An Initial Evaluation of the Safety and Performance of the Transcatheter Mitral Intrepid Valve Replacement System in Patients With Severe, Symptomatic Mitral Regurgitation
Phase: NA
Conditions: Mitral Valve Insufficiency
Sponsor: Medtronic Cardiovascular

 
 
 
Study Documents Summary 
• 
Early Feasibility Study of the TMVR Transseptal System 
Document Version: 4.0 
Document Date: 13-Sep-2023 
• 
Transcatheter Mitral Valve Replacement (TMVR) System Pilot Study 
Document Version: 4.0 
Document Date: 25-Oct-2019 
• 
Intrepid™ TMVR Pilot Study – Statistical Analysis Plan 
Document  Date: 20-May-2024 
 
ClinicalTrials.gov Identiﬁer (NCT Number): NCT02322840 
 

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Clinical Investigation Plan 
Clinical Investigation Plan/ 
Study Title 
Evaluation of the Safety and Performance of The Medtronic 
Intrepid™ Transcatheter Mitral Valve Replacement System with 
Transfemoral Transseptal access in Patients with Moderate-Severe 
or Severe, Symptomatic Mitral Regurgitation – The Early 
Feasibility Study of the TMVR Transseptal System 
Clinical Investigation Plan 
Identifier 
MDT19042TMV002 
Study Product Name 
The Intrepid™ Transcatheter Mitral Valve Replacement (TMVR) 
System – designed for transfemoral access enabling transseptal 
delivery of a self-expanding bioprosthetic valve within the mitral 
valve 
Sponsor/Local Sponsor 
Medtronic, Inc. 8200 Coral Sea St NE 
Mounds View, MN 55112 United States 
Document Version 
4.0 
Version Date 
 13-Sep-2023 
Lead Principal Investigator(s) 
David Adams, MD, Cardiothoracic Surgeon Mount Sinai Medical 
Center 
New York, New York USA 
Martin Leon, MD, Interventional Cardiologist 
New York Presbyterian Hospital / Columbia University Medical 
Center 
New York, New York USA 
Study Chairman 
Michael Mack, MD, Cardiothoracic Surgeon Baylor Scott & White 
Hospital 
Dallas, TX USA 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. 
Any distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly 
prohibited. Persons to whom the information is disclosed must know that it is confidential and that it 
may not be further disclosed by them. 
 
 
 

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Table of Contents 
1.0 
Glossary ...................................................................................................................................... 6 
2.0 
Synopsis .................................................................................................................................... 10 
3.0 
Introduction .............................................................................................................................. 14 
3.1 
Background ........................................................................................................................... 14 
3.2 
Purpose ................................................................................................................................. 15 
4.0 
Objectives and Endpoints ......................................................................................................... 16 
4.1 
Objectives ............................................................................................................................. 16 
4.1.1 
Primary Objective ......................................................................................................... 16 
4.1.2 
Secondary Objective ..................................................................................................... 16 
4.2 
Study Endpoints .................................................................................................................... 16 
4.2.1 
Primary Safety Endpoint ............................................................................................... 16 
4.2.2 
Secondary Performance Endpoints ............................................................................... 16 
4.2.3 
Additional exploratory endpoints: ................................................................................ 16 
5.0 
Study Design ............................................................................................................................. 18 
5.1 
Duration ................................................................................................................................ 18 
5.2 
Rationale ............................................................................................................................... 18 
5.3 
Study Oversight .................................................................................................................... 18 
6.0 
Product Description .................................................................................................................. 20 
6.1 
General.................................................................................................................................. 20 
6.2 
Manufacturer ........................................................................................................................ 20 
6.3 
Packaging.............................................................................................................................. 20 
6.4 
Intended Population .............................................................................................................. 21 
6.5 
Equipment ............................................................................................................................. 21 
6.6 
Product Use ........................................................................................................................... 21 
6.7 
Product Training Materials ................................................................................................... 21 
6.8 
Product Receipt and Tracking............................................................................................... 21 
6.9 
Product Storage ..................................................................................................................... 22 
6.10 
Product Return ...................................................................................................................... 22 
6.11 
Product Accountability ......................................................................................................... 22 
7.0 
Study Site Requirements ........................................................................................................... 23 
7.1 
Investigator/Investigation Site Selection .............................................................................. 23 
7.2 
Site Principal Investigators ................................................................................................... 23 
7.3 
Heart Team ........................................................................................................................... 24 
7.4 
Implant Team ........................................................................................................................ 24 
7.5 
Trial Training ........................................................................................................................ 25 
7.6 
Study Site Activation ............................................................................................................ 25 
7.7 
Role of the Sponsor Representatives .................................................................................... 25 
8.0 
Selection of Subjects ................................................................................................................. 27 
8.1 
Study Population ................................................................................................................... 27 
8.2 
Subject Enrollment ............................................................................................................... 27 
8.3 
Inclusion Criteria .................................................................................................................. 27 
8.4 
Exclusion Criteria ................................................................................................................. 28 
9.0 
Study Procedures ...................................................................................................................... 30 

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9.1 
Schedule of Events ............................................................................................................... 30 
9.2 
Data Collection ..................................................................................................................... 31 
9.3 
Scheduled Follow-up Visit Windows ................................................................................... 32 
9.4 
Subject Consent .................................................................................................................... 32 
9.5 
Subject Screening ................................................................................................................. 33 
9.5.1 
The process of screening and subject enrollment is as follows: ................................... 33 
9.5.2 
Clinical assessment including: ...................................................................................... 34 
9.6 
Additional Screening Assessments ....................................................................................... 35 
9.7 
Pre-Index Procedure ............................................................................................................. 35 
9.8 
Enrollment ............................................................................................................................ 35 
9.9 
Index Procedure .................................................................................................................... 36 
9.9.1 
No concomitant procedures are permitted during the index TMVR procedure. Any 
occurrence will be deemed a protocol deviation. ......................................................................... 36 
9.10 
Discharge .............................................................................................................................. 36 
9.11 
Scheduled Follow-up Visits .................................................................................................. 37 
9.12 
Stroke Evaluation.................................................................................................................. 38 
9.13 
Healthcare Utilization ........................................................................................................... 38 
9.14 
Quality of Life (QoL) Questionnaires .................................................................................. 38 
9.15 
Prior and Concomitant Medications ..................................................................................... 38 
9.16 
Assessment of Efficacy ......................................................................................................... 39 
9.17 
Assessment of Safety ............................................................................................................ 39 
9.18 
Recording Data ..................................................................................................................... 39 
9.19 
Deviation Handling ............................................................................................................... 40 
9.20 
Subject Exit, Withdrawal or Discontinuation ....................................................................... 41 
9.20.1 
Study Completed .......................................................................................................... 41 
9.20.2 
Lost to Follow-up ......................................................................................................... 41 
9.20.3 
Subject Death ................................................................................................................ 42 
9.20.4 
Subject Chooses to Exit (i.e., Revokes Consent) .......................................................... 42 
9.20.5 
Investigator Withdraws Subject .................................................................................... 42 
10.0 
Risks and Benefits .................................................................................................................... 43 
10.1 
Potential Risks ...................................................................................................................... 43 
10.2 
Risk Minimization ................................................................................................................ 45 
10.3 
Potential Benefits .................................................................................................................. 46 
10.4 
Risk-Benefit Rationale .......................................................................................................... 46 
10.5 
Risk Determination ............................................................................................................... 47 
11.0 
Adverse Events and Device Deficiencies ................................................................................. 48 
11.1 
Adverse Events ..................................................................................................................... 48 
11.2 
Device Deficiency ................................................................................................................ 48 
11.3 
Processing Updates and Resolution ...................................................................................... 48 
11.4 
Definitions/Classifications.................................................................................................... 49 
11.5 
Reporting of Adverse Events ................................................................................................ 51 
11.5.1 
Emergency Contact Details for Reporting SAE, SADE, U(S)ADE, and Device 
Deficiencies .................................................................................................................................. 52 
11.5.2 
Adverse Event and Device Deficiency Classification .................................................. 53 

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11.5.3 
Adverse Event and Device Deficiency Reporting Requirements ................................. 54 
11.6 
Subject Death ........................................................................................................................ 54 
11.6.1 
Death Classification and Reporting .............................................................................. 54 
12.0 
Data Review Committees ......................................................................................................... 56 
12.1 
Clinical Events Committee Review ...................................................................................... 56 
12.2 
CRO/Core Lab(s) .................................................................................................................. 56 
12.3 
Data Monitoring Committee ................................................................................................. 57 
13.0 
Statistical Design and Methods ................................................................................................. 58 
13.1 
General Aspects of Analysis ................................................................................................. 59 
14.0 
Ethics ........................................................................................................................................ 60 
14.1 
Statement(s) of Compliance .................................................................................................. 60 
14.1.1 
ISO14155:2020 Deviations .......................................................................................... 60 
15.0 
Study Administration ................................................................................................................ 61 
15.1 
Monitoring ............................................................................................................................ 61 
15.1.1 
Monitoring Visits .......................................................................................................... 61 
15.2 
Data Management ................................................................................................................. 62 
15.3 
Direct Access to Source Data/Documents ............................................................................ 62 
15.4 
Audits.................................................................................................................................... 63 
15.5 
Confidentiality ...................................................................................................................... 63 
15.6 
Liability/Warranty/Insurance Information ............................................................................ 63 
15.7 
CIP Amendments .................................................................................................................. 63 
15.8 
Record Retention .................................................................................................................. 63 
15.8.1 
Investigator Records ..................................................................................................... 64 
15.8.2 
Sponsor Records ........................................................................................................... 65 
15.9 
Reporting Requirements ....................................................................................................... 66 
15.9.1 
Investigator Reports ...................................................................................................... 66 
15.9.2 
Sponsor Reports ............................................................................................................ 67 
15.10 
Publication and Use of Information .................................................................................. 68 
15.11 
Suspension or Early Termination ..................................................................................... 68 
15.11.1 
Planned Study Closure .............................................................................................. 68 
15.11.2 
Early Termination or Suspension ............................................................................. 69 
16.0 
References ................................................................................................................................ 70 
17.0 
Appendices ............................................................................................................................... 72 
17.1 
Definition of Terms & Causal Relationships ........................................................................ 72 
17.1.1 
ACCESS SITE AND VASCULAR COMPLICATIONS ............................................ 72 
17.1.2 
ACUTE KIDNEY INJURY ......................................................................................... 73 
17.1.3 
AORTIC REGURGITATION ...................................................................................... 73 
17.1.4 
AORTIC STENOSIS .................................................................................................... 74 
17.1.5 
ARRHYTHMIAS AND CONDUCTION SYSTEM DISTURBANCES .................... 74 
17.1.6 
BLEEDING COMPLICATIONS ................................................................................. 75 
17.1.7 
BUNDLE BRANCH BLOCK ...................................................................................... 77 
17.1.8 
CARDIAC STRUCTURAL COMPLICATION-NON-ACCESS SITE RELATED ... 78 
17.1.9 
CARDIAC PERFORATION ........................................................................................ 78 
17.1.10 
CARDIAC TAMPONADE ...................................................................................... 78 

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17.1.11 
CARDIOGENIC SHOCK ........................................................................................ 78 
17.1.12 
CHRONIC RENAL INSUFFICIENCY ................................................................... 79 
17.1.13 
CONVERSION TO OPEN MITRAL VALVE SURGERY DURING A 
TRANSCATHETER PROCEDURE ........................................................................................... 79 
17.1.14 
CORONARY VESSEL COMPRESSION OR OBSTRUCTION ........................... 80 
17.1.15 
DAMAGE TO THE NATIVE MITRAL VALVE APPARATUS .......................... 80 
17.1.16 
DEEP WOUND INFECTION .................................................................................. 80 
17.1.17 
DEVICE FRACTURE .............................................................................................. 81 
17.1.18 
DEVICE MIGRATION AND MALPOSITIONING ............................................... 81 
17.1.19 
DEVICE THROMBUS ............................................................................................ 81 
17.1.20 
EMBOLISM (BLOOD CLOT) ................................................................................ 83 
17.1.21 
EMBOLISM (AIR)................................................................................................... 83 
17.1.22 
ENCEPHALOPATHY ............................................................................................. 83 
17.1.23 
ENDOCARDITIS ..................................................................................................... 83 
17.1.24 
HEMOLYSIS ........................................................................................................... 85 
17.1.25 
HOSPITALIZATION ............................................................................................... 85 
17.1.26 
IATROGENIC ATRIAL SEPTAL DEFECT .......................................................... 86 
17.1.27 
INTERACTION WITH NON-MITRAL VALVE INTRACARDIAC 
STRUCTURES ............................................................................................................................. 87 
17.1.28 
INTERACTION WITH PACEMAKER/CRT/ICD LEAD ...................................... 88 
17.1.29 
MITRAL REGURGITATION ................................................................................. 88 
17.1.30 
MITRAL STENOSIS ............................................................................................... 90 
17.1.31 
MITRAL VALVE DYSFUNCTION ....................................................................... 91 
17.1.32 
MORTALITY ........................................................................................................... 91 
17.1.33 
MYOCARDIAL INFARCTION .............................................................................. 92 
17.1.34 
NEUROLOGICAL EVENTS................................................................................... 93 
17.1.35 
PARAVALVULAR LEAK ...................................................................................... 94 
17.1.36 
PERICARDIAL EFFUSION .................................................................................... 94 
17.1.37 
PROLONGED VENTILATION .............................................................................. 94 
17.1.38 
REOPERATION OR REINTERVENTION ............................................................ 94 
17.1.39 
RESPIRATORY INSUFFICIENCY ........................................................................ 95 
17.1.40 
RESPIRATORY FAILURE ..................................................................................... 95 
17.1.41 
RIGHT VENTRICULAR INSUFFICIENCY .......................................................... 95 
17.1.42 
TRICUSPID REGURGITATION ............................................................................ 95 
17.1.43 
UNPLANNED USE OF CARDIOPULMONARY BYPASS (CPB) ...................... 95 
17.1.44 
VALVE IN VALVE DEPLOYMENT ..................................................................... 96 
17.2 
Sample Informed Consent .................................................................................................... 96 
17.3 
Instructions for Use ............................................................................................................... 96 
18.0 
Version History ......................................................................................................................... 97 
 
 
 

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1.0 
Glossary  
 
Term 
Definition 
ADE 
Adverse Device Effect 
AE 
Adverse Event 
AKI 
Acute Kidney Injury 
ASD 
Atrial Septal Defect 
BNP 
B-type Natriuretic Peptide 
BSE 
Bovine Spongiform Encephalopathy 
ASADE 
Anticipated Serious Adverse Device Effect 
CA 
Competent Authority 
CEC 
Clinical Event Committee 
CFR 
Code of Federal Regulation 
CIP 
Clinical Investigation Plan 
CK/CK-MB 
Creatine Kinase / Creatine Kinase Myocardial B 
fraction 
COPD 
Chronic Obstructive Pulmonary Disease 
CRO 
Clinical Research Organization 
CRT-D 
Cardiac Resynchronization Therapy Device 
CRF 
Case Report Form 
CTA 
Clinical Trial Agreement 
CV 
Curriculum Vitae 
CVA 
Cerebrovascular Accident 
DAPT 
Dual Antiplatelet Therapy 
DD 
Device Deficiency 
DES 
Drug Eluting Stent 
DMC / DSMB 
Data Monitoring Committee / Data Safety 
Monitoring Board 
DoH 
Declaration of Helsinki 
DTL 
Delegated Task List 
DVT 
Deep Vein Thrombosis 
eCRF 
Electronic Case Report Form 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
EFS 
Early Feasibility Study 

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Term 
Definition 
EROA 
Effective Regurgitant Orifice Area 
FAL 
Foreseeable Adverse Event List 
FD 
Financial Disclosure 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Amendments Act 
FEV1 
Forced Expiratory Volume 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GI 
Gastrointestinal 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator Brochure 
IC/ICF 
Informed Consent/Informed Consent Form 
ICD 
Implantable Cardiac Defibrillator 
ICH 
International Conference of Harmonization 
ICU 
Intensive Care Unit 
IDE 
Investigational Device Exemption 
IFU 
Instructions For Use 
ICU 
Intensive Care Unit 
INR 
International Normalized Ratio 
IPG 
Implantable Pulse Generator 
IRB 
Institutional Review Board 
IVC 
Inferior Vena Cava 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
LV 
Left Ventricle 
LVAD 
Left Ventricular Assist Device 
LVEDD 
Left Ventricular End Diastolic Diameter 
LVEDV 
Left Ventricular End Diastolic Volume 
LVEF 
Left Ventricular Ejection Fraction 
LVOT 
Left Ventricular Outflow Tract 
MDCT 
Multi-Dimensional Computed Tomography 
MDD 
Medical Device Directive 
MedDRA 
Medical Dictionary for Regulatory Activities 
MHLW 
Ministry of Health, Labour, and Welfare 

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Term 
Definition 
MI 
Myocardial Infarction 
MR 
Mitral Regurgitation 
MRI 
Magnetic Resonance Imaging 
mRS 
Modified Rankin Score 
MVARC 
Mitral Valve Academic Research Consortium 
NSR 
Non-Significant Risk 
NYHA 
New York Heart Association 
PA 
Pulmonary Artery 
PCI 
Percutaneous Coronary Intervention 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PPI 
Permanent Pacemaker Implant 
PVL 
Paravalvular Leak 
QoL 
Quality of Life 
RA 
Regulatory Authority 
RED 
Radio Equipment Directive 
RPI 
Report of Prior Investigations 
RSVP 
Right Systolic Ventricular Pressure 
SADE 
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SF-12 
Short Form (12) Health Survey 
SAP 
Statistical Analysis Plan 
SC 
Steering Committee 
SR 
Significant Risk 
SID 
Subject Identification 
STS 
Society of Thoracic Surgeons 
STS-PROM 
Society of Thoracic Surgeons Predictive Risk of 
Mortality 
TAVI 
Transcatheter Aortic Valve Implantation 
TEE 
Transesophageal Echocardiogram 
TIA 
Transient Ischemic Attack 
TMVR 
Transcatheter Mitral Valve Replacement 
TTE 
Transthoracic Echocardiogram 
TVL 
Transvalvular Leak 

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Term 
Definition 
UAE 
Unavoidable Adverse Event 
UADE 
Unanticipated Adverse Device Effect 
USADE 
Unanticipated Serious Adverse Device Effect 
WBC 
White Blood Count 
6MWT 
Six Minute Walk Test 
 
 
 

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2.0 
Synopsis  
Title 
Evaluation of the Safety and Performance of The Medtronic Intrepid™ 
Transcatheter Mitral Valve Replacement System with Transfemoral 
Transseptal access in Patients with Moderate-Severe or Severe, 
Symptomatic Mitral Regurgitation – The Early Feasibility Study of the 
Intrepid™ TMVR Transseptal System 
Clinical Study Type 
Early Feasibility Study 
Product Name 
The Intrepid™ Transcatheter Mitral Valve Replacement (TMVR) 
System 
Sponsor / Funding Source 
Medtronic, Inc. 
8200 Coral Sea St NE 
Mounds View, MN 55112 
United States 
External Organizations 
Clinical Events Committee (CEC) / Data Monitoring Committee 
(DMC): BAIM Institute for Clinical Research 
930 Commonwealth Ave, 3rd Floor 
Boston, MA 02215 
Echocardiography Core Laboratory: 
Mayo Clinic Core Laboratory 
200 First Street SW 
Rochester, MN 55905 
Medidata Solutions, Inc. (imaging sharing network): 
Medidata Solutions, Inc. 
350 Hudson Street, 9th Floor 
New York, NY 10014 
Indication 
under 
investigation 
Medtronic Intrepid™ TMVR System is intended for use in patients who 
have moderate-severe or severe symptomatic mitral regurgitation who 
are determined by a multidisciplinary heart team to be a candidate for 
bioprosthetic mitral valve replacement who are ineligible for 
conventional mitral valve surgery. 
Investigation Purpose 
The purpose of this early feasibility study is to evaluate the safety and 
performance of The Intrepid™ TMVR System with transseptal access in 
patients with moderate-severe or severe, symptomatic mitral 
regurgitation, who are ineligible for conventional mitral valve surgery. 
Product Status 
Investigational 

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Primary Objective 
The primary objective is to evaluate the safety of The Intrepid™ TMVR 
System by assessment of the nature, severity and frequency of 
complications associated with the delivery and/or implantation of the 
device. 
Secondary Objectives 
The secondary objective is to evaluate the performance of The 
Intrepid™ TMVR System 
1. The degree of improvement of MR grade and symptoms, and the 
durability of TMVR function 
2. The ability to accurately deliver and place the implant within the 
anatomy 
3. The fit of the implant within the anatomy, including fixation, sealing 
and compatibility with structures (e.g., other components of the 
mitral valve apparatus, the conduction system, and the left 
ventricular outflow tract/aortic valve) 
Study Design 
Multi-center, prospective, non-randomized, investigational, early 
feasibility study in patients with moderate-severe or severe, 
symptomatic mitral regurgitation, who are ineligible for conventional 
mitral valve surgery with a follow up period of 5 years post-index 
procedure. 
Sample Size 
Since this is a limited clinical investigation, this study will enroll and 
treat up to 45 subjects at up to 15 investigational sites in the United 
States who require replacement of their mitral valve because of 
moderate-severe or severe, symptomatic mitral regurgitation, but are 
ineligible for conventional mitral valve surgery 
Inclusion Criteria 
The subject must meet ALL of the following criteria: 
1. Heart Team agrees that a patient is a candidate for 
bioprosthetic mitral valve replacement 
2. Subjects with moderate-severe or severe symptomatic mitral 
regurgitation who are determined by a multidisciplinary heart team 
to be a candidate for bioprosthetic mitral valve replacement and are 
ineligible for conventional mitral valve surgery based on predicted 
risk of operative mortality or irreversible major morbidity ≥ 35% 
and <50% at 30 days 
3. Subject anatomically suitable for the Intrepid TMVR delivery 
system including transfemoral and transseptal access 
4. Subject and the treating physician agree that the subject will return 
for all required post-procedure follow-up visits 
5. Subject meets the legal minimum age to provide informed 
consent based on local regulatory requirements 

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Exclusion Criteria 
The subject may not meet any of the following criteria: 
1. Estimated life expectancy of less than 12 months due to associated 
non-cardiac co-morbid conditions 
2. Prior transcatheter mitral valve procedure with device currently 
implanted 
3. Prior transseptal intervention with occlusion device currently implanted 
4. Anatomic contraindications for Intrepid™ TMVR (e.g., annular dimensions, 
high risk of LVOT obstruction, etc.) 
5. Anatomically prohibitive mitral annular calcification (MAC) 
6. Aortic valve disease requiring intervention or previous 
intervention within 90 days of enrollment 
7. Severe tricuspid regurgitation 
8. Patients unsuitable for implantation because of congenital abnormalities 
of the IVC, thrombosis of the femoral vein and/or of IVC, history of 
venous stents (iliac and/or femoral), presence of a vena cava filter or 
intracardiac mass or intracardiac thrombus 
9. Right-sided congestive heart failure with echocardiographic evidence of 
severe right ventricular dysfunction 
10. Pulmonary hypertension with resting pulmonary artery systolic 
pressures ≥ 2/3 systemic pressure 
11. Left ventricular ejection fraction (LVEF) <30% 
12. Left ventricular end diastolic diameter (LVEDD) > 75mm 
13. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, 
constrictive pericarditis, or other structural heart disease causing heart 
failure other than dilated ischemic or non-ischemic cardiomyopathy 
14. Infiltrative cardiomyopathies (e.g., amyloidosis, 
hemochromatosis, sarcoidosis) 
15. Subject is contraindicated for transesophageal 
echocardiography (TEE) 
16. Need for emergent or urgent cardiac or non-cardiac surgery 
17. Hemodynamic instability requiring dependency of either inotropic 
agents or mechanical circulatory support 
18. Subject refuses a blood transfusion 
19. Subject unwilling or unable to adhere to the protocol specified 
anticoagulation treatment 
20. Blood dyscrasias as defined: leukopenia (WBC <1000 cells/mm3), 
thrombocytopenia (platelet count <50,000 cells/mm3) 
21. History of bleeding diathesis or coagulopathy that precludes 
anticoagulation 
22. Active gastrointestinal (GI) bleeding that would preclude 
anticoagulation 
23. Known hypersensitivity or contraindication to nitinol, or sensitivity to 
contrast media which cannot be adequately pre- medicated 

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24. Any cardiac or peripheral interventional procedure performed within 
30 days prior to enrollment in patients treated with bare-metal stent or 
drug-eluting stent (DES) with approved 1- month DAPT labeling or 
within 90 days prior to enrollment for subjects treated with DES 
without approved 1-month labeling. 
25. Untreated clinically significant coronary artery disease 
requiring revascularization 
26. Severe symptomatic carotid stenosis 
27. Stroke or TIA within 90 days of enrollment 
28. Evidence of an acute myocardial infarction within 90 days prior to 
enrollment 
29. Active endocarditis or active infection requiring antibiotic therapy 
30. Implant of any Cardiac Resynchronization Therapy (CRT) or 
Cardiac Resynchronization Therapy with cardioverter- defibrillator 
(CRT-D) within 90 days of enrollment 
31. End stage renal disease requiring chronic dialysis or creatinine 
clearance < 30 cc/min within 30 days of the Index Procedure 
32. Severe Chronic Obstructive Pulmonary Disease (COPD) 
demonstrated by Forced Expiratory Volume (FEV1) < 750cc 
33. Pregnancy, breastfeeding, or intent to become pregnant prior to 
completion of all protocol follow-up requirements 
34. Currently participating in an investigational drug or another device 
study that has not yet reached its primary endpoint 
35. Other medical, social, or psychological conditions that in the 
opinion of the Investigator precludes the subject from appropriate 
consent or adherence to the protocol required follow-up exams 
Study Procedures 
and Assessments 
[See Table 9-1: Schedule of Events Table] 
Safety Assessments 
Serious adverse events, device deficiencies, and non-serious 
adverse events will be collected from the time of enrollment until 
the end of the study or until study exit, whichever comes first. The 
safety assessment performed during this study will be based on the 
relatedness to the TMVR implant and index procedure. 
Statistics 
Study results will be summarized using standard descriptive 
statistics. The sample size is based upon industry standards for early 
feasibility stage studies of medical devices; the sample size is not 
statistically derived, as this is not a hypothesis-testing study. 
 

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3.0 
Introduction 
3.1 
Background 
Mitral regurgitation (MR) is a common form of valve disease and affects up to 10% of the 
general population. Mitral valve replacement surgery is an established form of treatment for MR, 
however less than 50% of patients are referred to surgery (1). The overall 5-year mortality rate 
for unoperated patients has been reported to be up to 50% and the proportion of surviving 
patients hospitalized for heart failure increased from 41% in the first year to 90% by 5 years (2). 
This lack of surgical referral signifies the need for alternative MR treatments and is in part due to 
a large subset of patients classified as poor surgical candidates. There is also a cohort of patients 
suffering from secondary MR and future treatment options for this population remain unclear 
(3,4). 
Percutaneous mitral valve repair has been commercially available in the United States since 2013 
and in Europe since 2008 as an option for less invasive approach for treatment of MR. While 
acute procedural success has been reported to be greater than 90%, repair has also been 
associated with a higher rate of reoccurrence of MR compared to replacement. This increased 
durability with replacement could have important long-term outcomes (5,6). 
The investigational device is not approved in any geography and is called the Intrepid™ 
Transcatheter Mitral Valve Replacement (TMVR) System, manufactured by Medtronic. The 
Intrepid™ TMVR implant is intended to function similarly to a standard bioprosthetic valve 
implant, in that it allows blood to flow only in the forward direction, thereby preventing mitral 
regurgitation. A standard valve implant, however, is sewn directly into the heart during surgery 
in which the chest is fully open, the patient is put on cardiopulmonary bypass support and the 
heart is temporarily stopped. The Intrepid™ TMVR implant is intended to be placed through a 
less invasive procedure, not requiring thoracotomy, cardiopulmonary bypass support and 
cardioplegia, thereby potentially reducing the surgical risks. Based on the current clinical 
experience, the Intrepid TMVR system is performing as intended with successful implant 
procedures and proper function of the TMVR valve. 
The Intrepid™ TMVR system has previously been designed and investigated using transapical 
access for delivery of a self-expanding bioprosthetic valve within the mitral valve. Transapical 
access was the common initial approach during the first decade of transcatheter aortic valve 
replacement but has since declined due to evidence of worse clinical outcomes compared to 
transfemoral approach. Transapical complications include but are not limited to impairment of 
the left ventricular function, excessive bleeding, development of atrial fibrillation, and pleural 
effusion (7). New transcatheter transseptal interventions for patients with MR has been gaining 
interest and multiple systems are in early phase of development particularly with mitral valve 
replacement (8). Data from MitraClip valve repair system has also confirmed procedural success 
of transseptal access for treatment of MR (6). 
 

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3.2 
Purpose 
The purpose of this early feasibility study is to evaluate the safety and performance of The 
Intrepid™ TMVR System with transseptal access in patients with moderate-severe or severe, 
symptomatic mitral regurgitation, who are ineligible for conventional mitral valve surgery. 
 

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4.0 
Objectives and Endpoints 
4.1 
Objectives 
4.1.1 
Primary Objective 
The primary objective of the study is to evaluate the safety of the Intrepid™ TMVR System by 
assessing the nature, severity and frequency of complications associated with the delivery and/or 
implantation of the device. 
4.1.2 
Secondary Objective 
The secondary objective of the study is to evaluate the performance of the Intrepid™ TMVR 
System by assessing the following: 
• 
The degree of improvement of MR grade and symptoms, and the durability of TMVR 
function 
• 
The ability to accurately deliver and place the implant within the anatomy 
• 
The fit of the implant within the anatomy, including fixation, sealing and 
compatibility with structures (e.g., other components of the mitral valve apparatus, 
the conduction system and the left ventricular outflow tract/aortic valve) 
4.2 
Study Endpoints 
4.2.1 
Primary Safety Endpoint 
The primary safety endpoint is implant, delivery or device related serious adverse events 
(through 30 days post-procedure). 
4.2.2 
Secondary Performance Endpoints 
• 
Successful access, delivery of implant, and retrieval of the delivery system 
• 
Reduction in MR Grade from baseline (measured by echo through 30 days post-
procedure) 
• 
No significant MV stenosis (measured by echo through 30 days post-procedure) 
• 
LV outflow tract (LVOT) patency (measured by echo through 30 days post-
procedure) 
• 
Change in NYHA Class from baseline (through 30 days post-procedure) 
4.2.3 
Additional exploratory endpoints: 
• 
Measured by echo post-procedure through 5 years: 
− Reduction in MR Grade from baseline 

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− No significant MV stenosis 
− LV outflow tract (LVOT) patency 
− Improvement in LVEF 
− Improvement in cardiac output/cardiac index 
− Reduction in LV end-systolic and end-diastolic dimensions 
− Presence of intra-atrial shunt with clinically significant pressure gradient 
requiring closure device 
• 
Change in NYHA Class from baseline though 5 years 
• 
Change in 6MWT from baseline through 5 years 
• 
Change in QoL from baseline through 5 years 
• 
Procedural times (e.g., deployment time, access duration, rapid pacing duration) 
• 
Re-hospitalizations for heart failure 
• 
MVARC defined outcomes of: (see Appendix 17.1 for specific definitions) 
− Technical success upon exit from operating room 
− Device success at 30 days and 1 year 
− Procedural success at 30 days 
− Individual subject success at 1 year 
 

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5.0 
Study Design 
The Early Feasibility Study of the Intrepid™ TMVR Transseptal System is designed as a multi-
center, prospective, non-randomized, investigational, early feasibility study to evaluate the safety 
and performance of transcatheter mitral valve replacement in patients with moderate-severe or 
severe, symptomatic mitral regurgitation who are deemed ineligible for conventional mitral valve 
surgery by the heart team. Subjects will be followed 5 years post-implant. The study methods 
include the following measures to minimize potential sources of bias: 
• 
An external, independent Clinical Events Committee (CEC) will review and 
adjudicate, at minimum, all deaths and endpoint related adverse events. Safety 
endpoint results will be based on CEC adjudications. 
• 
All sites will follow a standardized protocol for acquisition of echocardiographic 
endpoint data. 
• 
Core labs will evaluate all echocardiograms. Echocardiographic trial endpoint results 
will be based on Core Lab assessments. 
• 
Subjects will be screened to confirm eligibility for enrollment with pre-defined 
inclusion and exclusion criteria. 
5.1 
Duration 
The enrollment period is estimated to be approximately two (2) years and subjects will be 
followed for up to five years post index procedure; therefore, the estimated total duration of the 
study (first subject enrolled to last subject completing his/her last follow-up exam) is estimated 
to be 7 years. 
5.2 
Rationale 
Study design is based on industry standards and risk assessment for early feasibility stage studies 
of medical devices. The basis for the selection of the study endpoints include: 
Clinically relevant outcomes for mitral valve replacement devices, that are objectively defined 
and measurable in the majority of subjects. 
5.3 
Study Oversight 
The study will utilize an Executive Committee. This committee will advise on the scientific 
content of the study and provide input for the execution. Members may include study site 
investigators. The purpose of this committee is to provide unbiased opinions and expertise to the 
clinical study design and process. The committee will support the execution of the trial and 
provide guidance, feedback and direction to the study. Additional details, including committee 
membership, can be found in the Study Governance Committee Charter. 
A Screening Committee will be utilized to ensure subject selection is appropriate and consistent 
across study sites. The Screening Committee will include a minimum of: an interventional 
cardiologist, a cardiothoracic surgeon, an echocardiologist and a heart failure specialist. Prior to 
the onset of the study, the Screening Committee will establish a charter that describes its roles, 

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responsibilities, and processes. Final decisions on subject eligibility will be made by the 
Screening Committee. 

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6.0 
Product Description 
6.1 
General 
The Intrepid™ Transcatheter Mitral Valve Replacement (TMVR) System consists of the 
following components: an implantable bioprosthesis, a delivery system, and a loading system. 
The Intrepid™ TMVR bioprosthesis is comprised of three structures. The inner Nitinol stent 
supports a bioprosthetic valve composed of bovine pericardial tissue leaflets and woven 
polyester fabric. The outer Nitinol fixation ring structure engages the mitral valve annulus to 
provide fixation and sealing. As the inner stent and outer fixation ring structures are connected 
only at points along the ventricular rim, the fixation ring can conform to fit the dynamic anatomy 
of the mitral valve throughout the cardiac cycle, without distorting the inner stent or replacement 
valve. This isolation reduces the dynamic, asymmetrical loading of the valve leaflets and is 
intended to prolong valve durability and ensure consistent hemodynamics. In addition, a woven 
polyester skirt is attached to the top of the fixation ring and flares outward to form an atrial brim. 
The brim is reinforced with flexible Nitinol wire that is structurally independent of the fixation 
ring to allow each component to conform to the anatomy. 
The delivery system is designed for transfemoral access and consists of a transfemoral dilator kit, 
transfemoral sheath with a transfemoral dilator, flow reverser, cradle, and a delivery catheter. 
The bioprosthesis is compressed using Intrepid™ TMVR loading system before loading into the 
capsule. The delivery catheter is then used to deliver the bioprosthetic through the transfemoral 
sheath into the left atrium through the interatrial septum. When properly positioned (using 
fluoroscopy and echocardiography guidance), the capsule is retracted, to gradually deploy and 
fully release the self- expanding implant within the mitral valve. 
Refer to Appendix 17.3 Instructions for Use for additional details regarding the device 
description, packaging, sterilization and storage conditions. 
6.2 
Manufacturer 
Manufacturer details are provided in the Instructions for Use in Appendix 17.3 Instructions for 
Use. 
6.3 
Packaging 
Labeling of the Intrepid™ TMVR System will be provided in English and the local language as 
required. 
The Medtronic Intrepid™ System is considered investigational and will carry the applicable 
labeling required to indicate “For Investigational Use Only” as required by local regulations. The 
Intrepid™ TMVR System components are supplied sterile with some accessories provided non-
sterile, and each packaged separately. 
 

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6.4 
Intended Population 
The Medtronic Intrepid™ TMVR System is intended for use in patients who have moderate-
severe or severe symptomatic mitral regurgitation who are determined by a multidisciplinary 
heart team to be a candidate for bioprosthetic mitral valve replacement who are ineligible for 
conventional mitral valve surgery. 
6.5 
Equipment 
Medtronic will provide the Merit Medical BasixTouch™ inflation device to sites. No other trial-
specific equipment will be provided. Equipment used for assessing study variables (e.g., 
echocardiographic systems) should be maintained per the site’s standard procedures. 
Maintenance and calibration reports may be monitored periodically by the monitor. 
3mensio Workstation will be used by Medtronic for pre-operative planning and sizing for the 
TMVR procedure. 
6.6 
Product Use 
Instructions for Use for the Medtronic Intrepid™ TMVR System is provided in Appendix 17.3– 
Instructions for Use. 
6.7 
Product Training Materials 
Prior to a given site’s first use of any investigational product site personnel directly involved in 
the Index Procedure will receive device training (if necessary, usage and handling of device 
under investigation). Training may be conducted via Site Initiation Visits, Investigator and 
Coordinator Meetings, Medtronic training facilities, and/or other media sessions. The sponsor 
will maintain documentation of attendance at each of these training opportunities, as applicable. 
Additionally, Medtronic representative(s) will be present at each site’s TMVR procedures as part 
of the ongoing training process. 
6.8 
Product Receipt and Tracking 
Good Clinical Practice guidelines require accounting for the disposition of all investigational 
devices received by each clinical site. The Investigator is responsible for accounting for all used 
and unused devices. Sites are required to maintain investigational device records that contain the 
following information: 
• 
Investigational device name 
• 
Device Serial Numbers, if applicable 
• 
Device Lot Numbers 
• 
Expiration dates, if applicable 
• 
Date of Receipt 
• 
Name of person receiving the device 

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• 
Date of the implant or use 
• 
ID number of the subject receiving or using the device 
• 
Disposition (implanted, opened not used, disposed of, or returned to Medtronic) 
6.9 
Product Storage 
The Intrepid™ TMVR System will be hand carried or shipped to the sites at intervals dependent 
on the rate of subject accrual. The site will use a device accountability form to document the 
inventory and study device disposition. All Intrepid™ TMVR devices must be stored at room 
temperature in an area free of environmental extremes and with limited access. Medtronic will 
inspect the storage area and will monitor device accountability. In addition, all information for 
the use, storage and handling of the investigational device as indicated in the Instructions for 
Use, must be taken into account. 
Instructions for Use and storage recommendations are outlined in Appendix 17.3– Instructions 
for Use. 
6.10 
Product Return 
For devices that are returned to Medtronic or disposed of, centers are required to document the 
following information: 
• 
Device Serial Numbers, if applicable 
• 
Device Lot Numbers 
• 
Quantity and reason for the device being returned to Medtronic, or disposed of 
• 
Name of the person who returned or disposed of each device 
• 
Date of shipment back to Medtronic, or date of disposal 
Following the completion of each index procedure, the investigator must return to Medtronic any 
unused devices and a copy of the completed device inventory. The investigator’s copy of the 
device reconciliation records must document any unused devices that have been returned to 
Medtronic as well as all product usage including opened but non-implanted devices. All 
explanted devices should be returned to Medtronic for analysis when permissible by local laws 
and regulations. To receive a Returned Product Mailer Kit, please contact your local Medtronic 
field personnel. 
6.11 
Product Accountability 
Access to investigational devices shall be controlled and the investigational devices shall be used 
only in the clinical investigation according to this CIP. Medtronic shall keep records to document 
the location of all investigational devices from shipment to sites until implant, return, or disposal. 
The Investigator or an authorized designee shall maintain a device accountability log 
documenting the receipt, use, return and disposal of all investigational devices at their site. When 
study enrollment is complete, the Investigator shall return any unused devices to Medtronic. 
 

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7.0 
Study Site Requirements 
7.1 
Investigator/Investigation Site Selection 
This trial may be conducted at up to 15 US sites with appropriate regulatory approval. 
Investigational sites will meet the following criteria: 
• 
Presence or capacity of establishing an investigative team consisting of the following: 
− Interventional cardiologist 
− Cardiothoracic surgeon 
− Echocardiologist/Cardiac anesthesiologist 
− Heart failure specialist 
− Study coordinator(s) 
• 
Presence or capacity of establishing multidisciplinary heart team consisting of the 
requirements outlined in Section 7.3. 
• 
Investigators are not debarred, disqualified, or working under sanctions in applicable 
regions. 
• 
Access to an adequate number of eligible patients. 
• 
Adequate staff that is accessible and has time to manage the study for 7 days per 
week, 24 hours per day. 
• 
Willing to comply with the Clinical Investigation Plan and data requirements, 
including reporting Adverse Events. 
• 
Willing to comply with the Investigational Review Board (IRB)/ Ethics Committee 
(EC) and local regulatory requirements. 
• 
Non-invasive imaging including echocardiography, vascular ultrasound, computed 
tomography (CT) and magnetic resonance imaging (MRI). 
• 
Operating room or hybrid operating room/catheterization lab equipped with a fixed 
radiographic imaging system with flat-panel fluoroscopy, offering quality imaging. 
• 
All site personnel must provide his/her Curriculum Vitae. Additionally, each 
Investigator must sign and comply with the protocol-specific Investigator Agreement. 
• 
Information on the investigational sites (i.e., name, address, PI, etc.) will be 
maintained in a separate document. 
7.2 
Site Principal Investigators 
Each site will have two Co-Principal Investigators (PI), one who is an interventional cardiologist, 
and one who is a cardio(thoracic) surgeon. The Co-PIs have overall responsibility for the 
conduct of the study at the site, including protecting the rights, safety, and welfare of the study 

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subjects at their site, the integrity of the study data generated by their site, and for ensuring the 
study is conducted in compliance with the Clinical Investigation Plan, 21 CFR 50, 11, 54, 56 and 
812, the latest version of ISO 14155, the Declaration of Helsinki, International Conference on 
Harmonization (ICH) Good Clinical Practice (GCP) guidelines, IRB/EC requirements and local 
regulations. 
The site Co-PIs may also serve as members of the local Heart Team and/or Implant Team, as 
applicable. 
7.3 
Heart Team 
Each site will utilize a local Heart Team, experienced in mitral valve therapies, to assess 
eligibility of each potential subject for the study. 
At a minimum, the local Heart Team must include the following members: 
• 
Interventional cardiologist 
• 
Cardiothoracic surgeon 
• 
Echocardiologist/Cardiac anesthesiologist 
• 
Heart failure specialist 
Individuals may only fulfill one role on the Heart Team. The site Co-PIs may also serve as 
members of the local Heart Team and/or Implant Team, as applicable. 
7.4 
Implant Team 
Sites should establish a single implant team for all procedures and each Implant Team member 
must meet the minimum qualifications as outlined in Table 7-1 Implant team composition and 
roles will be defined for each site prior to activation and maintained for all investigational 
procedures. 
The site Co-PIs may also serve as members of the local Heart Team and/or Implant Team, as 
applicable. 
Table 7-1: Implant Team Membership [Minimum Qualifications] 
Implant Team Member – Minimum Qualifications 
Cardiothoracic Surgeon: Performing TMVR 
Procedures 
Interventional Cardiologist: Performing TMVR 
Procedures 
• 
At least 5 years of experience post-residency 
− 
Cardiac surgery experience including 
contemporaneous transfemoral experience 
• 
Interventional volume: 
− 
≥250 catheterizations in the prior year 
− 
≥25 structural heart procedures guided by TEE 
(e.g., transcatheter mitral valve repair or 
replacement) in the prior year 
• 
≥20 Transcatheter valve procedures in the prior year or 
≥40 transcatheter valve procedures in the prior two 
years 
Echocardiologist/Cardiac Anesthesiologist: TEE Management during TMVR Procedures 

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• 
≥25 structural heart procedures guided by TEE (e.g., transcatheter mitral valve repair or 
replacement) in the prior year 
7.5 
Trial Training 
Prior to investigational site involvement in trial activities, Medtronic (or designee) will provide 
study training relevant and pertinent to the involvement of personnel conducting trial activities, 
including investigator responsibilities, adverse event reporting as well as device training (if 
necessary, usage and handling of device under investigation). Training requirements are outlined 
in the study-specific Training Plan. Training may be conducted via Site Initiation Visits, 
Investigator and Coordinator Meetings, and/or other multi-media sessions. Medtronic will 
maintain documentation of attendance at each of these training opportunities, as applicable. 
Additionally, Medtronic representative(s) will be present at each site’s TMVR procedures as part 
of the ongoing training process and provide technical support relative to the use of the 
investigational device. 
7.6 
Study Site Activation 
All local and regional regulation requirements will be fulfilled prior to site activation and 
consenting of patients into the study. Medtronic and each investigational site must have written 
in documentation of site readiness, including, but not limited to: 
• 
IRB approval letter (and voting list, as required by local law) of the current version of 
the CIP and Informed Consent Form (ICF) 
• 
Fully executed Clinical Trial Agreement (CTA) 
• 
Financial Disclosure for Investigators 
• 
Investigator Agreements 
• 
Delegated Task List 
• 
Training documentation 
In addition, all participating study site staff must be trained on the current version of the CIP as 
well as on the applicable study requirements depending on their role and must be delegated by 
the Principal Investigator to perform study related activities. 
Medtronic will provide each study site with documentation of study site/investigator readiness; 
this letter must be received prior to performing study related activities. 
7.7 
Role of the Sponsor Representatives 
Sponsor representatives may provide support at the study site as required for the study under 
supervision of the Principal Investigator, including: 
• 
Provide study training relevant and pertinent to the involvement of personnel 
conducting study activities and investigator responsibilities 

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• 
Technical support at Index Procedure visit under the supervision of a study 
investigator, but no data entry, shall be performed by Medtronic personnel or their 
representatives at study sites 

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8.0 
Selection of Subjects  
8.1 
Study Population 
Since this is a limited clinical investigation, the study will enroll and treat up to 45 subjects (as 
approved by the FDA in 15 subject increments) at up to 15 investigational sites who require 
replacement of their mitral valve because of moderate-severe or severe, symptomatic mitral 
regurgitation, but are ineligible for conventional mitral valve surgery. 
Patients will be screened prior to study entry to determine if they meet the Eligibility Criteria. 
Patients who have signed an Informed Consent and fulfill the inclusion criteria and none of the 
exclusion criteria are eligible for enrollment. 
8.2 
Subject Enrollment 
Subjects will be considered enrolled into the trial once the subject is documented as enrolled in 
the Oracle Electronic Data Capture (EDC) database system. Prior to enrollment the patient must 
sign informed consent. Enrollment will only occur after confirmation the patient meets all 
inclusion criteria, does not meet any exclusion criteria, has been assessed by the Heart Team as 
being an appropriate candidate for enrollment and approved by the Screening Committee. 
Due to the inclusion/exclusion criteria, not all patients that consent to the trial will be enrolled. 
All sites will be required to maintain a record of patients screened for the trial meeting general 
inclusion criteria who have signed the approved informed consent document. For subjects who 
do not meet trial criteria, the reason for not continuing in the trial must be documented and 
recorded in the EDC system. Patients consented but not enrolled will be considered screen 
failures and no further trial-related follow-up will be required. 
The study will enroll and treat up to 45 subjects (as approved by the FDA in 15 subject 
increments). 
8.3 
Inclusion Criteria 
The subject must meet ALL of the following inclusion criteria: 
• 
Heart Team agrees that patient is a candidate for bioprosthetic mitral valve 
replacement 
• 
Subjects with moderate-severe or severe symptomatic mitral regurgitation who are 
determined by a multidisciplinary heart team to be a candidate for bioprosthetic mitral 
valve replacement and are ineligible for conventional mitral valve surgery based on 
predicted risk of operative mortality or irreversible major morbidity ≥ 35% and <50% 
at 30 days1 
 
1 The Early Feasibility Study of the TMVR Transseptal System utilizes a Heart Team approach to assess operative 
risk. The risk stratification is based on the STS predicted risk of operative mortality or irreversible major morbidity 
in conjunction with the Heart Team evaluation of additional risk factors including co-morbidities, frailty, heart 
failure status, and other factors not accounted for the in the risk calculation. 

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• 
Subject anatomically suitable for the Intrepid TMVR delivery system including 
transfemoral and transseptal access 
• 
Subject and the treating physician agree that the subject will return for all required 
post- procedure follow-up visits 
• 
Subject meets the legal minimum age to provide informed consent based on local 
regulatory requirements 
8.4 
Exclusion Criteria 
The subject may not meet any of the following exclusion criteria: 
1. Estimated life expectancy of less than 12 months due to associated non-cardiac co-
morbid conditions 
2. Prior transcatheter mitral valve procedure with device currently implanted 
3. Prior transseptal intervention with occlusion device currently implanted 
4. Anatomic contraindications for Intrepid™ TMVR (eg, annular dimensions, high risk 
of LVOT obstruction, etc.) 
5. Anatomically prohibitive mitral annular calcification (MAC) 
6. Aortic valve disease requiring intervention or previous intervention within 90 days of 
enrollment 
7. Severe tricuspid regurgitation 
8. Patients unsuitable for implantation because of congenital abnormalities of the IVC, 
thrombosis of the femoral vein and/or of IVC, history of venous stents (iliac and/or 
femoral), presence of a vena cava filter or intracardiac mass or intracardiac thrombus 
9. Right-sided congestive heart failure with echocardiographic evidence of severe right 
ventricular dysfunction 
10. Pulmonary hypertension with resting pulmonary artery systolic pressures ≥2/3 
systemic pressure 
11. Left ventricular ejection fraction (LVEF) <30% 
12. Left ventricular end diastolic diameter (LVEDD) > 75mm 
13. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy, constrictive 
pericarditis, or other structural heart disease causing heart failure other than dilated 
ischemic or non- ischemic cardiomyopathy 
14. Infiltrative cardiomyopathies (e.g., amyloidosis, hemochromatosis, sarcoidosis) 
15. Subject is contraindicated for transesophageal echocardiography (TEE) 
16. Need for emergent or urgent cardiac or non-cardiac surgery 

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17. Hemodynamic instability requiring dependency of either inotropic agents or 
mechanical circulatory support 
18. Subject refuses a blood transfusion 
19. Subject unwilling or unable to adhere to the protocol specified anticoagulation 
treatment 
20. Blood dyscrasias as defined: leukopenia (WBC <1000 cells/mm3), thrombocytopenia 
(platelet count <50,000 cells/mm3) 
21. History of bleeding diathesis or coagulopathy that precludes anticoagulation 
22. Active gastrointestinal (GI) bleeding that would preclude anticoagulation 
23. Known hypersensitivity or contraindication to nitinol, or sensitivity to contrast media 
which cannot be adequately pre-medicated 
24. Any cardiac or peripheral interventional procedure performed within 30 days prior to 
enrollment in patients treated with bare-metal stent or drug-eluting stent (DES) with 
approved 1-month DAPT labeling or within 90 days prior to enrollment for subjects 
treated with DES without approved 1-month labeling. 
25. Untreated clinically significant coronary artery disease requiring revascularization 
26. Severe symptomatic carotid stenosis 
27. Recent Stroke or TIA within 90 days of enrollment 
28. Evidence of an acute myocardial infarction within 90 days prior to enrollment 
29. Active endocarditis or active infection requiring antibiotic therapy 
30. Implant of any Cardiac Resynchronization Therapy (CRT) or Cardiac 
Resynchronization Therapy with cardioverter-defibrillator (CRT-D) within 90 days of 
enrollment 
31. End stage renal disease requiring chronic dialysis or creatinine clearance < 30 cc/min 
within 30 days of the Index Procedure 
32. Severe Chronic Obstructive Pulmonary Disease (COPD) demonstrated by Forced 
Expiratory Volume (FEV1) < 750cc 
33. Pregnancy, breastfeeding, or intent to become pregnant prior to completion of all 
protocol follow-up requirements 
34. Currently participating in an investigational drug or another device study that has not 
yet reached its primary endpoint 
35. Other medical, social, or psychological conditions that in the opinion of the 
Investigator precludes the subject from appropriate consent or adherence to the 
protocol required follow-up exams 
 

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9.0 
Study Procedures  
9.1 
Schedule of Events 
All enrolled subjects will undergo in-clinic follow-up evaluations through at least 5 years. A 
schedule of events is outlined below in Table 9-1. Upon completion of the final protocol visit 
(discontinuation) subject participation will be considered complete and the patient should then be 
followed per the local standard of care for their condition. 
Table 9-1: Schedule of Events Table 
 
Screening 
& 
Baseline 
Pre-Index 
Procedure 
Index 
Procedure Discharge 
1 
Month 
3 
Months 
6 
Months 
12 
Months 
Every 6 
Months 
through 
5 Years 
Informed consent 
X 
 
Inclusion/Exclusion 
X 
X 
 
Demographics & 
di
l
i
X 
 
Physical Examination 
X 
X 
X 
X 
X 
X 
X 
NYHA 
X 
X 
X 
X 
X 
X 
Frailty Assessments & 
A
X 
 
Pregnancy Test 
X1 
 
Modified Rankin Scale 
(mRS) 
X2 
 
Laboratory Tests3, 4 
X 
X 
X 
X 
X 
X 
X 
Transthoracic 
Echocardiogram 
(TTE) 
X 
X5 
X6 
X6 
X6 
X6 
X6 
X6 
Transesophageal 
Echocardiogram (TEE) 
X 
X 
 
Right Heart 
C h
i
i
X 
X7 
 
MDCT 
X8 
X9 
 
X9 
Coronary Arteriogram 
X 
 
12-lead ECG 
X 
X 
X 
X 
X 
X 
X 
6 Minute Walk Test12 
X 
X 
X 
X 
X 
X 
Quality of Live 
Questionnaire(s) 
QoL11 
X 
X 
X 
X 
X 
X 
Adverse Events & 
Device Deficiencies 
X10 
X 
X 
X 
X 
X 
X 

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Table 9-1: Schedule of Events Table 
 
Screening 
& 
Baseline 
Pre-Index 
Procedure 
Index 
Procedure Discharge 
1 
Month 
3 
Months 
6 
Months 
12 
Months 
Every 6 
Months 
through 
5 Years 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Heart Failure 
M
X 
X 
X 
X 
X 
X 
X 
X 
X 
1. If female and child-bearing age 
2. mRS is required to be collected at screening and conducted at 30 and 90 days following any stroke or TIA event, as 
applicable 
3. B-type Natriuretic Peptide (BNP) or NT-proBNP, along with Creatinine, CBC and Albumin required at follow-up visits 
4. INR levels to be monitored and reported for all subjects receiving warfarin anticoagulation therapy 
5. TTE with limited views is required within 7 days of the Index Procedure to assess cardiac status (i.e. cardiac index, LVEF, 
PA pressure and mitral regurgitation) 
6. If clinically necessary, or at Investigator discretion, TEE is to be conducted in addition to TTE to further evaluate any 
potential clinically significant findings during the follow-up period 
7. Right heart catheterization may be used to supplement TTE measurements, as applicable 
8. Complete visualization of femoral veins and inferior vena cava up to and including the mitral annulus 
9. Subjects declining the MDCT at time of follow-up or unable to have the assessment will not be considered a protocol 
deviation 
10. Adverse events collected after the subject is enrolled in the study. 
11. Quality of Life Questionnaires collected at baseline (Minnesota Living with Heart Failure Questionnaire, SF-12 and KCCQ) 
may be administered any time after the subject has been approved for enrollment 
 
9.2 
Data Collection 
The investigator must ensure accuracy, completeness and timeliness of the data reported in the 
EDC system and in all other required reports. Data reported on the CRFs which are derived from 
source documents must be consistent with the source documents or the discrepancies need to be 
justified in a documented rationale, signed and dated by the (principal) investigator, and are to be 
filed in the subject file. 
Required data will be recorded on the CRFs by authorized site personnel as indicated on the 
Delegation of Authority Log. The CRFs must be completed and/or updated to reflect the latest 
observations on the subjects participating in the trial. 
The investigator (or approved sub-investigator) will electronically sign the appropriate pages of 
each CRF. 
The EDC system maintains an audit trail on entries, changes, or corrections in CRFs. If a person 
only authorized to complete CRFs makes changes to an already signed CRF, the investigator 
shall re-sign this CRF. 
No trial document or image is permitted to be destroyed without prior written agreement between 
the Sponsor and the investigator. If the investigator wishes to assign the trial records to another 
party or move them to another location, advance written notice must be provided to the Sponsor.  
See Section15.8- Record Retention for additional requirements. 

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9.3 
Scheduled Follow-up Visit Windows 
After receiving notice of successful index procedure, Medtronic will provide the target dates and 
windows for each visit to the study site, if applicable. Should a subject miss a visit or the visit 
falls outside the pre-specified window, a study deviation must be reported and the original 
follow-up schedule maintained for subsequent visits. 
Data analyses include follow-up visits, regardless of whether the visit occurs within the window. 
Therefore, a late visit is preferred over a missed visit but must be accompanied by a protocol 
deviation. Follow-up visit windows are listed in Table 9-2 and are based on days post-implant. 
Table 9-2: Study Visit Windows 
Study Visit 
Visit Window 
Target (days post-implant) 
Window (days post-implant) 
1 Month 
30 
±14 
3 Month 
90 
±14 
6 Month 
183 
±14 
1 Year 
365 
±30 
18 Month 
548 
±30 
2 Year 
730 
±30 
30 Month 
913 
±30 
3 Year 
1095 
±30 
42 Month 
1278 
±30 
4 Year 
1460 
±30 
54 Month 
1643 
±30 
5 Year 
1825 
±30 
 
 
9.4 
Subject Consent 
Prior to enrolling in the trial, patients should be fully informed of the details of trial participation 
as required by applicable regulations, the site’s IRB and by Medtronic. Informed consent must be 
obtained from each patient or legally authorized representative prior to conducting any protocol-
induced activities beyond standard of care, by using the informed consent form (ICF) approved 
by that site’s IRB and by Medtronic. The ICF must be signed and dated by the patient or legal 
representative and by the person obtaining the consent. Any additional persons required by the 
site’s IRB to sign the informed consent form must also comply. Where applicable, ICF certified 
translations are permitted when in compliance with local IRB requirements and approved by 
Medtronic. 
Prior to the patient or legally authorized representative signing the ICF, the investigator or 
authorized delegate will fully explain to the patient or legally authorized representative the 

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nature of the research, trial procedures, anticipated benefits, and potential risks of participation in 
the trial. The investigator or delegate will allow adequate time for the patient or legally 
authorized representative to read and review the consent form and to ask questions. Signing the 
ICF serves to document the written and verbal information that the investigator or authorized 
delegate provides to the patient or legally authorized representative, the patient or legally 
authorized representative’s understanding of the information, and their agreement to participate. 
The investigator or authorized delegate must document in the patient’s medical records that the 
patient was consented and the date on which the consent was obtained. The original signed 
consent form will be retained in the patient’s trial records and a signed copy of the informed 
consent will be provided to the patient or legally authorized representative. 
In the event the subject or legally authorized representative cannot read and/or write, the ICF 
process shall be obtained through a supervised oral process. An independent and impartial 
witness must be present during this process. The ICF and any other information must be read 
aloud to the prospective subject or his/her legally designated representative. Whenever possible, 
either the subject or his/her legally authorized representative shall sign and personally date the 
informed consent form. The witness signs and personally dates the ICF attesting that the 
information was accurately explained, and that informed consent was freely given. 
Medtronic will inform the investigators whenever information becomes available that may be 
relevant to the subject’s continued participation in the study. The revised information will be sent 
to the investigator for approval by the IRB. After approval by the IRB, a copy of this information 
must be provided to each participating subject, and the informed consent process as described 
above needs to be repeated. The investigator or his/her authorized delegate should inform the 
subject in a timely manner. 
The ICF template will be provided under separate cover. 
9.5 
Subject Screening 
Standard examinations and tests, which are typically performed for patients undergoing similar 
procedures such as conventional mitral valve surgery, minimally invasive mitral valve repair 
(e.g., MitraClip), or Transcatheter Aortic Valve Implantation (TAVI) will be used both to screen 
eligible patients and provide baseline information for those patients that meet study criteria. 
9.5.1 
The process of screening and subject enrollment is as follows: 
1. Patients identified by or presented to the trial site with mitral regurgitation will be screened 
by the investigative team for the criteria described in Section 8.0 – Selection of Subjects, 
using available medical records, including list of comorbidities, current medical management 
and relevant imaging studies previously performed for diagnostic purposes. 
2. If the patient is deemed a potential candidate for the trial, the investigational status of the 
Intrepid™ TMVR System and all aspects of the trial will be explained to the patient. The 
patient will then be invited to participate in the trial. 
3. If the patient agrees to participate, written informed consent will be obtained and the patient 
will be assigned a Study ID number. 

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4. The patient will undergo screening evaluations not previously conducted as standard of care. 
5. Local Heart Team assessment of eligibility for enrollment 
9.5.2 
Clinical assessment including: 
6. Proposed enrollment within the EFS 
7. Evaluation of heart failure management including device therapy and assessment of guideline 
directed medical therapy 
8. Anatomical assessment including: 
• 
Anatomic suitability for the Intrepid™ valve 
• 
Anatomic suitability and access for the Intrepid ™ TMVR Delivery System 
9. If the local Heart Team considers the subject anatomically suitable for implantation and 
eligible for enrollment, the patients’ clinical information will be submitted to the Screening 
Committee. The Heart Team assessment must be documented. The following information 
should be submitted to the Screening Committee: 
• 
Clinical assessments including STS-PROM, medical history, medications, heart 
failure management & co-morbidities, 
• 
Demographic & Medical History 
• 
Physical Examination (inclusive of vital signs, height, weight, & NYHA Class) 
• 
Frailty Assessments (Frailty Toolset & KATZ Index of Independence) 
• 
Pregnancy Test (If female and child-bearing age) 
• 
Coronary Arteriogram 
• 
Right heart catheterization 
• 
12-lead Electrocardiogram (ECG) 
• 
Lab tests 
− Creatinine 
− Complete Blood Count (CBC) 
− Albumin 
− B-type Natriuretic Peptide (BNP) or NT-proBNP 
− INR, if applicable (INR levels to be monitored and reported for all subjects 
receiving warfarin anticoagulation therapy) 
• 
Resting TEE and TTE data on degree of mitral regurgitation 
• 
Multidetector Computed Tomography (MDCT) data on anatomical suitability 
including complete visualization of femoral veins and inferior vena cava up to and 
including the Mitral valve annulus 

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The Screening Committee will review the clinical information to confirm the eligibility of the 
patient for enrollment and implantation. Screening Committee approval must be obtained for the 
subject to move forward in the study. 
Written informed consent must be obtained prior to undergoing any protocol-required 
testing. If any of protocol-required screening evaluations (e.g., echocardiography, MDCT, 
coronary arteriography, lab work) have been performed for clinical diagnostic purposes 
prior to study consent, existing data/results may be used to satisfy the protocol-required 
exams, provided they contain the required information. 
All subjects who are considered for the study should be documented on the study screening log. 
The reasons for non-eligibility, as determined by the Investigator should be recorded on the 
study Enrollment and Screening Log. The screening log serves as a method for Medtronic to 
assess selection bias in the trial. 
9.6 
Additional Screening Assessments 
Additional screening assessments will be obtained for subjects that are deemed as anatomically 
suitable. The evaluations include: 
• 
Modified Rankin Score (mRS) 
• 
6-Minute walk test (6MWT) 
• 
Quality of Life (QOL) Questionnaires – Minnesota Living with Heart Failure 
Questionnaire, SF-12 and KCCQ 
Subjects physically unable to complete the 6MWT assessment will not be considered protocol 
deviations. The mRS assessment will occur at screening for all subjects, and is required to be 
conducted at 30 and 90 days following any stroke or transient ischemic attack (TIA) that occurs 
during the study period. 
9.7 
Pre-Index Procedure 
Cardiac status is required to be assessed for all subjects to confirm it is appropriate to proceed 
with the Index Procedure (i.e., subject has not decompensated since screening committee 
review). Assessment must be completed within one (1) to 7 days prior to the Index Procedure. 
Key cardiac assessments via TTE will be evaluated, at minimum: cardiac index, LVEF, 
pulmonary artery (PA) pressure and tricuspid regurgitation. A right heart catheterization may be 
used to supplement TTE measurements, as applicable. 
Subject status must be assessed to confirm the subject continues to meet all the inclusion criteria 
and none of the exclusion criteria by local heart team. Current Medications and Heart Failure 
management will be assessed and collected at this visit. 
9.8 
Enrollment 
Enrollment will only occur after confirmation that the patient meets all inclusion criteria, does 
not meet any exclusion criteria, has been assessed by the Heart Team as being an appropriate 
candidate for enrollment and approved by the Screening Committee. A subject is considered 

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enrolled into the study once the subject is documented as enrolled in the Oracle Electronic Data 
Capture (EDC) database system following a successful Pre-Index Procedure. The date that this is 
completed in Oracle EDC begins the Adverse Event reporting timeline for that subject. 
9.9 
Index Procedure 
The Intrepid™ TMVR procedure requires meticulous preparation and typically a multi-
disciplinary team approach involving among others, interventional cardiologists, cardiac imaging 
specialists, cardio- thoracic surgeons and anesthesiologists. 
The implant procedure itself takes place either in a hybrid suite or an operating room equipped 
for state-of-the-art transcatheter and/or surgical procedures. Procedural adverse event and device 
deficiency collection will be assessed throughout, as applicable and heart failure management 
will be collected. 
The execution of the TMVR procedure involves an operating team typically consisting of a 
minimum of 2 operators (one managing the delivery catheter and another managing the inflation 
device) and an echocardiographer. Members of the implant team must be study investigators for 
the site and meet the minimum qualifications as outlined in section 7.4. The Fourth Position 
TMVR Procedure role will be completed by a delegated study team member who has completed 
the case debrief training for intended procedure at that site and is activated as a sub-I on the 
study. Additional case support functions may include an anesthesia team and nurses/technicians. 
Medtronic representative(s) (e.g., Therapy Development Specialists, proctors, etc.) may be 
present during TMVR procedures for training purposes, to perform valve loading and/or to 
provide general case support. 
Device preparation, subject preparation and the implant procedure are to be completed in 
accordance with the Instructions for Use found in section 17.3. 
Note: Closure of the atrial septal defect (ASD) created for transseptal crossing of the delivery 
system is recommended at the completion of implantation for all subjects treated. 
9.9.1 
No concomitant procedures are permitted during the index TMVR 
procedure. Any occurrence will be deemed a protocol deviation. 
At the conclusion of the TMVR procedure, the following is assessed via TEE: 
• 
Cardiac function including MR grade 
• 
Paravalvular leak 
• 
Atrial septal defect (ASD) as applicable 
9.10 
Discharge 
Subjects will be cared for through discharge according to standard procedures for mitral valve 
replacement surgery. 
Antithrombotic medication is recommended to be initiated in accordance with local practice and 
no earlier than Day 1 post-operatively. The recommended post-implant regimen for all subjects 

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is dual anticoagulation/antiplatelet therapy for a minimum of 6 months with a target INR of 2.5. 
Dual warfarin and aspirin (81mg) are recommended. 
It is also recommended that deep vein thrombosis (DVT) prophylaxis be administered in 
accordance with local practice for any subject treated, until the INR reaches therapeutic level. 
Prior to discharge (or within 14 days post procedure whichever comes first), the following 
standard exams and tests will be performed: 
• 
Physical exam and review of adverse events and device deficiencies 
• 
Heart Failure Management & Medications 
• 
TTE (addition of TEE evaluation if deemed clinically necessary, or at Investigator 
discretion) 
• 
12-lead ECG 
• 
Laboratory tests 
− Creatinine 
− Complete Blood Count 
− Albumin 
− B-type Natriuretic Peptide (BNP) or NT-proBNP 
− INR, if applicable (INR levels to be monitored and reported for all subjects 
receiving warfarin anticoagulation therapy) 
• 
Multidetector Computed Tomography (MDCT) 
Subjects declining the MDCT at time of follow-up or unable to have the assessment 
will not be considered a protocol deviation 
9.11 
Scheduled Follow-up Visits 
Scheduled visits will occur at 1, 3, 6 months (± 2 weeks), at 12 months and every 6 months (± 30 
days) through 5 years. 
The following information is required to be collected at follow-up visits: 
• 
Physical exam (including NYHA Class) and review of adverse events and device 
deficiencies 
• 
Heart Failure Management & Medications 
• 
6-minute walk test (6MWT) 
• 
TTE (addition of TEE evaluation if deemed clinically necessary, or at Investigator 
discretion) 
• 
12-lead ECG 
• 
Laboratory tests: 

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− Creatinine 
− Complete Blood Count 
− Albumin 
− B-type Natriuretic Peptide (BNP) or NT-proBNP 
− INR, if applicable (INR levels to be monitored and reported for all subjects 
receiving warfarin anticoagulation therapy) 
• 
QoL surveys: Minnesota Living with Heart Failure Questionnaire, SF-12 and KCCQ 
• 
Multidetector Computed Tomography (MDCT)
2 (12-month visit only) 
Note: If a subject’s TMVR implant is replaced with surgical replacement valve, the subject will 
be followed through 1-month post-surgical replacement. 
Any unscheduled visits if deemed appropriate per physician discretion would be captured in the 
Unscheduled visit CRF. Data collected at an unscheduled visit would reflect similar follow-up 
visit assessments such as subject current status, NYHA Classification, medications, healthcare 
utilization, and echocardiography parameters as available. If this visit is associated with an 
Adverse Event, the information will be instead captured in the appropriate AE CRF entry as 
applicable. 
9.12 
Stroke Evaluation 
Modified Rankin Score (mRS) assessment is required to be conducted at 30 and 90 days 
following any new suspected stroke or TIA event during the study period. 
9.13 
Healthcare Utilization 
Health Care Utilization information will be collected at any new hospital admission (excluding 
the Index Procedure admission). Health Care Utilization to be collected includes facility type and 
location as well as the start and end date of healthcare utilization facility. 
9.14 
Quality of Life (QoL) Questionnaires 
Quality of Life questionnaires used in this protocol include Minnesota Living with Heart Failure 
Questionnaire, SF-12 and KCCQ 
9.15 
Prior and Concomitant Medications 
During subject screening, heart failure medications will be reviewed by the local Heart Failure 
Specialist and Screening Committee to evaluate the patient’s current medication regimen. It is 
recommended that patients with heart failure are on optimal guideline-directed medical therapy; 
if not, recommendations may be made by the Screening Committee to optimize medical therapy. 
Subjects on existing antithrombotic regimens may be required to discontinue current medications 
 
2 Subjects unable to have the CT assessment will not be considered a protocol deviation. 

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at the discretion of the local Heart Team for either the Index Procedure and/or in favor of 
alternative/preferred regimens post-procedure. 
Please refer to Section 9.10 Discharge for post-procedure medication recommendations. 
9.16 
Assessment of Efficacy 
The following methods will be used for assessing, recording, and analyzing efficacy. Refer to 
Section 9.1 Schedule of Events for timing of these assessments. 
• 
Heart team assessment 
• 
MDCT 
• 
TTE and TEE 
• 
NYHA functional classification 
• 
Quality of life questionnaires 
9.17 
Assessment of Safety 
All adverse events and device deficiencies will be collected from the time of enrollment until the 
end of the study or until study exit, whichever comes first. 
The safety assessment performed during this study will be based on the relatedness to the TMVR 
implant and index procedure. 
9.18 
Recording Data 
Data entered must be traceable to source documents. Source documentation is defined as the first 
time data appear, and may include original documents, data, and records (e.g., hospital records, 
clinical and office charts, procedure reports, laboratory notes, memoranda, or evaluation 
checklists, X-rays, subject files, device data and records kept at the pharmacy, at the laboratories 
and at medico-technical departments involved in the study). 
In general, eCRFs (or paper copies) may not serve as source documents. An exception may be 
the completion of QoL Questionnaires. Source documentation for data elements not routinely 
captured in medical records may vary from study site to study site; the study site may use source 
document worksheets if identified as source documents. 
The investigator must ensure the availability of source documents from which the information on 
the eCRFs was derived. The type and location of source documents should be documented. 
Where printouts of electronic medical records, are provided as source documents, or where 
copies of source documents are retained as source documents, those should be certified. 
Certification must contain (1) the signature of the individual making the copy, (2) the date the 
copy was made and (3) a statement attesting to the accuracy and completeness of the copy. 
The source documents must be made available for monitoring or auditing by Medtronic’s 
representative or representatives of the competent authorities and other applicable regulatory 
agencies. 

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9.19 
Deviation Handling 
A protocol deviation is defined as an event where the clinical investigator or site personnel did 
not conduct the trial according to the protocol or the Investigator agreement. Deviations will be 
reported regardless of whether medically justifiable, pre-approved by Medtronic, or taken to 
protect the patient in an emergency unless specified within the protocol. 
A protocol deviation form is to be completed for each trial protocol deviation, including, but not 
limited to: 
• 
Failure to obtain informed consent 
• 
Incorrect version of consent provided to patient 
• 
Failure to obtain IRB/EC protocol review and approval before starting the trial 
• 
Enrollment of patient during an IRB/EC approval lapse 
• 
Clinical investigator exceeding enrollment limits specified by sponsor 
• 
Patient did not meet inclusion/exclusion criteria 
• 
Incorrectly performed testing 
• 
Protocol-required testing and/or measurements not done or performed outside of 
window 
• 
Source data permanently missing 
• 
UADE or USADE not reported in the required timeframe 
FDA regulations [21 CFR 812.140] require that the Investigator maintain accurate, complete, 
and current records, including documents showing the dates of and reasons for each deviation 
from the protocol. 
Relevant information for each deviation will be documented on a deviation form completed by 
site personnel and reviewed by the Investigator. 
FDA regulations [21 CFR 812.150], the latest version of ISO 14155, and local regulatory 
authorities (where applicable), require Investigators to obtain prior approval from the sponsor 
before initiating changes in or deviations from the protocol, except when necessary to protect the 
rights, life or physical well-being of a patient in an emergency. 
Prior approval by the sponsor is expected in those situations in which the Investigator 
anticipates, contemplates, or makes a conscious decision to depart from procedures specified in 
the protocol. Prior approval is generally not expected in situations where unforeseen 
circumstances are beyond the Investigator’s control, but is still considered a deviation (e.g., a 
trial subject who fails to attend a scheduled follow-up visit, a trial subject too ill to perform a 
protocol-required test). To obtain approval, the Investigator must call or email and discuss the 
potential deviation with the Medtronic trial manager or designee prior to initiating any changes. 
If approval is granted, the Medtronic trial manager or designee will provide the applicable 
documentation to be maintained in the site files. 

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FDA regulations require the Investigator to notify the sponsor and the reviewing IRB/EC within 
5 working days of the following deviations [21 CFR 812.150]: 
• 
A deviation from protocol to protect the life or physical wellbeing of a patient in an 
emergency 
• 
Failure to obtain an informed consent 
The Investigator is required to adhere to local IRB/EC procedures for reporting deviations. 
Repetitive or serious investigator compliance issues may represent a need to initiate a corrective 
action plan with the investigator and trial site, and in some cases, terminating the investigator’s 
participation in the trial. 
The Data Monitoring Committee (DMC) may review protocol deviations to ensure compliance 
and overall study integrity. 
9.20 
Subject Exit, Withdrawal or Discontinuation 
All subjects will be encouraged to remain in the trial through the last follow-up visit applicable 
as listed in Section 9.3. Subjects who discontinue participation prematurely will be included in 
the analysis of results (as appropriate) and will not be replaced in the enrollment of total trial 
subjects. If a subject is discontinued from the trial early, the reason for discontinuation is to be 
documented in the subject file and a Trial Exit CRF must be completed. 
If a subject discontinues the trial at any time, is withdrawn from the trial early, or completes all 
protocol required follow-up it is recommended they continue to be followed by the implanting 
site per local clinical practice for mitral valve patients. If, for any reason, this is not possible for a 
particular subject, or if a subject needs to change their follow-up site at any time point after 
conclusion of the trial, investigators may refer subjects to a site with appropriate training and 
experience in managing patients with mitral valve disease. 
9.20.1 
Study Completed 
At the completion of the 5-Year follow-up visit, subjects will be exited from the study. 
9.20.2 
Lost to Follow-up 
A subject will not be considered lost to follow-up unless all efforts to obtain compliance are 
unsuccessful. At a minimum, the effort to obtain follow-up information must include 3 
documented attempts to make contact via telephone and if contact via phone is not successful, a 
traceable letter from the investigator is to be sent to the subject’s last known address. If both 
telephone and mail efforts to contact the subject are unsuccessful, the subject’s primary 
physician is to be contacted, per the subject’s informed consent. Subjects will then be deemed 
lost to follow up. All contact efforts to obtain follow-up must be documented in the subject’s 
medical records. Subjects will not be replaced. 

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9.20.3 
Subject Death 
In the event that a subject dies after implantation of the TMVR bioprosthesis, the Investigator 
will make reasonable effort to have an autopsy performed to help determine the extent to which 
the subject’s death was related to the device/procedure. If possible, the TMVR bioprosthesis will 
be explanted and returned to the Sponsor. Contact your Medtronic representative to obtain 
instructions for proper return of the device. 
9.20.4 
Subject Chooses to Exit (i.e., Revokes Consent) 
A subject can withdraw from the study at any time. If the subject wishes to exit from the study 
(i.e. the subject revokes consent), the study site is required to document the reason for exit on the 
Exit CRF. In addition, study sites shall follow the regulations set forth by the IRB. Reason for 
exit must be documented. 
9.20.5 
Investigator Withdraws Subject 
No subjects should be withdrawn by investigators unless compelling medical justification is 
present. It is recommended investigators discuss any withdrawals with the study team prior to 
withdrawing subjects. If an Investigator Withdrawal is necessary, the reason for withdrawal must 
be documented. 

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10.0 Risks and Benefits 
10.1 
Potential Risks 
The potential risks associated with the investigational TMVR procedure are similar to the risks 
of cardiac surgery and mitral valve replacement. These risks may include, but are not limited to, 
the following risks: 
• 
Death 
• 
Cardiac damage or perforation, cardiac tamponade or pericardial effusion 
• 
Coronary artery perforation, spasm, occlusion or obstruction 
• 
Heart rhythm disturbances (e.g., atrial fibrillation, cardiac arrest) 
• 
Conduction system disturbances (e.g., atrioventricular node block, left-bundle branch 
block, asystole), which may require a permanent pacemaker 
• 
Aortic valve dysfunction (e.g., regurgitation or stenosis) 
• 
Myocardial infarction, ischemia or angina 
• 
Reduced cardiac function or continuing or worsening heart failure 
• 
Stroke or transient ischemic attack (TIA) 
• 
Encephalopathy / neurological deficit 
• 
Renal insufficiency or failure (possibly requiring dialysis) 
• 
Pulmonary complications (e.g., pulmonary congestion, hypertension, 
thromboembolism, dyspnea, respiratory failure, atelectasis, pneumonia) 
• 
Surgical incision site complications (e.g., infection, inflammation, bleeding, 
hemothorax, hematoma, pain, irreversible nerve injury, wound dehiscence) 
• 
Bleeding (possibly requiring a transfusion or other intervention) 
• 
Emboli (air, thrombus) 
• 
Infection (e.g., at incision sites, endocarditis, septicemia) 
• 
Viral infection including Bovine Spongiform Encephalopathy (BSE) 
• 
Blood abnormality (e.g., coagulopathy, hemolysis, anemia) 
• 
Allergic or drug reaction (e.g., to anesthetic, contrast, Heparin, protamine, nickel 
alloy, latex) 
• 
Esophageal complications due to transesophageal echocardiography (e.g., irritation, 
perforation, stricture) 
• 
Tracheal complications due to intubation (e.g., irritation, perforation, dysphagia) 

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• 
Vascular access site complications (e.g., trauma, dissection, perforation, infection, 
inflammation, pain, bleeding, hematoma, pseudoaneurysm, irreversible nerve injury, 
compartment syndrome, arteriovenous fistula, stenosis) 
• 
Aortic complications (for example, trauma, dissection, perforation, tears, aneurysm, 
pseudoaneurysm, or occlusion) 
• 
Other systemic effects or symptoms (e.g., abnormal lab values, electrolyte imbalance, 
fever, hyperthermia, hypotension, hypertension, syncope, nausea, vomiting, edema, 
deep vein thrombosis, pleural effusion, lymphatic complications, urinary tract 
infection, multi-system organ failure, gastrointestinal bleeding, ischemia or infarction) 
• 
Valve implant dysfunction (e.g., fracture, bending, under-expansion, suture breaks, 
calcification, pannus, thrombus, inflammation, stenosis, leaflet wear, tear, prolapse, 
retraction, poor valve coaptation, leaks, regurgitation, mal-sizing [prosthesis-patient 
mismatch]) 
The risks of the investigational TMVR procedure are similar to the surgical risks listed above; 
however, some may be increased with the TMVR procedure or implant. For example, the risks of 
cardiac damage may be increased by the TMVR delivery procedure, and the risk of valve 
implant dysfunction (as compared to surgical replacement valves) has not yet been established. 
In addition to the risks listed above, the potential risks associated with the TMVR procedure and 
the Intrepid TMVR System may include, but are not limited to, the following risks: 
• 
Valve implant detachment, migration, malposition, and/or incorrect sizing 
• 
Injury to mitral valve apparatus complicating or preventing later surgical 
repair/replacement 
• 
Left ventricular outflow tract (LVOT) obstruction 
• 
Emergent surgical or transcatheter intervention (for example, coronary artery bypass, 
heart valve replacement or repair, transcatheter valve explant, percutaneous coronary 
intervention [PCI], balloon valvuloplasty, transcatheter valve or component retrieval) 
• 
Failure to deliver the bioprosthesis to the intended site 
• 
Failure to retrieve the system components 
• 
Delivery system component embolization 
• 
Delivery system thrombosis 
• 
Prolonged cardiopulmonary bypass 
• 
Prolonged ventilation, anesthesia, and/or procedure time 
• 
Radiation skin burn or tissue reaction 
• 
ASD with or without intervention 
• 
Deep venous thrombus (DVT) 

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• 
Dislodgement of previously implanted devices (e.g., Dislodgement of lead in patient 
with pre- existing permanent pacemaker, CRT-P, CRT-D or implantable defibrillator 
(ICD)) 
• 
Edema 
• 
Gastrointestinal bleeding or infarction 
• 
Hypotension/hypertension 
• 
Lymphatic complications 
• 
Mesenteric ischemia 
• 
Mitral stenosis 
• 
Multisystem organ failure 
• 
Nausea/vomiting 
• 
Peripheral ischemia 
• 
Respiratory failure/atelectasis/pneumonia 
• 
Urinary tract infection 
• 
Vessel spasm 
• 
Worsening heart failure 
The likelihood of these risks is unknown, as this is the initial introduction of the investigational 
TMVR system into a human population. However, bench-top testing and animal studies have 
demonstrated that the TMVR procedure can safely and reliably result in stable positioning of The 
Intrepid TMVR implant and the desired improvement in hemodynamic performance. 
There may be other, as yet unknown, complications that may occur as a result of this procedure. 
If these or any of the above complications occur, they may lead to repeat or prolonged 
hospitalization, repeat procedures, emergency surgery, other emergency procedures, or in rare 
cases, death. The study doctor and/or his research staff will make every effort to minimize 
additional risks. 
10.2 
Risk Minimization 
The potential risks associated with the Intrepid™ TMVR System were identified and have been 
mitigated to the extent possible. Any potential risks associated with this study are further 
minimized by selecting qualified investigators and training study personnel on the CIP. 
Medtronic has also attempted to minimize risk to subjects implementing a DMC to review safety 
issues as part of the study. 
In addition, investigators will be actively involved in the implantation and follow-up of the 
subjects implanted with the Intrepid™ TMVR Systems. 

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Risks will be minimized by careful assessment of each subject prior to, during, and after implant 
of the Intrepid™ TMVR valve. Prior to implant, it is recommended subjects undergo a complete 
physical evaluation. 
Medtronic has further minimized the possibility of risks by performing required laboratory and 
pre- clinical testing prior to this early feasibility study, implementing quality control measures 
into production processes, providing guidelines for subject selection and evaluation, and 
providing adequate instructions and labeling. 
After implantation, subjects in this early feasibility study will be followed at regular intervals to 
monitor the condition of the implanted system. At each protocol required follow-up, the 
investigator must evaluate the Intrepid™ TMVR valve via TTE to verify appropriate valve 
function and to assess any adverse events. 
10.3 
Potential Benefits 
Subjects who are eligible for this study suffer from moderate-severe or severe, symptomatic 
mitral regurgitation that requires definitive treatment. A participant may benefit from 
replacement of the mitral valve for treatment of mitral regurgitation. The potential benefits may 
include a reduction of mitral regurgitation and the possible health improvements and/or symptom 
relief associated with that reduction in mitral regurgitation. 
There may be no direct benefit associated to participation in this trial, but the information 
obtained during this trial will be used scientifically to help physicians understand the 
implications of transcatheter treatment of the patient’s mitral regurgitation. 
10.4 
Risk-Benefit Rationale 
This early feasibility study will enroll only patients with moderate-severe or severe, symptomatic 
mitral regurgitation, who are ineligible for conventional mitral valve surgery. These patients, 
nevertheless, require treatment. This less invasive TMVR procedure may provide an alternative 
mitral valve replacement for patients for whom conventional surgery is not an option. 
Transfemoral transseptal access may also mitigate procedural complications compared to 
transapical access from the TMVR procedure. 
The human clinical experience, to date, has demonstrated successful implantation of the Intrepid 
TMVR system, proper TMVR function, and elimination of mitral regurgitation, warranting 
continued study in additional patients, as proposed in this study. The potential benefit of a less 
invasive transseptal procedure to reduce their mitral regurgitation is considered to outweigh the 
risks from a MVR surgical procedure or a transcatheter valve replacement via transapical 
approach. 
The investigational plan is specifically designed to manage and minimize risks through careful 
patient selection, thorough training of investigators, adherence to the pre-determined time points 
to assess subject clinical status and regular clinical monitoring visits by Sponsor appointed 
monitoring personnel. 
Study subjects will be exposed to the procedural and device risks associated with TMVR, as well 
as the study specific risks listed in Section 10.1. However, evidence from the scientific literature 

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indicates subjects with moderate-to-severe or severe mitral regurgitation who do not receive 
therapy are exposed to the serious risks associated with their disease including worsening heart 
failure, irreversible ventricular functional impairment, and death. 
While the Intrepid TMVR System is a novel device, based on the results of the Pilot Study and 
the benefits observed by relieving mitral regurgitation in other transcatheter mitral valve repair 
and replacement trials, it is expected that these benefits will be conferred to the study subjects in 
the Mitral Early Feasibility Study, and that the benefit of mitral regurgitation reduction will 
outweigh the risks of intervention. 
In addition, an independent DMC will monitor safety of the subjects throughout the trial. 
Therefore, the risk/benefit ratio for the study is justified. 
10.5 
Risk Determination 
The devices used in this study are considered significant risk per 21 CFR 812. 
 
 

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11.0 Adverse Events and Device Deficiencies 
11.1 
Adverse Events 
Adverse Event (AE) definitions are provided in Section 11.4, Table 11-1. All subject AE 
information will be collected throughout the study duration, starting at the time of enrollment. 
Reporting of these events to Medtronic will occur on an AE Form. Each event must be reported 
separately. Documented pre-existing conditions are not considered AEs unless the nature or 
severity of the condition has worsened. 
For AEs that require immediate reporting (see Section 11.5, Table 11-3), initial reporting may be 
done on the CRF by completing as much information as possible. The completed AE CRF must 
be submitted to Medtronic as soon as possible. 
Any medication/treatment associated with the treatment of an AE must be reported. Subject 
deaths are also required to be reported. 
11.2 
Device Deficiency 
Device deficiency information will be collected throughout the trial and reported to Medtronic. 
Device deficiencies that led to an AE are reported on the AE CRF. Device deficiencies that did 
not lead to an AE are to be reported on a Device Deficiency CRF (one for each device 
deficiency). 
Device deficiencies will be assessed for SADE potential. Device deficiencies that did not lead to 
an adverse event but might have led to a SADE if: 
• 
a suitable action had not been taken, or 
• 
an intervention had not been made, or 
• 
circumstances had been less fortunate, 
Device deficiencies are to be reported to Medtronic as soon as possible, but no later than three 
(3) working days after the investigator first learns of the event. 
11.3 
Processing Updates and Resolution 
For any changes in status of a previously reported adverse event or DD (i.e. change in actions 
taken, change in outcome, change in relatedness), information needs to be updated on, or added 
to the original AE or DD form. All AEs must be followed until the AE has been resolved, is 
unresolved with no further actions planned, the subject dies or exits the study, or until study 
closure, whichever occurs first. 
At the time of study exit, all collected adverse events that are unresolved must be reviewed and 
an update to the original AE must be reported. 

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11.4 
Definitions/Classifications 
The definitions to be applied for the purposes of reporting adverse events are provided in Table 
11-1. 
Table 11-1: Adverse Event and Device Deficiency Definitions and Reporting 
Requirements 
Event Type 
Definition 
Adverse Event (AE) 
(ISO14155:2020 3.2) 
Any untoward medical occurrence, unintended disease or injury, or untoward 
clinical signs (including abnormal laboratory findings) in subjects, users or other 
parties, whether or 
not related to the investigational medical device and whether anticipated or 
unanticipated. 
This definition includes events related to the investigational medical device or the 
comparator. 
NOTE: This definition includes events related to the procedures involved. 
For users or other persons, this definition is restricted to events related to 
investigational medical devices or comparators. 
Serious Adverse Event 
(SAE) (ISO14155:2020 
3.45) 
Adverse event that led to any of the following: 
• death, 
• serious deterioration in the health of the subject, users or other persons as defined 
by one or more of the following: 
1. 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 or prolonged 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, 
• foetal distress, foetal death or a congenital abnormality or birth defect including 
physical or mental impairment 
NOTE: Planned hospitalization for a pre-existing condition, or a procedure required 
by the CIP, without serious deterioration in health, is not considered a serious 
adverse event. 
*The interpretation of Seriousness will exclude certain interventions considered 
standard of care during hospitalization (e.g., IV hydration, certain medications 
delivered intravenously due to available intravenous access or NPO (nothing by 
mouth) status, and the delivery of electrolytes to maintain electrolyte balance or to 
address mild electrolyte depletion). Any non-oral medication or fluid delivery used 
to treat an acute physical decompensation/deterioration episode or to otherwise 
resuscitate a subject will be considered serious by definition in that it prevents a 
permanent impairment of a body structure or deterioration of the health of a 
subject. 

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Table 11-1: Adverse Event and Device Deficiency Definitions and Reporting 
Requirements 
Event Type 
Definition 
Adverse Device Effect 
(ADE) (ISO14155:2020 3.1) 
Adverse event related to the use of an investigational medical device. 
Note: This definition includes adverse events resulting from insufficient or 
inadequate instructions for use, deployment, implantation, installation, or operation 
or any malfunction of the investigational medical device. 
Note: this definition includes any event resulting from use error or from intentional 
misuse of the investigation medical device. 
Note: this includes ‘comparator’ if the comparator is a medical device. 
Serious Adverse Device 
Effect (SADE) 
(ISO14155:2020 3.44) 
Adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event. 
Unanticipated Adverse 
Device Effect 
(UADE) 
(21 CFR 812.3) 
Any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), 
or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. 
Unanticipated Serious 
Adverse Device Effect 
(USADE) (ISO14155:2020 
3.51) 
Serious adverse device effect (SADE) which by its nature, incidence, severity or 
outcome has not been identified in the current risk assessment.P 
Note: Anticipated serious adverse device effect (ASADE) is an effect which by its 
nature, incidence, severity or outcome has been identified in the risk assessment. 
Device Deficiency 
(ISO 14155 :2020 
3.19) 
Inadequacy of a medical device with respect to its identity, quality, 
durability, reliability, usability, safety or performance. 
 
Note: Includes malfunctions, user errors, and inadequacy in the information 
supplied by the manufacturer including labelling. 
Note: This definition includes device deficiencies related to the investigational 
medical device or the comparator 
Serious Health 
Threat (ISO 
14155:2020 3.46) 
A signal from any adverse event or device deficiency that indicates an imminent 
risk of death or a serious deterioration in the health in subjects, users or other 
persons, and that requires prompt remedial action for other subjects, users or other 
persons. 
Note: 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 
 
 
Unavoidable events are conditions which do not fulfill the definition of an Adverse Event, such 
as those medical occurrences, clinical signs (including abnormal laboratory findings), diseases or 
injuries that are not untoward in nature, specifically, those resulting from the intended injury 
such as the index procedure. The events listed in Table 11-2 are expected for patients undergoing 
the Index Procedure, and do not need to be reported as an AE unless they occur outside of the 
stated timeframe, are otherwise considered to be an AE according to the treating investigator or 
are suspected or confirmed to be device-related. 

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Table 11-2: Non-Reportable Medical Occurrences Associated with the Index Procedure 
Event 
Timeframe (hours) from 
the Index Procedure 
Short transient episode of arrhythmias or conduction disturbances (including 
ventricular fibrillation) during index procedure 
0 
Confusion, anxiety and/or disorientation (other than TIA/stroke) starting within 48 
hours with or without medical intervention 
120 (5 days) 
Temporary change in mental status (other than TIA/stroke) not requiring additional 
medical interventions or new medical assessments (eg, CT) 
72 
Dizziness and/or lightheadedness with or without treatment 
24 
Headache with or without treatment 
72 
Sleep problems or insomnia with or without treatment 
120 (5 days) 
Mild dyspnea or cough with or without treatment 
72 
Oxygen supply after extubation / “forced breathing therapy” 
48 
Diarrhea with or without treatment 
48 
Obstipation / Constipation with or without treatment 
72 
Anesthesia-related nausea and/or vomiting with or without treatment 
24 
Low-grade fever (<101.3°F or <38.5°C) without confirmed infection 
48 
Low body temperature 
6 
Pain (eg, back, shoulder) related to laying on the procedure table with or without 
treatment 
72 
Incisional pain (pain at access site) with or without standard treatment and patient not 
returning to clinic to have additional treatment 
No time limit 
Pain in throat and/or trachea due to intubation 
72 
Stress hyperglycemia 
72 
Mild to moderate bruising or ecchymosis 
168 (7 days) 
Atelectasis / Pleural Effusion not requiring punctuation 
168 (7 days) 
Edema resulting in weight increase up to 4 kg / 9lbs from baseline 
68 (7 days) 
 
 
11.5 
Reporting of Adverse Events 
Adverse events and device deficiencies that occur during this trial are required to be reported to 
Medtronic via the AE or Device Deficiency CRF, as soon as possible after the event occurs, but 
no later than the timeframes listed in Table 11-3 or local requirements, whichever is more 
stringent. 

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Investigators are obligated to report adverse events in accordance with the requirements of their 
reviewing IRB and local regulations. 
The Sponsor is obligated to report adverse events and device deficiencies that occur during this 
trial to the Regulatory Authorities and IRB/EC as per local requirements. 
Table 11-3: Adverse Event Reporting Timelines [Investigator to Sponsor] 
Event Type 
Timeframe for Reporting 
Adverse Event (AE) 
Recommended within 10 working days of the investigator’s / site’s 
first 
knowledge of the event 
Serious Adverse Event (SAE) 
Immediately, but no later than three (3) working days of the 
investigator’s / site’s first knowledge of the event 
Adverse Device Effect (ADE) or Device 
Related Adverse Event 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
Serious Adverse Device Effect (SADE) 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
Unanticipated Adverse Device Effect 
(UADE) 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
Unanticipated Serious Adverse Device 
Effect (USADE) 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
Device Deficiency 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
Device Deficiency that might have led to a 
SADE 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
Mandatory Problem Reporting Incident 
(Canada ONLY) 
Immediately, but no later than three (3) working days of the 
investigator’s 
/ site’s first knowledge of the event 
 
 
11.5.1 
Emergency Contact Details for Reporting SAE, SADE, U(S)ADE, 
and Device Deficiencies 
Investigators should contact their designated Medtronic representative or clinical trial monitor 
immediately if they have any questions regarding reportable AEs. Medtronic will provide sites 

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with a copy and maintain a listing of current sponsor contact details, inclusive of safety 
reporting. 
 
11.5.2 
Adverse Event and Device Deficiency Classification 
All AEs and DDs will be reviewed by a Medtronic representative. AEs will be classified 
according to the definitions provided. 
Upon receipt of AE at Medtronic, a Medtronic representative will review the AE/DD for 
completeness and accuracy and when necessary will request clarification and/or additional 
information from the Investigator. Source documents to support adjudication may be requested. 
Medtronic will utilize MedDRA for Regulatory Activities, to assign a MedDRA term for each 
AE based on the information provided by the investigator. 
Regulatory reporting of AEs and DDs will be completed according to local regulatory 
requirements. Refer to Table 11-4 for a list of required investigator and Medtronic reporting 
requirements and timeframes. It is the responsibility of both to abide by any additional AE 
reporting requirements stipulated by the IRB responsible for oversight of the study. 
For emergency contact regarding a UADE, USADE, SAE and/or SADE, contact a study 
representative 
immediately (refer to the study contact list provided in the study site’s study documents binder). 
AEs and Deaths will be classified according to the standard definitions as outlined below: 
Table 11-4: Adverse Event Classification Responsibilities 
What is classified? 
Who classifies? 
Classification Parameters 
Relatedness 
Investigator 
Classifying causal relationships between the event and the 
Intrepid™ TMVR bioprosthesis (TMVR), delivery catheter 
system (DCS), Loading System, and the TMVR procedure. 
Sponsor 
Classifying causal relationships between the event and the 
Intrepid™ TMVR bioprosthesis (TMVR), delivery catheter 
system (DCS), Loading System and the TMVR procedure. 
Seriousness 
Investigator 
SAE, DD with SADE potential 
Sponsor 
SAE, UADE/USADE (for all system or procedure related 
adverse events), DD with SADE potential 
Diagnosis 
Investigator 
Based on presenting signs and symptoms and other 
supporting data 
Sponsor 
MedDRA term assigned based on the data provided by 
Investigator 
 

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11.5.3 
Adverse Event and Device Deficiency Reporting Requirements  
Regulatory reporting of AEs and DDs will be recorded and reported according to local regulatory 
requirements. It is the responsibility of the Investigator and the sponsor to abide by the AE 
reporting requirements stipulated by local law and the study site’s IRB. Refer to section 15.8.1 
and section 15.8.2 for reporting requirement. 
11.6 
Subject Death 
All subject deaths must be reported by the investigator to Medtronic on an AE form (AE with 
outcome of death) as soon as possible after the investigator first learns of the death. In case of 
death, there should be one AE with the outcome of death. 
In the event of a subject’s death, it is recommended that the implanted system be explanted and 
returned to Medtronic for analysis whenever possible per local process. Local laws and 
procedures must be followed where applicable. If any system component is returned to 
Medtronic, internal return product reporting systems may be used to gather additional 
information about the returned device/component. 
A copy of the death certificate, if available and allowed by state/local law, should be sent to the 
Medtronic clinical study team. When a death occurs in a hospital, a copy of the death summary 
report and all relevant hospital records, if available should be sent to the Medtronic clinical study 
team. If an autopsy is conducted, a copy of the autopsy report should also be sent to the 
Medtronic clinical study team if available and allowed by state/local law. When the death occurs 
at a remote study site, it is the investigative study site’s responsibility to attempt retrieval of 
information about the death. Additionally, device disposition information should be updated. 
In summary, the following data will be collected: 
• 
Date of death 
• 
Detailed description of death 
• 
Cause of death 
• 
Relatedness to system and/or procedure 
• 
Device disposition information 
• 
Death summary/hospital records (if available and allowed by state/local law) 
• 
Autopsy report (if available and allowed by state/local law) 
• 
Death certificate (if available and allowed by state/local law) 
11.6.1 
Death Classification and Reporting 
Sufficient information will be required in order to properly classify the subject’s death. 
For all deaths, investigators must assess and document the following information on the Study 
Exit CRF. 
 

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• 
Date of death 
• 
Primary death category 
Table 11-5: Subject Death Classification Responsibilities 
What is classified? 
Who classifies? 
Classification Parameters 
Relatedness 
Investigator 
Classifying causal relationships between the event and the 
Intrepid™ TMVR bioprosthesis (TMVR), delivery catheter 
system (DCS), loading system, and the TMVR procedure. 
Death Classification 
Investigator 
Sudden Cardiac, Non-sudden Cardiac, Non-cardiac, Unknown 
 
 
The CEC will review deaths and provide a final adjudication of the primary cause of death and 
classification of death. 
Regulatory reporting of Subject Deaths will be completed according to local regulatory 
requirements. 
 
 

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12.0 Data Review Committees 
 
12.1 
Clinical Events Committee Review 
An independent Clinical Events Committee (CEC) will review and adjudicate, at a minimum, all 
deaths and primary endpoint related adverse events. The CEC will consist of, at a minimum: an 
interventional cardiologist, a cardiothoracic surgeon, an echocardiologist and a heart failure 
specialist who are not participants in the trial. Additional specialists, such as neurologists, may 
also be selected as part of the CEC. 
The purpose of the CEC is to conduct a medical review and classify/adjudicate, at a minimum, 
all deaths and/or clinical endpoints collected in the trial according to definitions and processes 
outlined in the trial protocol and the CEC charter, which will be developed and approved by 
Medtronic and the CEC members.  Safety endpoint results will be based on CEC adjudication. 
All applicable events will be reviewed and adjudicated by a minimum of three CEC members. 
All other events will be reviewed and assessed by qualified internal Medtronic safety 
individual(s) to ensure that adjudication by the CEC is not required and that the events are 
appropriately classified by the investigator. 
Prior to event adjudication, the CEC will draft a charter, in collaboration with Medtronic, to 
establish explicit rules outlining the minimum amount of data required and the algorithm 
followed in order to classify/adjudicate a trial endpoint related clinical event. CEC decisions will 
be documented in meeting minutes, which will be maintained in the trial master file and 
adjudication results will be recorded in the trial database. 
12.2 
CRO/Core Lab(s) 
This information may be subject to change during the course of the study. Periodic updates to 
study contact information will be sent to study sites as needed. 
Table 12-1: CRO and Core Laboratory Information 
Contact Information 
Role 
Baim Institute for Clinical Research 
930 Commonwealth Ave 
3rd Floor 
Boston, MA 02215 
Clinical Events Committee (CEC) / Data Safety 
Monitoring Committee (DSMB) 
Mayo Clinic Core Laboratory 
200 First Street SW 
Rochester, MN 55905e.g. Echocardiography Core 
Laboratory 
Echocardiography Core Laboratory 
CVPath Institute, Inc. 
19 Firstfield Road 
Gaithersburg, MD 20878 
Explanted Device/Pathology Core Laboratory 

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Table 12-1: CRO and Core Laboratory Information 
Contact Information 
Role 
Medidata Solutions, Inc. 
350 Hudson Street 
9th Floor 
New York, NY 10014 
Medidata Solutions, Inc. (imaging sharing network) 
 
 
12.3 
Data Monitoring Committee 
An independent, unblinded Data Monitoring Committee (DMC) also referred to as a Data Safety 
Monitoring Board (DSMB) will be established and will be comprised of at least 4 members with 
one biostatistician and 3 physicians, including a chairperson. The DMC/DSMB will have a 
minimum of one cardiac surgeon, one interventional cardiologist and one statistician, and will be 
independent of Medtronic and the trial investigators. Investigators participating in the trial may 
participate in the meetings to offer clarification surrounding events but will not have voting 
privileges nor will Investigators be permitted to participate in closed sessions. Medtronic 
personnel may facilitate the DMC/DSMB meeting but will not have voting privileges nor attend 
closed sessions. 
A DMC/DSMB charter will be developed and approved by Medtronic and the DMC/DSMB 
members. The committee will outline the criteria for both the full DMC/DSMB meeting and 
supplemental DMC/DSMB reviews within the DMC/DSMB charter. 
The DMC/DSMB will meet on a periodic basis to perform a comprehensive data review and will 
also perform a supplemental review of, at a minimum, all serious adverse events and deaths and 
any other data requested by the DMC/DSMB to ensure patient safety. DMC/DSMB members 
will provide recommendations about the conduct of the study (e.g., continuing the trial without 
modifications, continuing the trial with modifications, stopping the enrollment in the trial or a 
specific trial arm, or recommendations about trial conduct including recommendations around 
enrollment or protocol deviations). 
In the case of UADEs or USADEs, if Medtronic and the DMC/DSMB determine that the event 
presents an unreasonable risk to the participating subjects, Medtronic must terminate the clinical 
trial within 5 working days after making that determination and not later than 15 working days 
after Medtronic first receives notice of the effect [21 CFR 812.46]. All clinical sites will be 
notified of this action. 
Additional details about the DMC/DSMB are outlined in the DMC/DSMB charter. 
 
 

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13.0 Statistical Design and Methods  
The objectives of this prospective, non-randomized Early Feasibility Study are to evaluate 
the safety and performance of The Intrepid™ TMVR System.  A comprehensive analysis of 
the feasibility study results, as a whole, will be assessed to evaluate the overall risk/benefit 
balance for the patient population being treated.  In addition, the following endpoints will 
be assessed and reported: 
Primary safety endpoint: 
Implant, delivery or device related serious adverse events (through 30 days post-procedure) 
Secondary performance endpoints: 
• 
Successful access, delivery of implant, and retrieval of the delivery system  
• 
Reduction in MR Grade from baseline (measured by echo through 30 days post-
procedure) 
• 
No significant MV stenosis (measured by echo through 30 days post-procedure) 
• 
LV outflow tract (LVOT) patency (measured by echo through 30 days post-
procedure) 
• 
Change in NYHA Class from baseline (through 30 days post-procedure) 
Additional exploratory endpoints: 
• 
Measured by echocardiography post-procedure through 5 years: 
− Reduction in MR Grade from baseline 
− No significant MV stenosis 
− LV outflow tract (LVOT) patency 
− Improvement in LVEF 
− Improvement in cardiac output/cardiac index 
− Reduction in LV end-systolic and end-diastolic dimensions 
• 
Presence of intra-atrial shunt with clinically significant pressure gradient requiring 
closure device 
• 
Change in NYHA Class from baseline through 5 years 
• 
Change in 6MWT from baseline through 5 years 
• 
Change in QoL from baseline through 5 years 
• 
Procedural times (e.g., deployment time, access duration, rapid pacing duration) 
• 
Re-hospitalizations for heart failure 

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• 
MVARC defined outcomes of: 
− Technical success upon exit from operating room 
− Device success at 30 days and 1 year 
− Procedural success at 30 days 
− Individual subject success at 1 year 
Event and endpoint definitions for this study’s analysis will be based on those definitions 
outlined in the MVARC Consensus (9). Each subject’s data will be reviewed individually and 
event summaries for all subjects will be provided to FDA. The data analysis will include all 
subjects who undergo the TMVR procedure and all available follow-up data (e.g., key 
echocardiographic measures and clinical status) at each post-procedure interval. 
Mitral regurgitation will be classified according to the Recommendations for Noninvasive 
Evaluation of Native Valvular Regurgitation: A report from the American Society of 
Echocardiography developed in Collaboration with the Society of Cardiovascular Magnetic 
Resonance; JASE, 2017 as outlined in Appendix 17.1:Definition of Terms & Causal 
Relationships. 
The sample size is based upon industry standards for early feasibility stage studies of medical 
devices; the sample size was not statistically derived, as this is not a hypothesis-testing study. 
13.1 
General Aspects of Analysis 
The analysis sets used for each objective are defined in the Statistical Analysis Plan. Study 
results will be summarized using standard descriptive statistics. Pre-defined statistical “success” 
or “pass” criteria for the study endpoints are not applicable for this feasibility study, as it is not a 
powered, hypothesis driven study.  Baseline demographic and clinical variables will be 
summarized. Continuous variables will be summarized with means, standard deviations, 
medians, interquartile ranges, minimums, and maximums.  Categorical variables will be 
summarized with frequencies and percentages. 
For each of the objectives the available data will be summarized. Number of subjects with 
available data will be presented so that the impact of missing data can be evaluated. The main 
analysis of the study objectives will be based on available data and missing data will not be 
imputed. 
 
 

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14.0 Ethics 
14.1 
Statement(s) of Compliance 
This trial will be conducted in compliance with the Declaration of Helsinki, the International 
Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines, the study 
protocol, the Sponsor’s standard operating procedures and/or guidelines, and in accordance to 
federal, national and local laws, regulations, standards and requirements of the 
countries/geographies in which the study is being conducted. These include but are not limited to 
the following: 
In the United States, the study will be conducted under a Food and Drug Administration (FDA) 
Investigational Device Exemption (IDE) in compliance with FDA Code of Federal Regulations 
(CFR): 
• 
21 CFR Part 11: Electronic Records, Electronic Signatures 
• 
21 CFR Part 50: Protection of Human Subjects 
• 
21 CFR Part 54: Financial Disclosure by Clinical Investigators 
• 
21 CFR Part 56: Institutional Review Boards 
• 
21 CFR Part 812: Investigational Device Exemptions 
• 
The latest version of ISO 14155 
This study will be publicly registered prior to first enrollment in accordance with the 2007 Food 
and Drug Administration Amendments Act (FDAAA) and Declaration of Helsinki on 
41T41TUUhttp://clinicaltrials.govUU41T41T (PL110-85, Section 810(a)). 
14.1.1 
ISO14155:2020 Deviations 
The Mitral Early Feasibility Study design includes three deviations from ISO14155:2020. The 
first is the time of enrollment which is defined as the date the clinical site indicated “enrolled” 
within Oracle Clinical, following Screening Committee approval, as opposed to the date of 
consent. Given the expected high screen failure rate this was done to reduce the burden of 
unnecessary assessments on subjects and reduce the burden of adverse event reporting by sites 
that would not be utilized in analyses. The second deviation is due to the fact that the study is an 
early feasibility study and therefore does not have statistically powered endpoints due to the 
purpose of the study. The third deviation from ISO is due to no non-subject AEs collected for 
this study, as these are not of interest in this study. 
 

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15.0 Study Administration  
15.1 
Monitoring 
It is the responsibility of Medtronic to ensure proper monitoring of this study. Trained Medtronic 
personnel or delegates appointed by Medtronic may perform study monitoring at the study site in 
order to ensure that the study is conducted in accordance with the CIP, the CTA, and the 
applicable regulatory and local requirements. Medtronic, or delegates, must therefore be allowed 
direct access to the subjects’ case histories (clinic and hospital records, and other source 
data/documentation) upon request as per the ICF and CTA.  The principal investigator should 
also be available during monitoring visits. 
15.1.1 
Monitoring Visits 
Frequency of monitoring visits may be based upon subject enrollment, study compliance, 
number of adverse events, number of deviations, observations from previous monitoring visits 
and any suspected inconsistency in data that requires investigation. Regulatory documents may 
be reviewed at each study site. Monitoring for the study, including site initiation visits, interim 
monitoring visits, and closeout visits, will be done in accordance to the study-specific monitoring 
plan. 
The investigational site will be monitored to assess study site progress (per the monitoring plan), 
ensure compliance with the trial protocol, adherence to applicable regulations, and accuracy of 
trial data. 
Monitoring visits will be conducted primarily to ensure the rights, safety and wellbeing of the 
subjects is preserved. Monitoring visits will also be used to verify that trial data submitted on 
case report forms (CRF) are complete and accurate with respect to the subject records and to 
verify device accountability. 
The Investigator(s), their delegate(s) and the study coordinator(s) shall be accessible during 
monitoring visits. Accessibility is of particular importance for reviewing data in the CRF. 
Site personnel will complete CRFs following each subject visit. Trial data submitted will be 
reviewed against patient charts and other sources containing original records of patient data. 
Source document verification will be conducted via a risk-based approach as outlined in the 
Monitoring Plan. 
The progress of the trial will be monitored according to the Monitoring Plan by: 
• 
On-site/Remote review, as deemed appropriate by the sponsor 
• 
Centralized review, as deemed appropriate by the sponsor 
• 
Essential communications between the site personnel (e.g., Investigator, Trial 
Coordinator) and trial monitors 
• 
Review of CRFs and the associated clinical records 
• 
Review of regulatory documents 

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• 
Review of Subject Informed Consent(s) 
• 
Review of Device Accountability Logs 
• 
Review of equipment maintenance and calibration documentation 
Upon study completion Site Closeout Visits will be conducted, as outlined in the Monitoring 
Plan. 
Monitoring and monitoring oversight will be provided by Medtronic, Inc. Representatives of the 
study sponsor (e.g., contractors and designees) may also act as the trial monitors to the site. 
Medtronic will maintain an updated list of applicable representatives and provide a copy to sites 
upon request. 
Prior to the first site activation a monitoring plan will be established outlining the above 
activities, as well as study materials to be supplied to sites, the process for corrective and 
preventive actions, and Investigator disqualification procedures. All monitoring activities shall 
be documented per the monitoring plan. 
15.2 
Data Management 
Data will be collected using an electronic data management system for studies.  CRF data will be 
stored in a secure, password-protected database which will be backed up nightly. Data will be 
reviewed using programmed and manual data checks. Data queries will be made available to 
study sites for resolution. Study management reports may be generated to monitor data quality 
and study progress. At the end of the study, the data will be frozen and will be retained by 
Medtronic in accordance with applicable regulations. 
All records and other information about subjects participating in this study will be treated as 
confidential. Data will be transferred and processed by Medtronic or a third party designated by 
Medtronic in a key coded form, unless it’s impossible to pseudonymize for instance, where the 
subject’s name cannot be removed from the data carrier, such as Echocardiogram images. The 
investigational study site team will upload images (e.g., Echocardiogram, ECG, CT) to Medidata 
Solutions as source data to be retrieved by the imaging core lab for review. Procedures in the CIP 
require source documentation. Source documentation will be maintained at the study site. Source 
documents, which may include worksheets and subject medical records must be created and 
maintained by the investigational study site team. 
The investigator will clearly mark clinical records to indicate that the subject is enrolled in this 
clinical investigation. 
The data reported on the CRFs shall be derived from source documents and be consistent with 
these source documents, and any discrepancies shall be explained in writing. 
15.3 
Direct Access to Source Data/Documents 
The investigator and/or institution shall permit Medtronic, IRBs and regulatory bodies direct 
access to source data and documents during monitoring, audits and regulatory inspections. 

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15.4 
Audits 
Medtronic may conduct audits at participating study sites. The purpose of an audit is to verify the 
performance of the monitoring process and the study conduct, independently of the personnel 
directly involved in the study. Regulatory bodies such as the FDA, may also perform inspections 
at participating study sites. 
15.5 
Confidentiality 
All information and data sent to parties involved in study conduct concerning subjects or their 
participation in this study will be considered confidential. Study sites will assign a unique subject 
number to each subject. Records of the subject/subject number relationship will be maintained by 
the study site. The subject number is to be recorded on all study documents to link them to the 
subject’s medical records at the study site. Confidentiality of data will be observed by all parties 
involved at all times throughout the clinical investigation. All data shall be secured against 
unauthorized access. The privacy of each subject and confidentiality of his/her information shall 
be preserved in reports and when publishing any data. In the US, “Protected Health Information” 
(PHI) will be maintained in compliance with the HIPAA of 1996. To maintain confidentiality, 
the subject’s name or any other PHI should not be recorded on any study document other than 
the ICF. This scenario will be covered in the ICF. In the event a subject’s name/PHI is included 
for any reason, it will be blinded as applicable. In the event of inability to blind the identification 
(e.g., digital media), it will be handled in a confidential manner by the authorized personnel.  
Data relating to the study might be made available to third parties (for example in case of an 
audit performed by a regulatory body), provided the data are treated as confidential and that the 
subject’s privacy is guaranteed. No identifiable subject information will be published. 
15.6 
Liability/Warranty/Insurance Information 
Medtronic Inc. maintains appropriate clinical study liability insurance coverage as required under 
applicable laws and regulations and will comply with applicable law and custom concerning 
specific insurance coverage. If required, a Clinical Trial Insurance statement/certificate will be 
provided to the IRB. 
15.7 
CIP Amendments 
Revisions to the Clinical Investigation Plan will be managed per Medtronic’s standard operating 
procedures. Medtronic will submit amendments to the CIP, including a justification for the 
amendment, to all affected regulatory agencies and to the investigators to obtain approval from 
their IRB, as applicable. The investigator will only implement the amendment after approval of 
the IRB, regulatory agencies, and Medtronic. 
15.8 
Record Retention 
The investigator must retain all study-related documents for a period of at least 2 years after 
market- release in his/her region and after study closure (or longer if required by local law). 
Medtronic will inform the investigator/study site when these documents are no longer required to 
be retained. 

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No study document or image will be destroyed without prior written agreement between 
Medtronic and the investigator. The investigator should take measures to prevent accidental or 
premature destruction of documents. Should the investigator wish to assign the study records to 
another party or move them to another location, advance written notice must be given to 
Medtronic. 
Medtronic will retain the study records according to Medtronic corporate policy and record 
retention schedule. 
15.8.1 
Investigator Records 
The investigator is responsible for the preparation and retention of the records cited below. All of 
the below records, with the exception of case history records and case report forms, should be 
kept in the Investigator Site File (i.e., the study binder provided to the investigator) or Subject 
Study Binder. CRFs must be maintained and signed electronically within the electronic data 
capture system during the study. The following records are subject to inspection and must be 
retained as noted above in Section 15.8. 
• 
All essential correspondence that pertains to the investigation 
• 
Device use/disposition records 
• 
Records of each subject’s case history and exposure to the device. Case histories 
include the 
• 
CRFs and supporting data (source documentation), including, for example: 
− Signed and dated consent forms 
− Medical records, including, for example, progress notes of the physicians, the 
subject’s hospital chart(s) and the nurses’ notes 
− All adverse event/device deficiency information 
− A record of the exposure of each subject to the investigational device (e.g., 
date of implant procedure and follow-up assessment dates) 
− Documentation of any deviation from the CIP, including the date and the 
rationale for such deviation 
• 
Signed Investigator Agreement, signed and dated curriculum vitae of the PI, sub-
investigator(s) and key members, signed Delegated Task List 
• 
The approved CIP, Patient Information/Informed Consent Form, Investigator 
Brochure or Report of Prior Investigations, and any amendments 
• 
Insurance certificate, where applicable 
• 
IRB/EC Approval documentation and voting list 
• 
Regulatory authority notification and approval documentation 
• 
List of sponsor contacts and monitoring contact list 

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• 
List of investigation sites 
• 
Training records 
• 
Disclosure of conflict of interest 
• 
Lab certificate/lab normal ranges 
• 
Subject ID and enrollment log 
• 
Sponsor’s interim analyses and clinical investigation report 
The Investigator may withdraw from responsibility to maintain records by transferring custody to 
another person, who will accept responsibility for record and report maintenance. The 
Investigator is responsible for the preparation, review, signature, and submission of the reports 
listed in Table 15-1 and Table 15-2, for their respective geographies. These are also subject to 
inspection by government agencies and must be retained. Reports will be submitted to regulatory 
authorities per local reporting requirements/regulations. Requirements for reporting Adverse 
Events to Medtronic are described in Table 11-3. 
15.8.2 
Sponsor Records 
Medtronic shall maintain the following accurate, complete, and current records including but not 
limited to: 
• 
All essential correspondence which pertains to the investigation 
• 
Investigational device traceability record containing Model and serial numbers of 
devices, shipping date and name and address of person that received shipped device, 
location (if different than person shipped to), transfer and receipt by Medtronic 
dates.> 
• 
Sample of label attached to investigational device 
• 
Signed and dated clinical trial agreement for each investigation study site 
• 
Signed investigator agreements, financial disclosure and current CV of principal 
investigators 
• 
Delegated task list for each investigation study site 
• 
All approved ICF templates, and other information provided to the subjects and 
advertisements, including translations 
• 
Copies of all IRB approval letters and relevant IRB correspondence and IRB voting 
list/roster/letter of assurance 
• 
Names of the institutions in which the study will be conducted 
• 
FDA correspondence, notification and approval as required by national legislation 
• 
Names/contact addresses of monitors 
• 
Device complaint documentation 
• 
Monitoring visit reports 

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• 
Statistical analyses and underlying supporting data 
• 
Final report of the study 
• 
The CIP, Investigator Brochure/Report of Prior Investigations summary and study 
related reports, and revisions 
• 
Study training records for study site personnel and Medtronic personnel involved in 
the study 
• 
Any other records that local regulatory agencies require to be maintained. 
Medtronic records and reports will be maintained in a password-protected document 
management system, and paper documents (where applicable) will be stored in stored in secured 
file cabinets at Medtronic during the course of this study. 
After closure of the study Medtronic will archive records and reports indefinitely. 
15.9 
Reporting Requirements 
15.9.1 
Investigator Reports 
The investigator is responsible for the preparation (review and signature) and submission to the 
sponsor of all case report forms, adverse events and adverse device effects, device deficiencies, 
deaths, and any deviations from the clinical investigation plan.  If any action is taken by an IRB 
with respect to this study, copies of all pertinent documentation must be forwarded to Medtronic 
in a timely manner. Reports are subject to inspection and to the retention requirements as 
described above for investigator records. 
Safety data investigator reporting requirements are listed in Section 11.5. The investigator shall 
prepare and submit in a complete, accurate and timely manner the reports listed in this section. 
Table 15-1: Investigator Reports Applicable for all Geographies per Medtronic 
Requirements 
Report 
Submit to 
Description/Constraints 
Withdrawal of IRB approval 
(either suspension or 
termination) 
Sponsor 
An investigator shall report to the sponsor, within 5 working 
days, a withdrawal of approval by the reviewing IRB of the 
investigator's part of an investigation. (21 CFR 812.150(a)(2)). 
Progress report 
Sponsor and IRB 
The investigator must submit this report to the sponsor and 
IRB at regular intervals, but in no event less than yearly. (21 
CFR 812.150 (3)). 
Study deviations 
Sponsor and IRB 
Notice of deviations from the CIP to protect the life or 
physical well-being of a subject in an emergency shall be 
given as soon as possible, but no later than 5 working days 
after the emergency occurred. (21 CFR 812.150(a)(4)) 
Failure to obtain IC prior to 
investigational device use 
Sponsor and 
IRBs 
If an investigator uses a device without obtaining informed 
consent, the investigator shall report such use within 5 
working days after device use. (21 CFR 812.150(a)(5)) 

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Table 15-1: Investigator Reports Applicable for all Geographies per Medtronic 
Requirements 
Report 
Submit to 
Description/Constraints 
Final investigator report 
Sponsor, IRB s 
and Relevant 
Authorities 
This report must be submitted within 3 months of study 
completion or termination of the investigation or the 
investigator’s part of the investigation. (21 CFR 
812.150(a)(6)) 
Other 
IRB and FDA 
An investigator shall, upon request by a reviewing IRB, FDA 
or any other regulatory agency, provide accurate, complete, 
and current information about any aspect of the investigation. 
(21 CFR 812.150(a)(7)) 
 
 
15.9.2 
Sponsor Reports 
Medtronic shall prepare and submit the following complete, accurate, and timely reports 
listed in the tables below (by geography).  In addition to the reports listed below, 
Medtronic shall, upon request of the reviewing IRB or FDA, provide accurate, complete 
and current information about any aspect of the investigation. Safety data Medtronic 
reporting requirements are listed in Table 15-2. 
Table 15-2: Sponsor Records and Reporting Responsibilities 
Report 
Submit to 
Description/Constraints 
Premature termination 
or suspension of the 
clinical investigation 
Investigators, IRB 
Relevant authorities and Head 
of the Institution 
Provide prompt notification of termination or 
suspension and reason(s). (ISO 14155:2020) 
Unanticipated Adverse 
Device Effect 
Investigators, IRB, FDA, and 
relevant authorities 
Notification within ten working days after the 
sponsor first receives notice of the effect.  (21 CFR 
812.150(b)(1)) 
Withdrawal of IRB 
approval 
Investigators, Head of 
Institution, IRB and relevant 
authorities 
Investigators, IRBs will be notified only if 
required by local laws or by the IRB 
Withdrawal of FDA 
approval 
Investigators, Head of 
Institution, IRB, and relevant 
authorities 
Notification within five working days after receipt of 
notice of the withdrawal of approval.  (21 CFR 
812.150(b)(3)) 
Investigator List 
FDA 
Submit at 6-month intervals, a current list of the 
names and addresses of all investigators 
participating in the investigation.  (21 CFR 
812.150(b)(4)) 
Progress Reports 
IRB and RAs 
Progress reports will be submitted at least annually. 
(21 CFR 812.150(b)(4)(5), 812.36(f) 

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Table 15-2: Sponsor Records and Reporting Responsibilities 
Report 
Submit to 
Description/Constraints 
Recall and device 
disposition 
Investigators, IRB, relevant 
authorities, and FDA 
Notification within 30 working days after the request 
is made and will include the reasons for any request 
that an investigator return, repair, or otherwise dispose 
of any devices.  (21 CFR 812.150(b)(6)) 
Failure to obtain 
Informed Consent 
FDA 
Investigator’s report will be submitted to FDA within 
five 
working days of notification.  (21 CFR 812.150(b)(8)) 
Final report 
Investigators, IRB, Regulatory 
authorities, and FDA 
Medtronic will notify FDA within 30 working days of 
the completion or termination of the investigation. A 
final report will be submitted to the FDA, 
investigators, and IRBs within six months after 
completion or termination of this study. (21 CFR 
812.150(b)(7)) 
Study deviation 
Investigators 
Ensure that all deviations from the CIP are reviewed 
with the appropriate clinical investigator(s), are 
reported on the CRFs and the final report of the 
clinical investigation. (ISO 14155:2020) 
Study site specific study deviations will be 
submitted to investigators periodically. 
 
 
15.10 
Publication and Use of Information 
Medtronic is committed to the widespread dissemination of all primary and secondary endpoint 
results. A Publication Plan will be implemented and followed as indicated in the CTA. 
A separate Publication Plan will provide detailed information about the publication committee, 
authorship, publication proposals, and requests for data. 
15.11 
Suspension or Early Termination 
15.11.1 Planned Study Closure 
Study Closure is a process initiated by distribution of a study closure letter. Study closure is 
defined as closure of a study that occurs when Medtronic and/or regulatory requirements have 
been satisfied per the CIP and/or by a decision by Medtronic or regulatory body), whichever 
occurs first. The study closure process is complete upon distribution of the Final Report or after 
final payments, whichever occurs last. Ongoing IRB oversight is required until the overall study 
closure process is complete. 

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15.11.2 Early Termination or Suspension 
Early Termination is the closure of a study that occurs prior to meeting defined endpoints. This is 
possible for the whole study or a single study site. Suspension is a temporary postponement of 
study activities related to enrollment and distribution of the product. This is possible for the 
whole study or a single study site. 

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16.0 References 
1. Wu S, Chai A, Arimie S et al. Incidence and treatment of severe primary mitral regurgitation 
in contemporary clinical practice. Cardiovasc Revasc Med 2018;19:960-963. 
2. Goel SS, Bajaj N, Aggarwal B et al. Prevalence and outcomes of unoperated patients with 
severe symptomatic mitral regurgitation and heart failure: comprehensive analysis to 
determine the potential role of MitraClip for this unmet need. J Am Coll Cardiol 
2014;63:185-6. 
3. Nishimura RA, Vahanian A, Eleid MF, Mack MJ. Mitral valve disease—current 
management and future challenges. The Lancet 2016;387:1324-1334. 
4. Regueiro A, Granada JF, Dagenais F, Rodes-Cabau J. Transcatheter Mitral Valve 
Replacement: Insights From Early Clinical Experience and Future Challenges. J Am Coll 
Cardiol 2017;69:2175- 2192. 
5. Goldstein D, Moskowitz AJ, Gelijns AC et al. Two-Year Outcomes of Surgical Treatment of 
Severe Ischemic Mitral Regurgitation. N Engl J Med 2016;374:344-53. 
6. Chhatriwalla AK, Vemulapalli S, Holmes DR, Jr. et al. Institutional Experience With 
Transcatheter Mitral Valve Repair and Clinical Outcomes: Insights From the TVT Registry. 
JACC Cardiovasc Interv 2019;12:1342-1352. 
7. Dvir D. Transseptal Instead of Transapical Valve Implantation. JACC: Cardiovascular 
Interventions 2016;9:1175-1177. 
8. Alkhouli M, Rihal CS, Holmes DR, Jr. Transseptal Techniques for Emerging Structural 
Heart Interventions. JACC Cardiovasc Interv 2016;9:2465-2480. 
9. Stone GW, Adams DH, Abraham WT et al. Clinical trial design principles and endpoint 
definitions for transcatheter mitral valve repair and replacement: part 2: endpoint definitions: 
A consensus document from the Mitral Valve Academic Research Consortium. Eur Heart J 
2015;36:1878-91 
10. Zoghbi et al. Recommendations for evaluation of prosthetic valves with echocardiography 
and doppler ultrasound: a report From the American Society of Echocardiography's 
Guidelines and Standards Committee and the Task Force on Prosthetic Valves, developed in 
conjunction with the American College of Cardiology Cardiovascular Imaging Committee, 
Cardiac Imaging Committee of the American Heart Association, the European Association of 
Echocardiography, a registered branch of the European Society of Cardiology, the Japanese 
Society of Echocardiography and the Canadian Society of Echocardiography, endorsed by 
the American College of Cardiology Foundation, American Heart Association, European 
Association of Echocardiography, a registered branch of the European Society of Cardiology, 
the Japanese Society of Echocardiography, and Canadian Society of Echocardiography. J Am 
Soc Echocardiogr. 2009;975-1014 
11. Zoghbi WA, Adams D, Bonow RO, Enriquez-Sarano M, Foster E, Grayburn PA, Hahn RT, 
Han Y, Hung J, Lang RM, Little SH, Shah DJ, Shernan S, Thavendiranathan P, Thomas JD, 
Weissman NJ. Recommendations for Noninvasive Evaluation of Native Valvular 

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Regurgitation: A Report from the American Society of Echocardiography Developed in 
Collaboration with the Society for Cardiovascular Magnetic Resonance. J Am Soc 
Echocardiogr. 2017 Apr;30(4):303-371. 
12. Bonow R, Carabello B, Chatterjee K, et al. 2008 Focused Update Incorporated Into the 
ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease. J 
Am Coll Cardiol. 2008 Sep, 52 (13) e1–e142. 
13. Kappetein AP, Head SJ, Généreux P, Piazza N, van Mieghem NM, Blackstone EH, Brott 
TG, Cohen DJ, Cutlip DE, van Es GA, Hahn RT, Kirtane AJ, Krucoff MW, Kodali S, Mack 
MJ, Mehran R, Rodés-Cabau J, Vranckx P, Webb JG, Windecker S, Serruys PW, Leon MB. 
Updated standardized endpoint definitions for transcatheter aortic valve implantation: the 
Valve Academic Research Consortium-2 consensus document. Eur Heart J. 2012 
Oct;33(19):2403-18. 
14. Stone GW, et al. Clinical Trial Design Principles and Endpoint Definitions for Transcatheter 
Mitral Valve repair and Replacement: Part 2: Endpoint Definitions. JACC. 2015; 66(3): 308-
321. 
15. American College of Cardiology/American Heart Association Task Force on Clinical Data 
Standards (ACC/AHA/HRS Writing Committee to Develop Data Standards on 
Electrophysiology); Buxton AE, Calkins H, Callans DJ, DiMarco JP, Fisher JD, Greene HL, 
Haines DE, Hayes DL, Heidenreich PA, Miller JM, Poppas A, Prystowsky EN, Schoenfeld 
MH, Zimetbaum PJ, Goff DC, Grover FL, Malenka DJ, Peterson ED, Radford MJ, Redberg 
RF. ACC/AHA/HRS 2006 key data elements and definitions for electrophysiological studies 
and procedures: a report of the American College of Cardiology/American Heart Association 
Task Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop 
Data Standards on Electrophysiology). Circulation. 2006 Dec 5;114(23):2534-70.  
 

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17.0 Appendices 
17.1 
Definition of Terms & Causal Relationships 
17.1.1 
ACCESS SITE AND VASCULAR COMPLICATIONS 
Access and vascular complications will be defined and classified according to the Mitral Valve 
Academic Research Consortium (MVARC); Clinical Trial Design Principles and Endpoint 
Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 
Access Site and Vascular Complications 
I. 
Vascular complications 
1. Major access site vascular complications, including: 
1. Aortic dissection or aortic rupture, or 
2. 
Access site-related† arterial or venous injury (dissection, stenosis, ischemia, arterial, or venous 
thrombosis including pulmonary emboli, perforation, rupture, arteriovenous fistula, pseudoaneurysm, 
hematoma, retroperitoneal hematoma, atrial septal defect‡), irreversible nerve injury, or compartment 
syndrome resulting in death; hemodynamic compromise; life- threatening, extensive, or major bleeding 
(MVARC bleeding scale); visceral ischemia; or neurological impairment, or 
3. 
Distal embolization (noncerebral) from a vascular source requiring surgery or resulting in amputation 
or irreversible end-organ damage, or 
4. 
Unplanned endovascular or surgical interventions resulting in death; life-threatening, extensive, or 
major bleeding (MVARC bleeding scale); visceral ischemia; or neurological impairment 
2. Minor access site vascular complications, including: 
1. 
Access site arterial or venous injury (dissection, stenosis, arterial, or venous thrombosis including 
pulmonary emboli, ischemia, perforation, rupture, arteriovenous fistula, pseudoaneurysm, hematoma, 
retroperitoneal hematoma, atrial septal defect‡) not resulting in death; life-threatening, extensive, or 
major bleeding (MVARC scale); visceral ischemia; or neurological impairment, or 
2. 
Distal embolization treated with embolectomy and/or thrombectomy not resulting in amputation or 
irreversible end-organ damage, or 
3. 
Any unplanned endovascular stenting or unplanned surgical intervention not meeting the criteria for a 
major vascular complication, or 
4. 
Vascular repair (via surgery, ultrasound-guided compression, transcatheter embolization, or stent-
II. 
Cardiac structural complications due to access-related issues 
3. Major cardiac structural complications, including: 
1. Cardiac perforation* or pseudoaneurysm resulting in death, life-threatening bleeding, hemodynamic 
compromise, or tamponade, or requiring unplanned surgical or percutaneous intervention 
4. Minor cardiac structural complications, including: 
1. Cardiac perforation* or pseudoaneurysm not meeting major criteria 
* Including the left ventricle, left atrium, coronary sinus, right atrium, and right ventricle. 
†  May arise from the access procedure per se or complications from vascular closure devices. 
‡ Meeting pre-specified criteria for a hemodynamically significant shunt, or requiring unplanned percutaneous or 
surgical closure. 
 

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17.1.2 
ACUTE KIDNEY INJURY 
Acute Kidney Injury (AKI) will be defined and classified according to the Mitral Valve 
Academic Research Consortium (MVARC); Clinical Trial Design Principles and Endpoint 
Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 
Definition and Stages of Acute Kidney Injury 
Definition 
Maximal changes in sCr from baseline to 7 days post-procedure 
Stages 
Stage 1 
Increase in sCr to 150%–199% (1.50–1.99x increase vs. baseline), increase of ≥0.3 mg/dl (≥26.4 mmol/l) within 
48 h, or urine output <0.5 ml/kg/h for ≥6 h but <12 h 
Stage 2 
Increase in sCr to 200%–299% (2.00–2.99x increase vs. baseline) or urine output <0.5 ml/kg/h for ≥12 h  but 
<24 h 
Stage 3 
Increase in sCr to ≥300% (≥3.0x increase vs. baseline), sCr of ≥4.0 mg/dl (≥354 mmol/l) with an acute increase 
of ≥0.5 mg/dl (44 mmol/l), urine output <0.3 ml/kg/h for ≥24 h, or anuria for ≥12 h; patients receiving renal 
replacement therapy are considered stage 3 irrespective of other criteria 
Adapted with permission from Kappetein et al. Updated standardized endpoint definitions for 
transcatheter aortic valve implantation: The Valve Academic Research Consortium-2 consensus 
document. J Am Coll Cardiol 2012;60: 1438–54. 
 
 
17.1.3 
AORTIC REGURGITATION 
Aortic regurgitation will be classified according to the 2008 Focused Update Incorporated into 
the ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease; 
JACC, 2008 (12). 
Aortic Regurgitation 
 
Mild 
Moderate 
Severe 
Qualitative 
Angiographic grade 
1+ 
2+ 
3-4+ 
Color Doppler jet width 
Central jet, width 
less than 25% of 
LVOT 
Greater than mild 
but no signs of 
severe AR 
Central jet, width 
greater than 65% 
LVOT 
Doppler vena contracta 
width (cm) 
Less than 0.3 
0.3–0.6 
Greater than 0.6 

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Aortic Regurgitation 
 
Mild 
Moderate 
Severe 
Quantitative (cath or echo) 
Regurgitant volume (ml per 
beat) 
Less than 30 
30–59 
Greater than or 
equal to 60 
Regurgitant fraction (%) 
Less than 30 
30–49 
Greater than or 
equal to 50 
Regurgitant orifice area 
(cm2) 
Less than 0.10 
0.10–0.29 
Greater than or 
equal to 0.30 
Additional essential criteria 
Left ventricular size 
-- 
-- 
Increased 
 
 
17.1.4 
AORTIC STENOSIS 
Aortic stenosis will be classified according to the 2008 Focused Update Incorporated into the 
ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease; 
JACC, 2008 (12). 
Aortic Stenosis 
Indicator 
Mild 
Moderate 
Severe 
Jet velocity (m/s) 
Less than 3.0 
3.0–4.0 
Greater than 4.0 
Mean gradient (mmHg)* 
Less than 25 
25–40 
Greater than 40 
Valve area (cm2) 
Greater than 1.5 
1.0–1.5 
Less than 1.0 
Valve area index (cm2 / m2) 
-- 
-- 
Less than 0.6 
* Valve gradients are flow dependent and when used as estimates of severity of valve stenosis should be 
assessed with knowledge of cardiac output or forward flow across the valve. Modified from the Journal of 
the American Society of Echocardiography, 16, Zoghbi WA, Recommendations for evaluation of the 
severity of native valvular regurgitation with two-dimensional and Doppler echocardiography, 777–802, 
Copyright 2003, with permission from American Society of Echocardiography (33). 
 
 
17.1.5 
ARRHYTHMIAS AND CONDUCTION SYSTEM DISTURBANCES 
Arrhythmias and conduction system disturbances will be defined and classified according to the 
Mitral Valve Academic Research Consortium (MVARC); Clinical Trial Design Principles and 
Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 

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Arrhythmias and Conduction System Disturbances 
For emerging mitral valve procedures in which the frequency of major arrhythmias and conduction system 
disturbances is unknown, continuous rhythm monitoring for at least 48 h in the post-procedural period is 
recommended to maximize the detection of arrhythmias and conduction system disturbances. 
Data elements to be collected for all patients should include: 
I. 
Baseline conduction abnormalities, paroxysmal or permanent atrial fibrillation (or flutter), ventricular 
arrhythmias, and the presence of permanent pacemaker and implantable defibrillators* 
II. 
Procedure-related new or worsened cardiac conduction disturbance (including first-, second- [Mobitz I 
or Mobitz II], or third-degree AV block; incomplete and complete right bundle branch block; 
intraventricular conduction delay; left bundle branch block; left anterior fascicular block; or left 
posterior fascicular block, including heart block) requiring a permanent pacemaker implant; each 
subclassified as persistent or transient 
III. 
New-onset atrial fibrillation (or flutter)† 
IV. 
New-onset ventricular tachycardia or fibrillation 
V. 
Pacemaker or defibrillator lead dislodgement 
Arrhythmias and conduction system disturbances are subclassified according to: 
I. 
The occurrence of hemodynamic instability 
II. 
Need for therapy including electrical/pharmacological cardioversion or initiation of a new medication 
(oral anticoagulation, rhythm, or rate control therapy) 
III. 
Need for new permanent pacemaker and/or defibrillator implantation, including the indication(s) and 
the number of days post-implant. For patients with defibrillators, the number of appropriate and 
i
i t
h
k
h
ld b
d d
* The type of permanent pacemaker should be recorded (e.g., single vs. dual chamber, biventricular). 
† Which lasts sufficiently long to be recorded on a 12-lead electrocardiogram, or at least 30 s on a rhythm strip. 
AV = atrioventricular 
 
17.1.6 
BLEEDING COMPLICATIONS 
Bleeding complications will be further defined and classified according to the Mitral Valve 
Academic Research Consortium (MVARC); Clinical Trial Design Principles and Endpoint 
Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 
Major bleeding will be defined as any bleeding event requiring transfusion of ≥4 U of whole 
blood or packed RBCs. 
Definition of Bleeding Complications 
MVARC Primary Bleeding Scale* 
I. 
Minor 
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 meets ≥1 of the following: requiring nonsurgical medical 
intervention by a health care professional; leading to hospitalization or increased level of care; prompting 
evaluation; or requires 1 or 2 U of whole blood or packed RBC transfusion and otherwise does not meet criteria for 
major, extensive, or life-threatening bleeding. 

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Definition of Bleeding Complications 
II. 
Major 
Overt bleeding either associated with a drop in the hemoglobin of ≥3.0 g/dl‡ or requiring transfusion of ≥3 U of 
whole blood or packed RBCs AND does not meet criteria of life-threatening or extensive bleeding. 
III. Extensive 
Overt source of bleeding with drop in hemoglobin of ≥4 g/dl‡ or whole blood or packed RBC transfusion ≥4 U 
within any 24-h period, or bleeding with drop in hemoglobin of ≥6 g/dl‡ or whole blood or packed RBC transfusion 
≥4 U (BARC type 3b) within 30 days of the procedure. 
IV. Life-threatening 
Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial necessitating surgery or 
intervention, or intramuscular with compartment syndrome OR bleeding causing hypovolemic shock or 
hypotension (systolic blood pressure <90 mm Hg lasting >30 min and not responding to volume resuscitation) or 
requiring significant doses of vasopressors or surgery. 
V. Fatal 
Bleeding adjudicated as being a proximate cause of death. Severe bleeding adjudicated as being a major 
contributing cause of a subsequent fatal complication, such as MI or cardiac arrest, is also considered fatal bleeding. 
Modified BARC Bleeding Scale (Secondary Use)§ 
Type 0 
No Bleeding. 
Type 1 
Bleeding that is not actionable and does not cause the patient to seek unscheduled performance of studies, 
hospitalization, or treatment by a health care professional. May include episodes leading to self- discontinuation of 
medical therapy by the patient without consulting a health care professional. 
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 ≥1 of the 
following: requiring nonsurgical medical intervention by a health care professional, leading to hospitalization or 
increased level of care, or prompting evaluation. 

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Definition of Bleeding Complications 
Type 3a 
• 
Overt* bleeding plus hemoglobin drop of 3 to <5 g/dl‡ (provided drop is related to bleed) 
• 
Any transfusion with overt bleeding 
Type 3b 
• 
Overt bleeding plus hemoglobin drop ≥5 g/dl‡ (provided drop is related to bleed) 
• 
Cardiac tamponade 
• 
Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) 
• 
Bleeding requiring IV vasoactive agents 
Type 3c 
• 
Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation but does include 
intraspinal bleeding) 
• 
Subcategories confirmed by autopsy, imaging, or lumbar puncture 
• 
Intraocular bleeding compromising vision 
Type 4 (periprocedural) 
• 
Perioperative intracranial bleeding ≤48 h 
• 
Reoperation after closure of incision site for the purpose of controlling bleeding 
• 
Transfusion of ≥5 U whole blood or packed RBCs within 48 h period of the index procedure 
• 
Chest tube output ≥2 l within 24 h period 
Type 5a 
Probable fatal bleeding. No autopsy or imaging confirmation but clinically suspicious. 
Type 5b 
Definite fatal bleeding. Overt bleeding, autopsy, or imaging confirmation. 
*  Modified with permission from VARC-2 (29). 
† “Overt” bleeding is defined by any of the following criteria being met: Reoperation after closure of sternotomy 
for the purpose of controlling bleeding; chest tube output >2 l within any 24 h period, >350 ml within the first post-
operative hour, ≥250 ml within the second post-operative hour, or >150 ml within the third post-operative hour; or 
visible bleeding from the vascular system either at or remote from the access/surgical site. 
‡ Adjusted for the number of units of blood transfused (1 U packed red blood cells or whole blood is equivalent to 
1 g/dl hemoglobin). 
§ Modified from BARC. 
BARC = Bleeding Academic Research Consortium; IV = intravenous; MVARC = Mitral Valve Academic Research 
Consortium; RBC = red blood cells; VARC = Valve Academic Research Consortium. 
 
 
17.1.7 
BUNDLE BRANCH BLOCK 
ACC/AHA/HRS 2006 Key Data Elements and Definitions for Electrophysiological Studies and 
Procedures; A Report of the American College of Cardiology/ American Heart Association Task 
Force on Clinical Data Standards (ACC/AHA/HRS Writing Committee to Develop Data 
Standards on Electrophysiology); JACC, 2006 (15). 
 

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Left Bundle Branch Block (LBBB) 
• 
QRS duration 120 ms or longer 
• 
Delayed onset of intrinsicoid deflection in 1, V5, and V6 >60 ms 
• 
Broad and notched or slurred R waves in I, aVL, V5, and V6 
• 
rS or QS complexes in right precordial leads 
• 
ST-segment and T waves in opposite polarity to the major QRS deflection  
Right Bundle Branch Block (RBBB) 
• 
QRS duration ≥120 ms 
• 
rsR’ or rSR’ complexes in V1 and V2 
• 
Delayed onset of intrinsicoid deflection in V1 and V2 >50 ms 
• 
Broad, slurred S wave in 1, V5, and V6 
• 
Secondary ST-T wave changes 
17.1.8 
CARDIAC STRUCTURAL COMPLICATION-NON-ACCESS SITE 
RELATED 
• 
Major cardiac structural complications, including: 
− Cardiac perforation* or pseudoaneurysm resulting in death, life-threatening 
bleeding, hemodynamic compromise, or tamponade, or requiring unplanned 
surgical or percutaneous intervention 
• 
Minor cardiac structural complications, including: 
− Cardiac perforation* or pseudoaneurysm not meeting major criteria 
*including the left ventricle, left atrium, coronary sinus, right atrium and right ventricle 
17.1.9 
CARDIAC PERFORATION 
A laceration or tearing of the walls of the ventricles or atria of the heart; of the interatrial or 
interventricular septum; of the papillary muscles or chordae tendineae; or of the one of the valves 
of the heart. 
17.1.10 CARDIAC TAMPONADE 
Clinical syndrome caused by the accumulation of fluid in the pericardial space, resulting in 
reduced ventricular filling and subsequent hemodynamic compromise. 
17.1.11 CARDIOGENIC SHOCK 
Cardiogenic shock will be defined as modified from the 2017 AHA Scientific Statement: 
Contemporary Management of Cardiogenic Shock 
Cardiac disorder that results in tissue hypoperfusion as supported by: 

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• 
Systolic BP<90 mmHg for ≥30 minutes 
OR 
• 
Cardiac Index of ≤1.8 L/min/m2 and PCWP ≥15mmHg 
OR 
• 
Intervention with pharmacological or mechanical support to maintain systolic BP ≥90 
mmHg1; 
AND 
• 
End-organ hypoperfusion documented by: 
− Urine output <30 mL/h2, or 
− Cool extremities, or 
− Clinical pulmonary congestion, or 
− Altered mental status, or 
− Lactate >2.0 mmol/L 
OR 
• 
Death 
Timing will be characterized as pre-operative, intra-operative (in the operating room), or post-
operative (operating room discharge through 30 days). 
Notes: 
• 
Excluding prophylactic use of pharmacological or mechanical support 
• 
Unless directly attributed to another medical condition 
17.1.12 CHRONIC RENAL INSUFFICIENCY 
Kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for ≥3 months. 
Kidney damage is defined as pathologic abnormalities or markers of damage, including 
abnormalities in blood or urine test or imaging studies. 
17.1.13 CONVERSION TO OPEN MITRAL VALVE SURGERY DURING A 
TRANSCATHETER PROCEDURE 
Conversion to open mitral valve surgery will be defined and classified according to the Mitral 
Valve Academic Research Consortium (MVARC); Clinical Trial Design Principles and Endpoint 
Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 
Subclassified as: 

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• 
Secondary to mitral valve apparatus damage or dysfunction, requiring surgical valve 
repair or replacement, or 
• 
Secondary to procedural complications (such as cardiac perforation, removal of an 
embolized device, and so on) 
17.1.14 CORONARY VESSEL COMPRESSION OR OBSTRUCTION 
Coronary vessel compression or obstruction will be defined and classified according to the 
Mitral Valve Academic Research Consortium (MVARC); Clinical Trial Design Principles and 
Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 
Angiographic evidence of any reduction in coronary artery luminal diameter or coronary sinus 
diameter due to either external compression, thrombosis, embolism, dissection, or other cause, 
subclassified as: 
• 
Major (≥50% diameter stenosis) or minor (<50%) 
• 
Symptomatic or not 
• 
Requiring treatment or not 
• 
Transient (intraprocedural only, resolved at procedure end) or persistent 
17.1.15 DAMAGE TO THE NATIVE MITRAL VALVE APPARATUS 
Damage to the native mitral valve apparatus will be defined and classified according to the 
Mitral Valve Academic Research Consortium (MVARC); Clinical Trial Design Principles and 
Endpoint Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint 
Definitions; JACC, 2015 (14). 
• 
Chords 
• 
Papillary muscles 
• 
Leaflets 
• 
Mitral annulus 
17.1.16 DEEP WOUND INFECTION 
Deep Wound Infection will be defined and classified according to The Society of Thoracic 
Surgeons’ (STS).  
Online Risk Calculator: Risk Model and Variables – STS Adult Cardiac Surgery Database 
Version 2.81. 
Deep sternal wound infection or mediastinitis (per CDC definition) diagnosed within 30 days of 
the operation or any time during the hospitalization for the Index Procedure. 

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17.1.17 DEVICE FRACTURE 
Device fracture will be defined and classified according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
• 
Major: a break, tear, perforation, or other structural defect in the device (stent, 
housing, leaflet, arm, and so on) resulting in device failure, resulting in recurrent 
symptoms, or requiring reintervention, or 
• 
Minor: a break, tear, perforation, or other structural defect in the device (stent, 
housing, leaflet, arm, and so on) not resulting in device failure, not resulting in 
recurrent symptoms, and not requiring reintervention 
Device fracture will be further classified as follows: 
• 
Primary: a break, tear, perforation, or other structural defect in the device (stent, 
housing, leaflet, arm, and so on) in the absence of canting, malposition, migration or 
rocking motion, or 
• 
Secondary: a break, tear, perforation, or other structural defect in the device (stent, 
housing, leaflet, arm, and so on) resulting from an unintended loading and strain 
when an implant functions in abnormal conditions due to canting, malposition, 
migration or rocky rocking motion 
17.1.18 DEVICE MIGRATION AND MALPOSITIONING 
• 
Device Malposition: Intrepid valve is deployed in a location other than intended 
• 
Migration with incomplete detachment: after initially correct transcatheter implantation of 
the Intrepid valve at the level of the mitral valve annulus, the device moves towards left 
atrium or left ventricle but stays partially or completely attached to the annulus. 
• 
Migration with complete detachment: after initially correct transcatheter implantation of the 
Intrepid valve at the level of the mitral valve annulus, the device moves towards left atrium or 
left ventricle and completely loses its contact with the annulus. 
17.1.19 DEVICE THROMBUS 
Device thrombus will be defined as any thrombus attached to or near an implanted valve and will 
be subclassified as: 
• 
Clinically significant valve thrombosis: visualization of thrombus by echo or by 
MDCT (including HALT ≥ 50%) and evidence of arterial embolism or 
new/worsening heart failure. 
• 
Significant thrombosis without clinical sequelae: visualization of thrombus by echo 
or by MDCT (including HALT ≥ 50%) in the absence of arterial embolism or 
new/worsening heart failure, meeting criteria of significant increase in mean gradient 

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across the implant* and warranting initiation or intensification of systemic 
anticoagulation. 
• 
Subclinical thrombosis: visualization of thrombus by echo or by MDCT (including 
HALT ≥ 50%) in the absence of arterial embolism or new/worsening heart failure and 
not meeting criteria of significant increase in mean gradient across the implant*. 
If thrombus is discovered on the implant at autopsy, it will be considered clinically significant 
with clinical sequelae if there was evidence of arterial embolism or new/worsening heart failure 
diagnosed ante- or postmortem. In the absence of arterial embolism or new/worsening diagnosed 
ante- or postmortem, thrombosis will be considered significant without clinical sequelae if last 
available echo met criteria of significant increase in mean gradient across the implant* and 
subclinical if last available echo does not meet criteria of significant increase in mean gradient 
across the implant*. 
*trans-mitral mean ∆≥6 mmHg AND ≥5 mmHg increase from discharge (10) 
The definition of Worsening Heart Failure is related to the valve thrombosis events. For Heart 
Failure admissions, please refer to Hospitalization subclassified as Heart Failure. 
Definition of Worsening Heart Failure* 
Presence of both: 
I. 
New or progressive symptoms/signs of decompensation heart failure 
a. 
History 
i. Significant weight gain 
ii. Worsening dyspnea 
iii. Worsening fatigue 
b. Physical Examination 
i. 
Newly elevated jugular venous pressure 
ii. 
New cardiac S3 gallop rhythm 
iii. 
New pulmonary rales 
iv. 
New hepatic congestion 
v. 
New peripheral edema 
vi. 
New development of cool extremities 
II. 
Unplanned intensification of decongestive therapy in response to progressive symptoms/signs of heart 
failure: 
a. 
Oral 
i. 
Increased dose of loop diuretic 
ii. 
Addition of thiazide diuretic to loop diuretic 
b. Intravenous administration of diuretic 
* Mallick et al. PROSPECT Trial. J Am Coll Cardiol HF 2016;4:749–55 
 
 

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17.1.20 EMBOLISM (BLOOD CLOT) 
• 
Free flowing blood clot or lesion material that is located in the systemic or pulmonary 
circulation that occurs in the absence of infection after the immediate perioperative period. 
Embolism may be manifested by a neurological event or a noncerebral embolic event. 
17.1.21 EMBOLISM (AIR) 
Venous air embolism – a subset of gas embolism that occurs when gas is introduced into the 
venous system. 
Arterial air embolism – a subset of gas embolism that occurs when gas is introduced into the 
arterial system. 
• 
Symptomatic = With Clinical Sequelae – (e.g. signs and/or symptoms of 
hemodynamic instability. ischemia, respiratory failure and/or new neurologic deficit) 
• 
Asymptomatic = Without clinical sequalae 
17.1.22 ENCEPHALOPATHY 
Altered mental state (e.g., seizures, delirium, confusion, hallucinations, dementia, coma, 
psychiatric episode, etc.). 
17.1.23 ENDOCARDITIS 
Endocarditis will be defined and classified according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
Any 1 of the following: 
• 
Fulfillment of the modified Duke endocarditis criteria (described below), or 
• 
Evidence of abscess, paravalvular leak, pus, or vegetation confirmed as secondary to 
infection by histological or bacteriological studies during an operation or autopsy. 
Should be further subclassified by organism, and early (<1 yr) vs. late (≥1 yr) 
Modified Duke Criteria 
Definite endocarditis according to the Modified Duke Criteria includes: 
• 
Histologic and/or microbiologic evidence of infection at surgery or autopsy, or 
• 
2 major criteria, or 
• 
1 major criteria or 3 minor criteria, or 
• 
5 minor criteria 
Major and minor criteria are as follows: 

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Modified Duke Criteria 
Major Criteria 
• Blood cultures positive for Infective Endocarditis (IE) 
• 
Typical microorganisms consistent with IE isolated from two separate blood cultures, as noted below 
− 
Viridans streptococci, Streptococcus bovis, Staphylcoccus aureus, or HACEK group 
− 
Community-acquired enterococci in the presence of a primary focus 
• 
Microorganisms consistent with IE isolated from persistently positive blood cultures defined as: 
− 
At least two positive cultures or blood samples obtained >12 hours apart, or 
− 
All of three, or a majority of four or more separate cultures of blood, the first and last sample 
obtained > one hour apart 
• 
Single blood culture positive for Coxiella burnetti or an antiphase I IG antibody titer >1:800 
• Evidence of endocardial involvement 
• 
Positive results of echocardiography for IE defined as: 
− 
Oscillating intracardiac mass on a valve or supporting structures in the path of regurgitant jets 
or on implanted material in the absence of an anatomic explanation, or 
− 
Abscess, or 
− 
New partial dehiscence of a valvular prosthesis 
New valvular regurgitation (worsening or changing or pre-existing murmur not sufficient) 
Minor Criteria 
• Predisposition: predisposing heart condition or intravenous drug use 
• Fever: temperature >38°C 
• Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial 
• hemorrhage, conjunctival hemorrhages, and Janeway’s lesions 
• Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor 
• Microbiological evidence: positive blood culture but does not meet a major criterion (as noted above) or 
serological evidence of active infection with organism consistent with infectious endocarditis. 
• Echocardiographic findings: consistent with IE but do not meet a major criterion as noted above 
Modified Duke Criteria 
If only 1 major and 1-2 minor criteria are fulfilled, or if only 3-4 minor criteria are fulfilled, the event will be coded 
as “possible endocarditis” 
 
 

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17.1.24 HEMOLYSIS 
Hemolysis will be defined and classified according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14).The presence of anemia requiring transfusion plus decreased/absent haptoglobin and/or 
increased LDH levels; recommended, but not required, to be confirmed by a hematologist. 
• 
Hemolysis will be further sub-classified to the following: 
− Hemolysis with PVL: The presence of anemia requiring transfusion plus 
decreased/absent haptoglobin and/or increased LDH levels and evidence of a 
Paravalvular leak on transesophageal or transthoracic echocardiography 
− Hemolysis without PVL: The presence of anemia requiring transfusion plus 
decreased haptoglobin/absent and/or increased LDH levels and no evidence of 
a Paravalvular leak on transesophageal or transthoracic echocardiography 
• (e.g. hemolysis due to other devices such as Impella, etc. would fall 
into this category) 
17.1.25 HOSPITALIZATION 
Hospitalization will be defined and classified according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
Heart Failure hospitalization will be defined and classified according to MVARC. 
Definition and Classification of Hospitalization (or Rehospitalization) 
Definition 
Hospitalization is defined as admission to an inpatient unit or ward in the hospital for ≥24 h, including an emergency 
department stay. Hospitalizations planned for pre-existing conditions are excluded unless there is worsening of the 
baseline condition. 
Hospitalization is further subclassified as: 

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Definition and Classification of Hospitalization (or Rehospitalization) 
I. 
Heart failure hospitalization: Both of the following additional criteria are present: 
• 
Symptoms, signs and/or laboratory evidence of worsening heart failure1 
• 
Administration of intravenous or mechanical heart failure therapies2 
Patients hospitalized with heart failure are further subclassified as:  
• 
IA. Primary (cardiac related) heart failure hospitalization 
• 
IB. Secondary (noncardiac related) heart failure hospitalization 
II. 
Other cardiovascular hospitalization: such as for coronary artery disease, acute myocardial infarction, 
hypertension, cardiac arrhythmias, cardiomegaly, pericardial effusion, atherosclerosis, stroke, or peripheral 
vascular disease without qualifying heart failure 
III. 
Non-cardiovascular hospitalization: not due to heart failure or other cardiovascular causes, as defined above 
1. The diagnosis of worsening heart failure is on the basis of: 1) symptoms of worsening heart failure such as 
increased dyspnea, orthopnea, paroxysmal nocturnal dyspnea, fatigue, decreased exercise tolerance, and/or 
history of weight gain; 2) physical examination evidence of worsening heart failure such as neck vein distention, 
the presence of a third heart sound, pulmonary rales, ascites or pedal edema, and/or hypotension or signs of 
worsening end-organ perfusion; and/or 3) diagnostic evidence of worsening heart failure such as radiographic 
pulmonary congestion, natriuretic peptide levels greater than the upper limit of normal in the absence of 
conditions known to affect these values (e.g., renal dysfunction, infection), arterial oxygen desaturation or 
increasing oxygen requirements, and/or acidosis. No single finding is necessarily diagnostic, and adjudication 
by the clinical events committee should be on the basis of all available clinical evidence, guided by the specifics 
of the protocol definition. 
2. 
Examples of intravenous heart failure therapies contributing to this definition would include bolus or 
continuous infusion of loop diuretic agents; continuous infusion of vasodilators such as nitroglycerin, 
nitroprusside, or nesiritide; inotropic agents such as dobutamine; inodilators such as milrinone; beta agonists; 
and vasopressors such as dopamine, epinephrine, and norepinephrine. Also included would be other invasive 
or mechanical heart failure treatments such as ultrafiltration, cardiac resynchronization therapy, and 
hemodynamic assist devices including intra-aortic balloon counterpulsation or left ventricular (LV) or 
biventricular assist devices. Treatment with intravenous antiarrhythmic medications or electrical cardioversion 
and/or ablation in the absence of other intravenous or invasive heart failure treatments would not per se 
constitute criteria for heart failure hospitalization (but would qualify as a cardiovascular hospitalization). 
Similarly, a heart failure exacerbation that can be managed solely by augmentation of oral heart failure therapies 
does not meet the pre-defined criteria for heart failure hospitalization. 
 
 
17.1.26 IATROGENIC ATRIAL SEPTAL DEFECT 
Iatrogenic ASD will be defined and classified according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
• 
Major: significant left-to-right shunt (Qp:Qs ≥2:1) or symptomatic requiring the 
need for closure 
• 
Minor: nonsignificant shunt that is still present at ≥6 months 

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17.1.27 INTERACTION WITH NON-MITRAL VALVE INTRACARDIAC 
STRUCTURES 
Interaction with non-mitral- valve intracardiac structures will be classified as 
• 
Left ventricular outflow tract obstruction: 
− Visual narrowing of the LVOT tract AND 
− Peak LVOT jet velocity ≥ 2.7 m/s (peak instantaneous gradient ≥30 mmHg) 
measured by CW Doppler under basal (resting) conditions or physiologically 
provoked (Valsalva maneuver or post premature ventricular contraction) AND 
− An increment in peak LVOT gradient ≥10 mm Hg from baseline 
− Additional notes and considerations: 
• LVOT obstruction will be considered severe if peak LVOT jet velocity 
≥ 3.5 m/s (peak instantaneous gradient ≥50 mm Hg). 
• Non-severe: Peak LVOT jet velocity greater than or equal to 2.7 ms/s 
to 3.4 m/s (peak instantaneous gradient ≥30 mm Hg 
• Non-event: Less than 2.7 m/s peak LVOT jet velocity 
• All cases with peak LVOT jet velocity ≥ 2.7 m/s (peak instantaneous 
gradient 
• ≥30 mm Hg) measured by CW Doppler will be submitted to the CEC 
for adjudication. 
• AEs/SAEs related to intraprocedural increase in LVOT gradient will 
be submitted to the CEC for adjudication. Cases of intraprocedural 
LVOTO resulting into death or explant will be considered severe 
LVOTO. 
• Cases of LVOTO resulting into septal reduction therapy (alcohol 
septal ablation or septal myectomy) will be considered severe LVOTO. 
• Cases of LVOTO incidentally discovered by pathology will be 
assessed based on the last available peak LVOT jet velocity measured 
by CW Doppler; any attempt should be done to submit this last echo to 
the Echo Core Lab and to the CEC. Alternatively, the last follow-up 
echo Core Lab CW measurements will be used to define LVOTO. 
Outflow Tract Gradient Severity Scale CW Doppler 
Mild 
Moderate 
Severe 
Velocity m/sec 
≥2.7-3.1 
3.2 - 3.4 
≥3.5 
Peak Gradient 
mmHg 
≥30-39 
40 - 49 
≥50 
 

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• 
Aortic valve regurgitation (≥ moderate or 2+) 
• 
Other 
17.1.28 INTERACTION WITH PACEMAKER/CRT/ICD LEAD 
• 
Lead Dislodgement: Radiographic, micro dislodgement, electrical or electrocardiographic 
evidence of electrode displacement from the original implant site or electrode displacement 
that adversely affects pacing and/or lead performance 
• 
Failure to Sense/Undersensing (Cardiac): Intermittent or complete loss of sensing or failure 
to detect the intended intrinsic cardiac signals (atrial or ventricular) during non-blanking 
periods at programmed sensitivity settings. 
• 
Failure to Capture (Cardiac): 
• 
Intermittent: Intermittent or irregular failure to achieve cardiac stimulation (atrial or 
ventricular) at programmed output delivered outside of the cardiac refractory period 
at settings previously effective 
• 
Sustained: Continuous failure to stimulate the heart with stimuli delivered outside of 
the cardiac refractory period at programmed setting previously effective 
• 
Lead Fracture: Visual, electrical, and/or radiographic evidence of mechanical break 
within the lead conductor (includes connectors, coils and/or electrodes) 
• 
Failure to Pace: lack of the pacer electrical output once the heart rate is below the 
programmed lower rate of the pacemaker. 
17.1.29 MITRAL REGURGITATION 
Mitral regurgitation will be classified according to the Recommendations for Noninvasive 
Evaluation of Native Valvular Regurgitation: A report from the American Society of 
Echocardiography developed in Collaboration with the Society of Cardiovascular Magnetic 
Resonance; JASE, 2017(11). 
Qualitative and Quantitative Parameters useful in Grading Mitral Regurgitation Severity 
MR Severity* 
Mild 
Moderate 
Severe 
Structural Parameters 

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Qualitative and Quantitative Parameters useful in Grading Mitral Regurgitation Severity 
MR Severity* 
Mild 
Moderate 
Severe 
MV morphology 
None or mild leaflet 
thickening 
(e.g., mild thickening, 
calciﬁcations or 
prolapse, mild 
tenting) 
Moderate leaflet 
abnormality of moderate 
tenting 
Severe valve lesions 
(primary: ﬂail leaﬂet, 
ruptured papillary muscle, 
severe retraction, large 
perforation; secondary: 
severe tenting, poor 
leaﬂet coaptation) 
LV and LA size† 
Usually normal 
Normal or mile dilated 
Dilated‡ 
Qualitative Doppler 
Color flow jet area§ 
Small, central, 
narrow, often brief 
Variable 
Large central jet (>50% of 
LA) or eccentric wall- 
impinging jet of variable 
size 
Flow convergenceǁ 
Not visible, transient 
or small 
Intermediate in size and 
duration 
Large throughout systole 
CWD jet 
Faint/partial/parabolic 
Dense but partial 
or parabolic 
Holosystolic/dense/triang 
ular 
Semiquantitative 
VCW(cm) 
<0.3 
Intermediate 
≥ 0.7 (>0.8 for biplane)¶ 
Pulmonary vein flow# 
Systolic dominance 
(may be blunted in LV 
dysfunction or AF) 
Normal or systolic 
blunting# 
Systolic flow reversal† 
Mitral inflow** 
A-wave dominant 
Variable 
E-wave dominant (>1.2 
m/sec) 
Quantitative††,‡‡ 
EROA, 2D PISA 
(cm2) 
<0.20 
0.20-0.29 
0.30-0.39 
≥ 0.40 (may be lower in 
secondary MR with 
elliptical ROA) 
RVol (mL) 
<30 
30-44 
45-59†† 
≥ 60 (may be lower in low 
ﬂow conditions) 
RF (%) 
<30 
30-39 
40-49 
≥ 50 

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Qualitative and Quantitative Parameters useful in Grading Mitral Regurgitation Severity 
MR Severity* 
Mild 
Moderate 
Severe 
ROA, Regurgitant oriﬁce area. 
Bolded qualitative and semiquantitative signs are considered speciﬁc for their MR grade. 
* All parameters have limitations, and an integrated approach must be used that weighs the strength of each 
echocardiographic measurement. All signs and measures should be interpreted in an individualized manner that 
accounts for body size, sex, and all other patient characteristics. 
† This pertains mostly to patients with primary MR. 
‡ LV and LA can be within the ‘‘normal’’ range for patients with acute severe MR or with chronic severe MR 
who have small body size, particularly women, or with small LV size preceding the occurrence of MR 
§ With Nyquist limit 50-70 cm/sec. 
" Small ﬂow convergence is usually <0.3 cm, and large is $ 1 cm at a Nyquist limit of 30-40 cm/sec. 
¶ For average between apical two- and four-chamber views 
# Inﬂuenced by many other factors (LV diastolic function, atrial ﬁbrillation, LA pressure). 
** Most valid in patients >50 years old and is inﬂuenced by other causes of elevated LA pressure. 
†† Discrepancies among EROA, RF, and RVol may arise in the setting of low or high ﬂow states. 
‡‡ Quantitative parameters can help subclassify the moderate regurgitation group. 
 
 
17.1.30 MITRAL STENOSIS 
Mitral stenosis will be classified according to the 2008 Focused Update Incorporated into the 
ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart Disease; 
JACC, 2008 (12). 
Mitral Stenosis 
Indicator 
Mild 
Moderate 
Severe 
Mean gradient (mmHg)* 
Less than 5 
5–10 
Greater than 10 
Pulmonary artery systolic pressure 
(mmHg) 
Less than 30 
30–50 
Greater than 50 
Valve area (cm2) 
Greater than 1.5 
1.0–1.5 
Less than 1.0 
* Valve gradients are flow dependent and when used as estimates of severity of valve stenosis should be assessed 
with knowledge of cardiac output or forward flow across the valve. Modified from the Journal of the American 
Society of Echocardiography, 16, Zoghbi WA, Recommendations for evaluation of the severity of native valvular 
regurgitation with two-dimensional and Doppler echocardiography, 777–802, Copyright 2003, with permission 
from American Society of Echocardiography. 
 
 

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17.1.31 MITRAL VALVE DYSFUNCTION 
Mitral valve dysfunction will be classified according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
The device performs as intended without complication but does not adequately reduce the degree 
of MR (MR > moderate [2+], or fails to relieve or creates new mitral stenosis [EROA <1.5 cm2 
or transmitral gradient ≥5 mm Hg]). 
17.1.32 MORTALITY 
Mortality will be classified according to the Mitral Valve Academic Research Consortium 
(MVARC); Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral 
Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 (14). 
Classification of All-Cause Mortality 
I. 
Cardiovascular vs. Noncardiovascular Mortality 
A. Cardiovascular Mortality 
Any of the following contributing conditions: 
Heart failure (subclassified into left ventricular vs. right ventricular dysfunction) Myocardial 
infarction 
Major bleeding 
Thromboembolism Stroke 
Arrhythmia and conduction system disturbance 
Cardiovascular infection and sepsis (e.g., mediastinitis and endocarditis) Tamponade 
Sudden, unexpected death Other 
cardiovascular Device failure 
Death of unknown cause (adjudicated as cardiovascular) 
B. Noncardiovascular Mortality 
Any death in which the primary cause of death is clearly related to another condition:  
Noncardiovascular infection and sepsis (e.g., pneumonia) 
Renal failure  
Liver failure  
Cancer  
Trauma  
Homicide  
Suicide 
Other noncardiovascular 
II. 
Periprocedural vs. Nonperiprocedural Mortality 
Death is considered periprocedural if occurring within 30 days of the intervention or beyond 30 days in the patient 
not yet discharged 

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17.1.33 MYOCARDIAL INFARCTION 
Myocardial infarction (MI) will be defined according to the Mitral Valve Academic Research 
Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
Definition of MI After Transcatheter and Surgical Mitral Valve Replacement 
I. 
Periprocedural MI (≤48 h after the index procedure)*† 
A. In patients with normal baseline CK-MB (or cTn): The peak CK-MB measured within 48 h of the procedure rises 
to ≥10x the local laboratory ULN plus new ST-segment elevation or depression of ≥1 mm in ≥2 contiguous 
leads (measured 80 ms after the J-point), or to ≥5x ULN with new pathological Q waves in ≥2 contiguous leads 
or new persistent LBBB, OR in the absence of CK-MB measurements and with a normal baseline cTn, a cTn (I 
or T) level measured within 48 h of the PCI rises to ≥70x the local laboratory ULN plus new ST-segment 
elevation or depression of ≥1 mm in ≥2 contiguous leads (measured 80 ms after the J-point), or ≥35_ ULN with 
new pathological Q waves in ≥2 contiguous leads or new persistent LBBB. 
B. In patients with elevated baseline CK-MB (or cTn): The CK-MB (or cTn) rises by an absolute increment greater 
than or equal to those levels recommended above from the most recent pre-procedure level plus, new ECG 
changes as described. 
II. 
Spontaneous MI (>48 h after the index procedure)‡ 
Detection of rise and/or fall of cardiac biomarkers (preferably cTn) with at least 1 value above the 99th percentile 
URL (or ULN in the absence of URL) together with at least 1 of the following: 
A. Symptoms of ischemia 
B. ECG changes indicative of new ischemia (new ST-segment or T-wave changes or new LBBB) or new 
pathological Q waves in ≥2 contiguous leads 
C. Imaging evidence of a new loss of viable myocardium or new wall motion abnormality 
III. 
MI associated with sudden, unexpected cardiac death‡ 
Sudden cardiac death or cardiac arrest, often with symptoms suggestive of myocardial ischemia, and accompanied 
by presumably new ST-segment elevation or new LBBB and/or evidence of fresh thrombus by coronary 
angiography and/or at autopsy, but death occurs before blood samples could be obtained or at a time before the 
appearance of cardiac biomarkers in the blood 
IV. 
Pathological findings of an acute myocardial infarction‡ 
The use of high sensitivity (hs)-troponins is recommended for diagnosis of type II (spontaneous) MI, but has not 
been studied for assessment of periprocedural MI. Standard troponin assays are therefore recommended for 
evaluation of type I MI. 
* Periprocedural biomarker elevation >ULN not meeting the criteria for MI should be categorized as 
“myonecrosis not meeting MI 
criteria.” 
† Adapted from Moussa et al. (43). 
‡ Adapted with permission from Thygesen et al. (39). 
CK-MB = creatine kinase-MB; cTn = cardiac troponin; ECG = electrocardiogram; LBBB = left bundle 
branch block; MI = myocardial infarction; ULN = upper limit of normal; URL = upper reference limit. 
 
 

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17.1.34 NEUROLOGICAL EVENTS 
Neurological Events will be defined and classified according to the Mitral Valve Academic 
Research Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
Stroke and Transient Ischemic Attack: Diagnosis and Classification 
Diagnostic Criteria 
Acute episode of a focal or global neurological deficit with at least 1 of the following: 
A. Change in the level of consciousness 
B. Hemiplegia, hemiparesis, numbness, or sensory loss affecting 1 side of the body 
C. Dysphasia or aphasia, hemianopia, amaurosis fugax, or other neurological signs or symptoms consistent 
with stroke 
In addition, there is no other readily identifiable nonstroke cause for the clinical presentation (e.g., brain tumor, 
trauma, infection, hypoglycemia, peripheral lesion, pharmacological influences) as determined by or in 
conjunction with the designated neurologist* 
The neurological event type classification 
Stroke: duration of a focal or global neurological deficit ≥24 h OR <24 h if available neuroimaging documents a 
new intracranial or subarachnoid hemorrhage (hemorrhagic stroke) or central nervous system infarction 
(ischemic stroke) OR the neurological deficit results in death 
TIA: duration of a focal or global neurological deficit <24h and neuroimaging does not demonstrate new 
hemorrhage or infarct 
Confirmation of the diagnosis of stroke or TIA requires at least 1 of the following 
Neurologist or neurosurgical specialist, or Neuroimaging 
procedure (CT scan or brain MRI) 
Stroke/TIA timing classification 
Periprocedural if it occurs within 30 days of the intervention, or if beyond 30 days in the patient not yet 
discharged. A periprocedural stroke/TIA may be further considered immediate if it occurs within 24 h of the 
procedure or within 24 h of awakening from general anesthesia if beyond 24 h. 
Nonperiprocedural if it occurs beyond 30 days after the intervention and after the patient has been discharged. 
Stroke/TIA etiology classification 
Ischemic: an acute episode of focal cerebral, spinal, or retinal dysfunction caused by infarction of the central 
nervous system tissue 
Hemorrhagic: an acute episode of focal or global cerebral or spinal dysfunction caused by intraparenchymal, 
intraventricular, or subarachnoid hemorrhage 
Undetermined: if there is insufficient information to allow categorization as ischemic or hemorrhagic 

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Stroke and Transient Ischemic Attack: Diagnosis and Classification 
Stroke severity† is further classified as 
Disabling stroke: an mRS score ≥2 at 90 days plus an increase in ≥1 mRS category from the pre-stroke baseline 
Nondisabling stroke: an mRS score <2 at 90 days or without an increase ≥1 mRS category from the pre- stroke 
baseline 
* Patients with nonfocal global encephalopathy will not be reported as having had a stroke without 
unequivocal evidence of cerebral infarction based upon neuroimaging studies (CT scan or cerebral MRI). 
† Modified Rankin scale (mRS) assessments should be made by qualified individuals (such as nurse 
practitioner, physician assistant, doctor of osteopathy, or medical doctor) according to a certification 
process (20,55,56). 
CT = computed tomography; MRI = magnetic resonance imaging; TIA = transient ischemic attack 
 
17.1.35 PARAVALVULAR LEAK 
PVL will be defined and classified according to the Mitral Valve Academic Research Consortium 
(MVARC); Clinical Trial Design Principles and Endpoint Definitions for Transcatheter Mitral 
Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 (14). 
• 
Major: moderate or severe (2þ, 3þ, or 4þ), or associated with hemolysis, or requiring 
intervention or surgery 
• 
Minor: trace or mild (1þ), without hemolysis 
17.1.36 PERICARDIAL EFFUSION 
Pericardial effusion will be defined and classified as adapted from the Mitral Valve Academic 
Research Consortium (MVARC); Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions; JACC, 2015 
(14). 
• 
Major: leading to cardiac tamponade or requiring intervention or hospitalization 
• 
Minor: not leading to cardiac tamponade and not requiring intervention 
17.1.37 PROLONGED VENTILATION 
Modified from The Society of Thoracic Surgeons’ (STS) Online Risk Calculator: Risk Model 
and Variables – STS Adult Cardiac Surgery Database Version 2.81. 
Prolonged postoperative pulmonary ventilation > 24.0 hours. (These hours include OR exit until 
extubation, plus any additional hours following re-intubation through 30 days or hospital 
discharge, whichever is longer.) 
17.1.38 REOPERATION OR REINTERVENTION 
Reoperation and reintervention will be defined as those events adjudicated as procedure or valve 
related. 

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Any cardiovascular surgical (reoperation) or percutaneous interventional (reintervention) 
procedure performed following the index procedure (discharge from the operating room). 
Reoperation and reintervention will be classified as procedure related (e.g. bleeding/tamponade, 
dissection), valve related (e.g. endocarditis, valve dysfunction, thrombosis), or for other 
cardiovascular reasons (e.g., coronary occlusion, VSD). 
17.1.39 RESPIRATORY INSUFFICIENCY 
Post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) 
ratio [FEV1/FVC] less than 70%. Post-bronchodilator FEV1 less than 80% predicted, with or 
without chronic symptoms (e.g. cough or sputum production). 
17.1.40 RESPIRATORY FAILURE 
The need for ventilatory support for >72 hours associated with an inability to wean from the 
respirator for any reason. 
17.1.41 RIGHT VENTRICULAR INSUFFICIENCY 
Defined as sequelae of right ventricular failure including the following: 
• 
Significantly decreased right ventricular systolic and/or diastolic function 
• 
Tricuspid valvular regurgitation secondary to elevated pressure  
Clinical symptoms to include: 
• 
Hepatic congestion 
• 
Ascites 
• 
Anasarca 
• 
Presence of “hepato-jugular reflux” 
• 
Edema 
17.1.42 TRICUSPID REGURGITATION 
Tricuspid regurgitation will be classified according to the 2008 Focused Update Incorporated 
into the ACC/AHA 2006 Guidelines for the Management of Patients with Valvular Heart 
Disease; JACC, 2008 (12). 
Severe tricuspid regurgitation: vena contracta width greater than 0.7cm and systolic reversal in 
hepatic veins. 
17.1.43 UNPLANNED USE OF CARDIOPULMONARY BYPASS (CPB) 
Modified from the Valve Academic Research Consortium (VARC)-2; Updated Standardized 
Endpoint Definitions for Transcatheter Aortic Valve Implantation (TAVI); 2012-10-09 (13). 
Unplanned use of CPB for hemodynamic support at any time during the TMVR procedure. 

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17.1.44 VALVE IN VALVE DEPLOYMENT  
Additional valve prosthesis is implanted within a previously implanted prosthesis because of 
sub-optimal device position and/or function, during or after the index procedure. 
17.1.45 CAUSAL RELATIONSHIPS 
 
Classification of Causality Relationships1 
Not related 
The event is due to an underlying or concurrent illness or effect of 
another device, drug or intervention and is not related to the 
investigational device or procedure. 
Unlikely (remotely) to be related 
The event’s relationship to the investigational device or 
procedure, cannot be completely ruled out, but is unlikely, and an 
alternative etiology is more likely. 
Possibly related 
The event has a strong temporal relationship to the investigational 
device or procedure, and an alternative etiology is equally or less 
likely. 
Probably related 
The event has a strong temporal relationship to the use of the 
investigational device or procedure and another etiology is 
unlikely or significantly less likely. 
Causal (Definite) relationship 
The event can only be attributed to the use of the investigational 
device or procedure. 
Not Assessable 
The event’s relationship to the use of the investigational device 
or procedure cannot be assessed. 
1The CEC will use these causality definitions to adjudicate whether an event is related to the presence of a device 
fracture, if applicable. 
17.2 
Sample Informed Consent 
Sample Informed Consent templates will be provided under separate cover. 
17.3 
Instructions for Use 
Instructions for Use (IFU) will be provided under separate cover for each device 
configuration/system that will be made available for clinical investigation under this protocol. 
The relevant regulatory and local requirements (IRB, etc.) for investigation of each configuration 
will be met prior to use of that system under this protocol. 
Transfemoral/Transeptal System: 
Investigational Device Configuration 
Model Numbers 
IFU Reference 
Intrepid™ Transcatheter 
Mitral Valve Replacement 
System (Recoverable) 
Bioprosthesis 
INTPDVL42F 
INTPDVL48F 
LBL-0087 
Delivery System 
INTPDTF42DS 
INTPDTF48DS 
Loading System 
INTPDTFLS 

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Version 4.0 
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18.0 Version History 
 
Version 
Summary of changes 
Justification 
of changes 
Potential 
impact of the 
change on 
performance, 
effectiveness, 
or safety or 
other 
endpoints 
Identificat
ion of the 
affected 
study 
documents 
Author(s)/ 
Title 
1.0 
• 
‘Not Applicable, New 
Document’ 
NA 
NA 
Sonia Diaz 
de Leon, 
Clinical 
Research 
Manager 
2.0 
• Added reference to 
transseptal where applicable 
• Changed “patient” to “subject” 
for assessments completed post 
screening 
• Added inclusion criteria for 
subject’s ineligibility for 
conventional mitral surgery and 
severity of mitral regurgitation 
• Added reference for STS 
predictive model for inclusion 
and exclusion criteria 
• Added assessment of ASD 
and PVL via TEE post 
procedure 
• Updated post procedure 
medication recommendation 
• Added no significant ASD 
requiring closure in exploratory 
endpoints 
• Added MR classification and 
definitions 
• Updated 
for 
consistent 
terminology for quality of life 
questionnaires 
• Updated the number of 
investigational sites from 6 to 
10 
Added for 
clarity and 
consistency 
prior to final 
site release 
N/A as 
version 1.0 
unreleased 
to sites 
Sonia Diaz 
de Leon, 
Clinical 
Research 
Manager 

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Version 4.0 
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Version 
Summary of changes 
Justification 
of changes 
Potential 
impact of the 
change on 
performance, 
effectiveness, 
or safety or 
other 
endpoints 
Identificat
ion of the 
affected 
study 
documents 
Author(s)/ 
Title 
3.0 
• Updates made throughout for 
alignment with ISO14155 
• Correction of typographical 
errors and administrative 
updates throughout 
• Updated to 056 Clinical 
Investigational Plan template 
and amended the following 
sections: 
o 
Glossary 
o 
Rationale / basis for study 
design 
o 
Trial training 
o 
Packaging 
Updates made 
to align with 
recent pivotal 
trial updates in 
APOLLO for 
clinical 
program 
alignment, new 
clinical 
investigation 
plan study 
template, and 
for compliance 
with ISO14155. 
Additional 
updates made 
per 
recommendatio
ns by safety, 
medical 
advisory, 
quality, and 
clinical 
leadership. 
Increased 
sample size 
and sites may 
impact 
timeline of 
primary 
endpoint 
analysis. 
Increased 
specificity to 
additional 
exploratory 
endpoint 
definitions 
and safety 
parameters to 
more 
Informed 
Consent 
Template, 
Case Report 
Forms, 
Protocol 
training 
slides, Safety 
Plan, 
Monitoring 
Plan, 
Statistical 
Analysis 
Plan, Clinical 
Trial 
Agreements 
Sarah 
Brown, Pr. 
Clinical 
Research 
Specialist 

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Transseptal System Clinical Investigation Plan 
Version 4.0 
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Version 
Summary of changes 
Justification 
of changes 
Potential 
impact of the 
change on 
performance, 
effectiveness, 
or safety or 
other 
endpoints 
Identificat
ion of the 
affected 
study 
documents 
Author(s)/ 
Title 
o 
Intended population 
o 
Equipment 
o 
Product Use 
o 
Product training 
requirements 
o 
Product receipt and 
tracking 
o 
Product return 
o 
Subject enrollment 
o 
Required evaluations 
o 
Assessment of efficacy and 
safety 
o 
Source documents 
o 
Potential benefits 
o 
Audits 
o 
Confidentiality 
• Instructions for lost to follow-up 
and when subjects die in 
Subject Withdrawal and 
Discontinuation section 
• Increased sample size to 45 total 
subjects enrolled at up to 15 
sites, along with extended 
enrollment prior to account for 
this increase 
• Applicable updates made to 
study Inclusion and Exclusion 
Criteria including Synopsis and 
Section 8.4 to align with 
APOLLO Pivotal Trial criteria 
v10 
• Clarification added for Heart 
Team specifications, study 
design language, and 
Investigational sites and 
Investigators section for 
increased specificity in 
definitions 
Additional 
recommendatio
ns post-
procedurally 
align with 
preliminary 
findings from 
initial subject 
data available. 
clearly define 
critical 
parameters of 
analysis for 
this study. 
Change in 
SAE reporting 
timeframe to 
align with 
program- wide 
standard for 
reporting 
timelines, may 
impact 
sponsor 
awareness of 
events. 

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Transseptal System Clinical Investigation Plan 
Version 4.0 
Page 100 of 102 
 
 
Version 
Summary of changes 
Justification 
of changes 
Potential 
impact of the 
change on 
performance, 
effectiveness, 
or safety or 
other 
endpoints 
Identificat
ion of the 
affected 
study 
documents 
Author(s)/ 
Title 
• Language added to distinguish 
point of enrollment within the 
study 
• Updated required labs at all 
study intervals 
• Removed urinalysis requirement 
at all study intervals 
• Clarified when TEE will be 
done in addition to TTE at 
follow-up intervals 
• Clarified quality of life 
questionnaires required at all 
follow-up intervals 
• Included Heart Failure 
Management and Medications 
• Added procedural adverse event 
collection and atrial septal 
defect as recommended for 
closure, along with 4th position 
role clarification during 
procedure 
• Recommendations at Discharge 
added for deep vein thrombosis 
and atrial septal defect 
• Updated table of assessments 
and Schedule of Events table to 
align with protocol updates in 
respective study sections 
• Updated MVARC defined 
outcomes and individual subject 
success in additional 
exploratory endpoints 
• Added non-reportable medical 
occurrences associated with the 
index procedure 
• Updated number of days to 
report UADEs and SAEs from 2 
to 3 working days 

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Transseptal System Clinical Investigation Plan 
Version 4.0 
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Version 
Summary of changes 
Justification 
of changes 
Potential 
impact of the 
change on 
performance, 
effectiveness, 
or safety or 
other 
endpoints 
Identificat
ion of the 
affected 
study 
documents 
Author(s)/ 
Title 
• Clarified additional exploratory 
endpoints are measured through 
5 year follow-up 
• Added details for subject exit, 
withdrawal, or discontinuation 
• Alignment of potential risks 
section and latest IFU with 
additional clarification on Risk 
minimization 
• Clarified membership for 
clinical events committee and 
data monitoring committee 
4.0 
Administrative changes 
throughout the document 
Added for clarity 
and consistency 
prior to final site 
release 
Language 
modified to 
accommodate 
recommendations 
made by DMC 
Clinical Safety 
Management 
and Potential 
Complaint 
Plan, Protocol 
training slides, 
Clinical Trial 
Agreements, 
CEC Charter 
Bridget 
Dahlen, Sr. 
Clinical 
Research 
Specialist 
Section 17 – Appendices 
• Updated device fracture 
definition & classification of 
causal relationships 
Updates made to 
this section to 
reflect 
recommendations 
made by the DMC 
Section 17 – Appendices 
• Added Valve in Valve 
deployment definition 
Updates made to 
align with recent 
pivotal trial 
updates in 
APOLLO for 
clinical program 
alignment 
N/A 
Section 2 – Synopsis 
• Correction to Indication under 
Investigation 
Updated to align 
with investigation 
purpose 
N/A 
Section 16 - References 
• Updated to appropriate 
references throughout the 
protocol. No new references 
were added 
Updated to align 
references through 
protocol 
N/A 
 

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CLINICAL INVESTIGATIONAL PLAN 
 
 
Evaluation of the Safety and Performance of The  
Intrepid™ Transcatheter Mitral Valve Replacement System in  
High Risk Patients with Severe, Symptomatic Mitral Regurgitation -  
 
The Intrepid™ TMVR Pilot Study 
 
 
 
 
Protocol Number: 
CIP-1403 
Version / Date: 
4.0 / 2019.10.15 
Sponsor: 
Medtronic, Inc. 
8200 Coral Sea St NE 
Mounds View, MN 55112 
United States 
 
 
 
CONFIDENTIAL 
This investigational protocol contains confidential and proprietary information provided by 
Medtronic to each Investigator in this clinical study.  This information is intended for review and 
use by the Investigator, his/her staff, and the IRB/Ethics Committee and is not to be disclosed to 
others without the written permission of Medtronic. 
 
 

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Page 2 
Summary and General Information 
 
Title: 
Evaluation of the Safety and Performance of The Intrepid™ 
Transcatheter Mitral Valve Replacement System in High Risk 
Patients with Severe, Symptomatic Mitral Regurgitation – The 
Intrepid™ TMVR Pilot Study 
Investigational 
Plan: 
CIP-1403 
Investigational 
Device: 
The Intrepid™ Transcatheter Mitral Valve Replacement (TMVR) System –
designed for trans-apical delivery of a self-expanding bioprosthetic valve
within the native mitral valve 
Study Design & 
Purpose: 
The study is a prospective, multi-center, non-randomized study to evaluate
the safety and performance of The Intrepid™ TMVR System in patients
with severe, symptomatic mitral regurgitation, who are at high risk for
conventional mitral valve surgery. 
Objectives: 
The primary objective is to evaluate the safety of The Intrepid™ TMVR
System  
 
The primary endpoint is assessment of the nature, severity and
frequency of complications associated with the delivery and/or
implantation of the device 
The secondary objective is to evaluate the performance of The Intrepid™
TMVR System 
 
The secondary endpoints include assessment of: 
- The degree of improvement of MR grade and symptoms, and
the durability of TMVR function 
- The ability to accurately deliver and place the implant within
the native anatomy 
- The fit of the implant within the native anatomy, including
fixation, sealing and compatibility with native structures  
Patient 
Population: 
This study will enroll and treat up to 70 subjects who require replacement
of their native mitral valve because of severe, symptomatic mitral
regurgitation, but are at high risk for conventional mitral valve surgery. 
Inclusion 
Criteria: 
1. Severe mitral regurgitation (MR Grade 3-4+) 
2. Symptomatic mitral regurgitation (NYHA Class II-IV)   
3. Deemed to be at high risk for conventional mitral valve surgery by the
local heart team (including, at minimum, a cardiac surgeon,
interventional cardiologist, and an echocardiologist) 
4. Age ≥ 18 
5. Native mitral valve geometry and size compatible with the Intrepid™
TMVR 
6. No or minimal mitral valve calcification 
7. Willing to sign Informed Consent for participation in the study and
return for all required post-procedure follow-up visits 
 

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Exclusion 
Criteria: 
1. Left ventricular ejection fraction (LVEF) < 20 
2. Evidence of intracardiac mass, thrombus, or vegetation 
3. Pulmonary hypertension (> 70 mmHg systolic)  
4. Hypertrophic Obstructive Cardiomyopathy (HOCM) 
5. Prior mitral valve surgery or endovascular procedure, any currently
implanted mechanical prosthetic valve, or need for other valve
surgery/procedure  
6. Any endovascular therapeutic interventional or surgical procedure
performed within 30 days prior to enrollment 
7. Prior stroke within 30 days 
8. Need for coronary revascularization 
9. Need for emergent surgery 
10. History of, or active, endocarditis 
11. GI bleeding within 6 months 
12. History of bleeding diathesis or coagulopathy or patient will refuse
blood transfusion 
13. Hemodynamic instability 
14. Platelet count of <75,000 cells/mm3 
15. Renal insufficiency (Creatinine > 2.5 mg/dL)   
16. Active infections requiring current antibiotic therapy (if temporary
illness, patients may enroll 2 weeks after discontinuation of antibiotics)
17. Contraindication to transesophageal echocardiography (TEE) 
18. Known hypersensitivity or contraindication to study or procedure
medications/contrast which cannot be adequately managed medically.
19. Pregnant, nursing or planning to be pregnant.  (Female participants of
childbearing potential must have a negative pregnancy test prior to
enrollment). 
Follow-up 
schedule: 
Treated subjects will be followed up at 1, 3, 6 and 12 months, and every 6
months through 5 years (see Appendix A).   
Study Duration: It is expected that study subjects will be enrolled over a period of
approximately 9 months and will be followed for 5 years post-implant.   
Sponsor 
Medtronic, Inc. 
8200 Coral Sea St NE 
Mounds View, MN 55112 
United States 

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Table of Contents 
 
1. 
Introduction and Rationale 
5 
2. 
Device Description 
5 
2.1 
Intended Use 
6 
2.2 
Shipping/Storage 
6 
3. 
Study Design 
6 
3.1 
Study Purpose 
6 
3.2 
Study Objectives 
6 
3.3 
Study Population 
7 
3.4 
Study Duration 
8 
3.5 
Subject Withdrawal 
8 
3.6 
Subject Identification and Confidentiality 
8 
4. 
Study Procedures 
8 
4.1 
Screening/Baseline 
9 
4.2 
Surgical Procedure 
9 
4.3 
Investigational TMVR Procedure 
10 
4.4 
Conclusion of the procedure 
10 
4.5 
Prior to Discharge 
10 
4.6 
Post-Procedure Follow-Up 
11 
4.7 
Subject Death 
11 
4.8 
Study Termination 
11 
4.9 
Protocol Deviations 
11 
4.10 
Protocol Exceptions 
12 
5. 
Risk/Benefit Analysis 
13 
5.1 
Potential Benefits 
13 
5.2 
Potential Risks 
13 
5.3 
Risk Minimization 
15 
5.4 
Risk/Benefit Summary 
15 
6. 
Adverse Events 
15 
6.1 
Adverse Events & Definitions 
15 
6.2 
Adverse Events Reporting 
16 
7. 
Statistical Considerations 
17 
8. 
Ethical, Regulatory and Administrative Considerations 
18 
8.1 
Informed Consent 
18 
8.2 
Investigator Responsibilities 
18 
8.3 
Sponsor Responsibilities 
19 
8.4 
Data Safety Monitoring Board 
21 
8.5 
Protocol Changes 
21 
8.6 
Investigational Device Accountability 
22 
8.7 
Publication Policy 
22 
Appendix A:   Schedule of Visits and Procedures 
23 
Appendix B:   Participant Information and Consent Form 
24 
Appendix C:   Instructions for Use 
25 
Appendix D:   Endpoint Definitions 
26 
 
 
 
 
 

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1. 
Introduction and Rationale 
In partnership with cardiac surgeons, cardiologists, and cardiac pathologists, Medtronic, Inc. 
(formally Twelve, Inc.)  has developed an implant to treat patients with severe, symptomatic mitral 
regurgitation.  Mitral regurgitation (MR) affects millions of people worldwide. It is the most 
common type of heart valve defect, affecting one in 10 people aged 75 and older.  The condition 
occurs when the heart’s mitral valve does not close completely, causing blood to leak backward 
into the left atrium with every heartbeat.  Over time, left ventricular dilatation and dysfunction 
occurs in an attempt to accommodate the increased volume load and maintain cardiac output.  
Ultimately, chronic volume overloading of the left ventricle results in contractile dysfunction, 
symptoms of heart failure, and in increased risk of sudden death.  Patients with severe 
symptomatic MR have a poor prognosis with an annual mortality rate of 5% per year without 
surgical intervention.  Progressive heart failure is the usual cause of death, but sudden death, 
stroke, and endocarditis are other causes of death. 
The investigational device is called the Intrepid™ Transcatheter Mitral Valve Replacement 
(TMVR) System, manufactured by Medtronic, Inc.  It is designed for trans-apical access and 
delivery of a self-expanding bioprosthetic valve within the native mitral valve.  The Intrepid™ 
TMVR implant is intended to function similarly to a standard bioprosthetic valve implant, in that it 
allows blood to flow only in the forward direction, thereby relieving mitral regurgitation.  A 
standard valve implant, however, is sewn directly into the heart during surgery in which the chest 
is fully open, the patient is put on cardiopulmonary bypass support and the heart is temporarily 
stopped.  The Intrepid™ TMVR implant is intended to be placed through a less invasive mini-
thoracotomy procedure, without requiring cardiopulmonary bypass support or stopping the heart, 
thereby reducing the risks associated with these more invasive procedures.  The concept of The 
Intrepid™ TMVR System for mitral valve disease is similar to the concept of currently approved 
systems for standard trans-apical Transcatheter Aortic Valve Implantation (TAVI) systems for 
aortic valve disease. 
Prior to human use, the Intrepid™ TMVR system underwent extensive bench-top testing and pre-
clinical animal studies demonstrating successful TMVR placement and function.   
The human clinical experience to date has demonstrated successful implantation of the Intrepid™ 
TMVR system, proper TMVR function, and substantial reduction or elimination of mitral 
regurgitation, warranting continued study in additional patients.   
2. 
Device Description 
The Intrepid™ Transcatheter Mitral Valve Replacement (TMVR) System consists of the following 
components: an implantable bioprosthesis, a delivery system, and a loading system.   
The Intrepid™ TMVR bioprosthesis is comprised of three structures.  The inner Nitinol stent 
supports a bioprosthetic valve composed of bovine pericardial tissue leaflets and woven 
polyester fabric.  The outer Nitinol fixation ring structure engages the native mitral valve annulus 
to provide fixation and sealing.  As the inner stent and outer fixation ring structures are connected 
only at points along the ventricular rim, the fixation ring can conform to fit the dynamic anatomy 
of the mitral valve throughout the cardiac cycle, without distorting the inner stent or replacement 
valve.  This isolation reduces the dynamic, asymmetrical loading of the valve leaflets and is 
intended to prolong valve durability and ensure consistent hemodynamics.  In addition, a woven 
polyester skirt is attached to the top of the fixation ring and flares outward to form an atrial brim.  
The brim is reinforced with flexible Nitinol wire that is structurally independent of the fixation ring 
to allow each component to conform to the anatomy. 

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The Intrepid™ TMVR delivery system is designed for trans-apical access and consists of an apical 
introducer sheath (with a dilator) and a delivery catheter.  The bioprosthesis is compressed using 
Intrepid™ TMVR loading system before loading into the capsule. The delivery catheter is then 
used to deliver the implant through the apical sheath into the left ventricle and across the mitral 
valve.  When properly positioned (using fluoroscopy and echocardiography guidance), the 
capsule is retracted, to gradually deploy and fully release the self-expanding implant within the 
native mitral valve.  
 
Refer to Instructions for Use (Appendix C) for additional details regarding the device description, 
packaging, sterilization and storage conditions. 
2.1 
Intended Use 
The Intrepid™ TMVR System is intended for use as a replacement mitral valve for treatment of 
mitral regurgitation. Currently, The Intrepid™ TMVR System is for Clinical Investigation use 
only, in accordance with this Clinical Investigation Plan. 
2.2 
Shipping/Storage 
Good Clinical Practice guidelines require accounting for the disposition of all investigational 
devices received by each clinical site.  Information on device disposition consists of the date 
received, date used, and the subject in whom the device was used.  The Investigator is 
responsible for accounting for all used and unused devices. 
 
 
The Intrepid™ TMVR System will be hand carried or shipped to the sites at intervals dependent 
on the rate of subject accrual.  The site will use a device accountability form to document the 
inventory and study device disposition.  All Intrepid™ TMVR devices must be stored at room 
temperature in an area free of environmental extremes and with limited access.  Medtronic will 
inspect the storage area and will monitor device accountability. 
 
3. 
Study Design  
3.1 
Study Purpose 
The study is a prospective, multi-center, non-randomized study to evaluate the safety and 
performance of The Intrepid™ TMVR System in patients with severe, symptomatic mitral 
regurgitation, who are at high risk for conventional mitral valve surgery. 
3.2 
Study Objectives  
The primary objective of the study is to evaluate the safety of The Intrepid™ TMVR System  
 
The primary endpoint is assessment of the nature, severity and frequency of complications 
associated with the delivery and/or implantation of the device 
 
The secondary objective of the study is to evaluate the performance of The Intrepid™ TMVR 
System: 
 
The secondary endpoints include assessment of: 
- The degree of improvement of MR grade and symptoms, and the durability of TMVR 
function 
- The ability to accurately deliver and place the implant within the native anatomy 

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- The fit of the implant within the native anatomy, including fixation, sealing and 
compatibility with native structures (e.g., other components of the mitral valve 
apparatus, the conduction system, and the left ventricular outflow tract/aortic valve) 
3.3 
Study Population 
This study will enroll and treat up to 70 subjects who require replacement of their native mitral 
valve because of severe, symptomatic mitral regurgitation, but are at high risk for conventional 
mitral valve surgery.  
 
Patients will be screened prior to study entry to determine if they meet the Eligibility Criteria. 
Patients who have signed an Informed Consent and fulfill the inclusion criteria and none of the 
exclusion criteria listed below are eligible for enrollment. 
3.3.1 Inclusion Criteria 
The subject must meet ALL of the following criteria: 
1. Severe mitral regurgitation (MR Grade 3-4+) 
2. Symptomatic mitral regurgitation (NYHA Class II-IV)   
3. Deemed to be at high risk for conventional mitral valve surgery by the local heart 
team (including, at minimum, a cardiac surgeon, interventional cardiologist, and an 
echocardiologist) 
4. Age ≥ 18 
5. Native mitral valve geometry and size compatible with The Intrepid™ TMVR 
6. No or minimal mitral valve calcification 
7. Willing to sign Informed Consent for participation in the study and return for all 
required post-procedure follow-up visits 
3.3.2 Exclusion Criteria 
The subject may not meet any of the following criteria: 
1. Left ventricular ejection fraction (LVEF) < 20 
2. Evidence of intracardiac mass, thrombus, or vegetation 
3. Pulmonary hypertension (> 70 mmHg systolic)  
4. Hypertrophic Obstructive Cardiomyopathy (HOCM) 
5. Prior mitral valve surgery or endovascular procedure, any currently implanted 
mechanical prosthetic valve, or need for other valve surgery/procedure  
6. Any endovascular therapeutic interventional or surgical procedure performed within 
30 days prior to enrollment 
7. Prior stroke within 30 days 
8. Need for coronary revascularization 
9. Need for emergent surgery 
10. History of, or active, endocarditis 
11. GI bleeding within 6 months 
12. History of bleeding diathesis or coagulopathy or patient will refuse blood transfusion 

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13. Hemodynamic instability 
14. Platelet count of <75,000 cells/mm3 
15. Renal insufficiency (Creatinine > 2.5 mg/dL)   
16. Active infections requiring current antibiotic therapy (if temporary illness, patients 
may enroll 2 weeks after discontinuation of antibiotics) 
17. Contraindication to transesophageal echocardiography (TEE) 
18. Known hypersensitivity or contraindication to study or procedure 
medications/contrast which cannot be adequately managed medically. 
19. Pregnant, nursing or planning to be pregnant.  (Female participants of childbearing 
potential must have a negative pregnancy test prior to enrollment). 
3.3.3 Patient Review Committee 
A Patient Review Committee (PRC) will consist of cardiac surgery, interventional cardiology, and 
echocardiology representatives who are not participating investigators.  The PRC will serve in an 
advisory capacity to Medtronic and will review potential patients’ clinical and imaging data to help 
ensure appropriate patient selection across all sites.  
3.4 
Study Duration 
It is expected that study subjects will be enrolled over a period of approximately 9 months and will 
be followed for 5 years post-implant.   
3.5 
Subject Withdrawal  
The subject’s participation in this study is completely voluntary.  If the subject decides not to 
participate or to withdraw from the study, their decision will have no effect on any services or 
treatment the subject is currently receiving and will not affect their relationship with their doctor. 
 
If a subject chooses to withdraw from the study, the reason for withdrawal will be investigated and 
carefully documented.  If subject withdraws after the investigational TMVR implant is implanted, 
the subject shall be instructed and encouraged to continue follow up visits for evaluation of the 
function of the implant and the subject’s health status.   
3.6 
Subject Identification and Confidentiality 
A study subject’s medical record, including subject identification, will be made available for review 
by the study Sponsor, their representatives, and appropriate regulatory authorities.  However any 
copies of medical records or Case Report Forms used to collect study data by the Sponsor, will 
only identify subjects by a unique reference number including the subjects’ initials.  Study results 
or information about the study that is made public, will in no way disclose any subject’s identity. 
4. 
Study Procedures 
The following sections outline the details of the clinical study methods for the Intrepid™ TMVR 
study. Refer to Appendix A: Schedule of Visits and Procedures. 
 
For details on specific use of The Intrepid™ TMVR refer to the Instructions for Use (Appendix C).   

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4.1 
Screening/Baseline 
Standard examinations and tests, which are typically performed for patients undergoing similar 
procedures such as conventional mitral valve surgery, minimally invasive mitral valve repair (e.g., 
MitraClip), or Transcatheter Aortic Valve Implantation (TAVI) will be used both to screen eligible 
patients and provide baseline information for those patients that meet study criteria. These tests 
include: 
 Demographic information and medical history including risk factors  
 Physical examination including vital signs, height and weight, and NYHA Class 
 Transthoracic Echocardiogram (TTE) 
 Transesophageal Echocardiography (TEE) 
 Cardiac Computed Tomography (CT) 
 Coronary angiography 
 Electrocardiogram (ECG) 
 Blood tests  
- Chemistry profile including creatinine 
- CK, CKMB 
- Complete Blood Count 
- Coagulation panel 
- Urinalysis 
- Plasma free hemoglobin 
 Pregnancy test (urine or blood) if female of child-bearing age 
 6-minute walk test (6MWT) 
 Quality of Life (QOL) survey – Minnesota Living with Heart Failure Questionnaire  
4.2 
Surgical Procedure  
 Subjects will be prepped for surgery according to standard procedures 
- Anesthesia and antibiotic therapy following standard hospital practices for surgery 
 Introducer sheath placement (via standard access for right heart catheterization and 
optional arterial access for pigtail catheter and optional left ventriculogram) 
 Transesophageal echocardiography (TEE) 
 Fluoroscopy to confirm C-arm angles 
 Electrocardiogram (ECG) 
 Hemodynamic measures (baseline)  
- Pulmonary capillary wedge pressure or LA pressure  
- Pulmonary artery pressure  
- Right atrial pressure 
- Systemic arterial pressure  
- Cardiac output 
- Left ventricular peak systolic and end-diastolic pressure (optional if pigtail is placed) 
- Pressure gradient across the aortic valve (optional if pigtail is placed) 
 Prepare for cardio-pulmonary bypass (CPB) per physician discretion 

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 Obtain surgical access to expose the LV apex via left mini-thoracotomy per physician 
discretion 
4.3 
Investigational TMVR Procedure  
Refer to The Intrepid™ TMVR Instructions for Use (Appendix C) for details of The Intrepid™ 
TMVR implantation procedure.   
 Anticoagulation therapy following standard hospital practices for surgery 
 Optional initiation of CPB per physician discretion 
 Purse-string sutures placed at apical access point  
 Trans-apical access with The Intrepid™ TMVR delivery system sheath 
 Optional left ventriculogram  
 Intrepid™ TMVR placement with echo and fluoro 
 Close apical access 
 Evaluate The Intrepid™ TMVR (off CPB, if previously initiated) 
- TEE 
- Fluoro 
- ECG 
- Hemodynamic measures (as above) 
 If The Intrepid™ TMVR implant is positioned and functioning satisfactorily, close the 
surgical incision per standard procedures 
 If The Intrepid™ TMVR implant is not positioned and functioning satisfactorily, consider 
removing the TMVR and replacing with a conventional surgical replacement valve per 
standard procedures. 
4.4 
Conclusion of the procedure  
 Assess cardiac function including MR grade via final TEE  
 Assess for adverse events  
4.5 
Prior to Discharge 
Subjects will be cared for through discharge according to standard procedures for mitral valve 
replacement surgery.  Specific anticoagulation/antiplatelet therapy will be prescribed per 
physician discretion, but is recommended for at least 3-6 months post-implant, and longer 
unless there is a clinical indication to cease it.  
 
Prior to discharge, the following standard exams and tests will be performed: 
 Physical exam and review of adverse events  
 TTE and/or TEE evaluation 
 ECG 
 Blood tests  
- Chemistry profile including creatinine 
- Complete Blood Count 
- CK, CKMB 
- Coagulation panel 

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- Urinalysis 
- Plasma free hemoglobin 
 Cardiac Computed Tomography (CT) – mandatory at US sites only 
4.6 
Post-Procedure Follow-Up 
The following standard exams and tests will be performed at 1, 3, 6 months (± 2 weeks), at 12 
months and every 6 months (± 30 days) through 5 years: 
 Physical exam (including NYHA Class) and review of adverse events  
 6 minute walk test (6MWT) 
 TTE and/or TEE evaluation 
 ECG 
 Blood tests  
- Chemistry profile including creatinine 
- CK, CKMB 
- Complete Blood Count 
- Coagulation panel 
- Urinalysis 
- Plasma free hemoglobin 
 
In addition, at 12 months only, the following will be performed: 
 Cardiac Computed Tomography (CT) 
 QOL survey – Minnesota Living with Heart Failure Questionnaire 
 
Note:  If a subject’s TMVR implant is replaced with surgical replacement valve, the subject will be 
followed through 1 month post-surgical replacement.  
4.7 
Subject Death 
In the event that a subject dies after implantation of the TMVR system, the Investigator will make 
reasonable effort to have an autopsy performed to help determine the extent to which the subject’s 
death was related to the device/procedure.  If possible, the TMVR system will explanted and 
returned to the Sponsor.  Sponsor will provide instructions for proper return of the device. 
4.8 
Study Termination 
The study may be terminated by the Sponsor or the Investigator at any time. However, scheduled 
follow-up, as described in Section 4.6, should continue for all subjects who were treated prior to 
the termination of the study. 
4.9 
Protocol Deviations 
A protocol deviation is a failure to comply with the requirements specified within this 
Investigational Plan without adequate justification. Examples of protocol deviations may include 
enrollment of a subject that does not meet all of the inclusion/exclusion criteria, or failure to 
conduct follow-up visits. 
 
All protocol deviations are reviewed by the Sponsor and assessed for their impact on subject 
safety. The Sponsor will notify the Investigator of deviations and will report all deviations to the 
appropriate regulatory bodies as required. 

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4.10 Protocol Exceptions 
A protocol exception is a special circumstance that necessitates a variance in the standard 
treatment procedures specified in this Investigational Plan. Such variances will be minimized and 
will not jeopardize subject safety or affect the integrity of the clinical study. 
 
Protocol exceptions require prior approval from the Sponsor. The Sponsor will provide written 
documents of such approval to the Investigator and this correspondence should be maintained 
within the subject’s file. 

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5. 
Risk/Benefit Analysis 
This pilot study will enroll only patients with severe, symptomatic mitral regurgitation, who are at 
high risk for conventional mitral valve surgery.   
 
These high risk patients, nevertheless, require treatment. This less invasive TMVR procedure 
may provide an alternative mitral valve replacement for patients for whom conventional surgery 
is not an option.     
5.1 
Potential Benefits 
Patients who are eligible for this study suffer from severe, symptomatic mitral regurgitation that 
requires treatment.  A participant may benefit from replacement of the native valve for treatment 
of mitral regurgitation. The potential benefits include a reduction of mitral regurgitation and the 
possible health improvements and/or symptom relief associated with that reduction in mitral 
regurgitation.  Other benefits of participation in this study are altruistic and are related to the 
knowledge and information that will be obtained to further the design and development of The 
Intrepid™ TMVR for transcatheter treatment of mitral regurgitation in the population of patients 
who cannot undergo open surgery for mitral valve repair or replacement.   
5.2 
Potential Risks  
The potential risks associated with the investigational TMVR procedure are similar to the risks of 
cardiac surgery and mitral valve replacement. These risks may include, but are not limited to, the 
following risks: 
 
Death 
 
Cardiac damage or perforation, cardiac tamponade or pericardial effusion 
 
Coronary artery perforation, spasm, occlusion or obstruction 
 
Heart rhythm disturbances (e.g., atrial fibrillation, cardiac arrest) 
 
Conduction system disturbances (e.g., atrioventricular node block, left-bundle branch 
block, asystole), which may require a permanent pacemaker  
 
Aortic valve dysfunction (e.g., regurgitation or stenosis) 
 
Myocardial infarction, ischemia or angina 
 
Reduced cardiac function or continuing or worsening heart failure 
 
Stroke or transient ischemic attack (TIA) 
 
Encephalopathy / neurological deficit 
 
Renal insufficiency or failure (possibly requiring dialysis) 
 
Pulmonary complications (e.g., pulmonary congestion, hypertension, thrombo-embolism, 
dyspnea, respiratory failure, atelectasis, pneumonia) 
 
Surgical incision site complications (e.g., infection, inflammation, bleeding, hemothorax, 
hematoma, pain, irreversible nerve injury, wound dehiscence) 
 
Bleeding (possibly requiring a transfusion or other intervention) 
 
Emboli (air, thrombus) 
 
Infection (e.g., at incision sites, endocarditis, septicemia) 
 
Viral infection including Bovine Spongiform Encephalopathy (BSE) 
 
Blood abnormality (e.g., coagulopathy, hemolysis, anemia) 
 
Allergic or drug reaction (e.g., to anesthetic, contrast, Heparin, protamine, nickel alloy, 
latex) 

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 
Esophageal complications due to transesophageal echocardiography (e.g., irritation, 
perforation, stricture) 
 
Tracheal complications due to intubation (e.g., irritation, perforation, dysphagia) 
 
Vascular access site complications (e.g., trauma, dissection, perforation, infection, 
inflammation, pain, bleeding, hematoma, pseudoaneurysm, irreversible nerve injury, 
compartment syndrome, arteriovenous fistula, stenosis)  
 
Vascular complications (e.g., trauma, dissection, perforation, pseudoaneurysm, spasm, 
or occlusion) 
 
Aortic complications (e.g., trauma, dissection, perforation, aneurysm, pseudoaneurysm, 
or occlusion) 
 
Other systemic effects or symptoms (e.g., abnormal lab values, electrolyte imbalance, 
fever, hyperthermia, hypotension, hypertension, syncope, nausea, vomiting, edema, 
deep vein thrombosis, pleural effusion, lymphatic complications, urinary tract infection, 
multi-system organ failure, gastrointestinal bleeding, ischemia or infarction) 
 
Valve implant dysfunction (e.g., fracture, bending, under-expansion, suture breaks, 
calcification, pannus, thrombus, inflammation, stenosis, leaflet wear, tear, prolapse, 
retraction, poor valve coaptation, leaks, regurgitation, mal-sizing [prosthesis-patient 
mismatch]) 
 
The risks of the investigational TMVR procedure are similar to the surgical risks listed above; 
however some may be increased with the TMVR procedure or implant.  For example, the risks of 
cardiac damage may be increased by the TMVR delivery, and the risk of valve implant dysfunction 
(as compared to surgical replacement valves) has not yet been established.   
 
In addition to the risks listed above, the potential risks associated with the TMVR procedure and 
the Intrepid TMVR System may include, but are not limited to, the following risks: 
 
Valve implant detachment, migration, malposition, and/or incorrect sizing  
 
Reduced ventricular function due to apical incision and sheath insertion 
 
Ventricular insertion site complications (e.g., bleeding, rupture, septal perforation, 
aneurysm or pseudoaneurysm) 
 
Injury to mitral valve apparatus complicating or preventing later surgical 
repair/replacement 
 
Left ventricular outflow tract (LVOT) obstruction 
 
Emergent surgical or transcatheter intervention (for example, coronary artery bypass, 
heart valve replacement or repair, transcatheter valve explant, percutaneous coronary 
intervention [PCI], balloon valvuloplasty, transcatheter valve or component retrieval) 
 
Failure to deliver the bioprosthesis to the intended site 
 
Failure to retrieve the system components 
 
Delivery system component(s) embolization 
 
Delivery system thrombosis 
 
Prolonged cardiopulmonary bypass 
 
Prolonged ventilation, anesthesia, and/or procedure time 
 
Radiation skin burn or tissue reaction 
 
The likelihood of these risks is unknown, as this is the initial introduction of the investigational 
TMVR system into a human population.  However, bench-top testing and animal studies have 

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demonstrated that the TMVR procedure can safely and reliably result in stable positioning of The 
Intrepid™ TMVR implant and the desired improvement in hemodynamic performance.   
 
There may be other, as yet unknown, complications that may occur as a result of this procedure.  
If these or any of the above complications occur, they may lead to repeat or prolonged 
hospitalization, repeat procedures, emergency surgery, other emergency procedures, or in rare 
cases, death. The study doctor and/or his research staff will make every effort to minimize 
additional risks. 
5.3 
Risk Minimization 
Every attempt will be made to minimize the chance that these risks occur.  For example, as stated 
above, subjects will be prepared for and may be connected to cardiopulmonary bypass (CPB) 
prior to the TMVR procedure, but CPB will not necessarily be started.  If there is a complication 
with the TMVR procedure or device, this allows for rapid initiation of CPB, and open heart surgery 
to resolve the problem. 
 
In addition, this protocol provides additional steps to minimize risk to study subjects.  These 
include the following: 
 
Investigator Selection:  The investigators in this study is selected based on their 
experience in performing cardiac surgery and cardiovascular interventional procedures. 
 
Investigator Training:  Investigator(s) will be trained in proper device operation prior to 
study start.  Training will include didactic and hands-on training with the TMVR System 
(bench-top model or animal). 
 
Subject Screening:  The study protocol includes appropriate precautions in subject 
selection and potential subjects will be reviewed with Investigators and advisors to select 
appropriate subjects who may benefit from the TMVR procedure. 
5.4 
Risk/Benefit Summary 
The human clinical experience, to date, has demonstrated successful implantation of the 
Intrepid™ TMVR system, proper TMVR function, and elimination of mitral regurgitation, 
warranting continued study in additional subjects, as proposed in this study.  The subjects who 
are eligible for this study suffer from severe, symptomatic mitral regurgitation, but are at high risk 
for conventional surgery and lack other treatment options.  As such, the potential benefit of a less 
invasive procedure to reduce their mitral regurgitation is considered to outweigh the risks of the 
TMVR procedure. 
 
6. 
Adverse Events 
Adverse Events are defined and must be reported as specified below. 
6.1 
Adverse Events & Definitions 
Adverse Event (AE): Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or other 
persons, whether or not related to the investigational medical device. 
 
Adverse Device Event (ADE):  Adverse event related to the use of an investigational medical 
device 
 

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Serious Adverse Event (SAE): Any adverse event that 
a) led to death, 
b) led to serious deterioration in the health of the subject, that either resulted in 
1) a life-threatening illness or injury, or 
2) a permanent impairment of a body structure or a body function, or 
3) in-patient or prolonged 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) led to foetal distress, foetal death or a congenital abnormality or birth defect 
 
NOTE:  Planned hospitalisation for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
 
Serious Adverse Device Effects (SADE): Adverse device effect that has resulted in any of the 
consequences characteristic of a Serious Adverse Event. 
 
AEs or SAEs will also be classified as to their relationship to the Investigational Device, as follows:   
Not Related: The event is due to an underlying or concurrent illness or effect of another 
device, drug or intervention and is not related to the investigational device or procedure.  
Remotely Related:  The event’s relationship to the investigational device or procedure, 
cannot be completely ruled out, but is unlikely, and an alternative etiology is more likely. 
Possible: The event has a strong temporal relationship to the investigational device or 
procedure, and an alternative etiology is equally or less likely.  
Probable: The event has a strong temporal relationship to the use of the investigational 
device or procedure and another etiology is unlikely or significantly less likely.  
Definite: The event can only be attributed to the use of the investigational device or 
procedure.   
Not Assessable: The event’s relationship to the use of the investigational device or 
procedure cannot be assessed. 
 
If an AE or SAE is determined to be probably or definitely related to the investigational device and 
has not been previously anticipated, the clinical finding would further be classified as an 
unanticipated device related adverse effect.   
 
Unanticipated Serious Adverse Device Effect (UADE/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.  
 
6.2 
Adverse Events Reporting 
The Investigator is ultimately responsible for reporting adverse events to the IRB/Ethics 
Committee, as required, and to Medtronic.  Adverse events should be reported to Medtronic on 
the appropriate Case Report Form (CRF).  
 
In addition, the Investigator must report USADEs and SAEs to Medtronic as soon as possible, but 
in no circumstances later than two (2) working days after the Investigator first learns of the event. 
 
The initial report must be followed by full and complete documentation, including the time and 
date of onset, complete description of the event, severity, duration, actions taken and outcome, 
and should also be recorded on the appropriate Case Report Form. 

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As required by national legislation, Medtronic will make the appropriate reports to the national 
competent authorities.  
7. 
Statistical Considerations 
The objectives of this prospective, non-randomized Early Feasibility Study are to evaluate the 
safety and performance of The Intrepid™ TMVR System.  A comprehensive analysis of the 
feasibility study results, as a whole, will be assessed to evaluate the overall risk/benefit balance 
for the patient population being treated.  In addition, the following endpoints will be assessed and 
reported: 
 
Primary safety endpoint: 
 
Implant or delivery related serious adverse events (through 30 days post-procedure) 
 
Secondary performance endpoints: 
 
Successful access, delivery of implant, and retrieval of the delivery system 
 
Reduction in MR Grade from baseline (measured by echo through 30 days post-
procedure) 
 
No significant MV stenosis (measured by echo through 30 days post-procedure) 
 
LV outflow tract (LVOT) patency (measured by echo through 30 days post-procedure) 
 
Improvement of NYHA Class from baseline (through 30 days post-procedure) 
 
Additional exploratory endpoints:   
 
Measured by echo post-procedure through 5 years: 
o Reduction in MR Grade from baseline  
o No significant MV stenosis 
o LVOT outflow tract (LVOT) patency  
o Improvement in LVEF  
o Improvement in cardiac output/cardiac index 
o Reduction in LV end-systolic and end-diastolic dimensions 
 
Change in 6MWT from baseline through 5 years 
 
Change in QOL (MLHF) from baseline through 5 years 
 
Change in NYHA from baseline through 5 years 
 
Procedural times (e.g., deployment time, apical access duration, rapid pacing 
duration) 
 
Re-hospitalizations for heart failure through 5 years 
 
MVARC1 defined outcomes of: (see Appendix D for specific definitions) 
- Technical success  
- Device success  
- Procedural success  
- Individual subject success  
 

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Event and endpoint definitions for this study’s analysis will be based on those definitions outlined 
in the MVARC Consensus Document1.  Each subject’s data will be reviewed individually and case 
summaries for all subjects will be provided to FDA.  The data analysis will include all subjects who 
undergo the TMVR procedure and all available follow-up data (e.g., key echocardiographic 
measures and subjects status) at each post-procedure interval.  
 
Study results will be summarized using standard descriptive statistics.  However pre-defined 
statistical “success” or “pass” criteria for the study endpoints are not applicable for this feasibility 
study, as it is not a powered, hypothesis driven study.  Baseline demographic and clinical 
variables will be summarized. Continuous variables will be summarized with means, standard 
deviations, medians, interquartile ranges, minimums, and maximums.  Categorical variables will 
be summarized with frequencies and percentages.  
 
The sample size is based upon industry standards for pilot stage studies of medical devices; the 
sample size was not statistically derived, as this is not a hypothesis-testing study.  
 
8. 
Ethical, Regulatory and Administrative Considerations 
8.1 
Informed Consent 
A Patient Information and Consent Form (PICF) template is provided in Appendix B.  The 
Investigator is responsible for obtaining an IRB/Ethics Committee (EC) approved version of the 
PICF prior to enrolling any subjects into the study.   
 
The Investigator must ensure that each study subject provides written informed consent for their 
inclusion in the study after explaining the rationale for and the details, aims and objectives of the 
study, the risks and benefits of participation, alternative treatments, and the extent of the patient’s 
involvement.  Each study subject must sign and date the informed consent, and the Investigator, 
or designee, must sign and date the consent confirming that he/she fully explained the study to 
the subject. The Investigator must ensure that no patient is subject to any non-standard study-
required procedures before the patient has given his/her written informed consent. 
 
After obtaining signature of the patient, duly signed informed consents, as well as written 
information given to patients shall be kept and archived in the Investigator file according to the 
requirements of the country’s regulations.  
8.2 
Investigator Responsibilities 
The Investigator is responsible for the management of subjects involved in this clinical study as 
well as for the clinical use of The Intrepid™ TMVR at the study site.  The Investigator will assume 
overall responsibility and accountability for the research team and for the clinical data obtained 
from subjects participating in the study.  The Investigator will be responsible for: 
- Ensuring EC approval for this Investigational Plan and any amendments. 
- Ensuring that the clinical study is conducted according to this Investigational Plan, 
federal, state and local regulations, and the signed agreement. 
                                                 
1 Stone GW, Vahanian AS, Adams DH, et al.  Clinical Trial Design Principles and Endpoint Definitions for 
Transcatheter Mitral Valve Repair and Replacement:  Part 1 Clinical Trial Design Principle, J Am Coll Cardiol 
2015;66:278-307 

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- Obtaining informed consent on the approved IRB/EC Informed Consent Form prior to 
any study participation. 
- Reporting adverse events to the IRB/EC, regulatory agencies, and the Sponsor, as 
required 
- Controlling any investigational device(s) stored at their site, if any. This includes 
supervising and disposal of devices. 
- Protecting the rights, safety and welfare of the subjects. 
- Maintaining records and reports as outlined in Section 8.2.1. 
- Reviewing and signing all case report forms for subjects enrolled in the clinical study 
under the Investigator’s care. 
8.2.1 Investigator Records 
The investigator will maintain complete, accurate and current study records during the course of 
the clinical study. The Sponsor will notify the Investigator when the records can either be 
destroyed or forwarded to the Sponsor, in accordance with applicable regulations. The clinical 
study records must be maintained by the site until that notice is provided. These records include: 
Subject Records: Signed informed consent forms, copies of all completed CRFs and 
supporting documentation (laboratory reports, angiograms, etc.) and records of exposure 
of each subject to the device (procedure note for example). 
Investigational Plan: A current copy of the Investigational Plan, including the Instructions 
for Use, the Investigator’s Brochure and a blank copy of the CRFs. 
Unanticipated Serious Adverse Device Effects: Record of all reports and information 
pertaining to unanticipated device effects.  
IRB/EC: All information pertaining to IRB/EC review and approval of this clinical study, 
including a copy of the IRB/EC approval letter and a blank informed consent form 
approved by the IRB/EC. 
Investigator Agreements: Copies of the singed Investigator’s Agreement with the 
Investigator’s Curriculum Vitae attached. 
Other: Any records that may be required by applicable laws and regulations 
8.2.2 Compliance to Regulations 
The investigational study will be performed in accordance with this Investigational Plan, the United 
States Food and Drug Administration (FDA) and local regulations where applicable, EN ISO 
14155:2011, applicable local regulations, the ethical requirements defined in the Declaration of 
Helsinki and any conditions of approval imposed by the reviewing IRB/Ethics Committee and the 
approving federal higher authority. Failure to comply with and/or inability to meet applicable 
national regulations may jeopardize continued participation in this study by the investigator or the 
study site. 
8.3 
Sponsor Responsibilities 
The Sponsor of this clinical study, Medtronic is responsible for the following: 
- Selecting qualified Investigators and investigation centers and providing them with the 
information they need to conduct the investigation properly including adequate training 
on use of the device and inclusion / exclusion criteria. 
- Ensuring that IRB/EC review and approval are obtained and remain current. 

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- Ensure that national regulatory bodies are duly informed of and allow the clinical study 
to commence. 
- Ensure that IRB/ECs and any applicable national regulatory bodies are informed of 
significant new information about the clinical study. 
- Conducting evaluations of unanticipated adverse device effects and reporting to 
IRB/ECs and regulatory bodies as required. 
- Controlling the device(s) under investigation. 
- Maintaining adequate contact with the Investigator and conducting periodic on-site 
monitoring visits to ensure compliance with the Investigational Plan and to ensure the 
facility continues to be adequate for this study. 
- Maintaining the following records: 
o All essential correspondence related to the clinical study 
o Signed Investigator Agreement 
o Curriculum vitae for each Investigator 
o Records of device shipment and disposition (shipping receipts, material 
destruct records, etc.) 
o Adverse event information  
o Complaint documentation 
o All data forms, prepared and signed by the Investigators and received 
source documentation and core lab reports, if applicable 
o Protocol and report of prior investigations 
o Site monitoring reports 
o Financial disclosure information 
 
The Sponsor is responsible for the preparation of, the accuracy of the data contained in, the 
review of and the submission of the reports listed in Table 1.  
 
Table 1:  Sponsor Reporting Responsibilities 
Report 
Submit to 
Description 
Unanticipated Adverse 
Device Effects (UADE) 
IRB, Investigators, 
FDA 
Sponsor will report on any confirmed 
unanticipated adverse device effect 
within 10 working days after first 
receiving notice of the effect. (21 CFR 
812.150) 
Withdrawal of IRB 
approval 
IRB, Investigators, 
FDA 
Notification, when appropriate, will be 
made within 5 working days after 
Sponsor receives notice of withdrawal of 
IRB approval. 
Withdrawal of FDA  
approval 
IRB, Investigators 
Notification will be made within 5 working 
days after Sponsor receives notice of 
withdrawal of FDA approval. 

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Report 
Submit to 
Description 
Current Investigator List 
FDA 
Sponsor will submit a current list of the 
names and addresses of all participating 
Investigators at six-month intervals, 
beginning six months after FDA approval 
of IDE. 
 
8.3.1 Study Monitoring  
Medtronic will conduct a Site Initiation visit with the Investigator and Research Team to review 
the details of the protocol, study procedures, device instructions and to confirm all required study 
documentation is in place prior to treatment of the first subject.  
 
Medtronic, or its representatives, will also conduct periodic monitoring visits to review the study 
information to ensure that the study investigators are in compliance with the protocol, applicable 
regulations and IRB/Ethics Committee requirements, and the Investigator’s Agreement.  Any 
evident pattern of non-compliance will be addressed with the Principal Investigator.  If appropriate 
corrective actions are not subsequently undertaken, Medtronic reserves the right to suspend 
enrollment at the site and/or withdraw the site from the study. 
 
During monitoring visits, the monitor will review subjects’ medical and study records to verify data 
collected on CRFs and to resolve any discrepancies.  The monitor will be provided with access to 
all pertinent records in connection with the study, including subject charts, laboratory data, etc., 
necessary to ensure integrity of the data.  Medtronic will work with participating sites to secure 
any necessary data clarifications and to obtain additional relevant medical documentation if 
necessary. 
8.3.2 Data Management 
Medtronic will be responsible for data management.  The CRFs will be provided by Medtronic, 
and CRF data will recorded using an Electronic Data Capture (EDC) system.   
CRFs will be completed in an expeditious fashion.  CRF completion may be delegated to 
appropriate study personnel but the Principal Investigator remains responsible for the accuracy 
and integrity of all data entered on CRFs.  All study-required data will be thoroughly documented 
in subject study files.   
8.4 
Data Safety Monitoring Board 
A Data and Safety Monitoring Board (DSMB) is an autonomous group that will serve in an advisory 
capacity to Medtronic.  The DSMB will consist of, at minimum, a cardiothoracic surgeon, an 
interventional cardiologist, and an echocardiologist. 
The DSMB will evaluate data periodically as subjects are enrolled and upon completion of the 
study.  The DSMB may also evaluate data if serious unanticipated adverse events are reported.  
Based upon their review of data, the DSMB can recommend continuing the study with or without 
protocol modifications, or recommend stopping the stud. 
8.5 
Protocol Changes 
Changes to this Clinical Investigation Plan will not be made without the written approval of 
Medtronic. Any protocol amendments will be approved by Medtronic and IRB/Ethics 
Committees/Regulatory bodies, as appropriate, prior to implementation of the amendment. 

The Intrepid™ TMVR Pilot Study 
 
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8.6 
Investigational Device Accountability 
Access to investigational devices shall be controlled and the investigational devices shall be used 
only in the clinical investigation according to this CIP.  Medtronic shall keep records to document 
the location of all investigational devices from shipment to sites until implant, return, or disposal.  
The Investigator or an authorized designee shall maintain a device accountability log documenting 
the receipt, use, return and disposal of all investigational devices at their site. When study 
enrollment is complete, the Investigator shall return any unused devices to Medtronic. 
8.7 
Publication Policy 
At the conclusion of the TMVR Pilot Study, a multi-center manuscript will be prepared for 
publication in a reputable scientific journal.  The publication of the principal results from any single 
site experience within the study is not allowed until the preparation and publication of the multi-
center results.  Any follow-up publications would require prior written approval by Publications 
Review Committee and the Sponsor.  
 
 
 

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Appendix A:   Schedule of Visits and Procedures  
 
Test / Evaluation 
Baseline 
Implant 
Procedure 
Discharge 
1, 3, 6M 
(± 2 wks) 
12M 
(± 30 
days) 
Every 
6M  
(± 30 
days) 
through 
5 yrs 
Informed Consent 
X 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
Physical Exam (including 
NYHA Class) 
X 
 
X 
X 
X 
X 
6-minute walk test 
X 
 
 
X 
X 
X 
Blood Tests:  Chemistries 
(incl. creatinine), CBC, 
CK/CK-MB, Coagulation 
panel, plasma free 
hemoglobin 
X 
X 
X 
X 
X 
X 
Pregnancy Test (blood or 
urine), if appropriate 
X 
 
 
 
 
 
ECG (12 lead) 
X 
X 
X 
X 
X 
X 
Coronary angiogram 
X 
 
 
 
 
 
Transthoracic 
Echocardiography (TTE) 
X 
 
X1 
X1 
X1 
X1 
Transesophageal 
Echocardiography (TEE) 
X 
X 
X1 
X1 
X1 
X1 
Cardiac Computed 
Tomography (CT) 
X 
 
X 
 
X 
 
Hemodynamics 
 
X 
 
 
 
 
Quality of Life (QOL) 
Survey 
X 
 
 
 
X 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
1 TTE or TEE per physician discretion 
 
 
 
 

The Intrepid™ TMVR Pilot Study 
 
CIP-1403 Version 4.0 2019.10.15 
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Appendix B:   Participant Information and Consent Form 

The Intrepid™ TMVR Pilot Study 
 
CIP-1403 Version 4.0 2019.10.15 
CONFIDENTIAL – May not be reproduced or distributed without written permission from Medtronic  
 
Appendix C:   Instructions for Use 

The Intrepid™ TMVR Pilot Study 
 
CIP-1403 Version 4.0 2019.10.15 
CONFIDENTIAL – May not be reproduced or distributed without written permission from Medtronic  
 
Appendix D:   Endpoint Definitions 
Analysis of study results will include the following additional MVARC defined exploratory 
endpoints: 
 
Technical Success (measures at exit from catheterization laboratory)  
All of the following must be present: 
I. Absence of procedural mortality; and  
II. Successful access, delivery, and retrieval of the device delivery system; and 
III. Successful deployment and correct positioning of the first intended device; and 
IV. Freedom from emergency surgery or reintervention related to the device or access procedure  
 
Device Success (measured at 30 days and at all later post-procedural intervals): 
All of the following must be present: 
I. Absence of procedural mortality or stroke; and  
II. Proper placement and positioning of the device; and  
III. Freedom from unplanned surgical or interventional procedures related to the device or access 
procedure; and 
IV. Continued intended safety and performance of the device, including: 
a. No evidence of structural or functional failure  
b. No specific device-related technical failure issues and complications 
c. Reduction of MR to either optimal or acceptable levels without significant mitral stenosis (i.e., 
post-procedure EROA is 1.5 cm2 with a transmitral gradient <5 mm Hg), and with no greater than 
mild (1+) paravalvular MR (and without associated hemolysis) 
 
Procedural Success (measured at 30 days)  
All of the following must be present: 
I. Device success (either optimal or acceptable), and 
II. Absence of major device or procedure related serious adverse event, including: 
a. Death 
b. Stroke 
c. Life-threatening bleeding (MVARC scale) 
d. Major vascular complications 
e. Major cardiac structural complications 
f. 
Stage 2 or 3 acute kidney injury (includes new dialysis) 
g. Myocardial infarction or coronary ischemia requiring PCI or CABG 
h. Severe hypotension, heart failure, or respiratory failure requiring intravenous pressors or 
invasive or mechanical heart failure treatments such as ultrafiltration or hemodynamic assist 
devices, including intra-aortic balloon pumps or left ventricular or biventricular assist devices, or 
prolonged intubation for 48 h 
i. 
Any valve-related dysfunction, migration, thrombosis, or other complication requiring surgery or 
repeat intervention 
 
Individual Subject Success (measured at 1 year) 
All of the following must be present: 
I. Device success (either optimal or acceptable), and 
II. Subject returned to the pre-procedural setting, and 
III. No rehospitalizations or reinterventions for the underlying condition (e.g., mitral regurgitation, heart 
failure); and 
IV. Improvement from baseline in symptoms (e.g., NYHA improvement by 1 functional class); 
V. Improvement from baseline in functional status (e.g., 6-min walk test improvement by 50 m); and  
VI. Improvement from baseline in quality-of-life (e.g., MLFH Questionnaire improvement by ≥10) 
 
 

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Statistical Analysis Plan 
Clinical Investigation Plan Title  Evaluation of the Safety and Performance of The 
Intrepid™ Transcatheter Mitral Valve Replacement 
System in High Risk Patients with Severe, 
Symptomatic Mitral Regurgitation - The Intrepid™ 
TMVR Pilot Study 
Clinical Investigation Plan Identifier CIP-1403 
Statistical Analysis Plan Version Date 20-MAY-2024 
Sponsor Medtronic, Inc. 
8200 Coral Sea St NE 
Mounds View, MN 55112 
United States 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. 
Any distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly 
prohibited. Persons to whom the information is disclosed must know that it is confidential and that it 
may not be further disclosed by them. 
 
 
 

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Table of Contents 
1. 
Version History ........................................................................................................................ 3 
2. 
List of Abbreviations and Definitions of Terms ............................................................................ 4 
3. 
Introduction............................................................................................................................. 5 
4. 
Study Objectives ...................................................................................................................... 6 
5. 
Investigation Plan .................................................................................................................... 6 
5.1 
Study Population ..................................................................................................................... 6 
5.2 
Patient Review Committee ..................................................................................................... 8 
5.3 
Clinical Events Committee and Data Safety Monitoring Board .............................................. 8 
6. 
Determination of Sample Size ................................................................................................... 8 
7. 
Statistical Methods ................................................................................................................... 9 
7.1 
Study Subjects ......................................................................................................................... 9 
7.2 
General Methodology ........................................................................................................... 10 
7.3 
Center Pooling ....................................................................................................................... 10 
7.4 
Handling of Missing, Unused, and Spurious Data and Dropouts .......................................... 11 
7.5 
Adjustments for Multiple Comparisons ................................................................................ 11 
7.6 
Demographic and Other Baseline Characteristics ................................................................. 11 
7.7 
Treatment Characteristics ..................................................................................................... 11 
7.8 
Interim Analyses .................................................................................................................... 11 
7.9 
Evaluation of Objectives ........................................................................................................ 12 
7.10 
Safety Evaluation ................................................................................................................... 27 
7.11 
Health Outcomes Analyses ................................................................................................... 27 
7.12 
Changes to Planned Analysis ................................................................................................. 27 
8. 
Validation Requirements ......................................................................................................... 28 
9. 
References ............................................................................................................................ 28 
10. Statistical Appendices ............................................................................................................. 28 
10.1 
Comparison of Inclusion and Exclusion Criteria Across Geographies ................................... 28 
 
 

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1. 
Version History 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
Not Applicable, New Document 
Sharla Chenoweth, Sr Prin 
Statistician 
2.0 
• 
Updated throughout to align with the 
current version of the CIP.  
• 
Added ISO 14155:2020 requirements 
per the current Statistical Analysis Plan 
Template B. 
• 
Section 7.8: Added description of the 
interim analyses performed.  
• 
Section 7.1.3: Added the analysis sets 
for consented subjects and approved 
subjects. Removed the per protocol 
and modified per protocol analysis 
datasets, since there were no previous 
analyses performed or future analyses 
planned for these populations. 
• 
Section 7.9.3: Added the MVARC 
criteria for technical, procedural, device 
and patient success per FDA request. 
Sherlly Xie, Senior Statistician 
3.0 
• 
Includes language to exclude 
echocardiography data after explant of 
the study valve from analysis. 
• 
Clarified greater severity between TTE 
and TEE will be reported where 
applicable. 
• 
Minor formatting updates and update to 
SAP template version C. 
Elizabeth Gearhart, Senior 
Statistician 
4.0 
• Updated definition of LVOT Patency to 
align with current Mitral study definitions. 
• Included an additional contemporary 
definition for Mitral Valve Stenosis. 
• 
Updated French CIP protocol number and 
date, and formatted Australian CIP version 
date. 
• 
Added “Mild-Moderate” and “Moderate-
Severe” as mitral regurgitation levels, and 
updated categorization. 
• 
Updated proportion confidence interval 
descriptions to exact confidence intervals 
• 
Added additional options for device 
relatedness to adverse event to align with 
current CEC charter. 
Nicholas Marka, Senior Statistician 

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Version 
Summary of Changes 
Author(s)/Title 
• 
Refined MVARC composite endpoint 
denominators to denote inclusion of 
subjects with any failures. 
• 
Replaced Approved with Attempted for the 
Analysis cohorts in various outcomes. 
• 
Updated the method for Kaplan-Meier 
standard errors to be Greenwood 
throughout. 
• 
Minor formatting updates. 
2. 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
MR 
Mitral Regurgitation  
TMVR 
Transcatheter Mitral Valve Replacement 
SAP 
Statistical Analysis Plan 
CIP 
Clinical Investigational Plan 
CRF 
Case Report Form 
LVOT 
Left Ventricular Outflow Tract 
NYHA 
New York Heart Association 
LVEF 
Left Ventricular Ejection Fraction 
HOCM 
Hypertrophic Obstructive Cardiomyopathy 
GI 
Gastrointestinal 
TEE 
Transesophageal Echocardiography 
TTE 
Transthoracic Echocardiography 
PRC 
Patient Review Committee 
CEC 
Clinical Events Committee 
DSMB 
Data Safety Monitoring Board 
SAE 
Serious Adverse Event 
MVARC 
Mitral Valve Academic Research Consortium 
6MWT 
Six Minute Walk Test 
MLHFQ 
Minnesota Living with Heart Failure Questionnaire 
MV 
Mitral Valve 
EOA 
Effective Orifice Area 
PCI 
Percutaneous Coronary Intervention 
CABG 
Coronary Artery Bypass Grafting 
UADE 
Unanticipated Adverse Device Effect 

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3. 
Introduction 
Mitral regurgitation (MR) affects millions of people worldwide. It is the most common type of 
heart valve defect, affecting one in 10 people aged 75 and older. The condition occurs when 
the heart’s mitral valve does not close completely, causing blood to leak backward into the left 
atrium with every heartbeat. Over time, left ventricular dilatation and dysfunction occurs in an 
attempt to accommodate the increased volume load and maintain cardiac output. Ultimately, 
chronic volume overloading of the left ventricle results in contractile dysfunction, symptoms of 
heart failure, and in increased risk of sudden death. Patients with severe symptomatic MR have 
a poor prognosis with an annual mortality rate of 5% per year without surgical intervention. 
Progressive heart failure is the usual cause of death, but patients also may die from sudden 
death, stroke, and endocarditis. 
The investigational device is called the Intrepid™ Transcatheter Mitral Valve Replacement 
(TMVR) System, manufactured by Medtronic (formerly Twelve, Inc.). It is designed for trans-
apical access and delivery of a self-expanding bioprosthetic valve within the native mitral valve. 
The Intrepid™ TMVR implant is intended to function similarly to a standard bioprosthetic valve 
implant, in that it allows blood to flow only in the forward direction, thereby relieving mitral 
regurgitation. A standard valve implant, however, is sewn directly into the heart during surgery 
in which the chest is fully open, the patient is put on cardiopulmonary bypass support and the 
heart is temporarily stopped. The Intrepid™ TMVR implant is intended to be placed through a 
less invasive mini-thoracotomy procedure, without requiring cardiopulmonary bypass support or 
stopping the heart, thereby reducing the risks associated with these more invasive procedures. 
The concept of the Intrepid™ TMVR System for mitral valve disease is similar to the concept of 
currently approved systems for standard trans-apical Transcatheter Aortic Valve Implantation 
(TAVI) systems for aortic valve disease. 
This Statistical Analysis Plan (SAP) has been designed to document, before data are analyzed, 
the rationale for the study design, and the planned analyses that will be included in study 
reports. Clinical Investigational Plan (CIP) 1403 was developed and used in multiple 
geographies. The same data collection case report forms (CRFs) and similar inclusion and 
exclusion criteria were utilized. This SAP is developed based on the following CIP Versions: 
Geography 
CIP Number 
Current Version 
United States (US) 
1403 
4.0 / 2019.10.15 
Australia 
1403 
A3 16 Dec 2019 
United Kingdom (UK) 
1403 
V2.0 16 Dec 2019 
Finland 
1403 
V2.0 16 Dec 2019 
Greece 
1403 
V2.0 16 Dec 2019 

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Denmark 
1403 
V2.0 16 Dec 2019 
France 
1403 
F5 20 Sep 2021 
 
 
 
4. 
Study Objectives 
The primary objective of the study is to evaluate the safety of the Intrepid™ TMVR System: 
• 
The primary endpoint is the assessment of the nature, severity and frequency of 
complications associated with the delivery and/or implantation of the device. 
The secondary objective of the study is to evaluate the performance of the Intrepid™ TMVR 
System: 
• 
The secondary endpoints include assessment of: 
o The degree of improvement of MR grade and symptoms, and the durability of TMVR 
function. 
o The ability to accurately deliver and place the implant within the native anatomy. 
o The fit of the implant within the native anatomy, including fixation, sealing and 
compatibility with native structures (e.g., other components of the mitral valve 
apparatus, the conduction system, and the left ventricular outflow tract 
(LVOT)/aortic valve). 
5. 
Investigation Plan 
The study is a prospective, multi-center, non-randomized study to evaluate the safety and 
performance of The Intrepid™ TMVR System in patients with severe, symptomatic mitral 
regurgitation, who are at high risk for conventional mitral valve surgery. 
The pilot study (also referenced as early feasibility study) is a single arm study without 
concurrent controls. The results will be evaluated referencing historical literature for surgical 
mitral replacement, surgical mitral repair, and transcatheter mitral repair. 
5.1 Study Population 
5.1.1 Inclusion Criteria 
The inclusion criteria listed are from the CIP for the US. Appendix 10.1 provides a side-by-side 
view of the enrollment criteria for the different geographies. The slight differences in the 
inclusion criteria do not change the patient population being studied. 
The subject must meet ALL of the following criteria: 
1. Severe mitral regurgitation (MR Grade 3-4+) 

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2. Symptomatic mitral regurgitation (New York Heart Association (NYHA) Class II-IV) 
3. Deemed to be at high risk for conventional mitral valve surgery by the local heart team 
(including, at minimum, a cardiac surgeon, interventional cardiologist, and an 
echocardiologist) 
4. Age ≥ 18 (years) 
5. Native mitral valve geometry and size compatible with The Intrepid™ TMVR 
6. No or minimal mitral valve calcification 
7. Willing to sign Informed Consent for participation in the study and return for all required 
post-procedure follow-up visits 
5.1.2 Exclusion Criteria 
The exclusion criteria listed are from the CIP for the US. Appendix 10.1 provides a side-by-
side view of the enrollment criteria for the different geographies. The slight differences in the 
exclusion criteria do not change the patient population being studied. 
The subject may not meet any of the following criteria: 
1. Left ventricular ejection fraction (LVEF) < 20 (%) 
2. Evidence of intracardiac mass, thrombus, or vegetation 
3. Pulmonary hypertension (> 70 mmHg systolic)  
4. Hypertrophic Obstructive Cardiomyopathy (HOCM) 
5. Prior mitral valve surgery or endovascular procedure, any currently implanted 
mechanical prosthetic valve, or need for other valve surgery/procedure  
6. Any endovascular therapeutic interventional or surgical procedure performed within 30 
days prior to enrollment 
7. Prior stroke within 30 days 
8. Need for coronary revascularization 
9. Need for emergent surgery 
10. History of, or active, endocarditis 
11. Gastrointestinal (GI) bleeding within 6 months 
12. History of bleeding diathesis or coagulopathy or patient will refuse blood transfusion 
13. Hemodynamic instability 
14. Platelet count of <75,000 cells/mm3 
15. Renal insufficiency (Creatinine > 2.5 mg/dL) 
16. Active infections requiring current antibiotic therapy (if temporary illness, patients may 
enroll 2 weeks after discontinuation of antibiotics) 
17. Contraindication to transesophageal echocardiography (TEE) 
18. Known hypersensitivity or contraindication to study or procedure medications/contrast 
which cannot be adequately managed medically 

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19. Pregnant, nursing or planning to be pregnant. (Female participants of childbearing 
potential must have a negative pregnancy test prior to enrollment) 
5.2 Patient Review Committee 
Subjects will be screened prior to study entry to determine if they meet the Eligibility Criteria. 
Subjects who have signed an Informed Consent and fulfill the inclusion criteria and none of the 
exclusion criteria are eligible for enrollment. 
A Patient Review Committee (PRC) will consist of cardiac surgery, interventional cardiology, and 
echocardiology representatives who are not participating investigators. The PRC will serve in an 
advisory capacity to Medtronic and will review potential patients’ clinical and imaging data to 
help ensure appropriate patient selection across all sites. 
5.3 Clinical Events Committee and Data Safety Monitoring Board 
The combined Clinical Events Committee (CEC) and Data Safety Monitoring Board (DSMB) will 
provide independent medical review and adjudication of adverse event data used in the safety 
assessment of the investigational device. The CEC will adjudicate all deaths, serious adverse 
events (SAEs), and safety endpoint events reported by the investigators. The CEC will follow the 
recommendations of the Mitral Valve Academic Research Consortium (MVARC) for classifying 
adverse events that relate to clinical safety endpoints. 
A DSMB will assess interim study data and provide recommendations to Medtronic regarding 
study conduct, should they identify any issues that may affect the safety of the study subjects. 
The DSMB consists of a minimum of three members: 1) cardiologist with expertise in the 
management of mitral disease, 2) a cardiothoracic surgeon with expertise in mitral valve repair 
and replacement, and 3) a biostatistician. DSMB members are free from bias towards the study 
and independent from both the study and investigators and Medtronic. 
6. 
Determination of Sample Size 
This study treats up to 95 subjects worldwide who require replacement of their native mitral 
valve because of severe, symptomatic mitral regurgitation, but are at high risk for conventional 
mitral valve surgery. The enrollment is capped at 70 in the US, 30 in Australia, and 20 in each 
of France, Denmark, Finland, Greece, and the UK. The geography-specific and overall sample 
sizes are not statistically derived, as this is not a hypothesis-driven study. 

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7. 
Statistical Methods 
7.1 Study Subjects 
7.1.1 
Disposition of Subjects 
Subject disposition will be summarized, including the number of subjects enrolled, implanted (if 
applicable), underwent attrition (died, explanted (if applicable), withdrew, lost to follow-up, 
exited the study due to other reasons), and completed each visit per follow-up schedule during 
the study. 
7.1.2 
Clinical Investigation Plan Deviations 
CIP deviations will be reported to Medtronic throughout the study by each site and may be 
identified through monitoring activities. CIP deviations will be provided in a listing and 
summarized by study interval and type of deviation using frequencies and percentages. 
7.1.3 
Analysis Sets 
Four analysis sets are defined for this study. The primary analysis will be based on the 
Approved Subjects analysis set. Analysis sets used for each objective are defined in the 
corresponding objective section. All data collected from consented and approved subjects will 
be utilized in the analyses as appropriate. 
• 
Consented Subjects: Includes all subjects who signed a study informed consent. Time zero 
begins on the date of informed consent. 
• 
Approved Subjects: Includes consented subjects who are reviewed and approved for 
implant by the PRC. Time zero begins on the date of informed consent. 
• 
Attempted Implant (Safety): Includes approved subjects who were reviewed and approved 
by the PRC and entered the procedure room with the intent to attempt a TMVR procedure. 
Time zero begins on the date of procedure. This analysis set will be used for evaluating all 
safety data and clinical outcomes (i.e., NYHA, 6 Minute Walk Test (6MWT), Minnesota Living 
with Heart Failure Questionnaire (MLHFQ)). 
• 
Implanted Subjects (Hemodynamic Performance): Composed of all attempted implant 
subjects with a functioning Intrepid device implanted at the time of exiting procedure room. 
Time zero begins on the date of procedure. This analysis set will be used for evaluating the 
valve performance (i.e., hemodynamics or imaging data). If the Intrepid valve is explanted 
or has a reintervention, then only data collected up to time of explant or reintervention are 
included in analysis regarding valve function. 

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7.2 General Methodology 
A comprehensive analysis of the pilot study results, as a whole, will be assessed to evaluate the 
overall risk/benefit balance for the patient population being treated. Pre-defined statistical 
“success” or “pass” criteria for the study endpoints are not applicable for this pilot study, as it is 
not a powered, hypothesis-driven study. 
Each subject’s data will be reviewed individually and case summaries for all subjects will be 
provided to the FDA. In addition, descriptive statistics will be used to summarize the 
preoperative, operative, discharge, and follow-up clinical data. No statistical hypothesis tests 
are planned. The endpoint measures will be summarized by time point. Additionally, change 
from baseline will be presented for each outcome, as applicable. 
To report the distributions of continuous variables, mean, standard deviation, minimum, 
median, first and third quartiles, and maximum will be presented. To report the distributions of 
categorical variables, counts and proportions will be provided. Proportions and associated 95% 
confidence intervals will be reported for endpoints, as applicable. For time to event data, 
Kaplan-Meier event rates will be presented at clinically meaningful post-operative time intervals, 
for instance, 30 days, 183 days, and annually thereafter (e.g., 365, 365×2, 365×3 days, etc.). 
At each time point with data, the product-limit estimate of the event rate, the number of 
subjects at risk, the number of subjects with events, the Greenwood standard error of the 
estimate, and the loglog transformed 95% confidence interval using the Greenwood standard 
error will be presented. 
For subjects without an event, the date of censoring will be the latest date of all follow-up visits 
(including video contact, phone and/or mail correspondence), assessments, events (including 
death in those endpoints where death is not the endpoint) and study exits. For subjects whose 
exit reason is lost to follow-up, the last follow-up date will be the latest date of the follow-up 
visits (including video contact, phone and/or mail correspondence), assessments and events. 
For analyses reporting the function of the study valve using echocardiographic or MDCT data, 
only data corresponding to the implanted study valve will be used; data post-explant or after 
reintervention in which the index study valve is no longer functioning will be excluded from the 
analysis. 
7.3 Center Pooling 
Although data for this study will be collected from multiple centers, no center pooling analyses 
are planned. 

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7.4 Handling of Missing, Unused, and Spurious Data and 
Dropouts 
Every effort will be undertaken to minimize missing, unused, and spurious data and dropouts. 
In time-to-event outcomes, drop-outs will be censored at the time of discontinuation, consistent 
with the Kaplan-Meier approach. 
Unless otherwise specified in each objective, no statistical techniques will be used to impute 
missing data for continuous or categorical outcomes. If a subject’s data are missing for any 
reason, that subject will not be included in that portion of the analysis. The number of subjects 
included in each analysis will be reported so that the reader can assess the potential impact of 
missing data. 
In the case of partial dates, if only the month and year are known, the event or assessment will 
be analyzed as if it occurred on the 15th of that month. If only the year is known, the event or 
assessment will be analyzed as if it occurred on June 30th of that year. These resolutions of 
partial dates are subject to the restrictions that events must occur no earlier than the procedure 
date or after study exit. For more complex imputations of dates, determination will be made on 
a case-by-case basis based on the most suitable date range. 
7.5 Adjustments for Multiple Comparisons 
No adjustments for multiple comparisons are planned. 
7.6 Demographic and Other Baseline Characteristics 
Demographics, hemodynamic measurements at screening, as well as medical history will be 
summarized using methods described in Section 7.2 for the subjects in the Consented 
Subjects and Approved Subjects analysis sets. 
7.7 Treatment Characteristics  
Treatment characteristics will be summarized using methods described in Section 7.2 for the 
subjects in the Approved Subjects analysis set. 
7.8 Interim Analyses  
Interim analyses are planned for publication when 50 subjects had the opportunity to be 
followed for 30 days and a second analysis for CE submission when 75 subjects had the 
opportunity to be followed for 30 days. The final analysis and report will be completed when all 
enrolled subjects have completed the 5-year follow-up. 

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7.9 Evaluation of Objectives 
7.9.1 Primary Safety Endpoint 
• 
Implant or delivery related SAEs (through 30 days post-procedure) 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and 
no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
The severity and relationship of an AE to the implant and delivery are collected on the AE CRFs. 
AEs are coded using MedDRA coding. AE are reported by sites and may be reviewed and 
adjudicated by the CEC. An AE through 30 days post-procedure is one that occurs between day 
0 (the date of index procedure) and the 30th day after the index procedure. 
An implant or delivery related SAE is defined as follows. 
If site AE CRF indicates the following: 
• 
“Serious adverse event?” is answered “Yes”. 
• 
“Relation to the TMVR device/procedure” is answered either “Possibly related”, 
“Probably related”, or “Definitely related”. 
However, if the event was reviewed and adjudicated by the CEC, then the seriousness and 
relationship recorded by the CEC will be used instead. 
Data Collection and Analysis Dataset: 
Data will be collected on AE CRFs. Analysis will be performed on the Attempted Subjects 
analysis set. 
Analysis Method: 
The number of events, the number and proportion of subjects who have at least one SAE 
recorded as TMVR device/procedure related and its associated 95% exact confidence interval 
will be reported. 
7.9.2 Secondary Performance Endpoints 
• 
Successful access, delivery of implant, and retrieval of the delivery system 

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Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the procedure CRF. 
- 
Successful access is “Yes” if “TMVR delivery catheter insertion time” is not blank. 
- 
Successful delivery of implant is “Yes” if “Was the TMVR implanted?” is answered 
“Yes” and “Conversion to open surgical MV replacement” is answered “No”. 
- 
Successful retrieval delivery system is “Yes” if “Delivery catheter removal time” is 
not blank. 
Data Collection and Analysis Dataset: 
Data for this endpoint are collected on the procedure CRF. Data will be summarized 
on the Attempted Subjects analysis set. 
Analysis Method: 
The proportion of subjects with each of successful access, successful delivery of 
implant, and successful retrieval of the delivery system and its associated 95% exact 
confidence interval will be calculated. 
• 
Reduction in MR Grade from baseline (measured by echo through 30 days post-
procedure) 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis for each of 
these endpoints will be descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the core lab echo CRF. 
The core lab echo CRF will report 7 grade levels of MR: “None”, “Trace”, “Mild”, “Mild-
Moderate", “Moderate”, “Moderate-Severe”, and “Severe”. These will be recategorized 
to the following 5 grade levels of MR: “None/Trace”, “Mild” (Mild + Mild-Moderate), 
“Moderate”, “Moderate Severe”, and “Severe”, with corresponding numerical values of 
0, 1, 2, 3, and 4 respectively. For the post-procedure echo, MR grade is defined as the 

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highest reported severity level of transvalvular leak and paravalvular leak. MR ≥ 2+ is 
considered as clinically significant. The number of grade level changes since baseline 
will be calculated. There are 4 possible grade change categories: improved (by 1, 2, 3, 
or 4 grades), no change, and worsened (by 1, 2, 3, or 4 grades). 
Data Collection and Analysis Dataset: 
Data will be collected on the core lab echo CRF (either TTE or TTE data, whichever 
demonstrates a higher MR grade, will be used). Analysis dataset is the Implanted 
Subjects analysis set. 
Analysis Method: 
The distribution of MR grade and clinically significant MR at each visit will be 
summarized using descriptive statistics for categorical variable described in Section 
7.2. For subjects with paired data, the proportion of subjects in each MR grade 
change category will be calculated. 
• 
No significant mitral valve (MV) stenosis (measured by echo through 30 days post-
procedure) 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the core lab echo CRF. 
No significant MV stenosis will be assessed by 2 definitions: 
1) A MV mean gradient < 5 mmHg and effective orifice area (EOA) ≥ 1.5 cm2 based 
on echocardiography core lab data1. 
2) A MV mean gradient <10 mmHg2. 
Data Collection and Analysis Dataset: 
Data will be collected on the core lab echo CRF (either TTE or TTE data, whichever 
demonstrates a higher MR grade, will be used). Analysis dataset is the Implanted 
Subjects analysis set. 
Analysis Method: 

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Number and percentage of subjects with no significant MV stenosis at each visit will 
be calculated as appropriate by definition. Statistics summarizing the distributions of 
the component endpoints (number and percentage of subjects with MV mean gradient 
≤ 5 mmHg and < 10 mmHg, number and percentage of subjects with EOA ≥ 1.5 cm2) 
will also be presented. 
• 
LVOT patency (measured by echo through 30 days post-procedure) 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the core lab echo CRF. 
LVOT patency is defined as not having an LVOT obstruction. LVOT obstruction is 
defined as having peak LVOT jet velocity ≥2.7 m/s (peak instantaneous gradient ≥30 
mmHg) measured by CW Doppler under basal (resting) conditions or physiologically 
provoked (Valsalva maneuver or post premature ventricular contraction) and having 
an increment in peak LVOT gradient ≥10 mmHg from baseline.  
Data Collection and Analysis Dataset: 
Data will be collected on the core lab echo CRF (either TTE or TTE data, whichever 
demonstrates a higher degree of LVOT obstruction (equivalent to lowest degree of 
patency), will be used). Analysis dataset is the Implanted Subjects analysis set. 
Analysis Method: 
Number and percentage of subjects with LVOT patency at each visit will be calculated. 
Statistics summarizing the distributions of the component endpoints (number and 
percentage of subjects with peak instantaneous gradient ≥30 mmHg, and number and 
percentage of subjects with an increment in peak LVOT gradient ≥10 mmHg from 
baseline) will also be presented. 
• 
Improvement of NYHA Class from baseline (through 30 days post-procedure) 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 

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Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the baseline and follow-up CRFs. 
NYHA class ranges from Class I to IV. The classes describe increasingly limited 
physical activity. The number and percentages of subjects who died prior to visit, as 
well as the number of classes changed from baseline through 30 days post-procedure 
for subjects with paired data, will be calculated. 
Data Collection and Analysis Dataset: 
Data will be collected on the screening and follow-up CRFs. Data will be summarized 
on the Attempted Subjects analysis set. 
Analysis Method: 
The NYHA class will be summarized as a categorical variable at each visit, and for 
subjects with paired data, change from baseline will be summarized both as a 
categorical and a continuous variable using appropriate statistics described in Section 
7.2. 
7.9.3 Additional Exploratory Endpoints 
Event and endpoint definitions for this study’s analysis will be based on those definitions 
outlined in the MVARC Consensus Document1. Each subject’s data will be reviewed individually 
and case summaries for all subjects will be provided. These endpoints are listed only in the CIP 
for the US and France. 
• 
Measured by echo post-procedure through 5 years: 
o Reduction in MR Grade from baseline 
o No significant MV stenosis 
o LVOT patency 
o Improvement in LVEF 
o Improvement in cardiac output/cardiac index 
o Reduction in LV end-systolic and end-diastolic dimensions 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the core lab echo CRFs. 

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Reduction in MR grade from baseline, No significant MV stenosis, and LVOT patency 
have been defined in Section 7.9.2. Improvement in LVEF is defined as a higher 
LVEF (%) compared to a reference value. Improvement in cardiac output/cardiac 
index is defined as a higher cardiac output/cardiac index compared to a reference 
value. Reduction in LV end-systolic and reduction in LV end-diastolic dimensions will 
be calculated separately. The reference values are collected at baseline. 
Change from baseline will be calculated using available data on the analysis set at 
each follow-up visit. Possible changes are “improved”, “no change” and “worsened”. 
Data Collection and Analysis Dataset: 
Data will be collected on the screening and follow-up CRFs. Data will be summarized 
on the Implanted Subjects analysis set. 
Analysis Method: 
MR grade, presence/absence of significant MV stenosis, LVOT patency and component 
endpoints will be summarized using analysis methods described in Section 7.9.2. 
LVEF, cardiac output/cardiac index, and LV end-systolic and end-diastolic dimensions 
will be summarized using descriptive statistics for continuous variables by visit. For 
subjects with paired data, change from baseline will also be summarized using 
appropriate statistics described in Section 7.2 by visit. 
• 
Change in 6MWT from baseline through 5 years 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the baseline and follow-up CRFs. 
Change in 6MWT from baseline is defined as the difference between the distance (in 
meters) a subject walks in 6 minutes at baseline and a later visit. 
Data Collection and Analysis Dataset: 
Data will be collected on the baseline and follow-up CRFs. Data will be summarized on 
the Attempted Subjects analysis set. 
Analysis Method: 

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6MWT will be summarized using descriptive statistics for continuous variable described 
in Section 7.2 by visit. For subjects with paired data, change in 6MWT from baseline 
will also be summarized using descriptive statistics for continuous variable described 
in Section 7.2 by visit. 
• 
Change in quality of life (MLHFQ) from baseline to 12 months 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the baseline and follow-up CRFs. 
The MLHFQ has a total score that can range from 0 to 105. A lower score indicates a 
higher quality of life. A negative change during follow-up compared to baseline 
represents an improvement in quality of life. 
Change in MLHFQ from baseline is defined as the difference between a subject’s 
score at baseline and a later visit. 
Data Collection and Analysis Dataset: 
Data will be collected on the baseline and 12-month follow-up CRFs. Data will be 
summarized on the Approved Subjects analysis set. 
Analysis Method: 
MLHFQ score will be summarized using descriptive statistics for continuous variable 
described in Section 7.2 by visit. For subjects with paired data, change in MLHFQ 
score from baseline will also be summarized using descriptive statistics for continuous 
variable described in Section 7.2 by visit. 
• 
Change in NYHA from baseline through 5 years 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the baseline and follow-up CRFs. 

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Change in NYHA class from baseline is defined as the difference between a subject’s 
NYHA class at baseline and a later visit. The number and percentages of subjects who 
died prior to visit, as well as the number of classes changed from baseline at each 
follow-up visit will be calculated for subjects with paired data. 
Data Collection and Analysis Dataset: 
Data will be collected on the baseline and follow-up CRFs. Data will be summarized on 
the Attempted Subjects analysis set. 
Analysis Method: 
NYHA class will be summarized using descriptive statistics for categorical variable 
described in Section 7.2 by visit. For subjects with paired data, change from baseline 
will be summarized as both a categorical and a continuous variable using appropriate 
statistics described in Section 7.2. 
• 
Procedural times 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the procedure CRF. 
- 
Anesthesia time is defined as anesthesia (procedure) stop time minus anesthesia 
(procedure) start time. 
- 
Intubation time is defined as extubation time minus anesthesia (procedure) start 
time. 
- 
Total procedure time (skin-to-skin) is defined as thoracic incision closure time 
minus thoracic incision start time. 
- 
Deployment time is defined as final TMVR deployment time minus TMVR delivery 
catheter insertion time. 
- 
Apical access duration is defined as apical access closure time minus apical incision 
time. 
- 
Rapid pacing duration is defined as the “Pacing duration during deployment”. 

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Data Collection and Analysis Dataset: 
Data will be collected on the procedure CRF. Data will be summarized on the 
Attempted Subjects analysis set. 
Analysis Method: 
Each procedure time will be summarized using descriptive statistics for continuous 
variable described in Section 7.2. 
• 
Re-hospitalizations for heart failure through 5 years 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using the CEC adjudication for re-hospitalization for heart 
failure on the AE CRF. 
Data Collection and Analysis Dataset: 
Data will be collected on the AE CRF. Data will be summarized on the Attempted 
Subjects analysis set. 
Analysis Method: 
This endpoint will be summarized using descriptive statistics for time to event data 
described in Section 7.2. Kaplan-Meier event rates at 30 days, 6 months, 12 months, 
and every 6 months through 5 years. 
• 
MVARC defined technical success 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the AE and procedure CRFs. 

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Technical success is measured at exit from the catheterization laboratory and all of 
the following must be present: 
- 
Absence of procedural mortality (free from death on day 0, which is day of 
procedure, AE CRF); and 
- 
Successful access, delivery, and retrieval of the delivery system (same definition 
as secondary endpoint, procedure CRF); and 
- 
Successful deployment and correct position of the first intended device (TMVR 
implant is “Yes”, no additional devices opened or used, TMVR device malfunction 
is “No”, and TMVR device failure is “No”, procedure CRF); and 
- 
Freedom from emergency surgery or reintervention related to the device or access 
procedure (Conversion to open MV replacement is “No” and Other repair surgery is 
“No”, procedure CRF). 
Data Collection and Analysis Dataset: 
Data will be collected on the AE and procedure CRFs. Data will be summarized on the 
Attempted Subjects analysis set. 
Analysis Method: 
The proportion of subjects with technical success will be presented with its associated 
95% exact confidence interval. The numerator will include subjects with success in all 
components of this endpoint. The denominator will include subjects who have success 
or at least one failure component present. 
The proportion of subjects with success for each component of this endpoint will also 
be presented; the numerator will include subjects with success, and the denominator 
will include subjects with non-missing data 
• 
MVARC defined device success 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the AE, procedure and core lab echo CRFs. 

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Device success is measured at discharge, 30 days and at all later post-procedure 
intervals. All of the following must be present: 
- 
Absence of procedural mortality or stroke (free from death and stroke within 30 
days of procedure, AE CRF); and 
- 
Proper placement and positioning of the device (TMVR implanted is “Yes”, 
procedure CRF); and 
- 
Freedom from unplanned surgical or interventional procedures related to the 
device or access procedure (Conversion to open MV replacement is “No” and 
Other repair surgery is “No”, procedure CRF); and 
- 
Continued intended safety and performance of the device, including 
o No evidence of structural or functional failure (free from AEs for device 
malfunction for structural or functional failures, and free from explant and MV 
reinterventions, AE CRF) 
▪ 
Delivery failure (i.e., technical failure) 
▪ 
Structural failure 
▪ 
Functional failure 
o No specific device-related technical failure issues and complications (core lab 
echo, AE, procedure CRF) 
▪ 
Paravalvular leak (core lab echo, AE CRF) 
• 
Major/Minor: Having a major paravalvular leak is considered as having 
a device failure. 
▪ 
Coronary vessel compression or obstruction (defined using CEC code, AE 
CRF) 
• 
Major/Minor: Having a major coronary vessel compression or 
obstruction is considered as having a device failure. 
• 
Symptomatic/Not symptomatic: Having a symptomatic coronary 
vessel compression or obstruction is considered as having a device 
failure. 

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• 
Requiring treatment/Not requiring treatment: Having a coronary 
vessel compression or obstruction requiring treatment is considered 
as having a device failure. 
• 
Transient/Persistent: Having a persistent coronary vessel compression 
or obstruction is considered as having a device failure. 
▪ 
Pericardial effusion (defined using CEC code, AE CRF) 
• 
Major/Minor: Having a major pericardial effusion is considered as 
having a device failure. 
▪ 
Conversion to open mitral valve surgery during a transcatheter procedure 
(Conversion to open MV replacement is “No”, procedure CRF) 
▪ 
Device malpositioning (defined using CEC code, AE CRF) 
▪ 
Device detachment (defined using CEC code, AE CRF) 
• 
Partial/Complete: Having a complete device detachment is considered 
as having a device failure. 
▪ 
Device fracture (defined using CEC code, AE CRF) 
• 
Major/Minor: Having a major device fracture is considered as having a 
device failure. 
▪ 
Damage to the native mitral valve apparatus (defined using CEC code, AE 
CRF) 
▪ 
Interaction with non-mitral valve intracardiac structures (defined using CEC 
code, AE CRF) 
▪ 
Device thrombosis (defined using CEC code, AE CRF) 
• 
Major/Minor: Having a major device thrombosis is considered as 
having a device failure. 
▪ 
Endocarditis (defined using CEC code, AE CRF) 
▪ 
Haemolysis (defined using CEC code, AE CRF) 
o Reduction of MR to either optimal (post-procedure MR reduced to 0+ to trace, 
with no more than 1+ paravalvular MR) or acceptable (post-procedure MR 
reduced by at least 1 grade from baseline and to 1+ to 2+ with no more than 

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1+ paravalvular MR) levels without significant mitral stenosis (i.e., post-
procedure EOA is ≥1.5 cm2 with a transmitral gradient <5 mmHg) and with no 
greater than mild (1+) paravalvular MR (and without associated hemolysis) 
(core lab echo CRF) 
Data Collection and Analysis Dataset: 
Data will be collected on the AE, procedure and core lab echo CRFs. Data will be 
summarized on the Attempted Subjects analysis set. 
Analysis Method: 
The proportion of subjects with device success will be presented with its associated 
95% exact confidence interval at discharge, 30 days and at all later post-procedure 
intervals. The numerator will include subjects with success in all components of this 
endpoint. The denominator will include subjects who have success or at least one 
failure component present. 
The proportion of subjects with success for each component of this endpoint will also 
be presented at discharge, 30 days and at all later post-procedure intervals; the 
numerator will include subjects with success, and the denominator will include subjects 
with non-missing data. 
• 
MVARC defined procedural success 
Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the AE, procedure, discharge, and core lab 
echo CRFs. 
Procedural success is measured at 30 days. All of the following must be present: 
- 
Device success (either optimal or acceptable, see definitions above); and 
- 
Absence of major device or procedure related serious adverse events (AE, 
procedure, discharge CRFs), including: 
o Death 

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o Stroke 
o Life-threatening bleeding (MVARC scale) 
o Major vascular complication 
o Major cardiac structural complications 
o Stage 2 or 3 acute kidney injury (includes new dialysis) 
o Myocardial infarction or coronary ischemia requiring percutaneous coronary 
intervention (PCI) or coronary artery bypass grafting (CABG) 
o Severe hypotension, heart failure, or respiratory failure requiring intravenous 
pressors or invasive or mechanical heart failure treatment such as 
ultrafiltration or hemodynamic assist device, including intra-aortic balloon 
pumps or left ventricular or biventricular assist devices, or prolonged 
intubation for ≥ 48 hours. 
o Any valve-related dysfunction, migration, thrombosis, or other complication 
requiring surgery or repeat intervention. 
Device success has been defined above. By MVARC criteria, “optimal” device success 
requires a reduction in post-procedural MR to no more than trace levels, and 
“acceptable” device success is defined as a reduction in post-procedure MR by at least 
1 class. 
Data Collection and Analysis Dataset: 
Data will be collected on the AE, procedure, discharge and core lab echo CRFs. Data 
will be summarized on the Attempted Subjects analysis set. 
Analysis Method: 
The proportion of subjects with device success will be presented with its associated 
95% exact confidence interval at 30 days post-procedure. The numerator will include 
subjects with success in all components of this endpoint. The denominator will include 
subjects who have success or at least one failure component present. 
The proportion of subjects with success for each component of this endpoint will also 
be presented; the numerator will include subjects with success, and the denominator 
will include subjects with non-missing data. 
• 
MVARC defined individual subject success 

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Hypothesis/Decision Criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be 
descriptive and no statistical hypothesis tests are planned. 
Endpoint Definition/Parameters to Be Estimated: 
This endpoint is defined using variables on the AE, procedure, discharge, baseline, 
follow-up, and core lab echo CRFs. 
Individual subject success is measured at 1 year. All of the following must be present: 
- 
Device success (either optimal or acceptable) (as defined above); and 
- 
No re-hospitalizations or reinterventions for the underlying condition (e.g., MR 
heart failure) (AE CRF); and 
- 
Improvement from baseline of symptoms (e.g., NYHA improvement ≥ 1 functional 
class) (baseline and follow-up CRFs); and  
- 
Improvement from baseline in functional status (e.g., 6MWT improvement ≥ 50 
meters) (baseline and follow-up CRFs); and 
- 
Improvement from baseline in QoL (e.g., MLHFQ decline ≥ 10 points) (baseline 
and follow-up CRFs). 
The following criterion in the MVARC definition is not included in the definition of 
individual subject success of this study due to data availability: 
- 
Subject returned to pre-procedural settings 
Data Collection and Analysis Dataset: 
Data will be collected on the AE, procedure, discharge, baseline, follow-up, and core 
lab echo CRFs. Data will be summarized on the Attempted Subjects analysis set. 
Analysis Method: 
The proportion of subjects with device success will be presented with its associated 
95% exact confidence interval at 1-year post-procedure. The numerator will include 
subjects with success in all components of this endpoint. The denominator will include 
subjects who have success or at least one failure component present. 

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The proportion of subjects with success for each component of this endpoint will also 
be presented; the numerator will include subjects with success, and the denominator 
will include subjects with non-missing data. 
7.10 Safety Evaluation  
The CEC will adjudicate all deaths, SAEs, and safety endpoint events reported by the 
investigators. The analysis of the study safety data will be based on CEC-adjudicated events. AE 
summaries will be based on MedDRA coding. 
To provide a comprehensive safety evaluation, the safety data will be presented at aggregate 
and individual event levels as tables and listings. The safety data will be summarized by 
severity, time point, treatment needed, resolution, and causal relationship with the 
investigational devices or procedure using descriptive statistics for categorical variable described 
in Section 7.2. Any Unanticipated Adverse Device Effects (UADEs) will be reported as 
proportions of subjects experiencing the event. Time to event data will be reported using the 
Kaplan-Meier estimate of the event rate, the number of subjects at risk, the number of subjects 
with events, the Greenwood standard error of the estimate, and the loglog transformed 95% 
confidence interval using the Greenwood standard error, as described in Section 7.2. 
A listing will be provided for: 
• 
Deaths and reasons for death 
• 
AEs related to the implant, delivery system, or procedure 
7.11 Health Outcomes Analyses  
No health outcomes analyses are planned. 
7.12 Changes to Planned Analysis  
The planned analyses in this SAP are aligned with the planned analyses noted in CIP-1403. Any 
change to the planned analyses made prior to performing the analyses will be documented in a 
protocol revision prior to performing the analyses. Any change to the planned analyses made 
after performing the analyses will be documented in the clinical study report along with a 
reason for the change. 

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8. 
Validation Requirements 
Level 1 validation (independent validation) will be used for the analysis datasets and the 
primary and secondary endpoints. Level 2 validation (peer review) will be used for additional 
analyses, data summaries, and listings. 
9. 
References  
1 Stone GW, Adams DH, Abraham WT, et al. Clinical Trial Design Principles and Endpoint 
Definitions for Transcatheter Mitral Valve Repair and Replacement: Part 2: Endpoint Definitions, 
J Am Coll Cardiol 2015;66:308–321. Doi: 10.1016/j.jacc.2015.05.049 
2 Zoghbi WA, Jone PN, Chamsi-Pasha MA, et al. Guidelines for the Evaluation of Prosthetic Valve 
Function With Cardiovascular Imaging: A Report From the American Society of 
Echocardiography Developed in Collaboration With the Society for Cardiovascular Magnetic 
Resonance and the Society of Cardiovascular Computed Tomography. J Am Soc Echocardiogr. 
2024 Jan;37(1):2-63. doi: 10.1016/j.echo.2023.10.004. 
 
10. Statistical Appendices  
10.1 Comparison of Inclusion and Exclusion Criteria Across 
Geographies 
Listed below are inclusion and exclusion criteria in the geography-specific CIPs. Criteria with 
variations are italicized. 
 
United States                      
CIP-1403 Version 4.0 
2019.10.15 
Australia                              
CIP-1403 Version A3 
16Dec2019 
Finland, Greece, United 
Kingdom, Denmark             
CIP-1403 Version 2.0 
16Dec2019 
France                                  
CIP-1403 Version F5 
20SEP2021 
Inclusion Criteria 
1 
Severe mitral regurgitation 
(MR Grade 3-4+) 
Severe mitral regurgitation 
(MR Grade 3-4+) 
Severe mitral regurgitation 
(MR Grade 3-4+) 
Severe mitral regurgitation 
(MR Grade 3-4+) 
2 
Symptomatic mitral 
regurgitation (NYHA Class 
II-IV)   
Symptomatic mitral 
regurgitation (NYHA Class 
II-IV)   
Symptomatic mitral 
regurgitation (NYHA Class 
II-IV)   
Symptomatic mitral 
regurgitation (NYHA Class 
II-IV)   
3 
Deemed to be at high risk 
for conventional mitral valve 
surgery by the local heart 
team (including, at 
minimum, a cardiac 
surgeon, interventional 
cardiologist, and an 
echocardiologist) 
Trans-apical access deemed 
feasible by the treating 
physician 
Trans-apical access deemed 
feasible by the treating 
physician 
Deemed to be at high risk 
for conventional mitral valve 
surgery [STS Score > 8 or 
EuroSCORE > 15, or by 
agreement by the local 
heart team (i.e., surgeon, 
cardiologist & 
anesthesiologist)] 
4 
Age ≥ 18 
Age ≥ 18 
Age ≥ 18 
Age ≥ 18 

The Intrepid™ TMVR Pilot Study Statistical Analysis 
Plan 
Form 
 
Version 4.0 
Page 29 of 30 
 
 
This document is electronically controlled 
Medtronic Business Restricted 
056-F286, Statistical Analysis Plan Template 
Version C 
 
United States                      
CIP-1403 Version 4.0 
2019.10.15 
Australia                              
CIP-1403 Version A3 
16Dec2019 
Finland, Greece, United 
Kingdom, Denmark             
CIP-1403 Version 2.0 
16Dec2019 
France                                  
CIP-1403 Version F5 
20SEP2021 
5 
Native mitral valve 
geometry and size 
compatible with the 
Intrepid™ TMVR 
Native mitral valve 
geometry and size 
compatible with the 
Intrepid™ TMVR 
Native mitral valve 
geometry and size 
compatible with the 
Intrepid™ TMVR 
Native mitral valve 
geometry and size 
compatible with the 
Intrepid™ TMVR 
6 
No or minimal mitral valve 
calcification 
No or minimal mitral valve 
calcification 
No or minimal mitral valve 
calcification 
No or minimal mitral valve 
calcification 
7 
Willing to sign Informed 
Consent for participation in 
the study and return for all 
required post-procedure 
follow-up visits 
Willing to sign Informed 
Consent for participation in 
the study and return for all 
required post-procedure 
follow-up visits 
Willing to sign Informed 
Consent for participation in 
the study and return for all 
required post-procedure 
follow-up visits 
Willing to sign Informed 
Consent for participation in 
the study and return for all 
required post-procedure 
follow-up visits 
8 
NA 
NA 
NA 
If enrolled in France, 
subject must be entitled to 
French social security 
Exclusion Criteria 
1 
Left ventricular ejection 
fraction (LVEF) < 20 
Left ventricular ejection 
fraction (LVEF) < 20 
Left ventricular ejection 
fraction (LVEF) < 20 
Left ventricular ejection 
fraction (LVEF) < 20 
2 
Evidence of intracardiac 
mass, thrombus, or 
vegetation 
Evidence of intracardiac 
mass, thrombus, or 
vegetation 
Evidence of intracardiac 
mass, thrombus, or 
vegetation 
Evidence of intracardiac 
mass, thrombus, or 
vegetation 
3 
Pulmonary hypertension (> 
70 mmHg systolic)  
Pulmonary hypertension (> 
70 mmHg systolic)  
Pulmonary hypertension (> 
70 mmHg systolic)  
Pulmonary hypertension (> 
70 mmHg systolic)  
4 
Hypertrophic Obstructive 
Cardiomyopathy (HOCM) 
Hypertrophic Obstructive 
Cardiomyopathy (HOCM) 
Hypertrophic Obstructive 
Cardiomyopathy (HOCM) 
Hypertrophic Obstructive 
Cardiomyopathy (HOCM) 
5 
Prior mitral valve surgery or 
endovascular procedure, 
any currently implanted 
mechanical prosthetic valve, 
or need for other valve 
surgery/procedure  
Prior valve surgery or need 
for other valve surgery  
Prior mitral valve surgery or 
endovascular procedure, 
any currently implanted 
mechanical prosthetic valve, 
or need for other valve 
surgery/procedure  
Prior mitral valve surgery or 
endovascular procedure, 
any currently implanted 
mechanical prosthetic valve, 
or need for other valve 
surgery/procedure  
6 
Any endovascular 
therapeutic interventional or 
surgical procedure 
performed within 30 days 
prior to enrollment 
Any endovascular 
therapeutic interventional or 
surgical procedure 
performed within 30 days 
prior to enrollment 
Any endovascular 
therapeutic interventional or 
surgical procedure 
performed within 30 days 
prior to enrollment 
Any endovascular 
therapeutic interventional or 
surgical procedure 
performed within 30 days 
prior to enrollment 
7 
Prior stroke within 30 days 
Prior stroke within 30 days 
Prior stroke within 30 days 
Prior stroke within 30 days 
8 
Need for coronary 
revascularization 
Need for coronary 
revascularization 
Need for coronary 
revascularization 
Need for coronary 
revascularization 
9 
Need for emergent surgery 
Need for emergent surgery 
Need for emergent surgery 
Need for emergent surgery 
10 
History of, or active, 
endocarditis 
History of, or active, 
endocarditis 
History of, or active, 
endocarditis 
History of, or active, 
endocarditis 
11 
GI bleeding within 6 months 
GI bleeding within 6 months 
GI bleeding within 6 months 
GI bleeding within 6 months 
12 
History of bleeding diathesis 
or coagulopathy or patient 
will refuse blood transfusion 
History of bleeding diathesis 
or coagulopathy or patient 
will refuse blood transfusion 
History of bleeding diathesis 
or coagulopathy or patient 
will refuse blood transfusion 
History of bleeding diathesis 
or coagulopathy or patient 
will refuse blood transfusion 
13 
Hemodynamic instability 
Hemodynamic instability 
Hemodynamic instability 
Hemodynamic instability 
14 
Platelet count of <75,000 
cells/mm3 
Platelet count of <75,000 
cells/mm3 
Platelet count of <75,000 
cells/mm3 
Platelet count of <75,000 
cells/mm3 
15 
Renal insufficiency 
(Creatinine > 2.5 mg/dL)   
Renal insufficiency 
(Creatinine > 2.5 mg/dL)   
Renal insufficiency 
(Creatinine > 2.5 mg/dL)   
Renal insufficiency 
(Creatinine > 2.5 mg/dL)   
16 
Active infections requiring 
current antibiotic therapy (if 
temporary illness, patients 
may enroll 2 weeks after 
discontinuation of 
antibiotics) 
Active infections requiring 
current antibiotic therapy (if 
temporary illness, patients 
may enroll 2 weeks after 
discontinuation of 
antibiotics) 
Active infections requiring 
current antibiotic therapy (if 
temporary illness, patients 
may enroll 2 weeks after 
discontinuation of 
antibiotics) 
Active infections requiring 
current antibiotic therapy (if 
temporary illness, patients 
may enroll 2 weeks after 
discontinuation of 
antibiotics) 

The Intrepid™ TMVR Pilot Study Statistical Analysis 
Plan 
Form 
 
Version 4.0 
Page 30 of 30 
 
 
This document is electronically controlled 
Medtronic Business Restricted 
056-F286, Statistical Analysis Plan Template 
Version C 
 
United States                      
CIP-1403 Version 4.0 
2019.10.15 
Australia                              
CIP-1403 Version A3 
16Dec2019 
Finland, Greece, United 
Kingdom, Denmark             
CIP-1403 Version 2.0 
16Dec2019 
France                                  
CIP-1403 Version F5 
20SEP2021 
17 
Contraindication to 
transesophageal 
echocardiography (TEE) 
Contraindication to 
transesophageal 
echocardiography (TEE) 
Contraindication to 
transesophageal 
echocardiography (TEE) 
Contraindication to 
transesophageal 
echocardiography (TEE) 
18 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
19 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
21 
NA 
NA 
NA 
If treated in France, any 
subject who is a “personne 
vulnerable” per French 
legislation, including 
protected adults and 
prisoners 
 
 

The Intrepid™ TMVR Pilot Study Statistical Analysis 
Plan 
Form 
 
Version 4.0 
Page 30 of 30 
 
 
This document is electronically controlled 
Medtronic Business Restricted 
056-F286, Statistical Analysis Plan Template 
Version C 
 
United States                      
CIP-1403 Version 4.0 
2019.10.15 
Australia                              
CIP-1403 Version A3 
16Dec2019 
Finland, Greece, United 
Kingdom, Denmark             
CIP-1403 Version 2.0 
16Dec2019 
France                                  
CIP-1403 Version F5 
20SEP2021 
17 
Contraindication to 
transesophageal 
echocardiography (TEE) 
Contraindication to 
transesophageal 
echocardiography (TEE) 
Contraindication to 
transesophageal 
echocardiography (TEE) 
Contraindication to 
transesophageal 
echocardiography (TEE) 
18 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
Known hypersensitivity or 
contraindication to study or 
procedure 
medications/contrast which 
cannot be adequately 
managed medically 
19 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
Pregnant, nursing or 
planning to be pregnant. 
(Female participants of 
childbearing potential must 
have a negative pregnancy 
test prior to enrollment) 
21 
NA 
NA 
NA 
If treated in France, any 
subject who is a “personne 
vulnerable” per French 
legislation, including 
protected adults and 
prisoners