1. Impella Innovation: Technical Tips
CRT 2011
Impella Innovation: Technical Tips
Samin Sharma, MD, FACC
Professor of Medicine (Cardiology)
Director Cardiac Cath Lab & Intervention
Co-Director Cardiovascular Institute
Mount Sinai Hospital, NY

2. Conflict of Interest Research Grant support & Speaker Bureau for:
- BSc
- Abbott Vascular
- DSI/Lilly
The Medicines Co
- Abiomed
- Angioscore

3. Impella Recover LP 2.5 MOTOR
Miniaturized technology for percutaneous access
Fast and easy insertion: via femoral artery
Actively unloads the ventricle
Provides up to 2.5 L/min of flow with support up to 5 days
MOTOR 3 3

4. Outline Technology Overview Clinical Experience and Investigations
Future Directions

5. Function and Implantation
Impella Technology 5
Function and Implantation
Miniaturized 12F pump
Single Femoral access
Placement with 0.014” wire
Actively unloads the LV
Forward Flow up to 2.5L/min
Low anticoagulation

6. Principles of Impella Design
Mimic Heart’s Natural Function
Inflow
(ventricle)
Outflow
(aortic root)
aortic
valve
EDV, EDP
AOP
Flow
O2 Demand
O2 Supply
Cardiac Power Output
Myocardial Protection
Systemic Hemodynamic Support

7. Regulatory Status Over 400 institutions in 40 countries Health Canada7
Health Canada
2.5: 2008 (7 days)
5.0: 2008 (7 days)
CE Mark
2.5: 2004 (10 days)
5.0: 2003 (10 days)
FDA – 510(k) / IDE trials
2.5: 2008 (6 hrs – 5 days in IDE trials)
5.0: 2009 (6 hrs – 7 days in IDE in trial)
Over 400 institutions in 40 countries
Approved
Approval Pending

8. Outline Technology Overview Clinical Experience and Investigations
Future Directions

9. Impella Adoption in the US9
Over 4000 patients Supported and 400 Participating Centers
Since FDA 510(k) Clearance in June’08*
Number of Patients Supported By Semester
* Data through 12/31/2010

10. Impella 2.5: High Risk PCI Insight from the USpella Registry & PROTECT II Trial10

11. USPELLA Registry: Reported Use in the US
By Specialty
By Application
Surgery, 18%
High Risk PCI
(71%)
Cardiology, 82% 11

12. Patient Characteristics Mean ± SD or %
USPELLA Registry: Patients Represent The Most Complex Set of PCI Performed in Contemporary Times
Patient Characteristics
Mean ± SD or %
Age (yrs)
70 ± 11
Gender (Male in %)
74%
Procedure (Elective vs Urgent)
45% vs 55%
LVEF (%)
30 ± 16
LVEF < 35%
71%
Unprotected LM
51%
Unprotected LM or LPC
52%
Multivessel Disease
88%
Nb of Segments Treated
2.5 ± 1.2
STS Score
5.6 ± 6.5
Syntax Score
36 ± 15
Simon R. Dixon 12

13. USPELLA Registry: 30-day MACE Outcome
12.5
10.0
8.2%
7.5
Incidence (%)
5.0
3.9%
2.6%
2.5
1.3%
0.9%
0.4%
N=9
N=3
N=2
N=6 MI
N=1
N=19
Death
Revasc.
Any vascular
Operation
Stroke/TIA
MACE
30-day or discharge (whichever was longer) site reported MACE

14. LVEF Improvement Post HRPCI14
All HRPCI
Combined
Elective PCI
Urgent PCI
Gain = + 16%
Gain = + 17%
Gain = + 15%
p <
p =
p = 0.002
37±15
36±14
35±14
32±15
31±15
30±15
N=91†
N=91
N=40
N=40
N=55
N=55
Pre-
PCI
Post-
PCI‡
Pre-
PCI
Post-
PCI‡
Pre-
PCI
Post-
PCI‡
N=91 patients had LVEF measurements available Pre and Post PCI (pair wise comparison)
Up to 30 days from PCI
Simon R. Dixon 14

15. AMI Shock: Impella Used Post PCI and Failed Inotropes, IABP15
AMI Shock: Impella Used Post PCI and Failed Inotropes, IABP
% of Patients
PCI
Inotropes
Already on
IABP
Therapies Usage Before Impella Implant
Simon R. Dixon 15

16. Mortality Predicted by Cardiac Power Output
Impella Improves Cardiac Power Output, the Strongest Correlate of in-hospital Mortality
Cardiac Power Output
in USpella AMI Shock
Mortality Predicted by Cardiac Power Output
Cardiac Power Output‡
N = 189 10 20 30 40 50 60 70 80 90
100
Estimated In-Hospital Mortality (%)
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Fincke et al. JACC 2004:44,n2: 304-8
[95% Confidence Interval]
p=0.0004
1.0±0.2
Pre-Impella
Cardiac Power Output
(Watts)
p=0.0004
0.5±0.2
On-Impella
Pre
Impella† On
Impella
‡ Cardiac Power Output (CPO) = CO x MAP x
Pre-Impella measurements were recorded under clinical conditions (i.e, with inotropes + IABP) 16

17. Gain on Hemodynamics When Switching from IABP to Impella in AMI Shock17
Patient serve as his/her own control (N=20)
Systolic Blood Pressure
Diastolic Blood Pressure
Mean Arterial Pressure
Gain = + 38%
Gain = + 40%
Gain = + 41%
p<0.0001
P=0.0002
p<0.0001
60 mmHg in MAP is the considered minimum threshold for adequate coronary, cerebral and renal perfusion
113±30
82±19
83±17
66±16
59±15
47±16
Blood Pressure (mmHg)
On IABP
Switched
to Impella
On IABP
Switched
to Impella
On IABP
Switched
to Impella
Comparisons made for ALL AMI shock patients that were on IABP then switched to Impella for
whom pre and post blood pressure values were available (N=20)

18. Timing of Impella Support vs Outcome
Impella ON
“Pre-PCI”
(n=22)
“Post PCI”
(n=34)
p-value
Baseline Characteristics
Age (Median, range in years)
64 (53-84)
63 (19-83)
0.4
Cardiac Index Pre-Impella (L/m2)
2.0±0.2
2.0±0.6
0.9
Heart rate Pre-Impella (beat/min)
73±24
77±26
0.6
MAP Pre-Impella (mmHg)
54±22
50±17
LVEF Pre-Impella (%)
26±11
26±12
STEMI presentation (%) 60 80
0.2
Outcome
30-day mortality
23%
56%
0.02
Simon R. Dixon 18

19. PROTECT II Trial Design
Hemodynamic support during high-risk, non-emergent PCI, N=654
Unprotected LM or last patent conduit & EF35%
or 3VD & EF30%
Assess Myocardium at Jeopardy and Indicate all stenoses considered for stenting R
1:1
IABP +
PCI
IMPELLA 2.5 +
PCI
Primary Endpoint = MAE at 30-days
3 Month Follow-up

20. PROTECT II Interim Results
Per Protocol Primary Endpoint:
30-day Combined Major Adverse Events (MAE)
Patients
Impella
MAE
IAB MAE
p value
All* (N=305, 100%)
38%
43%
0.40
No atherectomy (N=267, 88%)
32%
0.06
Atherectomy (N=38, 12%)
72%
46%
0.12
(Impella N=25, IAB N=13)
* For the entire study population, Impella significantly reduced out of hospital MAEs by 52% compared to IAB for the duration of the 90 day monitoring period (p=0.02, N=302)

21. Atherectomy Group Key Differences in Endpoint Components:
Trade-off Between CK-MB and Repeat Revasc
30-Days
90-Days
p=0.01
p=0.63
p=0.01
p=0.80
p=0.04
p=0.02
2X more frequent atherectomy use in Impella arm (16.1% Impella, 8.7% IAB, p=0.04)
2X more atherectomy passes per lesion in Impella arm (3.9 Impella, 1.7 IAB, p=0.003)
30% more atherectomy passes per patient in Impella arm (6.3 Impella, 3.8 IAB, p=0.14)

22. Clinical Roadmap Impella Clinical Studies and Trials
Product
Trial Name
Population
Nb pts/sites
Location
Status
Impella 2.5
ISAR/SHOCK
AMI Shock (feasibility)
26 / 2 EU
In JACC 2008
MACH 2
Infarct Size Reduction / LVEF (feasibility)
20 / 1
PROTECT I
High risk PCI (feasibility)
20 / 8
USA
In JACC Interv 2009
EUROPELLA Registry
High Risk PCI
144 / 10
In JACC 2009
PROTECT II
High risk PCI (Pivotal)
425 / 150
To be presented at ACC 2011
IMPRESS
Infarct Size Reduction / LVEF in Pre-Shock
130 / 11
On-going
MINI – AMI
Infarct Size Reduction in STEMI
50 / 5
PERMIT - 1
VT Ablation Prophylactic Support (feasibility)
USpella Registry
Voluntary registry on the use of Impella under FDA 510(k) clerance
400+ / 40+
Impella 5.0
BYPASS
Off-pump High Risk CABG
150 /10
In EJCTS
2002
RECOVER I
Post-Cardiotomy Shock or LOS
20 / 7
In press 22

23. Impella Recover 2.5 Vs TandemHeart Ventricular Assist Devices High Risk PCI
TandemHeart (n=32)
p=0.11
Impella 2.5 (n=36)
42.0
30.0
p=0.14 %
22.0
p=0.48
15.0
p=1.0
n/a
p=0.32
n/a
8.0
6.0
6.0
3.0
3.0
Death MI CVA uCABG Major Any F/U MACE
Access site in Hosp
Complications
Kovacic, Sharma, Kini et al. CCI Feb 2011.

24. Impella Recover 2.5 Vs TandemHeart Ventricular Assist Devices High Risk PCI
TandemHeart (n=32)
Impella 2.5 (n=36)
P value
Age (yrs)
0.55
LVEF (%)
27 + 6
0.02
STS Mortality
0.19
Number of lesions treated
0.82
Rotational Atherectomy (%) 28 44
0.21
B2/C lesion (%) 85 87
Total procedure time (min)
0.009
Procedural Success (%) 99
1.00
Kovacic, Sharma, Kini et al. CCI Feb 2011.

25. Impella 2.5 vs. TandemHeart LVAD in High-risk PCI
K-M Analyses of Event Free Survival
Kovacic, Sharma, Kini et al. CCI Feb 2011.

26. Outline Technology Overview Clinical Experience and Investigations
Future Directions

27. New Applications – EP Lab
Hemodynamic support for patients undergoing VT ablation
Sustain systemic flow
Maintain Patient Stability
More time for catheter placement, accurate Mapping and Ablating

28. Impella-Supported Aortic Valvuloplasty
New Applications – BAV
Impella-Supported Aortic Valvuloplasty
Sustain systemic flow during inflation
Maintain Patient Stability
More time for Balloon inflation

29. MPC Functions Keys Review of MPC keys and their Functions
P-Perf Key (P0-P9)
Flow Key (Not Used)
Zero Key
Signal Key:
Purge Pressure Screen
Motor Current Screen
Speed Screen
Flow Rate Screen
Placement Signal Screen
Placement Monitoring Screen
Dual Screen
Menu Key: OFF Function Default Limits
Pump ID
Up & Down Keys
Scale Key (time):
10sec, 5mins, 5hrs
OK Key
ON Key
Pressure Connector Socket
Pump Connector Socket
Review of MPC keys and their Functions 29

30. Impella Product Enhancements
Pre-assembled guiding lumen facilitates loading the placement guidewire
Integrated infusion pump, user interface and power supply
Bright, highly visible user display
Graphical user interface
Built in Alarm Help
Fast and simple to setup
Designed for transport

31. Simplified User Interface
Bright easy to read LCD display
Soft button function change depending on current operation
Combined rotating push button for navigation and selections
Continuous display of key Impella® Controller operating parameters

32. Home Screen Displays system status information Alarms Position Flow
Purge

33. Impella 2.5 Product Enhancements
Simplified Back-loading
Pre-assembled guiding lumen facilitates loading the placement guidewire

34. Impella 2.5 Product Enhancements
Simplified Back-loading
Step 1 Thread guidewire
Step 2
Remove guiding lumen

35. Impella 2.5 Product Enhancements
Improved Visibility for Placement
New position marker facilitates alignment with aortic valve
Position the marker at the level of the aortic valve annulus

36. Impella 2.5 Product Enhancements
New Repositioning Sheath Design

37. Wireless Insertion Eliminates: Guiding catheter placement guidewire
back-loading
Reduces the number of steps from 12 to 6
The pigtail of the Impella advanced through the sheath
Advance the Impella to the aortic valve, until the catheter begins to prolapse
Pull the catheter back slightly while turning, the catheter will “pop” across the valve

38. Impella RP Percutaneous implantation
Inlet
Area
Outlet
Percutaneous implantation
Inflow in the IVC proximal to the eustation valve
3-dimensional, S-shaped cannula placed across tricuspid and pulmonic valves
Outflow placed approximately 4 cm into the PA
Short pigtail at outflow provides stability in the PA

39. Impella RP
First patient was successfully supported for six days by the Impella Right Percutaneous (RP)
Providence Heart & Lung Institute at St. Paul’s Hospital in Vancouver, British Columbia
Anson Cheung, M.D.
Post-transplant patients with acute right heart failure

40. Impella Pediatric 5-15 kg patients Flow: 0.5 - 2 L/min
Pulsatile flow possible
Direct or peripherally
Up to 14 days of support
Impella Pediatric

41. Quick Set-up Kit for Impella® 2.5
Standard Set-Up Kit
Benefits of the Quick Set-up for Impella® 2.5
Shorten decision-to-Impella time
Ready to insert in less than 3 minutes
Eliminate set-up delays and confusion
Wide range of Dextrose solutions
Delays the need for anticoagulant in the purge
Moves the use of the B. Braun to after clinical procedures are complete
Maintains the goal of fast door-to-balloon times
Critical components included
“Pre-assembled”
Fewer steps (reduced by 50%)
Minimal console interaction
Quick Set-Up Kit

42. Summary Platform for catheter-based cardiac assist pumps designed to
directly unload and protect the heart while stabilizing the hemodynamics of the patient1,2,3,4,6,8,10
Designed for Safety and Ease of Use1-6,12,13
Minimum Priming time, no sternotomy, no cardiopulmonary bypass
Potential to reduce mortality, preserve the cardiac function & improve the patient QOL2,5,11,12,13
Cost-Effective2,11,14,15 .
Footnotes/References:
Burzotta et al, Journal of Card Vasc Med, 2008
Dixon et al, JACC 2009
Henriques et al, Journal of American Card, 2006
Seyfarth et al, JACC, 2008
Sjauw et al, MACH II, JACC 2008
6. Valgimigli et al, Cath Cardiov Interv (2005)
7. Reesink et al, CHEST (2004)
8. Fincke et al, JACC (2004)
9. Sauren et al (2007)
10. Meyns et al, JACC (2003)
11. MACH II 3-Year Follow up, TCT (2009)
12. USpella, TCT (2009)
13. Europella, Henriques et al, JACC (2009)
14. STEMI Guidelines, ACC/AHA, ICDs
15 AHA Heart Statistics 2009: CABG vs. PCI 42