H E R Z Z E N T R U M

CoreValve ReValving® Experience

Post-CE Mark Results of

Percutaneous Aortic Valve Replacement (PAVR) Procedures

through 30-April-2009 with

Data Collected through 12-May-2009

Gerhard Schuler

Herzzentrum Leipzig

H E R Z Z E N T R U M

Disclosures: None

CoreValve Technology

Outflow Aspect: low radial force serves to orient system

Inflow Aspect: radial force and elasticity of frame designed to maximize conformation to native annulus while intra-annular sealing skirt minimizes PVL

Valve Region:supra-annular valve function delivers optimal hemodynamics, frame designed to maintain coronary perfusion

18F Delivery Catheter System

12F Shaft

18F Capsule

Over-the-wire 0.035 compatible

Loading/Release Handle

CoreValve Procedure – Deployment

Before annular contact

After annular contact

Before devicerelease

Pat. B.: CoreValve Malpositioning I

Pat. B.: CoreValve Malpositioning II

Pat. B.: CoreValve Device Removal III

Blood Flow During Deployment

Normal blood pressure before annular contact

Reduced blood pressure only between 1/3 & 2/3 of

the deployment

At 2/3 point, BP returns to normal and valve is still

repositionable

Est. CoreValve Post CE Mark Implants

0

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

4,500

5,000

5,500

2007-

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Sep

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Oct

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Aug

Medtronic CoreValve® Experience (through Aug 2009)

• Over 5000 implants

• 184 centers in 27 countries

H E R Z Z E N T R U M

18F EER192454.5%

Outside 18F EER

160545.5%

Pacific Rim & North American Cases;

2009 Solo Cases & New Centers and

Cases without CRFs

Cases “Captured” with Baseline

& Procedural CRFs

18f Expanded Evaluation Registry

H E R Z Z E N T R U M

Known

148377.8%

Outstanding

42422.2%

18f EER 30-Day Follow-Up(1907 Cases through 31-Mar-2009)

H E R Z Z E N T R U M

In-Training

91861.9%

Solo565

38.1%

Training Status of CentersPts with 30 Day Follow-up

H E R Z Z E N T R U M

In-Training Solo Total EER

Mean ± SD or % N = 918 N = 565 N = 1483

Age (years) 80.8 6.7 81.7 5.9 81.2 6.4

Logistic EuroSCORE (%) 22.2 13.6 23.2 13.7 22.6 13.7

Female 55.8% 54.7% 55.4%

NYHAI-II: 17.2%

III-IV: 82.8%

I-II: 14.4%

III-IV: 85.6%

I-II: 16.1%

III-IV: 83.9%

Aortic Valve Area (cm2) 0.65 0.18 0.61 0.17 0.64 0.18

Peak gradient (mm Hg) 78.3 26.1 81.3 25.8 79.5 26.1

Mean gradient (mm Hg) 48.4 16.4 50.4 16.0 49.2 16.3

LVEF(%) 52.9 13.8 51.4 13.7 52.3 13.8

Patient Demographics

Risks & Mortality

Acute LV Failure

Tamponade

AMI

CVA

Hemorrhage

Renal Failure

Resp. Failure

Infection

LV Failure

Arrhythmias>30 days:

Natural history

30 days24h 6 months

[%]

Su

rviv

al

H E R Z Z E N T R U M

In-Training SoloTotal

EER

Angina 14.4% 17.9% 15.8%

Aortic Aneurysm 3.6% 2.0% 3.0%

Atrial Fib 29.6% 26.0% 28.3%

Carotid AD 13.1% 14.0% 13.4%

CAD 60.2% 59.6% 59.9%

COPD 23.7% 26.3% 24.7%

CHF 16.0% 17.1% 16.4%

Cardiomyopathy 5.9% 6.5% 6.1%

Diabetes Mellitus 25.2% 27.1% 25.9%

Hyperlipidemia 51.1% 48.2% 50.0%

Hypertension 70.2% 65.9% 68.6%

Pulmonary Hypertension 28.2% 28.4% 28.3%

Patient Co-Morbidities

H E R Z Z E N T R U M

98.4% 98.8% 98.5%

0%

20%

40%

60%

80%

100%

In-Training(N = 918)

Solo (N = 565)

Total EER (N = 1483)

Procedural Success

H E R Z Z E N T R U M

Mortality Rate

2.6%1.9%

2.4%

0%

2%

4%

6%

8%

10%

12%

In-Training

(N = 918)

Solo

(N = 565)

Total EER

(N = 1483)

24-Hour

10.7%9.7%

10.3%

0%

2%

4%

6%

8%

10%

12%

In-Training (N = 918)

Solo (N = 565)

Total EER (N = 1483)

30-Day

H E R Z Z E N T R U M

24h Adverse Events

In-Training Solo Total EER

Cardiac† Death 2.2% 1.7% 1.8%

Aortic Dissection 1.0% 0.4% 0.7%

Cardiac Perforation 2.7% 1.6% 2.3%

Cardiac Tamponade 3.7% 1.9% 3.0%

Access Site Bleeding 3.3% 1.6% 2.6%

Major Bleeding 6.0% 3.5% 5.0%

Conversion to Surgery 0.3% 0.5% 0.4%

Myocardial Infarction 0.8% 0.5% 0.7%

Major Arrhythmia 5.7% 5.5% 5.6%

Permanent Pacemaker 6.9% 7.7% 7.2%

Renal Failure 0.9% 0.5% 0.7%

Stroke 1.1% 1.2% 1.1%

TIA 0.3% 0.4% 0.3%

Pat. G.: Major Bleeding

H E R Z Z E N T R U M

30d Adverse Events

In-Training Solo Total EER

Cardiac† Death 6.4% 7.0% 6.7%

Aortic Dissection 1.2% 0.5% 0.9%

Cardiac Perforation 3.0% 2.1% 2.7%

Cardiac Tamponade 4.2% 2.6% 3.6%

Access Site Bleeding 3.5% 1.9% 2.9%

Major Bleeding 8.2% 4.7% 6.9%

Conversion to Surgery 0.5% 1.2% 0.8%

Myocardial Infarction 0.9% 0.9% 0.9%

Major Arrhythmia 16.3% 14.9% 15.7%

Permanent Pacemaker 25.7% 23.9% 25.0%

Renal Failure 2.2% 2.3% 2.2%

Stroke 2.2% 2.3% 2.2%

TIA 0.4% 0.4% 0.4%

AV-Block III°4 days after COREVALVE Implantation

Day 45 post Revalving

H E R Z Z E N T R U M

30-Day* Paired NYHA Class Comparison

0% 1%3%

14%

45%

35%

3%

0% 0%2%

15%

52%

30%

3%0% 0%

2%

15%

47%

32%

3%

0%

10%

20%

30%

40%

50%

60%

Worsened

3 Levels

Worsened

2 Levels

Worsened

1 Level

No Change Improved

1 Level

Improved

2 Levels

Improved

3 Levels

In-Training (N = 576)

Solo (N = 400)

Total EER (N = 976)

H E R Z Z E N T R U M

In-Training Solo Total EER

(N =362) (N = 188) (N = 550)

In-Training Solo Total EER

(N = 320) (N = 162) (N = 482)

76.2

16.9

82.0

17.5

78.1

17.1

0

20

40

60

80

100

120

Peak Gradient (mm Hg)Mean ± SD

47.0

8.8

50.3

9.2

48.1

8.90

20

40

60

80

100

120

Mean Gradient (mm Hg)Mean ± SD

30 Day Paired Gradient Comparison

H E R Z Z E N T R U M

30 Day Paired Echo Data

0.67

1.59

0.60

1.44

0.65

1.55

0.0

0.4

0.8

1.2

1.6

2.0

2.4

Effective Orifice Area (cm2)Mean ± SD

52.155.2

50.8

55.4

51.655.3

0

20

40

60

80

LVEF (%)Mean ± SD

In-Training Solo Total EER

(N = 202) (N = 79) (N = 281)

In-Training Solo Total EER

(N = 461) (N = 252) (N = 713)

Medtronic CoreValve® Upcoming Clinical Studies

Name Description Start Intent Patients/# Sites

CoreValve US PivotalClinical Trial

US IDE for FDA Approval

Early Summer, CY10-CY11

Secure FDA Approval/US Launch

TBDUS Only

CoreValve AdvanceInternational Registry

International Registry to follow EER

Q1 CY2010 Ensure ongoing and robust understanding of the CoreValve patient population

TBD

CoreValve EpicClinical Trial

Prospective clinical study

Fall 2009 Investigate frequency and predictors of conduction disturbances during CoreValve implant

TBD

Conclusions

Despite of a large number of implanted devices

data regarding mortality and clinical status are

far from complete.

Available data indicate that procedural success

is >98% and 30 day mortality ~ 10%.

A new registry with complete data collection is

urgently needed.