Vortex - First in Human Study to Evaluate the Feasibility, Safety, Clinical and Technical Success of the Vortex Temporary Percutaneous, Transvalvular Circulatory Support System (Vortex System)
Phase: NA
Conditions: Coronary Artery Disease
Sponsor: Boston Scientific Corporation

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Vortex Temporary Percutaneous Transvalvular Circulatory Support 
System Feasibility Study 
 
 
 Vortex Feasibility Study  
S2465 
CLINICAL INVESTIGATION PLAN 
 
Sponsored By 
Boston Scientific Corporation 
300 Boston Scientific Way 
Marlborough, MA 01752 USA 
 
European Authorized Representative 
Boston Scientific International S.A. 
Le Val Saint-Quentin 
2 rue René Caudron, 78960 
Voisins le Bretonneux, France 
 
Australian Representative 
Boston Scientific Pty. Ltd. 
Building 1, Level 6 
191 O’Riordan Street 
Mascot, NSW 2020, Australia 
 
 
This protocol contains confidential information for use by the Investigators and their 
designated representatives participating in this clinical investigation. The protocol should be 
held confidential and maintained in a secure location. 
Do not copy or distribute without written permission from Boston Scientific Corporation. 
 
 
 

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Contact Information 
 
Role 
Contact  
 
Clinical 
Contact 
Arjun Bhat, MBBS, MBA 
Sr. Clinical Trial Manager, Interventional 
Cardiology 
Boston Scientific  
300 Boston Scientific Way 
Marlborough, MA 01752 
E-mail: arjun.bhat@bsci.com 
 
Coordinating 
Principal 
Investigator 
and Site 
Principal 
Investigator  
Antony Walton, MBBS 
Deputy Director and Head of Catheter 
Laboratory 
Department of Cardiology 
The Alfred Hospital 
55 Commercial Road 
Melbourne VIC 3004  
Australia 
 
Site Principal 
Investigator 
Matthias Götberg, MD, PhD 
Director, Cardiac Catheterization Laboratory  
University Hospital of Lund 
Getingevagen 
Department of Coronary Heart Disease 
SE-221 85 Lund, Sweden 
 
 
 
Original Release: 10-Feb-2020 
Current Version: 21-May-2021 
 
Revision History 
Revision Number 
Release Date 
Template Version 
Reason for Change 
 
A 
10-Feb-2020 
90702637 Rev/Ver AL 
Not Applicable 
 
B 
13-Nov-2020 
90702637 Rev/Ver AM 
See Table 25.1-1 

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Revision History 
Revision Number 
Release Date 
Template Version 
Reason for Change 
              C 
3-Mar-2021 
90702637 Rev/Ver AO 
Change in Inclusion 
Criteria 3. LVEV is 
changed from left 
ventricular ejection 
fraction (LVEF) ≤ 
35% into left 
ventricular ejection 
fraction (LVEF) ≤ 50% 
to be consistent with 
the inclusion criteria of 
other contemporary 
mechanical circulatory 
support device studies 
and the labelling of the 
commercially approved 
(Abiomed) device 
              C 
3-Mar-2021 
90702637 Rev/Ver AO 
In Table 18.4-1 is the 
Serious Health Threat 
removed to follow the 
new protocol template 
where this is no longer 
required for the 
Investigator Reportings. 
D 
21-May-2021 
90702637 Rev/Ver AP 
See Table 25.1-1 
 
 
 

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2. Protocol Synopsis 
Vortex Temporary Percutaneous Transvalvular Circulatory Support 
System Feasibility Study: Vortex Feasibility Study 
Study 
Objective(s) 
To evaluate the feasibility and safety of the Vortex Temporary 
Percutaneous Transvalvular Circulatory Support System (Vortex 
System) in subjects undergoing elective high-risk percutaneous 
coronary intervention (HR-PCI) 
Planned 
Indication(s) 
for Use  
The Vortex System is indicated to provide temporary (≤ 4 hours) 
circulatory support in subjects undergoing elective high-risk 
percutaneous coronary intervention (HR-PCI). 
Test Device  
The Vortex System is a minimally invasive device that is in direct 
contact with the heart while in use. Components are summarized below. 
Component 
Description 
Vortex 
Pump 
 
- Axial flow pump magnetically coupled to the impeller 
with an expandable flexible cannula in a membrane-
covered pre-shaped braid and a proximal catheter    
- Introduced percutaneously via femoral artery access; 
advanced across the aortic valve into the left ventricular 
outflow tract; outlet ports are near the sinotubular 
junction  
Vortex 
Delivery 
System 
- Starter tube 
- Introducer sheath with 16 Fr profile, 35-cm length 
- Dilator (compatible with 0.035” wire) 
-  Cannula delivery tool  
Vortex Wire 
- 0.018” diameter, 300-cm length, shapeable tip 
Vortex 
Console 
- Interface to control/monitor the pump; connected to the 
pump using a sterile extension cable, which is plugged into 
the wall and controls power to the pump 
 
 

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Vortex Temporary Percutaneous Transvalvular Circulatory Support 
System Feasibility Study: Vortex Feasibility Study 
Study Design 
The Vortex Feasibility Study is a prospective, open-label, single-arm 
study designed to assess the safety and feasibility of the Vortex System 
to provide temporary (≤ 4 hours) circulatory support in subjects 
undergoing HR-PCI. 
The study design is summarized in the figure below. 
 
Vortex Feasibility Study Design Overview 
The Vortex study will be conducted in accordance with the 
International Standard ISO 14155:2020 Clinical Investigation of 
Medical Devices for Human Subjects – Good Clinical Practice; 
European Medical Device Regulations; ethical principles that have their 
origins in the Declaration of Helsinki; and pertinent individual 
country/state/local laws and regulations. The study shall not begin until 
the required approval/favorable opinion from the Independent Ethics 
Committee (IEC)/Human Research Ethics Committee (HREC) and/or 
regulatory authority has been obtained, if appropriate. 
Planned 
Number of 
Subjects / 
Investigational 
Centers / 
Countries 
There will be up to 10 subjects enrolled in up to 3 centers in Australia 
and Europe. 
Primary 
Endpoint 
The primary endpoint consists of Technical Success and Clinical 
Success, defined as follows. 
Technical Success 
• Successful delivery of the device to the correct anatomical 
position; and 

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Vortex Temporary Percutaneous Transvalvular Circulatory Support 
System Feasibility Study: Vortex Feasibility Study 
• Successful operation and removal of the Vortex circulatory 
support system 
Clinical Success 
• No conversion to open heart surgery; and 
• No in-hospital mortality  
Additional 
Measurements 
Safety events will be collected through 72 hours post-procedure or 
hospital discharge, whichever comes first, as listed below.  
• Stroke/transient ischemic attack (TIA; see Note 1 below) 
• Cardiac tamponade 
• Cardiac death (see Note 1 below) 
• Myocardial infarction (MI) 
• Bleeding complications: Type 3–5 based on the Mechanical 
Circulatory Support Academic Research Consortium (MCS-
ARC) definitionsa (see Note 1 below) 
• Acute kidney injury (AKI; based on the AKIN System Stage 3 
[including renal replacement therapy] or Stage 2) 
• Major vascular complications (see Note 1 below) 
• Any device-related adverse event (adverse device effect 
[ADE]/serious adverse device effect [SADE]) 
• Any procedure-related adverse event 
• Any adverse event related to management practices 
• Any adverse event related to patient specific adherence 
• Any unanticipated serious adverse device effect (USADE) 
Note 1: Death, stroke, bleeding complications, and major vascular 
complications are adjudicated by an Independent Medical Reviewer 
(IMR). 
a:  Kormos RL, et al. J Heart Lung Transplant 2020;39:735-50 
Method of 
Assigning 
Subjects who provide written informed consent and are confirmed 
eligible for the study are considered enrolled in the study as soon as an 

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Vortex Temporary Percutaneous Transvalvular Circulatory Support 
System Feasibility Study: Vortex Feasibility Study 
Patients to 
Treatment 
attempt is made to insert any part of the Vortex System into the 
subject’s femoral artery (e.g., Vortex sheath).  
Follow-up 
Schedule 
Follow up will occur through 72 hours or hospital discharge, 
whichever comes first. 
Study Duration Enrollment/total study duration may be completed in approximately 12 
months. 
Participant 
Duration 
The study duration for each subject is expected to be through 72 hours 
or hospital discharge, whichever comes first. 
Inclusion 
Criteria 
A subject will be considered for enrollment if all of the following 
inclusion criteria are met, provided no exclusion criteria are met. 
IC1. 
Subject provides signed informed consent.  
IC2.  Subject is ≥ 18 years and < 90 years of age.  
IC3.  Subject is indicated for NON-emergent PCI of at least one de 
novo or restenotic lesion in a native coronary vessel or coronary 
artery bypass graft (CABG) and has left ventricular ejection 
fraction (LVEF) ≤ 50% with the following: 
• Unprotected left main -OR- 
• Last remaining vessel -OR- 
• Three vessel disease (≥ 50% diameter stenoses by visual 
estimate or total occlusion)  
Exclusion 
Criteria 
A subject will be excluded from the study if any of the following 
exclusion criteria are met. 
EC1. Subject has had ST-elevation myocardial infarction (STEMI) 
within 24 hours. 
EC2. Subject has had pre-procedure cardiac arrest requiring 
cardiopulmonary resuscitation (CPR) within 24 hours of 
enrollment. 
EC3. Subject is in shock, defined as follows: 
• Cardiac index (CI) < 2.2 L/min/m2 and pulmonary capillary 
wedge pressure (PCWP) > 15 mmHg -AND- 
• Hypotension (systolic blood pressure < 90 mmHg for 
> 30 minutes) -OR- 

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• Need for supportive measures (i.e., inotropes or mechanical 
support) to maintain systolic blood pressure ≥ 90 mmHg 
and end organ hypoperfusion (cool extremities or urine 
< 30 mL/hour and a heart rate > 60 beats per minute) 
EC4. Subject has left ventricular mural thrombus. 
EC5. Subject has a prosthetic aortic valve. 
EC6. Subject has pericarditis or constrictive heart disease 
(constrictive pericarditis or restrictive cardiomyopathy). 
EC7. Subject has moderate or greater aortic valve stenosisb or 
moderate or greater aortic valve insufficiencyb (by 
echocardiographic assessment, graded as ≥ 2+). 
EC8. Subject has abnormalities of the aorta that preclude safe 
delivery of the device, including severe calcification, 
tortuosity, aneurysm, or prior surgery. 
EC9. Subject has peripheral vessel disease (PVD) preventing passage 
of the device (e.g., calcification, small caliber) or tortuosity that 
would preclude safe placement of the 16 Fr introducer sheath. 
 
Note 2: Minimum required vessel diameter is > 5.5 mm. 
EC10. Subject has advanced renal dysfunction (AKIN Stage 3). 
EC11. Subject has a history of liver dysfunction (Childs Class C) with 
elevation of liver enzymes and bilirubin > 3× upper limit of 
normal (ULN) or international normalization ratio (INR) ≥ 2. 
EC12. Subject has had a recent (within 1 month) stroke or TIA. 
EC13. Subject has known hypersensitivity to intravenous contrast 
agents that cannot be adequately pre-medicated or has known 
hypersensitivity to heparin, aspirin, ADP receptor inhibitors or 
nitinol. 
EC14. Subject has current or a history of heparin induced 
thrombocytopenia (HIT). 
EC15. Subject has uncorrected abnormal coagulation or platelet count 
≤ 75,000/mm³ or INR ≥ 2.0.  
EC16. Subject has significant right heart failure (right atrial pressure 
[RAP] > 15 mmHg, right ventricular stroke work index 

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[RVSWI] < 0.30 mmHg·L/m², pulmonary vascular resistance 
[PVR] > 3.6 Woods units).  
EC17. Subject requires mechanical ventilation.  
EC18. Subject has an atrial or ventricular septal defect (including post-
infarct ventricular septal defect [VSD]). 
EC19. Subject has left ventricular rupture.  
EC20. Subject has cardiac tamponade. 
EC21. Subject has severe pulmonary disease (FEV1 < 1L). 
EC22. Subject has sustained or non-sustained ventricular tachycardia. 
EC23. Subject is breast feeding or is pregnant. 
EC24.  Subject has other disease condition(s) resulting in the subject 
being unsuitable for participation in the clinical trial (e.g. 
advanced malignancy with limited expected survival) 
EC25.  Subject has other disease condition(s) which the Investigator has 
determined may cause non-compliance to the study 
requirements. 
b: Nishimura RA, et al. J Am Coll Cardiol 2014;63:e57-185. 
Index 
Procedure 
The Vortex sheath will be inserted percutaneously into the femoral 
artery. The Vortex wire and Vortex pump will pass though this sheath 
during the procedure and will be advanced through the aorta, across the 
aortic valve, and into the left ventricle. The wire will be withdrawn 
before the pump is turned on, but the sheath and pump will stay in 
place throughout the HR-PCI procedure and will be withdrawn as soon 
as the mechanical circulatory support is deemed to be unnecessary. 
Statistical Methods  
Primary 
Statistical 
Hypothesis 
There is no formal statistical hypothesis in this observational feasibility 
study.  
Statistical Test 
Method 
Descriptive statistics will be used for baseline, procedure, and follow-
up data collected during the study.  
The primary endpoint and additional measurements will be analyzed on 
an intention-to-treat (ITT) basis and a per-protocol basis. Analysis sets 

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Vortex Temporary Percutaneous Transvalvular Circulatory Support 
System Feasibility Study: Vortex Feasibility Study 
are listed below. Subjects are considered enrolled in the study as soon 
as an attempt is made to insert any part of the Vortex System into the 
subject's femoral artery. 
• ITT: This population includes all subjects who sign an Informed 
Consent Form (ICF) and are enrolled in the study, whether or 
not a study device is successfully inserted and used. 
• Per-protocol: This population includes all ITT subjects in whom 
the device is successfully advanced across the aortic valve into 
the left ventricular outflow tract and turned on. 
Sample Size 
Parameters 
This is a prospective, multicenter, non-randomized feasibility study 
with no formal pre-specified hypothesis and therefore sample size 
estimates are not applicable. In order to support the stated objectives 
of this feasibility study, the study sample size has been limited to a 
maximum of up to 10 subjects enrolled. 
 
 

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3. Table of Contents 
1. 
TITLE PAGE  .......................................................................................................................1 
2. 
PROTOCOL SYNOPSIS .........................................................................................................4 
3. 
TABLE OF CONTENTS .......................................................................................................11 
3.1. Table of Figures .....................................................................................................14 
3.2. Table of Tables ......................................................................................................15 
4. 
INTRODUCTION ................................................................................................................16 
4.1. Background ............................................................................................................16 
4.1.1. 
High-Risk Percutaneous Coronary Intervention .......................................16 
4.1.2. 
Mechanical Circulatory Support ...............................................................16 
4.2. Study Rationale .....................................................................................................18 
5. 
DEVICE DESCRIPTION ......................................................................................................18 
5.1. Vortex System ........................................................................................................19 
5.1.1. 
Vortex Pump .............................................................................................19 
5.1.2. 
Vortex Delivery System ...........................................................................20 
5.1.3. 
Vortex Console .........................................................................................21 
5.2. Device Labeling .....................................................................................................22 
5.3. Ancillary Devices and Procedures .......................................................................22 
6. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................................22 
6.1. Objectives ...............................................................................................................22 
6.2. Primary Endpoint .................................................................................................22 
6.3. Additional Measurements ....................................................................................23 
6.4. Overview of Objectives and Endpoints ...............................................................23 
7. 
STUDY DESIGN .................................................................................................................24 
7.1. Scale and Duration ................................................................................................24 
7.2. Treatment Assignment .........................................................................................24 
7.3. Justification for the Study Design ........................................................................25 
8. 
SUBJECT SELECTION ........................................................................................................25 
8.1. Study Population and Eligibility ..........................................................................25 

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8.2. Inclusion Criteria ..................................................................................................25 
8.3. Exclusion Criteria .................................................................................................25 
9. 
SUBJECT ACCOUNTABILITY .............................................................................................28 
9.1. Point of Enrollment ...............................................................................................28 
9.2. Withdrawal ............................................................................................................28 
9.3. End-of-Study Definition .......................................................................................28 
10. STUDY METHODS .............................................................................................................29 
10.1. Data Collection ......................................................................................................29 
10.2. Study Candidate Screening ..................................................................................32 
10.3. Informed Consent .................................................................................................32 
10.4. Screening Assessments ..........................................................................................32 
10.5. Baseline Assessments ............................................................................................33 
10.6. Pre-procedure/Procedural Medications ..............................................................33 
10.7. Index Procedure ....................................................................................................33 
10.7.1. Vortex System Procedure .........................................................................33 
10.7.2. Intraprocedural Cardiac Imaging ..............................................................34 
10.7.3. Intraprocedural Hemodynamic Measurements .........................................34 
10.8. Post-procedure (≤ 72 Hours)/Prior to Hospital Discharge ................................35 
10.9. Study Completion ..................................................................................................35 
10.10. 
Source Documents ..................................................................................35 
10.11. 
Local Laboratory/Vendor Documentation ...........................................36 
11. STATISTICAL CONSIDERATIONS ......................................................................................36 
11.1. Endpoints ...............................................................................................................36 
11.1.1. Primary Endpoint ......................................................................................36 
11.1.1.1. Hypotheses ...............................................................................36 
11.1.1.2. Sample Size ..............................................................................36 
11.1.1.3. Statistical Methods ...................................................................36 
11.1.2. Additional Measurements .........................................................................37 
11.2. General Statistical Methods .................................................................................37 
11.2.1. Analysis Sets .............................................................................................37 
11.2.2. Control of Systematic Error/Bias ..............................................................37 
11.3. Data Analyses ........................................................................................................37 

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12. DATA MANAGEMENT .......................................................................................................38 
12.1. Data Collection, Processing, and Review ............................................................38 
12.2. Data Retention .......................................................................................................38 
13. DEVIATIONS .....................................................................................................................39 
14. DEVICE ACCOUNTABILITY FOR PRODUCTS LABELLED INVESTIGATIONAL ..................39 
15. COMPLIANCE ....................................................................................................................40 
15.1. Statement of Compliance ......................................................................................40 
15.2. Investigator Responsibilities ................................................................................40 
15.2.1. Delegation of Responsibility ....................................................................42 
15.3. Independent Ethics Committee / Human Research Ethics Committee ...........43 
15.4. Sponsor Responsibilities .......................................................................................43 
15.4.1. Training .....................................................................................................43 
15.4.2. Role of Boston Scientific Representatives ...............................................44 
15.5. Insurance ................................................................................................................45 
16. MONITORING ....................................................................................................................45 
17. POTENTIAL RISKS AND BENEFITS ...................................................................................46 
17.1. Anticipated Adverse Events and Adverse Device Effects ..................................46 
17.2. Risks Associated with the Study Device ..............................................................47 
17.3. Risks Associated with Participation in the Clinical Study ................................47 
17.4. Possible Interactions with Concomitant Medical Treatments ..........................47 
17.5. Risk Minimization Actions ...................................................................................48 
17.6. Anticipated Benefits ..............................................................................................49 
17.7. Risk to Benefit Rationale ......................................................................................49 
18. SAFETY REPORTING .........................................................................................................49 
18.1. Reportable Events by Investigational Center to Boston Scientific ...................49 
18.2. Definitions and Classification ..............................................................................50 
18.3. Relationship to Study Device(s) and/or Study Procedure .................................52 
18.4. Investigator Reporting Requirements .................................................................53 
18.5. Boston Scientific Device Deficiencies ...................................................................55 
18.6. Reporting to Regulatory Authorities / IECs / HRECs/ Investigators ..............55 

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19. INFORMED CONSENT ........................................................................................................55 
20. COMMITTEES ...................................................................................................................57 
20.1. Safety Monitoring Process ....................................................................................57 
20.2. Independent Medical Reviewer ...........................................................................57 
21. SUSPENSION OR TERMINATION ........................................................................................57 
21.1. Premature Termination of the Study ..................................................................57 
21.1.1. Criteria for Premature Termination of the Study ......................................57 
21.2. Termination of Study Participation by the Investigator or Withdrawal of 
IEC/HREC Approval ............................................................................................58 
21.3. Requirements for Documentation and Subject Follow-up ................................58 
21.4. Criteria for Suspending/Terminating a Study Center .......................................58 
22. STUDY REGISTRATION AND RESULTS .............................................................................59 
22.1. Study Registration .................................................................................................59 
22.2. Clinical Investigation Report ...............................................................................59 
22.3. Publication Policy ..................................................................................................59 
23. BIBLIOGRAPHY .................................................................................................................60 
24. ABBREVIATIONS AND DEFINITIONS .................................................................................63 
24.1. Abbreviations ........................................................................................................63 
24.2. Definitions ..............................................................................................................64 
25. REVISION HISTORY ..........................................................................................................74 
25.1. Summary of Protocol Revision History ...............................................................74 
 
3.1. Table of Figures 
Figure 5.1-1: Vortex Pump ..................................................................................................... 20 
Figure 5.1-2: Vortex Wire and Vortex Introducer Sheath and Dilator ................................... 21 
Figure 5.1-3: Vortex Console ................................................................................................. 21 
Figure 7.1-1: Vortex Feasibility Study Design Overview ...................................................... 24 
Figure 10.1-1: Vortex Study Data Collection Schedule ......................................................... 30 
 

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3.2. Table of Tables 
Table 5.1-1: Summary of Vortex System Components .......................................................... 19 
Table 6.4-1: Overview of Objectives and Endpoints .............................................................. 23 
Table 8.2-1: Inclusion Criteria ................................................................................................ 25 
Table 8.3-1: Exclusion Criteria ............................................................................................... 26 
Table 10.1-1: Data Collection Schedule ................................................................................. 31 
Table 10.10-1: Source Documentation Requirements ............................................................ 36 
Table 17.1-1: Risks Associated with Use of the Vortex System During High-Risk 
Percutaneous Coronary Intervention ................................................................... 46 
Table 18.2-1: Safety Definitions ............................................................................................. 50 
Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to Adverse 
Event .................................................................................................................... 52 
Table 18.4-1: Investigator Reporting Requirements ............................................................... 54 
Table 24.1-1: Abbreviations ................................................................................................... 63 
Table 24.2-1: Definitions ........................................................................................................ 64 
Table 25.1-1: Protocol Revision History ................................................................................ 75 
 
 
 

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4.  Introduction 
4.1. Background 
Coronary artery disease (CAD) is a leading cause of morbidity and mortality globally1. 
Treatments to reduce adverse clinical events and improve quality of life in patients with 
symptomatic CAD include guideline-directed medical therapy, percutaneous coronary 
intervention (PCI), and coronary artery bypass grafting (CABG)2,3. As PCI technology has 
evolved, an expanded population eligible for percutaneous treatment has emerged, including 
high-risk patients who are older, have complex anatomic lesions, and/or have multiple 
comorbidities that preclude surgical revascularization4,5. 
4.1.1. High-Risk Percutaneous Coronary Intervention 
High-risk percutaneous coronary intervention (HR-PCI) has become a valuable therapeutic 
approach for the growing patient population referred to as "complex high-risk and indicated 
patients" (CHIP)6. This patient group is characterized by technically complex CAD 
(multivessel or left main disease, anatomically complex coronary lesions, target vessel 
providing collateral supply to an occluded second vessel supplying > 40% of the 
myocardium [anticipated high ischemic burden during the procedure or last remaining 
conduit]), adverse hemodynamics (including abnormal ventricular/valvular function), and/or 
significant medical comorbidities (including advanced age, diabetes, peripheral vascular 
disease, heart failure, acute coronary syndromes, or previous cardiac surgery)4. While 
registry data and retrospective analysis of randomized trials suggest that complete 
revascularization results in the best patient outcomes7,8, members of the CHIP population 
often undergo incomplete revascularization or staged PCI. This is due to prolonged 
procedure times and/or procedural complications owing to multiple balloon inflations or 
atherectomy and can lead to a higher incidence of adverse clinical outcomes7,9. Patients with 
severe CAD and reduced left ventricular ejection fraction (LVEF) are especially prone to 
peri-procedural complications and often have poorer long-term outcomes10,11. Among these 
patients, temporary mechanical circulatory support (MCS) may improve short- and long-term 
results12. 
4.1.2. Mechanical Circulatory Support 
Percutaneous MCS devices are designed to temporarily decrease the load on the heart and 
ensure adequate organ perfusion12-15. They are increasingly used prophylactically or as part 
of an anticipatory strategy for HR-PCI patients to enable more complex procedures and 
provide protection from adverse events until the benefits of reperfusion are achieved 
(protected PCI)12,16. There are several percutaneous MCS devices available, with variable 
impact on cardiovascular hemodynamics13,15,17. They include the intra-aortic balloon pump 
(IABP), centrifugal pumps, venous arterial extracorporeal membrane oxygenation devices, 
and micro-axial pumps6,15,17. Society guidelines state that elective insertion of an appropriate 
hemodynamic support device as an adjunct to PCI may be reasonable in carefully selected 
high-risk patients14,18. 

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The IABP has been studied extensively and used most widely in HR-PCI15. It displaces blood 
volume in the descending aorta by inflating during diastole and producing a potential space 
during systole that supports cardiac filling of the aorta. The effect is to reduce myocardial 
work and oxygen demand. It provides a modest increase in cardiac index (cardiac output 
from 0.5 to 1.0 L/min).  
The Impella® device (Abiomed, Inc., Danvers, MA, USA) is a catheter-mounted, 
nonpulsatile, microaxial pump that continuously pulls oxygenated blood from the left 
ventricle and propels it into the ascending aorta15. This extraction unloads the left ventricle 
and reduces myocardial wall stress, pulmonary capillary wedge pressure, and myocardial 
oxygen demand. The increased unloading results in ventriculoarterial uncoupling19. In the 
presence of critical stenoses, use of Impella improves distal coronary pressure and coronary 
perfusion pressure, thereby lessening the ischemic burden20. The Impella LD®, Impella 5.0®, 
and Impella 2.5® received CE Mark in 2002, 2003, and 2004, respectively. The Impella 2.5, 
Impella CP®, and Impella CP® with SmartAssist® are CE marked for treatment of HR-PCI 
and acute myocardial infarction cardiogenic shock patients for up to 5 days. The United 
States Food and Drug Administration approved the Impella 2.5® and Impella CP® Systems as 
temporary (≤6 hours) ventricular support devices indicated for use during HR-PCI performed 
in elective or urgent, hemodynamically stable patients with severe CAD, when a heart team, 
including a cardiac surgeon, has determined HR-PCI is the appropriate therapeutic option21. 
Safety and effectiveness of Impella support in HR-PCI was examined in the prospective, 
single-arm PROTECT I feasibility study22. Patients (N=20) had LVEF ≤35% and underwent 
PCI on an unprotected left main coronary artery or last patent coronary conduit. Patients with 
recent ST-elevation myocardial infarction (STEMI) or cardiogenic shock were excluded. The 
Impella 2.5 device was implanted successfully in all patients; mean duration of circulatory 
support was 1.7±0.6 hours (range of 0.4 to 2.5 hours) with a mean pump flow during PCI of 
2.2±0.3 L/min. Through 30 days, there were 2 deaths, 2 cases of periprocedural myocardial 
infarction (MI) and no cases of aortic valve injury, cardiac perforation, or limb ischemia. No 
patient developed hemodynamic compromise during PCI.  
The 1:1 randomized PROTECT II trial compared outcomes during nonemergent HR-PCI 
with Impella 2.5 versus IABP in symptomatic patients with complex 3-vessel disease or 
unprotected left main CAD and severely depressed left ventricular function23. The primary 
end point was the 30-day incidence of major adverse events; there was also a protocol-
mandated 90-day follow-up. After an interim data review, the trial was stopped prematurely 
for futility (69% of planned enrollment). The prespecified per-protocol analysis set included 
patients who met the protocol-mandated eligibility criteria (N=216 for Impella, N=211 for 
IABP). At 30 days, mortality in the per protocol population was similar between the 2 groups 
(6.9% with Impella vs. 6.2% with IABP, P=0.744). The 30-day primary endpoint was also 
not different between the groups (34.3% for Impella vs. 42.2%, P=0.092), but the 90-day rate 
of major adverse events was significantly lower with Impella (40.0% vs. 51.0%, P=0.023). 
Notably, the Impella 2.5 provided significantly better hemodynamic support compared to the 
IABP; maximal decrease in cardiac power was 0.04±0.24 W with Impella vs. 0.14±0.27 W 
with IABP (P=0.001). The duration of hemodynamic support was also significantly shorter 
with Impella (1.9±2.7 hours vs. 8.4±21.8 hours, P <0.001).  

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The safety, feasibility, and hemodynamic usefulness of Impella in HR-PCI have been 
examined in various registries. In the multicenter USpella registry (N=175), mortality was 
3.4% in-hospital; the 30-day rate of major adverse cardiac events (MACE) was 8%24. 
Angiographic revascularization was successful in 99% of patients and ejection fraction 
improved significantly from 31±15% to 36±14% (P <0.001). Median support time was 
1.0 hour (range 0.1–72 hours) and the average pump flow was 2.1±0.2 L/min. Among 144 
consecutive patients receiving Impella support in the Europella Registry25 there was 1 
intraprocedural death and 30-day mortality was 5.5%. The duration of hemodynamic support 
was 87.8±50.7 minutes and placement/retrieval of the device was considered easy/suitable in 
>99% of cases. In the multicenter German Impella registry (N=154), Impella was 
successfully placed in 99.4% of cases and removed in the cath lab in 87.0%26. In-hospital 
mortality was 2.6%. Among 86 patients treated with Impella in the Roma-Verona registry, 
there was 1 procedural death27. The median value for duration of Impella support was 104 
minutes (range 55–3151 minutes).  
In conclusion, the success of performing HR-PCI has become increasingly dependent on the 
availability and improvement of MCS devices to provide hemodynamic support and left 
ventricular unloading. The use of MCS as an adjunct to HR-PCI may, therefore, be an 
important component for improvement in clinical outcomes.      
4.2. Study Rationale 
The Vortex System is intended to support stable subjects undergoing HR-PCI by temporarily 
decreasing the load on the heart and ensuring adequate organ perfusion. Prophylactic use of 
the Vortex System during HR-PCI procedures should improve patient hemodynamics and 
may improve patient outcomes. The Vortex design provides a therapeutic approach and 
mechanism of action like that of commercially available devices but may also provide 
improved conformation to subject anatomy and a less complex arrangement during the 
interventional procedure. The Vortex design has been assessed in animals, in benchtop 
models, and via computational simulations. However, there are currently no animal or bench 
models that can adequately represent the disease state of subjects undergoing HR-PCI. 
Therefore, a first-human-use study is required to assess and confirm device safety, and 
technical feasibility of device use during the HR-PCI procedure to aid in optimization of 
device functionality and design. 
5. Device Description 
The Vortex System is a minimally invasive, temporary device that is in direct contact with 
the heart while in use. It is intended to run for up to 4 hours to support subjects undergoing 
HR-PCI as determined by an appropriately trained medical team. The Vortex design provides 
a therapeutic approach and mechanism of action similar to that of the commercially available 
Impella® devices (Abiomed, Inc., Danvers, MA, USA). A summary of the device is provided 
below. Additional information on the device can be found in the Investigator’s Brochure and 
Instructions For Use (IFU).  

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5.1. Vortex System 
Components of the Vortex System are summarized in Table 5.1-1 and discussed briefly 
below in Section 5.1.1, Section 5.1.2, and5.1.3.  Please see the Investigator’s Brochure for 
additional detailed information. 
Table 5.1-1: Summary of Vortex System Components 
Component 
Descriptiona 
Vortex Pump 
 
- Axial flow pump magnetically coupled to the impeller with an expandable flexible 
cannula in a membrane-covered pre-shaped braid and a proximal catheter    
- Introduced percutaneously via femoral artery access; advanced across the aortic valve 
into the left ventricular outflow tract; outlet ports are near the sinotubular junction  
Vortex 
Delivery 
System 
- Starter tube 
- Introducer sheath with 16 Fr profile, 35-cm length 
- Dilator (compatible with 0.035” wire) 
-  Cannula delivery tool  
Vortex Wire 
- 0.018” diameter, 300-cm length, shapeable tip 
Vortex Console 
- Interface to control/monitor the pump; connected to the pump using a sterile extension 
cable, which is plugged into the wall and controls power to the pump 
a: Detailed information is provided in the Investigator’s Brochure. 
 
5.1.1. Vortex Pump 
The Vortex pump and its major components are shown in Figure 5.1-1. The pump is a 
catheter-based device designed to reduce left ventricular preload by pulling blood from the 
left ventricle across the aortic valve into the aorta. It is delivered via a retrograde 
transfemoral approach and is advanced until the distal portion of the device crosses the aortic 
valve into the left ventricular outflow tract. The expandable, flexible cannula is in a 
membrane-covered pre-shaped braid and sits near the sinotubular junction with the tip of the 
device near the apex of the left ventricle. The pump is an axial flow pump magnetically 
coupled to the impeller. The proximal catheter is a layered sheath of polymer internally 
supported by a braid that contains the wires that supply power to the pump and communicate 
with the Vortex console (see Section 5.1.3). The extension cable connector is adjacent to the 
handle and enables electrical and mechanical connection to the sterile extension cable. 

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Figure 5.1-1: Vortex Pump 
Patient-contacting components include the inflow and outflow windows, cannula, flexible tip, cannula delivery 
tool and proximal catheter. Non-patient-contacting components include the starter tube, handle, and extension 
cable connector. 
5.1.2. Vortex Delivery System 
The Vortex pump is provided with 6 components to aid in delivery. The Vortex wire is 
shown in  Figure 5.1-2 (Panel A). It is 0.018 inches in diameter and 300 cm long with a 
shapeable tip. The Vortex introducer sheath and dilator are also shown in Figure 5.1-2 (Panel 
B). The Vortex introducer sheath has a 16 Fr profile (OD: 5.9 mm, ID: 5.3 mm) and is 35 cm 
long. The Vortex dilator has wire compatibility up to a 0.035-inch wire and a luer lock 
attachment on the proximal end to enable flushing. The other 3 delivery components are 
preloaded on the Vortex pump and are shown above in Figure 5.1-1. The wire loading tube 
is threaded from the tip of the pump through the cannula and out the outflow window that 
aligns with the inside curve of the cannula. The starter tube on the catheter portion of the 
pump aids introduction of the pump into the introducer sheath. The cannula delivery tool 
reduces the delivery force required to advance the expandable cannula through the introducer 
sheath.  

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Figure 5.1-2: Vortex Wire and Vortex Introducer Sheath and Dilator 
A: Vortex Wire; the wire is the same as the commercially available Platinum Plus™ Wire (Boston Scientific, 
Marlborough, MA, USA) but does not include the polymeric or hydrophilic coating layers.   
B: Vortex Introducer Sheath and Dilator; the dilator has wire compatibility up to a 0.035-inch wire. 
5.1.3. Vortex Console 
The Vortex Console, shown in Figure 5.1-3, provides an interface to control/monitor the 
pump. Overall features are shown in Panel A and the LED display is shown in Panel B. The 
console is connected to the pump using a sterile extension cable, which is plugged into the 
wall and controls power to the pump. 
 
Figure 5.1-3: Vortex Console 
A: Vortex Console; included are power cord and connector cables to enable connections to an auxiliary device.   
B: LED displays on the Vortex console. 
 
 
 
 
 
 
 
 
 
 
 
 

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5.2. Device Labeling 
A copy of the Vortex IFU is included in the study Manual of Operations.  
Packaging includes peelable, self-adhesive labels applied to both the sterile barrier pouch and 
the carton for each unit shipped. The labels on the shelf cartons and sterile pouch include the 
following information. 
• Product name 
• Product number  
• Lot number or serial number 
• Expiration date (use by) date (labeled as month/year, device not to be used after the 
last day of the indicated month) 
The following statement appears on the study device product labeling:  
Exclusively for Clinical Investigations. 
5.3. Ancillary Devices and Procedures  
The Vortex System requires the use of several medical instruments to ensure correct delivery 
and positioning of the pump and other devices to characterize pump performance during use.  
Please see the Investigator's Brochure for a list of devices that may be used with the Vortex 
System. 
6. Study Objectives and Endpoints 
6.1. Objectives 
The objective of the Vortex feasibility study is to evaluate the feasibility and safety of the 
Vortex Temporary Percutaneous Transvalvular Circulatory Support System (Vortex System) 
in subjects undergoing elective HR-PCI. 
6.2. Primary Endpoint 
The primary endpoint consists of Technical Success and Clinical Success, defined as 
follows. 
Technical Success 
• Successful delivery of the device to the correct anatomical position; and 
• Successful operation and removal of the Vortex circulatory support system  
Clinical Success 
• No conversion to open heart surgery; and 

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• No in-hospital mortality (see Note 1 in Section 6.3) 
6.3. Additional Measurements 
Safety events will be collected through 72 hours post-procedure or hospital discharge, 
whichever comes first, as listed below. 
• Stroke/transient ischemic attack (TIA; see Note 1 below) 
• Cardiac tamponade 
• Cardiac death (see Note 1 below) 
• Myocardial infarction (MI) 
• Bleeding complications: Type 3–5 based on the Mechanical Circulatory Support 
Academic Research Consortium (MCS-ARC)28 definitions (see Note 1 below) 
• Acute kidney injury (AKI; based on the AKIN29,30 System Stage 3 [including renal 
replacement therapy] or Stage 2) 
• Major vascular complications (see Note 1 below) 
• Any device-related adverse event (adverse device effect [ADE]/serious adverse 
device effect [SADE]) 
• Any procedure-related adverse event 
• Any adverse event related to management practices 
• Any adverse event related to patient specific adherence 
• Any unanticipated serious adverse device effect (USADE) 
Note 1: Death, stroke, bleeding complications, and major vascular complications are 
adjudicated by an Independent Medical Reviewer (IMR).  
6.4. Overview of Objectives and Endpoints 
Table 6.4-1 provides an overview of the aforementioned study objectives and endpoints and 
a justification for the specific endpoints. 
Table 6.4-1: Overview of Objectives and Endpoints 
Objective 
Endpoint 
Rationale for Endpoint 
Primary Endpoint 
 Evaluate feasibility 
and safety of the 
device and the 
procedure 
Technical success (successful delivery 
of the device to the correct anatomical 
position and successful operation and 
removal of the Vortex circulatory 
support system) and clinical success 
(no conversion to open heart surgery 
and no in-hospital mortality). 
Assess the ability of the device to be 
delivered and removed as intended and 
operate as intended without in-hospital 
mortality or conversion to open heart 
surgery during HR-PCI. Mortality events 
are adjudicated by an IMR. 

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Table 6.4-1: Overview of Objectives and Endpoints 
Objective 
Endpoint 
Rationale for Endpoint 
Additional Measurements  
 Evaluate safety of 
the device and 
procedure 
Safety events collected through 
72 hours post-procedure or hospital 
discharge, whichever comes first. 
Evaluate safety using event definitions 
based on MCS-ARC recommendations28. 
Mortality, stroke, bleeding complications, 
and major vascular complications are 
adjudicated by an IMR. 
Abbreviations: HR-PCI=high-risk percutaneous coronary intervention; IMR=independent medical reviewer; 
MCS-ARC=Mechanical Circulatory Support Academic Research Consortium 
 
7. Study Design 
The Vortex Feasibility Study is a prospective, multicenter, open-label, single-arm study to 
assess the safety and feasibility of the Vortex System in subjects undergoing elective high-
risk percutaneous coronary intervention (HR-PCI). 
7.1. Scale and Duration 
The Vortex Feasibility Study will be conducted at up to 3 centers in Australia and Europe 
with planned enrollment up to 10 subjects. All subjects will be screened according to the 
protocol inclusion and exclusion criteria. Follow-up will occur through 72 hours or hospital 
discharge, whichever comes first. The study design is summarized below in Figure 7.1-1. 
 
 
Figure 7.1-1: Vortex Feasibility Study Design Overview 
7.2. Treatment Assignment 
7.3. Subjects who are candidates for high-risk percutaneous coronary intervention, 
provide written informed consent, and are eligible to be treated with the Vortex 
System will be evaluated for enrollment in this study. Prior to being eligible for 

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the study, a subject must meet all of the inclusion criteria (Section 8.2) and none 
of the exclusion criteria (Section 8.3). Justification for the Study Design 
In order to provide an assessment of safety and performance of the Vortex System while also 
limiting the potential exposure of study subjects to risk, the sample size in this feasibility 
study has been limited to up to 10 subjects at up to 3 investigative centers in Australia and 
Europe. Technical Success, Clinical Success, and safety results will be reported on all 
enrolled subjects through 72 hours or hospital discharge, whichever comes first. 
8. Subject Selection  
8.1. Study Population and Eligibility  
Subjects who are candidates for high-risk percutaneous coronary intervention, provide 
written informed consent, and are eligible to be treated with the Vortex System will be 
evaluated for enrollment in this study. Prior to being eligible for the study, a subject must 
meet all of the inclusion criteria (Section 8) and none of the exclusion criteria (Section 8.2).  
8.2. Inclusion Criteria 
Subjects who meet all of the following criteria (see Table 8.2-1) may be given consideration 
for inclusion in this clinical investigation, provided no exclusion criterion (see Section 8.2) is 
met.  
Table 8.2-1: Inclusion Criteria 
IC1. Subject provides signed informed consent.  
IC2.  Subject is ≥ 18 years and < 90 years of age.  
IC3.  Subject is indicated for NON-emergent PCI of at least one de novo or restenotic lesion in a native 
coronary vessel or coronary artery bypass graft and has left ventricular ejection fraction (LVEF) 
≤ 50% with the following: 
• Unprotected left main -OR- 
• Last remaining vessel -OR- 
• Three vessel disease (≥ 50% diameter stenoses by visual estimate or total occlusion)  
Abbreviations: LVEF=left ventricular ejection fraction; PCI=percutaneous coronary intervention 
 
8.3. Exclusion Criteria 
Subjects who meet any one of the following criteria (Table 8.3-1) cannot be included in this 
study or will be excluded from this clinical study. 

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Table 8.3-1: Exclusion Criteria 

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EC1. 
Subject has had STEMI within 24 hours. 
EC2. 
Subject has had pre-procedure cardiac arrest requiring CPR within 24 hours of enrollment. 
EC3. 
Subject is in shock, defined as follows: 
• 
CI < 2.2 L/min/m2 and PCWP > 15 mmHg -AND- 
• 
Hypotension (systolic blood pressure < 90 mmHg for > 30 minutes) -OR- 
• 
Need for supportive measures (i.e., inotropes or mechanical support) to maintain systolic 
blood pressure ≥ 90 mmHg and end organ hypoperfusion (cool extremities or urine 
< 30 mL/hour and a heart rate > 60 beats per minute) 
EC4. 
Subject has left ventricular mural thrombus. 
EC5. 
Subject has a prosthetic aortic valve. 
EC6. 
Subject has pericarditis or constrictive heart disease (constrictive pericarditis or restrictive 
cardiomyopathy). 
EC7. 
Subject has moderate or greater aortic valve stenosis31 or moderate or greater aortic valve 
insufficiency31 (by echocardiographic assessment, graded as ≥ 2+). 
EC8. 
Subject has abnormalities of the aorta that preclude safe delivery of the device, including severe 
calcification, tortuosity, aneurysm, or prior surgery. 
EC9. 
Subject has PVD preventing passage of the device (e.g., calcification, small caliber) or tortuosity 
that would preclude safe placement of the 16 Fr introducer sheath. 
 
Note: Minimum required vessel diameter is > 5.5 mm. 
EC10. 
Subject has advanced renal dysfunction (AKIN29,30 Stage 3). 
EC11. 
Subject has a history of liver dysfunction (Childs Class C) with elevation of liver enzymes and 
bilirubin > 3× ULN or INR ≥ 2. 
EC12. 
Subject has had a recent (within 1 month) stroke or TIA. 
EC13. 
Subject has known hypersensitivity to intravenous contrast agents that cannot be adequately pre-
medicated or has known hypersensitivity to heparin, aspirin, ADP receptor inhibitors or nitinol. 
EC14. 
Subject has current or a history of heparin induced thrombocytopenia. 
EC15. 
Subject has uncorrected abnormal coagulation or platelet count ≤ 75,000/mm³ or INR ≥ 2.0.  
EC16. 
Subject has significant right heart failure (RAP > 15 mmHg, RVSWI < 0.30 mmHg·L/m², PVR 
> 3.6 Woods units)32.  
EC17. 
Subject requires mechanical ventilation.  
EC18. 
Subject has an atrial or ventricular septal defect (including post-infarct VSD). 
EC19. 
Subject has left ventricular rupture.  
EC20. 
Subject has cardiac tamponade. 
EC21. 
Subject has severe pulmonary disease (FEV1 < 1L).  
EC22. 
Subject has sustained or non-sustained ventricular tachycardia. 
EC23. 
Subject is breast feeding or is pregnant. 
EC24.    Subject has other disease condition(s) resulting in the subject being unsuitable for participation in 
the clinical trial (e.g. advanced malignancy with limited expected survival) 

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Table 8.3-1: Exclusion Criteria 
EC25.    Subject has other disease condition(s) which the Investigator has determined may cause non-
compliance to the study requirements. 
Abbreviations: CI=cardiac index; CPR=cardiopulmonary resuscitation; FEV=forced expiratory volume; 
INR=international normalization ratio; PCWP=pulmonary capillary wedge pressure; PVD=peripheral 
vessel disease; PVR=pulmonary vascular resistance; RAP=right atrial pressure; RVSWI=right ventricular 
stroke work index; STEMI=ST-elevation myocardial infarction; TIA=transient ischemic attack; 
ULN=upper limit of normal; VSD=ventricular septal defect 
 
9. Subject Accountability 
9.1. Point of Enrollment 
Subjects who provide written informed consent and are confirmed eligible for the study are 
considered enrolled in the study as soon as an attempt is made to insert any part of the Vortex 
System into the subject’s femoral artery (e.g., Vortex sheath). 
9.2. Withdrawal 
All subjects enrolled in the clinical study (including those withdrawn from the clinical study) 
shall be accounted for and documented. If a subject withdraws from the clinical 
investigation, the reason(s) shall be reported. If such withdrawal is due to problems related to 
investigational device safety or performance, the investigator shall ask for the subject’s 
permission to follow his/her status/condition outside of the clinical study.   
While all efforts should be made to minimize attrition, subjects may withdraw from the study 
at any time, with or without reason and without prejudice to further treatment. Withdrawn 
subjects will not undergo any additional study follow-up, nor will they be replaced. The 
investigator may discontinue a subject from participation in the study if the investigator feels 
that the subject can no longer fully comply with the requirements of the study or if any of the 
study procedures are deemed potentially harmful to the subject. Data that have already been 
collected on withdrawn subjects will be retained and used for analysis, but no new data will 
be collected after withdrawal. All applicable case report forms up to the point of subject 
withdrawal and an “End of Study” form for the subject must be completed. 
9.3. End-of-Study Definition  
This clinical study will be considered completed when subjects are no longer being examined 
or the last subject’s last study visit as outlined in the data collection schedule (Table 10.1-1) 
has occurred. 

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10. Study Methods 
10.1. Data Collection 
This section indicates the data needed to fulfill the objectives of this clinical study. Boston 
Scientific Corporation (BSC) considers data collected from clinical trial subjects to be 
personal data (see definitions of different data categories in Table 24.2-1) and compliance 
with privacy and data protection laws and regulations (for example, the General Data 
Protection Regulation [GDPR], see Table 24.2-1) to be critically important. Data collection 
for this clinical study has been carefully considered to comply with data privacy laws. The 
data collection schedule is shown in Figure 10.1-1 and Table 10.1-1. Additional information 
on data collection can be found in Sections 10.3 through 10.10. 
 

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Figure 10.1-1: Vortex Study Data Collection Schedule 
See Table 10.1-1 for additional information. 
 

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Table 10.1-1: Data Collection Schedule 
Assessment 
Baseline 
Index 
Procedure 
≤72 Hours / 
Dischargea 
Signed Informed Consent Form 
X 
− 
− 
Demographics and medical historyb 
X 
− 
− 
Physical assessmentc 
X 
− 
− 
New York Heart Association classification 
X 
− 
X 
CCS Angina classification 
X 
− 
− 
Electrocardiogramd 
X 
− 
X 
Laboratory testse 
X 
O 
X 
Assessment of iliofemoral diameter and tortuosityf 
X 
− 
− 
Anticoagulant medications 
X 
X 
X 
Other cardiovascular medications 
X 
X 
X 
Transthoracic echocardiographyg,h 
X 
X 
− 
Coronary angiogramh,i 
X 
X 
− 
Intracardiac echocardiographyh 
− 
O 
− 
Activated clotting time 
− 
X 
− 
Device deficienciesj 
− 
X 
X 
Adverse event assessmentk 
– 
X 
X 
Note: X = required; O = optional; – = not required.  
Additional information on data collection can be found in Sections 10.3 through 10.10. 
a: Data collected through 72 hours or hospital discharge, whichever comes first. 
b: Including cardiac, neurological, renal, and peripheral vascular disease. 
c: Including weight, height, and vital signs. 
d: 12-lead ECG; baseline ECG should be done within 30 days prior to the index procedure; post-procedure 
timing is per standard of care for HR-PCI.  
e: Laboratory tests at baseline include CBC with platelets, serum creatinine, plasma-free hemoglobin, and 
cardiac enzymes. Post-procedure, cardiac enzymes (CK or troponin is required, CK-MB or troponin if CK 
is elevated) must be collected once per standard of care within 6–24 hours; if readings are abnormal, a 
second collection per standard of care is required. Plasma-free hemoglobin must be collected pre-
discharge (≥ 6 hours post procedure). Plasma-free hemoglobin may be collected during the index 
procedure per the standard of care. 
f: Minimum required iliofemoral diameter is > 5.5 mm; any assessment technique to determine diameter and 
tortuosity is permitted; assessment must be done within 365 days prior to the index procedure. 
g: TTE assessment should be done within 180 days prior to the index procedure. 
h: Deidentified copies of the imaging assessments should be provided to Boston Scientific. 
i: Coronary angiogram should be done within 365 days prior to the index procedure per standard of care for 
HR-PCI. 
j: Information on device deficiencies for the test device will be monitored and reported to Boston Scientific. 
k: The adverse event assessment includes AE, SAE, ADE, SADE, USADE, and IMR events, which will be 
collected from the time of enrollment through 72 hours post-procedure or hospital discharge, whichever 
comes first, in all subjects. Please refer to Section 18.1 for reportable events, including a list of IMR 
events, and to Table 24.2-1 for definitions of these events, which specify data required for IMR 
adjudication. 
Abbreviations: AE=adverse event; ADE=adverse device effect; CBC=complete blood count; CCS=Canadian 
Cardiovascular Society; CK=creatine kinase; CK-MB=creatine kinase myoglobin band; 
ECG=electrocardiogram; HR-PCI=high risk percutaneous coronary intervention; IMR=independent medical 

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Table 10.1-1: Data Collection Schedule 
Assessment 
Baseline 
Index 
Procedure 
≤72 Hours / 
Dischargea 
reviewer; SADE=serious adverse device effect; SAE=serious adverse event; USADE=unanticipated serious 
adverse device effect 
  
10.2. Study Candidate Screening 
Subjects will be evaluated for eligibility by the center’s heart team. 
10.3. Informed Consent 
Before any study specific tests or procedures are performed, subjects who meet eligibility 
criteria will be asked to sign the study Informed Consent Form (ICF) that was approved by 
the Independent Ethics Committee (IEC)/Human Research Ethics Committee (HREC). 
Subjects must be given ample time to review the ICF and have questions answered before 
signing. 
Study personnel should explain to the subject that even if the subject agrees to participate in 
the study and signs the ICF, screening tests and procedures may demonstrate that the subject 
is not a suitable candidate for the study.  
10.4. Screening Assessments 
The screening tests and procedures listed below must be performed to confirm a subject’s 
eligibility for the study. Specific data points will be collected in the electronic Case Report 
Forms (eCRFs) as shown below. 
• Clinical assessments  
o Demographics including age and gender 
o Medical history, including cardiac, neurological, renal disease, peripheral disease 
and other medical conditions 
o Physical assessment, including weight, height, and vital signs  
o New York Heart Association (NYHA) classification  
o Canadian Cardiovascular Society (CCS) angina classification  
o 12-lead electrocardiogram (ECG; see Note 1 below) 
o Current anticoagulant and other cardiovascular medications 
• Imaging assessments (see Note 1 and Note 2 below)  
o Transthoracic echocardiography (TTE) 
o Coronary angiogram  

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o Evaluation of iliofemoral diameter and tortuosity (any assessment technique is 
permitted) 
Note 1: Baseline ECG should be done within 30 days prior to the index procedure, TTE 
within 180 days prior to the index procedure, coronary angiogram per standard of care for 
HR-PCI, and iliofemoral diameter/tortuosity assessment within 365 days prior to the 
index procedure. 
Note 2: Imaging assessments should include basic cardiac measurements, including 
ventricular dimensions, function of the left and right ventricle, and function of all cardiac 
valves. Deidentified copies of the imaging assessments should be provided to Boston 
Scientific. 
10.5. Baseline Assessments 
The following assessments must be completed prior to the index procedure. The eCRFs 
identify the specific data points to be collected. 
• Confirmation of eligibility criteria 
• NYHA classification 
• Laboratory tests 
o Cardiac enzymes (CK [creatine kinase] or troponin is required, CK-MB [creatine 
kinase myoglobin band] or troponin if CK is elevated) 
o Plasma-free hemoglobin 
o Complete blood count (CBC) with platelets 
o Serum creatinine 
10.6. Pre-procedure/Procedural Medications 
Subjects should be treated with heparin during the procedure. Activated clotting time (ACT) 
should be measured as standard of care with a recommended target of >250 and <400 
seconds for the duration of the procedure.  
10.7. Index Procedure 
The preparation of the subject for the percutaneous procedure will be performed following 
standard techniques. 
10.7.1. Vortex System Procedure 
The investigational device will be delivered on a guidewire through a Vortex introducer 
sheath catheter from the femoral artery access site to the aorta and positioned across the 
aortic valve. During the transcatheter approach, the subject is under conscious sedation.  

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Please refer to the Vortex IFU and investigator training materials (see Section 15.4.1) for 
detailed instructions on procedural steps.  
Note 1: All Vortex procedures will be performed with the support/presence of trained BSC 
personnel. 
Note 2: Plasma-free hemoglobin may be collected during the index procedure per the 
standard of care. 
The following information will be collected during the procedure. Additional data to be 
collected will be outlined in the eCRF.  
• Date of procedure 
• Time of first vascular puncture (femoral) and vascular closure (skin-to-skin time) 
• Vortex System insertion and removal time 
• Additional information regarding use of the Vortex System  
o Descriptive information on Vortex System insertion procedure 
o Descriptive information on Vortex System positioning and retrieval 
o Descriptive information on the impact of the Vortex System on cardiac anatomy 
and physiology 
o Impact of Vortex System usage on HR-PCI procedure success 
• ECG changes (per standard of care) 
• Adverse event assessment; see Section 18 
• Device deficiencies assessment  
10.7.2. Intraprocedural Cardiac Imaging 
Subjects will undergo heart catheterization with radiographic imaging as per standard of care.  
Imaging may include fluoroscopy, ventriculography, and/or sonography before and after 
placement of the Vortex System to assess the left ventricle and verify freedom from coronary 
interference. Minimization of contrast media injected into subjects with compromised renal 
function is recommended.  
Deidentified copies of the imaging assessments should be provided to Boston Scientific. 
10.7.3. Intraprocedural Hemodynamic Measurements 
Intraprocedural hemodynamic assessment is primarily based on TTE (or intracardiac 
echocardiography33 as per standard of care) and catheter-based pulmonary artery 
measurements. Cardiac output (CO), pulmonary artery (PA) pressure, pulmonary capillary 
wedge pressure (PCWP), central venous pressure (CVP), mean arterial pressure (MAP), and 
right atrial pressure (RAP) should be measured before and after the pump is placed and 
switched on via the pulmonary artery catheter and also when the pump is switched off and 

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removed (post-procedure).  Left ventricular pressure may be measured via the pigtail 
catheter. 
10.8. Post-procedure (≤ 72 Hours)/Prior to Hospital Discharge 
Within 72 hours post procedure or before discharge (whichever comes first), the following 
assessments must be performed. 
• 12-lead ECG 
• Laboratory tests 
o Cardiac enzymes (CK or troponin required, CK-MB or troponin if CK is elevated) 
must be collected once per standard of care within 6–24 hours post-procedure; if 
readings are abnormal, a second collection per standard of care is required. 
o Plasma-free hemoglobin must be collected ≥ 6 hours post procedure (before 
discharge) 
• NYHA classification 
• Anticoagulation therapy and other cardiovascular medications 
• Adverse event assessment (see Section 18) 
• Device deficiencies assessment 
10.9. Study Completion 
All subjects will be evaluated through 72 hours or hospital discharge, whichever comes first. 
A subject’s participation in the study will be considered complete after 72 hours or hospital 
discharge (whichever comes first). 
10.10. 
Source Documents 
It is preferable that original source documents, when available, are maintained at the 
investigative center. In lieu of original source documents, certified copies are required to be 
maintained. A certified copy is a copy (irrespective of the type of media used) of the original 
record that has been verified (i.e., by a dated signature or by generation through a validated 
process) to have the same information, including data that describe the context, content, and 
structure, as the original. Source documentation includes but is not limited to those items 
noted in Table 10.10-1. Source documentation provided to the Sponsor for 
assessment/adjudication will be deidentified per local law and regulations. 

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Table 10.10-1: Source Documentation Requirements 
Requirement 
Disposition 
Printed, optical, or electronic document containing source data. Examples may include but 
are not limited to hospital records, laboratory notes, device accountability records, 
photographic negatives, radiographs, records kept at the investigation center, at the 
laboratories and at the medico-technical departments involved in the clinical investigation. 
Retain at center. 
Note: Please see Table 24.2-1 for definitions of “source data” and “source document.” 
 
10.11. 
Local Laboratory/Vendor Documentation 
This study requires local laboratory results. Appropriate certifications and documentation 
records are required to be maintained at the center.   
11. Statistical Considerations 
Event definitions can be found in Table 24.2-1. 
11.1. Endpoints 
11.1.1. Primary Endpoint 
The primary endpoint consists of Technical Success and Clinical Success. Technical Success 
is defined as successful delivery of the device to the correct anatomical position and 
successful operation and removal of the Vortex System. Clinical Success is defined as no 
conversion to open heart surgery or in-hospital mortality. 
11.1.1.1. Hypotheses 
There is no formal statistical hypothesis in this observational feasibility study.  
11.1.1.2. Sample Size  
This is a prospective non-randomized feasibility study with no formal pre-specified 
hypothesis and therefore sample size estimates are not applicable. To support the stated 
objective of this feasibility study, while also limiting the potential exposure to risk of study 
subjects, the study sample size has been arbitrarily set at a maximum of 10 subjects enrolled. 
11.1.1.3. Statistical Methods 
Descriptive statistics will be used for baseline, procedure, and follow-up data collected 
during the study. See Section 11.2.1 for a discussion of analysis sets. 

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11.1.2. Additional Measurements 
Additional measurements are listed in Section 6.3. There are no statistical hypotheses for the 
additional measurements. 
11.2. General Statistical Methods 
All statistical analyses will be performed using the SAS System software, version 9.2 or later 
(Copyright© 2000 SAS Institute Inc., SAS Campus Drive, Cary, North Carolina 27513, USA. 
All rights reserved).  
All statistical analyses will be conducted according to applicable Standard Operating 
Procedures, Work Instructions, and the study-specific statistical analysis plan. 
11.2.1. Analysis Sets 
The primary endpoint and additional measurements will be analyzed on an intention-to-treat 
(ITT) basis and a per-protocol basis. Analysis sets are listed below. Subjects are considered 
enrolled in the study as soon as an attempt is made to insert any part of the Vortex System 
into the subject's femoral artery. 
• ITT: This population includes all subjects who sign an ICF and are enrolled in the 
study, whether or not a study device is successfully inserted and used. 
• Per-protocol: This population includes all ITT subjects in whom the device is 
successfully advanced across the aortic valve into the left ventricular outflow tract and 
turned on. 
11.2.2. Control of Systematic Error/Bias 
The selection of subjects will be made from the Investigator’s usual case load. Subjects who 
are candidates for HR-PCI, provide written informed consent, and are eligible to be treated 
with the Vortex System will be evaluated for enrollment in this study. The study center’s 
heart team assessments and imaging measurements before device placement will contribute 
to the determination of subject eligibility for the study.  
To control for inter-observer variability, an independent IMR (see Section 20.2) will 
adjudicate mortality, stroke, major vascular complications, and bleeding endpoints. 
11.3. Data Analyses 
Baseline data, procedural data, and follow-up data (72 hours post procedure or hospital 
discharge, whichever comes first) collected for the ITT subjects will be summarized using 
descriptive statistics (e.g., mean, standard deviation, n, minimum, maximum) for continuous 
variables and frequency tables or proportions for discrete variables. Data will be collected as 
detailed in the clinical study schedule (Table 10.1-1).  

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12. Data Management 
12.1. Data Collection, Processing, and Review 
Subject data will be recorded in a limited access secure electronic data capture (EDC) 
system.  
The clinical database will reside on a production server hosted by Medidata EDC System. All 
changes made to the clinical data will be captured in an electronic audit trail and available for 
review by the sponsor or its representative. The associated Rave software and database have 
been designed to meet regulatory compliance for deployment as part of a validated system 
compliant with laws and regulations applicable to the conduct of clinical studies pertaining to 
the use of electronic records and signatures. Database backups are performed regularly. 
The Investigator provides his/her electronic signature on the appropriate electronic case 
report forms (eCRFs) in compliance with local regulations. A written signature on printouts 
of the eCRFs must also be provided if required by local regulation. Changes to data 
previously submitted to the sponsor require a new electronic signature by the Investigator 
acknowledging and approving the changes. 
Visual and/or electronic data review will be performed to identify possible data 
discrepancies. Manual and/or automatic queries will be created in the Medidata EDC system 
and will be issued to the center for appropriate response. Center staff will be responsible for 
resolving all queries in the database. 
All access to the clinical database will be changed to “Read Only” after all data are either 
“Hard Locked” or “Entry Locked.” Once acceptance of the final study report or finalization 
of publications (as applicable) is received, final database storage and archiving activities can 
begin. When all closeout activities are completed, a request to the BSC Information 
Technology department is submitted to have the database locked or decommissioned and all 
database access revoked. 
12.2. Data Retention 
The Principal Investigator or his/her designee or Investigational site will maintain all 
essential study documents and source documentation that support the data collected on the 
study subjects in compliance with applicable regulatory requirements.   
The Principal Investigator or his/her designee will take measures to prevent accidental or 
premature destruction of these documents. If for any reason the Principal Investigator or 
his/her designee withdraws responsibility for maintaining these essential documents, custody 
must be transferred to an individual who will assume responsibility and BSC must receive 
written notification of this custodial change. Centers are required to inform BSC in writing 
where paper or electronic files are maintained in case files are stored off site and are not 
readily available. 

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13. Deviations 
An Investigator must not make any changes or deviate from this protocol, except to protect 
the life and physical well-being of a subject in an emergency. An investigator shall notify the 
sponsor and the reviewing IEC/HREC, and regulatory authorities if applicable, of any 
deviation from the investigational plan to protect the life or physical well-being of a subject 
in an emergency, and those deviations which affect the scientific integrity of the clinical 
investigation. Such notice shall be given as soon as possible, but no later than 5 working days 
after the emergency occurred, or per prevailing local requirements, if sooner than 5 working 
days.  
All deviations from the investigational plan, with the reason for the deviation and the date of 
occurrence, must be documented and reported to BSC using the EDC eCRF. Centers may 
also be required to report deviations to the IEC/HREC, and the regulatory authority, per local 
guidelines and national/government regulations.  
Deviations will be reviewed and evaluated on an ongoing basis and, as necessary, appropriate 
corrective and preventive actions (including IEC/HREC notification, center re-training, or 
center discontinuation/termination) will be put into place by the sponsor. 
The sponsor will not approve protocol waivers.  
14. Device Accountability for Products Labelled Investigational 
The investigational devices shall be securely maintained, controlled, and used only in this 
clinical study. Equipment shall be returned in the condition in which it was provided, 
reasonable wear and tear excepted. 
For items labelled "investigational," the principal investigator or an authorized designee shall 
do the following: 
• Securely maintain and control access to these items to ensure they are used only in this 
clinical study and only per the protocol.  
• Ensure the storage environment for these items is appropriate for maintaining 
conditions per the items’ labeling (e.g., temperature, humidity, etc., as applicable)  
• Return remaining items upon sponsor request and in the condition in which they were 
provided, reasonable wear and tear excepted. 
The sponsor shall keep records to document the physical location of all investigational 
devices from shipment of investigational devices from BSC or designated facility to the 
investigation centers until return or disposal. 
Records shall be kept by the sponsor to document the physical location and conditions of 
storage of all investigational devices/equipment.  
The principal investigator or an authorized designee shall maintain accurate and timely 
records, providing copies to BSC upon request. These records shall document the receipt, 

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use, return, and disposal of the investigational devices, and shall include minimally the 
following content.  
• Name(s) of person(s) who received, used, returned, or disposed of each item; 
• Date of receipt;  
• Identification and quantity of each item (examples of identification include batch 
number, serial number or unique code); 
• Expiry date for each item (or batch of items), as applicable; 
• Date or dates of use; 
• Subject identification; 
• Date on which the item was returned, if applicable; 
• Date of return (and number) of unused, expired, no longer needed, and/or 
malfunctioning items, as applicable;  
• Date and documentation of item disposal, as directed by sponsor, if applicable. 
15. Compliance 
15.1. Statement of Compliance 
This clinical investigation is financed by the study sponsor. Before an investigational center 
can be considered “Authorized to Enroll,” the investigational center must enter into a Clinical 
Study Agreement with the sponsor that details the financing of the study as well as the rights 
and obligations of the investigational center and the investigator. 
This study will be conducted in accordance with the International Standard ISO 14155:2020 
Clinical Investigation of Medical Devices for Human Subjects-Good Clinical Practices 
(GCP), European Medical Device Regulations, ethical principles that have their origins in the 
Declaration of Helsinki, and applicable individual country laws and regulations. The study 
shall not begin until the required approval/favorable opinion from the IEC/HREC and/or 
regulatory authority has been obtained, if appropriate. Also, the study shall not begin prior to 
issuance of the center Authorization to Screen/Enroll, as provided by the sponsor. Any 
additional requirements imposed by the IEC/HREC or regulatory authority shall be followed, 
if appropriate. 
15.2. Investigator Responsibilities 
The Principal Investigator of an investigational site is responsible for ensuring that the study 
is conducted in accordance with the Clinical Study Agreement, the clinical investigation 
plan, ISO 14155:2020, ethical principles that have their origins in the Declaration of 
Helsinki, any conditions of approval imposed by the reviewing IEC/HREC, and prevailing 

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local and/or country laws and/or regulations, whichever affords the greater protection to the 
subject. 
The Principal Investigator’s responsibilities include, but are not limited to, the following.  
• Prior to beginning the study, sign the Clinical Study Agreement and comply with the 
Investigator responsibilities as described in such Agreement. 
• Prior to beginning the study, sign the Investigator Brochure Signature Page and 
Protocol Signature page documenting his/her agreement to conduct the study in 
accordance with the protocol. 
• Provide his/her qualifications and experience to assume responsibility for the proper 
conduct of the study and that of key members of the site team through up-to-date 
curriculum vitae or other relevant documentation and disclose potential conflicts of 
interest, including financial, that may interfere with the conduct of the clinical study or 
interpretation of results. 
• Make no changes in or deviate from this protocol, except to protect the life and 
physical well-being of a subject in an emergency; document and explain any deviation 
from the approved protocol that occurred during the course of the clinical 
investigation. 
• Create and maintain source documents throughout the clinical study and ensure their 
availability with direct access during monitoring visits or audits; ensure that all 
clinical-investigation-related records are retained per requirements. 
• Ensure the accuracy, completeness, legibility, and timeliness of the data reported to the 
sponsor in the case report forms and in all required reports. 
• Record, report, and assess (seriousness and relationship to the device/procedure) every 
adverse event as applicable per the protocol and observed device deficiency. 
• Report to sponsor, per the protocol requirements, all reportable events. 
• Report to the IEC/HREC and regulatory authorities any SAEs and device deficiencies 
that could have led to a SADE and potential/USADE, if required by applicable laws or 
regulations or this protocol or by the IEC/HREC, and supply BSC with any additional 
requested information related to the safety reporting of a particular event. 
• Maintain the device accountability records and control of the device, ensuring that the 
investigational device is used only by authorized/designated users and in accordance 
with this protocol and instructions for use. 
• Allow the sponsor to perform monitoring and auditing activities and be accessible to 
the clinical research monitor or auditor and respond to questions during monitoring 
visits or audit(s). 
• Allow and support regulatory authorities and the IEC/HREC when performing 
auditing activities. 

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• Ensure that informed consent is obtained in accordance with applicable laws, this 
protocol and local IEC/HREC requirements. 
• Provide adequate medical care to a subject during and after a subject’s participation in 
a clinical study in the case of adverse events, as described in the ICF. 
• Inform the subject of the nature and possible cause of any adverse events experienced. 
• As applicable, provide the subject with necessary instructions on proper use, handling, 
storage, and return of the investigational device when it is used/operated by the 
subject. 
• Inform the subject of any new significant findings occurring during the clinical 
investigation, including the need for additional medical care that may be required. 
• Provide the subject with well-defined procedures for possible emergency situations 
related to the clinical study, and make the necessary arrangements for emergency 
treatment, including decoding procedures for blinded/masked clinical investigations, 
as needed. 
• Ensure that clinical medical records are clearly marked to indicate that the subject is 
enrolled in this clinical study. 
• Ensure that, if appropriate, subjects enrolled in the clinical investigation are provided 
with some means of showing their participation in the clinical investigation, together 
with identification and compliance information for concomitant treatment measures 
(contact address and telephone numbers shall be provided). 
• Inform, with the subject’s approval or when required by national regulations, the 
subject’s personal physician about the subject’s participation in the clinical 
investigation. 
• Make all reasonable efforts to ascertain the reason(s) for a subject’s premature 
withdrawal from clinical investigation while fully respecting the subject’s rights. 
• Ensure that an adequate investigation site team and facilities exist and are maintained 
and documented during the clinical investigation. 
All investigators will provide their qualifications and experience to assume responsibility for 
their delegated tasks through up-to-date curriculum vitae or other relevant documentation and 
disclose potential conflicts of interest, including financial, that may interfere with the conduct 
of the clinical study or interpretation of results. 
15.2.1. Delegation of Responsibility 
When specific tasks are delegated by an investigator, including but not limited to conducting 
the informed consent process, the Principal Investigator is responsible for providing 
appropriate training, so the delegate is competent to perform the tasks they have been 
delegated, and adequate supervision of those to whom tasks are delegated. Where there is a 
sub-investigator at a center, the sub-investigator should not be delegated the primary 

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supervisory responsibility for the site. The investigator is accountable for regulatory 
violations resulting from failure to adequately supervise the conduct of the clinical study.  
15.3. Independent Ethics Committee / Human Research Ethics Committee 
The investigational center will obtain the written and dated approval/favorable opinion of the 
IEC/HREC for the clinical investigation before recruiting subjects and implementing all 
subsequent amendments, if required. 
A copy of the written IEC/HREC and/or competent authority (CA) approval of the protocol 
(or permission to conduct the study) and ICF, must be received by the sponsor before 
recruitment of subjects into the study and shipment of investigational product/equipment.  
Any amendment to the protocol and/or ICF will require review and approval by the 
IEC/HREC and the Swedish Medical Products Agency (MPA) before changes to the study 
are implemented. All changes to the ICF will be IEC/HREC approved; a determination will 
be made regarding whether a new ICF needs to be obtained from subjects who provided 
consent using a previously approved ICF. Annual IEC/HREC approval and renewals will be 
obtained throughout the duration of the study as required by applicable local/country laws or 
regulations or IEC/HREC requirements. Copies of the study reports and the IEC/HREC 
continuance of approval must be provided to the sponsor.  
15.4. Sponsor Responsibilities 
All information and data sent to BSC concerning subjects or their participation in this study 
will be considered confidential by BSC and will be kept confidential in accordance with all 
applicable laws and regulations. Only authorized BSC personnel and/or a BSC representative 
including, but not limited to, a Contract Research Organization (CRO), will have access to 
this information. Authorized regulatory personnel have the right to inspect and copy all 
records pertinent to this study. Study data collected during this study may be used by BSC 
for the purposes of this study, publication, and to support future research and/or other 
business purposes, such as overseeing and improving the performance of its device, new 
medical research, and proposals for developing new medical products and procedures. All 
data used in the analysis and reporting of this study or shared with a third-party researcher 
will be without identifiable reference to specific subjects. 
Information received during the study will not be used to market to subjects; subject names 
will not be placed on any mailing lists or sold to anyone for marketing purposes.  
15.4.1. Training 
The Sponsor is responsible for providing Investigators with the information and training they 
need to conduct the study properly. The Sponsor is also responsible for maintaining 
documentation of attendance at each of the training sessions provided.   
Training for operators includes the following elements. 
• Detailed description of all Vortex System components  

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• Detailed description of the step-by step procedure on how to use the Vortex System, 
including insertion, positioning, pump operation, and retrieval 
• Hands-on demonstration and use of the Vortex System: deliver the device across the 
aortic valve, switch the device on and then off, withdraw the device. 
15.4.2. Role of Boston Scientific Representatives 
Boston Scientific personnel who are trained in the use of the investigational device can 
provide technical support to the investigator and other health care personnel (collectively 
HCP) as needed during the procedure and testing required by the protocol. Support may 
include HCP training (see Section 15.4.1), addressing HCP questions, or providing 
clarifications to HCPs concerning the operation of BSC equipment/devices (including 
programmers, analyzers, and other support equipment). 
At the request of the investigator and while under investigator supervision, BSC personnel 
may operate equipment during the procedure, assist with the conduct of testing specified in 
the protocol, and interact with the subject to accomplish requested activities.  
Typical tasks may include the following. 
• Providing instructions for the safe return of investigational products; for potentially 
hazardous items, providing specialized instructions and materials, as applicable. 
• Interrogating the device or programming device parameters to investigator-requested 
settings as well as operating investigational equipment  
• Clarifying device behavior, operation or diagnostic output as requested by the 
investigator or other health care personnel 
• Providing technical expertise/support to the principal investigator or delegated center 
staff  
In addition, BSC personnel may perform certain activities to ensure study quality. These 
activities may include the following. 
• Observing testing or medical procedures to provide information relevant to protocol 
compliance 
• Reviewing collected data and study documentation for completeness and accuracy 
Boston Scientific personnel will not do the following.  
• Practice medicine 
• Provide medical diagnosis or treatment to subjects 
• Discuss a subject’s condition or treatment with a subject  
• Independently collect critical study data (defined as primary or secondary endpoint 
data) 
• Enter data in electronic data capture systems or on paper case report forms 

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15.5. Insurance  
Where required by local/country regulation, proof and type of insurance coverage for 
subjects in the study will be obtained by BSC. 
16. Monitoring 
Monitoring will be performed during the study to assess continued compliance with the 
protocol and applicable regulations. In addition, the clinical research monitor verifies that 
study records are adequately maintained, that data are reported in a satisfactory manner with 
respect to timeliness, adequacy, and accuracy, and that the Principal Investigator continues to 
have sufficient staff and facilities to conduct the study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original source documents by BSC 
personnel, their designees, and appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific monitoring requirements. A 
general outline of the monitoring plan is described below - 
Site Initiation Visits 
All sites participating in the study will have Site Initiation Visits (SIVs). A live, online 
training session with slides will be conducted virtually via the Web. A checklist of activities 
(as specified in the monitoring plan: e.g. protocol training, ICH/GCP, monitoring 
expectations, PI responsibilities, safety reporting requirements, documentation requirements, 
local law requirements such as: data protection, EC reporting) will be conducted and 
confirmed complete, prior to site authorization to enroll to ensure preparedness of the 
investigator and site staff. Additional training may be done on an as-needed basis throughout 
the study for study procedures and updates, clinical events, unanticipated adverse device 
effect reporting process, regulatory requirements, CRF completion, and compliance issues 
noted during monitoring. 
 
Interim Monitoring Visits 
Interim Monitoring Visits (IMVs) will be conducted for each site. Each visit will require a 
written confirmation letter, a monitoring visit report, and a follow up letter.  
At each interim monitoring visit, the monitor will assess: 
• Regulatory documents and contents of the Investigator Site File to ensure that they 
are complete, accurate and current. 
• Accuracy of data: the monitor will compare subject medical records and other 
supporting documents with the CRFs to determine that they are complete, accurate, 
and legible. 
• Informed consent forms: monitor will review the ICFs and documentation of the 
consent process in the source documents. 
• Safety reporting: monitor will verify and/or discuss that all reportable events and 
device deficiencies are reported and recorded in accordance with the protocol and the 
local regulatory requirements and ensures necessary source documents are obtained.    

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• Site resources, adequacy of facilities, any changes in study personnel, location, etc. 
• Device accountability to ensure the log is complete and accurate 
Site compliance to the study protocol will be assessed over the life of the study.   
 
Closeout Visits 
A Closeout monitoring visit (COV) will be performed for each site. Closeout activities can 
be performed separately or in conjunction with an interim monitoring visit. When preparing 
the site for closure, the monitor will verify and/or discuss that: 
• All essential documents are complete and up to date 
• All CRFs are completed 
• All outstanding queries are resolved 
• The current status of all ongoing adverse events is documented and protocol 
compliant. 
• All CRF pages are signed by the designated investigator 
• Device reconciliation is accurate and documented 
• Arrangements are made for archiving and record retention. 
The study may also be subject to a quality assurance audit by BSC or its designees, as well as 
inspection by appropriate regulatory authorities. It is important that the Principal Investigator 
and relevant study personnel are available during on-site monitoring visits or audits and that 
sufficient time is devoted to the process. 
17. Potential Risks and Benefits 
17.1. Anticipated Adverse Events and Adverse Device Effects 
Adverse events/adverse device effects (in alphabetical order) potentially associated with use 
of the Vortex System during HR-PCI include but may not be limited to the risks listed in 
Table 17.1-1. These potentially fatal complications may require the subject to undergo 
medical, percutaneous, or surgical intervention.  
As the Vortex System is an investigational device, uncertainty remains over risks of 
experiencing some or all of the complications listed below. There may be risks that are 
unknown at this time. 
Table 17.1-1: Risks Associated with Use of the Vortex System During High-Risk 
Percutaneous Coronary Intervention 
Access site complications (including hematoma, lymph vessel damage, pseudoaneurysm, arteriovenous 
fistula [myocardial contusion or rupture]) 
Acute kidney injury 
Allergic reaction or unfavorable response to procedure medications (including to medications, anesthesia, 
contrast, or device materials) 
Aneurysm 

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Table 17.1-1: Risks Associated with Use of the Vortex System During High-Risk 
Percutaneous Coronary Intervention 
Angina 
Aortic or mitral valve insufficiency or injury 
Arrhythmia or new conduction system injury (including need for pacemaker insertion) 
Bleeding  
Blood loss resulting in anemia 
Cardiac failure and pulmonary edema 
Cardiac ischemia possibly requiring surgical intervention 
Cardiogenic shock from low cardiac output 
Death 
Device malfunction 
Device related thrombus 
Dislodgement of the pump or interventional equipment from operating position 
Embolization (device, thrombus or other)  
Failure to achieve angiographic success 
Hemodynamic instability or shock 
Hemolysis  
Inability to complete coronary procedure 
Infection (including sepsis and endocarditis)  
Organ failure (including kidney, lungs and liver) 
Perforation or rupture of the heart or blood vessels including dissection or spasm 
Pericardial effusion/cardiac tamponade  
Peripheral ischemia or infarction 
Repeat revascularization 
Stroke/cerebrovascular accident/transient ischemic attack  
Thrombocytopenia 
 
17.2. Risks Associated with the Study Device 
Overall, there are no incremental risks expected with the investigational device compared to 
similar mechanical circulatory support system devices on the market. 
17.3. Risks Associated with Participation in the Clinical Study 
Risks associated with HR-PCI and participation in this clinical study are listed above in 
Table 17.1-1. 
17.4. Possible Interactions with Concomitant Medical Treatments 
Medications to be used in the Vortex Feasibility Study constitute standard of care for subjects 
undergoing HR-PCI as described in society guidelines3.  

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17.5. Risk Minimization Actions 
Additional risks may exist. Risks can be minimized through compliance with this protocol, 
performing procedures in the appropriate hospital environment, adherence to subject 
selection criteria, close monitoring of the subject's physiologic status during research 
procedures and/or follow-ups and by promptly supplying BSC with all pertinent information 
required by this protocol. 
The aforementioned risks are mitigated with the following approaches. 
• Estimation of risks associated with the investigational device in accordance with 
ISO 14971 prior to conducting the clinical investigation 
• Preclinical testing and bench testing of the Vortex System to establish safety and 
performance  
• Selection of investigators who are experienced and skilled in interventional HR-PCI 
procedures supported by mechanical circulatory support devices 
• Completion of training provided by the sponsor 
• Clearly defining the inclusion/exclusion criteria to ensure only appropriate subjects are 
enrolled  
• Confirmation of eligible subjects by investigators experienced in HR-PCI with MCS 
procedures 
• Performing all procedures in accordance with the Vortex System IFU 
• Ensuring that treatment of subjects is consistent with current medical practices, 
including adjunctive pharmacologic therapy 
• On-site support by BSC representatives during the procedure 
• Dynamic safety review processes, with Independent Medical Reviewer (IMR) 
adjudication 
Anticoagulation medication (e.g., heparin) will be administered during the procedure per 
standard of care to reduce the risk of thrombosis, embolism, and stroke.  
Cardiac enzyme, serum creatinine and plasma free hemoglobin measurements and 
electrocardiograms will be performed post-procedure to detect cardiac or renal injury. 
Subjects will be carefully monitored during the procedure, and through 72 hours or hospital 
discharge, whichever comes first.  
Data will be monitored as they are submitted to BSC. 
In addition, BSC has implemented specific design and clinical mitigations to address 
observations from prior preclinical and clinical studies. Please refer to the Investigator 
Brochure for a detailed description of risk mitigations. 

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17.6. Anticipated Benefits 
The Vortex System is intended to support stable subjects undergoing HR-PCI by temporarily 
decreasing the load on the heart and ensuring adequate organ perfusion. The benefit of 
mechanical circulatory support devices is that they provide support in the event the subject 
becomes hemodynamically unstable during a procedure. Society guidelines state that elective 
insertion of an appropriate hemodynamic support device as an adjunct to PCI may be 
reasonable in carefully selected high-risk patients18. The Vortex design provides mechanical 
circulatory support and a mechanism of action similar to that of the commercially available 
Impella® devices (Abiomed, Inc., Danvers, MA, USA). Both designs use a cannula and 
impeller to move blood from the left ventricle into the aorta. The Vortex System may provide 
improved conformation to subject anatomy and a less complex arrangement during the 
interventional procedure.  
Please see the Investigator Brochure for existing clinical data regarding use of mechanical 
circulatory support devices and additional information on the Vortex design. Prophylactic use 
of the Vortex System during HR-PCI procedures should improve patient hemodynamics and 
may improve patient outcomes. 
17.7. Risk to Benefit Rationale 
Review of the aforementioned clinical benefits versus risks takes into account the known 
risks/benefits that have been identified in the published literature on other mechanical 
circulatory support devices. Risks associated with the investigational device have been 
estimated, risk controls have been implemented, and an evaluation of residual risk (individual 
risks and overall risk) has been performed. When used according to the IFU, investigator 
training, and proctoring, all risks have been reduced as low as possible, and the medical 
benefits of the investigational device have been determined to outweigh the residual risk. 
18. Safety Reporting 
18.1. Reportable Events by Investigational Center to Boston Scientific 
It is the responsibility of the investigator to assess and report to BSC any event which occurs 
in any of following categories from time of enrollment through end of study (see definitions 
in Table 18.2-1). 
• All serious adverse events (SAE)  
• All adverse events (AE) 
• All serious adverse device effects (SADE)  
• All adverse device effects (ADE)  
• All investigational device deficiencies  
• All unanticipated serious adverse device effects (USADE) 

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• All IMR events 
• New findings/updates in relation to already reported events 
When possible, the medical diagnosis should be reported as the Event Term instead of 
individual symptoms. 
If it is unclear whether or not an event fits one of the above categories, or if the event cannot 
be isolated from the device or procedure, it should be submitted as an adverse event and/or 
device deficiency. 
Any reportable AE required by the protocol and experienced by the study subject after 
informed consent and once considered enrolled in the study (see Section 9.1), whether during 
or subsequent to the study procedure, must be recorded in the eCRF. 
Underlying diseases and chronic conditions are not reported as AEs unless there is an 
increase in severity or frequency during the course of the investigation. Death should not be 
recorded as an AE but should only be reflected as an outcome of one (1) specific SAE (see 
Table 18.2-1 for AE definitions).  
Refer to Section 16 for the known risks associated with the study device. 
18.2. Definitions and Classification 
Adverse event definitions are provided in Table 18.2-1. Administrative edits were made on 
the safety definitions from applicable regulations and guidance including (but not limited to) 
ISO 14155 and EU MDR 2017/745/MDCG 2020-10/1 Guidance on Safety Reporting in 
Clinical Investigations for clarification purposes. 
Table 18.2-1: Safety Definitions 
Term 
Definition 
Adverse Event (AE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Any untoward medical occurrence, unintended disease or injury, or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or 
other persons, in the context of a clinical investigation, whether or not related to 
the investigational medical device and whether anticipated or unanticipated.  
NOTE 1: This includes events related to the investigational medical device or 
comparator. 
NOTE 2: This definition includes events related to the procedures involved. 
NOTE 3: For users or other persons, this definition is restricted to events related 
to the investigational medical device.  
NOTE 4: This definition includes events related to management practices 
NOTE 5: This definition includes patient related events 
Adverse Device Effect 
(ADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse event related to the use of an investigational medical device 
NOTE 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the procedural 
treatment, the installation, the operation, or any malfunction of the 
investigational medical device. 

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Table 18.2-1: Safety Definitions 
Term 
Definition 
NOTE 2: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
NOTE 3: This includes "comparator" if the comparator is a medical device. 
Serious Adverse Event 
(SAE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse event that led to any of the following: 
 a)  Death, 
 b)  Serious deterioration in the health of the subject, users or other persons as 
defined by either: 
 
 
1) a life-threatening illness or injury, or 
 
 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases, or  
 
 
3) in-patient hospitalization or prolongation of existing hospitalization, or 
 
 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
 c) Foetal distress, foetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
NOTE 1: Planned hospitalization for a pre-existing condition, or a procedure 
required by the clinical investigational plan, without a serious deterioration in 
health, is not considered a serious adverse event.  
Serious Adverse 
Device Effect (SADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event. 
 
Unanticipated Serious 
Adverse Device Effect 
(USADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Serious adverse device effect which by its nature, incidence, severity, or outcome 
has not been identified in the current risk assessment.  
NOTE 1: Anticipated serious adverse device effect (ASADE) is an effect which 
by its nature incidence, severity or outcome has been identified in the risk 
assessment. 
Serious Health Threat 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an imminent 
risk of death or a serious deterioration in the health of subjects, users or other 
persons, and that requires prompt remedial action for other subjects, users or 
other persons. 
NOTE 1: This would include events that are of significant and unexpected 
nature such that they become alarming as a potential serious health hazard or 
possibility of multiple deaths occurring at short intervals. 
Device Deficiency 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
An inadequacy of a medical device related to its identity, quality, durability, 
reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include malfunctions, use errors, and inadequacy 
in the information supplied by the manufacturer including labelling. 
NOTE 2: This definition includes device deficiencies related to the 
investigational medical device or the comparator. 
The following definitions will be used for defining hospitalization or prolongation of hospitalization for SAE 
classification purposes: 

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Table 18.2-1: Safety Definitions 
Term 
Definition 
Hospitalizations  
Hospitalization does not include: 
• Emergency room visit that does not result in in-patient admission  
NOTE 1: Although an emergency room visit does not itself meet the 
definition for hospitalization, it may meet other serious criteria (e.g., 
medical or surgical intervention to prevent permanent impairment or 
damage) 
• Elective and pre-planned treatment/surgery for a pre-existing condition that 
is documented in the subject’s record at the time of consent/enrollment 
• Admission for social reasons and/or respite care in the absence of any 
deterioration in the subject’s general condition (e.g., subject is homeless, 
caregiver relief) 
• Pre-planned, protocol-specified admission related to the clinical study (e.g., 
procedure required by protocol) 
Prolongation of 
Hospitalization  
In-patient admission to the hospital that is prolonged beyond the expected 
standard duration for the condition under treatment. 
NOTE 1: New adverse events occurring during the hospitalization are evaluated 
to determine if they prolonged hospitalization or meet another SAE criterion. 
 
18.3. Relationship to Study Device(s) and/or Study Procedure 
The Investigator must assess the relationship of the reportable adverse events to the study 
device or study procedure. See criteria in Table 18.3-1:  
Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
Not Related 
Ref: MDCG 2020-10/1 
Relationship to the device, comparator, or procedures can be excluded when: 
• the event has no temporal relationship with the use of the investigational 
device or the procedures related to the use of the investigational device; 
• the serious event does not follow a known response pattern to the medical 
device (if the response pattern is previously known) and is biologically 
implausible; 
• the discontinuation of medical device application or the reduction of the 
level of activation/exposure - when clinically feasible – and reintroduction 
of its use (or increase of the level of activation/exposure), do not impact on 
the serious event; 
• the event involves a body-site or an organ that cannot  be affected by the 
device or procedure; 
• the serious event can be attributed to another cause (e.g., an underlying or 
concurrent illness/clinical condition; an effect of another device, drug, 
treatment or other risk factors); 

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Table 18.3-1: Criteria for Assessing Relationship of Study Device or Procedure to 
Adverse Event 
Classification 
Description 
• the event does not depend on a false result given by the investigational 
device used for diagnosis, when applicable;  
In order to establish the non-relatedness, not all the criteria listed above might be 
met at the same time, depending on the type of device/procedures and the serious 
event. 
Possibly Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the investigational device or comparator or the 
relationship with procedures is weak but cannot be ruled out completely. 
Alternative causes are also possible (e.g., an underlying or concurrent 
illness/clinical condition and/or an effect of another device, drug or treatment). 
Cases where relatedness cannot be assessed, or no information has been obtained 
should also be classified as possible. 
Probably Related 
Ref: MDCG 2020-10/1 
The relationship with the use of the investigational device, comparator, or the 
relationship with procedures seems relevant and/or the event cannot be 
reasonably explained by another cause. 
Causal Relationship 
Ref: MDCG 2020-10/1 
The serious event is associated with the investigational device or comparator or 
with procedures beyond reasonable doubt when: 
• the event is a known side effect of the product category the device belongs 
to or of similar devices and procedures; 
• the event has a temporal relationship with investigational device 
use/application or procedures; 
• the event involves a body-site or organ that 
- the investigational device or procedures are applied to; 
- the investigational device or procedures have an effect on; 
• the serious event follows a known response pattern to the medical device (if 
the response pattern is previously known); 
• the discontinuation of medical device application (or reduction of the level 
of activation/exposure) and reintroduction of its use (or increase of the level 
of activation/exposure), impact on the serious event (when clinically 
feasible); 
• other possible causes (e.g., an underlying or concurrent illness/clinical 
condition or/and an effect of another device, drug or treatment) have been 
adequately ruled out; 
• harm to the subject is due to error in use; 
• the event depends on a false result given by the investigational device used 
for diagnosis, when applicable 
In order to establish the relatedness, not all the criteria listed above might be met 
at the same time, depending on the type of device/procedures and the serious 
adverse event. 
 
18.4. Investigator Reporting Requirements 
The communication requirements for reporting to BSC are as shown in Table 18.4-1. 

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Table 18.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline (Pre-market Studies) 
(MDCG 2020-10/1) 
Unanticipated 
Serious Adverse 
Device Effects  
(USADE) 
Complete AE electronic case 
report form (eCRF) page with 
all available new and updated 
information.  
• Within 1 business day of first becoming 
aware of the event 
• Terminating at the end of the study 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event.  
• Upon request of sponsor  
Serious Adverse 
Events (SAE) and 
IMR eventsa  
Complete AE eCRF page with 
all available new and updated 
information.  
• Immediately but not later than 3 calendar 
days of first becoming aware of the event or 
as per local/regional regulations  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-identified 
/pseudonymized) for reported 
event. 
• Upon request of sponsor 
Serious Adverse 
Device Effects 
(SADE) 
 
Complete AE eCRF page with 
all available new and updated 
information. 
• Immediately but not later than  3 calendar 
days of first becoming aware of the event or 
as per local/regional regulations  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event.  
• When documentation is available 
• Upon request of sponsor  
Device Deficiencies 
(including but not 
limited to , 
malfunctions, use 
errors and 
inadequacy in 
information supplied 
by the manufacturer, 
including labeling) 
Note:  Any Device 
Deficiency that might 
have led to a serious 
adverse event if 
appropriate action 
had not been taken, 
intervention had not 
occurred, 
circumstances had 
Complete Device Deficiency 
eCRF with all available new 
and updated information.  
• Immediately but not later than  3 calendar 
days of first becoming aware of the event.  
• Reporting required through the end of the 
study 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event. 
• Upon request of sponsor  

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Table 18.4-1: Investigator Reporting Requirements 
Event Classification 
Communication Method  
Communication Timeline (Pre-market Studies) 
(MDCG 2020-10/1) 
been less fortunate is 
considered a 
reportable event. 
Adverse Event (AE) 
including Adverse 
Device Effects 
(ADE) 
Complete AE eCRF page, 
which contains such 
information as date of AE, 
treatment of AE resolution, 
assessment of seriousness and 
relationship to the device.  
• Adverse Device Effects: In a timely manner 
but not later than 10 business days after 
becoming aware of the information 
• Adverse Events: In a timely manner but 
recommend within 10 business days after 
becoming aware of the information 
• Reporting required through the end of the 
study  
• Upon request of sponsor 
Provide all relevant source 
documentation (de-identified/ 
pseudonymized) for reported 
event.  
a: All Independent Medical Reviewer (IMR) events must be reported using the timeframe for SAE, 
regardless of whether they meet serious criteria. 
 
18.5. Device Deficiencies 
Vortex System device deficiencies will be documented in the appropriate eCRF and reported 
to BSC. If possible, the device(s) should be returned to BSC for analysis. Instructions for 
returning the investigational device(s) will be provided in the Manual of Operations. Device 
deficiencies should also be documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an adverse event that results from a 
device deficiency would be recorded as an adverse event on the appropriate eCRF. 
18.6. Reporting to Regulatory Authorities / IECs / HRECs/ Investigators 
Boston Scientific Corporation is responsible for reporting adverse event information to all 
participating Principal Investigators, IECs/HRECs and regulatory authorities, as applicable.  
The Principal Investigator is responsible for informing the IEC/HREC and regulatory 
authorities of USADEs and SAEs as required by local/regional regulations. 
19. Informed Consent 
Subject participation in this clinical study is voluntary. Informed Consent is required from 
each subject or his/her legally authorized representative. The Investigator is responsible for 
ensuring that Informed Consent is obtained prior to the use of any investigational devices, 
study-required procedures and/or testing, or data collection.  
The obtaining and documentation of Informed Consent must be in accordance with the 
principles of the Declaration of Helsinki, the relevant parts of ISO 14155:2020, any 

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applicable national regulations, and local Ethics Committee and/or Regulatory authority, as 
applicable. The ICF must be accepted by BSC or its delegate (e.g., CRO), and approved by 
the center’s IEC/HREC, if applicable. 
Boston Scientific Corporation will provide a study-specific template of the ICF to 
investigators participating in this study. The ICF template may be modified to meet the 
requirements of the investigative site’s IEC/HREC. Any modification requires acceptance 
from BSC or authorized representative prior to use of the form. The ICF must be in a 
language understandable to the subject and if needed, BSC will assist the center in obtaining 
a written consent translation. Translated consent forms must also have IEC/HREC approval 
prior to their use. Privacy language shall be included in the body of the form or as a separate 
form as applicable.   
The process of obtaining Informed Consent shall at a minimum include the following steps, 
as well as any other steps required by applicable laws, rules, regulations and guidelines: 
• be conducted by the Principal Investigator or designee authorized to conduct the 
process,  
• include a description of all aspects of the clinical study that are relevant to the 
subject’s decision to participate throughout the clinical study, 
• avoid any coercion of or undue influence of subjects to participate, 
• not waive or appear to waive subject’s legal rights, 
• use native language that is non-technical and understandable to the subject or his/her 
legal representative, 
• provide ample time for the subject to consider participation and ask questions if 
necessary, 
• ensure important new information is provided to new and existing subjects throughout 
the clinical study.  
The ICF shall always be signed and personally dated by the subject or legal representative 
competent to sign the ICF under the applicable laws, rules, regulations and guidelines and by 
the investigator and/or an authorized designee responsible for conducting the informed 
consent process. If a legal representative signs, the subject shall be asked to provide informed 
consent for continued participation as soon as his/her medical condition allows. The original 
signed ICF will be retained by the center and a copy of the signed and dated document and 
any other written information must be given to the person signing the form.  
Failure to obtain subject consent will be reported by BSC to the applicable regulatory 
authority according to their requirements. Any violations of the informed consent process 
must be reported as deviations to the sponsor and local regulatory authorities (e.g., 
IEC/HREC), as appropriate. 
If new information becomes available that can significantly affect a subject's future health 
and medical care, that information shall be provided to the affected subject(s) in written form 
via a revised ICF or, in some situations, enrolled subjects may be requested to sign and date 

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an addendum to the ICF. In addition to new significant information during the course of a 
study, other situations may necessitate revision of the ICF, such as if there are amendments 
to the applicable laws, protocol, a change in Principal Investigator, administrative changes, or 
following annual review by the IEC/HREC. The new version of the ICF must be approved by 
the IEC/HREC. Acceptance by Boston Scientific is required if changes to the revised ICF are 
requested by the center's IEC/HREC. The IEC/HREC will determine the subject population 
to be re-consented. 
Study personnel should explain to the subject that even if the subject agrees to participate in 
the study and signs the ICF, screening tests and procedures may demonstrate that the subject 
is not a suitable candidate for the study. 
20. Committees 
20.1. Safety Monitoring Process 
The BSC personnel from the Medical Safety and Safety Trial Operations team review safety 
data as the data are reported by the centers throughout the duration of the study.  During 
scheduled monitoring activities, clinical research monitors will further support this review 
through their review of source documents and other data information. The BSC Medical 
Safety and Safety Trial Operations team include health care providers with expertise in HR-
PCI and with the necessary therapeutic and subject matter expertise to evaluate and classify 
the events into the categories outlined above. 
20.2. Independent Medical Reviewer 
An Independent Medical Reviewer (IMR) will be used in this study. The IMR will review a 
safety event dossier which may include copies of subject source documents provided by 
study centers and adjudicate study endpoint related clinical events as per the IMR charter. 
The responsibilities, qualifications, and procedures of the IMR are outlined in the IMR 
charter. 
21. Suspension or Termination 
21.1. Premature Termination of the Study 
Boston Scientific reserves the right to terminate the study at any stage but intends to exercise 
this right only for valid scientific or business reasons and reasons related to protection of 
subjects. Investigators, associated IECs/HRECs, and regulatory authorities, as applicable, 
will be notified in writing in the event of study termination.  
21.1.1. Criteria for Premature Termination of the Study 
Possible reasons for premature study termination include, but are not limited to, the 
following. 

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• Suspicion of an unacceptable risk, including serious health threat. In this case, the 
sponsor shall suspend the clinical investigation while the risk is assessed. The sponsor 
shall terminate the clinical investigation if an unacceptable risk which cannot be 
controlled is confirmed. 
• Instructions by the IEC/HREC or regulatory authorities to suspend or terminate the 
clinical investigation. 
• An enrollment rate far below expectation that prejudices the conclusion of the study.  
• A decision on the part of Boston Scientific to suspend or discontinue development of 
the device. 
21.2. Termination of Study Participation by the Investigator or Withdrawal of 
IEC/HREC Approval  
Any investigator, or associated IEC/HREC or regulatory authority may discontinue 
participation in the study or withdraw approval of the study, respectively, with suitable 
written notice to BSC. Investigators, associated IECs/HRECs, and regulatory authorities, as 
applicable, will be notified in writing in the event of these occurrences. 
21.3. Requirements for Documentation and Subject Follow-up 
In the event of premature study termination, a written statement as to why the premature 
termination has occurred will be provided to all participating sites by BSC. The IEC/HREC 
and regulatory authorities, as applicable, will be notified. Detailed information on how 
enrolled subjects will be managed thereafter will be provided.  
In the event an IEC/HREC terminates participation in the study, participating investigators, 
associated IECs/HRECs, and regulatory authorities, as applicable, will be notified in writing. 
Detailed information on how enrolled subjects will be managed thereafter will be provided 
by BSC. 
In the event a Principal Investigator terminates participation in the study, study responsibility 
will be transferred to another investigator, if possible. In the event there are no opportunities 
to transfer Principal Investigator responsibility, detailed information on how enrolled 
subjects will be managed thereafter will be provided by BSC. 
The Principal Investigator or his/her designee must return all study-related documents and 
investigational product to BSC, unless this action would jeopardize the rights, safety, or 
welfare of the subjects. 
21.4. Criteria for Suspending/Terminating a Study Center 
Boston Scientific Corporation reserves the right to stop the inclusion of subjects at a study 
center at any time after the study initiation visit if no subjects have been enrolled or if the 
center has multiple or severe protocol violations/noncompliance without justification and/or 
fails to follow remedial actions. 

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In the event of termination of center participation, all study devices and testing equipment, as 
applicable, will be returned to BSC unless this action would jeopardize the rights, safety or 
well-being of the subjects. The IEC/HREC and regulatory authorities, as applicable, will be 
notified. Study participants will be contacted, as applicable, and be informed of changes to 
study visit schedule. 
22. Study Registration and Results 
22.1. Study Registration 
To comply with applicable laws and regulations, the study will be registered on a publicly 
accessible database before enrollment of the first subject. 
22.2. Clinical Investigation Report 
Study results will be made available in accordance with the legal requirements and the 
recognized ethical principles, in accordance with the Boston Scientific Policy. A Clinical 
Investigation Report will be made available to all investigators, IECs/HRECs, and regulatory 
authorities, as applicable in accordance with the Boston Scientific Policy and local 
requirements. 
22.3. Publication Policy 
Boston Scientific Corporation requires disclosure of its involvement as a sponsor or financial 
supporter in any publication or presentation relating to a BSC study or its results. Boston 
Scientific Corporation may submit study results for publication (regardless of study outcome) 
following the conclusion or termination of the study. Boston Scientific Corporation adheres 
to the Contributorship Criteria set forth in the Uniform Requirements of the International 
Committee of Medical Journal Editors (ICMJE; http://www.icmje.org). In order to ensure the 
public disclosure of study results in a timely manner, while maintaining an unbiased 
presentation of study outcomes, BSC personnel may assist authors and investigators in 
publication preparation provided the following guidelines are followed.  
• All authorship and contributorship requirements as described above must be followed. 
• BSC involvement in the publication preparation and the BSC Publication Policy 
should be discussed with the Coordinating Principal Investigator(s) and/or 
Executive/Steering Committee at the onset of the project. 
• The First and Senior authors are the primary drivers of decisions regarding publication 
content, review, approval, and submission.  
The data, analytic methods, and study materials for this clinical trial may be made available 
to other researchers in accordance with the Boston Scientific Data Sharing Policy 
(https://www.bostonscientific.com/). 

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23. Bibliography 
1. 
Virani SS, Alonso A, Benjamin EJ, et al. Heart disease and stroke statistics-2020 
update: A report from the American Heart Association. Circulation 2020;141:e139-
e596. 
2. 
Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for 
Percutaneous Coronary Intervention. A report of the American College of Cardiology 
Foundation/American Heart Association Task Force on Practice Guidelines and the 
Society for Cardiovascular Angiography and Interventions. Circulation 2011;124:e574-
e651. 
3. 
Neumann FJ, Sousa-Uva M, Ahlsson A, et al. 2018 ESC/EACTS Guidelines on 
myocardial revascularization. Eur Heart J 2019;40:87-165. 
4. 
Kirtane AJ, Doshi D, Leon MB, et al. Treatment of higher-risk patients with an 
indication for revascularization: evolution within the field of contemporary 
percutaneous coronary intervention. Circulation 2016;134:422-31. 
5. 
Riley RF, Henry TD, Mahmud E, et al. SCAI position statement on optimal 
percutaneous coronary interventional therapy for complex coronary artery disease. 
Catheter Cardiovasc Interv 2020;96:346-62. 
6. 
Simonton C, Thompson C, Wollmuth JR, Morris DL, Dahle TG. The role of 
hemodynamic support in high-risk percutaneous coronary intervention US Cardiol 
Review 2020;14:e13. 
7. 
Hannan EL, Wu C, Walford G, et al. Incomplete revascularization in the era of drug-
eluting stents: impact on adverse outcomes. JACC Cardiovasc Interv 2009;2:17-25. 
8. 
Ahn JM, Park DW, Lee CW, et al. Comparison of stenting versus bypass surgery 
according to the completeness of revascularization in severe coronary artery disease: 
patient-level pooled analysis of the SYNTAX, PRECOMBAT, and BEST trials. J Am 
Coll Cardiol Intv 2017;10:1415-24. 
9. 
Watkins S, Oldroyd KG, Preda I, et al. Five-year outcomes of staged percutaneous 
coronary intervention in the SYNTAX study. EuroIntervention 2015;10:1402-8. 
10. Dangas G, Mehran R, Feldman D, et al. Postprocedure creatine kinase-MB elevation 
and baseline left ventricular dysfunction predict one-year mortality after percutaneous 
coronary intervention. Am J Cardiol 2002;89:586-9. 
11. Herrmann J. Peri-procedural myocardial injury: 2005 update. Eur Heart J 
2005;26:2493-519. 
12. Atkinson TM, Ohman EM, O'Neill WW, Rab T, Cigarroa JE. A practical approach to 
mechanical circulatory support in patients undergoing percutaneous coronary 
intervention: An interventional perspective. J Am Coll Cardiol Intv 2016;9:871-83. 

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13. Myat A, Patel N, Tehrani S, Banning AP, Redwood SR, Bhatt DL. Percutaneous 
circulatory assist devices for high-risk coronary intervention. J Am Coll Cardiol Intv 
2015;8:229-44. 
14. Rihal CS, Naidu SS, Givertz MM, et al. 2015 SCAI/ACC/HFSA/STS Clinical Expert 
Consensus Statement on the Use of Percutaneous Mechanical Circulatory Support 
Devices in Cardiovascular Care: Endorsed by the American Heart Assocation, the 
Cardiological Society of India, and Sociedad Latino Americana de Cardiologia 
Intervencion; Affirmation of Value by the Canadian Association of Interventional 
Cardiology-Association Canadienne de Cardiologie d'intervention. J Am Coll Cardiol 
2015;65:e7-e26. 
15. Aggarwal B, Aman W, Jeroudi O, Kleiman NS. Mechanical circulatory support in 
high-risk percutaneous coronary intervention. Methodist Debakey Cardiovasc J 
2018;14:23-31. 
16. Becher T, Eder F, Baumann S, et al. Unprotected versus protected high-risk 
percutaneous coronary intervention with the Impella 2.5 in patients with multivessel 
disease and severely reduced left ventricular function. Medicine 2018;97:e12665. 
17. Asleh R, Resar JR. Utilization of percutaneous mechanical circulatory support devices 
in cardiogenic shock complicating acute myocardial infarction and high-risk 
percutaneous coronary interventions. J Clin Med 2019;8:1209;doi: 
10.3390/jcm8081209. 
18. Levine GN, Bates ER, Blankenship JC, et al. 2011 ACCF/AHA/SCAI Guideline for 
Percutaneous Coronary Intervention: executive summary: a report of the American 
College of Cardiology Foundation/American Heart Association Task Force on Practice 
Guidelines and the Society for Cardiovascular Angiography and Interventions. Catheter 
Cardiovasc Interv 2012;79:453-95. 
19. Burkhoff D, Sayer G, Doshi D, Uriel N. Hemodynamics of mechanical circulatory 
support. J Am Coll Cardiol 2015;66:2663-74. 
20. Alqarqaz M, Basir M, Alaswad K, O'Neill W. Effects of Impella on coronary perfusion 
in patients with critical coronary artery stenosis. Circ Cardiovasc Interv 
2018;11:e005870. 
21. Impella® Ventricular Support Systems for Use During Cardiogenic Shock and High-
Risk PCI Instructions for Use. Abiomed®, Inc., Danvers, MA, USA. 2020. 
22. Dixon SR, Henriques JP, Mauri L, et al. 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. J Am Coll Cardiol Intv 
2009;2:91-6. 
23. O'Neill WW, Kleiman NS, Moses J, et al. 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;126:1717-27. 

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24. Maini B, Naidu SS, Mulukutla S, et al. Real-world use of the Impella 2.5 circulatory 
support system in complex high-risk percutaneous coronary intervention: the USpella 
Registry. Catheter Cardiovasc Interv 2012;80:717-25. 
25. Sjauw KD, Konorza T, Erbel R, et al. Supported high-risk percutaneous coronary 
intervention with the Impella 2.5 device the Europella registry. J Am Coll Cardiol 
2009;54:2430-4. 
26. Baumann S, Werner N, Ibrahim K, et al. Indication and short-term clinical outcomes of 
high-risk percutaneous coronary intervention with microaxial Impella® pump: results 
from the German Impella® registry. Clin Res Cardiol 2018;107:653-7. 
27. Burzotta F, Russo G, Ribichini F, et al. Long-term outcomes of extent of 
revascularization in complex high risk and indicated patients undergoing Impella-
protected percutaneous coronary intervention: Report from the Roma-Verona Registry. 
J Interv Cardiol 2019;5243913:doi:10.1155/2019/5243913. 
28. Kormos RL, Antonides CFJ, Goldstein DJ, et al. Updated definitions of adverse events 
for trials and registries of mechanical circulatory support: A consensus statement of the 
mechanical circulatory support academic research consortium. J Heart Lung Transplant 
2020;39:735-50. 
29. Bellomo R, Ronco C, Kellum JA, Mehta RL, Palevsky P. Acute renal failure - 
definition, outcome measures, animal models, fluid therapy and information technology 
needs: the Second International Consensus Conference of the Acute Dialysis Quality 
Initiative (ADQI) Group. Crit Care 2004;8:R204-12. 
30. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an 
initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R31. 
31. Nishimura RA, Otto CM, Bonow RO, et al. 2014 AHA/ACC Guideline for the 
management of patients with valvular heart disease: a report of the American College 
of Cardiology/American Heart Association task force on practice guidelines. J Am Coll 
Cardiol 2014;63:e57-185. 
32. Konstam MA, Kiernan MS, Bernstein D, et al. Evaluation and management of right-
sided heart failure: A Scientific Statement from the American Heart Association. 
Circulation 2018;137:e578-e622. 
33. Enriquez A, Saenz LC, Rosso R, et al. Use of intracardiac echocardiography in 
interventional cardiology: Working with the anatomy rather than fighting it. Circulation 
2018;137:2278-94. 
34. Kirklin JK, Naftel DC, Stevenson LW, et al. INTERMACS database for durable 
devices for circulatory support: first annual report. J Heart Lung Transplant 
2008;27:1065-72. 
35. Thygesen K, Alpert JS, Jaffe AS, et al. Fourth Universal Definition of Myocardial 
Infarction (2018). J Am Coll Cardiol 2018;72:2231-64. 
 

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24. Abbreviations and Definitions 
24.1. Abbreviations 
Abbreviations are shown in Table 24.1-1.   
Table 24.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
ACT 
activated clotting time 
ADE 
adverse device effect 
ADP  
adenosine diphosphate  
AE 
adverse event 
AKI 
acute kidney injury 
BP  
blood pressure 
BSC 
Boston Scientific Corporation 
CABG 
coronary artery bypass grafting 
CAD 
coronary artery disease 
CCS 
Canadian Cardiovascular Society  
CHIP 
complex high-risk and indicated patients 
CI 
cardiac index 
CK 
creatine kinase 
CK-MB 
creatine kinase-myoglobin band 
CPR 
cardiopulmonary resuscitation 
CRF 
case report form 
CV 
cardiovascular 
CVP 
central venous pressure 
ECG 
electrocardiogram 
EDC 
electronic data capture 
FEV1 
forced expiratory volume in the first second 
GCP 
Good Clinical Practices 
HIT 
heparin induced thrombocytopenia 
HREC 
Human Research Ethics Committee 
HR-PCI 
high risk percutaneous coronary intervention 
IABP 
intra-aortic balloon pump 
ICF 
informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
INR 
international normalization ratio 
IMR 
Independent Medical Reviewer 
ISO 
International Organization for Standardization 
LVEF 
left ventricular ejection fraction 
MI 
myocardial infarction 
MCS 
mechanical circulatory support 
MCS-ARC  
Mechanical Circulatory Support Academic Research Consortium 

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Table 24.1-1: Abbreviations 
Abbreviation/Acronym 
Term 
NYHA 
New York Heart Association 
PA 
pulmonary artery 
PCI 
percutaneous coronary intervention 
PCWP 
pulmonary capillary wedge pressure 
PVD 
peripheral vessel disease 
PVR 
pulmonary vascular resistance 
RAP 
right atrial pressure 
RVSWI 
right ventricular stroke work index 
SADE  
serious adverse device effect 
SAE 
serious adverse event 
STEMI 
ST-elevation myocardial infarction 
TIA 
transient ischemic attack 
TTE 
transthoracic echocardiogram 
ULN 
upper limit of normal 
URL 
upper reference limit 
USADE 
unanticipated serious adverse device effect 
VSD 
ventricular septal defect 
 
24.2. Definitions 
Terms are defined in Table 24.2-1. 
Table 24.2-1: Definitions 
Term 
Definition 
ACUTE KIDNEY 
INJURY (AKI) 
(AKIN System29,30) 
Maximal change in serum creatinine from baseline through discharge or 72 hours 
post-procedure, whichever comes first. 
• Stage 1: Increase in serum creatinine to 150–199% (1.5–1.99 × increase 
compared with baseline) OR increase of ≥0.3 mg/dl (≥26.4 mmol/L), or urine 
output <0.5 ml/kg per hour for >6 but <12 hours  
• Stage 2: Increase in serum creatinine to 200–299% (2.0–2.99 × increase 
compared with baseline) or urine output <0.5 ml/kg per hour for >12 but <24 
hours 
• Stage 3: Increase in serum creatinine to ≥300% (>3 × increase compared with 
baseline) OR serum creatinine of ≥4.0 mg/dL (≥354 mmol/L) with an acute 
increase of at least 0.5 mg/dL (44 mmol/L) OR urine output <0.3 ml/kg per hour 
for ≥24 hours or anuria for ≥12 hours 
Note: Subjects receiving renal replacement therapy are considered to meet Stage 3 
criteria irrespective of other criteria. 
ACUTE VESSEL 
OCCLUSION 
The state of complete luminal obstruction with no antegrade blood flow. 
ADVERSE EVENT 
(AE) 
Ref: ISO 14155 
Any untoward medical occurrence, unintended disease or injury, or any untoward 
clinical signs (including an abnormal laboratory finding) in subjects, users or other 

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Table 24.2-1: Definitions 
Term 
Definition 
Ref: MDCG 2020-10/1 
 
persons, in the context of a clinical investigation, whether or not related to the 
investigational medical device and whether anticipated or unanticipated. 
Note 1: This includes events related to the investigational medical device or the 
comparator. 
Note 2: This definition includes events related to the procedures involved. 
Note 3: For users or other persons, this definition is restricted to events related to 
the investigational medical device.  
Note 4: This definition includes events related to management practices. 
Note 5: This definition includes patient related events. 
ADVERSE EVENT 
BECOME AWARE 
DATE 
The become aware date for an adverse event that requires reporting per the protocol 
is the date that study personnel listed on the Delegation of Authority Log identify or 
are notified of the event. 
ADVERSE DEVICE 
EFFECT (ADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
 
 
Adverse event related to the use of an investigational medical device 
Note 1: This includes any adverse event resulting from insufficiencies or 
inadequacies in the instructions for use, the deployment, the procedural treatment, 
the installation, the operation, or any malfunction of the investigational medical 
device.  
Note 2: This definition includes any event resulting from use error or from 
intentional misuse of the investigational medical device. 
Note 3: This includes "comparator" if the comparator is a medical device. 
AORTIC DISSECTION 
Intimal tear resulting in blood splitting the aortic media and producing a false 
lumen that can progress in an antegrade or retrograde direction. Aortic dissection is 
further classified using Stanford classification (Types A and B depending on 
whether ascending or descending aorta involved) or DeBakey classification (Types 
I, II and III) [see Figure below]. 
 

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Table 24.2-1: Definitions 
Term 
Definition 
ARRHYTHMIA28 
MCS-ARC Cardiac Arrhythmias 
Any documented arrhythmia that results in clinical compromise (e.g., abnormal 
Vortex System function [e.g., diminished Vortex System flow or suction events], 
oliguria, pre-syncope or syncope, angina, dyspnea), or requires hospitalization or 
treatment (drug therapy, defibrillation, cardioversion, ICD therapy (e.g., shock or 
anti-tachycardia pacing) or arrhythmia ablation procedure). Cardiac arrhythmias are 
classified as 1 of 2 types. 
• Sustained ventricular arrhythmia resulting in clinical compromise, or requiring 
hospitalization or drug treatment, defibrillation, cardioversion, ICD therapy, or 
arrhythmia ablation procedure. 
• Sustained supraventricular arrhythmia resulting in clinical compromise, or 
requiring hospitalization or drug treatment, cardioversion, ICD therapy, or 
arrhythmia ablation procedure 
The association of the cardiac arrhythmia event should be classified as follows: 
• Patient-related (e.g., recurrence of pre-operative arrhythmia non-adherence with 
medications) 
• Management-related (e.g., related to uncorrected electrolyte imbalance, Swan 
Ganz malposition, secondary to cardiac tamponade) 
• Device-related (e.g., Vortex System malfunction, malposition of Vortex System 
or inflow cannula) 
BLEEDING 
COMPLICATIONS28  
MCS-ARC Bleeding Adverse Event 
• Type 1: Bleeding that is not actionable and does not cause the patient to seek 
unscheduled performance of studies, hospitalization, or treatment by a healthcare 
professional; may include episodes leading to self-discontinuation of medical 
therapy by the patient without consulting a healthcare professional. This type is 
not relevant during a hospitalization. 
• Type 2: Any overt, actionable sign of hemorrhage (e.g., more bleeding than 
would be expected for a clinical circumstance, including bleeding found by 
imaging alone) that does not fit the criteria for Type 3, 4, or 5 but does meet at 
least one of the following criteria:  
1) requiring nonsurgical medical intervention by a health care professional;  
2) leading to hospitalization or increased level of care; or  
3) prompting evaluation.  
• Type 3:  
- Type 3a: 
o Overt bleeding accompanied by hemoglobin drop of 3 to < 5 g/dl or 
(1.86−3.1 mmol/liter SI units) (provided hemoglobin drop is related to 
bleed) 
o Any transfusion with overt bleeding 
- Type 3b: 
o Overt bleeding plus hemoglobin drop 5 g/dl (3.1 mmol/liter) or greater 
(provided hemoglobin drop is related to bleed). 
o Cardiac tamponade 
o Bleeding requiring surgical intervention for control (excluding 
dental/nasal/skin/hemorrhoid) 
o Bleeding requiring intravenous vasoactive agents 

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Table 24.2-1: Definitions 
Term 
Definition 
• Type 4: Vortex System-related bleeding (includes concomitant cardiac or non-
cardiac surgical procedures)  
1) Reoperation after the closure of incision or incisions used to place the Vortex 
System to control bleeding.  
2) ≥ 50 kg: ≥ 4 U packed red blood cells (PRBC) within any 48 hours through 
discharge or 72 hours post-procedure (whichever comes first). 
3) < 50 kg: ≥ 20 cm3/kg PRBC within any 24 hours through discharge or 
72 hours post-procedure (whichever comes first). 
4) Chest tube output > 2 liters within 24 hours.  
• Type 5: Fatal bleeding 
- Type 5a: Probable fatal bleeding; no autopsy or imaging confirmation but 
clinically suspicious 
- Type 5b: Definite fatal bleeding; overt bleeding or autopsy or imaging 
confirmation 
The association of the bleeding event should be classified as follows: 
• Patient-related (e.g., coagulopathy unrelated to surgical technique such as non-
adherence with anti-coagulation medication resulting in an inappropriately high 
level of anti-coagulation, hepatic failure) 
• Management-related (e.g., related to surgical technique; hypertension; bleeding 
in the setting of inappropriate levels of anti-coagulation or to mismanagement of 
anti-coagulants) 
• Device-related (e.g., bleeding from the outflow graft, apical connector, or other 
internal components) 
Note: The forms recording the presence of bleeding will continue to record the key 
sources of bleeding as outlined in the INTERMACS34 User Manual. These include 
mediastinal: chest wall; mediastinal: outflow-aorta anastomosis; mediastinal: 
outflow conduit; mediastinal: inflow conduit; mediastinal: cardiopulmonary bypass 
cannulation site; mediastinal: coagulopathy with no surgical site; mediastinal: other 
surgical sites; pump or implanted component pocket (battery or controller); 
mediastinal: unspecified; pleural space; intra-abdominal; retroperitoneal; 
pulmonary; genitourinary tract; GI: upper gastrointestinal (esophagus, stomach, 
duodenum, and small bowel); GI: lower gastrointestinal (colon, rectum, and anus); 
GI: unknown, but guaiac positive stools; ENT/dental; other. 
CARDIAC 
TAMPONADE 
Evidence of a new pericardial effusion associated with hemodynamic instability 
and clearly related to the procedure. Clinical syndrome caused by the accumulation 
of fluid in the pericardial space, resulting in reduced ventricular filling and 
subsequent hemodynamic compromise. 
CARDIOGENIC 
SHOCK 
An insufficient forward cardiac output to maintain adequate perfusion of vital 
organs to meet ongoing demands for oxygenation and metabolism. Cardiogenic 
shock is due to either inadequate left ventricular pump function (such as in 
congestive heart failure) or inadequate left ventricular filling (such as in cardiac 
tamponade). Cardiogenic shock is defined as sustained hypotension (>30 minutes) 
with evidence of tissue hypoperfusion including oliguria (<30 mL/h), cool 
extremities, cyanosis, and altered mental status. 
CLINICAL SUCCESS 
Clinical success is defined as follows: 
• No conversion to open heart surgery; and 
• No in-hospital mortality 

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Table 24.2-1: Definitions 
Term 
Definition 
DATA CATEGORIES 
Data categories as defined by General Data Protection Regulation (GDPR) are 
listed below. 
Personal Data: 
GDPR defines “Personal Data” to be any information relating to an identified or 
identifiable natural person (‘data subject’); an identifiable natural person is one who 
can be identified, directly or indirectly, in particular by reference to an identifier 
such as a name, an identification number, location data, an online identifier or to 
one or more factors specific to the physical, physiological, genetic, mental, 
economic, cultural or social identity of that natural person. 
Sensitive Personal Data: 
GDPR defines “Sensitive Personal Data” as a subset of Personal Data, which, due 
to their nature have been classified as deserving additional privacy and security 
protections because their processing may create a risk for an individual’s 
fundamental right and freedom. This subset includes but is not limited to the 
following: racial, ethnic origin or ethnicity; political opinions; religious or 
philosophical beliefs; trade union membership; genetic data; biometric data for the 
purpose of uniquely identifying a natural person; health data (including gender, 
family medical history, etc.); sex life or sexual orientation; criminal records or 
allegations of crimes (requires an even higher standard of protection). 
Identifiers: 
“Identifiers” are Personal Data that can be used alone or in combination with other 
identifiers to identify an individual. Identifiers include but are not limited to the 
following:  
• All government-issued identification numbers (including but not limited to 
names, social security number, certificate/license numbers, passport, national 
ID) 
• All financial account numbers (including but not limited to bank account 
numbers, payment numbers, bank or credit card numbers)  
• All geographic subdivisions smaller than a state, including street address, city, 
county, precinct, ZIP code, and their equivalent geocodes, except for the 
initial three digits of the ZIP code if, according to the current publicly 
available data from the Bureau of the Census, the geographic unit formed by 
combining all ZIP codes with the same three initial digits contains more than 
20,000 people and/or the initial three digits of a ZIP code for all such 
geographic units containing 20,000 or fewer people is changed to 000 
• All elements of dates (except year) for dates that are directly related to an 
individual, including birth date, admission date, discharge date, death date, 
and all ages over 89 and all elements of dates (including year) indicative of 
such age, except that such ages and elements may be aggregated into a single 
category of age 90 or older 
• Telephone numbers 
• Fax numbers 
• Device identifiers and serial numbers 
• E-mail addresses 
• Web Universal Resource Locators (URLs) 
• Internet Protocol (IP) addresses 
• Medical record numbers 
• Biometric identifiers, including finger and voice prints 

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Table 24.2-1: Definitions 
Term 
Definition 
• Health plan beneficiary numbers 
• Full-face photographs and any comparable images 
• Any other unique identifying number, characteristic, or code (including 
subject ID number) 
DEATH  
 
All-cause Death 
Death from any cause after percutaneous coronary intervention using circulatory 
support. Death is categorized as cardiac or non-cardiac. 
Cardiac Death 
Cardiac death is defined as death due to any of the following. 
• Acute myocardial infarction 
• Cardiac perforation/pericardial tamponade 
• Arrhythmia or conduction abnormality 
• Cerebrovascular accident (CVA) through hospital discharge or CVA suspected 
of being related to the procedure 
• Death due to complication of the procedure, including bleeding, vascular repair, 
transfusion reaction, or bypass surgery 
• Any death in which a cardiac cause cannot be excluded 
Non-cardiovascular Death 
Non-cardiac death is defined as a death not due to cardiac causes as defined above. 
DEVICE DEFICIENCY 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
An inadequacy of an investigational medical device related to its identity, quality, 
durability, reliability, safety or performance.  
Note 1: Device deficiencies include malfunctions, use errors, or inadequacy in the 
information supplied by the manufacturer. 
DEVICE 
MALFUNCTION28 
Major Device Malfunction 
Major device malfunction, otherwise known as failure, occurs when one or more of 
the components of the Vortex System either directly causes or could potentially 
induce a state of inadequate circulatory support (low cardiac output state) or death. 
A failure that was iatrogenic or recipient-induced will be classified as an 
Iatrogenic/Recipient-Induced Failure.  
A device malfunction or failure is categorized as Major when one of the following 
conditions occurs: 
• Death 
• Hospitalization, emergency room visit or prolongation of hospitalization, or 
escalation of the level of care in an ongoing hospitalization (i.e., transfer to the 
intensive care unit) 
• Life-threatening event (i.e., stroke or transient ischemic attack, cardiac arrest, 
heart failure, syncope or near syncopal event, arrhythmia, etc.) 
• Results in significant disability or incapacity 
• Requires an intervention to prevent impairment/injury including: 
o 
Urgent transplantation listing (immediate urgent listing for the transplant) 
o 
Pump replacement 
o 
Pump explant 
o 
Pump deactivation without explant or partial explant of components 
o 
Breach of integrity of percutaneous lead requiring repair 

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Table 24.2-1: Definitions 
Term 
Definition 
o 
Operation to repair or replace any internal component of the circulatory 
support system 
o 
Procedure to repair or stent an outflow graft 
• Suspected or confirmed device thrombus 
Note: Replacement of the external controller that is done in an inpatient setting for 
logistical reasons, in an otherwise stable patient, should be considered a minor 
device malfunction rather than major. 
Minor Device Malfunction 
Minor device malfunction includes inadequately functioning external components 
that require repair or replacement but do not result in the conditions listed above for 
major device malfunctions. Device malfunction does not apply to routine 
maintenance including replacement of external controller, pneumatic drive unit, 
electric power supplies, batteries, and interconnecting cables that are not related to 
a failed component. 
The association of the device malfunction should be classified as follows: 
• Patient-related (i.e., non-adherence with care of device or its peripheral 
components, or the Instructions for Use, or non-adherence with the anti-
coagulation regimen, or pro-coagulation abnormalities) 
• Management-related (i.e., surgical protocol deviation, suboptimal anti-
coagulation) 
• Device-related (i.e., detected in a device at explant or on contrast studies or 
associated with hemolysis or other controller data consistent with device 
malfunction) 
DEVICE RELATED 
COMPLICATIONS 
Complications associated with the device as it relates to delivery, placement, 
efficacy or durability; these may involve the temporarily inserted device or the 
delivery system.   
DEVICE 
THROMBOSIS 
Device thrombosis, defined as any thrombus attached to or near the temporarily 
inserted device, subclassified as: 
• Major: occludes part of the blood flow path, interferes with valve function 
(e.g., immobility of 1 or more leaflets), is symptomatic, 
• or is sufficiently large to warrant treatment, or 
• Minor: incidental finding on echocardiography or other imaging test that is not 
major 
EMBOLISM 
Examples include a free-flowing blood clot or lesion material that is located in the 
systemic or pulmonary circulation. Embolism may be manifested by a neurological 
event or a noncerebral embolic event. 
GENERAL DATA 
PROTECTION 
REGULATION 
The General Data Protection Regulation (GDPR) is a legal framework that sets 
guidelines for the collection and processing of personal information of individuals 
within the European Union. 
INTENT TO TREAT 
(ITT) ANALYSIS SET 
This population includes all subjects who sign an informed consent form and are 
enrolled in the study, whether or not a study device is successfully inserted and 
used.  
INTRACRANIAL 
HEMORRHAGE 
Collection of blood between the brain and skull; subcategorized as epidural, 
subdural, and subarachnoid bleeds. 
MYOCARDIAL 
INFARCTION/INJURY 
(MI)35  
Universal Definitions of Myocardial Injury and Myocardial Infarction 
• Criteria for Myocardial Injury  

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Table 24.2-1: Definitions 
Term 
Definition 
 
The term myocardial injury should be used when there is evidence of elevated 
cardiac troponin values (cTn) with at least one value above the 99th percentile 
upper reference limit (URL). The myocardial injury is considered acute if there 
is a rise and/or fall of cTn values. 
• Criteria for Acute Myocardial Infarction (types 1, 2 and 3 MI) 
The term acute myocardial infarction should be used when there is acute 
myocardial injury with clinical evidence of acute myocardial ischaemia and 
with detection of a rise and/or fall of cTn values with at least one value above 
the 99th percentile URL and at least one of the following: 
o Symptoms of myocardial ischaemia; 
o New ischaemic electrocardiogram (ECG) changes; 
o Development of pathological Q waves; 
o Imaging evidence of new loss of viable myocardium or new regional wall 
motion abnormality in a pattern consistent with an ischaemic aetiology; 
o Identification of a coronary thrombus by angiography or autopsy (not for 
type 2 or 3 MIs). 
Type 1 MI: Post-mortem demonstration of acute athero-thrombosis in the artery 
supplying the infarcted myocardium meets criteria for type 1 MI. 
Type 2 MI: Evidence of an imbalance between myocardial oxygen supply and 
demand unrelated to acute athero-thrombosis meets criteria for type 2 MI. 
Type 3 MI: Cardiac death in patients with symptoms suggestive of myocardial 
ischaemia and presumed new ischaemic ECG changes before cTn values 
become available or abnormal meets criteria for type 3 MI. 
• Criteria for Coronary Procedure-Related Myocardial Infarction (types 4 and 5 
MI) 
Percutaneous coronary intervention (PCI) related MI is termed type 4a MI. 
Coronary artery bypass grafting (CABG) related MI is termed type 5 MI. 
Coronary procedure-related MI ≤ 48 hours after the index procedure is 
arbitrarily defined by an elevation of cTn values > 5 times for type 4a MI and 
> 10 times for type 5 MI of the 99th percentile URL in patients with normal 
baseline values. Patients with elevated pre-procedural cTn values, in whom 
the pre-procedural cTn level are stable (≤ 20% variation) or falling, must 
meet the criteria for a > 5- or > 10-fold increase and manifest a change from 
the baseline value of > 20%. In addition, with at least one of the following: 
o New ischaemic ECG changes (this criterion is related to type 4a MI only); 
o Development of new pathological Q waves; 
o Imaging evidence of loss of viable myocardium that is presumed to be new 
and, in a pattern, consistent with an ischaemic aetiology; 
o Angiographic findings consistent with a procedural flow-limiting 
complication such as coronary dissection, occlusion of a major epicardial 
artery or graft, side-branch occlusion-thrombus, disruption of collateral flow 
or distal embolization. 
Type 4a MI or Type 5 MI: Isolated development of new pathological Q waves 
meets the type 4a MI or type 5 MI criteria with either revascularization 
procedure if cTn values are elevated and rising but less than the pre-specified 
thresholds for PCI and CABG.  

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Table 24.2-1: Definitions 
Term 
Definition 
Type 4b MI and Type 4c MI: Other types of 4 MI include type 4b MI stent 
thrombosis and type 4c MI criteria. 
Type 4a MI and Type 4b MI: Post-mortem demonstration of a procedure-related 
thrombus meets the type 4a MI criteria or type 4b MI criteria if associated with a 
stent.  
• Criteria for Prior or Silent/Unrecognized Myocardial Infarction 
Any one of the following criteria meets the diagnosis for prior or silent/ 
unrecognized MI: 
o Abnormal Q waves with or without symptoms in the absence of 
nonischaemic causes 
o Imaging evidence of loss of viable myocardium in a pattern consistent with 
ischaemic aetiology 
o Patho-anatomical findings of a prior MI 
NEUROLOGICAL 
EVENT  
Any central, new neurological deficit, whether temporary or permanent and 
whether focal or global, that occurs after the subject emerges from anesthesia 
NEW YORK HEART 
ASSOCIATION 
CLASSIFICATION 
(NYHA) 
Classification system for defining cardiac disease and related functional limitations 
into four broad categorizations: 
Class I 
Subject with cardiac disease but without resulting limitations of 
physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea, or anginal pain. 
Class II 
Subjects with cardiac disease resulting in slight limitation of 
physical activity. They are comfortable at rest. Ordinary physical 
activity results in fatigue, palpitation, dyspnea, or anginal pain. 
Class III 
Subjects with cardiac disease resulting in marked limitation of 
physical activity. They are comfortable at rest. Less than ordinary 
physical activity causes fatigue, palpitation, dyspnea, or anginal 
pain. 
Class IV 
Subjects with cardiac disease resulting in inability to carry on any 
physical activity without discomfort. Symptoms of cardiac 
insufficiency or of the anginal syndrome may be present even at 
rest. If any physical activity is undertaken, discomfort is increased. 
 
PER-PROTOCOL 
ANALYSIS SET 
This population includes all subjects who sign an ICF, are enrolled in the study, and 
in whom the device is successfully advanced across the aortic valve into the left 
ventricular outflow tract and turned on. 
PROCEDURE-
RELATED EVENTS 
Events occurring during or as a direct result of the index procedure.  
SERIOUS ADVERSE 
DEVICE EFFECT 
(SADE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse device effect that has resulted in any of the consequences characteristic of 
a serious adverse event 
SERIOUS ADVERSE 
EVENT (SAE) 
Ref: ISO 14155 
Ref: MDCG 2020-10/1 
Adverse event that led to any of the following: 
 a)  Death, 
 b) Serious deterioration in the health of the subject, users or other persons as 
defined by either: 

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Term 
Definition 
 
 
1) a life-threatening illness or injury, or 
 
 
2) a permanent impairment of a body structure or a body function, 
including chronic diseases, or  
 
 
3) in-patient hospitalization or prolongation of existing hospitalization, or 
 
 
4) medical or surgical intervention to prevent life-threatening illness or 
injury or permanent impairment to a body structure or a body function 
 c) Foetal distress, foetal death, or a congenital abnormality or birth defect 
including physical or mental impairment. 
Note 1: Planned hospitalization for a pre-existing condition, or a procedure required 
by the clinical investigational plan, without a serious deterioration in health, is not 
considered a serious adverse event.  
SERIOUS HEALTH 
THREAT 
Ref: ISO 14155 
 
Signal from any adverse event or device deficiency that indicates an imminent risk 
of death or a serious deterioration in the health of subjects, users or other persons, 
and that requires prompt remedial action for other subjects, users or other persons. 
Note 1: This would include events that are of significant and unexpected nature 
such that they become alarming as a potential serious health hazard or possibility of 
multiple deaths occurring at short intervals. 
SOURCE DATA 
(per ISO 14155) 
All information in original records of clinical findings, observations, or other 
activities in a clinical investigation, necessary for the reconstruction and evaluation 
of the clinical investigation 
SOURCE DOCUMENT 
(per ISO 14155) 
Original or certified copy of printed, optical or electronic document containing 
source data. 
STROKE 
Stroke is defined as an acute symptomatic episode of neurological dysfunction 
attributed to a vascular cause lasting more than 24 hours or lasting 24 hours or less 
with a brain imaging study or autopsy showing infarction.  
Stroke Classification 
• Ischemic Stroke: an acute symptomatic episode of focal cerebral, spinal, or 
retinal dysfunction caused by an infarction of central nervous system tissue.  
• Hemorrhagic Stroke: an acute symptomatic episode of focal or global cerebral 
or spinal dysfunction caused by a nontraumatic intraparenchymal, 
intraventricular, or subarachnoid hemorrhage 
• Undetermined Stroke: a stroke with insufficient information to allow 
categorization as ischemic or hemorrhagic 
An event that lasts < 24 hours may be adjudicated as a stroke if the following 
treatments were used: 
• Pharmacologic, i.e., thrombolytic drug administration, or  
• Non-pharmacologic, i.e., neuro-interventional procedure (e.g., intracranial 
angioplasty) 
TECHNICAL SUCCESS  Technical success is defined as follows: 
• Successful delivery of the device to the correct anatomical position; and 
• Successful operation and removal of the Vortex circulatory support system 
TRANSIENT 
ISCHEMIC ATTACK 
(TIA) 
A TIA is a focal ischemic neurological deficit of abrupt onset and of presumed 
vascular etiology that resolves completely within 24 hours of onset. 

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Table 24.2-1: Definitions 
Term 
Definition 
UNANTICIPATED 
SERIOUS ADVERSE 
DEVICE EFFECT  
Ref: ISO 14155 
(USADE) 
Serious adverse device effect which by its nature, incidence, severity, or outcome 
has not been identified in the current version of the risk analysis report  
Note 1: An anticipated serious adverse device effect (ASADE) is an effect which 
by its nature, incidence, severity, or outcome has been identified in the risk analysis 
report. 
VASCULAR 
COMPLICATION - 
MAJOR  
(MCS-ARC28) 
Major vascular complications include any of the events below that require a 
diagnostic investigation to be confirmed and require surgical or endovascular 
intervention. 
• Pseudo-aneurysm  
• Arteriovenous fistula  
• Vessel thrombosis/Distal embolization 
• Vessel dissection, perforation or rupture  
• Vessel stenosis 
• Cannulation site bleeding (would have to fulfill durable device bleeding 
definition) 
• Limb ischemia 
• Vascular access site infection 
VESSEL 
PERFORATION 
Unexpected puncture of the vessel with evidence of extravasation into extraluminal 
surrounding tissue or space requiring treatment using interventional or surgical 
techniques 
Abbreviations: ADE=adverse device effect; AE=adverse event; CABG=coronary artery bypass graft; CK-
MB=creatine kinase-myoglobin band; CT=computed tomography; cTn=cardiac troponin; 
ECG=electrocardiogram; GDPR=General Data Protection Regulation; ICD=implantable cardioverter-
defibrillators; LVEF=left ventricular ejection fraction; MI=myocardial infarction; MRI=magnetic resonance 
imaging; NYHA=New York Heart Association; PCI=percutaneous coronary intervention; PRBC=packed red 
blood cells; SADE=serious adverse device effect; SAE=serious adverse event; TIA=transient ischemic attack; 
ULN=upper limit of normal; URL=upper reference limit (defined as 99th percentile of normal reference range); 
USADE=unanticipated serious adverse device effect 
 
25. Revision History 
25.1. Summary of Protocol Revision History 
Protocol revision history is provided in Table 25.1-1. 

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Table 25.1-1: Protocol Revision History 
Revision 
Version 
Protocol 
Date 
Template 
Number and 
Version 
Protocol Sections 
Modified 
Summary of Changes 
Justification for 
Changes 
A 
10-Feb-2020 
90702637 
Rev/Ver AL 
Not applicable. 
Not applicable. 
Not applicable. 
B 
13-Nov-2020 
90702637 
Rev/Ver AM 
Page 1 
Vortex Temporary Percutaneous… 
 
National Clinical Trial (NCT) Identification Number: TBD 
 
European Authorized Representative 
Boston Scientific International S.A. 
Le Val Saint-Quentin 
2 rue René Caudron, 78960 
Voisins le Bretonneux, France 
 
Australian Representative 
Boston Scientific Pty. Ltd. 
Building 1, Level 6 
191 O’Riordan Street 
Mascot, NSW 2020, Australia 
Added for clarity 
 
Registration number 
to be determined later 
 
BSC representative in 
Australia and Europe 
added because the 
study centers will be 
there. 
Page 2, 
Coordinating 
Principal 
Investigator 
Antony Walton, MBBS 
Deputy Director and Head of Catheter Laboratory 
Department of Cardiology, The Alfred Hospital 
55 Commercial Road, Melbourne VIC 3004 Australia  
 
Current Version: 10-Feb-12-Nov-2020 
Updated revision table 
Coordinating 
principal investigator 
 
 
 
Updated to reflect 
new protocol version 
Section 2, Synopsis, 
Title 
Vortex Temporary Percutaneous… 
Added for clarity 
Section 2, Synopsis, 
Study Objective(s) 
To evaluate the feasibility and safety, clinical success, and 
technical success of the Vortex Temporary Percutaneous 
Transvalvular Circulatory Support System (Vortex System) in 

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Summary of Changes 
Justification for 
Changes 
subjects undergoing elective high-risk percutaneous coronary 
intervention (HR-PCI) 
Section 2, Synopsis, 
Planned Indication 
for Use 
The Vortex System is indicated to provide temporary (≤ 4 
hours) circulatory support in subjects undergoing elective 
high-risk… 
Section 2, Synopsis, 
Test Device and 
Sizes if Applicable 
Vortex temporary percutaneous, transvalvular circulatory 
support system.  
The Vortex System includes a starter tube, introducer sheath, 
and 0.018” wire that are used to position the pump. A 
controller is used to run the pump and collect and display data 
on pump performance; it is connected to the pump using a 
sterile extension cable is a minimally invasive device that is in 
direct contact with the heart while in use. Components are 
summarized below. 
Component 
Description 
Vortex Pump 
 
- Axial flow pump magnetically coupled to 
the impeller with an expandable flexible 
cannula in a membrane-covered pre-shaped 
braid and a proximal catheter    
- Introduced percutaneously via femoral 
artery access; advanced across the aortic 
valve into the left ventricular outflow tract; 
outlet ports are near the sinotubular junction  
Vortex 
Delivery 
System 
- Starter tube 
- Introducer sheath with 16 Fr profile, 35-cm 
length 
- Dilator (compatible with 0.035” wire) 
-  Cannula delivery tool  
Vortex Wire 
- 0.018” diameter, 300-cm length, shapeable tip 

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Changes 
Vortex 
Console 
- Interface to control/monitor the pump; 
connected to the pump using a sterile extension 
cable, which is plugged into the wall and 
controls power to the pump 
Section 2, Synopsis, 
Study Design 
The Vortex Feasibility Study is a prospective, open-label, 
single-arm study designed to assess the safety and feasibility of 
the Vortex System to provide temporary (≤ 4 hours) 
circulatory support in subjects undergoing HR-PCI. 
The study design is summarized in the figure below. 
 
Vortex Feasibility Study Design Overview 
The Vortex study will be conducted in accordance with the 
International Standard ISO 14155 Clinical Investigation of 
Medical Devices for Human Subjects – Good Clinical 
Practice; European Medical Device Regulations; ethical 
principles that have their origins in the Declaration of Helsinki; 
and pertinent individual country/state/local laws and 
regulations. The study shall not begin until the required 
approval/favorable opinion from the Independent Ethics 
Committee (IEC)/Human Research Ethics Committee (HREC) 
and/or regulatory authority has been obtained, if appropriate. 
Section 2, Synopsis, 
Planned Number… 
There will be up to 10 subjects enrolled in up to 3 centers in 
Asia-Pacific Australia and Europe. 

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Section 2, Synopsis 
Primary Endpoint 
The primary endpoint consists of Technical Success and 
Clinical Success, defined as follows. 
Technical Success 
• Successful delivery… 
Clinical Success 
• Without No conversion to open heart surgery or; and 
• No in-hospital mortality and freedom of procedural Q-wave 
MI 
Section 2, Synopsis 
Additional 
Endpoints 
Measurements 
Safety events will be collected through 72 hours post-
procedure or hospital discharge… 
• Stroke/transient ischemic attach (TIA; see Note 1 below)… 
• Cardiac death: all cause (see Note 1 below)… 
• Bleeding complications: Type 3–5 based on the Mechanical 
Circulatory Support Academic Research Consortium (MCS-
ARC) definitionsa (see Note 1 below) 
• Acute kidney injury (AKI; based on the AKIN System Stage 
3 [including renal replacement therapy] or Stage 2 or 3)… 
• Procedure time 
• Any device-related adverse event (adverse device effect 
[ADE]/serious adverse device effect [SADE])… 
• Any unanticipated serious adverse device effect (USADE)… 
• Device deficiencies 
Note 1: Death, stroke, bleeding complications, and major 
vascular complications are adjudicated by an Independent 
Medical Reviewer (IMR). 
a:  Kormos RL, et al. J Heart Lung Transplant 2020;39:735-50 
Note 1: Death, stroke, MI and cardiac tamponade will be based 
on theVARC-2 definitions and endpoints. 
Note 2: Bleeding events will be based on the BARC 
definitions 

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Protocol Sections 
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Changes 
Section 2, Synopsis 
Study Duration 
Enrollment/total study duration may is expected to be 
completed in approximately 12–3 months. 
Section 2, Synopsis 
Participant Duration 
The study duration for each subject is expected to be through 
72 hours or hospital discharge, whichever comes first. 
Section 2, Synopsis 
Inclusion Criteria 
IC1. Subject provides signed informed consent.  
IC2.  Subject is ≥ 18 years and < 90 years of age.  
IC3.  Subject is indicated for NON-emergent PCI of at least 
one de novo or restenotic lesion in a native coronary vessel or 
coronary artery bypass graft (CABG) and has left ventricular 
ejection fraction (LVEF) ≤ 35% with the following: 
• Unprotected left main or last remaining vessel and LVEF≤ 
35% -OR- 
• Last remaining vessel -OR- 
• Three vessel disease (≥ 50% diameter stenoses by visual 
estimate or total occlusion) and LVEF ≤ 35% 
Section 2, Synopsis 
Exclusion criteria 
EC1. Subject has had ST-elevation myocardial infarction 
(STEMI) within 24 hours. 
EC2. Subject has had pre-procedure cardiac arrest requiring 
cardiopulmonary resuscitation (CPR) within 24 hours of 
enrollment. 
EC3. Subject is in cardiogenic shock, defined as follows: 
• Cardiac index (CI) < 2.2 L/min/m2 and pulmonary capillary 
wedge pressure (PCWP) > 15 mmHg -AND- 
• Hypotension… 
EC5. Subject has a Presence of mechanical or prosthetic aortic 
valve. 
EC6. Subject has pericarditis or constrictive heart disease 
(constrictive pericarditis or restrictive cardiomyopathy), 
moderate or greater aortic valve stenosis (effective orifice area 
< 1.5 cm²), severe aortic calcification. 

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EC7. Subject has moderate to severe or greater aortic valve 
stenosisb or moderate or greater aortic valve insufficiencyb 
(by… 
EC8. Subject has abnormalities of the aorta that preclude safe 
delivery of the device, including severe calcification, 
tortuosity, aneurysm, or prior surgery. 
EC9. Subject has severe peripheral vessel disease (PVD) 
preventing passage of the device (e.g., calcification, small 
caliber) or severe tortuosity that would preclude safe 
placement of the 16 Fr introducer sheath. 
Note 2: Minimum required vessel diameter is > 5.5 mm. 
EC10. Subject has with advanced renal failure dysfunction 
(creatinine ≥AKIN Stage 3 mg/dL)… 
EC13. Subject has known allergy hypersensitivity to 
intravenous contrast agents that cannot be adequately pre-
medicated or has known hypersensitivity to heparin… 
EC17. Subject requires mechanical ventilation combined 
cardiorespiratory failure… 
• Participation in another clinical trial that has not reached it is 
primary endpoint 
EC21. Subject has severe pulmonary disease (FEV1 > < 1L). 
EC22. Subject has sustained or non-sustained ventricular 
tachycardia. 
EC23. Subject is breast feeding or is pregnant. 
b: Nishimura RA, et al. J Am Coll Cardiol 2014;63:e57-185 
Section 2, Synopsis 
Multiple 
Interventions During 
Index Procedure 
The Vortex sheath… pump will pass though this sheath at 
various times throughout during the procedure… as soon as the 
mechanical circulatory support is deemed to be unnecessary 
Section 2, Synopsis 
Primary Statistical 
Hypothesis 
There is no formal statistical hypothesis in this observational 
feasibility study. No formal sample size calculation will be 
performed. Descriptive summaries will be provided. 

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Section 2, Synopsis 
Statistical Test 
Method 
Descriptive statistics will be used for baseline, procedure, and 
follow-up data collected through during the study.  
The primary endpoint and additional measurements will be 
analyzed on an intention-to-treat (ITT) basis and a per-protocol 
basis. Analysis sets are listed below. Subjects are considered 
enrolled in the study as soon as an attempt is made to insert 
any part of the Vortex System into the subject's femoral artery. 
• ITT: This population includes all subjects who sign an 
Informed Consent Form (ICF) and are enrolled in the study, 
whether or not a study device is successfully inserted and used. 
• Per-protocol: This population includes all ITT subjects in 
whom the device is successfully advanced across the aortic 
valve into the left ventricular outflow tract and turned on. 
Section 2, Synopsis 
Sample Size 
Parameters 
This is… and therefore sample size estimates are not 
applicable. In order to support the stated objectives of this 
feasibility study, the study sample size has been limited to a 
maximum of up to 10 subjects enrolled. 
Sections 3–25 
Sections 3–25 are all new. 
Added the rest of the 
protocol information 
to the Synopsis 
C 
5-Mar-2021 
90702637 
Rev/Ver AO 
Section 2, Protocol 
Synopsis, Inclusion 
Criteria 3 
Section 8.2; Table 
8.2-1 
A subject will be considered for enrollment if all of the 
following inclusion criteria are met, provided no exclusion 
criteria are met. 
IC1. 
Subject provides signed informed consent.  
IC2.  
Subject is ≥ 18 years and < 90 years of age.  
IC3.  
Subject is indicated for NON-emergent PCI of at 
least one de novo or restenotic lesion in a native 
coronary vessel or coronary artery bypass graft 
(CABG) and has left ventricular ejection fraction 
(LVEF) ≤ 3550% with the following: 
LVEV is changed 
from left ventricular 
ejection fraction 
(LVEF) ≤ 35% into 
left ventricular 
ejection fraction 
(LVEF) ≤ 50% to be 
consistent with the 
inclusion criteria of 
other contemporary 
mechanical 
circulatory support 

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Justification for 
Changes 
• 
Unprotected left main -OR- 
• 
Last remaining vessel -OR- 
Three vessel disease (≥50% diameter stenoses by visual 
estimate or total occlusion) 
device studies and the 
labelling of the 
commercially 
approved (Abiomed) 
device 
C 
5-Mar-2021 
90702637 
Rev/Ver AO 
Section 18.4; Table 
18.4-1 
Serious Health 
Threat 
Complete 
applicable eCRF 
page with all 
available new and 
updated 
information. 
• Within 1 
business day 
of first 
becoming 
aware of the 
event. 
Terminating at the 
end of the study 
In Table 18.4-1 is the 
Serious Health Threat 
removed to follow 
the new protocol 
template where this is 
no longer required for 
the Investigator 
Reportings 
 
Provide all 
relevant source 
documentation 
(de-identified/ 
pseudonymized) 
for reported event. 
Upon request of 
sponsor 
D 
21-May-2021 
90702637 
Rev/Ver AP 
Contact Information 
Role 
Contact  
 
Clinical 
Contact 
Arjun Bhat, MBBS, MBA 
Sr. Clinical Trial Manager, 
Interventional Cardiology 
Boston Scientific  
300 Boston Scientific Way 
Marlborough, MA 01752 
E-mail: arjun.bhat@bsci.com 
 
Coordin
ating 
Principal 
Antony Walton, MBBS 
Deputy Director and Head of 
Catheter Laboratory 
 
Clinical contact 
updated to reflect 
Arjun Bhat as new 
trial manager for the 
study. 
 
List of investigation 
sites with 
corresponding names 
of their principal 
investigators added 
per MPA request. 

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Investiga
tor and 
Site 
Principal 
Investiga
tor  
Department of Cardiology 
The Alfred Hospital 
55 Commercial Road 
Melbourne VIC 3004  
Australia 
Site 
Principal 
Investiga
tor 
Matthias Götberg, MD, PhD 
Director, Cardiac 
Catheterization Laboratory  
University Hospital of Lund 
Getingevagen 
Department of Coronary 
Heart Disease 
SE-221 85 Lund, Sweden 
 
 
 
 
Section 2; Protocol 
Synopsis 
Vortex Feasibility Study Design Overview 
The Vortex study will be conducted in accordance with the 
International Standard ISO 14155:2020 Clinical Investigation 
of Medical Devices for Human Subjects – Good Clinical 
Practice; European Medical Device Regulations; ethical 
principles that have their origins in the Declaration of Helsinki; 
and pertinent individual country/state/local laws and 
regulations. The study shall not begin until the required 
approval/favorable opinion from the Independent Ethics 
Committee (IEC)/Human Research Ethics Committee (HREC) 
and/or regulatory authority has been obtained, if appropriate 
For clarity; to specify 
which version of the 
GCP standard that is 
applied for this 
clinical investigation. 

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Section 8.3; Table 
8.3 1, Protocol 
Synopsis 
A subject will be excluded from the study if any of the 
following exclusion criteria are met. 
EC1. 
Subject has had ST-elevation myocardial infarction 
(STEMI) within 24 hours. 
EC2. 
Subject has had pre-procedure cardiac arrest 
requiring cardiopulmonary resuscitation (CPR) 
within 24 hours of enrollment. 
EC3. 
Subject is in shock, defined as follows: 
• 
Cardiac index (CI) < 2.2 L/min/m2 and 
pulmonary capillary wedge pressure (PCWP) 
> 15 mmHg -AND- 
• 
Hypotension (systolic blood pressure < 90 
mmHg for > 30 minutes) -OR- 
• 
Need for supportive measures (i.e., inotropes or 
mechanical support) to maintain systolic blood 
pressure ≥ 90 mmHg and end organ 
hypoperfusion (cool extremities or urine 
< 30 mL/hour and a heart rate > 60 beats per 
minute) 
EC4. 
Subject has left ventricular mural thrombus. 
EC5. 
Subject has a prosthetic aortic valve. 
EC6. 
Subject has pericarditis or constrictive heart disease 
(constrictive pericarditis or restrictive 
cardiomyopathy). 
EC7. 
Subject has moderate or greater aortic valve 
stenosisb or moderate or greater aortic valve 
Per MPA request, 
EC24 and EC25 
added to include 
other disease 
conditions resulting 
in the patient being 
unsuitable to 
participate in the 
clinical trial or non-
compliant per 
protocol 
requirements. 

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insufficiencyb (by echocardiographic assessment, 
graded as ≥ 2+). 
EC8. 
Subject has abnormalities of the aorta that preclude 
safe delivery of the device, including severe 
calcification, tortuosity, aneurysm, or prior surgery. 
EC9. 
Subject has peripheral vessel disease (PVD) 
preventing passage of the device (e.g., calcification, 
small caliber) or tortuosity that would preclude safe 
placement of the 16 Fr introducer sheath. 
 
Note 2: Minimum required vessel diameter is > 5.5 
mm. 
EC10. 
Subject has advanced renal dysfunction (AKIN 
Stage 3). 
EC11. 
Subject has a history of liver dysfunction (Childs 
Class C) with elevation of liver enzymes and 
bilirubin > 3× upper limit of normal (ULN) or 
international normalization ratio (INR) ≥ 2. 
EC12. 
Subject has had a recent (within 1 month) stroke or 
TIA. 
EC13. 
Subject has known hypersensitivity to intravenous 
contrast agents that cannot be adequately pre-
medicated or has known hypersensitivity to heparin, 
aspirin, ADP receptor inhibitors or nitinol. 
EC14. 
Subject has current or a history of heparin induced 
thrombocytopenia (HIT). 
EC15. 
Subject has uncorrected abnormal coagulation or 
platelet count ≤ 75,000/mm³ or INR ≥ 2.0.  

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EC16. 
Subject has significant right heart failure (right atrial 
pressure [RAP] > 15 mmHg, right ventricular stroke 
work index [RVSWI] < 0.30 mmHg·L/m², 
pulmonary vascular resistance [PVR] > 3.6 Woods 
units).  
EC17. 
Subject requires mechanical ventilation.  
EC18. 
Subject has an atrial or ventricular septal defect 
(including post-infarct ventricular septal defect 
[VSD]). 
EC19. 
Subject has left ventricular rupture.  
EC20. 
Subject has cardiac tamponade. 
EC21. 
Subject has severe pulmonary disease (FEV1 < 1L). 
EC22. 
Subject has sustained or non-sustained ventricular 
tachycardia. 
EC23. 
Subject is breast feeding or is pregnant. 
EC24.  Subject has other disease condition(s) resulting in the 
subject being unsuitable for participation in the 
clinical trial (e.g. advanced malignancy with limited 
expected survival) 
EC25.  Subject has other disease condition(s) which the 
Investigator has determined may cause non-
compliance to the study requirements. 
b: Nishimura RA, et al. J Am Coll Cardiol 2014;63:e57-185. 

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Section 2; Protocol 
Synopsis, Section 
7.1; Figure 7.1 1  
 
 
Figure 7.1 1 updated 
per MPA request to 
match study 
enrollment definition.  
 
 
 
Section 7.2 
Subjects who are candidates for high-risk percutaneous 
coronary intervention, provide written informed consent, and 
are eligible to be treated with the Vortex System will be 
evaluated for enrollment in this study. Prior to being eligible 
for the study, a subject must meet all of the inclusion criteria 
(Section 8.2) and none of the exclusion criteria (Section 8.3).  
Section 7.2 
(treatment 
assignment) updated 
to match language in 
Section 8.1 (Study 
Population and 
Eligibility) per MPA 
request. 

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Section 15.2 
The Principal Investigator of an investigational site is 
responsible for ensuring that the study is conducted in 
accordance with the Clinical Study Agreement, the clinical 
investigation plan, ISO 14155:2020, ethical principles that 
have their origins in the Declaration of Helsinki, any 
conditions of approval imposed by the reviewing IEC/HREC, 
and prevailing local and/or country laws and/or regulations, 
whichever affords the greater protection to the subject. 
 
For clarity; to specify 
which version of the 
GCP standard that is 
applied for this 
clinical investigation. 
 
 
 
Section 15.3 
Any amendment to the protocol and/or ICF will require review 
and approval by the IEC/HREC and the Swedish Medical 
Products Agency (MPA) before changes to the study are 
implemented. All changes to the ICF will be IEC/HREC 
approved; a determination will be made regarding whether a 
new ICF needs to be obtained from subjects who provided 
consent using a previously approved ICF. Annual IEC/HREC 
approval and renewals will be obtained throughout the 
duration of the study as required by applicable local/country 
laws or regulations or IEC/HREC requirements. Copies of the 
study reports and the IEC/HREC continuance of approval must 
be provided to the sponsor.  
 
Language modified 
per MPA request. 

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Section 16 
Monitoring will be performed during the study to assess 
continued compliance with the protocol and applicable 
regulations. In addition, the clinical research monitor verifies 
that study records are adequately maintained, that data are 
reported in a satisfactory manner with respect to timeliness, 
adequacy, and accuracy, and that the Principal Investigator 
continues to have sufficient staff and facilities to conduct the 
study safely and effectively. The Principal 
Investigator/institution guarantees direct access to original 
source documents by BSC personnel, their designees, and 
appropriate regulatory authorities. 
The sponsor will put a plan in place to document the specific 
monitoring requirements. A general outline of the monitoring 
plan is described below - 
Site Initiation Visits 
All sites participating in the study will have Site Initiation 
Visits (SIVs). A live, online training session with slides will be 
conducted virtually via the Web. A checklist of activities (as 
specified in the monitoring plan: e.g. protocol training, 
ICH/GCP, monitoring expectations, PI responsibilities, safety 
reporting requirements, documentation requirements, local law 
requirements such as: data protection, EC reporting) will be 
conducted and confirmed complete, prior to site authorization 
to enroll to ensure preparedness of the investigator and site 
staff. Additional training may be done on an as-needed basis 
throughout the study for study procedures and updates, clinical 
events, unanticipated adverse device effect reporting process, 
regulatory requirements, CRF completion, and compliance 
issues noted during monitoring. 
 
Interim Monitoring Visits 
General outline of 
monitoring plan 
included per MPA 
request. 

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Interim Monitoring Visits (IMVs) will be conducted for each 
site. Each visit will require a written confirmation letter, a 
monitoring visit report, and a follow up letter.  
At each interim monitoring visit, the monitor will assess: 
• 
Regulatory documents and contents of the 
Investigator Site File to ensure that they are complete, 
accurate and current. 
• 
Accuracy of data: the monitor will compare subject 
medical records and other supporting documents with 
the CRFs to determine that they are complete, 
accurate, and legible. 
• 
Informed consent forms: monitor will review the ICFs 
and documentation of the consent process in the 
source documents. 
• 
Safety reporting: monitor will verify and/or discuss 
that all reportable events and device deficiencies are 
reported and recorded in accordance with the protocol 
and the local regulatory requirements and ensures 
necessary source documents are obtained.    
• 
Site resources, adequacy of facilities, any changes in 
study personnel, location, etc. 
• 
Device accountability to ensure the log is complete 
and accurate 
Site compliance to the study protocol will be assessed over the 
life of the study.   
 
Closeout Visits 
A Closeout monitoring visit (COV) will be performed for each 
site. Closeout activities can be performed separately or in 

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conjunction with an interim monitoring visit. When preparing 
the site for closure, the monitor will verify and/or discuss that: 
• 
All essential documents are complete and up to date 
• 
All CRFs are completed 
• 
All outstanding queries are resolved 
• 
The current status of all ongoing adverse events is 
documented and protocol compliant. 
• 
All CRF pages are signed by the designated 
investigator 
• 
Device reconciliation is accurate and documented 
• 
Arrangements are made for archiving and record 
retention. 
The study may also be subject to a quality assurance audit by 
BSC or its designees, as well as inspection by appropriate 
regulatory authorities. It is important that the Principal 
Investigator and relevant study personnel are available during 
on-site monitoring visits or audits and that sufficient time is 
devoted to the process. 
 

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Section 18, Table 
18.2-1, Section 18.3, 
Table 18.3-1, 
Section 18.4, Table 
18.4-1 
Adverse event definitions are provided in Table 18.2-1. 
Administrative edits were made on the safety definitions from 
applicable regulations and guidance including (but not limited 
to) ISO 14155 and EU MDR 2017/745/MDCG 2020-10/1 
Guidance on Safety Reporting in Clinical Investigations for 
clarification purposes. 
Table 25.1-2: Safety Definitions 
Term 
Definition 
Adverse 
Event (AE) 
Ref: ISO 
14155 
Ref: MDCG 
2020-10/1 
Any untoward medical occurrence, 
unintended disease or injury, or any 
untoward clinical signs (including an 
abnormal laboratory finding) in subjects, 
users or other persons, in the context of a 
clinical investigation, whether or not 
related to the investigational medical 
device and whether anticipated or 
unanticipated.  
NOTE 1: This includes events related to 
the investigational medical device or 
comparator. 
NOTE 2: This definition includes events 
related to the procedures involved. 
NOTE 3: For users or other persons, this 
definition is restricted to events related to 
the investigational medical device.  
NOTE 4: This definition includes events 
related to management practices 
NOTE 5: This definition includes patient 
related events 
 

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Adverse 
Device 
Effect 
(ADE) 
Ref: ISO 
14155 
Ref: MDCG 
2020-10/1 
Adverse event related to the use of an 
investigational medical device 
NOTE 1: This includes any adverse event 
resulting from insufficiencies or 
inadequacies in the instructions for use, the 
deployment, the procedural treatment, the 
installation, the operation, or any 
malfunction of the investigational medical 
device. 
NOTE 2: This definition includes any 
event resulting from use error or from 
intentional misuse of the investigational 
medical device. 
NOTE 3: This includes "comparator" if the 
comparator is a medical device. 
Serious 
Adverse 
Event (SAE) 
Ref: ISO 
14155 
Ref: MDCG 
2020-10/1 
Adverse event that led to any of the 
following: 
 a)  Death, 
 b)  Serious deterioration in the health of 
the subject, users or other persons as 
defined by either: 
 
 
1) a life-threatening illness or 
injury, or 
 
 
2) a permanent impairment of a 
body structure or a body 
function, including chronic 
diseases, or  

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3) in-patient hospitalization or 
prolongation of existing 
hospitalization, or 
 
 
4) medical or surgical intervention 
to prevent life-threatening illness 
or injury or permanent 
impairment to a body structure or 
a body function 
 c) Foetal distress, foetal death, or a 
congenital abnormality or birth defect 
including physical or mental 
impairment. 
NOTE 1: Planned hospitalization for a 
pre-existing condition, or a procedure 
required by the clinical investigational 
plan, without a serious deterioration in 
health, is not considered a serious adverse 
event.  
Serious 
Adverse 
Device 
Effect 
(SADE) 
Ref: ISO 
14155 
Ref: MDCG 
2020-10/1 
Adverse device effect that has resulted in 
any of the consequences characteristic of a 
serious adverse event. 
 
Unanticipate
d Serious 
Adverse 
Serious adverse device effect which by its 
nature, incidence, severity, or outcome has 

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Device 
Effect 
(USADE) 
Ref: ISO 
14155 
Ref: MDCG 
2020-10/1 
not been identified in the current risk 
assessment.  
NOTE 1: Anticipated serious adverse 
device effect (ASADE) is an effect which 
by its nature incidence, severity or outcome 
has been identified in the risk assessment. 
Serious 
Health 
Threat 
Ref: ISO 
14155 
 
Signal from any adverse event or device 
deficiency that indicates an imminent risk 
of death or a serious deterioration in the 
health of subjects, users or other persons, 
and that requires prompt remedial action 
for other subjects, users or other persons. 
NOTE 1: This would include events that 
are of significant and unexpected nature 
such that they become alarming as a 
potential serious health hazard or 
possibility of multiple deaths occurring at 
short intervals. 
Device 
Deficiency 
Ref: ISO 
14155 
Ref: MDCG 
2020-10/1 
An inadequacy of a medical device related 
to its identity, quality, durability, 
reliability, usability, safety or performance.  
NOTE 1: Device deficiencies include 
malfunctions, use errors, and inadequacy in 
the information supplied by the 
manufacturer including labelling. 
NOTE 2: This definition includes device 
deficiencies related to the investigational 
medical device or the comparator. 

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The following definitions will be used for defining 
hospitalization or prolongation of hospitalization for SAE 
classification purposes: 
Hospitalizati
ons  
Hospitalization does not include: 
• Emergency room visit that does not 
result in in-patient admission  
NOTE 1: Although an emergency 
room visit does not itself meet the 
definition for hospitalization, it may 
meet other serious criteria (e.g., 
medical or surgical intervention to 
prevent permanent impairment or 
damage) 
• Elective and pre-planned 
treatment/surgery for a pre-existing 
condition that is documented in the 
subject’s record at the time of 
consent/enrollment 
• Admission for social reasons and/or 
respite care in the absence of any 
deterioration in the subject’s general 
condition (e.g., subject is homeless, 
caregiver relief) 
• Pre-planned, protocol-specified 
admission related to the clinical study 
(e.g., procedure required by protocol) 
Prolongation 
of 
In-patient admission to the hospital that is 
prolonged beyond the expected standard 
duration for the condition under treatment. 

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Hospitalizati
on  
NOTE 1: New adverse events occurring 
during the hospitalization are evaluated to 
determine if they prolonged hospitalization 
or meet another SAE criterion. 
 
The Investigator must assess the relationship of the 
reportable adverse events to the study device or 
study procedure. See criteria in Table 18.3-1:  
Table 25.1-3: Criteria for Assessing 
Relationship of Study Device or Procedure to 
Adverse Event 
Classificatio
n 
Description 
Not Related 
Ref: MDCG 
2020-10/1 
Relationship to the device, comparator, or 
procedures can be excluded when: 
• the event has no temporal relationship 
with the use of the investigational 
device or the procedures related to the 
use of the investigational device; 
• the serious event does not follow a 
known response pattern to the 
medical device (if the response 
pattern is previously known) and is 
biologically implausible; 
• the discontinuation of medical device 
application or the reduction of the 
level of activation/exposure - when 
clinically feasible – and 

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reintroduction of its use (or increase 
of the level of activation/exposure), 
do not impact on the serious event; 
• the event involves a body-site or an 
organ that cannot  be affected by the 
device or procedure; 
• the serious event can be attributed to 
another cause (e.g., an underlying or 
concurrent illness/clinical condition; 
an effect of another device, drug, 
treatment or other risk factors); 
• the event does not depend on a false 
result given by the investigational 
device used for diagnosis, when 
applicable;  
In order to establish the non-relatedness, 
not all the criteria listed above might be 
met at the same time, depending on the 
type of device/procedures and the serious 
event. 
Possibly 
Related 
Ref: MDCG 
2020-10/1 
The relationship with the use of the 
investigational device or comparator or the 
relationship with procedures is weak but 
cannot be ruled out completely. Alternative 
causes are also possible (e.g., an underlying 
or concurrent illness/clinical condition 
and/or an effect of another device, drug or 
treatment). Cases where relatedness cannot 
be assessed, or no information has been 

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obtained should also be classified as 
possible. 
Probably 
Related 
Ref: MDCG 
2020-10/1 
The relationship with the use of the 
investigational device, comparator, or the 
relationship with procedures seems relevant 
and/or the event cannot be reasonably 
explained by another cause. 
Causal 
Relationshi
p 
Ref: MDCG 
2020-10/1 
The serious event is associated with the 
investigational device or comparator or 
with procedures beyond reasonable doubt 
when: 
• the event is a known side effect of the 
product category the device belongs 
to or of similar devices and 
procedures; 
• the event has a temporal relationship 
with investigational device 
use/application or procedures; 
• the event involves a body-site or 
organ that 
- the investigational device or 
procedures are applied to; 
- the investigational device or 
procedures have an effect on; 
• the serious event follows a known 
response pattern to the medical device 
(if the response pattern is previously 
known); 

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• the discontinuation of medical device 
application (or reduction of the level 
of activation/exposure) and 
reintroduction of its use (or increase 
of the level of activation/exposure), 
impact on the serious event (when 
clinically feasible); 
• other possible causes (e.g., an 
underlying or concurrent 
illness/clinical condition or/and an 
effect of another device, drug or 
treatment) have been adequately ruled 
out; 
• harm to the subject is due to error in 
use; 
• the event depends on a false result 
given by the investigational device 
used for diagnosis, when applicable 
In order to establish the relatedness, not all 
the criteria listed above might be met at the 
same time, depending on the type of 
device/procedures and the serious adverse 
event. 
 
The communication requirements for reporting to 
BSC are as shown in Table 18.4-1. 

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Table 25.1-4: Investigator Reporting 
Requirements 
Event 
Classificat
ion 
Communicatio
n Method  
Communication 
Timeline (Pre-market 
Studies) 
(MDCG 2020-10/1) 
Unanticipat
ed Serious 
Adverse 
Device 
Effects  
(USADE) 
Complete AE 
electronic case 
report form 
(eCRF) page 
with all 
available new 
and updated 
information.  
• Within 1 business 
day of first becoming 
aware of the event 
• Terminating at the 
end of the study 
Provide all 
relevant source 
documentation 
(de-identified/ 
pseudonymized
) for reported 
event.  
• Upon request of 
sponsor  
Serious 
Adverse 
Events 
(SAE) and 
IMR 
eventsa  
Complete AE 
eCRF page with 
all available 
new and 
updated 
information.  
• Immediately but not 
later than 3 calendar 
days of first 
becoming aware of 
the event or as per 
local/regional 
regulations  
• Reporting required 
through the end of 
the study 
Provide all 
relevant source 
documentation 
• Upon request of 
sponsor 

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(de-identified 
/pseudonymized
) for reported 
event. 
Serious 
Adverse 
Device 
Effects 
(SADE) 
 
Complete AE 
eCRF page with 
all available 
new and 
updated 
information. 
• Immediately but not 
later than  3 calendar 
days of first becoming 
aware of the event or 
as per local/regional 
regulations  
• Reporting required 
through the end of the 
study 
Provide all 
relevant source 
documentation 
(de-identified/ 
pseudonymized
) for reported 
event.  
• When documentation 
is available 
• Upon request of 
sponsor  
Serious 
Health 
Threat 
Complete 
applicable 
eCRF page with 
all available 
new and 
updated 
information. 
• Within 1 business day 
of first becoming 
aware of the event. 
• Terminating at the end 
of the study 
Provide all 
relevant source 
documentation 
• Upon request of 
sponsor 

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(de-identified/ 
pseudonymized
) for reported 
event. 
Device 
Deficiencie
s 
(including 
but not 
limited to , 
malfunctio
ns, use 
errors and 
inadequacy 
in 
informatio
n supplied 
by the 
manufactur
er, 
including 
labeling) 
Note:  Any 
Device 
Deficiency 
that might 
have led to 
a serious 
adverse 
event if 
appropriate 
action had 
Complete 
Device 
Deficiency 
eCRF with all 
available new 
and updated 
information.  
• Immediately but not 
later than  3 calendar 
days of first becoming 
aware of the event.  
• Reporting required 
through the end of the 
study 
Provide all 
relevant source 
documentation 
(de-identified/ 
pseudonymized
) for reported 
event. 
• Upon request of 
sponsor  

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not been 
taken, 
interventio
n had not 
occurred, 
circumstan
ces had 
been less 
fortunate is 
considered 
a 
reportable 
event. 
Adverse 
Event (AE) 
including 
Adverse 
Device 
Effects 
(ADE) 
Complete AE 
eCRF page, 
which contains 
such 
information as 
date of AE, 
treatment of AE 
resolution, 
assessment of 
seriousness and 
relationship to 
the device.  
• Adverse Device 
Effects: In a timely 
manner but not later 
than 10 business days 
after becoming aware 
of the information 
• Adverse Events: In a 
timely manner but 
recommend within 10 
business days after 
becoming aware of the 
information 
• Reporting required 
through the end of the 
study  
• Upon request of 
sponsor 
Provide all 
relevant source 
documentation 
(de-identified/ 
pseudonymized

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) for reported 
event.  
a: All Independent Medical Reviewer (IMR) events must 
be reported using the timeframe for SAE, regardless of 
whether they meet serious criteria. 
 
 
 
 
 
 
Section 18.5 
18.5  Device Deficiencies 
Vortex System device deficiencies will be documented in the 
appropriate eCRF and reported to BSC. If possible, the 
device(s) should be returned to BSC for analysis. Instructions 
for returning the investigational device(s) will be provided in 
the Manual of Operations. Device deficiencies should also be 
documented in the subject’s source records. 
Device deficiencies are not adverse events. However, an 
adverse event that results from a device deficiency would be 
recorded as an adverse event on the appropriate eCRF. 
 
For clarity