1. Cardiogenic Shock Where Do We Go After The SHOCK Trial
William W. O’Neill, MD
Henry Ford Health System
Medical Director
Center for Structural Heart Disease
Detroit, MI

4. Pathogenesis of Myocardial Dysfunction During Cardiogenic Shock
Diffuse Multivessel
Disease 
Border Zone
Dysfunction
Diffuse Multivessel
Disease 
Lack of Compensatory
Hyperkinesis
Central Zone
Dyskinesis
PROFOUND FORWARD
PUMP FAILURE
Systemic
Hypotension
Acidosis
Coronary
Hypoperfusion

5. Probability of Survival Based On Arterial Blood Lactate
100 75 50 25 2 4 6 8 10
Probability of Survival (%)
Lactate mM

6. Cardiogenic Shock Complicating Acute Myocardial Infarction
U MICHIGAN EPERIENCE
Cardiogenic Shock Complicating Acute Myocardial Infarction
Lee et al Circulation 1987

7. SHOCK Trial 1-Year Survival
p=0.025
p=0.01

8. Mortality Based on Admission Blood Pressure in Thrombolytic Trials
Hypotension
SBP <= 90 *
SBP <= 80
* systolic blood pressure in mmHg

9. Incidence of Cardiogenic Shock Growing
Cardiogenic Shock in STEMI Increasing 1
STEMI Cardiogenic Shock in Medicare Age Increasing 2
56,508
36,969
53%
A recent increase in the incidence of cardiogenic shock in both the overall STEMI population and the Medicare patient population emphasizes the importance of focusing on this critical patient population.
While some believe this is partially driven by better documentation, the result is a rate approximately 50% higher than that documented in previous literature (10-12% vs 5-7%).
2010
2014
Age >65 only, excludes non-Medicare population
1. Dhaval Kolte et al. J Am Heart Assoc NATIONWIDE INPATIENT SAMPLE
2. Centers for Medicare and Medicaid database, MEDPAR FY14
HCS-PMA-PP rA

10. Limitations of Conventional Therapy
2/21/2018
Limitations of Conventional Therapy
Mortality Risk with Inotropes/Vasopressors1
N = 40
IABP-SHOCK II
Randomized Controlled Trial2
N = 600
IABP (n=301)
Medical Therapy (n=299)
41.3%
39.7%
Conventional therapy is largely driven by the use of inotropes and vasopressors, which have long been known to be associated with high mortality rates as both dosage and number is increased.
Recent randomized controlled trials have challenged the benefit of IABP in the setting in AMI cardiogenic shock . Even basic hemodynamic benefit was not observed because IABP is only augmenting the native heart function, which is low or nonexistent in this population. Large randomized controlled trials have also shown no mortality benefit. Meta-analysis of IABP and the PAMI-II trial showed an increased hazard risk for stroke leading to a class 3, harm/no benefit, level of evidence A, in 2014 ESC guideline updates
1- Samuels LE et al , J Card Surg. 1999
2- Thiele H et al. NEJM Clinicaltrial.gov # NCT
HCS-PMA-PP rA

11. Inotrope Harm in Cardiogenic Shock
Marked increase in MVO2 at a time of oxygen starvation.
Tachycardia increases MVO2 and decreases diastolic interval.
Marked increase in LVEDP causes further decrease in diastolic perfusion pressure and increased wall tension.
Tachycardia mediated apoptosis may decrease myocardial recovery.

12. New FDA Indication For Cardiogenic Shock
2/21/2018
The Impella 2.5™, Impella CP®, Impella 5.0 ™ and Impella LD ™ catheters, in conjunction with the Automated Impella Controller console, are intended for short-term use (<4 days for the Impella 2.5 and Impella CP and <6 days for the Impella 5.0 and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (<48 hours) following acute myocardial infarction (AMI) or open heart surgery as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures with or without an intra-aortic balloon pump.
The intent of the Impella system therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function.
* Optimal medical management and conventional treatment measures include volume loading and use of pressors and inotropes, with or without IABP
HCS-PMA-PP rA

13. Hemodynamic Effects of Impella® Support
Outflow
(aortic root)
Inflow
(ventricle)
aortic
valve
Cardiac Power Output
Flow
End Organ Perfusion
MAP
Coronary Perfusion
Microvascular
Resistance
LVEDP and LVEDV
O2 Demand
Unloading to Myocardial Recovery
O2 Supply
Mechanical
Work
Wall
Tension
Est. In-Hospital Mortality
Cardiac Power Output (Watts)
Cardiac Power Output
(MAP x Cardiac Output x )
Fincke, et. al. JACC, 2009 SHOCK TRIAL
(n=189)
The principles of the Impella heart pump design allow for direct unloading of the left ventricle from the inflow, and increased MAP and flow in the aorta from the outflow of the device. The ability to unload the left ventricle by reducing your Left ventricular end diastolic pressures and volumes reduce wall tension, microvascular resistance, and increasing coronary perfusion. This results in overall improvement in oxygen supply while simultaneously reducing oxygen demand.
Fincke J, et al. Am Coll Cardiol 2004
den Uil CA, et al. Eur Heart J 2010
Mendoza DD, et al. AMJ 2007
Torgersen C, et al. Crit Care 2009
Torre-Amione G, et al. J Card Fail 2009
Suga H. et al. Am J Physiol 1979
Suga H, et al. Am J Physiol 1981
Burkhoff D. et al. Am J Physiol Heart Circ 2005
Burkhoff D. et al. Mechanical Properties Of The Heart And Its Interaction With The Vascular System. (White Paper) 2011
Sauren LDC, et al. Artif Organs 2007
Meyns B, et al. J Am Coll Cardiol 2003
Remmelink M, et al. atheter.Cardiovasc Interv 2007
Aqel RA, et al. J Nucl Cardiol 2009
Lam K,. et al. Clin Res Cardiol 2009
Reesink KD, et al. Chest 2004
Valgimigli M, et al.Catheter Cardiovasc Interv 2005
Remmelink M. et al. Catheter Cardiovasc Interv 2010
Naidu S. et al. Novel Circulation.2011
Weber DM, et al. Cardiac Interventions Today Supplement Aug/Sep 2009
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14. Improvement in Cardiac Index
ISAR SHOCK Randomized Controlled Trial
Hemodynamic Stability & LV Unloading with Impella ®
(L/min/m2)
Seyfarth et al., JACC, 2008
Augmented CI
Ventricular Unloading
Impella 2.5
Native
Heart
Pre-Support
On Impella
1.71±0.45
2.20±0.64
1.73±0.59
1.84±0.71 On
IABP
N.S.
P= 0.02
Native CI
N=26
The same hemodynamic improvements can be seen in a randomized controlled trial called ISAR SHOCK with the Impella Improvement in cardiac index while simultaneously unloading the left ventricle with statistical improvement over results observed with the IABP.
HCS-PMA-PP rA

15. Impella® Reduces Need for Inotropes/Pressors
2/21/2018
Impella® Reduces Need for Inotropes/Pressors
Impella 2.5
Reduction in Inotropes/Pressors
in 24 Hours
Impella 5.0
Reduction in Inotropes/Pressors
Over days
ISAR-SHOCK RCT1
N=25
RECOVER I FDA IDE Study2
(N=16)
1- Seyfarth et al. JACC 2008
2- Griffith et a. J Thorac Cardiovasc Surg 2012
HCS-PMA-PP rA

16. Decrease in Inotropes/Pressors in Right Heart Failure
2/21/2018
Pump Implant
TO UPDATE
Cohort A
Cohort B
Average time of Impella RP support
Anderson MB. et al., J Ht Lg Transplant. 2015
HCS-PMA-PP rA

17. The cVAD Registry: A Global Initiative
The catheter based VAD Registry is a worldwide observational clinical registry designed to monitor patient safety and real-world outcomes of patients supported with Impella 2.5/CP/5.0/LD/RP
Impella Approved: USA, Canada, Panama, Colombia, Venezuela, Brazil, Portugal, Spain, France, Italy, Greece, Switzerland, Austria, Germany, Belgium, Luxemburg, Netherland, Ireland, UK, Denmark, Norway, Sweden, Finland, Russia, China, Saudi Arabia, Kuwait
Impella Approved and cVAD Registry Active: USA, Canada, Spain, France, Italy, Switzerland, Germany, Netherland, UK, Denmark

18. Global cVAD Registry Overview (as of March 2016)
~3,000 existing patients (legacy)
74 Sites (932 Impella users) and growing
10 Countries
5 sub-specialties (Interventional cardiology, Cardiac Surgery, Heart Failure, Electrophysiology, Structural Heart)
Representative of real world setting
Well established operating mechanisms and operations
Baseline, procedural, hemodynamic, imaging, outcome and adverse events data with up to 1 year follow-up

19. Mortality Based on the Number of Inotropes Used Before Impella Support
Early Initiation of Impella Support Is Associated with Improved Outcomes in AMICS
Mortality Based on the Number of Inotropes Used Before Impella Support
p<0.001, (N=287)
Number of Inotropes

20. Early Initiation of Impella Support Is Associated with Improved Outcomes in AMICS
Mortality Based on Duration of Cardiogenic Shock Before Impella Support
p=0.01, (N=140)
[ hrs[
[ hrs[
[ hrs]
Duration of Cardiogenic Shock Distribution

21. Early Initiation of Impella Support Is Associated with Improved Outcomes in AMICS
Log-rank test, p=0.004

22. SG Use Associated with Improved Outcomes
Distribution of Survival to Explant at Impella Sites
(379 sites supported >4 AMICS patients)
Survival
Total # of Patients
N=68
N=147
N=277
N=488
N=777
N=465
N=425
N=331
N=99
N=62
Abiomed Internal Clinical Quality Data AMI/CGS April 2015 – March 2016

23. Significant Increase in Survival with Use of Swan
p<.00001
N=1894
N=1612
Abiomed Internal Clinical Quality Data AMI/CGS April 2015 – March 2016

24. Detroit Cardiogenic Shock Initiative

25. CARDIOGENIC SHOCK A CHANGE IN PARADIGM
DOOR TO BALLOON DOOR TO SUPPORT