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)