Updated Dec 2008

Patient Demographics

In-Training Certified Total

Mean ± SD or % N = 809 N = 456 N = 1265

Age (years) 80.9 ± 6.8 81.6 ± 6.3 81.1 ± 6.6

Logistic EuroSCORE (%) 21.3 ± 13.0 25.2 ± 15.2 22.7 ± 13.9

Female 55.2% 54.9% 55.1%

NYHA I-II: 17.5%III-IV: 82.5%

I-II: 15.5%III-IV: 84.5%

I-II: 16.7%III-IV: 83.3%

Aortic Valve Area (cm2) 0.65 ± 0.18 0.62 ± 0.19 0.64 ± 0.18

Peak gradient (mm Hg) 79.0 ± 25.7 80.3 ± 27.2 79.5 ± 26.2

Mean gradient (mm Hg) 49.2 ± 16.0 49.8 ± 17.5 49.4 ± 16.5

LVEF(%) 52.8 ± 13.6 51.2 ± 14.5 52.2 ± 13.9

Patient Co-Morbidities / HistoryIn-

Training Certified Both

Angina 16.5% 14.7% 15.8%

Ao. Aneurysm 3.9% 2.6% 3.4%

Atrial Fib 25.6% 34.0% 28.7%

Carotid AD 12.3% 14.7% 13.2%

CAD 58.9% 61.7% 59.9%

COPD 25.6% 22.2% 24.4%

CHF 19.1% 9.0% 15.5%

Cardiomyopathy 7.1% 5.0% 6.3%

Diabetes M 25.3% 26.6% 25.8%

Hyperlipidemia 46.9% 50.2% 48.1%

Hypertension 63.7% 67.0% 64.9%

Pulmonary Hypertension

25.7% 34.0% 28.8%

In-Training

Certified Both

Mediastinal Radiation

2.9% 2.2% 2.6%

MI 11.4% 11.5% 11.5%

PVD 22.9% 24.4% 23.4%

Porcelain Aorta 7.0% 8.0% 7.4%

Renal Failure 24.6% 30.9% 27.0%

Stroke or TIA 8.8% 9.5% 9.1%

Pacemaker 13.5% 11.7% 12.8%

Defibrillator 1.3% 1.5% 1.4%

CABG 19.8% 24.6% 21.5%

Valvular Surgery 3.7% 4.3% 3.9%

PCI 29.4% 23.3% 27.2%

Procedural Results

In-Training (N = 809)

Certified (N = 456)

Both(N = 1265)

100100

8080

2020

4040

6060

00

Procedural success

%

200200

160160

4040

8080

120120

00

mn

130.9118.3

126.5

Procedure Mean Time SD (minutes)

97.5 %98.9 % 98.0 %

Mean Logistic Euroscore vs 30-Day Mortality


Certified (N = 456)

Both(N = 1265)

00

%

1010

2020

3030

10.5 %8.3 %

9.7 %

21.3%25.2% 22.7%

LogisticLogisticEuroscoreEuroscore

30-Day30-DayMortalityMortality





≤ 30-Day Mortality


Certified (N = 456)

Both(N = 1265)

00

%

55

1010

1515

10.5 %

8.3 %9.7 %

≤ 30-Day Adverse Events*(Site Reported & Non-Adjudicated)

In-Training Certified Both

CARDIAC Deaths† 5.4% 3.9% 4.9%

Aortic Dissection 0.7% 0.2% 0.6%

Cardiac Tamponade 3.5% 2.2% 3.0%

Cardiac Perforation 2.3% 1.8% 2.1%

Access Site Complication 2.5% 0.7% 1.8%

Major Bleeding 5.1% 3.3% 4.4%

Conversion to Surgery 0.6% 0.9% 0.7%

Myocardial Infarction 0.9% 0.4% 0.7%

Major Arrhythmia 9.1% 4.6% 7.5%

Pacemaker 18.8% 17.8% 18.4%

Renal Failure 1.9% 1.5% 1.7%

Stroke 2.2% 2.2% 2.2%

TIA 0.2% 0.4% 0.3%

Structural Valve Dysfunction 0.0% 0.0% 0.0%

Valve Migration 0.0% 0.0% 0.0%

* Multiple events in same patients = data not cumulative† Includes deaths where cause is not known

Paired NYHA Comparison Baseline to 30-Day Follow-up

74.9% 73.4% 74.3%

23.8% 25.2% 24.3%

1.3% 1.4% 1.3%0%

20%

40%

60%

80%


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

Paired Comparative Gradient Data at 30 Days

80.0

17.4

81.7

18.0

80.4

17.6

-20

0

20

40

60

80

100

120

Baseline 30-Day Follow-up




Peak Gradient (mm Hg)Mean ｱ SD

48.4

9.5

48.4

9.9

48.4

9.6

0

10

20

30

40

50

60

70





Mean Gradient (mm Hg)Mean SD

Paired Comparative Echo Data at 30 Days

0.69

1.58

0.65

1.42

0.68

1.55

0.0

0.5

1.0

1.5

2.0

2.5





Effective Orifice Area (cm2)Mean SD

52.454.9

52.556.0

52.455.2

0

20

40

60

80





LVEF (%)Mean ｱ SD

Conclusions

• Results from the initial safety and efficacy trials have demonstrated transcatheter aortic valve implantation to be a potential alternative treatment for high risk and inoperable patients with symptomatic AVD

• Results from the Expanded Evaluation Registry further confirm this potential in a larger cohort of patients

• Randomized controlled trials will be needed to confirm what we are already doing and possibly extend this technology to lesser risk patients

24

Documents

THE COREVALVE ReValving SYSTEM LEADING THE WAY TO PERCUTANEOUS AORTIC VALVE REPLACEMENT Laborde JC,MD Chief Physician Proctor, January 28, 2009 * CoreValve