Brij Maini, MD, FACCPinnacle Health, Harrisburg, PA

On behalf of all USpella Registry Investigators

High Risk PCI With Impella 2.5:

Registry Perspectives

and an Ongoing Trial

1

Conflict of Interest

• Investigator: PROTECT II, RECOVER II,

USPELLA

• Member Advisory Board: ABIOMED

• Member: Impella Trials Steering Committee

Impella 2.5 Technology

Clinical Adoption in US

FDA Clearance in June’08

1000+ patients treated

300+ US Centers

2 Trials OpenUSpella Registry

3

USpella Registry

• Retrospective look at patients supported with 510(k) device

• All sites with N> 4 patients invited to participate on June 10th 09

• All “comers” considered without limitation of indications

• Data obtained after IRB submission

• 16 sites have responded so far for a total of 181 patients

4

Main Indications For Support(N=181)

5

Others includes Elective CABG, Myocarditis with shock, Post-cardiotomy shock, septic shock, toxic shock, post partum cardiomyopathy,

other cardiomyopathies with shock

Without

Shock

(20%)Elective

(37%)

With Shock

(14%)

Urgent

(18%)

ADHF

w/ Shock

(6%)

Other

(5%)

Acute

Myocardial

Infarction

(34%)

High Risk

PCI

(55%)

Analysis By Sub-Group

• High Risk PCI

• Acute Myocardial Infarction

6

69 ± 11

74 %

65 % vs 35%

32 ± 17

58 %

85 %

2 ± 1

6 ± 5

39 ± 16

60

2.1 ± 0.2

Age (yrs)

Gender (Male in %)

Procedure (Elective vs Urgent)

LVEF (%)

Un protected LM or LPC

Multivessel Disease

Nb of lesions treated

STS Score

Syntax Score

Median Duration of support (min)

Average Pump Flow

Patient Characteristics Mean ± SD or %

High Risk PCI Demographics (N=99)7

Patient CharacteristicsIn 85% of the cases, CABG was declined

(when requested) because of Patient’s Morbidity

0%

20%

40%

60%

80% 74%

Class IV

(42%)

Class III

(58%)

64%

49%

38%

21% 20%

29%

70%

USpella 8

Very Complex Anatomy

0

5

10

15

20

25

30

% O

bse

rva

tio

ns

0 10 20 30 40 50 60 70 80Syntax Score

USpella High Risk PCI Population Presents with Much Complex

Anatomy than SYNTAX Trial and Registry Populations

SYNTAX Population USPella Population*

Mean~23 Mean=39

*Only 3VD and LM considered

USpella 9

Effective RevascularizationUSpella

*All comers, including SVG revascularization

0

10

20

30

40

50

60

70

80

Syn

tax S

co

re in

US

pell

a

Hig

hR

isk P

CI P

op

ula

tio

n*

Post PCIPre-PCI

p<0.0001

Median =38

Median =18

10

Effective RevascularizationUSpella

0

2

4

6

8

10

12

14

16

18

-10 10 30 50 70 90Pre-PCI Syntax Score

0

2

4

6

8

10

12

14

16

% O

bse

rvatio

ns

-10 10 30 50 70 90

Post PCI Syntax Score

% O

bse

rvatio

ns

Shift in the distribution

post-PCI towards lower

Syntax Score

Median= 38Events Free MACCE

According to SYNTAX Score

USpella HR PCI Population

11

Median= 18

Ejection Fraction ImprovementUSpella

p = 0.01

LVEF Within Subject Pair wise Comparison

(N=22*)

*N=22 subjects have LVEF measurements available Pre and Post PCI

** Longest available follow-up from PCI

Pre-PCI

29±15

0%

10%

20%

30%

40%

Post-PCI**

34±14

12

30-Day Reported MACE

USpella

0

2.5

5.0

7.5

Death MI Revasc. Em CABG Stroke/TIA MACE

Incid

en

ce (

%)

N=99

10.0

12.5

3% 3%

1%

3%

0%

6%

Aortic Insufficiency

Aortic Valve Injury

Renal Failure

Bleeding requiring surgery

Bleeding requiring transfusion*

Hypotension on support

Device Malfunction

Hemolysis

Infection

Vascular Complications (not requiring surgery)

Ventricular Tachycardia or CPR

Hematoma

30-day Reported Adverse Events n (%)

Other USpella Safety Profile

0 (0%)

0 (0%)

4 (4%)

0 (0%)

9 (9%)

3 (3%)

0 (0%)

0 (0%)

4 (4%)

3 (3%)

4 (4%)

5 (5%)

*The manufacturer has introduced a new sheath that has addressed the groin site bleeding

Registry 6 Month Follow-upUSpella

*All comers, including SVG revascularization

15

30 day survival = 97%

.6

.7

.8

.9

1

Su

rviv

al

(%)

0 20 40 60 80 100 120 140 160 180

Follow-up (days)

Censored

Death

USpella 16

Other Modalities

In-Hospital Available AE rate

AE Rate for Elective Support in HR PCI Reported Data: Impella vs other Modalities

• Age (yrs)

• History of CHF (%)

• Multivessel disease (%)

• Left Main Disease (%)

• LVEF<35% (%)

• Mean EF (%)

• In-Hospital MAE

• Death (%)

• Q-wave MI (%)

• Non Q-wave MI (%)

• Stroke (%)

• CABG (%)

• Angiographic failure (%)

• Vascular repair (%)

• Hypotension (%)

• Any Revascularization (%)

Cumulative MAE Range

IABP*

66 11

35

89

22

62

32 14

8.7

2.2

NR

1.1

6.5

13

3

NR

NR

13-34.5

(n=58)

CPS*

63 9

59

95

28

77

26 13

12.0

3.4

NR

3.4

1.7

1

14

NR

NR

14-35.5

(n=91)

Maini et al(2009)

69 11

80

85

58

70

32 17

3

1

2

0

3

1

0

3

1

3-13

(n=99)

Shreiber et al(1998)

Vogel et al(1995)

65

85

90

15

NR

28

7 - 18

1

NR

NR

2.5

7

NR

NR

NR

18-28.5

(n=576*)

NHLBI CPS registry*

MAE = Major Adverse Events; NR: Not reported. * Only prophylactic support reported here; All events are in-hospital events except **at 1 mo.

‡ Sjauw et al – Europella registry 30 day-MAE Amer. Jr of Cardiology – Vol 102 (Suppl 8A) -487 pp 186i; JACC 2009 (in press)

USpellaRegistry

Briguori et al(2006)

67 12

-

NR

100

<22

53 15

1.4**

5.8

NR

NR

2.9

6

12

10

NR

12-38.1

(n=69)

IABP*

Mishra et al(2006)

69 10

39

20

9

~35

29 13

4**

0

20

NR

0

2

4

10

NR

20-40

(n=69)

IABP*

Urban et al(2004)

~65 13

NR

NR

NR

NR

~35 15

~11

NR

NR

NR

NR

NR

NR

NR

NR

11-?

(n=69)

IABP*

Sjauw et al(2008)

71.8 10

NR

82

53

~50-64

26 6

5.5**

0**

0**

0.7**

0**

NR

4.0**

NR

NR

5.5-10.2

(n=144)

EuropellaRegistry‡

Impella

30-Day AE rate

Analysis By Sub-Group

• High Risk PCI

• Acute Myocardial Infarction

17

USpella AMI Population18

Baseline CharacteristicsMean ± SD or % Mean ± SD or %

ShockNo Shockp-value

64 ± 16

92 %

69% (31%)

31 ± 14

50 %

91 %

65% / 23% / 12%

14%

2.2 ± .4

Age (yrs)

Gender (Male in %)

STEMI (NSTEMI)

LVEF (%)

Unprotected LM or LPC

Multivessel Disease

Revasc (PCI/CABG/None)

Impella placement Pre-PCI

Pump Flow (L/min)

74 ± 10

72 %

3% (97%)

33 ± 15

50 %

75 %

100% / 0 / 0

95%

2.2 ± .3

0.003

0.04

<0.001

0.6

0.9

0.2

0.002

0.001

0.9

USpella AMI Shock Patients

Impella Used After Failed Conventional Therapies

(i.e, Revascularization, Inotropes and IABP)

USpella 19

Emergent

Revascularization

High Dose

Inotropes

Already on

IABP

0%

25%

50%

75%

100%88%

68%

88%

Th

era

py U

sa

ge

Pre

-Im

pe

lla

Su

pp

ort

Cardiac Index

Ca

rdia

c In

de

x(l

/min

/m2)

Wedge Pressure

0

1.6

1.8

2.0

2.2

2.4

2.6

On

Impella

PC

WP

(mm

Hg

)

0

20

24

28

22

26

30

Pre

Impella*

1.9 0.5

SVR

SV

R(x

1000 d

yn

es/s

ec x

cm

-5)

0

1.2

1.4

1.6

1.8

2.0

1.0

1.8 0.7

Impella Improves Hemodynamicsin AMI Shock

On

Impella

Pre

Impella*On

Impella

Pre

Impella*

2.5 0.6

28 8

20 10

p=0.02

p=0.001p=0.01

Mean Arterial Pressure

62 19

87 16p=0.003

*Pre-Impella measurements were recorded with optimal medical management measures (inotropes + IABP)

1.3 0.5M

AP

(mm

Hg

)

0

50

60

70

80

90

On

Impella

Pre

Impella*

100

LVEF Improvement Post SupportUSpella

p = 0.01

*N=25 subjects have LVEF measurements available Pre and Post PCI

** Longest available follow-up from PCI

0%

10%

20%

30%

40%

21

Pre-

PCI

29±12

Post-

PCI**

Pre-

PCI

Post-

PCI**

Pre-

PCI

Post-

PCI**

All AMICombined

AMINo Shock

AMIShock

37±15 37±17 37±12

30±1228±12

Survival to Discharge

By Indication

0%

25%

50%

75%

100%

AMI with

Shock

(n=36)

89%

(n=26)

58%

USpella 22

Impella Supported the AMI Refractory Shock Patients Successfully

Patients in AMI Refractory

Shock Support with Impella

N=26

Recovery

N=12

Bridge to Other

Support Devices

N=5

Death

N=4

Transplant

N=1

Transplant

N=1

Death

N=8

69% Survival to the Next Therapy or

to Recovery (18 out of 26), 58% to Discharge

Conclusion

USPella is the largest study reported so far for

Impella 2.5 that confirms prior results:

- Impella 2.5 is Safe and Easy to Use

- Provides excellent support to stabilize the

patients during high risk interventions and

restore the hemodynamics in unstable

conditions and refractory shock

USpella

Acknowledgements25

Brij Maini, MD, Anita Todd, RN, (Moffitt Heart & Vascular Group)

Simon Dixon, MD, Jim Wegner, RN (William Beaumont Hospital)

Theordore Schreiber, MD, Deb King, RN (Harper Hospital)

Srihari S. Naidu, MD, Dipti Patel, RN, (Winthrop University Hospital)

Chat Rihal, MD, Lynn Polk, RN (Mayo Clinic)

David Wohns, MD, Brianna Beilfuss, RN (Spectrum Memorial Hospital)

David Roberts, MD, Beverly Seiler, RN (Sutter Memorial Hospital)

Yakubov, MD & Anthony Chapekis, MD, Greta Robb, RN (Riverside Methodist Hospital)

Igor F. Palacios, MD, Maureen Daher, RN (Massachusetts General Hospital)

Chandan Devireddy, MD, Elizabeth Bleakley, RN, (Emory University Hospital Midtown)

James Revenaugh, MD, Bev Campbell , RN (Intermountain Medical Center)

Neeraj Jolly, MD, Bridge Galetti, RN (University of Chicago)

Suresh Mulukutla, MD, Lisa Baxendell, RN (UPMC)

Ali E. Denktas, MD, Yolanda Stiner, RN (University of Texas Herman)

James Blankenship, MD, Michelle Zarko, RN (Geisinger Medical Center)

Renzo Cecere, MD, Charlene Barber, RN (Royal Victoria Hospital)

Additional sites that have joined later the USpella:

William O’Neill, MD, Barbara Lang, RN (University of Miami)

Samin Sharma, MD, Michael Fusilero, MD (Mt. Sinai)

Michael Collins, MD & Jeffrey Moses, MD, Diana Wong, RN (Columbia Presbyterian)

Peter Reyes, MD, Dana Beach, RN (University of Maryland)

Alan Gass, MD, Mary-Evelyn Kennelty, RN (Westchester)

Neal Kleiman, MD, Nicole Hakala, RN (Methodist Debakey)

Laura Mauri, MD, Denise Cinamon, RN (Brigham & Women)

Paul Kramer, MD, Millie L. Salkind, RN (Shawnee Mission)

Thank You !

USpella

USpella Registry: Definitions

• Survival = Reported survival at 30-day or discharge whichever

is longer

• Adverse event definitions = FDA approved Protect II and

Recover II protocol definitions

• Syntax Score and Angiographic analysis performed at single

location (Pinnacle Health, PA, Brij Maini, MD, FACC)

• All statistical tests were two tailed and considered significant

when p-value<0.05

27

LV Unloading Correlates With Pump

Speed

60%

65%

70%

75%

80%

85%

90%

95%

100%

Baseline P2 P4 P6 P8 P9

Pt1

Pt2

Pt 3

Pt4

Pt5

Pump Speed Level

LV

En

d D

iasto

lic V

olu

me

(% f

rom

baselin

e)

28

LV Unloading Correlates With Pump SpeedUsing 3D Trans-Thoracic Echo

Pump Speed Level

LV

E

nd

Dia

sto

lic V

olu

me

(% f

rom

baselin

e)

70%

75%

80%

85%

90%

95%

100%

Baseline P2 P4 P6 P8 P9

p<0.001

29

Survival to Discharge

By Indication

0%

25%

50%

75%

100%

High Risk

PCI

AMI With

Shock

(n=99)

98%

(n=36)

89%

(n=26)

58%

USPella 30

Procedure Characteristics

Time to 1st Balloon

Inflation*

Median Time to

1st Balloon

Inflation

(N=51)

12 min.

USpella

* Median time from Impella insertion in the sheath to the first PCI balloon inflation or stent deployment in the target vessel

** Pump run in average at a performance level 7 (of a 9 scale, maximum)

Average Pump Flow

During PCI**

Median Duration

of Support*

(N=92)

2.1± 0.2 L/min

During

Procedure

Pump Flow

(N=59)

60 min.

[0.1-72hrs]

31