1. Advanced Circulatory Support Trials
Clifford J Kavinsky, MD, PHD
Professor of Medicine and pediatrics
Associate Director, Center for Congenital and Structural Heart Disease
Rush University Medical Center

2. Conclusions
Mechanical circulatory support devices do not improve survival or reduce infarct size
in high risk patients undergoing PCI or in AMI complicated
by cardiogenic shock
There is no convincing randomized trial data that suggests that
newer pVADs are superior to traditional IABP in terms of mortality benefit
pVADs provide superior hemodynamic support then IABP
Newer pVADs require a greater learning curve and their own
set of complications
mechanical circulatory support devices may provide greater
hemodynamic stability and safety in performing coronary revascularization
procedures in high risk and unstable patient subsets

3. Adrian Kantrowitz ( )
Performed first Heart transplant in US (1967)
Designed and implanted first LVAD (1972)
Designed and first used Intra-aortic Balloon Pump (IABP)

4. Introduction of the IABP
Kantrowitz et al 1968 JAMA 203:135

5. BenchmarkSM Counterpulsation Outcomes Registry*
JACC 2001

6. 856 patients with acute myocardial Infarction complicated
by cardiogenic shock
Examined impact of Thrombolytic therapy and IABP on mortality
Shock Trial registry (Should we emergently revascularize Occluded Coronaries for cardiogenic shocK)

7. Shock Trial Registry In-hospital Mortality rates
Revascularization rates differed in the four groups and impacted survival significantly
No TT, No IABP-18%
IABP only-70%
TT only-20%
TT and IABP-68%
Mortality- 39% with revascularization and 78% without revascularization
Sanborn et al 2000 JACC 36, Supp A:1123

8. Antman et al 2004 Circ 110:588

9. ACC/AHA Guidelines for
STEMI
Class I Indications for IABP
Intra-aortic balloon counterpulsation should be used in STEMI
patients with hypotension who do not respond to other interventions,
unless further support is futile because of the patient’s wishes or
contraindications/unsuitability for further invasive care (level of evidence B)
Intra-aortic balloon counterpulsation is recommended for STEMI patients
with low-output state (level of evidence B).
when cardiogenic shock is not quickly reversed with pharmacologic therapy
(level of evidence B)
Intra-aortic balloon counterpulsation should be used in addition to medical therapy
for STEMI patients with recurrent ischemic-type chest pain, poor LV function,
or a large area of myocardium at risk (level of evidence C)
1) Hypotension defined as SBP <90 or 30 mm below baseline

10. Prophylactic IABP for High Risk
AMI PCI
Ongoing CP up to 12 hours
ECG evidence of STEMI
Cardiogenic shock excluded
All went to cath lab. PCI deferred if infarct related vessel patent with ,70% lesion, or small vessel
After cath procedure patients stratified into high or low risk groups
High risk defined as one or more of the following: >70 y/o, LVEF <45%, vein graft occlusion, persistent ventricular arryhthmias, or suboptimal PCI result
Multicenter, randomized trial (34 institutions)
Primary PCI for AMI
High risk patients randomized to h IABP or not
Primary endpoint: in-hospital death, reinfarction, vessel
reocclusion, stroke, sustained hypotension or CHF
Stone et al 1997 JACC 29:1459

11. Prophylactic IABP in High Risk
AMI PCI
Stone et al 1997 JACC 29:1459

12. Seven randomized trials of IABP therapy in STEMI
1009 patients. High risk had varying inclusion criteria: STEMI with suboptimal PCI result, STEMI with poor ST segment resolution, failed thrombolysis, Killip class >1, large ischemic area at risk.
STEMI patients with cardiogenic shock (10,529 patients
Seven randomized trials of IABP therapy in STEMI
Nine non-randomized cohort studies of IABP therapy in STEMI
patients with cardiogenic shock
No randomized trial of STEMI patients in cardiogenic shock

13. IABP In High Risk STEMI
IABP support was not associated with change in 30 mortality or LVEF
Sjauw et al 2009 Eur H J 30:459

14. IABP in Cardiogenic Shock
11% reduction in mortality with IABP
Sjauw et al 2009 Eur H J 30:459

15. IABP-SHOCK II Trial
First randomized trial of IABP in Cardiogenic shock
University of Leipzig and others, all in Germany
randomized, prospective, open-label, multicenter trial
600 patients with cardiogenic shock complicated AMI
randomized to IABP (301 patients) or not (299 patients)
all patients were expected to receive early revascularization
and best medical therapy
30-day all-cause mortality

16. IABP-SHOCK II Trial
Clinical Outcomes
Thiele et al 2012 NEJM 367:1287

17. IABP-SHOCK II Trial Time-to-Event Curves for the Primary End Point
Thiele et al 2012 NEJM 367:1287

18. Open, multicenter, randomized controlled trial
337 patients with acute anterior STEMI without cardiogenic shock
30 sites in 9 countries
IABP before primary PCI and continued for at least 12 hours
Primary endpoint was Infarct size as determined by MRI (3-5 days)
CRISP AMI-Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction Trial
Patel et al 2011 JAMA 306:1329

19. CRISP-AMI Trial
Among patients with acute anterior STEMI without shock, IABP plus
primary PCI compared with PCI alone did not reduce Infarct size

20. TandemHeart™pLVAD CardiacAssist, Pittsburgh, Pa
Left atrial-to-femoral arterial LVAD
Low speed centrifugal continuous flow pump
21F venous transseptal cannula
17F arterial cannula
Maximum flow 4L/minute
FDA approved for up to 6 hours
Used in over 2000 patients

21. TandemHeart™pLVAD
p=NS
Thiele- randomized followup study to compare use of IABP to TandemHeart for patients with AMI complicated by CS. Twenty patients in each arm. No difference in Mortality. Improved hemodynamics.
Burkoff-Randomized multicenter trial in the US comparing TandemHeart to IABP for patients presenting within 24 hours of developing CS. Primary endpoint was superior hemodynamics. Secondary endpoint was 30 day survival. 33 patients randomized. TandemHeart provided greater increases in CI and decreases in PCWP. Independent data safety monitoring board reviewed data and concluded that hemodynamic effects of TandemHeart were superior and that no conclusion could be made regarding survival and the study was halted.
Improved haemodynamic parameters (Cardiac Index, MAP,PCWP)
Increase in bleeding, limb ischemia, and sepsis
Thiele EHJ 2005;26:1276. Burkhoff AHJ 2006;152:e1

22. IMPELLA® RECOVER®2.5 pVAD System
Advances retrograde across AV
Single arterial access
Advances over .018” wire
2.5 L/Min flow
FDA approved for up
to 6 hours
no need for inotropic
support

23. IMPELLA® RECOVER®2.5 pVAD System
Clinical Studies

24. Protect II Randomized Trial
A prospective Randomized Trial of Hemodynamic Support
With Impella 2.5™versus Intra-Aortic Balloon Pump
In Patients undergoing High risk Percutaneous
Coronary Intervention
O’neill et al 2012 Circ

25. Protect II Randomized Trial
Elective PCI
Unprotected Left main or last remaining patent coronary vessel
Three vessel CAD
LVEF 30-35%
1:1 randomization of Impella 2.5™ vs IABP
Composite endpoint Major Adverse Events at discharge or 30 day followup
all-cause death
Myocardial infarction
TIA/stroke
Repeat revascularization
Need for cardiovascular surgery
Acute Renal Failure
Severe hypotension
Cardiopulmonary Resuscitation
Ventricular Tachycardia requiring cardiovresion
Aortic insufficiency
Failed PCI
Data and satety monitoring Board terminated trial early based on futility

26. Assessed for Eligibility
Protect II Randomized Trial
Assessed for Eligibility
N=1082
Randomized
Intent-to-Treat
N=447
Intent-To-Treat (ITT) population
(N=447)
IMPELLA
N= 224
90day F/U, N=222
IABP
N= 223
90day F/U, N=220
(N=12)
(N=9)
1 withdrew consent post PCI (alive)
1 EF >=35%
1 Not 3VD or ULM
3 Active MI
1 Severe PVD
1 Platelets<70000
1 Creatinine>4
2 withdrew consent post PCI (alive)
3 EF >=35%
3 Not 3VD or ULM
1 Active MI
2 Severe PVD or AS
IMPELLA
30day N= 215
90day F/U, N=213
IABP
30day N= 211
90day F/U, N=210
Per Protocol (PP) population
(N=426)

27. Protect II Randomized Trial
Procedural Characteristics
IABP
(N=223)
Impella
(N=224)
p-value
Use of Heparin
82.4%
93.5%
<0.001
IIb/IIIa Inhibitors
26.1%
13.5%
0.001
Total Contrast Media (cc)
241±114
267±142
0.037
Rotational Atherectomy (RA)
9.5%
14.9%
0.088
Median # of RA Passes/lesion (IQ range)
1 (1-2)
3 (2-5)
Median # of RA passes/pt (IQ range)
2.0 ( )
5.0 ( )
0.004
Median RA time/lesion (IQ range sec)
40 (20-47)
60 (40-97)
0.005
RA of Left Main Artery
3.1%
8.0%
0.024
% of SVG Treatment or RA use
17.5%
25.4%
0.041
Total Support Time (hour)
8.2±21.1
1.9±2.7
Discharge from CathLab on device
37.7%
5.7%

28. Per Protocol= Patients that met all incl./ excl. criteria.
PROTECT II MAE Outcome
IABP
IMPELLA
MAE= Major Adverse Event Rate
Intent to Treat (N=447)
p=0.312
N=224
N=223
p=0.087
N=222
N=220
p=0.100
N=215
N=211
↓ 21% MAE
p=0.029
N=213
N=210
Per Protocol (N=426)
Per Protocol= Patients that met all incl./ excl. criteria.

29. PROTECT II 90-day Outcome (PP)
HRPCI w/o Atherectomy (N=371, 88%)
HRPCI with Atherectomy (N=52, 12%)
IMPELLA
IABP
IMPELLA
IABP
Composite
35.9%
51.1%
(p=0.003)
68.8%
55.0%
(p=0.316)
Death
MI (>3x ULN)
Stroke/TIA
Repeat Revascularization
Vascular Complication
Acute Renal Dysfunction
Severe Hypotension
CPR / VT
Aortic Insufficiency
Angio Failure
11.6%
8.9%
(p=0.399)
12.5%
10.0%
(p=0.784)
14.9%
17.4%
(p=0.522)
(p=0.03)
37.5%
10.0%
1.1%
2.6%
(p=0.280)
3.1%
0.0%
(p=0.425)
6.6%
10.5%
(p=0.181)
3.1%
30.0%
(p=0.006)
2.8%
3.7%
(p=0.616)
0.0%
5.0%
(p=0.202)
7.7%
11.6%
(p=0.211)
21.9%
10.0%
(p=0.271)
9.4%
12.1%
(p=0.400)
18.8%
20.0%
(p=0.911)
12.7%
10.0%
(p=0.411)
9.4%
15.0%
(p=0.537)
0.0%
0.0%
0.0%
0.0%
4.4%
2.1%
(p=0.208)
0.0%
0.0%
Per Protocol (PP)= Patients that met all incl./ excl. criteria.

30. Conclusions
Mechanical circulatory support devices do not improve survival or reduce infarct size
in high risk patients undergoing PCI or in AMI complicated
by cardiogenic shock
There is no convincing randomized trial data that suggests that
newer pVADs are superior to traditional IABP in terms of mortality benefit
pVADs provide superior hemodynamic support then IABP
Newer pVADs require a greater learning curve and their own
set of complications
mechanical circulatory support devices may provide greater
hemodynamic stability and safety in performing coronary revascularization
procedures in high risk and unstable patient subsets