Form 8-K

0001193125-12-495588.txt : 20121207 0001193125-12-495588.hdr.sgml : 20121207 20121207172938 ACCESSION NUMBER: 0001193125-12-495588 CONFORMED SUBMISSION TYPE: 8-K PUBLIC DOCUMENT COUNT: 65 CONFORMED PERIOD OF REPORT: 20121206 ITEM INFORMATION: Other Events ITEM INFORMATION: Financial Statements and Exhibits FILED AS OF DATE: 20121207 DATE AS OF CHANGE: 20121207 FILER: COMPANY DATA: COMPANY CONFORMED NAME: ABIOMED INC CENTRAL INDEX KEY: 0000815094 STANDARD INDUSTRIAL CLASSIFICATION: SURGICAL & MEDICAL INSTRUMENTS & APPARATUS [3841] IRS NUMBER: 042743260 STATE OF INCORPORATION: DE FISCAL YEAR END: 0331 FILING VALUES: FORM TYPE: 8-K SEC ACT: 1934 Act SEC FILE NUMBER: 001-09585 FILM NUMBER: 121251082 BUSINESS ADDRESS: STREET 1: 22 CHERRY HILL DR CITY: DANVERS STATE: MA ZIP: 01923 BUSINESS PHONE: 9787775410 MAIL ADDRESS: STREET 1: 22 CHERRY HILL DRIVE CITY: DANVERS STATE: MA ZIP: 01923 8-K 1 d450930d8k.htm FORM 8-K Form 8-K

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM 8-K

CURRENT REPORT

PURSUANT TO SECTION 13 OR 15(D) OF THE

SECURITIES EXCHANGE ACT OF 1934

Date of Report (Date of earliest event reported): December 6, 2012

ABIOMED, Inc.

(Exact Name of Registrant as Specified in Charter)

Delaware

001-09585

04-2743260

(State or other jurisdiction

of incorporation)

(Commission

File Number)

(IRS Employer

Identification Number)

22 Cherry Hill Drive

Danvers, MA 01923

(Address of principal executive offices) (Zip Code)

(978) 646-1400

(Registrant’s telephone number, including area code)

Not Applicable

(Former Name or Former Address, if Changed Since Last Report)

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below).

¨	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

¨	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

¨	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

¨	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Item 8.01

Other Events.

On December 6, 2012, we issued a press release announcing that the U.S. Food and Drug Administration’s (FDA) Circulatory System Devices Panel voted to retain Class III status for the temporary ventricular support devices within the non-roller type cardiopulmonary bypass blood pumps category, under which our Impella products are categorized. A copy of the press release is attached as exhibit 99.1 to this current report on Form 8-K and incorporated herein by reference.

Dr. David Weber our Chief Operating Officer, Dr. Jeffrey Popma of Beth Israel Deaconess Medical Center in Boston and Dr. William O’Neill of Henry Ford Hospital led a presentation to the FDA’s Circulatory System Devices Panel related to the classification of our Impella devices on December 6, 2012. A copy of the slides used in the presentation is attached as exhibit 99.2 to this current report on Form 8-K and incorporated herein by reference. Also attached as exhibit 99.3 to this current report on Form 8-K and incorporated herein by reference is a copy of a summary we provided to the FDA on December 6, 2012 listing clinical and scientific publications on the Impella 2.5, Impella 5.0 and Impella LD.

Item 9.01

Financial Statements and Exhibits

(d) Exhibits


Number		Description

99.1		Press release dated December 6, 2012.

99.2		Abiomed Presentation to FDA 515i Panel Classification Determination for Non-roller Type CPB Pumps dated December 6, 2012.

99.3		Impella Clinical Literature Summary.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.


ABIOMED, Inc.

By:		/s/ Robert L. Bowen
		Robert L. Bowen
		Vice President and Chief Financial Officer

Date: December 7, 2012

EX-99.1 2 d450930dex991.htm PRESS RELEASE DATED DECEMBER 6, 2012 Press release dated December 6, 2012

Exhibit 99.1

LOGO

FDA 515i RECLASSIFICATION PANEL RECOMMENDS CLASS III STATUS FOR TEMPORARY

VENTRICULAR SUPPORT DEVICES IN THE NON-ROLLER

TYPE CARDIOPULMONARY BYPASS BLOOD PUMPS CATEGORY

DANVERS, Mass. — December 6, 2012 – Abiomed, Inc. (NASDAQ: ABMD), a leading provider of breakthrough heart support technologies, today announced that the U.S. Food and Drug Administration’s (FDA) Circulatory System Devices Panel voted to retain Class III status for the temporary ventricular support devices within the non-roller type cardiopulmonary bypass blood pumps category, which includes Impella^®. The 515i Reclassification Panel’s confirmation of this category of device as Class III devices is consistent with both the current Class III classification for these device types and as recommended in the FDA’s briefing documents, released on December 3, 2012.

“We would like to thank the 515i Panel and FDA for their time and consideration, as well as Dr. Jeffrey Popma of Beth Israel Deaconess Medical Center and Dr. William O’Neill of Henry Ford Hospital, who highlighted the compelling body of clinical evidence supporting Impella, including the PROTECT II data set,” said Michael R. Minogue, President, Chairman and Chief Executive Officer, Abiomed. “We look forward to collaborating with the FDA on next steps and agree with the 515i Panel’s feedback that our existing data, combined with our U.S. registry, position us to work with the FDA to submit a PMA application. We welcome the opportunity for a PMA to strengthen our existing marketing clearances and expand the indications for Impella patients.”

The FDA’s 515i program is designed to review all previously 510(k) cleared Class III devices and determine the appropriate controls to ensure safety and effectiveness for the intended use of these product categories. The classification of Impella as a Class III device requires Pre-Market Approval (PMA) controls (versus prior 510(k) Class III special controls) to ensure safety and effectiveness in the intended use. As per the 515i Reclassification Process and confirmed by the FDA Panel, products will remain on the market for a sufficient period to allow for manufacturers to submit and the FDA to review Pre-Market Approval applications.

As per the statues of the 515i program, there is no change to the current 510(k) clearance for Impella throughout the remaining steps of the reclassification process for Non-Roller Type Cardiopulmonary Bypass Pumps. Following yesterday’s Panel recommendation, the next steps in the 515i process include FDA issuance of a Proposed Final Order, followed by a period of public comment, FDA issuance of a Final Order, and then submission of Pre-Market Approval applications by manufacturers with devices in the category. Throughout this series of reclassification steps, Abiomed will continue to market the Impella family of heart pumps and looks forward to working with FDA to submit the necessary clinical data under the PMA application process.

Abiomed will host a conference call on Wednesday, December 12, 2012 at 1:00 p.m. ET to discuss the 515i Reclassification Panel in further detail. To listen to the call live, please tune into the webcast via http://investor.abiomed.com or dial (855) 212-2361; the international number is (678) 809-1538. A replay of this conference call will be available beginning at 4:00 p.m. ET on December 12, 2012 through 11:59 p.m. ET on December 19, 2012. The replay phone number is (855) 859-2056; the international number is (404) 537-3406. The replay access code is 79263798.

ABOUT ABIOMED

Based in Danvers, Massachusetts, Abiomed, Inc., is a leading provider of medical devices that provide circulatory support. Our products are designed to enable the heart to rest by improving blood flow and/or performing the pumping of the heart. For additional information please visit: www.abiomed.com

FORWARD-LOOKING STATEMENTS

This release contains forward-looking statements, including statements regarding expected patient outcomes, development of Abiomed’s existing and new products, the Company’s progress toward commercial growth, and future opportunities and expected regulatory approvals. The Company’s actual results may differ materially from those anticipated in these forward-looking statements based upon a number of factors, including uncertainties associated with development, testing and related regulatory approvals, including anticipated future losses, complex manufacturing, high quality requirements, dependence on limited sources of supply, competition, technological change, government regulation, future capital needs and uncertainty of additional financing, and other risks and challenges detailed in the Company’s filings with the Securities and Exchange Commission, including the Annual Report filed on Form 10-K and most recently filed Quarterly Report on Form 10-Q. Readers are cautioned not to place undue reliance on any forward-looking statements, which speak only as of the date of this release. The Company undertakes no obligation to publicly release the results of any revisions to these forward-looking statements that may be made to reflect events or circumstances that occur after the date of this release or to reflect the occurrence of unanticipated events.

For further information please contact:

Susie Lisa, CFA

Senior Director, Investor Relations and Corporate Development

978-646-1590

slisa@abiomed.com

Aimee Genzler

Corporate Communications Manager

978-646-1553

ir@abiomed.com

EX-99.2 3 d450930dex992.htm ABIOMED PRESENTATION TO FDA 515I PANEL CLASSIFICATION Abiomed Presentation to FDA 515i Panel Classification

Abiomed Presentation to FDA 515i Panel

Classification Determination for Non-roller

Type CPB Pumps

December 6, 2012

David Weber, PhD

Product and Regulatory Operations

Abiomed

Exhibit 99.2

Abiomed

•

U.S. Medical Device firm

•

Headquartered in Danvers, Massachusetts

•

450 employees

•

Expertise in pumping blood for over 30 years

•

Products & Clearance/Approvals:

–

Extracorporeal Ventricular Assist Devices (1

VADs in US); PMA for

Heart Recovery, 1992

–

Total Artificial Heart; HDE, 2007

–

IABP; 510(k) Clearance, 2007

–

Impella Microaxial Pumps; First 510(k) Clearance, 2008

•

Considerations for classification of

Impella for durations of support up to

6 hours

•

Discussion of Supporting Valid

Scientific Evidence

•

Controls & Concluding

Recommendations

•

Q&A

David Weber, PhD

Abiomed

Jeffrey Popma, MD

Beth Israel Deaconess

Medical Center, Boston

David Weber, PhD

William O’Neill, MD

Henry Ford Hospital, Detroit

Outline

Evolution of Nonroller-Type CPB Pumps

Expansion of “On Pump”

Concept to Cath Lab, EP lab

Surgical

Cardiopulmonary Bypass

(centrifugal)

Percutaneous

Cardiac Support

(centrifugal)

Percutaneous

Cardiac Support

(micro-axial)

Percutaneous

Cardiopulmonary Support (CPS)

(centrifugal)

1960s

1980s

Surgery suite

Cath Lab

•

Reduced size

•

Reduced invasiveness

•

Faster set up

EP Lab

FDA

Clearance

for

Impella

2.5

(K063723)

Supporting Clinical Data

•

Total of 129 patients

•

100% from patients provided partial

circulatory support (

6 hrs) during

high risk PCI procedures

(n=20 from

FDA Safety Study

, n=109 from EU

registry)

•

510(k) Summary for K063723:

“Abiomed provided a detailed analysis

based on clinical data from a

combination of 109 OUS and 20 US

patients to address patient safety”

1. Dixon, et al., JACC, 2009

Since its 510(k) clearance in 2008, > 15,000 implants have been performed,

~12,000 in the U.S.

Impella

Device

Impella

Use in United States Since Clearance

For use up to 6 hours, 90% of Impella use is for temporary

ventricular support in the setting of HRPCI

•

Median duration of support during HRPCI is 60-80mins

1,2

•

Majority of patients are surgical turn-downs

mins

median

support

duration,

Registry

(Maini

al.,

CCI,

2012)

78 mins median support duration, PROTECT II Study (O’Neill et al., Circulation, 2012)

64%

deemed

inoperable

site

surgical

consultants

PROTECT

(O’Neill

al.,

Circulation,

2012)

Sufficient

Evidence

Impella

Identify

Risks and Benefits

193 peer-reviewed publications since 1994

124 publications Meet Definition of “Valid Scientific Evidence”

57 pertain to use 6 hours

CFR

Section

860.7(c)(2):

“Valid

Scientific

Evidence”

–

Well-controlled investigations

–

Partially controlled studies

–

Studies or objective trials without matched controls

–

Well-documented case histories

–

Reports of significant human experience

Largest Studies Supporting Reasonable

N = 564 patients, 245 in FDA-approved protocol

EU Registry

US Registry

IDE Safety

Study

IDE Randomized

Study

Study name

Europella

USpella

PROTECT I

PROTECT II

Period

2004 -

2007

2009 -

2010

2006

-2007

2007-

2010

Tot. Patients

HR PCI , N=144

HR PCI , N=175

HR PCI, N=20

HR PCI, N=225 (Impella)

Tot. Centers

112

Publication

JACC, 2009

CCI, 2012

JACC, 2009

Circulation, 2012

Conclusion

“This large

multicenter registry

supports the safety,

feasibility, and

potential usefulness

of hemodynamic

support with Impella

2.5 in HR PCI.”

“The use of

Impella 2.5 in

HR PCI

appeared

feasible and safe

in the real-world

setting.”

“The Impella 2.5

system is safe,

easy to implant,

and provides

excellent

hemodynamic

support during

HR PCI.”

“The 30

day incidence of MAE

was not different for patients

with IABP or Impella

2.5

hemodynamic support.

However, trends for improved

outcomes were observed for

Impella

2.5 supported patients

at 90-days.”

Assurance of Safety & Effectiveness

FDA 515i Panel Classification Determination

for Non-roller Type CPB Pumps

Clinical Evidence

December 6, 2012

Jeffrey J. Popma, MD

Director, Interventional Cardiology, BIDMC

Professor of Medicine, Harvard Medical School

Disclosures: Research Grant, Advisory Board (1), Travel

Clinical Summary: Objectives-I

•

FDA Executive Summary identified 5 studies using the

Impella 2.5 device, comprising 231 patients undergoing

HR-PCI. We would request that the Panel also consider

additional analyses published after the 2011

ACC/AHA/SCAI guidelines not included in the FDA

Summary.

•

O’Neill et al The PROTECT II study. Circ 2012;126(14):1717-27.

Dangas

et al (abstr). J Am Coll

Cardiol

2012:60:B21

Popma

et al. (abstr), J Am Coll

Cardiol

2012:59:A372

•

The USpella

Registry. CCI 2012;80(5):717-25.

Clinical Summary: Objectives-II

•

FDA Executive Summary provides a preliminary

overview of the primary endpoint of the PROTECT-II

study as described by the DSMB. We would request that

the Advisory Panel also consider:

PROTECT-II Pre-defined analysis population (PP)

PROTECT-II: Four pre-defined subgroup analyses

Other Registries and post-hoc analyses that describe

the totality of clinical evidence supporting the

reasonable safety and efficacy of the Impella 2.5

Impella 2.5 Clinical Evidence Base (N=799*)

Three

Prospective

Clinical Trials

Design Type

Used in FDA

Submissions

Number of

Patients

Published in

PROTECT

Safety

Feasibility

Yes

JACC Interv.

2009

PROTECT

Randomized

Yes

452 (225)

Circulation 2012

Cardio

ByPass

Randomized

199 (105)

EJCTS 2002

Two Post Market High Risk PCI Registries

Euro Registry

Multicenter

Open

Yes

144

JACC 2009

U.S. Registry

Multicenter

Open

175

CCI 2012

* Does not include control arm patients for randomized trials

•

In cardiogenic shock

Improvement in cardiac index (ISAR-SHOCK)

0.49±0.46 L/min/M

v. 0.11±0.31 L/min/M

with IABP (P < 0.02)

Increase in mean arterial pressure (USPella)

83±17 mmHg v. 59±15 with control-IABP (P < 0.0001)

•

In Elective High Risk PCI

Improved Hemodynamics with Impella 2.5

Seyfarth

al.

JACC.

2008;42:1594-8;

USpella

Registry.

Transcatheter

Therapeutics

2011

O’Neill, et al., Circulation. 2012;126:1717-1727

Preserved cardiac power output with Impella v. IABP

-4.2±24 v. -14.2±27 with IABP (P=0.001)

Pre-PCI

During PCI

Inoperable High-Risk PCI:

Hemodynamic Stability with Impella 2.5

Left Main –

Sole Remaining Vessel

LVEF < 35%

Inoperable High-Risk PCI:

Hemodynamic Stability with Impella 2.5

Safety: Risks For Temp Ventricular Support

Adapted from FDA Executive Summary: References in Appendix

Potential Risks (use <

6 hrs)

Reasonable Assurance to Support Safety

Alteration in

Blood Composition

Large prospective RCT (N=199 patients) showed

favorable results of Impella compared to CPB in OPCABG

with respect to blood interaction

Inadequate

Tissue Perfusion

Prospective RCT showed superior hemodynamic support

and better tissue perfusion with Impella vs IABP

Embolism

Stroke = 0.5%

1,2,4,5

Non-CNS

thromboembolism

0.8%

Duration of Use

Median

ranges

from

[45;127]

[52,113]

min.

1,2,4,5

Fluid Leakage

Access

site

bleeding

req.

transfusion

3.6%

1,3,7

Device leakage malfunction = 0.2%

1,3

References in Appendix

Safety: Risks For Temp Ventricular Support

Potential Risk (use <

6 hrs)

Reasonable Assurance to Support Safety

Adverse Tissue Reaction

Two Large prospective RCT showed no evidence

of adverse tissue

or blood

reaction compared to

IABP

or CPB

respectively

Infection

3.2%

1,2,4,5

Structural / Tissue Damage

0% in 3 FDA trials and registries (N=564)

1,2,3,5,6,7

0.06% including all Impella literature in PubMed

(1/1697 patients in 197 publications)

Local Heat Generation

Stroke= 0.5%

Non-CNS Thromboembolism (PE, DVT) = 0.8%

Flow Dynamics

Hemolysis rate = 0.8%

1,3,6,7

RCT showed no complement activation and lower

inflammatory response compared to CPB

1,3

CABG is Preferred in Patients with Complex

Anatomy and Less Than High Surgical Risk

PROTECT II Trial Design

IMPELLA 2.5 +

PCI

IABP +

PCI

Primary Endpoint = 30-day Composite MAE* rate

1:1

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, MI (>3xULN CK-MB or Troponin) , Stroke/TIA, 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

Risk Assessment: SYNTAX vs PROTECT-II

SYNTAX

(n=903)

PROTECT

(n=448)

Age (Mean±SD)

65±10

67±11

Diabetes (%)

Prior MI (%)

CHF (%)

Prior PCI (%)

Prior CABG (%)

LVEF

30%

(%)

1.3

Not Surgical Candidate (%)

Euroscore

(Mean±SD)

4±3

18±18

PCI

arm

SYNTAX

trial,

Serruys

al.

Engl

Med.

2009;

O’Neill

al.

Circulation

2012

PROTECT II Enrollment & Milestones

Initial

Goal: 654 pts

Time for data collection

for interim analysis

2008

2010

2009

2011

+ 125 Patients

11/27/2007

PROTECT II

1st

Patient

6/2/2008

510(k)

Clearance

2/26/2010

50% Enrollment

Achieved

(N=327)

12/6/2010

69% Enrollment

(N=452)

12/6/2010

Trial Halted for Futility

Determination*

*PROTECT

protocol

Stopping

rule

for

futility

power at interim analysis <40%.

Conditional

PROTECT II: ITT MAE (N=448)

IABP

IMPELLA

MAE= Major Adverse Event Rate.

p=0.277

N=225

N=223

p=0.066

N=224

N=219

Log rank test, p=0.147

IABP

IMPELLA

40.1%

49.3%

35.1%

40.6%

30 day MAE

90 day MAE

Adverse Events Directly Attributed to the

Device (90 days)

Impella

(N=225)

IABP

(N=223)

Death

Stroke/TIA

Myocardial Infarction

Repeat Revascularization

Need for Cardiac ,Thorac. or Vasc. Operation

Acute Renal Dysfunction

CPR or VT req. Cardioversion

Increase in Aortic Insufficiency

Severe Hypotension

Total

CEC Adjudicated Adverse Events Directly

Related to the Device in PROTECT II

PROTECT-II: Additional Analyses in SAP

•

Pre-Specified Population Analyses: Per Protocol

•

Predefined Secondary Analysis:

Learning Curve

Operator-Technique (Rotational Atherectomy)

Anatomic Indications (Left Main v. 3 V CAD)

Extreme Surgical Co-Morbidity (STS PROM)

PROTECT II: Per Protocol MAE (N=427)

p=0.092

N=216

N=211

p=0.023

N=215

N=210

IABP

IMPELLA

42.2%

51.0%

34.3%

40.0%

30 day MAE

90 day MAE

Log rank test, p=0.048

IABP

IMPELLA

90 day MAE

Relative Risk

[95% CI]

Relative Risk

[95% CI]

Group

p-value

1.02 [0.70, 1.48]

0.936

0.76 [0.59, 0.97]

0.029

0.92 [0.62, 1.38]

0.697

0.74 [0.58, 0.95]

0.016

Learning Curve: 1st

Patient Excluded

1 Impella/IABP Patient @ each site (n=119)

Intent-to-Treat

Impella better

IABP better

0.0

0.5

1.0

1.5

2.0

Per Protocol

After 1 Impella/IABP Pt @ each site

(n=324)

1 Impella/IABP Pt @ each site (n=116)

After 1 Impella/IABP Pt @ each site

(n=309)

90 day MAE

Relative Risk

[95% CI]

Relative Risk

[95% CI]

Group

p-value

0.75 [0.59, 0.95]

0.014

1.19 [0.75, 1.91]

0.444

0.70 [0.55, 0.89]

0.003

1.19 [0.75, 1.91]

0.444

Rotational Atherectomy: Sub-group

Atherectomy (n=52)

Atherectomy (n=391)

Intent-to-Treat

Impella better

IABP better

0.0

0.5

1.0

1.5

2.0

Atherectomy (n=52)

Atherectomy (n=373)

Per Protocol

90 day MAE

Relative Risk

[95% CI]

Relative Risk

[95% CI]

Group

p-value

0.88 [0.59, 1.33]

0.552

0.81 [0.63, 1.03]

0.077

0.82 [0.53, 1.25]

0.351

0.78 [0.61, 0.99]

0.039

Anatomy Sub-group: Left Main vs 3VD

Left Main / Last Conduit (n=106)

Intent-to-Treat

Impella better

IABP better

0.0

0.5

1.0

1.5

2.0

Per Protocol

Left Main/ Last conduit (n=101)

3VD (n=324)

3VD (n=337)

90 day MAE

Relative Risk

[95% CI]

Relative Risk

[95% CI]

Group

p-value

1.08 [0.71, 1.63]

0.733

0.77 [0.61, 0.98]

0.030

1.14 [0.75, 1.71]

0.540

0.71 [0.56, 0.91]

0.006

Excessive Surgical Co-Morbidity

STS

10 (n=73)

Intent-to-Treat

Impella better

IABP better

0.0

0.5

1.0

1.5

2.0

Per Protocol

STS < 10 (n=370)

STS 10 (n=71)

STS < 10 (n=354)

Ongoing US Impella Registry

•

Observational open registry for Impella in North America

•

Sites invited to participate on June 10, 2009

•

949 patients enrolled to-date at 41 centers

•

Includes all consecutive, unselected patients at each site

•

Data obtained after IRB approval

•

Data monitoring against source documentation

•

Independent CEC for events adjudication (2 Cardiologists + 1

CT Surgeon)

•

CEC adjudicated events per FDA Impella 2.5 study definitions

Consistent Results in High-Risk PCI Impella Registries

Registry

(175)

Registry

(N=144)

30 day Outcomes (%)

Death related to the device

All causes of Death

Myocardial Infarction

Stroke

Revascularization

Bleeding req. surgery

Site bleeding req. transfusion

Vascular complications

Valve damage

Hemolysis

4.0

1.1

0.6

1.7

3.4

4.0

5.5

0.7

5.5

4.0

0.7

Sjauw et al. J Am Coll Cardiol. 2009;54(25):2430-4. ²Maini et al. Catheter Cardiovasc Interv. 2012;80(5):717-25.;

Summary

•

Safety concerns mitigated with review of all

available clinical evidence associated with the use

of the Impella 2.5

•

Substantial improvements in hemodynamics have

been demonstrated with Impella 2.5 v. IABP

•

Examination of the totality of the clinical evidence

associated with the use of the Impella 2.5 v. IABP

support efficacy in defined patient populations

Conclusion

•

Comprehensive review of the totality of clinical

evidence associated with the use of the Impella

2.5 device for its labeled “< 6 hour”

indication

supports the safety and efficacy of this device,

particularly in patients undergoing high-risk PCI

•

Ongoing surveillance with a comprehensive

National Registry is recommended to understand

patient outcomes for these and other indications

when applied beyond a randomized study

References

1. Dixon SR, Henriques JP, Mauri L, Sjauw K, Civitello A, Kar B, Loyalka P, Resnic FS, Teirstein P, Makkar R, Palacios IF, Collins M, Moses J, Benali K, O'Neill WW. A

prospective feasibility trial investigating the use of the Impella 2.5 system in patients undergoing high-risk percutaneous coronary intervention (The PROTECT I Trial): initial

U.S. experience.. JACC Cardiovasc Interv. 2009 (2):91-6.

2. Griffith BP, Anderson MB, Samuels LE, Pae WE Jr, Naka Y, Frazier OH.The RECOVER I: A multicenter prospective study of Impella 5.0/LD for postcardiotomy circulatory

support. J Thorac Cardiovasc Surg. 2012 Mar 9. [Epub ahead of print]

3. O'Neill WW, Kleiman NS, Moses J, Henriques JP, Dixon S, Massaro J, Palacios I, Maini B, Mulukutla S, Dzavík V, Popma J, Douglas PS, Ohman M. A prospective,

randomized clinical trial of hemodynamic support with Impella 2.5 versus intra-aortic balloon pump in patients undergoing high-risk percutaneous coronary intervention: the

PROTECT II study. Circulation. 2012 ;126(14):1717-27.

4. Seyfarth M, Sibbing D, Bauer I, Fröhlich G, Bott-Flügel L, Byrne R, Dirschinger J, Kastrati A, Schömig A. A randomized clinical trial to evaluate the safety and efficacy of a

percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction. J Am Coll Cardiol.

2008;52(19):1584-8.

5. Meyns B, Autschbach R, Böning A, Konertz W, Matschke K, Schöndube F, Wiebe K, Fischer. Coronary artery bypass grafting supported with intracardiac microaxial pumps

versus normothermic cardiopulmonary bypass: a prospective randomized trial. E. Eur J Cardiothorac Surg. 2002;22(1):112-7

6. Sjauw KD, Konorza T, Erbel R, Danna PL, Viecca M, Minden HH, Butter C, Engstrøm T, Hassager C, Machado FP, Pedrazzini G, Wagner DR, Schamberger R, Kerber S,

Mathey DG, Schofer J, Engström AE, Henriques JP. Supported high-risk percutaneous coronary intervention with the Impella 2.5 device the Europella registry. J Am Coll

Cardiol. 2009;54(25):2430-4.

7. Real-world use of the Impella 2.5 circulatory support system in complex high-risk percutaneous coronary intervention: The USpella Registry. Maini B, Naidu SS, Mulukutla

S, Kleiman N, Schreiber T, Wohns D, Dixon S, Rihal C, Dave R, O'Neill W. Catheter Cardiovasc Interv. 2012;80(5):717-25.

8. ABIOMED IDE G050017- Autopsy reports 2006 and 2007.

9. Dangas et al. Impact of Hemodynamic Support with Impella vs. Intraaortic Balloon Counterpulsation on Prognostically Important Ischemic Endpoints: Results

from the PROTECT-II Trial. ., J Am Coll Cardiol 2012:60:B21

10. Popma et al., Impella Improves Clinical Outcomes When Extensive Revascularization is Performed: The PROTECT II Study. ., J Am Coll Cardiol 2012:59:13-

ppA372

11. Alasnag MA, Gardi DO, Elder M, Kannam H, Ali F, Petrina M, Kheterpal V, Hout MS, Schreiber TL.Use of the Impella 2.5 for prophylactic circulatory support during

elective high-ris11.k percutaneous coronary intervention. Cardiovasc Revasc Med. 2011;12(5):299-303

Special Controls Have Been Identified

and

Implemented

to Mitigate Known Risks

Extensive testing submitted for 510(k):

Non-clinical Performance/Bench testing (41 tests on average per

application)

Clinical data (Impella 2.5: 129 patients)

Testing includes evaluations of structural/tissue damage to heart,

local heat generation and flow dynamics

Impella Post Market Registry:

Local IRB approval, Independent CEC, Corelab

Physician and Staff Certification Programs

Appropriate caution and warnings added to package insert based on

post market data (studies, registries)

General and Special Controls are In Place

to Mitigate Potential Risks to Public Health

Potential Risk (use <

6 hrs)

Implemented Controls

Alteration in blood composition

Performance/Bench Testing, Labeling, Registry

Inadequate tissue perfusion

Performance/Bench Testing, Labeling, Registry

Embolism

Performance/Bench Testing, Labeling, Registry

Duration of use

Labeling, Registry

Fluid leakage

Performance/Bench Testing, Labeling, Registry

Adverse tissue reaction

Biocompatibility Testing

Infection

Sterility and Shelf-life testing, Registry

General and Special Controls are In Place

to Mitigate Potential Risks to Public Health

Potential Risk (use <

6 hrs)

Implemented Controls

Structural/tissue damage to heart

Performance/Bench Testing, Labeling, Training, Registry

Local heat generation

Performance/Bench Testing, Registry

Flow dynamics

Performance/Bench Testing, Registry

•

Abiomed Recommendation:

Establish

inclusive

Prospective

National

Registry

Percutaneous

Circulatory

Support

•

Leveraging current infrastructure of the Impella Registry

•

On-going registry, in cooperation with FDA and the appropriate

professional society, would enhance the current risk mitigation

controls for class II regulation of these devices

•

Combined with existing data, can potentially support future PMA

indications

Recommendation to Expand US Impella

Registry

Impella

Safety

Record

Supports

Effectiveness of Current Controls

•

Since 2008, Impella has been used over 15,000 times worldwide and

has

had

recalls

the

United

States

and

recall

outside

the

which effected a total of 4 units

•

There have been a total of 49 MDR’s since its introduction for an

overall MDR rate of 0.32%

•

Only 16 of these MDR’s were associated with Adverse Events, for an

MDR with AE rate of 0.11%

Conclusion

For temporary ventricular support up to 6 hours, including support

provided during HRPCI, Impella meets the requirements for a class II

designation

Conclusion

Further, we recommend the establishment of a prospective national

registry of percutaneous circulatory support as an added special

control for class II regulation of current and future devices

Sufficient information (valid scientific evidence) exists to identify risks

and benefits

The risks to health have been identified and quantified

Special

controls

have

been

currently

implemented

mitigate

these

risks

Impella safety record supports effectiveness of current controls

Thank you

APPENDIX

(thru 11/15/12)

Impella

MDR

Rate

Compared

IAB

* Assumes 75,000 IABs used each year

0.01%

0.07%

0.16%

0.03%

0.07%

0.73%

Death

Injury

Malfunction

Impella

IAB

1.13%

0.32%

0.44%

0.26%

0.23%

0.44%

0.88%

1.36%

0.78%

0.42%

2008

2009

2010

2011

2012

Impella

IAB

Procedural Characteristics

IABP

(N=211)

Impella

(N=216)

p-value

Use of Heparin

82.4%

93.5%

<0.001

IIb/IIIa Inhibitors

26.5%

13.4%

<0.001

Total Contrast Media (cc)

241±115

267±141

0.035

Rotational Atherectomy (RA)

9.0%

14.2%

0.083

Median # of RA Passes/lesion (IQ range)

1 (1-2)

3 (2-5)

0.001

Median # of RA passes/pt (IQ range)

2.0 (2.0-4.0)

5.0 (3.5-8.5)

0.003

Median RA time/lesion (IQ range sec)

40 (20-47)

60 (40-97)

0.004

RA of Left Main Artery

3.1%

8.0%

0.024

Total Support Time (hours)

8.23±21.0

1.86±2.7

<0.001

Discharge from Cath Lab on device

37.7%

5.6%

<0.001

Hemodynamic Support Effectiveness

CPO=

Cardiac

Power

Output

Cardiac

Output

Mean

Arterial

Pressure

0.0022

(Fincke

Hochman

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 ±

14.2 ±

p=0.001

CPO

data

available

only

for

279

patients

(N=138

IABP

and

N=141

Impella)

CoreLab Analysis Shows No Evidence of

Damage to Cardiac or Valve Structures

Aortic/Mitral valve injury

Valve prolapse

Chordal rupture

Papillary muscle rupture

Aortic aneurysm

Structural damage to heart chambers

or septum

Structure

PROTECT I

(N=20)

PROTECT II

(N=225)

Dixon et al. JACC Interv. 2009;

O’Neill et al Circulation 2012

O’Neill et al 2012

Maini et al 2012

Chandola et al 2012

Dixon et al. 2009

Henriques and al. 2006

Valgimigli and al. 2005

Vlasselaers and al. 2005

Meyns and al. 2003

Siengenthaler and al. 2005

Cantena and al. 2005

Catena and al. 2004

Colombo and al. 2003

Strecker and al. 2004

Jurmann and al. 2004

1.2 hrs

1 hr

2 weeks

1.3 hrs

Up to 2 hrs

~ 2.5 hrs

6 days

2-8 days

1-10 days

N.A

2-19 days

18 days

6 days

1-7 days

2.5

5.0

2.5

5.0

225

175

TTE

TTE / Angio

Angio

Serial TEE

3D TTE / 2D TEE

Serial TEE

1 patient

Study

Device

LOS

Imaging

Modality

Aortic

Regurgitation

Echo findings

Trauma / valve

LOS=length

support;

TEE

Trans-oesophageal

echocardiogram

Over 330 Cases with Imaging Showed No

Device Related Valve Regurgitation or Trauma

Results of a Randomized Study Supports

Blood Compatibility of IMPELLA

Leucocytes (10x9/l)

Granulocytes (%)

Eosinophilic leucocytes (%)

Basophilic leucytes (%)

Monocytes (%)

Lymphocytes (%)

Platelets (10x9/l)

Antithrombin III (%)

D-Dimers (ug/dl)

Granulocyte elastase (ug/l)

Complement C3 (g/l)

IMPELLA

(n=105)

12.3 ±

4.4

78 ±

8.1

1.48 ±

0.98

0.65 ±

0.41

5.31 ±

2.56

14 ±

7.5

144 ±

60 ±

0.75 ±

0.65

150 ±

126

0.65 ±

0.2

Cardio-Pulmonary

Bypass

p-value

11.3 ±

4.4

78 ±

6.1

1.26 ±

0.97

0.65 ±

0.41

5.1 ±

2.72

13 ±

6.8

163 ±

68 ±

1.06 ±

2.2

259 ±

195

0.73 ±

0.2

N.S

0.0007

N.S

0.00001

0.008

Meyns and al. Eur. J. Cardio-thoracic Surgery 22 (2002): 112-117

(n=94)

MAE= Major Adverse Event Rate

N=91

N=85

N=64

N=68

N=69

N=66

Study Device Learning Curve Effect

90day MAE Outcome

Intent-to-Treat

IABP

IMPELLA

2008

2009

2010

PROTECT II MAE Outcome

Pre-specified High Risk PCI Without Atherectomy Group

MAE= Major Adverse Event Rate

39.6%

48.7%

30.6%

38.5%

30 day MAE

90 day MAE

21% MAE

p=0.014

N=192

N=202

p=0.06

N=193

N=203

23% MAE

IMPELLA

IABP

Log rank test, p=0.03

Intent-to-Treat (N=396)

IABP

IMPELLA

90 day MAE

Relative Risk

[95% CI]

Relative Risk

[95% CI]

Group

p-value

Interaction

p-value

0.79 [0.64, 0.97]

0.023

0.70 [0.55, 0.89]

0.003

1.25 [0.75, 1.91]

0.444

Confounder: Use of Atherectomy

Pre-Specified Sub-group Analysis

With Atherectomy (n=52, 12%)

Without Atherectomy (n=373, 88%)

PCI Procedure

Overall

–

Per

Protocol

(n=425)

Impella better

IABP better

0.08

MAE = Major Adverse Event ; Per Protocol (PP)= Patients that met

all incl./ excl. criteria.

Without Atherectomy

MI (>3x ULN)

Repeat Revascularization

14.8%

6.6%

17.4%

10.5%

IMPELLA

IABP

37.5%

3.1%

10.0%

With Atherectomy

IMPELLA

IABP

(p=0.006)

(p=0.03)

(p=0.492)

(p=0.171)

30.0%

0.0

0.5

1.0

1.5

2.0

Earnshaw, et al. Arch. of Intern Med., 2011.

Feldman, et al. JACC, 2005. COMPANION

Choudhry, et al. JACC, 2011. JUNIPER

Chen, et al. ISPOR, 2009.CHARISMA

<$100,000 Threshold

Winkelmayer, et al. Medical Decision Making, 2002.

10.

Moore, et al.

BMC Health Services Research 2009

11.

Slaughter, et al. AHA, 2011.

12.

Russo, et al. ACC 2010.

Maini, et al. TCT, 2011 PROTECT II

Feldman, et al. JACC, 2005. COMPANION

Reynolds, et al. ACC, 2011.

Reynolds, et al. Circ Arrhythm Electrophysiol, 2009

$274k

$199k

$39,367

Comparative Cost-Effectiveness Studies

$25

$50

$75

$100

$125

$150

$175

Aspirin

CRT-P

C-reactive

Protein

Clopidogrel

Impella

PROTECT II

CRT-D

TAVI

(LYG)

ablation

Dialysis

(LYG)

MRI v.

Mammo

LVAD 1

DT(LYG)

LVAD 2

DT(LYG)

EX-99.3 4 d450930dex993.htm IMPELLA CLINICAL LITERATURE SUMMARY Impella Clinical Literature Summary

Exhibit 99.3

Impella Clinical Literature Summary

November 2012

TABLE OF CONTENTS


1.0	SCOPE OF SEARCH	2

2.0	METHODS	2

2.1	Database Selected	2
2.2	Selection Justification	2
2.3	Search Period	2
2.4	Queries	3

3	SEARCH RESULTS	3

3.1	Publications from Output of Search	3
3.2	Brief Summary of Each Publication	15

Impella Clinical Literature Search Report

1.0	SCOPE OF SEARCH

A comprehensive literature search was performed in November 2012 to collect clinical and scientific publications on the Impella 2.5, Impella 5.0, and Impella LD.

2.0

METHODS

2.1

Database Selected

PubMed was the database used for the on-line literature search to identify publications related to the clinical and scientific evidence for the Impella devices.

2.2

Selection Justification

PubMed was selected as the database of choice because it comprises approximately 20 million citations for biomedical literature from MEDLINE, life science journals, and online books. PubMed citations and abstracts include the fields of medicine, nursing, dentistry, veterinary medicine, the health care system, and preclinical sciences. PubMed is a free resource that is developed and maintained by the National Center for Biotechnology Information (NCBI), at the U.S. National Library of Medicine (NLM), located at the National Institutes of Health (NIH).

2.3

Search Period

The search period was from January 1994 to November 2012. This time period covers clinical use of the Impella from earliest developmental prototypes to the present.

IMPELLA Clinical Literature Search Report

Page 2 of 42

2.4

Queries

The following keywords were used to query the PubMed database:

•

Keywords: percutaneous left ventricular assist device [347 publications]

•

Keyword: Impella [177 publications]

•

Keywords: left ventricular support rotary blood pump [93 publications]

•

Keywords: microaxial blood pump [42 publications]

•

Keywords: intracardiac microaxial pump [ 9 publications]

•

Keywords: left intracardiac short term assist [3 publications]

3	SEARCH RESULTS

3.1

Publications from Output of Search

In total 671 publications were identified. Once duplicate publications, publications not available in English, and publications that did not materially relate to the Impella were also screened out, there were 193 publications remaining in the output.

These 193 publications were reviewed against the FDA definition of “Valid Scientific Evidence” from 21 CFR Section 860.7(c)(2):

“Valid scientific evidence is evidence from well-controlled investigations, partially controlled studies, studies and objective trials without matched controls, well-documented case histories conducted by qualified experts, and reports of significant human experience with a marketed sevice, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use.”

The 193 publications were categorized into three categories:

Publications meeting Valid Scientific Evidence Definition for Durations < 6 hours (n=57)

Publications meeting Valid Scientific Evidence Definition for Durations > 6 hours (n=67)

Other publications (Technical Reports, Animal Studies, Reviews, etc.) (n=69)

The publications are listed in alphabetical order by author in Tables 1-3.

IMPELLA Clinical Literature Search Report

Page 3 of 42

Table 1. Publications meeting Valid Scientific Evidence Definition for Durations < 6 hours


		Publication Citation

1		Abuissa H, Roshan J, Lim B, Asirvatham SJ. Use of the Impella Microaxial Blood Pump for Ablation of Hemodynamically Unstable Ventricular Tachycardia. J Cardiovasc Electrophysiol. 2009.

2		Akay MH, Frazier OH. Impella Recover 5.0 assisted coronary artery bypass grafting. J Card Surg. 2010 Sep;25(5):606-7.

3		Alasnag MA, Gardi DO, Elder M, Kannam H, Ali F, Petrina M, Kheterpal V, out MS, Schreiber TL. Use of Impella 2.5 for prophylactic circulatory support during elective high-risk percutaneous coronary intervention. Cardiovasc Revasc Med. 2011 Mar 29.

4		Arieti M, Pesarini G, Ribichini F. Percutaneous Impella Recover circulatory support in high-risk coronary angioplasty. Cardiovasc Revasc Med. 2008 Oct-Dec;9(4):269-74.

5		Atoui R, Samoukovic G, Al-Tuwaijri F, Malas T, Giannetti N, Barkun J, Lash V, Cecere R. The Use of the Impella LP 2.5 Percutaneous Microaxial Ventricular Assist Device as Hemodynamic Support During High-Risk Abdominal Surgery. J Card Surg. 2009 Nov 23.

6		Badawi RA, Grise MA, Thornton SN. Impella 2.5 assisted balloon aortic valvuloplasty and percutaneous coronary intervention as a bridge to heart transplantation. J Invasive Cardiol. 2012 May;24(5):229-30.

7		Badhey N, Banerjee S, Brilakis ES. Amplatzer vascular plugs for occlusion of a left internal mammary artery graft anastomosed to the anterior interventricular vein. Catheter Cardiovasc Interv. 2010 Jan 20.

8		Bautista-Hernández V, Gutiérrez F, Pinar E, Gimeno JR, Arribas JM, García-Puente J, Ray VG, Arcas R, Valdés M. Initial experience with the Impella left ventricular assist device for post-cardiotomy cardiogenic shock and unprotected left coronary artery angioplasty in patients with a low left ventricular ejection fraction. Rev Esp Cardiol. 2007 Sep;60(9):984-7.

9		Bhat TM, Waked A, Teli S, Lafferty J, Gala B. Acute complication due to impella 2.5 device (superficial femoral artery thrombosis): managed successfully with novel aspiration thrombectomy catheter (pronto v3). Clin Med Insights Cardiol. 2011 Feb 10;5:17-21.

10		Burzotta F, Paloscia L, Trani C, Mascellanti M, Mongiardo R, Materazzo G, Niccoli G, Di Marco M, Leone AM, Porto I, Mazzari MA, Rebuzzi AG, Schiavoni G, Crea F. Feasibility and long-term safety of elective Impella-assisted high-risk percutaneous coronary intervention: a pilot two-centre study.J Cardiovasc Med (Hagerstown). 2008 Oct;9(10):1004-10.

11		Burzotta F, Trani C, Coroleu S. Retrograde recanalization of left main from saphenous vein graft supported by percutaneous Impella Recover LP 2.5 assist device. J Invasive Cardiol. 2009 Aug;21(8):E147-50.

12		Cohen R, Domniez T, Elhadad S.High-risk left main coronary stenting supported by percutaneous Impella Recover LP 2.5 assist device. J Invasive Cardiol. 2007 Oct;19(10):E294-6.

13		Dahdouh Z, Roule V, Lognoné, Sabatier R, Grollier G. Left main coronary artery transradial rescue percutaneous coronary intervention for acute myocardial infarction complicated by cardiogenic shock with Impella ventricular mechanical support. Cardiovasc Revasc Med. 2011 Oct 20.

14		Dens J, Meyns B, Hilgers RD, Maessend J, van Ommen V, Gerckens U, Grube E. First experience with the Impella Recover(R) LP 2.5 micro axial pump in patients with cardiogenic shock or undergoing high-risk revascularisation. EuroIntervention. 2006 May;2(1):84-90.

15		Dixon SR, Henriques JP, Mauri L, Sjauw K, Civitello A, Kar B, Loyalka P, Resnic FS, Teirstein P, Makkar R, Palacios IF, Collins M, Moses J, Benali K, O’Neill WW. A prospective feasibility trial investigating the use of the Impella 2.5 system in patients undergoing high-risk percutaneous coronary intervention (The PROTECT I Trial): initial U.S. experience. JACC Cardiovasc Interv. 2009 Feb;2(2):91-6.

16		Eichhöfer J, Osten M, Horlick E, Dzavík V. First Canadian experience with high-risk percutaneous coronary intervention with assistance of a percutaneously deployed left ventricular assist device.Can J Cardiol. 2008 Nov;24(11):e82-5.

IMPELLA Clinical Literature Search Report

Page 4 of 42


		Publication Citation

17		Farhat F, Sassard T, Attof Y, Jegaden O. Abdominal aortic aneurysm surgery with mechanical support using the Impella microaxial blood pump. Interact Cardiovasc Thorac Surg. 2008 May;7(3):524-5.

18		Ferreiro JL, Gómez-Hospital JA, Cequier AR, Angiolillo DJ, Roura G, Teruel L, Maristany J, Gómez-Lara J, Jara F, Bass TA, Esplugas E. Use of Impella Recover LP 2.5 in elective high risk percutaneous coronary intervention. Int J Cardiol. 2009 Sep 2.

19		Fishberger SB, Asnes JD, Rollinson NL, Cleman MW. Percutaneous right ventricular support during catheter ablation of intra-atrial reentrant tachycardia in an adult with a mustard baffle--a novel use of the Impella device. J Interv Card Electrophysiol. 2010 Oct;29(1):69-72.

20		Froesch P, Martinelli M, Meier P, Cook S, Hullin R, Windecker S, Mohacsi P, Meier B. Clinical use of temporary percutaneous left ventricular assist devices. Catheter Cardiovasc Interv. 2011 Aug 1;78(2):304-13. doi: 0.1002/ccd.22948.

21		Griffith KE, Jenkins E. Abiomed Impella^® 2.5 patient transport: lessons learned. Perfusion. 2010 Nov;25(6):381-6.

22		Guirgis M, Kumar K, Zieroth S, Philipp R, Menkis AH, Freed DH. Interprovincial spoke-to-hub transport using the Impella Recover LP 5.0 left ventricular assist device as a bridge to long-term circulatory support. Can J Cardiol. 2010 Oct;26(8):320-2.

23		Harjai KJ, O’Neill WW. Hemodynamic Support Using the Impella 2.5 Catheter System during High-Risk Percutaneous Coronary Intervention in a Patient with Severe Aortic Stenosis. J Interv Cardiol. 2009 Dec 17.

24		Henning A, Schreieck J, Riessen R, Gawaz M, May AE. Successful bridge to recovery using a microaxial blood pump in a patient with electrical storm and cardiogenic shock. Med Klin (Munich). 2011 Oct;106(2):132-6.

25		Henriques JP, Remmelink M, Baan J Jr, van der Schaaf RJ, Vis MM, Koch KT, Scholten EW, de Mol BA, Tijssen JG, Piek JJ, de Winter RJ. Safety and feasibility of elective high-risk percutaneous coronary intervention procedures with left ventricular support of the Impella Recover LP 2.5. Am J Cardiol. 2006 Apr 1;97(7):990-2.

26		Iliodromitis KE, Kahlert P, Plicht B, Hoffmann AC, Eggebrecht H, Erbel R, Konorza TF. High risk PCI in acute coronary syndromes with Impella LP 2.5 device support. Int J Cardiol. 2010 Sep 6.

27		Jolly N. Role of Impella 2.5 heart pump in stabilizing diastolic aortic pressure to avert acute hemodynamic collapse during coronary interventions. J Invasive Cardiol. 2009 Jul;21(7):E134-6.

28		Jouan J, Grinda JM, Bricourt MO, Cholley B, Fabiani JN. Successful left ventricular decompression following peripheral extracorporeal membrane oxygenation by percutaneous placement of a micro-axial flow pump. J Heart Lung Transplant. 2010 Jan;29(1):135-6

29		Kovacic JC, Nguyen HT, Karajgikar R, Sharma SK, Kini AS.. The Impella 2.5 and TandemHeart ventricular assist devices are safe and associated with equivalent clinical outcomes in patients undergoing high-risk percutaneous coronary intervention. Catheter Cardiovasc Interv. 2011 Jan 13.

30		Kucukaksu S, Ergenoglu MU, Yildiz CE, Yerebakan H, Sayin MM, Degertekin M. High-risk left main coronary artery bypass surgery supported by the Impella Recover LP 2.5 assist device: an alternative insertion technique. Heart Surg Forum. 2009 Dec;12(6):E324-6.

31		Londoño JC, Martinez CA, Singh V, O’Neill WW. Hemodynamic support with impella 2.5 during balloon aortic valvuloplasty in a high-risk patient. J Interv Cardiol. 2011 Apr;24(2):193-7.

32		Lotun K, Shetty R, Patel M, Arain SA. Percutaneous left axillary artery approach for Impella 2.5 liter circulatory support for patients with severe aortoiliac arterial disease undergoing high-risk percutaneous coronary intervention. J Interv Cardiol. 2012 Apr;25(2):210-3.

33		Ludeman DJ, Schwartz BG, Burstein S. Impella-assisted balloon aortic valvuloplasty. Invasive Cardiol. 2012 Jan;24(1):E19-20.

34		Maini B, Naidu SS, Mulukutla S, Kleiman N, Schreiber T, Wohns D, Dixon S, Rihal C, Dave R, O’Neill W. Real-world use of the impella 2.5 circulatory support system in complex high-risk percutaneous coronary intervention: The uspella registry. Catheter Cardiovasc Interv. 2011 Nov 22.

IMPELLA Clinical Literature Search Report

Page 5 of 42


		Publication Citation

35		Marella PC, Lassetter JE, Heuser RR. The Impella ventricular assist device: use in patients at high risk for coronary interventions: successful multivesselpercutaneous coronary intervention in a 62-year-old high-risk patient. CardiovascRevasc Med. 2011 Jan-Feb;12(1):69.e9-12.

36		Martinez CA, Singh V, Heldman AW, O’Neill WW. Emergent use of retrograde left ventricular support in patients after transcatheter aortic valve replacement. Catheter Cardiovasc Interv. 2012 Aug 6.

37		Martinez CA, Singh V, Londoño JC, Cohen MG, Alfonso CE, O’Neill WW, Heldman AW. Percutaneous retrograde left ventricular assist support for interventions in patients with aortic stenosis and left ventricular dysfunction. Catheter Cardiovasc Interv. 2012 Apr 17.

38		Miller MA, Dukkipati SR, Mittnacht AJ, Chinitz JS, Belliveau L, Koruth JS, Gomes JA, d’Avila A, Reddy VY. Activation and entrainment mapping of hemodynamically unstable ventricular tachycardia using a percutaneous left ventricular assist device. J Am Coll Cardiol. 2011 Sep 20;58(13):1363-71.

39		Minden HH, Lehmann H, Meyhöfer J, Butter C. Transradial unprotected left main coronary stenting supported by percutaneous Impella Recover LP 2.5 assist device. Clin Res Cardiol. 2006 May;95(5):301-6.

40		Niccoli G, Siviglia M, De Vita M, Altamura L, Fusco B, Leone AM, Ferrante G, Rebuzzi AG, Crea F. A case of fatal stent thrombosis after Carbostent implantation: is clopidogrel alone antiplatelet therapy a safe alternative to aspirin alone antiplatelet therapy? Int J Cardiol. 2007 Jan 8;114(2):279-81.

41		O’Neill WW, Kleiman NS, Moses J, Henriques JP, Dixon S, Massaro J, Palacios I, Maini B, Mulukutla S, Dzavík V, Popma J, Douglas PS, Ohman M. A Prospective Randomized Clinical Trial of Hemodynamic Support with Impella 2.5^TM versus Intra-Aortic Balloon Pump in Patients Undergoing High-Risk Percutaneous Coronary Intervention: the PROTECT II Study. Circulation. 2012 Aug 30.

42		Ramondo A, Napodano M, Tarantini G, Calzolari D, Nalli C, Cacciavillani L, Iliceto S. High-risk percutaneous coronary intervention using the intracardiac microaxial pump ‘Impella recover’. J Cardiovasc Med (Hagerstown). 2006 Feb;7(2):149-52.

43		Remmelink M, Sjauw KD, Henriques JP, de Winter RJ, Vis MM, Koch KT, Paulus WJ, de Mol BA, Tijssen JG, Piek JJ, Baan J Jr. Effects of mechanical left ventricular unloading by Impella on left ventricular dynamics in high-risk and primary percutaneous coronary intervention patients. Catheter Cardiovasc Interv. 2010 Feb 1;75(2):187-94.

44		Schuler G. Left ventricular assist devices in cardiogenic shock and high-risk PCI. EuroInterv 2006 2:28-29.

45		Sciahbasi A, Pendenza G, Romagnoli E, Summaria F, Chiappa R, Patrizi R, Caselli G, Lioy E. Successful high-risk percutaneous coronary revascularization using Impella Recover LP 5.0 l/min. J Cardiovasc Med (Hagerstown). 2009 Dec 23.

46		Shah R, Thomson A, Atianzar K, Somma K, Mehra A, Clavijo L, Matthews RV, Shavelle DM. Percutaneous left ventricular support for high-risk PCI and cardiogenic shock: who gets what? Cardiovasc Revasc Med. 2012 Mar 13(2):101-5.

47		Sibbald M, Džavík V. Severe hemolysis associated with use of the impella LP^2.5 mechanical assist device. Catheter Cardiovasc Interv. 2012 Apr 17.

48		Sjauw KD, Remmelink M, Lam K, Baan J, Van Der Schaaf RJ, Vis MM, Scholten EW, De Mol BA, De Winter RJ, Piek JJ, Henriques JP. Demonstrating LV unloading on echocardiography during high risk PCI with a left ventricular assist device. Acute Card Care. 2007;9(2):125-6.

49		Sjauw KD, Konorza T, Erbel R, Danna PL, Viecca M, Minden HH, Butter C, Engstrøm T, Hassager C, Machado FP, Pedrazzini G, Wagner DR, Schamberger R, Kerber S, Mathey DG, Schofer J, Engström AE, Henriques JP. Supported high-risk percutaneous coronary intervention with the Impella 2.5 device the Europella registry. J Am Coll Cardiol. 2009 Dec 15;54(25):2430-4.

50		Strecker T, Fischlein T, Pfeiffer S. Impella Recover 100: successful perioperative support for off pump coronary artery bypass grafting surgery in a patient with end-stage ischemic cardiomyopathy. J Cardiovasc Surg (Torino). 2004 Aug;45(4):381-4.

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		Publication Citation

51		Thomopoulou S, Manginas A, Cokkinos DV. Initial experience with the Impella Recover LP 2.5 micro-axial pump in patients undergoing high-risk coronary angioplasty. Hellenic J Cardiol. 2008 Nov-Dec;49(6):382-7.

52		Valgimigli M, Steendijk P, Serruys PW, Vranckx P, Boomsma F, Onderwater E, Vaina S, Ligthart JM, McFadden E, van der Ent M, de Jaegere P, Sianos G. Use of Impella Recover(R) LP 2.5 left ventricular assist device during high-risk percutaneous coronary interventions; clinical, haemodynamic and biochemical findings. EuroIntervention. 2006 May;2(1):91-100.

53		Valgimigli M, Steendijk P, Sianos G, Onderwater E, Serruys PW.Left ventricular unloading and concomitant total cardiac output increase by the use of percutaneous Impella Recover LP 2.5 assist device during high-risk coronary intervention. Catheter Cardiovasc Interv. 2005 Jun;65(2):263-7.

54		Vecchio S, Chechi T, Giuliani G, Lilli A, Consoli L, Spaziani G, Giannotti F, Margheri M. Use of Impella Recover 2.5 left ventricular assist device in patients with cardiogenic shock or undergoing high-risk percutaneous coronary intervention procedures: experience of a high-volume center. Minerva Cardioangiol. 2008 Aug;56(4):391-9.

55		Vlasselaers D, Desmet M, Desmet L, Meyns B, Dens J. Ventricular unloading with a miniature axial flow pump in combination with extracorporeal membrane oxygenation. Intensive Care Med. 2006 Feb;32(2):329-33.

56		Windecker S, Meier B. Impella assisted high risk percutaneous coronary intervention. Kardiovaskuläre Medizin 2005;8:187-189

57		Yildiz CE, Sayin M, Yerebakan H, Kucukaksu S. First Turkish experiences of assisted beating-heart coronary artery bypass graft with the Impella Microaxial Ventricular Assist Device. Heart Surg Forum. 2010 Feb 1;13(1):E60-2.

Table 2. Publications meeting Valid Scientific Evidence Definition for Durations > 6 hours


Pub#		Publication Citation

1		Abusaid GH, Ahmad M. Transthoracic real time three-dimensional echocardiography in Impella placement. Echocardiography. 2012 Apr;29(4):E105-6.

2		Andrade JG, Al-Saloos H, Jeewa A, Sandor GG, Cheung A. Facilitated cardiac recovery in fulminant myocarditis: pediatric use of the Impella LP 5.0 pump. J Heart Lung Transplant. 2010 Jan;29(1):96-7.

3		Baldi T, Wolff T, Aschwanden M, Thalhammer C, Jaeger KA. Giant arteriovenous fistula after implantation of a percutaneous left ventricular assist device. Vasa. 2009 May;38(2):190-2.

4		Bell BP, Iqtidar AF, Pyne CT. Impella assisted transradial coronary intervention in patients with acute coronary syndromes and cardiogenic shock: Case series. Catheter Cardiovasc Interv. 2011 Apr 26.

5		Bennett MT, Virani SA, Bowering J, Ignaszewski A, Kaan AM, Cheung A. The use of the Impella RD as a bridge to recovery for right ventricular dysfunction after cardiac transplantation. Innovations (Phila). 2010 Sep;5(5):369-71.

6		Beurtheret S, Mordant P, Pavie A, Leprince P. Impella and extracorporeal membrane oxygenation: a demanding combination. ASAIO J. 2012 May-Jun;58(3):291-3

7		Beyer AT, Hui PY, Hauesslein E. The Impella 2.5 L for percutaneous mechanical circulatory support in severe humoral allograft rejection. J Invasive Cardiol.2010 Mar;22(3):E37-9.

8		Bresson D, Sibellas F, Farhat F, Jegaden O, Kirkorian G, Bonnefoy E. Preliminary experience with Impella Recover^® LP5.0 in nine patients with cardiogenic shock: a new circulatory support system in the intensive cardiac care unit. Arch Cardiovasc Dis. 2011 Aug;104(8-9):458-64.

IMPELLA Clinical Literature Search Report

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Pub#		Publication Citation

9		Catena E, Barosi A, Milazzo F, Paino R, Pelenghi S, Garatti A, Colombo T, Vitali E.Three-dimensional echocardiographic assessment of a patient supported by intravascular blood pump Impella recover 100. Echocardiography. 2005 Sep;22(8):682-5.

10		Catena E, Milazzo F, Merli M, Paino R, Garatti A, Colombo T, Vitali E. Echocardiographic evaluation of patients receiving a new left ventricular assist device: the Impella recover 100. Eur J Echocardiogr. 2004 Dec;5(6):430-7.

11		Catena E, Milazzo F, Pittella G, Paino R, Colombo T, Garatti A, Vitali E, Merli M. Echo-cardiographic approach in a new left ventricular assist device: Impella Recover 100. J Am Soc Echocardiogr. 2004 May;17(5):470-3.

12		Chandola R, Cusimano R, Osten M, Horlick E. Postcardiac transplant transcatheter core valve implantation for aortic insufficiency secondary to Impella device placement. Ann Thorac Surg. 2012 Jun;93(6):e155-7.

13		Chaparro SV, Badheka A, Marzouka GR, Tanawuttiwat T, Ahmed F, Sacher V, Pham SM. Combined use of Impella left ventricular assist device and extracorporeal membrane oxygenation as a bridge to recovery in fulminant myocarditis. ASAIO J. 2012 May-Jun;58(3):285-7.

14		Choi DC, Anderson MB, Batsides GP. Insertion of the Impella 5.0 left ventricular assist device via right anterior mini-thoracotomy: a novel practical approach. Innovations (Phila). 2011 Jul;6(4):265-6.

15		Christiansen S, Brose S, Demircan L, Autschbach R. A new right ventricular assist device for right ventricular support. Eur J Cardiothorac Surg. 2003 Nov;24(5):834-6.

16		Christiansen S, Dohmen G, Autschbach R. Treatment of right heart failure with a new microaxial blood pump. Asian Cardiovasc Thorac Ann. 2006 Oct;14(5):418-21.

17		Colombo T, Garatti A, Bruschi G, Lanfranconi M, Russo C, Milazzo F, Catena E, Frigerio M, Vitali E. First successful bridge to recovery with the Impella Recover 100 left ventricular assist device for fulminant acute myocarditis. Ital Heart J. 2003 Sep;4(9):642-5.

18		Cubeddu RJ, Lago R, Horvath SA, Vignola PA, O’Neill W, Palacios IF. Use of the Impella 2.5 system alone, after and in combination with an intra-aortic balloon pump in patients with cardiogenic shock: case description and review of the literature. EuroIntervention. 2012 Apr;7(12):1453-60.

19		Dahlin LG, Peterzén B. Impella used for hemostasis by left ventricular unloading, in a case with left ventricular posterior wall rupture. Ann Thorac Surg. 2008 Apr;85(4):1445-7.

20		Dhar G, Jolly N. Mechanical versus pharmacologic support for cardiogenic shock. Catheter Cardiovasc Interv. 2009 Jul 23.

21		Engström AE, Cocchieri R, Driessen AH, Sjauw KD, Vis MM, Baan J, de Jong M, Lagrand WK, van der Sloot JA, Tijssen JG, de Winter RJ, de Mol BA, Piek JJ, Henriques JP. The Impella 2.5 and 5.0 devices for ST-elevation myocardial infarction patients presenting with severe and profound cardiogenic shock: the Academic Medical Center intensive care unit experience. Crit Care Med. 2011 Sep;39(9):2072-9.

22		Engström AE, Sjauw KD, Baan J, Remmelink M, Claessen BE, Kikkert WJ, Hoebers LP, Vis MM, Koch KT, Meuwissen MM, Tijssen JG, De Winter RJ, Piek JJ, Henriques JP. Long-term safety and sustained left ventricular recovery: long-term results of percutaneous left ventricular support with Impella LP2.5 in ST-elevation myocardial infarction. EuroIntervention. 2011 Feb;6(7):860-5. Erratum in EuroIntervention. 2011 Jun;7(2):289. multiple author names corrected.

23		Ferrari M, Pfeifer R, Poerner TC, Figulla HR. Bridge to recovery in a patient with Churg-Strauss myocarditis by long-term percutaneous support with microaxial blood pump. Heart. 2007 Nov;93(11):1419.

24		Freitas HF, Falcão BA, Silva RC, Ribeiro JC, Velloso LG, Brito Junior FS. Circulatory support in cardiogenic shock after acute myocardial infarction. Arq Bras Cardiol. 2012 Jun;98(6):e96-e98.

25		Garatti A, Colombo T, Russo C, Lanfranconi M, Milazzo F, Catena E, Bruschi G, Frigerio M, Vitali E. Left ventricular mechanical support with the Impella Recover left direct microaxial blood pump: a single-center experience. Artif Organs. 2006 Jul;30(7):523-8.

26		Granfeldt H, Hellgren L, Dellgren G, Myrdal G, Wassberg E, Kjellman U, Ahn H. Experience with the Impella recovery axial-flow system for acute heart failure at three cardiothoracic centers in Sweden.Scand Cardiovasc J. 2009 Aug;43(4):233-9.

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Pub#		Publication Citation

27		Griffith BP, Anderson MB, Samuels LE, Pae WE Jr, Naka Y, Frazier OH. The RECOVER I: A multicenter prospective study of Impella 5.0/LD for postcardiotomy circulatory support. J Thorac Cardiovasc Surg. 2012 Mar 9.

28		Gupta A, Allaqaband S, Bajwa T. Combined use of Impella device and intra-aortic balloon pump to improve survival in a patient in profound cardiogenic shock post cardiac arrest. Catheter Cardiovasc Interv. 2009 Nov 15;74(6):975-6.

29		Harmon L, Boccalandro F. Cardiogenic shock secondary to severe acute ischemic mitral regurgitation managed with an Impella 2.5 percutaneous left ventricular assist device. Catheter Cardiovasc Interv. 2011 Jul 29.

30		Higgins J, Lamarche Y, Kaan A, Stevens LM, Cheung A. Microaxial devices for ventricular failure: a multicentre, population-based experience. Can J Cardiol. 2011 Nov;27(6):725-30.

31		Hollander SA, Reinhartz O, Chin C, Yeh J, Maeda K, Mallidi H, Bernstein, Rosenthal D. Use of the Impella 5.0 as a bridge from ECMO to implantation of the HeartMate II left ventricular assist device in a pediatric patient. Pediatr Transplant. 2011 Sep 16.

32		Jennings DL, Nemerovski CW, Khandelwal A. Extended use of a percutaneous left-ventricular assist device without a heparin-based purge solution. Am J Health Syst Pharm. 2010 Nov 1;67(21):1825-8.

33		Jung C, Ferrari M, Rödiger C, Fritzenwanger M, Figulla HR. Combined Impella and intra-aortic balloon pump support to improve macro- and microcirculation: a clinical case. Clin Res Cardiol. 2008 Nov;97(11):849-50.

34		Jurmann MJ, Siniawski H, Erb M, Drews T, Hetzer R. Initial experience with miniature axial flow ventricular assist devices for postcardiotomy heart failure. Ann Thorac Surg. 2004;77(5):1642-7.

35		Khouzam RN, Parizianu C, Hafiz AM, Chawla S, Schwartz R. Fulminant myocarditis associated with novel H1N1 influenza A. Heart Lung. 2011 Nov-Dec;40(6):566-8.

36		Koeckert MS, Jorde UP, Naka Y, Moses JW, Takayama H. Impella LP 2.5 for left ventricular unloading during venoarterial extracorporeal membrane oxygenation support. J Card Surg. 2011 Nov;26(6):666-8.

37		Kumar K, Guirgis M, Zieroth S, Lo E, Menkis AH, Arora RC, Freed DH. Influenza myocarditis and myositis: case presentation and review of the literature. Can J Cardiol. 2011 Jul-Aug;27(4):514-22.

38		Lam K, Sjauw KD, Henriques JP, Ince C, de Mol BA. Improved microcirculation in patients with an acute ST-elevation myocardial infarction treated with the Impella LP2.5 percutaneous left ventricular assist device. Clin Res Cardiol. 2009 May;98(5):311-8.

39		Lam K, Sjauw KD, van der Meulen J, Symersky P, Biervliet JD, Henriques JP, de Mol BA. A combined surgical and percutaneous approach through the axillary artery to introduce the Impella LP5.0 for short-term circulatory support. Int J Cardiol. 2009 May 15;134(2):277-9.

40		Lamarche Y, Cheung A, Ignaszewski A, Higgins J, Kaan A, Griesdale DE, Moss R. Comparative outcomes in cardiogenic shock patients managed with Impella microaxial pump or extracorporeal life support. J Thorac Cardiovasc Surg. 2011 Jul;142(1):60-5.

41		La Rocca GM, Shimbo D, Rodriguez CJ, Stewart A, Naka Y, Weinberger J, Homma S, Pizzarello R. The Impella Recover LP 5.0 left ventricular assist device: a bridge to coronary artery bypass grafting and cardiac transplantation. J Am Soc Echocardiogr. 2006 Apr;19(4):468.e5-7.

42		La Torre MW, Centofanti P, Attisani M, Patanè F, Rinaldi M. Posterior ventricular septal defect in presence of cardiogenic shock: early implantation of the Impella recover LP 5.0 as a bridge to surgery. Tex Heart Inst J. 2011;38(1):42-9.

43		Lauten A, Franke U, Strauch JT, Kaluza M, Wahlers T. Postocardiotomy failure after Ross operation: implantation of intravascular flow pump through pulmonary autograft. Thorac Cardiovasc Surg. 2007 Sep;55(6):399-400.

44		Lauten A, Strauch JT, Groetzner J, Wahlers T. Myocardial failure caused by traumatic dissection of left coronary system--ventricular recovery with temporary circulatory support. J Card Surg. 2007 May-Jun;22(3):238-9.

45		Lilli A, Vecchio S, Chechi T, Vittori G, Giuliani G, Spaziani G, Consoli L, Giannotti F, Baldereschi G, Margheri M. Left ventricular support device for cardiogenic shock during myocardial infarction due to stent thrombosis: A single centre experience. Int J Cardiol. 2009 Dec 22

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Pub#		Publication Citation

46		Marty P, Méjean S, Boudou N, Mayeur N, Minville V, Galinier M. Patent foramen ovale appearance with association of left ventricular assist device and mechanical ventilation. Am J Emerg Med. 2012 Jan;30(1):259.e1-3.

47		Mastroianni C, Pozzi M, Niculescu M, Makri R, Clarissou J, Pavie A, Leprince P. Elective Impella Recover LP 5.0 utilization for postcardiotomy low-output syndrome after aortic valve replacement. Int J Cardiol. 2011 Jul 25

48		Meyns B, Dens J, Sergeant P, Herijgers P, Daenen W, Flameng W. Initial experiences with the Impella device in patients with cardiogenic shock - Impella support for cardiogenic shock. Thorac Cardiovasc Surg. 2003 Dec;51(6):312-7.

49		Onorati F, Cristodoro L, Borrello F, Esposito A, Merola S,Renzulli A. Ventricular assistance with microaxial flow pump following mitral repair for dilated cardiomyopathy. Int J Artif Organs. 2006 Jun;29(6):591-5.

50		Patanè F, Grassi R, Zucchetti MC, Ceresa F, Amata AD, Zingarelli E, Sansone F, Marte F, Patanè S. The use of Impella Recover in the treatment of post-infarction ventricular septal defect: A new case report. Int J Cardiol. 2010 Oct 8;144(2):313-5.

51		Patanè F, Zingarelli E, Sansone F, Rinaldi M. Acute ventricular septal defect treated with an Impella recovery as a ‘bridge therapy’ to heart transplantation. Interact Cardiovasc Thorac Surg. 2007 Dec;6(6):818-9.

52		Rajagopal V, Steahr G, Wilmer CI, Raval NY. A novel percutaneous mechanical biventricular bridge to recovery in severe cardiac allograft rejection. J Heart Lung Transplant. 2010 Jan;29(1):93-5.

53		Romeo F. The successful combined use of Impella LP 2.5 and intra-aortic balloon pump in ST-elevation myocardial infarction with refractory cardiogenic shock. J Cardiovasc Med (Hagerstown). 2012 Aug;13(8):531-2.

54		Rossiter-Thornton M, Arun V, Forrest AP, Bayfield MS, Wilson MK. Left ventricular support with the Impella LP 5.0 for cardiogenic shock following cardiac surgery. Heart Lung Circ. 2008 Jun 17(3):243-5.

55		Samoukovic G, Al-Atassi T, Rosu C, Giannetti N, Cecere R. Successful treatment of heart failure due to acute transplant rejection with the Impella LP 5.0. Ann Thorac Surg. 2009 Jul 88(1):271-3.

56		Samoukovic G, Rosu C, Giannetti N, Cecere R. The Impella LP 5.0 as a bridge to long-term circulatory support. Interact Cardiovasc Thorac Surg. 2009 Jun 8(6):682-3.

57		Sassard T, Scalabre A, Bonnefoy E, Sanchez I, Farhat F, Jegaden O. The right axillary artery approach for the Impella Recover LP 5.0 microaxial pump. Ann Thorac Surg. 2008 Apr;85(4):1468-70.

58		Schroeter MR, Unsöld B, Holke K, Schillinger W. Pro-thrombotic condition in a woman with peripartum cardiomyopathy treated with bromocriptine and an Impella LP 2.5 heart pump. Clin Res Cardiol. 2012 Jul 25.

59		Seyfarth M, Sibbing D, Bauer I, Fröhlich G, Bott-Flügel L, Byrne R, Dirschinger J, Kastrati A, Schömig A. A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction. J Am Coll Cardiol. 2008 Nov 4 52(19):1584-8.

60		Siegenthaler MP, Brehm K, Strecker T, Hanke T, Nötzold A, Olschewski M, Weyand M, Sievers H, Beyersdorf F. The Impella Recover microaxial left ventricular assist device reduces mortality for postcardiotomy failure: a three-center experience. J Thorac Cardiovasc Surg. 2004 Mar 127(3): 812-22.

61		Sjauw KD, Remmelink M, Baan J Jr, Lam K, Engström AE, van der Schaaf RJ, Vis MM, Koch KT, van Straalen JP, Tijssen JG, de Mol BA, de Winter RJ, Piek JJ, Henriques JP. Left Ventricular Unloading in Acute ST-Segment Elevation Myocardial Infarction Patients Is Safe and Feasible and Provides Acute and Sustained Left Ventricular Recovery. J Am Coll Cardiol. 2008 Mar 11;51(10):1044-6.

62		Stoliński J, Rosenbaum C, Flameng W, Meyns B. The heart-pump interaction: effects of a micro-axial blood pump. Int J Artif Organs. 2002 Nov;25(11):1082-8.

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Pub#		Publication Citation

63		Strauch JT, Franke UF, Breuer M, Wippermann J, Wittwer T, Madershahian N, Kaluza M, Wahlers T. Technical feasibility of Impella Recover 100 microaxial left ventricular assist device placement after biologic aortic valve replacement (21 mm) for postcardiotomy failure. J Thorac Cardiovasc Surg. 2005 Dec;130(6):1715-6.

64		Suradi H, Breall JA. Successful use of the Impella 2.5 device in giant cell myocarditis as a bridge to permanent left ventricular mechanical support. Tex Heart Inst J. 2011;38(4):437-40.

65		Tevaearai HT, Schmidli J, Mohacsi P, Rothen HU, Eckstein FS, Carrel TP. Leakage of the arterial prosthesis of an Impella RVAD. Ann Thorac Surg. 2006 Oct;82(4):1527-9.

66		Toggweiler S, Jamshidi P, Erne P. Functional mitral stenosis: a rare complication of the Impella assist device. Eur J Echocardiogr. 2008 May;9(3):412-3.

67		Wiktor DM, Sawlani N, Kanthi Y, Sipahi I, Fang JC, Blitz A. Successful combined use of Impella Recover 2.5 device and intra-aortic balloon pump support in cardiogenic shock from acute myocardial infarction. ASAIO J. 2010 Nov-Dec;56(6):519-21.

Table 3. Other Publications


Pub#		Publication Citation

1		Apel J, Paul R, Klaus S, Siess T, Reul H. Assessment of hemolysis related quantities in a microaxial blood pump by computational fluid dynamics. Artif Organs. 2001 May;25(5):341-7.

2		Autschbach R, Rauch T, Engel M, Brose S, Ullmann C , Diegeler A, Mohr FW. A New Intracardiac Microaxial Pump: First Results of a Multicenter Study Artif Organs. 2001 May;25(5):327-30.

3		Badheka AO, Cohen MG. Percutaneous left ventricular assist devices—still waiting for the final word. Catheter Cardiovasc Interv. 2011 Aug 1;78(2):314-5.

4		Bashir J, Klas M, Cheung A. Peripheral insertion techniques for the Impella 5.0 circulatory support system. Innovations (Phila). 2010 Sep;5(5):341-4.

5		Basra SS, Loyalka P, Kar B. Current status of percutaneous ventricular assist devices for cardiogenic shock.Curr Opin Cardiol. 2011 Nov;26(6):548-54.

6		Bierbach B, Kasper-König W, Haist T, Meier M, Pritzer H, Hanenkamp U, Horstick G, Kempski O, Oelert H. Effect of different operative techniques for myocardial revascularisation on hemodynamics and myocardial perfusion in a porcine model. Thorac Cardiovasc Surg. 2005 Apr;53(2):103-9.

7		Boccalandro F. The use of PTCA in acute mitral regurgitation and cardiogenic shock: Revisited with impella. - response from the authors. Catheter Cardiovasc Interv. 2012 Sep 25.

8		Boening A, Friedrich C, Caliebe D, Cremer J. Efficacy of intracardiac right ventricular microaxial pump support during beating heart surgery. Interact Cardiovasc Thorac Surg. 2004 Sep;3(3):495-8.

9		Bunch TJ, Mahapatra S, Madhu Reddy Y, Lakkireddy D. The role of percutaneous left ventricular assist devices during ventricular tachycardia ablation. Europace. 2012 Aug;14 Suppl 2:ii26-ii32.

10		Cheng JM, den Uil CA, Hoeks SE, van der Ent M, Jewbali LS, van Domburg RT, Serruys PW. Percutaneous left ventricular assist devices vs. intra-aortic balloon pump counterpulsation for treatment of cardiogenic shock: a meta-analysis of controlled trials. Eur Heart J. 2009 Sep;30(17):2102-8.

11		Christiansen S, Perez-Bouza A, Reul H, Autschbach R. In vivo experimental testing of a microaxial blood pump for right ventricular support. Artif Organs. 2006 Feb;30(2):94-100.

12		Cook S, Windecker S. Percutaneous left ventricular assist devices during cardiogenic shock and high-risk percutaneous coronary interventions. Curr Cardiol Rep. 2009 Sep;11(5):369-76.

13		Desai NR, Bhatt DL. Evaluating percutaneous support for cardiogenic shock: data shock and sticker shock. Eur Heart J. 2009 Sep;30(17):2073-5.

14		De Souza CF de, de Souza Brito F, De Lima VC, De Camargo Carvalho AC. Percutaneous mechanical assistance for the failing heart. J Interv Cardiol. 2010 Apr;23(2):195-202.

IMPELLA Clinical Literature Search Report

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Pub#		Publication Citation

15		El Oakley R. Commentary: successful combined use of the Impella Recover 2.5 device and intraaortic balloon pump support for cardiogenic shock after acute myocardial infarction. ASAIO J. 2010 Nov-Dec;56(6):517-8.

16		Ender J, Anwar N, Brose S, Engel M, Retry A, Autschbach R. Epicardial echocardiography for correct placement of the intracardial biventricular assist device (Impella). Thorac Cardiovasc Surg. 2002 Apr;50(2):92-4.

17		Engström AE, Piek JJ, Henriques JP. Percutaneous left ventricular assist devices for high-risk percutaneous coronary intervention. Expert Rev Cardiovasc Ther. 2010 Sep;8(9):1247-55.

18		Engström AE, Sjauw KD, Henriques JP. Percutaneous assist devices vs. intra-aortic balloon pump for cardiogenic shock: evidence under construction vs. expert opinion. Eur Heart J. 2010 Feb;31(4):502; author reply 502-3.

19		Garatti A, Colombo T, Vitali E. Placement of the Impella Recover LD microaxial blood pump through a bioprosthesis is technically feasible. J Thorac Cardiovasc Surg. 2006 Oct;132(4):989-90.

20		Garratt KN, Holmes DR. Benefit with Impella? J Am Coll Cardiol. 2010 Jun 8;55(23):2608.

21		Goldstein JA, Kern MJ. Percutaneous mechanical support for the failing right heart. Cardiol Clin. 2012 May;30(2):303-10.

22		Haggerty CM, Fynn-Thompson F, McElhinney DB, Valente AM, Saikrishnan N, Del Nido PJ, Yoganathan AP. Experimental and numeric investigation of Impella pumps as cavopulmonary assistance for a failing Fontan. J Thorac Cardiovasc Surg. 2012 Sep;144(3):563-9.

23		Henriques JPS; de Mol BAJM. New percutaneous mechanical left ventricular support for acute MI: the AMC MACH program. Nat Clin Pract Cardiovasc Med. 2008 Feb;5(2):62-3.

24		Hermansen SE, Naesheim T, How OJ, Myrmel T.Circulatory assistance in acute heart failure-where do we go from here? Scand Cardiovasc J. 2009 Aug;43(4):211-6.

25		Heuser R. The use of PTCA in acute mitral regurgitation and cardiogenic shock: Revisited with impella. Catheter Cardiovasc Interv. 2012 Sep 25.

26		Isgro F, Kiessling AH, Rehn E, Lang J, Saggau W. Intracardiac left ventricular support in beating heart, multi-vessel revascularization. J Card Surg. 2003 May-Jun;18(3):240-4.

27		Kawashima D, Gojo S, Nishimura T, Itoda Y, Kitahori K, Motomura N, Morota T, Murakami A, Takamoto S, Kyo S, Ono M. Left ventricular mechanical support with Impella provides more ventricular unloading in heart failure than extracorporeal membrane oxygenation. ASAIO J. 2011 May-Jun;57(3):169-76.

28		Krenn L, Delle Karth G. Myocardial Infarction complicated by cardiogenic shock: a possible role for the Impella device? Crit Care Med. 2011 Sep;39(9):2186-7.

29		Lee MS, Makkar RR. Percutaneous left ventricular support devices. Cardiol Clin. 2006;24(2):265-75.

30		Martin J, Benk C, Yerebakan C, Derjung G, Sarai K, Beyersdorf F. The new Impella intracardiac microaxial pump for treatment of right heart failure after orthotopic heart transplantation. Transplant Proc. 2001 Nov-Dec;33(7-8):3549-50.

31		McCulloch B. Use of the Impella 2.5 in high-risk percutaneous coronary intervention. Crit Care Nurse. 2011 Feb;31(1):e1-16.

32		Meyns B, Autschbach R, Böning A, Konertz W, Matschke K, Schöndube F, Wiebe K, Fischer E. Coronary artery bypass grafting supported with intracardiac microaxial pumps versus normothermic cardio-pulmonary bypass: a prospective randomized trial. Eur J Cardiothorac Surg. 2002 Jul;22(1):112-7.

33		Meyns B, Stolinski J, Leunens V, Verbeken E, Flameng W. Left ventricular support by catheter-mounted axial flow pump reduces infarct size. J Am Coll Cardiol. 2003 Apr 2;41(7):1087-95.

34		Miller MA, Dukkipati SR, Koruth JS, d’Avila A, Reddy VY. How to perform ventricular tachycardia ablation with a percutaneous left ventricular assist device. Heart Rhythm. 2012 Jul;9(7):1168-76.

35		Mueller XM, Boone Y, Augstburger M, Horisberger J, von Segesser LK. Bi-ventricular axial micropump: impact on blood cell integrity. Swiss Surg. 2001;7(5):213-7.

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36		Myers TJ. Temporary ventricular assist devices in the intensive care unit as a bridge to decision. AACN Adv Crit Care. 2012 Jan-Mar;23(1):55-68.

37		Oses P, Casassus F, Leroux L, Calderon J, Barandon L. Optimization of Impella 5.0 implantation using mini-sternotomy approach in postmyocardial infarction cardiogenic shock. J Card Surg. 2012 Sep;27(5):605-6.

38		Ostadal P, Mlcek M, Holy F, Horakova S, Kralovec S, Skoda J, Petru J, Kruger A, Hrachovina V, Svoboda T, Kittnar O, Reddy VY, Neuzil P. Direct Comparison ofPercutaneous Circulatory Support Systems in Specific Hemodynamic Conditions in a Porcine Model. Circ Arrhythm Electrophysiol. 2012 Oct 10.

39		Ouweneel DM, Henriques JP. Percutaneous cardiac support devices for cardiogenic shock: current indications and recommendations. Heart. 2012 Aug;98(16):1246-54.

40		Palacios IF. Left ventricular assistant device Impella 2.5 usage for patients undergoing high-risk PCI. Catheter Cardiovasc Interv. 2012 Jun 1;79(7):1135-7.

41		Patanè F, Centofanti P, Zingarelli E, Sansone F, La Torre M. Potential role of the Impella Recover left ventricular assist device in the management of postinfarct ventricular septal defect. J Thorac Cardiovasc Surg. 2009 May;137(5):1288-9.

42		Patel KM, Sherwani SS, Baudo AM, Salvacion A, Herborn J, Soong W, Kendall MC. Echo rounds: the use of transesophageal echocardiography for confirmation of appropriate Impella 5.0 device placement. Anesth Analg. 2012 Jan;114(1):82-5.

43		Paul R, Marseille O, Hintze E, Huber L, Schima H, Reul H, Rau G. In vitro thrombogenicity testing of artificial organs. Int J Artif Organs. 1998 Sep;21(9):548-52

44		Raess DH, Weber DM. Impella 2.5. J Cardiovasc Transl Res. 2009 Jun;2(2):168-72.

45		Remmelink M, Sjauw KD, Henriques JP, de Winter RJ, Koch KT, van der Schaaf RJ, Vis MM, Tijssen JG, Piek JJ, Baan J Jr. Effects of left ventricular unloading by Impella recover LP2.5 on coronary hemodynamics. Catheter Cardiovasc Interv. 2007 Oct 1;70(4):532-7.

46		Reul H. Technical requirements and limitations of miniaturized axial flow pumps for circulatory support. Cardiology. 1994;84(3):187-93.

47		Rosarius N, Siess T, Reul H, Rau G. Concept, realization, and first in vitro testing of an intraarterial microaxial blood pump with an integrated drive unit. Artif Organs. 1994 Jul;18(7):512-6.

48		Sarkar K, Kini AS. Percutaneous left ventricular support devices. Cardiol Clin. 2010 Feb;28(1):169-84.

49		Sauren LD, Accord RE, Hamzeh K, de Jong M, van der Nagel T, van der Veen FH, Maessen JG. Combined Impella and intra-aortic balloon pump support to improve both ventricular unloading and coronary blood flow for myocardial recovery: an experimental study. Artif Organs. 2007 Nov 31(11):839-42.

50		Sayer GT, Baker JN, Parks KA. Heart rescue: the role of mechanical circulatory support in the management of severe refractory cardiogenic shock. Curr Opin Crit Care 2012 Oct 18(5):409-16.

51		Schampaert S, van’t Veer M, van de Vosse FN, Pijls NH, de Mol BA, Rutten MC. In vitro comparison of support capabilities of intra-aortic balloon pump and Impella 2.5 left percutaneous. Artif Organs. 2011 Sep;35(9):893-901.

52		Schmidt T, Siefker J, Spiliopoulos S, Dapunt O. New experience with the paracardial right ventricular axial flow micropump impella elect 600. Eur J Cardiothorac Surg. 2003 Aug 24(2):307-8.

53		Schwartz BG, Ludeman DJ, Mayeda GS, Kloner RA, Economides C, Burstein S. High-risk percutaneous coronary intervention with the TandemHeart and Impella devices: a single-center experience. J Invasive Cardiol. 2011 Oct 23(10):417-24.

54		Siess T, Meyns B, Spielvogel K, Reul H, Rau G, Flameng W. Hemodynamic system analysis of intraarterial microaxial pumps in vitro and in vivo. Artif Organs.1996 Jun;20(6):650-61.

55		Siess T, Nix C, Menzler F. From a lab type to a product: a retrospective view on Impella’s assist technology. Artif Organs. 2001 May 25(5):414-21

56		Siess T, Reul H, Rau G. Hydraulic refinement of an intraarterial microaxial blood pump. Int J Artif Organs. 1995 May;18(5):273-85.

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Pub#		Publication Citation

57		Siess T, Reul H, Rau G. Concept, realization, and first in vitro testing of an intraarterial microaxial blood pump. Artif Organs. 1995 Jul;19(7):644-52.

58		Sjauw KD, Engström AE, Henriques JP. Percutaneous mechanical cardiac assist in myocardial infarction. Where are we now, where are we going? Acute Card Care. 2007;9(4):222-30.

59		Song X, Throckmorton AL, Untaroiu A, Patel S, Allaire PE, Wood HG, Olsen DB. Axial flow blood pumps. ASAIO J. 2003 Jul-Aug;49(4):355-64.

60		Speiser BS. Percutaneously implanted left ventricular assist device: establishing a program from implant to intensive care unit. Dimens Crit Care Nurs. 2011 Sep-Oct;30(5):236-40.

61		Spillner J, Stoppe C, Hatam N, Amerini A, Menon A, Nix C, Steinseifer U, Abusabha Y, Giessen H, Autschbach R, Haushofer M. Feasibility and efficacy of bypassing the right ventricle and pulmonary circulation to treat right ventricular failure: an experimental study. J Cardiothorac Surg. 2012 Feb 6;7:15.

62		Sugiki H, Nakashima K, Vermes E, Loisance D, Kirsch M.Temporary right ventricular support with Impella Recover RD axial flow pump. Asian Cardiovasc Thorac Ann. 2009 Aug;17(4):395-400.

63		Syed AI, Kakkar A, Torguson R, Li Y, Ben-Dor I, Collins SD, Lemesle G, Maluenda G, Xue Z, Scheinowitz M, Kaneshige K, Satler LF, Kent KM, Suddath WO, Pichard AD, Lindsay J, Waksman R. Prophylactic use of intra-aortic balloon pump for high-risk percutaneous coronary intervention: will the Impella LP 2.5 device show superiority in a clinical randomized study? Cardiovasc Revasc Med. 2010 Apr-Jun;11(2):91-7.

64		Tuseth V, Pettersen RJ, Epstein A, Grong K, Husby P, Farstad M, Wentzel-Larsen T, Rotevatn S, Nordrehaug JE.Percutaneous left ventricular assist device can prevent acute cerebral ischemia during ventricular fibrillation. Resuscitation 2009;80(10):1197-1203.

65		Tuseth V, Salem M, Pettersen R, Grong K, Rotevatn S, Wentzel-Larsen T, Nordrehaug JE. Percutaneous left ventricular assist in ischemic cardiac arrest. Crit Care Med. 2009;37(4):1365-72.

66		Vaina S, Ligthart J, Vijayakumar M, Ten Cate FJ, Witsenburg M, Jordaens LJ, Sianos G, Thornton AS, Scholten MF, de Jaegere P, Serruys PW. Intracardiac echocardiography during interventional procedures. EuroIntervention. 2006 Feb;1(4):454-64.

67		Vercaemst L, Vandezande E, Janssens P, Yvan T, Peter D, Meyns B. Impella: a miniaturized cardiac support system in an era of minimal invasive cardiac surgery. J Extra Corpor Technol. 2002 Jun;34(2):92-100.

68		Windecker S. Percutaneous left ventricular assist devices for treatment of patients with cardiogenic shock. Curr Opin Crit Care. 2007 Oct;13(5):521-7.

69		Yoshitake I, Hata M, Sezai A, Unosawa S, Wakui S, Kimura H, Nakata KI, Hata H, Shiono M. The effect of combined treatment with Impella and landiolol in a swine model of acute myocardial infarction. J Artif Organs. 2012 Apr 13.

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3.2

Brief Summary of Each Publication

A brief description of each of the 193 publications is listed below, alphabetically by aurhor, in Table 4, below.

Table 4: Brief Summary of Publications


Pub#	Abbreviated Publication Citation	Brief Summary

1	Abuissa H et al. J Cardiovasc Electrophysiol. 2009.	Successful use of the Impella microcirculatory axial blood flow pump is reported in 3 patients with hemodynamically unstable ventricular tachycardia that allowed successful completion of the EP ablation procedure.

2	Abusaid GH et al. Echocardiography 2012.	A 33-year-old patient with nonischemic cardiomyopathy presented with cardiogenic shock requiring percutaneous left ventricular assist device placement despite inotropic support. Under transthoracic two-dimensional echocardiographic guidance, an Impella 2.5 L heart pump was placed. The inflow catheter was distal to the aortic valve, however patient remained in shock. Real time three-dimensional transthoracic echocardiography showed the inflow catheter imbedded into the papillary muscle causing inlet occlusion. By cropping 3D data set in multiple planes, a better spatial visualization of the inflow catheter and its distance from the aortic valve was easily obtained and the device was adjusted, with immediate improvement in patient’s hemodynamic status.

3	Akay MH, et al. J Card Surg. 2010 Sep;25(5):606-7.	We used the Impella Recover LD 5.0 Left Ventricular Assist Device to support a 61-year-old woman with an acute myocardial infarction, compromised pulmonary function, and severe cardiovascular disease during coronary artery bypass grafting (CABG). Off-pump CABG or CABG with cardiopulmonary bypass would have been risky. Our case highlights the usefulness of the Impella Recover LD, which can be inserted into the ascending aorta via a prosthetic graft, for providing hemodynamic support during and after CABG in patients with complex cardiovascular disease.

4	Alasnag MA, et al. Cardiovasc Revasc Med. 2011.	Impella 2.5 was used to support 60 consecutive high-risk PCI patients. Overall angiographic success was achieved in 96% of cases. At 30 days mortality was 5%, and rates of myocardial infarction, stroke, target vessel revascularization and urgent bypass surgery were 0%.

5	Andrade JG, et al. J Heart Lung Transplant. 2010.	13-year-old boy with fulminant biopsy-proven viral myocarditis supported with Impella device. The patient made a complete recovery.

6	Apel J, et al. Artif Organs. 2001.	In this article, a general approach of hemolysis analysis by means of computational fluid dynamics (CFD) is discussed.

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Pub#	Abbreviated Publication Citation	Brief Summary

7	Arieti M, et al. Cardiovasc Revasc Med. 2008.	Two cases of high-risk complete myocardial revascularization in patients older than 80 years assisted by the Impella 2.5 are presented. Authors report that the device proved to be relatively easy to set up and hemodynamically useful for patients with left ventricular dysfunction and end-stage coronary atherosclerosis.

8	Atoui R, et al. J Card Surg. 2009.	Case reported for successful use of Impella to hemodynamically support a high-risk abdominal surgery of a male awaiting cardiac transplantation for ischemic cardiomyopathy with a left ventricular ejection fraction (LVEF) of 15%.

9	Autschbach R, et al. Artif Organs. 2001.	Use reported of ELECT microaxial cardiac pump in assisted beating heart coronary artery bypass graft (CABG) operation. Authors concluded “There were no pump related life threatening or severe adverse events. Beating heart procedures with ICC (intra-corporeal circulation) can be reliably and safely achieved. As the device is easy to use, it may deserve a more widespread use in the future”.

10	Badawi, RA et al. J Invasive Cardiol. 2012	We report a case of high-risk balloon aortic valvuloplasty and percutaneous coronary intervention using the Impella 2.5 pLVAD in a patient with severely depressed left ventricular function as a bridge to heart transplantation. In our case, there did not appear to be any adverse events resulting from the use of the Impella for BAV.

11	Badheka AO, et al. Catheter Cardiovasc Interv. 2011.	This editorial comments on the clinical data supporting use of temporary percutaneous left ventricular assist devices in patients with cardiogenic shock or undergoing high-risk PCI. The authors state that the final word must come from randomized clinical trials.

12	Badhey N, et al. Catheter Cardiovasc Interv. 2010.	A case of left internal mammary artery graft anastomosis to the anterior interventricular vein leading to congestive heart failure. The patient underwent successful left main stenting using an Impella left ventricular assist device and left internal mammary graft occlusion using two Amplatzer vascular plugs.

13	Baldi T, et al.Vasa. 2009.	The authors report on a large arteriovenous fistula that required surgical repair after use of an Impella 2.5 for 6 days for support of a patient in post-AMI cardiogenic shock.

14	Bashir J, et al. Innovations (Phila). 2010.	The authors describe two novel insertion techniques for the Impella 5.0: a graft approach and a purse-string approach, that can be used in patients with small femoral arteries and also allow removal of the device at the bedside.

15	Basra SS, et al.Curr Opin Cardiol. 2011	A review of the current evidence on the use of pVADs (TandemHeart LVAD, Impella, percutaneous ECMO), their indications, relative merits, and adverse effects; discussion of the current approach to the appropriate use of pVADs in patients with cardiogenic shock; proposal of an algorithm for device selection tailored to each patient’s needs based on severity of cardiogenic shock, amount of support needed, and the overall clinical scenario.

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Pub#	Abbreviated Publication Citation	Brief Summary

16	Bautista-Hernández V et al. Rev Esp Cardiol. 2007.	Use of the Impella device for the treatment of cardiogenic shock following cardiopulmonary bypass (n=7) and for maintaining hemodynamic stability in high-surgical-risk patients undergoing unprotected left coronary artery angioplasty (n=6). Per the authors, “Impella ventricular assist device is easy to implant and has a low rate of complications. It can prove useful in specific patients with low output following open heart surgery as a bridge prior to heart transplantation and in patients with acute heart failure as in acute mitral failure or myocarditis”.

17	Bell BP, et al. Catheter Cardiovasc Interv. 2011 Apr 26.	We report three cases of patients with cardiogenic shock with successful transradial intervention (TRI) whilst using unilateral femoral access for Impella 2.5 mechanical support.

18	Bennett MT, et al. Innovations (Phila). 2010.	Impella RD was used to successfully bridge a patient to recovery after isolated right ventricular dysfunction post-cardiac transplant.

19	Beurtheret S, et al. ASAIO J. 2012	We report the case of a 34-year-old woman admitted for cardiogenic shock related to acute myocarditis. Initial hemodynamic instability required mechanical ventilation and peripheral venoarterial extracorporeal membrane oxygenation (ECMO). Secondary acute pulmonary edema after ECMO implantation required emergency left ventricular decompression with a percutaneous Impella 5.0. Hemodynamics improved but after one hour the Impella 5.0 failed due to a kinked purge line caused by difficulty in crossing the aortic valve, as the valve often does not open in patients on ECMO. The patient finally died. This case highlights the usefulness of Impella pump to unload left cardiac chambers but also its technical challenge when used in a patient on ECMO

20	Beyer AT, J Invasive Cardiol.2010 Mar;22(3):E37-9.	We report a case of a 64-year-old male with cardiogenic shock due to allograft rejection requiring mechanical support while undergoing intense immunosuppression. He underwent implantation of a micro-axial endovascular pump (Impella 2.5). To our knowledge, this is the first reported case of successful Impella device deployment as a bridge-to-recovery strategy.

21	Bhat TM, et al. Clin Med Insights Cardiol. 2011	First case of a serious local vascular complication-superficial femoral artery thrombus formation during Impella Recover LP 2.5 use in a high risk PCI which was managed successfully with novel aspiration thrombectomy catheter, which in itself is the first reported use of this catheter in such a vascular complication.

22	Bierbach B, et al. Thorac Cardiovasc Surg. 2005.	In 24 pigs various assists during bypass surgery were tested (ECC, OPCAB techniques, or Impella support device; n = 8 in each arm). Study demonstrated that hemodynamic depression can be reduced by use of the Impella pump.

23	Boccalandro F. Catheter Cardiovasc Interv. 2012.	In their editorial response, the authors note that new percutaneous left ventricular assist devices such as the Impella 2.5 that aim to actively support and unload the left ventricle are best suited for cases of acute increase in the left ventricular preload such as acute mitral regurgitation, both to support a percutaneous intervention if appropriate or as a bridge to mitral valve surgery when necessary.

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Pub#	Abbreviated Publication Citation	Brief Summary

24	Boening A, et al. Interact Cardiovasc Thorac Surg. 2004.	Efficacy of intracardiac right ventricular microaxial pump (ELECT) support during beating heart surgery is described. Per the authors, “Our results show that an IRVP (intracardiac right ventricular pump) can be applied safely and effectively in patients undergoing beating heart coronary surgery”.

25	Bunch TJ, et al. Europace. 2012.	This review article considers the published clinical experience for use of pVAD technologies to maintain perfusion in order to allow induction and mapping of VT in the setting of severe cardiomyopathy and haemodynamic instability.

26	Bresson D, et al. Arch Cardiovasc Dis. 2011	Report of experience with Impella 5.0 in 9 pts with severe ischemic heart failure. Six pts (group 1) presented with cardiogenic shock at the acute phase of an STEMI. Three pts (group 2) had severe ischemic cardiomyopathy with temporary contra-indication to LVAD or transplantation. In all pts Impella 5.0 was safely placed through the right subclavian artery. Cardiac power output increased from baseline to 72hrs. Impella remained in place for 12±7 days. In group 1, 5 pts were in INTERMACS Profile 3 at the time of pump insertion. Three could be weaned and survived. One pt in INTERMACS Profile 1 died of intractable heart failure within hours. In group 2, two pts underwent HTx. Hemorrhage requiring transfusions was observed in 4 pts but only one case was directly related to the Impella 5.0.

27	Burzotta F, et al. J Cardiovasc Med 2008.	Ten patients with poor LV function and multivessel or left main coronary artery disease underwent PCI with prophylactic Impella implantation. One patient died after Impella removal due to acute stent thrombosis. The other patients had an uncomplicated in-hospital course. At 1-year follow-up, no patient died nor suffered acute myocardial infarction. Two patients required repeat revascularization. LVEF at follow-up increased significantly (from 31% to 41%, p=0.02). Per the authors, “Our results support the feasibility and safety of Impella-assisted percutaneous coronary intervention in high-risk patients”.

28	Burzotta F, et al. J Invasive Cardiol 2009.	Case report of successful retrograde transradial recanalization and stenting of a chronically occluded left main coronary artery (LMCA) from a saphenous vein graft supported by the Impella 2.5 assist device.

29	Catena E, et al. Echocardiography. 2005.	We described the use of 3D echocardiography in a patient who underwent Impella support for postcardiotomy shock. 3D echocardiography allowed complete visualization of the pump and provided excellent intraoperative assessment of the complex spatial location into the left ventricle.

30	Catena E, et al. Eur J Echocardiogr. 2004.	Report on serial echocardiographic evaluations in 8 patients undergoing circulatory support by a new miniaturized microaxial pump, the Impella. Per the authors, “Before implantation echocardiography was useful to rule out anatomic contraindications. During and after implantation echocardiography provided information for correct positioning and evaluation of left ventricular filling necessary to optimize pump performance. During assistance it gave important information to assess left and right ventricular function”.

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Pub#	Abbreviated Publication Citation	Brief Summary

31	Catena E, et al. J Am Soc Echocardiogr. 2004.	We report our experience with echocardiographic monitoring on a patient with ischemic cardiomyopathy who underwent Impella implant as a bridge to heart transplant. During the surgical procedure echocardiography had an essential role for anatomic evaluation of the heart and correcting intraventricular positioning of the device.

32	Chandola R, et al. Ann Thorac Surg. 2012	We report the case of a 45-year-old woman who developed severe aortic insufficiency after insertion of a 5.0 L Impella device 16 weeks after heart transplantation due to acute rejection. The Impella 5.0 was used for 2 weeks to provide hemodynamic stability. A 29-mm CoreValve prosthesis was inserted percutaneously. At 6 months after prosthesis implantation, the patient was asymptomatic in New York Heart Association functional class II with no aortic insufficiency.

33	Chaparro SV, et al. ASAIO J. 2012	This is the first reported case of an Impella percutaneous left ventricular assist device being used in combination with extracorporeal membrane oxygenation in a patient with biventricular and respiratory failure, as a bridge to recovery.

34	Cheng JM, et al. Eur Heart J. 2009.	Meta-analysis of three studies of percutaneous LVAD vs. IABP in cardiogenic shock patients shows that the percutaneous LVAD provides superior hemodynamic support in patients compared with IABP but did not show a statistically significant difference in early survival. Two of the three trials summarized included Tandem Heart as the p-LVAD and one trial used Impella.

35	Choi DC, et al. Innovations (Phila). 2011	We report the first case in which the Impella 5.0 device was placed directly into the ascending aorta via a small right anterior thoracotomy in a patient following acute myocardial infarction complicated by cardiogenic shock.

36	Christiansen S, et al. Eur J Cardiothorac Surg. 2003.	Case reports for the first use of a new paracardiac microaxial blood pump for postcardiotomy right heart failure in two patients undergoing emergency CABG.

37	Christiansen S, et al. Asian Cardiovasc Thorac Ann. 2006.	The authors report their first successful clinical use of a new paracardiac right ventricular microaxial blood pump which was developed for postcardiotomy right heart failure.

38	Christiansen S, et al. Artif Organs. 2006.	The authors report results of an animal study (sheep model) for use of a micro-axial blood pump for right ventricular support.

39	Cohen R, et al. J Invasive Cardiol. 2007.	Case report of a successful distal left main coronary artery T-stenting supported by the Impella 2.5 assist device in a patient with severe LV dysfunction.

40	Colombo T, et al. Ital Heart J. 2003.	A patient with septic and cardiogenic shock secondary to acute myocarditis was successfully treated by left ventricular unloading using the Impella.

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Pub#	Abbreviated Publication Citation	Brief Summary

41	Cook S, et al. Curr Cardiol Rep. 2009.	In this review article the authors discuss the use of percutaneous left ventricular assist devices in patients with cardiogenic shock, in patients with acute STEMI without shock, and during high-risk percutaneous coronary interventions. They note that “preventive or bailout pVAD implantation can restore or maintain hemodynamic stability and represents an important advance in the management of patients with acute left ventricular dysfunction or cardiogenic shock. Although improvement of hemodynamic parameters by pVADs appears promising compared with IABP support alone, it remains to be determined whether this benefi t translates into improved clinical outcome.”

42	Cubeddu RJ, et al. EuroIntervention 2012	Literature review of use of the Impella 2.5 system compared to the use of IABP in patients with cardiogenic shock. We also discuss the potential role for combination therapy for a patient with refractory shock. We describe a case in which an IABP was used as a bail-out strategy to provide additional hemodynamic support in a patient with refractory cardiogenic shock after the Impella 2.5 system was in place.

43	Dahdouh Z, et al. Cardiovasc Revasc Med. 2011	Case report of transradial rescue percutaneous intervention for cardiogenic shock in a young man with support of an Impella device via femoral access.

44	Dahlin LG, et al. Ann Thorac Surg. 2008.	Case report of a patient with combined mitral valve annuloplasty and CABG procedure with severe, life-threatening bleeding complication due to left ventricular posterior wall rupture. The patient was successfully treated with the Impella left ventricular assist device to decompress the left ventricle and minimize the bleeding, as the patient’s condition did not allow standard repair of the left ventricle.

45	Dens J, et al. EuroIntervention. 2006.	Developmental study of the RECOVER 2.5 assist device in patients scheduled for high risk off-pump CABG, PCI, or support of patients in cardiogenic shock that gave direction for further device improvements. Conclusions from the report: “The Recover 2.5 micro axial pump allows, via percutaneous approach, partial unloading of the left ventricle. The technique is, after design modifications, feasible and safe and results in hemodynamic improvement”.

46	Desai NR, et al. Eur Heart J. 2009.	In this editorial, the authors argue that “large randomized trials comparing percutaneous LVADs and IABPs with each other as well as with appropriate controls need to be performed before we can more convincingly offer our patients evidence-based care.”

47	De Souza CF de, et al. J Interv Cardiol. 2010	Review describing the history of percutaneous LVAD, from its beginning, to the other devices currently available, including those created for right ventricle and biventricular support.

48	Dhar G, et al. Catheter Cardiovasc Interv. 2009.	Case report in which the circulatory support provided by Impella 2.5 heart pump, in addition to discontinuation of inotropic support and intra-aortic balloon pump, allowed stabilization and successful high-risk percutaneous revascularization.

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Pub#	Abbreviated Publication Citation	Brief Summary

49	Dixon SR, et al. JACC Cardiovasc Interv. 2009.	Results of the PROTECT I FDA feasibility study for use of Impella 2.5 in high-risk PCI (n=20) demonstrate safety and potential efficacy. The results were noted as follows. “The Impella 2.5 device was implanted successfully in all patients. The mean duration of circulatory support was 1.7 +/- 0.6 h (range: 0.4 to 2.5 h). Mean pump flow during PCI was 2.2 +/- 0.3 l/min. At 30 days, the incidence of major adverse cardiac events was 20% (2 patients had a periprocedural myocardial infarction; 2 patients died at days 12 and 14). There was no evidence of aortic valve injury, cardiac perforation, or limb ischemia. Two patients (10%) developed mild, transient hemolysis without clinical sequelae. None of the patients developed hemodynamic compromise during PCI”. The conclusion from the authors was “The Impella 2.5 system is safe, easy to implant, and provides excellent hemodynamic support during high-risk PCI”.

50	Eichhöfer J, et al. Can J Cardiol. 2008.	Canada’s first implantations of an Impella device providing circulatory support in patients undergoing complex, high-risk PCI are reported (n=2)

51	El Oakley R. ASAIO J. 2010.	In a commentary to an article about the successful combined use of the Impella 2.5 and IABP in a cardiogenic shock patient, the aurhor notes previous animal experiments in which concurrent use of an IABP helped to reduce an increase in aortic pressure seen with use of a synchronized left atrial-to-aorta LVAD.

52	Ender J, et al. Thorac Cardiovasc Surg. 2002.	Use of EE (Epicardial echocardiography) for monitoring the correct placement of the new intracardial biventricular assist devices (ELECT) during beating-heart surgery is reported. Per the authors, “Epicardial echocardiography is a useful, innovative method for monitoring the correct placement of the new intracardial biventricular assist device during beating-heart surgery”.

53	Engström AE, et al. Crit Care Med. 2011	A total of 34 STEMI patients with profound cardiogenic shock were admitted to intensive care and treated with either the Impella 2.5 or the Impella 5.0 device. Twenty five (25) patients initially received the Impella 2.5, whereas nine patients received immediate Impella 5.0 support. Eight out of 25 patients in the Impella 2.5 group were upgraded to 5.0 support. After 48 hrs, 14 of 25 patients in the 2.5 group were alive, five of whom had been upgraded. In the 5.0 group, eight out of nine patients were alive. After 30 days, six of 25 patients in the 2.5 group were alive, three of whom had been upgraded. In the 5.0 group, three of nine patients were alive at 30 days. In conclusion, STEMI patients with severe and profound cardiogenic shock, our initial experience suggests improved survival in patients who received immediate Impella 5.0 treatment, as well as in patients who were upgraded from 2.5 to 5.0 support, when compared to patients who received only Impella 2.5 support.

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Pub#	Abbreviated Publication Citation	Brief Summary

54	Engström AE, et al. EuroIntervention. 2011	In 2006, 10 patients with anterior STEMI received 3-way support with the Impella LP2.5 after PCI. The control group consisted of 10 comparable patients, treated according to routine care. For the current study, echocardiography was performed and adverse events were recorded. Mean duration of follow-up was 2.9±0.6 years in the Impella group and 3.0±0.3 years in the control group. No differences in aortic valve abnormalities and LVEF were demonstrated between the groups; LVEF increase from baseline was significantly greater in Impella-treated patients (23.6±8.9% versus 6.7±7.0%, p=0.008).

55	Engström AE, et al. Expert Rev Cardiovasc Ther. 2010	PCI strategies have become an established alternative to CABG. However, treatment options for surgery-ineligible patients with complex coronary artery disease used to be limited, especially in patients with a reduced left ventricular function. Those patients are at high risk of profound hypotension and mortality, which may be adequately prevented by prophylactic placement of a percutaneous mechanical assist device. The Impella 2.5 seems to be promising as it is easily applicable, carries a low complication rate and provides adequate circulatory support.

56	Engström AE, et al. Eur Heart J. 2010..	In response to recently published meta-analysis of IABP vs. p-LVADs in cardiogenic shock patients: more complications were observed in patients treated with IABP. Another issue with the meta-analysis is the fact that two very different p-LVADs are combined in the data analysis. The majority of patients (74 of 100) were randomized to TandemHeart vs. IABP. As emphasized by the authors, complication rate is high in TandemHeart-treated patients. Complication rate is much lower with the Impella 2.5.

57	Farhat F, et al. Interact Cardiovasc Thorac Surg. 2008.	A 50-year-old man with an end-stage cardiac failure was successfully operated on for an infrarenal aortic aneurysm with the support of an Impella 5.0 LP.

58	Ferrari M, et al. Heart. 2007.	Case report of bridge to recovery in a patient with Churg-Strauss myocarditis by long-term percutaneous support with microaxial blood pump (Impella 2.5). Despite implantation of an IABP for an EF of less than 10 %, organ hypoperfusion worsened indicated by increasing Lactat levels. The IABP was replaced by an Impella 2.5. Blood lactate decreased within 12 hours of support. LVEF increased to 30 % after 6 days. No signs of leg ischemia occurred during that period. Patient was discharged from hospital with an EF of 45%. The authors conclude that the Impella 2.5 provides a sufficient support for patients with severe cardiogenic shock.

59	Ferreiro JL, et al. Int J Cardiol. 2009.	Report of single-center experience in using the Impella 2.5 in the support of high-risk elective percutaneous coronary interventions (n=30). Per the authors, “Our study shows that the use of the Impella 2.5 device is feasible, has an overall favorable safety profile, and may help prevent periprocedural and short-term complications derived from high-risk procedures”.

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Pub#	Abbreviated Publication Citation	Brief Summary

60	Fishberger SB, et al. J Interv Card Electrophysiol. 2010	Report of the novel use of the Impella percutaneous microaxial flow pump to support cardiac output in an adult patient with a Mustard operation for TGA who experienced a cardiac arrest during a prior ablation attempt. The Impella device was placed via a retrograde approach across the aortic valve into the ventricle providing hemodynamic stability for successful mapping and ablation of intra-atrial reentrant tachycardia.

61	Freitas HF, et al. Arq Bras Cardiol. 2012	This is a case report of a patient with STEMI who developed cardiogenic shock refractory to vasoactive drugs and intra-aortic balloon. The patient was successfully supported with an Impella 2.5 device.

62	Froesch P, et al. Catheter Cardiovasc Interv. 2011	Retrospective analysis of 75 patients who received temporary percutaneous LV assist to treat cardiogenic shock (n = 49) or to facilitate high-risk PCI (n = 26). Seven patients with cardiogenic shock and 10 patients with high-risk PCI received Impella 2.5, the others received TandemHeart. One-month survival was 53% in patients with shock and 96% in patients with PCI. Twenty-seven patients (36%) had complication - 21 cases in the shock-group (43%), and 6 cases in the PCI-group (23%). Complications comprised 11 ischemic legs from which 6 suffered a compartment syndrome with 2 needing fasciotomy; a femoral arteriovenous fistula (1 patient); a femoral artery pseudoaneurysm (1); dissection of the common femoral artery (1); entry site bleeding (2); stroke chronologically related to the intervention (1); persistent hemodynamically significant atrial septal defect after the transseptal TandemHeart cannula removal (2); retroperitoneal hematoma (1); inguinal hematoma by cannula dislodgement (1); severe hemolysis (1); floating thrombus in the inferior vena cava (2); atrial perforation during TandemHeart implantation (1) eventually leading to tamponade corrected by surgical drainage. Fifty-four percent of the complications occurred after a CPR and 78% of complications after CPR and shock. Four 4 device failures were encountered (3 with TandemHeart, 1 with Impella)

63	Garatti A, et al. Artif Organs. 2006.	Left ventricular mechanical support with the Impella 5.0 LD microaxial blood pump: a single-center experience (n=6 bridge to transplant, n=3 fulminant myocarditis, and n=3 postcardiotomy low-output syndrome). Per the authors, “Our initial experience with Impella LD as mechanical support for patients in cardiogenic shock of various etiology is promising, yielding a good survival in a population of particularly compromised patients”.

64	Garatti A, et al. J Thorac Cardiovasc Surg. 2006.	Placement of the Impella 5.0 LD microaxial blood pump through a bioprosthesis is technically feasible.

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Pub#	Abbreviated Publication Citation	Brief Summary

65	Garratt KN, et al. J Am Coll Cardiol. 2010.	In this letter to the editor, the authors discuss the results from the 144 high-risk PCI patients supported by Impella 2.5 in the Europella registry. The authors note that “Ease of use is an attractive feature of the Impella device, but ease should not drive its use in the absence of demonstrated efficacy. We anxiously await the completion of PROTECT II trial, which will clarify possible benefits of this intermediate support device in elective high-risk percutaneous coronary intervention.”

66	Goldstein JA, et al. Cardiol Clin. 2012.	This review article considers the available mechanical approaches to provide hemodynamic support to treat profound right ventricular failure, including two percutaneous devices, the Impella RP and TandemHeart.

67	Granfeldt H, et al. Scand Cardiovasc J. 2009.	This retrospective study reports the use of the Impella devices at three sites in Sweden. Implantation was performed because of postcardiotomy heart failure (surgical group, n=33) or for various states of heart failure in cardiological patients (non-surgical group, n=17). The intention for the treatments was mainly to use the pump as a “bridge-to-recovery”. The authors conclude “The Impella recovery axial-flow system facilitates treatment in acute heart failure. Early intervention in patients with acute heart failure and optimized hemodynamics in the post-implantation period seem to be of importance for long-term survival”.

68	Griffith BP, et al. J Thorac Cardiovasc Surg. 2012	Sixteen patients suffering from PCCS/LOS were consented into the RECOVER I study and were supported with an Impella 5.0 or Impella LD. Hemodynamics improved immediately after the initiation of mechanical support: cardiac index, 1.65 versus 2.7 L/min/m(2) (P = .0001); mean arterial pressure, 71.4 versus 83.1 mm Hg (P = .01); and pulmonary artery diastolic pressure, 28.0 versus 19.8 mm Hg (P < .0001). The pump provided an average of 4.0 ± 0.6 L/min of flow for an average duration of 3.7 ± 2.9 days. The primary safety endpoint occurred in 2 patients (13%; 1 stroke and 1 death). For the primary efficacy endpoint, recovery of the native heart function was obtained in 93% of the patients discharged, with bridge-to-other-therapy in 7%. Survival to 30 days, 3 months, and 1 year was 94%, 81%, and 75%, respectively.

69	Griffith KE, et al. Perfusion. 2010	Based on the recent experience of transporting patients in cardiogenic shock supported on the Impella^® 2.5 within the setting of a “hub-and-spoke” regional referral network system, system operation, pump position, monitoring, and recommendations for providing safe and efficient transport is reviewed.

70	Guirgis M, et al. Can J Cardiol. 2010	Report describing the first case demonstrating successful use of the Impella 5.0, implanted under local anesthetic, for the purposes of interprovincial spoke-to-hub transport in a bridge-to-bridge-to-transplant procedure. By providing an economical and technically straightforward alternative to traditional ECMO, the case demonstrates that less invasive LVADs are valuable to the spoke-and-hub model for delivery of specialized cardiac care.

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Pub#	Abbreviated Publication Citation	Brief Summary

71	Gupta A, et al. Catheter Cardiovasc Interv. 2009.	We describe a case where IABP was not enough to provide hemodynamic support in a patient with cardiogenic shock after cardiac arrest. The Impella 2.5 system was successfully used along with the balloon pump for hemodynamic support and resulted in dramatic improvement of the patient’s condition.

72	Haggerty CM, et al. J Thorac Cardiovasc Surg. 2012	Bench testing was conducted for performance of Impella devices for the purposes of supporting failing Fontan physiology by decreasing central venous pressure. Results showed that left-sided Impella pumps are not well suited for cavopulmonary support but that the right-ventricular Impella device provided modestly improved performance by directing flow into the pulmonary artery.

73	Harjai KJ, et al. J Interv Cardiol. 2009.	Case report of successfully providing hemodynamic support using the Impella 2.5 during High-Risk PCI in a patient with severe aortic stenosis (valve area 0.9 cm²).

74	Harmon L, et al. Catheter Cardiovasc Interv. 2011 Jul 29.	We report a case of a patient successfully treated with an Impella 2.5 left ventricular assist device, in the setting of cardiogenic shock secondary to severe acute mitral regurgitation associated with an acute myocardial infarction.

75	Henning A, et al. Med Klin (Munich). 2011	A 59-year-old patient with dilated cardiomyopathy and incessant ventricular tachycardia presented with progressive cardiogenic shock. Due to hemodynamic instability, high dose catecholamines were required in addition to the implantation of an IABP, which, however, appeared to further augment the frequency and duration of VTs. The implantation of an Impella 2.5 allowed catecholamine administration to be terminated, thereby, ending this vicious circle of catecholamine-driven electrical storm. Within 5 days, the patient was hemodynamically stabilized and kidney and liver function recovered. Patient remained stable over a 24-month follow-up period.

76	Henriques JP, et al. Am J Cardiol. 2006.	Study demonstrating safety and feasibility of elective high-risk percutaneous coronary intervention procedures with left ventricular support of the Impella 2.5 (n=19 patients). Per the authors, “We studied the feasibility and safety of LV support with the percutaneous implantable Impella 2.5 system in 19 consecutive high-risk patients with percutaneous coronary intervention. Procedural success using the device and percutaneous coronary intervention was achieved in all 19 patients, who were very poor candidates for surgery. The patients were elderly (84% were >60 years of age), 74% had previous myocardial infarction, 63% had LV ejection fractions of < or =25%, and all had LV ejection fractions of < or =40%. There were no procedural deaths and 2 device-unrelated in-hospital late deaths. Mean decrease in hemoglobin level was 0.7 +/- 0.4 mmol/L. The device did not induce or increase aortic valve regurgitation. There were no important device-related adverse events during LV support with the Impella 2.5 system”.

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Pub#	Abbreviated Publication Citation	Brief Summary

77	Henriques JPS; et al. Nat Clin Pract Cardiovasc Med. 2008.	Description of the AMC MACH (Academic Medical Center Mechanical support for Acute Congestive Heart failure in STEMI patients) program targeting treatment for acute myocardial infarction that includes schematic for providing increasing levels of LV support as required, moving patients from IABP to Impella 2.5 to Impella 5.0 and finally a surgical LVAD.

78	Hermansen SE, et al. Scand Cardiovasc J. 2009.	The comment concerns two short-term assist systems, namely the Impella axial-flow recovery system and extra-corporeal membrane oxygenation (ECMO) used for circulatory assistance in patients with acute heart failure. The results, particularly for patients in cardiogenic shock not related to cardiac surgery, calls for cautious optimism.

79	Heuser R. Catheter Cardiovasc Interv. 2012.	In an editorial response the authors report earlier results treating patients with acute mitral regurgitation with an IABP. They regard the Impella 2.5 as a ‘new treatment option’ for patients such as this that represents an evolution and improvement in LV support.

80	Higgins J, et al. Can J Cardiol. 2011	Impella devices were inserted for acute cardiogenic shock refractory to maximal therapy, as a bridge to decision or to long-term mechanical support. Thirty-five patients received 37 Impella devices (Impella 2.5, n=2; Impella 5.0, n=29; and Impella RD 5.0, n=6) for dilated cardiomyopathy (n=13), acute myocardial infarction (n=6), postcardiotomy shock (n=6), and other etiologies (n=12). Mean age was 53.0±13.7 years. Mean LVEF was 19±9% at the time of insertion. Nineteen patients required aggressive resuscitation, all patients were on inotropic support, 97% of patients were intubated, and 46% of patients received mechanical circulatory support prior to insertion of the Impella devices. Mean duration of support was 3.7±3.0 days. In all, 49% were successfully weaned, and 22% were transferred to long-term mechanical support. Four patients have subsequently undergone successful cardiac transplantation. The 30-day mortality was 40%, and 6-month mortality was 49%. Complications included gastrointestinal bleeding (n=1), hemoptysis (n=1), and thrombocytopenia (n=4). There were no cardiovascular or cerebrovascular events. Conclusion: Temporary support with Impella microaxial ventricular assist devices adds a valuable therapeutic option in selected patients with acute decompensated heart failure.

81	Hollander SA, et al. Pediatr Transplant. 2011	A 10-yr-old previously healthy boy presented in cardiogenic shock after collapsing was subsequently diagnosed with a dilated cardiomyopathy at an outside hospital. Within hours following transfer to intensive care unit the patient quickly decompensated, necessitating emergent VA ECMO cannulation. Social service issues initially precluded listing for cardiac transplantation. On hospital day 14, an Impella 5.0 device was surgically implanted via the right femoral artery leading to successful weaning from ECMO. The Impella required replacement 10 days after implantation because of mechanical failure. On hospital day no. 27, the Impella was removed and a HeartMate II LVAD was implanted for long-term management.

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Pub#	Abbreviated Publication Citation	Brief Summary

82	Iliodromitis KE, et al. Int J Cardiol. 2010.	38 consecutive high-risk patients with multivessel disease underwent HRPCI supported by the Impella 2.5. Device insertion and explantation was feasible in all patients without vascular complications and continuous hemodynamic stability was obtained during PCI. One non procedure-related death occurred 7 days after the intervention, accounting for a total 30-day mortality of 2.86%. Other major cardiac or cerebrovascular events did not occur.

83	Isgro F, et al. J Card Surg. 2003.	Report on 15 patient supported with the ELECT Intracardiac left ventricular support in beating heart, multi-vessel revascularization. Per the conclusion of the authors, “In summary, it appeared that the application of a left ventricular coaxial pump with comparable results seemed to make possible complete revascularization in nearly all patients”.

84	Jennings DL, et al. Am J Health Syst Pharm. 2010	An Impella 2.5 was used for 75 hours with a purge solution that contained no heparin. There were no thrombotic or bleeding complications. The patient was a 58-year-old Asian man with no history of cardiac disease, hypertension, or diabetes mellitus who had an AMI and subsequent cardiogenic shock, deteriorating on dopamine, norepinephrine and IABP, with an LVEF of 25% and mid-distal anteroseptal akinesis.

85	Jolly N, et al. J Invasive Cardiol. 2009.	Case report demonstrating role of Impella 2.5 heart pump in stabilizing diastolic aortic pressure to avert acute hemodynamic collapse during high-risk coronary interventions.

86	Jouan J, et al. J Heart Lung Transplant. 2010.	A case is described of a woman with severe cardiomyopathy on ECMO as a bridge to transplant. The Impella 2.5 was used successfully to decompress and unload the left ventricle.

87	Jung C,et al. Clin Res Cardiol. 2008.	We report the case of a 70-year old male patient with severe cardiogenic shock. Combined Impella and intra-aortic balloon pump support was utilized to improve macro- and microcirculation.

88	Jurmann MJ, et al. Ann Thorac Surg. 2004.	Report of initial experience with miniature axial flow ventricular assist devices (Impella 5.0) for postcardiotomy heart failure in 6 patients. The conclusions of the authors were that “The initial experience with the Impella VADs proved the new systems to be advantageous regarding the ease of implantation and device removal, low anticoagulation requirements, and advanced weaning features. In cases of severe heart failure, survival was improved by using LVADs when compared to that predicted by solely continuing IABP and drug support”.

89	Kawashima D, et al. ASAIO J. 2011.	A canine study was used to compare ventricular loading reduction and reversibility of ventricular fibrillation (VF) with either Impella or ECMO. PV loops demonstrated superior ventricular unloading with Impella vs. ECMO. Successful defibrillation was achieved more effectively while under Impella support.

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Pub#	Abbreviated Publication Citation	Brief Summary

90	Khouzam RN, et al. Heart Lung. 2011	A 36-year-old man with no significant medical history presented with flu-like symptoms of 3-week duration. When he sought medical attention, he was already manifesting heart failure secondary to fulminant myocarditis, along with multiorgan failure. Despite aggressive management, including circulatory support with Impella 2.5 as a bridge to cardiac transplant, and aggressive antiviral and antibacterial therapy, the patient died of cardiac arrest. An H1N1 polymerase chain reaction postmortem assay produced positive results, and a diagnosis of fulminant viral myocarditis and multiorgan system failure was established.

91	Koeckert MS et al. J Card Surg. 2011	Case report on the use of Impella 2.5 for LV decompression in a 70-year-old man with decompensated heart failure who was placed on VA-ECMO for cardiogenic shock with severe pulmonary edema and respiratory failure. Both devices were successfully weaned on day 5 of VA-ECMO support, after myocardial recovery.

92	Kovacic JC,et al. Catheter Cardiovasc Niter. 2011.	36 patients were supported with Impella 2.5 vs. 32 patients supported with Tandem Heart for HRPCI. PCI was successful in 99%, with 30 day MACE of 5.8%. There were no differences between the Impella 2.5 and TH groups with respect to short- or long-term clinical outcomes.

93	Krenn L, et al. Crit Care Med. 2011.	This editorial response concerned the retrospective analysis of Engstrom et al describing the use of the Impella 2.5/5.0 devices in patients with refractory cardiogenic shock. The authors argue that prospective clinical trials need to be conducted in order to properly evaluate use of the Impella devices in profound shock.

94	Kucukaksu S, et al. Heart Surg Forum. 2009.	We report the case of a successful CABG supported by the Impella 2.5 assist device and using an alternative insertion technique for the ascending aorta in a patient with high-risk coronary lesions, such as left main disease.

95	Kumar K, et al. Can J Cardiol. 2011.	The authors present a case of myocarditis that was treated with escalating cardiac support; from a percutaneous left ventricular assist device, to extracorporeal membrane oxygenation, to eventual biventricular assist device support for bridge-to-transplantation.

96	Lam K, et al. Clin Res Cardiol. 2009.	A combined surgical and percutaneous approach through the axillary artery to introduce the Impella 5.0 for short-term circulatory support was demonstrated in 5 STEMI patients.

97	Lam K, et al. Int J Cardiol. 2008.	Demonstrated Improved microcirculation in patients with an acute ST-elevation myocardial infarction treated with the Impella 2.5 percutaneous left ventricular assist device (n=3). Microcirculation assessed by SDF improved in STEMI patients treated with the Impella 2.5 to levels observed in healthy persons and remained suboptimal after 72 h in patients without support.

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Pub#	Abbreviated Publication Citation	Brief Summary

98	Lamarche Y, et al. J Thorac Cardiovasc Surg. 2011	A retrospective, single center review on all patients receiving circulatory assistance with either extracorporeal life support or Impella device. Twenty-nine patients received Impella support (Impella 5.0; n = 24; and Impella RD; n = 5), whereas 32 patients were placed on extracorporeal life support. All Impella LP 5.0 were inserted via the femoral artery, while the RD system required sternotomy. The baseline characteristics of patients with cardiogenic shock, assisted by Impella or extracorporeal life support, were similar, but the etiology of cardiogenic shock was distributed differently in the 2 groups (P = .008). Forty-one percent of the Impella patients and 47% of the extracorporeal life support patients were weaned from support. The 30-day mortality (44% in the extracorporeal life support vs. 38% in the Impella group) and proportion of patients discharged home (41% in the extracorporeal life support vs. 59% in the Impella group) were not statistically different between the 2 groups. Arterial thrombosis was less frequent in the Impella group (3.4%vs 18.8%; P = .04). Blood product transfusions were less frequent in the Impella group (P<.001).

99	LaRocca GM, et al. J Am Soc Echocardiogr. 2006.	Two cases are reported in which the Impella 5.0 LP left ventricular assist device was used as a bridge to coronary artery bypass grafting in an AMI patient in cardiogenic shock and as a bridge to cardiac transplantation in the second patient with congestive heart failure and ischemic cardiomyopathy.

100	La Torre MW, et al. Tex Heart Inst J. 2011;38(1):42-9.	Urgent repair of posterior ventricular septal defect in the presence of cardiogenic shock, consequent to AMI, is associated with a very high mortality rate. The use of left ventricular support devices has the potential to impart hemodynamic stability and to delay surgical treatment until such time as scar tissue forms around the defect, sufficient to hold a suture patch. From May 2004 through July 2007, 5 patients who were in cardiogenic shock as a consequence of acute posterior VSD underwent early implantation of a transfemoral microaxial Impella 5.0 System as bridge to surgery.

101	Lauten A, et al. Thorac Cardiovasc Surg. 2007.	Case report of a patient with postcardiotomy failure-to-wean after aortic valve replacement who was supported with implantation of an intravascular flow pump, the Impella 5.0 LD, which was placed through a pulmonary autograft.

102	Lauten A, et al. J Card Surg. 2007.	We report a case of a patient suffering from massive myocardial infarction after traumatic dissection of the left coronary system. The dissection involved the left coronary artery including peripheral segments of the coronary circulation. The patient was revascularized; however, she could not be weaned from cardiopulmonary bypass thereafter. An Impella microaxial hemopump was implanted and the patient’s left ventricular function markedly improved during the following days. Eight days later hemodynamics had stabilized far enough to explant the device, after explantation the patient remained hemodynamically stable and free of inotropic support.

103	Lee MS, et al. Cardiol Clin. 2006.	The TandemHeart percutaneous left ventricular assist device and the Impella Recover LP 2.5 System may provide rapid circulatory support in high-risk PCI patients and in those who have cardiogenic shock.

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Pub#	Abbreviated Publication Citation	Brief Summary

104	Lilli A, et al. Int J Cardiol. 2009.	Report from a single center for left ventricular support devices for cardiogenic shock during myocardial infarction due to stent thrombosis. Three subjects were supported with the Impella 2.5 device after support by an IABP was deemed inadequate.

105	Londoño JC, et al. J Interv Cardiol. 2011 Apr;24(2):193-7.	Aortic stenosis (AS) has been considered an exclusion criterion for the use of the Impella 2.5 catheter. We describe a case in which the Impella catheter was successfully implanted and used for hemodynamic support during balloon aortic valvuloplasty in a high-risk patient of severe AS with a calculated aortic valve area of 0.59 cm².

106	Lotun K, et al. J Interv Cardiol. 2012	We describe the successful percutaneous use of the Impella 2.5 L device for hemodynamic support via the left axillary artery in 2 patients undergoing high-risk PCI with concomitant severe aortoiliac disease

107	Ludeman DJ, et al. J Invasive Cardiol. 2012	A 77-year-old woman with severe aortic stenosis, severe coronary artery disease, an ejection fraction of 20%, severe peripheral vascular disease, and other comorbidities presented with shortness of breath that had been worsening over 2 weeks. The patient underwent a successful, Impella-assisted balloon aortic valvuloplasty (BAV) without complications.

108	Maini B, et al. Catheter Cardiovasc Interv. 2011	Report on the real-world, multicenter experience of the Impella 2.5 during high-risk PCI, a subset of the larger USpella Registry. 175 consecutive patients with compromised ventricular function with multi-vessel or high-risk coronary lesions who underwent PCI with prophylactic support of the Impella 2.5 were evaluated. Overall angiographic revascularization was successful in 99% of patients and in 90% of those with multi-vessel revascularization, resulting in a reduction of the mean SYNTAX score post-PCI from 36±15 to 18±15 (P < 0.0001) and an improvement of the ejection fraction (from 31±15% to 36±14%, P < 0.0001). In 51% of patients, the functional status improved by one or more NYHA class (P < 0.001). At 30-day follow-up, the rate of MACE was 8%, and survival was 96%, 91% and 88% at 30 days, 6 months and 12 months, respectively. CONCLUSIONS: The use of Impella 2.5 in high-risk PCI appeared feasible and safe in the real-world setting. The utilization of the Impella 2.5 was successful, resulting in favorable short- and mid-term angiographic, procedural and clinical outcomes.

109	Marella PC, Cardiovasc Revasc Med. 2011.	Impella 2.5 was used to successfully support a very high risk PCI case with intervention required on two critical lesions in LAD and circumflex.

110	Martin J, et al. Transplant Proc. 2001.	Hearts of domestic pigs (n = 5, 60 to 80 kg) were flushed with Bretschneider´s HTK solution and transplanted orthotopically after a cold ischemic time of 24 hours. One hour after the start of reperfusion, cardiopulmonary bypass was discontinued and right ventricular circulatory support was maintained by the “Impella” pump for 5 hours.

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Pub#	Abbreviated Publication Citation	Brief Summary

111	Martinez CA, et al. Catheter Cardiovasc Interv. 2012 (August)	Transcatheter aortic valve replacement (TAVR) is currently a therapeutic alternative to open aortic valve replacement for high-risk patients with severe symptomatic aortic valve stenosis. The procedure is associated with some life-threatening complications including circulatory collapse which may require temporary hemodynamic support. We describe our experience with the use of Impella 2.5 system to provide emergent left ventricular support for hemodynamic collapse in two patients after TAVR with Edwards SAPIEN prosthesis.

112	Martinez CA, et al. Catheter Cardiovasc Interv. 2012 (April)	We reviewed procedural and clinical findings and 30-day outcomes in 21 patients with symptomatic aortic stenosis (AS) who underwent high-risk percutaneous procedures (PCI or BAV) supported by the Impella 2.5 system. All patients carried a high-risk of operative mortality. Impella was inserted successfully in all patients attempted. Retrograde advancement of two catheters across the aortic valve (for concomitant BAV in 15 patients) was technically feasible. Retrograde continuous flow LV assist produced a reduction in LV end-diastolic pressure and an increase in arterial pressure. Periprocedural complications occurred in 19% (n = 4) patients, with no periprocedural deaths. Mortality at 30 days was 14.2%. Our data suggests that continuous flow LV assist with Impella 2.5 can be used in high-risk patients with severe AS who require periprocedural hemodynamic support.

113	Marty P, et al. Am J Emerg Med. 2012	Case report on a 62-year-old man with anterior STEMI, developing cardiogenic shock requiring elective intubation, vasopressor, inotropic support, emergency coronary angiography, revascularization, and insertion of an IABP. As the hemodynamic situation remained unstable Impella 5.0 support was initiated. Severe hypoxemia occurred several minutes after initiating the support. Transesophageal echocardiography allowed diagnosis of patent foramen ovale. The shunt resulted from abnormal left-to-right pressure gradient due to LV unloading and increased RV afterload induced by mechanical ventilation. Transesophageal echocardiography was used to regulate both LVAD output and positive end-expiratory pressure settings to optimize oxygen transport.

114	Mastroianni C, et al. Int J Cardiol. 2011 Jul 25.	Elective Impella Recover LP 5.0 utilization for postcardiotomy low-output syndrome after aortic valve replacement.

115	McCulloch B. Crit Care Nurse. 2011	One community hospital’s approach to establishing a multidisciplinary program for use of the Impella 2.5 is described.

116	Meyns B, et al. Eur J Cardiothorac Surg. 2002.	Coronary artery bypass grafting supported with intracardiac microaxial ELECT pumps versus normothermic cardiopulmonary bypass: a randomized study. Conclusions: “The intracardiac pump for the right heart is difficult to introduce. As a consequence the right side pump underwent design modifications. There were no differences in clinical outcome between both groups. The inflammatory response is significantly reduced in the intracardiac pump group”.

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Pub#	Abbreviated Publication Citation	Brief Summary

117	Meyns B, et al. Thorac Cardiovasc Surg. 2003.	Report on initial experiences with the Impella 5.0 LD or LP device supporting patients with cardiogenic shock (n=16). Conclusions: “Left ventricular unloading with the Impella pump via the transthoracic or femoral approach is feasible and safe. Support led to a decrease in pulmonary capillary wedge pressure, increase in cardiac output and mean blood pressure, and improved organ perfusion in patients with severe cardiogenic shock”.

118	Meyns B, et al. J Am Coll Cardiol. 2003.	Myocardial infarction was induced by occlusion in 26 sheep. The animals were allocated to groups either without support or varying levels of support with the Impella 5.0 pump. The study demonstrated that use of the Impella 5.0 support during MI reduced infarct size.

119	Miller MA, et al. Heart Rhythm. 2012.	This article focuses on patient selection, implantation, anticoagulation, hemodynamic monitoring, and electromagnetic interference (EMI) when using the Impella 2.5 percutaneous left ventricular assist device (pLVAD) during scar-VT ablation.

120	Miller MA, et al. J Am Coll Cardiol. 2011.	In patients with scar-related VT undergoing catheter ablation, pLVAD support was able to safely maintain endorgan perfusion despite extended periods of hemodynamically unstable VT. Randomized studies are necessary to determine whether this enhanced ability to perform entrainment and activation mapping will translate into a higher rate of clinical success.

121	Minden HH, et al. Clin Res Cardiol. 2006.	Case report of a transradial unprotected left main coronary stenting supported by percutaneous Impella 2.5 assist device in a patient with high mortality risk in case of cardiac surgery due to history of chronic lymphatic leukemia with immune hemolysis.

122	Mueller XM, et al. Swiss Surg. 2001.	Animal study on 5 calves was done to test hemocompatibility of two ELECT devices (right-side and left-side) during CABG. Both right and left-sided micro-pumps performed well, maintained flow, and demonstrated negligible hemolysis.

123	Myers TJ, et al. AACN Adv Crit Care. 2012	Review article for use of temporary ventricular assist devices (VADs) such as CentriMag, TandemHeart, and Impella as “bridge to decision” devices for patients in cardiogenic shock.

124	Niccoli G, et al. Int J Cardiol. 2007.	Case report of a fatal stent thrombosis after carbostent implantation: “is clopidogrel alone antiplatelet therapy a safe alternative to aspirin alone antiplatelet therapy?” The complication occurred two hours after a high-risk circumflex PCI performed under left ventricular assistance by Impella device with an optimal final angiographic result and was attributed to inadequate anticoagulation therapy.

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Pub#	Abbreviated Publication Citation	Brief Summary

125	O’Neill WW, et al. Circulation. 2012	While (CABG) is generally preferred in symptomatic patients with severe, complex multivessel or left main disease, some patients present with clinical features that make CABG clinically unattractive. Percutaneous coronary revascularization (PCI) with hemodynamic support may be feasible for these patients. In the Protect II study 452 patients with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function were randomly assigned to support with intra-aortic balloon (IABP) (n=226) or Impella 2.5 (n=226) during non-emergent high risk PCI. The primary endpoint was the 30-day incidence of major adverse events (MAE). A 90 day follow-up was required as well by protocol. Impella 2.5 provided superior hemodynamic support compared to IABP, with maximal decrease in cardiac power output from baseline of -0.04 ± 0.24 Watts compared with -0.14 ± 0.27 Watts for IABP (P=0.001). The primary endpoint (30 day MAE) was not statistically different between groups: 35.1% for Impella 2.5 vs. 40.1% for IABP, P=0.227 in the intent-to-treat (ITT) population and 34.3% vs. 42.2%, P=0.092 in the per protocol (PP) population. At 90 days, a strong trend toward decreased MAE was observed in Impella 2.5-supported patients compared to IABP: 40.6% vs 49.3%, P=0.066 in ITT and 40.0% vs 51.0%, P=0.023 in PP populations, respectively. We conclude that, while the 30-day incidence of MAE was not different for patients with IABP or Impella 2.5 hemodynamic support, trends for improved outcomes were observed for Impella 2.5-supported patients at 90 days.

126	Onorati F, et al. Int J Artif Organs. 2006.	Case of ventricular assistance with microaxial flow pump (Impella 2.5) following mitral repair for dilated cardiomyopathy. The patient was unweanable from cardiopulmonary bypass until microaxial flow pump unloaded the left ventricle and restored adequate cardiac function. Conclusions: “The mini-invasive insertion and withdrawal, low anticoagulation protocols, and the possibility of coupling with IABP make the microaxial flow LVAD promising for patients with end-stage heart failure undergoing surgery”.

127	Oses P, et al. J Card Surg. 2012	14 patients in cardiogenic shock post-AMI were supported with an Impella 5.0 implanted by a new mini-sternotomy technique. All these patients had severe iliac artery lesions, or small diameter subclavian vessels. The mean duration of support was 8.5 ± 4.9 days. One patient developed a pericardial effusion requiring drainage. Nine patients were weaned from the Impella 5.0, one required the implantation of a HeartMate II. Four patients died in the follow-up, two due to multiorgan failure, one for sepsis, and one with severe hemoptysis.

128	Ostadal P, et al. Circ Arrhythm Electrophysiol. 2012.	A porcine model was used to compare hemodynamic effectiveness of ECMO, TandemHeart, and the Impella 2.5 in ventricular fibrillation. No significant differences were found for pacing of 200 beats/min or 300 beats/min. In ventricular fibrillation ECMO maintained the highest MAP, followed by the TandemHeart and Impella 2.5. However, the Impella 2.5 provided short-term MAP support during VFib when norepinephrine was added.

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Pub#	Abbreviated Publication Citation	Brief Summary

129	Ouweneel DM, et al. Heart. 2012.	This review article compares the available percutaneous cardiac assist devices for use in cardiogenic shock. The ideal device generates sufficient hemodynamic support to prevent end-organ failure, but also myocardial protection to prevent myocardial ischaemia, and has a low complication rate. In the future, mechanical circulatory support may even become equally important as opening the occluded artery in STEMI patients with cardiogenic shock. Eventually, the focus of these patients may therefore shift from door-to-balloon time to door-to-circulatory support time but only in the light of clinical evidence.

130	Palacios IF. Catheter Cardiovasc Interv. 2012	Editorial response supporting usage of Impella 2.5 in high risk PCI summarizes data from Protect I, Protect II, USPella registry, and Europella registry.

131	Patanè F, et al. J Thorac Cardiovasc Surg. 2009..	This is a review article for use of the role of the Impella 5.0 left ventricular assist device in the management of post-infarct ventricular septal defects.

132	Patanè F, et al. Int J Cardiol. 2010.	Case study of a 45 year-old male referred to us for a cardiogenic shock, caused by a post-infarction ventricular septal defect. “We were able to delay surgical closure for 2 weeks using extended hemodynamic support with the Impella 5.0 device”.

133	Patanè F,et al. Interact Cardiovasc Thorac Surg. 2007.	Case study of a 59-year-old male, admitted to hospital for cardiogenic shock with a large posterior ventricular septal defect (VSD). The patient was successfully bridged to heart transplantation using the Impella 5.0 device to maintain hemodynamic stability.

134	Patel KM, et al. Anesth Analg. 2012	The use of transesophageal echocardiography (TEE) as an adjunct to fluoroscopy for confirmation of appropriate Impella 5.0 device placement is discussed.

135	Paul R, et al. Int J Artif Organs. 1998.	The authors demonstrate an in vitro testing procedure that allows the accelerated examination of the thrombogenic potential of different types of blood pumps. First results presented show accelerated clotting results indicative of thrombus formation at locations such as bearing for the centrifugal pump BioMedicus and two microaxial pumps.

136	Raess D, et al. J Cardiovasc Transl Res. 2009	This article describes the Impella 2.5 including the insertion method, fundamental principles of action, and clinical results from the completed Protect I clinical trial as well as general use under FDA clearance.

137	Rajagopal V, et al. J Heart Lung Transplant. 2010.	36-year-old man with acute cardiac transplant rejection bridged to recovery using simultaneous Impella 2.5 and TandemHeart percutaneous support devices. Nine months later, his left ventricular ejection fraction had stabilized from 10% to 55%.

138	Ramondo A, et al. J Cardiovasc Med (Hagerstown). 2006.	Case report of high-risk percutaneous coronary intervention in a 67-year-old man with a severe left ventricular dysfunction and three-vessel coronary artery disease using a novel left ventricular assist device (Impella 2.5), concluding that the use of LVAD may prevent catastrophic consequences of PCI-related complications and provide stable hemodynamic support.

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Pub#	Abbreviated Publication Citation	Brief Summary

139	Remmelink M, et al. Catheter Cardiovasc Interv. 2007.	Effect of left ventricular unloading by Impella 2.5 on coronary hemodynamics was studied in 11 patients with compromised LV function. Conclusions: “Unloading of the left ventricle by the Impella increased aortic and intracoronary pressure, increased hyperemic flow velocity, and decreased myocardial resistance. The Impella-induced increase in coronary flow probably results from both an increased perfusion pressure and a decreased LV volume-related intramyocardial resistance”.

140	Remmelink M, et al. Catheter Cardiovasc Interv. 2010.	The effects of the Impella 2.5 device on LV dynamics were studied in 11 patients (elective high-risk PCI, n = 6; primary PCI, n = 5). Conclusions: “LV unloading decreases end-diastolic wall stress and improves diastolic compliance dose-dependently. Our results indicate beneficial LV unloading effects of Impella 2.5 during high-risk PCI and primary PCI for AMI with STEMI”.

141	Reul H. Cardiology. 1994.	The engineering principles of rotary blood pumps are elucidated by means of a basic introduction into turbomachinery.

142	Romeo F. et al J Cardiovasc Med 2012	A case of successful combined use of Impella LP 2.5 and intra-aortic balloon pump in ST-elevation myocardial infarction with refractory cardiogenic shock is described.

143	Rosarius N, et al. Artif Organs. 1994.	A new microaxial pump concept is presented with an extracorporeal power supply and a proximally attached microelectric motor.

144	Rossiter-Thornton M, et al. Heart Lung Circ. 2008.	Case study of left ventricular support with the Impella 5.0 for post-cardiotomy cardiogenic shock. Conclusion: “This device has several advantages over existing forms of left ventricular support, and has the potential for widespread use in Australian centers”.

145	Samoukovic G, et al. Ann Thorac Surg. 2009.	We present a 52-year-old patient with multiorgan failure secondary to acute graft rejection after orthotopic heart transplantation. Maximal medical therapy was not successful, and the patient was bridged to recovery with an Impella 5.0 left ventricular assist device (LVAD). The relative merits of this therapeutic approach are outlined and discussed. The patient was discharged 3 weeks after LVAD removal and remains clinically stable.

146	Samoukovic G et al . Interact Cardiovasc Thorac Surg. 2009.	Case study of successful treatment of heart failure due to acute transplant rejection with the Impella 5.0.

147	Sarkar K, et al. Cardiol Clin. 2010.	This review article discusses the use of ercutaneous left ventricular support devices in the Cath Lab for support of patients in cardiogenic shock post-AMI and undergoing high-risk PCI.

148	Sassard T, et al. Ann Thorac Surg. 2008.	We describe a new Impella 5.0 implantation approach to the right axillary artery with the aims of avoiding vascular problems due to atherosclerosis of the peripheral arteries and improving patient mobility and rehabilitation during mechanical support.

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Pub#	Abbreviated Publication Citation	Brief Summary

149	Sauren LD, et al. Artif Organs. 2007.	Animal study to test combined Impella and intra-aortic balloon pump support to improve both ventricular unloading and coronary blood flow for myocardial recovery. The Impella support increased coronary flow by 47% and the IABP increased coronary flow by 13%. A stronger effect was provided when using the IABP support additional to Impella support.

150	Sayer GT, et al. Curr Opin Crit Care. 2012	Review article for management of cardiogenic shock using percutaneous mechanical circulatory support (intra-aortic balloon pump, Impella, TandemHeart, venoarterial extracorporeal membrane oxygenation) and surgically implanted devices (CentriMag). Review includes mechanisms involved in cardiogenic shock and discusses management and device selection strategies.

151	Schampaert S, et al. Artif Organs 2011.	This was an in-vitro study in a model controlled mock circulation loop to compare the hemodynamic benefits of the 40 cc IABP and the Impella 2.5 LP. Under cardiogenic shock or pre-shock conditions, both systems yield a 10% cardiac output increase and a 10% coronary flow increase. However, since the Impella 2.5 LP provides significantly better left ventricular unloading, the hemodynamic differences are slightly in favor of the Impella 2.5 LP.

152	Schmidt T, et al. Eur J Cardiothorac Surg. 2003.	We evaluated clinical outcome following beating heart myocardial revascularization using the ELECT system with intracardial left ventricular (LV) and pericardial right ventricular (RV) microaxial pumps in eight patients. Clinical course was uneventful. There were no device-related complications.

153	Schroeter MR, et al. Clin Res Cardiol. 2012	The authors describe a woman with peripartum cardiomyopathy and a pro-thrombotic condition who was successfully treated with bromocriptine and an Impella LP 2.5 heart pump.

154	Schuler G. et al. EuroInterv 2006.	Risk/benefit comparison of current cardiac support devices in cardiology, based on study reviews

155	Schwartz BG, et al. J Invasive Cardiol. 2011	A retrospective analysis of all cases involving prophylactic percutaneous LVAD support during HR-PCI. This institution treats patients with the least, intermediate, and highest risk of LV failure with an IABP, Impella, or TandemHeart, respectively. Fifty cases were identified (5 IABP, 13 Impella, 32 TandemHeart). Mean ejection fraction was 31±17%. All devices (100%) were initiated successfully. Angiographic success was achieved in 96% (80% IABP, 100% Impella, 97% TandemHeart). Of the 38 patients not in cardiogenic shock, death occurred in 1 (2.6%), recurrent ischemia in 3 (8%), and stroke in 0%. Shortly after device removal, systolic blood pressure (mean increase, +5±22 mmHg) and ejection fraction (mean increase, +7.4±11%; p = 0.0006) increased in all 3 groups, suggesting a beneficial effect on the myocardium.

156	Sciahbasi A, et al. J Cardiovasc Med 2009.	We describe a case of successful high-risk percutaneous coronary intervention in an octogenarian patient using the Impella 5.0 ventricular assist device.

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Pub#	Abbreviated Publication Citation	Brief Summary

157	Seyfarth M, et al. J Am Coll Cardiol. 2008.	A randomized clinical trial to evaluate the safety and efficacy of a percutaneous left ventricular assist device versus intra-aortic balloon pumping for treatment of cardiogenic shock caused by myocardial infarction (ISAR-SHOCK). Conclusion: “In patients presenting with cardiogenic shock caused by AMI, the use of a percutaneously placed LVAD (Impella 2.5) is feasible and safe, and provides superior hemodynamic support compared with standard treatment using an intra-aortic balloon pump”.

158	Shah R, et al. Cardiovasc Revasc Med. 2012	Seventy-four consecutive patients undergoing high-risk PCI and those with cardiogenic shock received IABP, TandemHeart, or Impella device. Patient undergoing high-risk PCI (n=57) and those treated for CS (n=17) were analyzed as separate cohorts. Patients undergoing IABP-assisted PCI were compared to those undergoing PLVAD (TandemHeart and Impella) assisted PCI. The primary end point was in-hospital major adverse cardiovascular events, and the secondary end point was in-hospital vascular complications. For the high-risk PCI cohort (n=57), 22 received PLVAD and 35 received IABP. Patients receiving IABP were younger and less likely to have a prior myocardial infarction (MI) and less likely to be on dialysis compared to those receiving PLVAD support. Patients receiving PLVAD support had a higher baseline Syntax score, had a higher prevalence of unprotected left main disease, underwent treatment of more coronary lesions, received more coronary stents, and more likely received drug-eluting stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. For the CS cohort (n=17), 4 received PLVAD and 13 received IABP. Patients receiving PLVAD support were more likely to have a prior MI, had a lower ejection fraction, underwent treatment of more coronary lesions, and received more coronary stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. The conclusions of the study were that IABP compared with PLVAD use for high-risk PCI and CS is associated with significantly different baseline patient, clinical, procedural, and angiographic characteristics. In-hospital clinical outcome was similar between both groups in both the high-risk PCI and the CS cohorts.

159	Sibbald M, et al. Catheter Cardiovasc Interv. 2012	We report a case of a 66-year-old woman with hemodynamic collapse during an elective PCI who was successfully resuscitated with an Impella device. She developed marked biochemical evidence of intravascular hemolysis. This necessitated device removal which resulted in prompt resolution of the hemolysis. We advise routine measurement of biochemical markers of hemolysis and serial hemoglobin values during Impella device support to allow timely detection and treatment of this important complication.

160	Siegenthaler MP, et al. J Thorac Cardiovasc Surg. 2004.	The Impella 5.0 LD microaxial left ventricular assist device reduces mortality for postcardiotomy failure and low-output syndrome: a three-center experience (n=24). Conclusion: “The Impella device provides 3 to 4 L/min flow. It improves survival in patients with low-output syndrome if the heart is able to pump 1 L/min or more above device flow”.

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Pub#	Abbreviated Publication Citation	Brief Summary

161	Siess T, et al. Artif Organs.1996.	In vitro and in vivo (sheep model) were used to demonstrate that more sophisticated pump management systems were required in order to deal with impaired flow conditions.

162	Siess T, et al. Artif Organs. 2001.	Technical report on the evolution of the Impella cardiac assist device, demonstrating the importance of generating high-quality lab prototypes in order to minimize iterations in product development.

163	Siess T, et al. Artif Organs. 1995 May.	Development of a new pump concept with the drive shaft cable replaced by a proximally integrated micro electric motor and an extra-corporeal power supply.

164	Siess T, et al. Artif Organs. 1995 July.	Techical report on in vitro testing of a new microaxial pump concept with an integrated microelectronic motor.

165	Sjauw KD, et al. Acute Card Care. 2007.	A case study: Demonstrating LV unloading on echocardiography during high risk PCI with a left ventricular assist device (the Impella 2.5).

166	Sjauw KD, et al. J Am Coll Cardiol. 2009.	The Europella registry included 144 consecutive patients who underwent a high-risk PCI supported with Impella 2.5. RESULTS: Patients were older (62% >70 years of age), 54% had an LV ejection fraction < or = 30%, and the prevalence of comorbid conditions was high. 43% of the patients were refused for coronary artery bypass grafting. A PCI was considered high-risk due to left main disease, last remaining vessel disease, multivessel coronary artery disease, and low LV function. Mortality at 30 days was 5.5%. Rates of myocardial infarction, stroke, bleeding requiring transfusion/surgery, and vascular complications at 30 days were 0%, 0.7%, 6.2%, and 4.0%, respectively. Conclusion: “This large multicenter registry supports the safety, feasibility, and potential usefulness of hemodynamic support with Impella 2.5 in high-risk PCI”.

167	Sjauw KD, et al. J Am Coll Cardiol. 2008.	Left Ventricular Unloading in Acute ST-Segment Elevation Myocardial Infarction Patients Is Safe and Feasible and Provides Acute and Sustained Left Ventricular Recovery. A head-to-head randomized comparison of IABP and Impella support in hemodynamically compromised patients with large anterior STEMI (n=20). Conclusion: “Findings concerning the safety and feasibility of prolonged Impella 2.5 support in the setting of STEMI are encouraging. Furthermore, LV unloading resulted in unexpected acute and sustained LV recovery compared with standard care patients. Percutaneous LVAD therapy may prove to be a promising alternative for the passive support offered by IABP”.

168	Sjauw KD, et al. Acute Card Care. 2007.	Although IABP therapy showed to be effective for stabilization of hemodynamically compromised patients, it has failed to show any long-term survival benefit in any setting of acute myocardial infarction. The rapid developments in ventricular assist device technology have led to the availability of several percutaneous implantable left ventricular assist devices (LVADs). These more potent percutaneous LVADs herald a promising alternative therapeutic approach for mechanical cardiac assistance other than IABP therapy.

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Pub#	Abbreviated Publication Citation	Brief Summary

169	Song X, et al. ASAIO J. 2003.	Review of design details, and experimental or clinical experience with the following axial flow support systems: Hemopump, MicroMed DeBakey VAD, Jarvik 2000, HeartMate II, Streamliner, Impella, Berlin INCOR I, Valvo pump, and IVAP.

170	Speiser BS. Dimens Crit Care Nurs. 2011.	This review discusses how to establish a percutaneous LVAD program at a hospital in order to meet the needs of the facility and patient population served.

171	Spillner J, et al. J. Cardiothorac Surg. 2012.	An animal model was used to demonstrate the feasibility of treating acute right ventricular failure by bypassing the right ventricle and pulmonary circulation with an oxygenating assist device, which may offer the advantages of enhanced right ventricular decompression and augmented left atrial filling.

172	Stoliński J, et al. Int J Artif Organs. 2002.	The heart-pump interaction and the pump performance were studied for a microaxial blood pump (ELECT) in 5 animals (sheep) and one human case for post-cardiotomy cardiogenic shock. Conclusion: “The heart-pump interaction based on the pump flow-differential pressure relationship can be useful in predicting the possibility to wean the patient from the device”.

173	Strauch JT, et al. J Thorac Cardiovasc Surg. 2005.	Technical feasibility of Impella 5.0 LD microaxial left ventricular assist device placement after biologic aortic valve replacement (21 mm) for postcardiotomy failure.

174	Strecker T, et al. J Cardiovasc Surg (Torino). 2004.	Impella 5.0 LD: successful perioperative support for off pump coronary artery bypass grafting surgery in a patient with end-stage ischemic cardiomyopathy.

175	Sugiki H, et al. Asian Cardiovasc Thorac Ann. 2009.	Six patients were studied for temporary right ventricular support with RECOVER RD axial flow pump. Effective support with pump flows of 4.0-4.5 L/min and adequate unloading as measured by central venous pressure was achieved in all patients.

176	Suradi H, et al. Tex Heart Inst J. 2011;38(4):437-40.	We describe a case of giant cell myocarditis in a previously healthy 44-year-old woman who presented with cardiogenic shock. She was supported hemodynamically with the Impella 2.5 left ventricular assist device until a permanent device could be surgically implanted.

177	Syed A, et al. Cardiovasc Revasc Med. 2010.	The authors state their opinion that the Protect II study will be significantly underpowered, based on their retrospective analysis of the adverse event rate with IABP-supported high-risk PCI at their institution.

178	Tevaearai HT, et al. Ann Thorac Surg. 2006.	A case study reporting leakage of the arterial prosthesis of an Impella RD implanted for support in right ventricular failure.

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Pub#	Abbreviated Publication Citation	Brief Summary

179	Thomopoulou S, et al. Hellenic J Cardiol. 2008.	Initial experience with the Impella 2.5 micro-axial pump in three patients undergoing high-risk coronary angioplasty. All were very poor candidates for surgery because of severe comorbidities, with mean logistic EuroSCORE 39.3%. The Impella was used for a mean time of 9.3 hours (range 2 to 24 hours).The device did not induce or increase aortic valve regurgitation. Mean blood pressure increased in all 3 pts without pulmonary wedge pressure reduction, presumably due to a combination of pump function and PCI-induced ischemia.

180	Toggweiler S et al. Eur J Echocardiogr. 2008.	Case study demonstrating functional mitral stenosis as a rare complication of the Impella 2.5 assist device. In a patient with cardiogenic shock after MI in whom an Impella 2.5 was implanted, the Impella device dislocated with the shaft of the device lying on the anterior mitral leaflet causing a functional mitral stenosis. After removing the device, the patient’s hemodynamics improved within minutes.

181	Tuseth V, et al. Resuscitation 2009.	A 12-pig animal study investigated whether a percutaneous left ventricular assist device, the Impella 2.5, can prevent acute cerebral ischemia during ventricular fibrillation. Conclusion was that a left ventricular assist device may prevent ischemic cerebral injury during cardiac arrest for a limited time.

182	Tuseth V, et al. Crit Care Med. 2009.	A 16-pig animal study was conducted to investigate the impact of percutaneous left ventricular support (Impella 2.5) during ventricular fibrillation (VF). The conclusion was that, during VF, a percutaneous left ventricular assist device may sustain vital organ perfusion.

183	Vaina S, et al. EuroIntervention.2006.	A new intracardiac echocardiography (AcuNaV - Siemens) was used at the site during interventional procedures, which included 6 high-risk PCI procedures performed with the Impella 2.5.

184	Valgimigli M, et al. EuroIntervention.2006.	An investigation was conducted of the clinical, hemodynamic and biochemical profile of the Impella 2.5 left ventricular assist device during elective high risk percutaneous coronary interventions (HR-PCI) in 12 patients. They concluded that their findings in 10 of the 12 patients on the efficacy of the Impella 2.5 during HR-PCI cannot support its routine use in this setting. They suggest that additional studies are required to confirm and investigate the mechanisms of the acute LV overload observed in the majority of the cases enrolled in the present study

185	Valgimigli M, et al. Catheter Cardiovasc Interv. 2005.	Left ventricular unloading and concomitant total cardiac output increase by the use of percutaneous Impella 2.5 assist device was investigated for a high-risk coronary intervention. The activation of the pump resulted in a rapid and sustained unloading effect of the LV. At the same time, the continuous expulsion of blood into ascending aorta throughout the cardiac cycle produced by the pump resulted in an increase of systemic overall CO, measured by the TD technique, of 1.43 L/min.

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Pub#	Abbreviated Publication Citation	Brief Summary

186	Vecchio S, et al. Minerva Cardioangiol. 2008.	The aim of this study was to evaluate the feasibility, safety and efficacy of the Impella 2.5 left ventricular assist device in patients with cardiogenic shock or undergoing high-risk percutaneous coronary interventions. Eleven patients presenting cardiogenic shock (N=6) or scheduled for high-risk percutaneous revascularization (N=5) were evaluated. During high-risk procedures, the Impella pump succeeded in obtaining hemodynamic stability, while in only two patients with cardiogenic shock the device determined a significant improvement of hemodynamic variables. All elective patients and two patients with cardiogenic shock were discharged from the hospital and were still alive at 30-day follow-up.

187	Vercaemst L, et al. J Extra Corpor Technol. 2002.	An in-vivo analysis of the flow performance of the Impella, a miniaturized cardiac support system, used in beating heart surgery in 12 patients in order to sustain hemodynamic stability and protect the heart from warm ischemia.

188	Vlasselaers et al. Intensive Care Med. 2006.	Case study report of ventricular unloading with a miniature axial flow pump, the Impella 2.5, in combination with extracorporeal membrane oxygenation (ECMO) for acute cardiorespiratory failure in a 13-year old boy. Conclusions: “A percutaneous miniature rotary blood pump can be an alternative to decompress a failing LV in the setting of veno-arterial ECMO”.

189	Wiktor DM, et al. ASAIO J. 2010	Case report of a patient who received the combined support of both an IABP and the Impella device for profound cardiogenic shock.

190	Windecker S, et al. Kardiovaskuläre Medizin 2005.	We describe the first Swiss Case of a high-risk percutaneous coronary intervention assisted by a new, percutaneously inserted left ventricular assist device: the Impella 2.5 pump.

191	Windecker S. Curr Opin Crit Care. 2007.	The review discusses the rationale and clinical utility of percutaneous left ventricular assist devices in the management of patients with cardiogenic shock. He reports about his experience with left ventricular assists, including the Impella 2.5. Clinical use of the Impella 2.5 device has been reported in 19 patients undergoing high-risk PCI. The device was successfully placed in all patients; there were no aortic valve regurgitation and no device-related complications. In conclusion the advent of easily manageable percutaneous LVADs constitutes an important advance in the management of patients with severe LV dysfunction and cardiogenic shock and may serve as a bridge to recovery or heart transplantation in selected patients.

192	Yildiz CE, et al. Heart Surg Forum. 2010.	We report the first assisted beating-heart coronary artery bypass graft surgery performed with the Impella Microaxial VAD (Impella 2.5 and 5.0 LD) in our country. The surgery was performed on 2 patients considered high risk on the basis of EUROSCORE testing. From the authors, “In patients with serious comorbidity, complete revascularization may be performed off pump, with the heart beating, because of the hemodynamic stability provided with the support of the microaxial intracardiac pump”.

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Pub#	Abbreviated Publication Citation	Brief Summary

193	Yoshitake I, et al. J Artif Organs. 2012	In a swine model, “heart rest therapy” (consisting of use of an Impella plus a beta blocker) after AMI stabilized hemodynamic conditions and reduced infarct size.

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