Impella Ventricular Systems Instructions for Use and Clinical Reference Manual Rev C Aug 2016

IMPORTANT NOTICE: Read this entire manual before using the Automated Impella® Controller and Impella® 2.5, 5.0, LD, or Impella CP® Circulatory Support System (Impella® System). The Impella® System is to be used only in accordance with this manual. This manual is only applicable to Impella® Systems using the Automated Impella® Controller. Information contained in this document is subject to change without notice. ©2016 Abiomed®, Inc. All rights reserved. The ABIOMED logo and ABIOMED are registered trademarks of Abiomed, Inc. in the U.S.A. and certain foreign countries. Recovering hearts. Saving lives. is a trademark of Abiomed, Inc. Impella is a registered trademark of Abiomed Europe GmbH, a wholly owned subsidiary of Abiomed, Inc., in the U.S.A. and certain foreign countries.

IMPELLA VENTRICULAR SUPPORT SYSTEMS FOR USE DURING CARDIOGENIC SHOCK INSTRUCTIONS FOR USE & CLINICAL REFERENCE MANUAL (UNITED STATES ONLY)

Rx Only

Abiomed, Inc. 22 Cherry Hill Drive Danvers, MA 01923 978-646-1400 (voice) 978-774-7240 (fax) [email protected] (email) Abiomed Europe GmbH Neuenhofer Weg 3 52074 Aachen, Germany +49 (241) 8860-0 (voice) +49 (241) 8860-111 (fax) [email protected] (email) www.abiomed.com 24-Hour Clinical Support Center: N. America 1-800-422-8666 Europe +49 (0) 1805 2246633 August 2016 Document No. 0042-9023 Rev. C

TABLE OF CONTENTS Introduction... I 1 INDICATIONS, CONTRAINDICATIONS, AND POTENTIAL ADVERSE EVENTS Indications (United States)... 1.1 Contraindications (United States)... 1.1 Potential Adverse Events (United States)... 1.2 2 WARNINGS AND CAUTIONS Warnings... 2.1 Cautions... 2.3 3 THE IMPELLA® CATHETER AND AUTOMATED IMPELLA® CONTROLLER Overview... 3.1 Impella® Catheter... 3.5 Automated Impella® Controller... 3.11 Purge Cassette... 3.12 Accessories... 3.14 4 USING THE AUTOMATED IMPELLA® CONTROLLER Overview... 4.1 Automated Impella® Controller Features... 4.2 Home Screen... 4.6 Placement Screen... 4.9 Purge Screen... 4.10 Infusion History Screen... 4.11 Mobile Operation... 4.12 5 USING THE AUTOMATED IMPELLA® CONTROLLER WITH THE IMPELLA® CATHETER Pre-support Evaluation... 5.1 Startup... 5.2 Case Start... 5.5 Impella® 2.5 Catheter Insertion (Wired)... 5.11 Wireless Insertion of the Impella® 2.5 Catheter... 5.16 Impella CP® Catheter Insertion... 5.17 Axillary Insertion of the Impella® 2.5, 5.0, or Impella CP® Catheter... 5.21 Alternate Insertion Technique for the Impella® 5.0 Catheter... 5.26 Implanting and Starting the Impella® LD Catheter... 5.30 Positioning and Starting the Impella® 2.5 and Impella CP® Catheters... 5.33 Positioning and Starting the Impella® 5.0 Catheter... 5.39 Positioning and Starting the Impella® LD Catheter... 5.43 Purge Cassette Procedures... 5.46 Troubleshooting the Purge System... 5.49 Patient Weaning... 5.51 Removing the Impella® 2.5, 5.0, or Impella CP® Catheter... 5.51 Explanting the Impella® LD Catheter... 5.53 6 CLINICAL EXPERIENCE Cardiac shock after acute myocardial infarction... 6.1 summary of primary clinical studies... 6.1 SUMMARY OF SUPPLEMENTAL CLINICAL INFORMATION... 6.7 Cardiac shock after open heart surgery... 6.17 summary of primary clinical studies... 6.17 SUMMARY OF SUPPLEMENTAL CLINICAL INFORMATION... 6.23 7 PATIENT MANAGEMENT TOPICS Patient Management Overview... 7.1 General Patient Care Considerations ... 7.1 Transport Within the Hospital... 7.2

Right Heart Failure... 7.2 ECG Interference... 7.3 Latex... 7.3 Use of Echocardiography for Positioning of the Impella® Catheter... 7.3 Understanding and Managing Impella®Catheter Position Alarms... 7.10 Impella Stopped... 7.18 Suction... 7.18 Hemolysis... 7.19 Operating the Impella® Catheter without Heparin in the Purge Solution... 7.21 Placement Signal Lumen (for Impella® 2.5 and Impella CP®)... 7.21 Pressure Sensor Drift and Placement Signal Not Reliable (for Impella® 5.0 and LD)... 7.23 Enabling Purge Flow Notifications... 7.24 Disabling Audio for Placement Signal Lumen Blocked Alarm (Impella® 2.5 and Impella CP®)... 7.24 Disabling Audio for SUCTION ALARM... 7.25 DISABLING AUDIO FOR PLACEMENT SIGNAL NOT RELIABLE ALARM ... 7.25 Disabling Audio for PURGE PRESSURE HIGH AND PURGE SYSTEM BLOCKED ALARMS... 7.25 Surgical Mode... 7.25 Timed Data Recording... 7.26 Operating the Impella® Catheter in Electromagnetic Fields... 7.26 Transferring from the Automated Impella® Controller to a New Automated Impella® Controller... 7.28 Emergency Shutdown Procedure... 7.29 8 AUTOMATED IMPELLA® CONTROLLER ALARMS Alarms Overview... 8.1 Alarm Message Summary... 8.3 9 GENERAL SYSTEM INFORMATION Terminology, Abbreviations, and Symbols... 9.1 Automated Impella® Controller Mechanical Specifications... 9.3 Automated Impella® Controller Electrical Specifications... 9.3 Equipment Design... 9.4 Equipment Classifications... 9.5 Federal Communications Commission (FCC) Notice... 9.5 Electromagnetic Compatibility... 9.6 Transport Between Hospitals... 9.7 VGA Monitor Connection... 9.11 Alarm Delay Information... 9.12 Patient Environment... 9.12 White Connector Cable... 9.13 Impella® Catheter Parameters... 9.13 Impella® 2.5 Catheter Dimensions... 9.14 Impella CP® Catheter Dimensions... 9.14 Impella® 5.0 Catheter Dimensions... 9.15 Impella® LD Catheter Dimensions... 9.15 Cleaning... 9.16 Storing the Automated Impella® Controller... 9.16 Returning an Impella® Catheter to Abiomed (United States)... 9.16 APPENDICES Appendix A: Impella VENTRICULAR SUPPORT SystemS Limited Service Warranty (United States)... A.1 Appendix B: Abiomed-Approved Guidewires and Introducers (Impella® 2.5 and Impella CP®)... B.1 Appendix C: Automated Impella® Controller Menu Structure... C.1

TABLE OF CONTENTS FIGURES Figure 3.1 Impella® Catheter in the Heart... 3.1 Figure 3.2a S et-up Configuration of the Automated Impella® Controller, Impella® 2.5 or Impella CP® Catheter, and Accessories (Impella CP® shown) 3.3 Figure 3.2b Standard Configuration of the Automated Impella® Controller, Impella® 2.5 or Impella CP® Catheter, and Accessories (Impella CP® shown)... 3.3 Figure 3.3 S et-up Configuration of the Automated Impella® Controller, Impella® 5.0 or LD Catheter, and Accessories (Impella® 5.0 shown)... 3.4 Figure 3.4 Impella® Catheters... 3.5 Figure 3.5 Impella® 5.0 and LD Differential Pressure Sensor (Impella® 5.0 shown) 3.9 Figure 3.6 Electrical Signal Generated by the Cardiac Cycle... 3.9 Figure 3.7 Correct Impella® 5.0/LD Catheter Positioning and Pulsatile Placement Signal... 3.10 Figure 3.8 Incorrect Impella® 5.0/LD Catheter Positioning and Flat Placement Signal... 3.10 Figure 3.9 Automated Impella® Controller – Front View... 3.11 Figure 3.10 Purge Cassette... 3.12 Figure 3.11 White Connector Cable... 3.14 Figure 3.12 Impella® 2.5 Introducer Kit... 3.14 Figure 3.13 Impella CP® Introducer Kit... 3.14 Figure 3.14 S ilicone Plugs (Impella® 5.0/LD)... 3.14 Figure 3.15 Impella® Axillary Insertion Kit (Impella® 2.5, 5.0, and Impella CP®) 3.15 Figure 3.16 Placement Guidewire... 3.15 Figure 3.17 Dextrose Solution... 3.15 Figure 3.18 A  utomated Impella® Controller Cart... 3.15 Figure 4.1 Automated Impella® Controller Features – Front View... 4.2 Figure 4.2 Automated Impella® Controller Features – Side Views... 4.4 Figure 4.3 Home Screen... 4.6 Figure 4.4 Placement Screen... 4.9 Figure 4.5 Purge Screen... 4.10 Figure 4.6 Infusion History Screen... 4.12 Figure 5.1 Automated Impella® Controller Power Switch... 5.3 Figure 5.2 Automated Impella® Controller Startup Screen... 5.4 Figure 5.3 Initial Case Start Screen... 5.5 Figure 5.4 Inserting Purge Cassette into Automated Impella® Controller... 5.6 Figure 5.5 Inserting the Catheter Plug into the Connector Cable... 5.7 Figure 5.6 Snapping Purge Clip to Connector Cable (Impella CP® shown) ..5.7 Figure 5.7 Connecting the Luer(s) to the Impella® Catheter (Impella CP® shown) 5.8 Figure 5.8 Connecting the Impella Catheter using the luers... 5.8 Figure 5.9 Squeezing the White Flush Valve to Prime the Placement Signal Lumen 5.9 Figure 5.10 Entering Purge Fluid Information... 5.9 Figure 5.11 Changing the Purge Fluid Information... 5.10 Figure 5.12 Connecting the Purge Tubing to the Connector Cable... 5.10 Figure 5.13 S et-up Configuration of the Impella Ventricular Support Systems (Impella CP® shown)... 5.11 Figure 5.14 Inserting the Peel-Away Introducer... 5.12 Figure 5.15 Inserting the Diagnostic Catheter... 5.12 Figure 5.16 Loading the Catheter on the Guidewire using the EasyGuide Lumen 5.13 Figure 5.17 Loading the Catheter on the Guidewire without the EasyGuide Lumen and Aligning the Placement Guidewire... 5.14 Figure 5.18 Inserting the Impella® Catheter... 5.14 Figure 5.19 Aortic Waveform on Final Case Start Screen... 5.15 Figure 5.21 Inserting the Diagnostic Catheter... 5.18 Figure 5.22 L oading the Catheter on the Guidewire using the EasyGuide Lumen

5.19 Figure 5.23 Loading the Catheter on the Guidewire without the EasyGuide Lumen and Aligning the Placement Guidewire... 5.19 Figure 5.24 Inserting the Impella® Catheter... 5.20 Figure 5.25 Aortic Waveform on Final Case Start Screen... 5.21 Figure 5.26 Introducer, Graft Lock, and Hemashield Platinum Graft (Graft Not Supplied)... 5.23 Figure 5.27 Correct Positioning If Second Graft Lock Required... 5.23 Figure 5.28 Closing the Graft Lock... 5.24 Figure 5.29 Releasing the Graft Lock... 5.25 Figure 5.30 Cut-Down Insertion of the Impella® 5.0 Catheter... 5.26 Figure 5.31 Guidewire Placement... 5.27 Figure 5.32 Femoral Artery Insertion of the Impella® 5.0 Catheter Using a Sidearm Graft... 5.29 Figure 5.33 Impella® LD Catheter with Silicone Plugs... 5.31 Figure 5.34 Waveform as Catheter is Advanced into the Aorta... 5.32 Figure 5.35 Pulsatile Waveform on Final Case StartScreen... 5.32 Figure 5.36 Starting the Impella® 2.5 and Impella CP® Catheter... 5.33 Figure 5.37 FLOW CONTROL Options for the Impella® 2.5 and Impella CP® Catheter... 5.33 Figure 5.38 Ventricular Waveform on Placement Signal Screen... 5.34 Figure 5.39 Transfer to P-level Mode... 5.34 Figure 5.40 Adjusting P-level... 5.36 Figure 5.41 Removing the Peel-Away Introducer (14 Fr Introducer shown)... 5.37 Figure 5.42 Standard Configuration for Impella Ventricular Support Systems after Transfer from the Set-up Configuration... 5.39 Figure 5.43 Waveform as Catheter is Advanced into the Aorta... 5.40 Figure 5.44 Pulsatile Waveform on Placement Screen... 5.41 Figure 5.45 Selecting P-level... 5.41 Figure 5.46 Confirming Placement on the Placement Signal Screen... 5.42 Figure 5.47 Selecting P-Level... 5.44 Figure 5.48 Confirming Placement on the Placement Signal Screen... 5.44 Figure 5.49 Impella® LD Catheter After Implantation... 5.45 Figure 5.50 Disconnecting the Y Connector from the Purge Cassette Tubing 5.47 Figure 5.51 Removing the Stylet... 5.52 Figure 5.52 Inserting the Guidewire with the Cheater... 5.53 Figure 5.53 Loosening the Tuohy-Borst Valve... 5.53 Figure 6.1 Kaplan-Meier survival curves survival (to 30 days) for the ISARSHOCK trial... 6.4 Figure 6.2 Lactate levels seen post-implant during the trial... 6.5 Figure 6.3 Increase in cardiac index from baseline, Impella vs. IABP 30 minutes post-support, in patients treated for cardiogenic shock after an AMI (ISAR-SHOCK)... 6.5 Figure 6.4 Change in inotropic dosage at 24 hours, Impella vs. IABP in patients treated for cardiogenic shock after an AMI (ISAR-SHOCK)... 6.6 Figure 6.5 Time intervals for Impella implants data collection by type of device 6.8 Figure 6.6 Kaplan-Meier curve estimates for 30 day survival – All patient cohort 6.9 Figure 6.7 Kaplan-Meier curve estimates, 30 day survival (by device) - All patient cohort... 6.9 Figure 6.8 Outcomes between Impella Registry subgroups: Patients likely to be eligible for RCTs vs. Patients likely to be excluded from RCTs (“salvage” patients)... 6.10 Figure 6.9 30-day outcomes (by device) between Impella Registry subgroups: Patients likely to be eligible for RCTs vs. Patients likely to be excluded from RCTs (“salvage” patients)... 6.11 Figure 6.10 Survival to discharge outcomes (by device) between Impella Registry subgroups: Patients likely to be eligible for RCTs vs. Patients likely to be excluded from RCTs (“salvage” patients)... 6.11 Figure 6.11 Kaplan-Meier curve estimates for 30-day survival... 6.12

TABLE OF CONTENTS Figure 6.12 Survival to discharge in AMICS cohort... 6.12 Figure 6.13 Improvement in patient hemodynamics (from baseline to 48hrs post device implant) for RECOVER I patients... 6.15 Figure 6.14 Decrease in inotropes and pressors (post-device placement) for RECOVER I patients... 6.15 Figure 6.15 RECOVER I enrollment... 6.19 AMI: Acute Myocardial Infarction; CABG: Coronary Artery Bypass Grafting; FDA: Food and Drug Administration; MVR: Mitral Valve Repair or Replacement; OHT: Orthotopic Heart Transplant; VAD: Ventricular Assist Device ... 6.19 Figure 6.16 Kaplan-Meier survival curve for freedom from death (to 1 year).6.21 Figure 6.17 Time intervals for Impella implants data collection by type of device 6.23 Figure 6.18 Kaplan-Meier curve estimates for 30 day survival – all patients cohort... 6.24 Figure 6.19 Kaplan-Meier curve estimates for 30 day survival – for difference devices... 6.24 Figure 6.20 Groups used for each classification analysis... 6.25 Figure 6.21 Kaplan-Meier curve for 30-day survival using Classification A (all patients)... 6.25 Figure 6.22 Kaplan-Meier curve for 30-day survival using Classification A (patients with Impella 5.0/LD)... 6.26 Figure 6.23 Kaplan-Meier curve for 30-day survival using Classification A (patients with Impella CP)... 6.26 Figure 6.24 Kaplan-Meier curve for 30-day survival using Classification A (patients with Impella 2.5)... 6.26 Figure 6.25 Kaplan-Meier curve for 30-day survival using Classification B (all patients)... 6.27 Figure 6.26 Kaplan-Meier curve for 30-day survival using Classification B (patients with Impella 5.0/LD)... 6.27 Figure 6.27 Kaplan-Meier curve for 30-day survival using Classification B (patients with Impella CP)... 6.27 Figure 6.28 Kaplan-Meier curve for 30-day survival using Classification B (patients with Impella 2.5)... 6.28 Figure 6.29 Flow diagram of the distribution of the AB5000 LVAD PCCS patient cohort... 6.29 Figure 6.30 Kaplan-Meier curve estimates for 30 day survival... 6.29 Figure 6.31 Improvement in patient hemodynamics (from baseline to 48 hr post-device implant) for RECOVER I patients... 6.31 Figure 6.32 Decrease in inotropes and pressors (post-device placement) for RECOVER I patients... 6.32 Figure 7.1 Labeled TEE and TTE Images of the Impella® Catheter Position... 7.4 Figure 7.2 Transesophageal Echocardiographic (TEE) Illustrations of Impella® Catheter Position... 7.7 Figure 7.3 Transthoracic Echocardiographic (TTE) Illustrations of Impella® Catheter Position... 7.8 Figure 7.4 Correct and Incorrect Impella® Catheter Position (Color Doppler TTE) 7.9 Figure 7.5 Correct Impella CP® Catheter Position (similar for Impella® 2.5).. 7.11 Figure 7.6 Correct Impella® 5.0 Catheter Position (similar for Impella® LD).. 7.11 Figure 7.7 Impella CP® Catheter Fully in Ventricle (similar for Impella® 2.5).. 7.12 Figure 7.8 Impella CP® Catheter Completely in the Aorta or Inlet and Outlet Areas in Ventricle and Open Pressure Area in Aorta (similar for Impella® 2.5)... 7.13 Figure 7.9 Impella CP® Catheter Position Unknown (similar for Impella® 2.5) 7.14 Figure 7.10 Impella® 5.0 Catheter Position Wrong (similar for Impella® LD).. 7.15 Figure 7.11 Impella® 5.0 Catheter Position Unknown (similar for Impella® LD) 7.16 Figure 7.12 Impella® 5.0 Catheter Outlet Area on or near Aortic Valve (similar for Impella® LD)... 7.17 Figure 7.13 Displacing Air During Flush Solution Change Out Procedure... 7.22

Figure 7.14 Surgical Mode Enabled... 7.26 Figure 8.1 Alarm Window... 8.2 Figure 9.1 Automated Impella® Controller Patient Environment... 9.12 Figure 9.2 Impella® 2.5 Catheter Dimensions... 9.14 Figure 9.3 Impella CP® Catheter Dimensions... 9.14 Figure 9.4 Impella® 5.0 Catheter Dimensions... 9.15 Figure 9.5 Impella® LD Catheter Dimensions... 9.15

TABLE OF CONTENTS TABLES Table 3.1 Impella® Set-up and Insertion Kit Components... 3.2 Table 3.2 Impella® Axillary Insertion Kit... 3.2 Table 3.3 Impella® Catheter Components... 3.7 Table 3.4 Purge Cassette Components... 3.13 Table 3.5 Impella® Catheter and Automated Impella® Controller Accessories 3.14 Table 4.1 Automated Impella® Controller Front View Features... 4.3 Table 4.2 Automated Impella® Controller Side View Features... 4.5 Table 4.3 Automated Impella® Controller Display Elements... 4.6 Table 5.1 Evaluation Prior to Inserting the Impella® Catheter... 5.1 Table 5.2 Additional Considerations Prior to Inserting the Impella® LD Catheter 5.1 Table 5.3 P-level Flow Rates for the Impella® 2.5 Catheter... 5.35 Table 5.4 P-level Flow Rates for the Impella CP® Catheter... 5.35 Table 5.5 P-Level Flow Rates for the Impella® 5.0 Catheter... 5.43 Table 5.6 P-Level Flow Rates for the Impella® LD Catheter... 5.46 Table 6.1 Baseline demographics and characteristics... 6.3 Table 6.3 Adverse Events Monitoring... 6.4 Table 6.4 Site-reported adverse events (to discharge) by classification... 6.13 Table 6.4 Site-reported adverse events (to discharge) by classification (continued) 6.14 Table 6.5 Baseline patient characteristics... 6.19 Table 6.5 Baseline patient characteristics (continued)... 6.20 Table 6.6 Baseline patient hemodynamics... 6.20 Table 6.6 Baseline patient hemodynamics (continued)... 6.21 Table 6.7 Site-reported adverse events (to discharge) by classification ... 6.30 Table 7.1 Guide for Managing Hemolysis in Various Circumstances... 7.20 Table 7.2 Recommended Standards for Maintenance of the Placement Signal for Impella® 2.5 and Impella CP® Catheters... 7.22 Table 7.3 Troubleshooting When Operating the Impella® Catheter in the Presence of an EAM System... 7.27 Table 7.4 Troubleshooting When Operating the Impella® Catheter in the Presence of a MNS System... 7.28 Table 8.1 Alarm Levels... 8.1 Table 8.2 Automated Impella® Controller Alarm Messages... 8.3 Table 9.1 Terminology and Abbreviations... 9.1 Table 9.2 Symbols... 9.1 Table 9.2 Symbols (continued)... 9.2 Table 9.3 Mechanical specifications for the Automated Impella Controller... 9.3 Table 9.4 Electrical specifications for the Automated Impella Controller... 9.3 Table 9.5 Equipment classifications... 9.5 Table 9.6 Guidance and manufacturer’s declaration - emissions, all equipment and systems... 9.9 Table 9.7 Guidance and manufacturer’s declaration - immunity... 9.9 Table B.1 Alternative Guidewires for Impella® 2.5 System... B.1 Table B.2 Alternative Introducer Sheaths for Impella® 2.5 and Impella CP® System... B.1

INTRODUCTION INTRODUCTION

PURPOSE OF MANUAL This Instructions for Use & Clinical Reference Manual is designed for healthcare professionals. It contains clinical and technical information to guide healthcare professionals in their use of the Impella® 2.5, 5.0, LD, and Impella CP® Catheters during cardiogenic shock. The Impella Ventricular Support Systems perform life-sustaining functions. To use the system you must understand and follow these instructions. The Impella Ventricular Support Systems may be used only for its intended purpose. MANUAL OVERVIEW This manual provides instructions for use of the Impella® 2.5, 5.0, LD, and Impella CP® Catheters with the Automated Impella® Controller. The following summarizes the contents of each section of the manual. • S ection 1: Indications, Contraindications, and Potential Adverse Events discusses indications for use of the Impella® Catheter with the Automated Impella® Controller, contraindications, and potential adverse events that may be associated with the use of the system. • S ection 2: Warnings and Cautions discusses the warnings and cautions pertaining to the use of the Impella® Catheter with the Automated Impella® Controller. • S ection 3: The Impella® Catheter and Automated Impella® Controller provides an overview of the system and describes its major components and features. • S ection 4: Using the Automated Impella® Controller describes the controls and various screen types on the Automated Impella® Controller. • Section 5: Using the Automated Impella® Controller with the Impella® Catheter provides the procedures for using the Impella Ventricular Support Systems. • S ection 6: Clinical Experience provides an overview of clinical studies of the Impella Ventricular Support Systems. • S ection 7: Patient Management Topics provides key information on various topics related to management of patients with the Impella® Catheter and Automated Impella® Controller. • S ection 8: Automated Impella® Controller Alarms provides a listing of Automated Impella® Controller alarms as well as information on what to do to resolve them. • S ection 9: General System Information contains information including definitions for key terms that appear in the manual, descriptions of the abbreviations and symbols that appear on Impella® Catheter and Automated Impella® Controller components and packaging, technical information pertaining to the Impella® Catheter and Automated Impella® Controller, and instructions on cleaning and storing system components as well as returning components to Abiomed. •A  ppendices at the end of the manual provide supplemental information about topics including the Impella® Limited Service Warranty; Abiomed-approved guidewires and introducers; and the Automated Impella® Controller menu structure. Impella Ventricular Support Systems for Use During Cardiogenic Shock

I

1 INDICATIONS, CONTRAINDICATIONS, AND POTENTIAL ADVERSE EVENTS

INDICATIONS (UNITED STATES)... 1.1 Impella® 2.5, Impella CP®, Impella® 5.0, and Impella® LD... 1.1 CONTRAINDICATIONS (UNITED STATES)... 1.1 POTENTIAL ADVERSE EVENTS (UNITED STATES)...1.2

1

INDICATIONS (UNITED STATES)

INDICATIONS, CONTRAINDICATIONS, AND POTENTIAL ADVERSE EVENTS

IMPELLA® 2.5, IMPELLA CP®, IMPELLA® 5.0, AND IMPELLA® LD The Impella® 2.5, Impella CP®, Impella® 5.0, and Impella® LD Catheters, in conjunction with the Automated Impella® Controller, are temporary ventricular support devices intended for short term use (< 4 days for the Impella® 2.5 and Impella CP®, and < 6 days for the Impella® 5.0 and Impella® LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (< 48 hours) following acute myocardial infarction or open heart surgery as a result of isolated left ventricular failure that is not responsive to optimal medical management and conventional treatment measures.* The intent of the Impella Ventricular Support Systems therapy is to reduce ventricular work and to provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function. *Optimal medical management and conventional treatment measures include volume loading and use of pressors and inotropes, with or without IABP

CONTRAINDICATIONS (UNITED STATES) Patients with aortic stenosis or other abnormal aortic valve performance may be compromised by the use of the Impella® Catheter. Patients with aortic valve disease should be observed for aortic insufficiency.

The Impella® System is contraindicated in patients with: • Mural thrombus in the left ventricle • Mechanical aortic valve or heart constrictive device • Aortic valve stenosis/calcification (equivalent to an orifice of 0.6 cm2 or less) • Moderate to severe aortic insufficiency (echocardiographic assessment of aortic insufficiency graded as ≥ +2) • Severe peripheral arterial disease that precludes the placement of the Impella® System • Significant right heart failure • Combined cardiorespiratory failure • Presence of an atrial or ventricular sepal defect (including post-infarct VSD) • Left ventricular rupture • Cardiac tamponade

Impella Ventricular Support Systems for Use During Cardiogenic Shock

1.1

POTENTIAL ADVERSE EVENTS (UNITED STATES) • Acute renal dysfunction

• Myocardial infarction

• Aortic insufficiency • Aortic valve injury

• Need for cardiac, thoracic or abdominal operation

• Atrial fibrillation

• Perforation

• Bleeding

• Renal failure

•C  ardiogenic shock

• Repeat revascularization

• Cardiac tamponade

• Respiratory dysfunction

• Cardiopulmonary resuscitation

• Sepsis

• Cerebral vascular accident / Stroke

• Severe hypotension

• Death

• Thrombocytopenia

• Device malfunction

• Thrombotic vascular (non-CNS) complication

• Failure to achieve angiographic success

• Transient ischemic attack

• Hemolysis

• Vascular injury

•H  epatic failure

• Ventricular arrhythmia, fibrillation or tachycardia

• Insertion site infection • Limb ischemia

1.2

Instructions for Use & Clinical Reference Manual (US)

2 WARNINGS AND CAUTIONS

WARNINGS...2.1 CAUTIONS... 2.3

WARNINGS 2

Institution of circulatory support using Impella® has not been studied in the following conditions: • Presence of irreversible end-organ failure • Presence of severe anoxic brain injury

Warnings Warnings alert you to situations that can cause death or serious injury. The red symbol appears before warning messages.

Fluoroscopy is required to guide placement of the Impella® Catheter and, for the Impella CP®, during rewire through the guidewire access port. The small placement guidewire must be reliably observed at all times. Be sure that the stopcock on the peel-away introducer or repositioning sheath is always kept in the closed position. Significant bleed back can result if the stopcock is open. Avoid manual compression of the inlet and outlet areas of the cannula assembly. The sterile components of the Impella Ventricular Support Systems can be used only if the sterilization indicators show that the contents have been sterilized, the packaging is not damaged, and the expiration date has not elapsed. Do NOT resterilize or reuse the Impella® Catheter. It is a disposable device and is intended for single use only. Reuse, reprocessing, or resterilization may compromise the structural integrity of the catheter and/or lead to catheter failure which, in turn, may result in patient injury, illness, or death. Retrograde flow will occur across the aortic valve if the flow rate of the Impella® Catheter is less than 0.5 L/min. To prevent malfunction of the locking mechanism of the peel-away introducer, do NOT hold the hemostatic valve while inserting into the artery. To prevent failure of the peel-away introducer, remove the peel-away introducer prior to transport when activated clotting time (ACT) is less than 150 seconds. Do NOT use saline in the purge system. Do NOT use an Impella Ventricular Support Systems if any part of the system is damaged. To prevent the risk of explosion, do NOT operate the Impella Ventricular Support Systems near flammable anesthetics. If at any time during the course of support with the Impella® Catheter, the Automated Impella® Controller alarms “Purge Pressure Low” or “Purge System Open,” follow the instructions presented in section 5 of this manual. MR Unsafe - Do NOT subject a patient who has been implanted with an Impella System to magnetic resonance imaging (MRI). The strong magnetic energy produced by an MRI machine may cause the Impella System components to stop working, and result in injuries to the patient. An MRI may also damage the Impella System electronics. Impella® System for Use During Cardiogenic Shock

2.1

WARNINGS AND CAUTIONS

Use of the Impella Ventricular Support Systems by trained and experienced practitioners has been associated with improved outcomes. Consequently, the first use of Impella® should be preceded by the completion of a contemporary Abiomed Impella® training program and include on-site proctoring during the first use by Abiomed clinical support personnel certified in the use of Impella®.

Cardiopulmonary support (CPR) should be initiated immediately per hospital protocol if indicated for any patient supported by the Impella® Catheter. When initiating CPR, reduce the Impella® Catheter flow rate. When cardiac function has been restored, return flow rate to the previous level and assess placement signals on the controller. During defibrillation, do NOT touch the Impella® Catheter, cables, or Automated Impella® Controller. Power the Automated Impella® Controller using its internal battery if the integrity of the protective earth conductor is questionable. Lithium-ion battery replacement by inadequately trained personnel could result in excessive temperatures, fire, or explosion. Only technicians authorized by Abiomed should remove or change the battery. To avoid risk of electric shock, this equipment must only be connected to a supply mains with protective earth. No modification of this equipment is allowed. Medical electrical equipment needs special precautions regarding EMC and needs to be installed and put into service according to the electromagnetic compatibility (EMC) information provided in section 9 of this manual. During transport, the Automated Impella® Controller may be exposed to stronger electromagnetic disturbance than during in-hospital use. Strong electromagnetic disturbance may cause the Automated Impella® Controller to display soft button menu selections that were not selected by the user. Operators should be aware that, under these conditions, the operating parameters are not affected. No user intervention is required. Monitor Impella® Catheter flow and patient hemodynamics to confirm normal operation. The condition will resolve itself once the Automated Impella® Controller is no longer exposed to the disturbance. Portable and mobile RF communications equipment can affect medical electrical equipment. The equipment or system should not be used adjacent to or stacked with other equipment. If adjacent or stacked use is necessary, the equipment or system should be observed to verify normal operation in the configuration in which it will be used. Use of cables, other than those sold by Abiomed, may result in increased emissions or decreased immunity of the Automated Impella® Controller. The Automated Impella® Controller uses RFID (radio frequency identification) to identify and communicate with the purge cassette. Other equipment may interfere with the Automated Impella® Controller even if that other equipment complies with CISPR emission requirements. Infusion through the sideport of the introducer can be done only after all air is removed from the introducer. If performed, the infusion should be done for flushing purposes only and NOT for delivering therapy or monitoring blood pressure. Do NOT use the guidewire access port on the Impella CP® as an arterial line. The stylet should remain in place until guidewire access is required through the Impella® Catheter.

2.2

Instructions for Use & Clinical Reference Manual (US)

CAUTIONS 2

Physicians should exercise special care when inserting the Impella® Catheter during active Cardiopulmonary Resuscitation (CPR). In addition, active CPR maneuvers may change the position of the Impella device. Check that the pump is positioned correctly in the left ventricle after CPR with echocardiography guidance. Patients with aortic stenosis or other abnormal aortic valve performance may be compromised by the use of the Impella® Catheter. Patients with aortic valve disease should be observed for aortic insufficiency.

Cautions Cautions indicate situations in which equipment may malfunction, be damaged, or cease to operate. The yellow symbol appears before caution messages.

Partial circulatory support with Impella® has been associated with more extensive use of rotational atherectomy. Extensive use of rotational atherectomy has been associated with a periprocedural increase in cardiac biomarkers indicative of myocardial injury. Rotational atherectomy, with or without the use of hemodynamic support, should be used in accordance with the manufacturer’s instructions for use. Physicians should exercise special care when inserting the Impella® Catheter in patients with known or suspected unrepaired abdominal aortic aneurysm or significant descending thoracic aortic aneurysm or dissection of the ascending, transverse, or descending aorta. Use only original accessories and replacement parts supplied by Abiomed. Do NOT use damaged or contaminated connector cables. To prevent device failure, do NOT start the Impella® Catheter until the guidewire has been removed. Do NOT remove the Impella® Catheter over the length of the guidewire. When replacing the purge cassette, the replacement process must be completed within 2 minutes. The Impella® Catheter may be damaged if replacement takes longer than 2 minutes. To prevent malfunction of the Automated Impella® Controller, avoid long-term exposure to direct sunlight and excessive heat (40°C). To prevent overheating and improper operation, do NOT block the cooling vents of the Automated Impella® Controller while it is operating. Do NOT kink or clamp the Impella® Catheter with anything other than a soft jaw vascular clamp. Do NOT kink or clamp the peel-away introducer. During case start, make sure the yellow luer connection between the purge tubing and Y connector is tightened and not leaking. The Li-Ion batteries must be charged for 5 hours prior to system operation in order to meet the runtime requirement of 1 hour. Failure to do so will yield a shorter runtime. After being unplugged, the Automated Impella® Controller will operate for at least 60 minutes after the batteries have been fully charged.

Impella® System for Use During Cardiogenic Shock

2.3

WARNINGS AND CAUTIONS

Handle with care. The Impella® Catheter can be damaged during removal from packaging, preparation, insertion, and removal. Do NOT bend, pull, or place excess pressure on the catheter or mechanical components at any time.

Minimize exposure of Impella Ventricular Support Systems components to sources of electromagnetic interference (EMI). Exposure to sources of EMI, such as cell phones and two-way radios, may cause operational interference. To clear interference, either increase the distance between system components and the EMI source or turn off the EMI source. During use with the Remote Link, a Medical Device Data System (MDDS), if the Automated Impella® Controller is exposed to strong electromagnetic disturbances, the Remote Link may either restart or shut down. Operators should be aware that, under these conditions, the Automated Impella® Controller operating parameters are not affected. If the Remote Link stops working because of electromagnetic disturbances, a hard restart (by first disconnecting, and then reconnecting its AC power) will correct the problem. Operation of Impella Ventricular Support Systems components may interfere with the operation of other devices. If interference occurs, increase the distance between the device and system components. Have a backup Automated Impella® Controller, purge cassette, connector cable, and Impella® Catheter available in the unlikely event of a device failure. Do NOT use the bed mount as a handle. Do NOT alter the Impella® Introducer kit in any way. Aspiration and saline flushing of the Impella® Introducer kit sheath, dilator, and valve should be performed to help minimize the potential for air embolism and clot formation. Indwelling introducer sheaths should be internally supported by a catheter or dilator. Dilators and catheters should be removed slowly from the sheath. Rapid removal may damage the valve, resulting in blood flow through the valve. Never advance the guidewire or sheath when resistance is met. Determine the cause of resistance using fluoroscopy and take remedial action. When injecting or aspirating through the sheath, use the sideport only. Operation of the system without heparin in the purge solution has not been tested. In the event that a patient is intolerant to heparin, due to heparin-induced thrombocytopenia or bleeding, physicians should use their clinical judgment to assess the risks versus benefits of operating the Impella Ventricular Support Systems without heparin. If it is in the best interest of the patient to operate the system without heparin, the dextrose solution is still required, and physicians should consider systemic delivery of an alternative anticoagulant. Do NOT add any alternative anticoagulant (such as a direct thrombin inhibitor) to the purge fluid. The Impella® Catheter has not been tested with any alternative anticoagulants in the purge solution.

2.4

Instructions for Use & Clinical Reference Manual (US)

3 THE IMPELLA® CATHETER AND AUTOMATED IMPELLA® CONTROLLER

OVERVIEW...3.1 Reusable System Components... 3.1 Single-use System Components...3.2 Impella® Set-up and Insertion kits (Impella® 2.5 and Impella CP®)...3.2 Impella® Axillary Insertion kit (Impella® 2.5, 5.0 and Impella CP®)...3.2 System Configurations...3.3 IMPELLA® CATHETER...3.5 Differential Pressure Sensor for Impella® 5.0 and LD...3.8 AUTOMATED IMPELLA® CONTROLLER... 3.11 PURGE CASSETTE... 3.12 ACCESSORIES... 3.14

OVERVIEW 3 THE IMPELLA® CATHETER AND AUTOMATED IMPELLA® CONTROLLER

The Impella® Catheter is an intravascular microaxial blood pump that supports a patient’s circulatory system during cardiogenic shock, low output syndrome, or other conditions. The Impella® 2.5, 5.0, and Impella® CP Catheters can be inserted percutaneously through the femoral or axillary artery and into the left ventricle. The Impella® LD is inserted directly through the ascending aorta and into the left ventricle.

Femoral Insertion

Axillary Insertion

Impella® 2.5, 5.0 and Impella CP®

Impella® 2.5, 5.0 and Impella CP®

Direct Insertion into Ascending Aorta Impella® LD only

Figure 3.1 Impella Catheter in the Heart ®

When properly positioned, the Impella® Catheter delivers blood from the inlet area, which sits inside the left ventricle, through the cannula, to the outlet opening in the ascending aorta. Physicians and device operators monitor the correct positioning and functioning of the Impella® Catheter on the display screen of the Automated Impella® Controller. This section describes the components of the Impella® Catheter and the Automated Impella® Controller, as well as the accessory components.

REUSABLE SYSTEM COMPONENTS The Impella Ventricular Support Systems consist of the following reusable components: • Automated Impella® Controller-provides the user interface, alarm indications, and portable battery • Automated Impella® Controller cart-for easy transport of the Automated Impella® Controller

Impella Ventricular Support Systems for Use During Cardiogenic Shock

3.1

SINGLE-USE SYSTEM COMPONENTS The Impella Ventricular Support Systems also include the following single-use components: • Impella® Catheter • Purge cassette • Introducer kit (Impella® 2.5 and Impella CP®) • 0.018 inch, 260 cm placement guidewire (Impella® 2.5, 5.0, and Impella CP®) • Impella® Axillary Insertion kit (Impella® 2.5, 5.0, and Impella CP®) • Connector cable • Incision template (Impella® LD) IMPELLA® SET-UP AND INSERTION KITS (IMPELLA® 2.5 AND IMPELLA CP®) The components of the Impella® 2.5 and Impella CP® Systems are each packaged into a single box called the Impella® Set-up and Insertion kit. Table 3.1 describes the contents of these kits. Table 3.1 Impella® Set-up and Insertion Kit Components

The Impella® Set-up and Insertion kit contains the following:

• Impella® Catheter • 0.018 inch, 260 cm placement guidewire • Connector cable • Purge cassette • Introducer kit »» Peel-away introducer (13 Fr for Impella® 2.5, 14 Fr for Impella CP®) »» Dilator(s) (13 Fr for Impella® 2.5, 8 Fr, 10 Fr, 12 Fr, and 14 Fr for Impella CP®) »» 18 G Seldinger needle (Impella® 2.5) »» 12 cc syringe (Impella® 2.5) »» 0.035 inch stiff access guidewire

IMPELLA® AXILLARY INSERTION KIT (IMPELLA® 2.5, 5.0 AND IMPELLA CP®) Table 3.2 describes the contents of the Impella® Axillary Insertion kit. Table 3.2 Impella® Axillary Insertion Kit

The Impella® Axillary Insertion kit contains the following:

• 23 Fr diameter x 6 cm length peel-away introducer • 2 graft locks used to attach a graft onto the introducer (Note: Only one graft lock is required when used with the recommended Hemashield Platinum graft; a back-up is provided.)

• 8 Fr silicone-coated lubrication dilator • 2 silicone plugs It is recommended that the Impella® Axillary Insertion kit be used in conjunction with a 10 mm diameter x 20 cm length Hemashield Platinum graft. 3.2

Instructions for Use & Clinical Reference Manual (US)

SYSTEM CONFIGURATIONS 3

Initial set-up configuration for Impella® 2.5 and Impella CP®

THE IMPELLA® CATHETER AND AUTOMATED IMPELLA® CONTROLLER

Figure 3.2a illustrates how the Automated Impella® Controller connects to the Impella® 2.5 or Impella CP® Catheter and accessory components in the initial set-up configuration. D20 D5

Dextrose Solution Automated Impella® Controller

Impella® Catheter

Purge Cassette

Connector Cable

Y-Connector

Figure 3.2a Set-up Configuration of the Automated Impella® Controller, Impella® 2.5 or Impella CP ® Catheter, and Accessories (Impella CP ® shown)

Standard configuration for Impella® 2.5 and Impella CP® Figure 3.2b illustrates the standard configuration of the Impella® 2.5 or Impella CP® Catheter, Automated Impella® Controller, and accessory components. D5

Dextrose Solution

Sodium Chloride (NaCl) Solution in Pressure Bag

Automated Impella® Controller

Impella® Catheter

Purge Cassette

Connector Cable

Y-Connector

Figure 3.2b S  tandard Configuration of the Automated Impella® Controller, Impella® 2.5 or Impella CP ® Catheter, and Accessories (Impella CP ® shown)

Impella Ventricular Support Systems for Use During Cardiogenic Shock

3.3