1. Hemodynamic Support of High Risk PCI
George D. Dangas, MD, FACC, FSCAI
Professor of Medicine (Cardiovascular Disease)
Icahn School of Medicine at Mount Sinai
New York, NY

2. Conflict of Interest Disclosure
Abiomed
Personal: None
Sponsor of PROTECT-II trial
Off-label use will be discussed

3. In order for revascularization to provide a benefit to patients…
The revascularization being performed has to be performed on disease that is
actually prognostically important or
causing a reduction in quality of life
The revascularization must be able to be done safely and with high quality and/or durability

4. Cardiac Power Is The Most Important Mortality Predictor in the SHOCK Trial
100
Cardiac
Power
(Mean Arterial Pressure x Cardiac Output) 90 =
451 80 70 60
Estimated In-hospital Mortality (%) 50 40 30 20 10
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Cardiac Power Output
Finke et al JACC 2004; 44:340

5. Patients That Benefit from Support
Protected PCI
Cardiogenic Shock Therapy
HCS-PMA-PP rA

6. Patients Most Appropriate for Revascularization
9/13/2018
Patients Most Appropriate for Revascularization
Coronary Revascularization Appropriateness Guidelines ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT1
Heart Failure
Angina
High Risk Findings on Noninvasive Study
Symptoms Med. Rx
Class III or IV Max Rx A
Class I or II Max Rx
Asymptomatic Max Rx U
Class III or IV No/min Rx
Class I or II No/min Rx
Asymptomatic No/min Rx
Coronary Anatomy
CTO of 1 vz.; no other disease
1-2 vz. disease; no Prox. LAD
1 vz. disease of Prox. LAD
2 vz. disease with Prox. LAD
3 vz. disease; no Left Main
CCS Class III or IV Angina
Stress Test Med. Rx
High Risk Max Rx A
High Risk No/min Rx
Int. Risk Max Rx
Int. Risk No/min Rx U
Low Risk Max Rx
Low Risk No/min Rx I
Coronary Anatomy
CTO of 1-vz; no other disease
1-2-vz. disease; no prox. LAD
1-vz. disease of prox. LAD
2-vz. disease with prox. LAD
3-vz. disease; no left main
Protected PCI Patients =
More Heart Failure
More Angina
More Complex
More likely to be appropriate
Symptoms
Symptoms
A = Appropriate, U = Uncertain, I= Inappropriate
A = Appropriate, U = Uncertain, I= Inappropriate
Complexity
Complexity
HCS-PP rB
1. Patel MR, et al, J AM Coll Cardiol. 2012;59(9);

7. Why are hemodynamics so essential?
Catheters can obstruct native aorto-ostial flow (especially larger catheters). Wires, balloons, stents, devices can obstruct flow and when inflated by definition are producing ischemia
Contrast does not contain hemoglobin and is a myocardial depressant
Patient smay have acute or longstanding LV dysfuction and CHF
Adverse hemodynamics will make it difficult to complete the case and can worsen short/long term outcomes by allowing …disasters!

8. Revascularization Strategy by Risk Category
9/13/2018
Surgical Risk
Low
Medium
High
PCI
CABG or PCI
PCI or CABG
Support & PCI
CABG
Often inoperable
SYNTAX
Study
Protected PCI
FDA Indicated
Safe & Effective
ACC/AHA PCI Guidelines1,2
Anatomic Risk
Furthering the considerations of PCI vs CABG, the Institution’s Heart Team can addresses the question based on the procedural risk considerations consistent with current ACC/AHA Guidelines. The vertical axis shows degrees of anatomic risk and the horizontal axis shows degree of patient surgical risk. Using this presentation of the risk stratification, the SYNTAX Study patients are all located in the far left column corresponding to lower surgical risk, since all were eligible for cardiac surgery. The lower right hand column is where the Protected PCI patients are found.
In patients with medium to high anatomic complexity and high surgical risk, Impella 2.5 is FDA indicated to be safe and effective during a Protected PCI procedure.
1. Levine GN, et al. J Am Coll Cardiol, 2011 Dec 6;58(24):e44-122,
2 Amsterdam EA, et al. Circulation Dec 23; 130(25):e

9. Intra-Aortic Balloon Pump
PROs:
Well known technology
Increases coronary perfusion
Mild increase in cardiac output
Ease of use
Cost
CONs:
Requires a minimum of cardiac function
Requires a stable rhythm
Modest unloading
Negative studies
Pioneered at Grace Sinai Hospital in the early 1960s by Kantrowitz et al.
First clinical implant was performed at Maimonides Medical Center in Brooklyn, NY in 1968.
The size of the original balloons was 15 Fr, but eventually 9 and 8 Fr balloons were developed.
Since 1979, placement is via modified Seldinger technique.
First publication on aortic counterpulsation was by Kantrowitz, et al in JAMA in 1968.
The patient, a 48 year old woman, was in cardiogenic shock and unresponsive to traditional therapy. An IABP was inserted by a cut down on the left femoral artery. Pumping was performed for 6 hours. Shock reversed and the patient was discharged.

10. 50% No Planned IABP Use (N=151) 12% Required Bailout IABP Use
BCIS-1 Trial
Design
301 patients enrolled between December 2005 an January 2009 in 17 clinical sites in the United Kingdom
DESIGN: Prospective, randomized, control trial
OBJECTIVE: To evaluate all cause long term mortality in patients with LV impairment (EF <30%) and severe CAD:
Extensive Myocardium at Risk
BCIS-1 Jeopardy Score > 8
Or Target vessel supplying occluded vessel which supplies >40% of myocardium
50% No Planned IABP Use (N=151)
50% Planned IABP Use (N=150)
12% Required Bailout IABP Use
(N=18)
Perera et al, Am Heart J 2009;158:

11. BCIS-1: Major Outcomes Adverse Events (%)
HR 1.86
( )
HR 0.94
( )
HR 0.11
( )
OR 0.61
( )
Perera et al, JAMA 2010; 304(8):

12. IABP SHOCK-2
Design
790 patients enrolled between June 2009 and March 2012 in 37 clinical sites in Germany
DESIGN: Prospective, multicenter, randomized, open-label controlled trial comparing IABP vs. medical therapy.
OBJECTIVE: To compare the efficacy and safety of the IABP vs. early medical therapy on the background of early revascularization by PCI or CABG (87% AFTER the PCI).
190 patients excluded
600 patients randomized
Medical Therapy
IABP
Clinical follow-up at 30 days in 99.7% (N=298)
Clinical follow-up at 30 days in 99.7% (N=300)
Thiele H. et al, NEJM 2012

13. IABP SHOCK II Primary Study Endpoint (30-Day Mortality) Mortality (%)50
Control
41.3% 40
IABP
39.7% 30
Mortality (%) 20
P=0.92 by log-rank test
Relative risk 0.96; 95% CI ; P=0.69 by Chi2-Test 10 5 10 15 20 25 30
Time after Randomization (Days)
Thiele et al NEJM 2012

14. Impella: FDA approved for High risk PCI
Impella hemodynamic support device has been proven safe and effective at reducing peri-procedural and post-procedure adverse events in elective and urgent High Risk PCI patients

15. Randomized Trial of Impella vs. IABP in AMI with Shock (ISAR-SHOCK)
(primary endpoint)
N=25
Adapted from Seyfarth et al., JACC 2008

16. Hemodynamic Support Effectiveness: PROTECT II
Cardiac Power Output
Maximal Decrease in CPO on device Support from Baseline (in x0.01 Watts)
IABP
Impella
N=138
N=141
- 4.2 ± 24
p=0.001
± 27
CPO= Cardiac Power Output = Cardiac Output x Mean Arterial Pressure x
(Fincke R, Hochman J et al JACC 2004; 44: )

17. PROTECT-II Trial Design
Patients Requiring Prophylactic Hemodynamic Support
During Non-Emergent High Risk PCI on
Unprotected LM/Last Patent Conduit and LVEF≤35% OR
3 Vessel Disease and LVEF≤30% R
1:1
IABP +
PCI
IMPELLA 2.5 +
PCI
Primary Endpoint = 30-day Composite MAE* rate
Follow-up of the Composite MAE* rate at 90 days
*Major Adverse Events (MAE) : Death, Stroke/TIA, MI (>3xULN CK-MB or Troponin) , Repeat Revasc, Cardiac or Vascular Operation of Vasc. Operation for limb ischemia, Acute Renal Dysfunction, Increase in Aortic insufficiency, Severe Hypotension, CPR/VT, Angio Failure

18. Impella Reduces Peri & Post Procedural MACCE
9/13/2018
MACCE
MACCE = Death, Stroke, MI, Repeat revasc. 10 15 20 25 30
29% reduction
In MACCE
IABP
N=211
MACCE (%)
Impella
N=216
This slide shows the overall MACCE Kaplan-Meyer curves from the PROTECT II study. Use of Impella during the PROTECT II trial resulted in a 29%, overall reduction in MACCE events as compared to use of the IABP at 90 days.
p=0.042 10 20 30 40 50 60 70 80 90
Time Post Procedure (day)
FDA Approved Randomized Controlled Trial
Protect II
Dangas et al, Am J Cardiol 2014; 113(2):222-8

19. PROTECT II Multivariate analysis predictors of MACCE at 90 days
Odds Ratio Estimate
95% confidence interval
P-Value
Per-Protocol Population
Use of atherectomy rotablation during index procedure
1.2984 –
0.1161
Renal Insufficiency
1.2324 –
0.1089
Baseline worst TIMI flow: 0-1
1.3112
Device: IMPELLA vs IABP
0.7651
0.0206
Intention-To-treat Population
1.2787
0.1366
1.2466
0.0829
1.2340
0.1777
0.7944
0.0417
Dangas et al, Am J Cardiol 2014; 113(2):222-8

20. Open Questions in Hemodynamic Support
How much support is necessary?
What is the role of IABP / Do we believe IABP SHOCK II?
Which patients should get upfront treatment with an LVAD?
What is the optimal use for Impella LVAD support?
Relevance of cost/complications vs. benefit of active LVADs
How do we manage biventricular failure?
SOME OF THESE WILL BE DISCUSSED DURING THE LIVE CASE 19

21. Access Comparison Among pVADs
Atkinson TM, et al. JACC Cardiovasc Interv. 2016;9(9):
IMP

22. Femoral Access: Duplex Guidance or Micro Puncture Angiography or Iliac Angiogram After selecting site for large sheath insertion, deploy two Perclose sutures at 10 and 2 o’clock positions
Deployment at 10 o’clock
Deployment at 2 o’clock
IMP

23. Vascular Closure Device (VCD) & Complication Management
VCDs
Preclose – double vs. single
Double Angioseal
Preclose + Angioseal
Local Lido&Epi SQ
Crossover sheath for dry closure
Crossover sheath for management of complications
Sheath replacement with retained wire
Antegrade balloon tamponade at arteriotomy
Covered Stent
IMP

24. Large Sheath Removal
Techniques and equipment for large bore access are improving
Educational opportunities and improved techniques and equipment are increasingly available
It is incumbent on Interventional Cardiologists to seek and acquire skills for rapid and effective deployment of MCS for best patient outcomes
Large bore access and closure is a critical element
IMP