1. Washington University School of Medicine
Percutaneous Mechanical Devices For Circulatory Support- IABP and Impella
John M. Lasala, MD, PhD
Professor of Medicine
Washington University School of Medicine
St. Louis, MO

2. Short-term Devices for Cardiogenic Shock
Impella Recover
Short-term
Percutaneous
Axial flow
2.5-5 L/min
Percutaneous
IABP
0.5 L/min
ECMO
TandemHeart pVAD
Percutaneous
Centrifugal axial flow L/min
As technology improves, distinction between short, intermediate and long term is blurred. But this will not be aboput weaning from short-term, which is a separate and difficult issue.
Centrifugal axial flow extracorporeal
Bridge
3M Sarns
Medtronic
Bio-Medicus
Levitronix Centrimag 1

3. 5 Simple Reasons IABP are Currently 1st Line Therapy for “Cardiogenic Shock”
Avaliability/Convenience (in multiple settings including chronic use)
Significantly smaller access size compared to alternatives
Cost (up to 10x difference compared to alternatives)
Despite the naysayers… IABP does have clinical benefits!
Differences between trials (the podium) and clinical practice
Cardiogenic shock is a mixed bag of clinical scenarios!
For true shock, only alternatives are devices that provide “full support”

4. Problems with IABP “Mono”therapy
More modest hemodynamic effects
But these can be beneficial – don’t discount completely!
No active unloading of the ventricle
Minimal effects in patients with awful forward function or arrhythmias (particularly the dangerous ones)
Physician INERTIA can set in!!

5. No Mortality Benefit of IABP in Prospective Randomized Trials
Sjauw et al. Eur Heart J 2009:30:

6. No Hemodynamic Benefit of IABP in
a Recent Prospective Randomized Trial
1.5
1.0
0.5
Cardiac Power Output (CPO in Watts)
Prior 24 48 72 96
p<0.011
N.S
IABP (n=19)
No IABP(n=21)
Inotrope dosage was similar between the 2 groups
Time in hours
Prondzinsky et al. SHOCK 2012;37:
(Clinical Trials.gov ID NCT )

7. Higher Stroke and Bleeding Rates With IABP in AMI Cardiogenic Shock
Sjauw et al. Eur Heart J 2009:30:

8. No Survival Benefit With IABP in AMI Cardiogenic Shock

9. ESC 2014 Guidelines for AMI Shock
Routine use of IABP in CGS not recommended; Class III, Level A

10. Paradigm Shift in The Near Future:
Percutaneous Cardiac Assist Devices Have Been Integrated in
the 2011 PCI Guidelines
Adapted from
The purpose of this meeting is to make sure that you take full advantage of all
of the services that are offered under the Partnership in Healthcare support
Program. Some of the goals that I would like to achieve today is finding out
Key contacts for each element so that when information is new or updated
From this day forward….we would be able to contact you with that update. I
Would also like to spend some time talking about the Six Sigma Performance
Improvement Service that is part of this program.
Percutaneous Cardiac Assist Device

11. ISAR-SHOCK RANDOMIZED TRIAL:
IMPELLA 2.5 vs. IABP in AMI Cardiogenic Shock
Primary Endpoint:
Increase in Cardiac Index From Baseline
(measured after 20 min of support)
0.75
1.50
P<0.01
P<0.01
0.60
1.25
0.45
0.75
1.10
0.53
Cardiac Index Increase (L/min/m2)
Cardiac Output (L/min)
0.30
0.50
0.15
0.25
0.11
0.20
Impella
IABP
Impella
IABP
Seyfarth et al. JACC 2007

12. EUROSHOCK-Registry 9/10/2018
HCS-PP00611 rA_Impella Technology - Clinical Evidence and Investigations_DRAFT, SF edits incorporated

13. Lauten et al, Circ heart Fail. 2013;6:23-30
9/10/2018
Lauten et al, Circ heart Fail. 2013;6:23-30
HCS-PP00611 rA_Impella Technology - Clinical Evidence and Investigations_DRAFT, SF edits incorporated

14. Outcome Lauten et al, Circ heart Fail. 2013;6:23-30 9/10/2018
1.0
0.8
0.6
0.4
0.2
Years
Cum survival
1.0
0.8
0.6
0.4
0.2
Days
Cum survival
Lactate≥3.8 mmol/l
Lactate<3.8 mmol/l
Lauten et al, Circ heart Fail. 2013;6:23-30
HCS-PP00611 rA_Impella Technology - Clinical Evidence and Investigations_DRAFT, SF edits incorporated

15. Outcome First step Final step OR (96% CI) P Age>65 6.6 (1.6-27.5)
9/10/2018
First step
Final step
OR (96% CI) P
Age>65
6.6 ( )
0.009
6.2 ( )
0.001
Renal insufficiency
0.73 ( )
0.70
Previous MI
0.45 ( )
0.20
CPR
1.9 ( )
0.38
IABP
2.2( )
0.31
Systolic BP<90mmHg
1.5 ( )
0.56
Lactate>3.8 mmol/l
5.0 ( )
0.02
5.2 ( )
0.01
Lauten et al, Circ heart Fail. 2013;6:23-30
HCS-PP00611 rA_Impella Technology - Clinical Evidence and Investigations_DRAFT, SF edits incorporated

16. How fast can LV assist be initiated
How fast can LV assist be initiated ? PTCA with CPR in double stent thrombosis
Strong tendency to vessel thrombosis
Profound circulatory depression
QRS broader and broader
Repeated VT/VF -> Defibrillations
Severe pump failure
CPR =>MAP 60, but less and less
efficient over time (MAP->35mmHg)
© Patrick Hunziker, Basel

17. In cath lab –during CPR: Emergency percutaneous LV assist device (Impella 2.5)
Implantation of Impella during CPR
=> Stabilization of ABP
>50mmHg without CPR
Continue PTCA w/o CPR
Successful PTCA
Patient alive and well
© Patrick Hunziker, Basel

18. Results from the USpella Registry
The Current Use of Impella 2.5 in Acute Myocardial Infarction Complicated by Cardiogenic Shock:
Results from the USpella Registry
William W. O’Neill, MD*; Theodore Schreiber, MD‡; David H. W. Wohns, MD±; Charanjit Rihal, MD¶; Srihari S. Naidu, MD#; Andrew B. Civitello, MD†; Simon R. Dixon, MBChB**; Joseph M. Massaro, PhD ║; Brijeshwar Maini, MD††; E. Magnus Ohman, MD ¶¶.
From the *Henry Ford Hospital, Detroit, MI, USA; ‡ Detroit Medical Center, Detroit, MI, USA; ± Spectrum Health, Grand Rapids, MI, USA; ¶ Mayo Clinic, Rochester, MN, USA; # Winthrop University Hospital, Mineola, NY, USA; † Texas Heart Institute, Houston, TX, USA;
** Beaumont Hospital, Royal Oak, MI, USA; ║Harvard Research Institute, Boston, MA, USA;
††Pinnacle Health Medical Center, Wormleysburg, PA, USA; ¶¶Duke University Medical Center, Durham, NC, USA.
O’Neill et al, J Interven Cardiol 2013;9999:1-11

19. Impella® Insertion Timing (N= 154)
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

20. O’Neill et al, J Interven Cardiol 2013;9999:1-11
Hemodynamics
P<0.0001
Pre-Support
On Support
Pre- Support On
Support
Mean arterial pressure (n=143)
P<0.0001
Pre-Support On
Support
P=0.04
Cardiac power output (n=23)
All patients
N = 154
Impella Pre-PCI
N = 63
Impella Post-PCI
N = 91
Pre Support
On Support
p value
MAP, mmHg
62.7±19.2 (143)
94.4±23.1 (143)
<0.0001
67.9±20.7 (59)
94.5±21.3 (59)
59.1±17.3 (84)
94.4±24.4 (84)
PCWP, mmHg
31.9±11.1 (25)
19.2± (25)
30.8±7.8 (11)
19.7±7.9 (11)
0.004
32.7±13.4 (14)
18.9±11.1 (14)
Cardiac Index, L/min/m2
1.9±0.7
(23)
2.7± (23)
1.9±0.9
(7)
2.3±0.8 (7)
0.055
1.9± (16)
2.9±0.6 (16)
Cardiac Power Output, Watt
0.48±0.17 (23)
1.06±0.48 (23)
0.54±0.2
0.83±0.4 (7)
0.035
0.46±0.1 (16)
1.2±0.5 (16)
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

21. O’Neill et al, J Interven Cardiol 2013;9999:1-11
Hemodynamics
P<0.0001
Pre-Support On
Support
P=0.04
Cardiac power output (n=23)
All patients
N = 154
Impella Pre-PCI
N = 63
Impella Post-PCI
N = 91
Pre Support
On Support
p value
MAP, mmHg
62.7±19.2 (143)
94.4±23.1 (143)
<0.0001
67.9±20.7 (59)
94.5±21.3 (59)
59.1±17.3 (84)
94.4±24.4 (84)
PCWP, mmHg
31.9±11.1 (25)
19.2± (25)
30.8±7.8 (11)
19.7±7.9 (11)
0.004
32.7±13.4 (14)
18.9±11.1 (14)
Cardiac Index, L/min/m2
1.9±0.7
(23)
2.7± (23)
1.9±0.9
(7)
2.3±0.8 (7)
0.055
1.9± (16)
2.9±0.6 (16)
Cardiac Power Output, Watt
0.48±0.17 (23)
1.06±0.48 (23)
0.54±0.2
0.83±0.4 (7)
0.035
0.46±0.1 (16)
1.2±0.5 (16)
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

22. Procedural Characteristics
All
N = 154
Impella Pre-PCI
N = 63
Impella Post-PCI
N = 91
p value
Duration of support, (hrs)
23.7 [ ]
22.8 [ ]
24.2 [ ]
0.3873
Median DTB Time*, min
63.5 [ ]
112 [79 112]
52 [34 81]
<0.0001
Suspected IRA Territory LM
16.1%
23.8%
9.5%
0.0226
LAD
52.6%
53.9%
51.4%
0.7598
Left Cx.
10.9%
4.8%
16.2%
0.0324
RCA
16.8%
12.7%
20.3%
0.2373
Graft
3.7%
2.7%
0.5218
Number of diseased vessels
1.8±0.76
1.94±0.72
1.70±0.79
0.0735
Number of significant Lesions
2.57±1.39
2.74±1.49
2.42±1.28
0.1868
Number of vessel treated
1.42±0.63
1.57±0.67
1.30±0.57
0.0102
TIMI Flow [0-1] Prior to PCI
80.2%
71.9%
84.8%
0.1411
TIMI Flow [0-1] Post PCI
8.7%
4.6%
11.9%
0.1932
p=0.01
p=0.006
p=0.007
Pre-PCI
Post-PCI
Extent of Revascularization
O’Neill et al, J Interven Cardiol 2013;9999:1-11
*: DTB time for patients admitted for STEMI
HCS-PP rA

23. Procedural Characteristics
All
N = 154
Impella Pre-PCI
N = 63
Impella Post-PCI
N = 91
p value
Duration of support, (hrs)
23.7 [ ]
22.8 [ ]
24.2 [ ]
0.3873
Median DTB Time*, min
63.5 [ ]
112 [79 112]
52 [34 81]
<0.0001
Suspected IRA Territory LM
16.1%
23.8%
9.5%
0.0226
LAD
52.6%
53.9%
51.4%
0.7598
Left Cx.
10.9%
4.8%
16.2%
0.0324
RCA
16.8%
12.7%
20.3%
0.2373
Graft
3.7%
2.7%
0.5218
Number of diseased vessels
1.8±0.76
1.94±0.72
1.70±0.79
0.0735
Number of significant Lesions
2.57±1.39
2.74±1.49
2.42±1.28
0.1868
Number of vessel treated
1.42±0.63
1.57±0.67
1.30±0.57
0.0102
TIMI Flow [0-1] Prior to PCI
80.2%
71.9%
84.8%
0.1411
TIMI Flow [0-1] Post PCI
8.7%
4.6%
11.9%
0.1932
p=0.01
p=0.006
p=0.007
Pre-PCI
Post-PCI
Extent of Revascularization
EuroShock
O’Neill et al, J Interven Cardiol 2013;9999:1-11
*: DTB time for patients admitted for STEMI
HCS-PP rA

24. Outcome Cum survival Days from initiation of Impella 2.5 support
9/10/2018
1.0
0.8
0.6
0.4
0.2
Cum survival
Post-PCI
Pre - PCI
Number of patients at risk
154
101 88 79 69 67 63
Days from initiation of Impella 2.5 support
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP00611 rA_Impella Technology - Clinical Evidence and Investigations_DRAFT, SF edits incorporated
HCS-PP rA

25. Survival to Discharge by Timing of PCI
Timing of Support Initiation (154)
Pre-PCI
65.1%
Post-PCI
40.7%
Impella Support Initiation
Survival to Discharge
By timing of PCI
P=0.003
N=63
N=91
All Pts
50.9%
Post-PCI
60.0%
Pre-PCI
40.0%
Impella Support Initiation
STEMI
N=35
N=80
71.4%
45.5%
NSTEMI
N=28
N=11
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

26. O’Neill et al, J Interven Cardiol 2013;9999:1-11
Independent Predictors of In-Hospital Mortality Using a Multivariate Analysis*
Parameter Tested*
Odds-ratio
[CI 95%]
p-value
Initiation of Impella support prior to PCI
0.37
0.0105
Age
1.05
0.0025
Number of inotropes
1.56
0.0098
Cardiogenic shock onset prior to admission
2.42
0.0248
Mechanical ventilation
4.59
0.0003
* The multivariate analysis logistic model included the following as candidates for entry age, gender, history of chronic obstructive pulmonary disease, diabetes, peripheral vascular disease or prior stroke, STEMI vs. NSTEMI, cardiac arrest prior to admission, onset and duration of CS, patient transfer from outlying facility, evidence of anoxic brain injury pre-Impella support, need for mechanical ventilation, systolic and diastolic blood pressure , level of inotropic support pre-Impella support and potential use of IABP prior to Impella support, and baseline serum creatinine levels.
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

27. Outcome to Discharge by Sub-groups
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

28. Outcome By Support Strategy
Support Strategy (N=154)
No support Pre-PCI
(N=38)
IABP Pre-PCI
(N=53)
Impella Pre-PCI
(N=63)
PCI
PCI
PCI
Impella
Post PCI
Impella
Post PCI
Continue
Impella
N=38
N=53
N=63
Survival to discharge
HCS-PP rA
O’Neill et al, J Interven Cardiol 2013;9999:1-11

29. Conclusion and Limitations
These results are in favour of early initiation of hemodynamic support with active unloading of the LV prior to PCI in terms of completeness of revascularization and survival in the setting of CS complicating an AMI.
Retrospective data, therefore hypothesis generating and no definite conclusion on causality
Decision for the timing to implant Impella and extent of revascularization was operator
Although multivariate analysis reduces the bias of potential confounding factors there might be still some biases
O’Neill et al, J Interven Cardiol 2013;9999:1-11
HCS-PP rA

30. Griffith et. al. J Thorac Cardiovasc Surg. 2013 Feb;145(2):548-54

31. Hemodynamics Improvement After Pump Support
Cardiac Index
Mean Arterial Pressure
P=0.001
P=0.01
2.5±0.4
2.6
100
2.4
83.1±7.5 90
MAP
(mmHg)
2.2 80
71.4±12.5
Cardiac Index
(l/min/m2)
2.0 70
1.8
1.6±0.4 60
1.6 50
Pre
Impella On
Impella
Pre
Impella On
Impella
Pulmonary Artery Diastolic Pressure
P<0.0001 35
28.0±3.9 30
PAD
(mmHg) 25
19.8±3.2 20 15 10
Pre
Impella On
Impella
Griffith et. al. J Thorac Cardiovasc Surg Feb;145(2):548-54

32. Outcome to Next Therapy (n=16)
Over all 88% were weaned of Impella and recovered native heart function making heart recovery the most likely outcome following use of Impella
BTB 6%
(1)
Alive
94 %
(15)
Recovery of
native heart
function
88 %
(14)
Expired 6%
(1)
BTB: Bridge to bridge
Griffith et. al. J Thorac Cardiovasc Surg Feb;145(2):548-54

33. Survival Outcome is Favorable (N=16)
30 day
6 months
1 year
Survival
94%
81%
75%
Griffith et. al. J Thorac Cardiovasc Surg Feb;145(2):548-54

35. Indication for Support
Postcardiotomy
Cardiogenic Shock
(n=32)
Other (n=15)
AMICS (n=11)
ADIC (n=3)
Myocarditis with CS (n=1)
AMICS: Acute Myocardial Infraction with Cardiogenic shock
ADIC: Acute Decompensated Ischemic Cardiomyopathy
CS: Cardiogenic Shock
Lemaire A et al. Ann Thorac Surg Jan;97(1):133-8.

36. Outcome to Next Therapy (n=47)
Over all 72% were weaned of Impella and recovered native heart function making heart recovery the most likely outcome following use of Impella
BTB: Bridge to bridge
Lemaire A et al. Ann Thorac Surg Jan;97(1):133-8.

37. Lemaire A et al. Ann Thorac Surg. 2014 Jan;97(1):133-8.
Survival to One year
Lemaire A et al. Ann Thorac Surg Jan;97(1):133-8.

38. IABP drawbacks
Only modestly augments cardiac output and coronary blood flow
Unable to provide total circulatory support when hemodynamic collapse occurs .
Although the IABP restored epicardial perfusion in animal models, it had little effect on microvascular flow in the setting of acute myocardial infarction .
Requires a certain level of left ventricular function- it is not a pump!
Has not been independently associated with improved cardiac function or able to reverse cardiogenic shock and provide a survival benefit.

39. Conclusions
Management of Cardiogenic shock remains a challenge despite the progress made in reperfusion techniques and pharmacotherapy
Without clear supporting evidence, hemodynamic support with IABP remains controversial and is being challenged
The newly developed percutaneous left ventricular assist devices provide better hemodynamic support compared IABP
As the technology continues to evolve and the experience matures, paradigm shifts and new protocols will emerge for the management of cardiogenic shock with circulatory support
Stronger clinical evidence is required to define the selection criteria to identify the patients who would benefit the most from these new technologies

40. Rise of the Machines * Surgical VADs Percutaneous MCSDs
LVADs can be grouped according to mode of implantation…
Next Gen: Minimally Invasive VADs
* Fang J, NEJM 2001
Synergy
Symphony 57