Conflict of Interest Disclosure
• Abiomed
¡ Personal: None ¡ Sponsor of PROTECT-II trial and EBC travel
Hollenberg Ann Int Med 1999; 131:47-99
Pathophysiology
• When a critical mass of LV is necrotic and fails to pump, stoke volume and CO falls
• Myocardial and coronary perfusion are compromised causing tachycardia and hypotension
• Increased LVEDP further decreases coronary perfusion
• Increase LV wall stress increases myocardial oxygen demand
• Lactic acidosis worsens myocardial performance
Reducing the Work of the Heart Muscle Ventricular “Unloading”
3
Pres
sure
Volume
A
B C
D
A. End Diastole – Mitral Valve Closure B. Aortic Valve Opening C. End Systole - Aortic Valve Closure D. Mitral Valve Opening
§ Work = Pressure x Volume
§ Ventricular “Work” = Area of PV Loop
§ Unloading Work = Reducing Area of PV Loop
“PV Loop” of the Cardiac Cycle
Shock – Steps to be followed • STABILIZE the patient as rapidly as possible
¡ Pressors, fluids, WHATEVER to prevent the downward spiral
• Hemodynamic support!!
¡ Selection based upon risk-benefit assessment
• Revascularization as appropriate
¡ Make sure the revascularization targets the lesion(s) that are causing the shock
Finke et al JACC 2004; 44:340
Cardiac Power Is The Most Important Mortality Predictor in the SHOCK Trial
(Mean Arterial Pressure x Cardiac Output)
451
Cardiac Power =
0.2 0.4 0.6 0.8 1.0 1.2 1.4 1.6 1.8 2.0
0
10
20
30
40
50
60
70
80
90
100 Es
timat
ed In
-hos
pita
l Mor
talit
y (%
)
Cardiac Power Output
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 do the case and can worsen short and long term outcomes – ignore them at your peril..
High Risk PCI Patients (bifurcations)
Patient Comorbidities
Heart failure, diabetes, advanced age, peripheral vascular disease, complex lesions, unstable angina/NSTEMI, prior surgery
Hemodynamic Compromise
Depressed ejection fraction (LVEF<35%)
Complex Coronary
Artery Disease
Multi-vessel disease, Left Main disease Protected
PCI Patients
CCS Class III or IV Angina
Stress Test ���Med. Rx
High Risk ���Max Rx A A A A A
High Risk ���No/min Rx A A A A A
Int. Risk���Max Rx A A A A A Int. Risk���
No/min Rx U U A A A Low Risk���Max Rx U A A A A
Low Risk���No/min Rx I U A A A
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
Patients Most Appropriate for Revascularization
Coronary Revascularization Appropriateness Guidelines ACCF/SCAI/STS/AATS/AHA/ASNC/HFSA/SCCT1
1. Patel MR, et al, J AM Coll Cardiol. 2012;59(9); 857-881
Heart Failure Angina
Protected PCI Patients
= More Heart Failure
More Angina More Complex
= More likely to be
appropriate
Complexity
Sym
ptom
s
High Risk Findings on Noninvasive Study
Symptoms ���Med. Rx
Class III or IV ���
Max Rx A A A A A Class I or II���
Max Rx A A A A A Asymptomatic Max Rx U A A A A Class III or
IV ���No/min Rx A A A A A Class I or II���No/min Rx U A A A A Asymptoma
tic ���No/min Rx U U A A A
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
Complexity
Sym
ptom
s
A = Appropriate, U = Uncertain, I= Inappropriate A = Appropriate, U = Uncertain, I= Inappropriate
Revascularization Strategy by Risk Category
1. Levine GN, et al. J Am Coll Cardiol, 2011 Dec 6;58(24):e44-122, 2 Amsterdam EA, et al. Circulation. 2014 Dec 23; 130(25):e344-426
Low Medium High
Low PCI PCI PCI
Medium CABG or PCI
PCI or CABG Support & PCI
High CABG CABG or PCI Support & PCI
Surgical Risk
Ana
tom
ic R
isk
Protected PCI FDA Indicated
Safe & Effective
ACC/AHA PCI Guidelines1,2
SYNTAX Study
Often inoperable
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
IABP History
History: 1962 Animal studies
Moulopoulos et al, Am Heart J 1962;63:669-675 1968 Clinical description in shock
Kantrowitz et al, JAMA 1968;203:135-140 1973 Hemodynamic effects in shock,
Mortality unchanged Scheidt et al, NEJM 1973;288:979-984
>40 yrs >1 Million patients treated, low
complication rate, Benchmark registry Ferguson et al, JACC 2001;38:1456-1462
c/o H. Thiele
BCIS-1 Trial Design
• DESIGN: Prospective, randomized, control trial
• OBJECTIVE: To evaluate all cause long term mortality in patients with LV impairment (EF <30%) and severe CAD receiving elective IABP support during PCI.
• PRINCIPAL INVESTIGATOR Divika Perera, MD Kings College London, London, UK
301 patients enrolled between December 2005 an January 2009 in 17 clinical sites in
the United Kingdom
50% Planned IABP Use (N=150)
50% No Planned IABP Use (N=151)
12% Required Bailout IABP Use
(N=18)
Impaired LV function (EF < 30%) and
Extensive Myocardium at Risk BCIS-1 Jeopardy Score > 8
or...Target vessel supplying occluded vessel which supplies >40% of
myocardium
Perera et al, Am Heart J 2009;158:910-916
BCIS-1: Inclusion Criteria
Adverse Even
ts (%
) HR 0.94 (0.51 -‐ 1.76)
HR 0.11 (0.01 -‐ 0.49)
HR 1.86 (0.93 -‐ 3.79)
OR 0.61 (0.24 -‐ 1.62)
BCIS-1: Major Outcomes
Perera et al, JAMA 2010; 304(8):867-874
Hazard ratio 0.66 (95% CI 0.44 to 0.98)
0%
10%
20%
30%
40%
50%
Cum
ulat
ive
perc
enta
ge
150 139 130 117 93 52 19No IABP151 144 137 127 111 66 21IABP
0 6 m 1 year 2 years 3 years 4 years 5 years
Time since randomisation
IABP
No IABP
BCIS-1: All Cause Mortality
Perera et al, Circulation 2013; 127(2):207-12
IABP SHOCK-2 Design
• 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.
790 patients enrolled between June 2009 and March 2012 in 37 clinical sites in
Germany
190 patients excluded
600 patients randomized
Clinical follow-up at 30 days in
99.7% (N=300)
Medical Therapy
Clinical follow-up at 30 days in
99.7% (N=298)
Thiele H. et al, NEJM 2012
IABP
Mor
talit
y (%
)
Time after Randomization (Days)
P=0.92 by log-rank test Relative risk 0.96; 95% CI 0.79-1.17; P=0.69 by Chi2-Test
Primary Study Endpoint (30-Day Mortality)
Control 41.3%
IABP 39.7%
0
10
20
30
40
50
0 5 10 15 20 25 30
IABP SHOCK II
Thiele et al NEJM 2012
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
Randomized Trial of Impella vs. IABP in AMI with Shock (ISAR-SHOCK)
!
Adapted from Seyfarth et al., JACC 2008
(primary endpoint)
N=25
Hemodynamic Support Effectiveness: PROTECT II
CPO= Cardiac Power Output = Cardiac Output x Mean Arterial Pressure x 0.0022 (Fincke R, Hochman J et al JACC 2004; 44:340-348)
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
- 14.2 ± 27
p=0.001
PROTECT-II Trial Design
IMPELLA 2.5 + PCI
IABP + PCI
Primary Endpoint = 30-day Composite MAE* rate
1:1 R
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%
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
Impella ® Reduces Peri & Post Procedural MACCE
Dangas et al, Am. Journ of Cardiol. 2014: 113(2):222-8
MACCE = Death, Stroke, MI, Repeat revasc.
Impella
Time Post Procedure (day)
MA
CC
E (%
)
10 0 20 30 40 50 60 70 80 90
10
15
20
25
30
p=0.042
IABP
29% reduction
In MACCE
N=216
N=211
MACCE
FDA Approved Randomized
Controlled Trial Protect II
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 0.9374 – 1.7983 0.1161
Renal Insufficiency 1.2324 0.9545 – 1.5912 0.1089
Baseline worst TIMI flow: 0-1 1.3112 0.9596 - 1.7918 0.00889
Device: IMPELLA 0.7651 0.6099 - 0.9298 0.0206
Intention-To-treat Population
Use of atherectomy rotablation during index procedure
1.2787 0.9251 - 1.7676 0.1366
Renal Insufficiency 1.2466 0.9717 - 1.5992 0.0829
Baseline worst TIMI flow: 0-1 1.2340 0.9089 - 1.6752 0.1777
Device: IMPELLA 0.7944 0.6365 - 0.9914 0.0417
American Journal of Cardiology 2014
Clinical Guidelines for Impella ®
2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. Circulation ¡ Revascularization in Heart Failure: Class I ¡ Revascularization strategy based on degree,
severity, & extent of CAD; cardiac lesions; extent of LV dysfunction; prior revascularization. PVADS: Large amount of ischemic territory/poor LV function
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC ¡ High risk patients: Class IIb ¡ CLASS III: HARM without Hemodynamic support;
for PCI at hospitals without on-site cardiac surgery
Reimbursement and coding information: Inpatient Hospital = ICD.9 Code 37.68, commonly MS-DRG 216/217 Physician = CPT codes 33990 (insertion), 33992 (removal), 33993 (repositioning)
Categories referencing Impella include Percutaneous LVAD, PVAD, Non-durable MCS, TCS and percutaneous MCSD
2011 ACCF/AHA/SCAI Guideline for Percutaneous Coronary Intervention. JACC – PCI and Cardiogenic Shock: Class I Use of Mechanical Circulatory Support: American Heart Association. Circulation 2012 – Acutely decompensated heart failure patients: Class IIa
2013 Int’l Society for Heart & Lung Transplantation Guidelines for Mechanical Circulatory Support. Jnl of Heart & Lung Transplantation – Temporary mechanical support for patients with multi-organ failure:
Class I
2013 ACCF/AHA Guideline for the Management of Heart Failure, JACC – “Bridge to Recovery” or “Bridge to Decision” for patients with
acute, profound hemodynamic compromise: Class IIa
2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. Circulation – STEMI and Cardiogenic Shock: Class IIb – STEMI and urgent CABG: Class IIa
Protected PCI Additional Guidelines
FDA Indications for Use – Impella ® 2.5
• “The Impella 2.5 is a temporary (≤ 6 hours) ventricular support device indicated for use during high risk percutaneous coronary interventions (PCI) performed in elective or urgent, hemodynamically stable patients with severe coronary artery disease and depressed left ventricular ejection fraction, when a heart team, including a cardiac surgeon, has determined high risk PCI is the appropriate therapeutic option.
• Use of the Impella 2.5 in these patients may prevent hemodynamic instability which can result from repeat episodes of reversible myocardial ischemia that occur during planned temporary coronary occlusions and may reduce peri- and post-procedural adverse events.”
The product labeling allows for the clinical decision to leave Impella 2.5 in place beyond the intended duration of <6 hours due to unforeseen circumstances.
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?
There are no randomized, controlled studies on the efficacy
of parachutes
Umbrellas protect from rain – randomized studies not useful
Certain limitations of evidence-based medicine…
Courtesy H. Thiele (left) & A. DeMaria (right)