Feasibility Study of the Tendyne Mitral Valve System for Use in Subjects With Mitral Annular Calcification
Phase: NA
Conditions: Mitral Regurgitation, Mitral Insufficiency, Mitral Annular Calcification, Mitral Annulus Calcification, Cardiovascular Diseases, Valve Heart Disease, Heart Valve Diseases, Heart Valve Calcification, Mitral Valve Disease
Sponsor: Abbott Medical Devices

Tendyne Holdings, Inc. 
 
CONFIDENTIAL 
 
25APR2018 
Clinical Investigation Plan 
CS0005-P Version A 
Page 1 of 64 
 
 
 
CS0005-P 
MAC Feasibility Study 
Feasibility study of the Tendyne Mitral Valve System in Mitral Annular Calcification 
 
IDE Number 
G140240 
Version Number 
Version A 
Date 
25APR2018 
National Primary 
Investigator  
(Interventional Cardiologist) 
 
Paul Sorajja, M.D., FACC, FAHA, FSCAI 
Director, Center for Valve and Structural Heart Disease  
Minneapolis Heart Institute ‐ Abbott Northwestern Hospital 
National Primary 
Investigator  
(Cardiothoracic Surgeon) 
Vinod Thourani, M.D., FACS, FACC 
Professor of Surgery 
Chair, Department of Cardiac Surgery  
MedStar Heart and Vascular Institute Washington Hospital 
Center 
Study Type 
Prospective, single-arm, multicenter feasibility clinical 
study of the Tendyne Mitral Valve System 
Sponsor 
 
 
Tendyne Holdings, Inc. (a subsidiary of Abbott Vascular, 
Inc.)  
177 County Road B East 
St. Paul, MN 55117 
Protocol Author 
Aaron Fuchs 
Sr. Clinical Research Associate, Tendyne Holdings, Inc. 

Tendyne Holdings, Inc. 
 
CONFIDENTIAL 
 
25APR2018 
Clinical Investigation Plan 
CS0005-P Version A 
Page 2 of 64 
No use or disclosure of information contained within this document is permitted  
without prior written authorization from Tendyne Holdings, Inc. (a subsidiary of Abbott 
Vascular, Inc.). 
 
Mitral Valve System 
CLINICAL INVESTIGATION PLAN SIGNATURE PAGE 
Feasibility study of the Tendyne Mitral Valve System in Mitral Annular Calcification 
Clinical Investigation Plan No. CS0005-P 
Version A 
25APR2018 
I have read this Clinical Investigation Plan (CIP) and agree to adhere to conduct the investigation 
in accordance with the agreement, the CIP, applicable regulations, and any conditions of approval 
imposed by the Institutional Review Board (IRB).  I will provide copies of this CIP and all 
pertinent information to the study personnel under my supervision and my hospital IRB.  I will 
discuss this material with them and ensure they are fully informed regarding the Tendyne Mitral 
Valve System and the conduct of the study according to this CIP, applicable laws and regulatory 
regulations, including hospital IRB requirements. 
 
Investigational Site Name 
 
_______________________________________________________________________ 
Site Investigator Signature 
 
 
 
 
 
Date 
 
_______________________________________________    
Site Investigator Printed Name                                                                        
 

Tendyne Holdings, Inc. 
 
CONFIDENTIAL 
 
25APR2018 
Clinical Investigation Plan 
CS0005-P Version A 
Page 3 of 64 
 
Table of Contents 
TABLE OF CONTENTS ..............................................................................................................3 
TABLE OF FIGURES ...................................................................................................................6 
TABLE OF TABLES .....................................................................................................................6 
COMPLIANCE STATEMENT ....................................................................................................7 
CLINICAL INVESTIGATION PLAN SUMMARY ..................................................................8 
1 
INTRODUCTION................................................................................................................13 
2 
BACKGROUND INFORMATION ...................................................................................13 
2.1 
Mitral Valve Disease......................................................................................................13 
2.1.1  Mitral Regurgitation...................................................................................................13 
2.1.2  Mitral Annular Calcification ......................................................................................13 
2.2 
Treatment of Mitral Valve Disease ................................................................................14 
2.2.1  Current Guidelines .....................................................................................................14 
2.2.2  Treatment of Mitral Annular Calcification ................................................................15 
2.3 
Therapeutic Need ...........................................................................................................15 
2.3.1  Mitral Regurgitation...................................................................................................15 
2.3.2  Mitral Annular Calcification ......................................................................................16 
2.4 
Compassionate Use Experience with the Tendyne Mitral Valve System ......................16 
2.4.1  Rationale for Conducting this Clinical Study / Investigation ....................................16 
2.5 
Summary of Investigational Device ...............................................................................17 
2.5.1  Name of the Investigational Device ...........................................................................17 
2.5.2  Intended Use ..............................................................................................................17 
2.5.3  Indications for Use .....................................................................................................17 
2.5.4  Description of the Investigational Device (Tendyne Mitral Valve System) ..............17 
2.5.5  Procedures Involved in the Use of the Device ...........................................................18 
2.5.6  Training Required for the Use of the Device .............................................................18 
2.5.7  Investigational Device Accountability .......................................................................18 
3 
STUDY OBJECTIVES / ENDPOINTS .............................................................................19 
3.1 
Primary Safety Endpoint ................................................................................................19 
3.2 
Clinical Endpoints ..........................................................................................................20 
4 
STUDY DESIGN, SCOPE AND DURATION ..................................................................20 
4.1 
Study Design ..................................................................................................................20 
4.2 
Number of Subjects to be Registered .............................................................................20 
4.3 
Total Expected Duration of the Clinical Investigation ..................................................21 
5 
SUBJECT SELECTION AND WITHDRAWAL .............................................................21 
5.1 
Subject Screening and Informed Consent ......................................................................21 
5.1.1  Enrollment of Medicare Beneficiaries .......................................................................22 
5.2 
Eligibility Criteria ..........................................................................................................22 
5.2.1  General Eligibility Criteria ........................................................................................22 
5.2.2  Inclusion Criteria .......................................................................................................22 
5.2.3  Exclusion Criteria ......................................................................................................23 
5.3 
Subject Discontinuation .................................................................................................24 
5.3.1  Subject Lost-to-Follow-up .........................................................................................25 
5.4 
Early Termination of the Clinical Study ........................................................................25 
5.5 
Study Completion ..........................................................................................................25 
6 
SUBJECT SCREENING .....................................................................................................26 

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6.1 
Screening and Baseline Assessments .............................................................................26 
6.2 
Notification by Sponsor of Subject Screening Pass or Fail ...........................................27 
7 
TREATMENT AND PRE-DISCHARGE VISITS ...........................................................27 
7.1 
Concomitant Procedures ................................................................................................27 
7.2 
Tendyne Procedure ........................................................................................................28 
7.2.1  Tendyne Procedure - Access ......................................................................................28 
7.2.2  Tendyne Procedure - Device Delivery .......................................................................28 
7.2.3  Tendyne Procedure - Tensioning ...............................................................................28 
7.2.4  Tendyne Implant Identification Card .........................................................................29 
7.3 
Procedural Data Requirements ......................................................................................29 
7.3.1  12-Lead ECG .............................................................................................................29 
7.3.2  Intraoperative Hemodynamic Measurement ..............................................................29 
7.3.3  Intraoperative Angiography .......................................................................................29 
7.3.4  Additional Procedural Data Collection ......................................................................29 
7.3.5  Immediate Post-Operative Care .................................................................................30 
7.3.6  Anticoagulation Regimen ..........................................................................................30 
7.3.7  Pre-Discharge .............................................................................................................30 
8 
FOLLOW-UP FOR EVALUATION OF SAFETY AND EFFECTIVENESS ..............31 
8.1 
Clinical Follow-up .........................................................................................................31 
8.2 
30 Day, 3 Month, 6 Month, and Annual Visits ..............................................................31 
9 
ADVERSE EVENTS ...........................................................................................................32 
9.1 
Definitions / Types of Events ........................................................................................32 
9.1.1  Adverse Event ............................................................................................................32 
9.1.2  Serious Adverse Event ...............................................................................................33 
9.1.3  Anticipated Adverse Events .......................................................................................33 
9.1.4  Unanticipated Adverse Device Effect (UADE) .........................................................34 
9.2 
Device Deficiency ..........................................................................................................34 
9.3 
Device / Procedure Relationship ....................................................................................34 
9.4 
Adverse Event / Device Deficiency Reporting ..............................................................35 
9.4.1  AE Monitoring ...........................................................................................................35 
9.4.2  SAE Reporting to Sponsor and IRB ..........................................................................35 
9.4.3  UADE Reporting to Sponsor and IRB .......................................................................35 
9.4.4  Device Deficiency ......................................................................................................36 
9.4.5  Investigational Site AE Reporting Requirements to Sponsor ....................................36 
9.4.6  UADE Reporting to FDA by the Sponsor .................................................................36 
9.5 
Adjudication of AEs ......................................................................................................36 
10  STATISTICAL METHODS ...............................................................................................37 
10.1 
Sample Size Considerations ...........................................................................................37 
10.2 
Data Analysis Plan .........................................................................................................37 
10.2.1  General Principles ......................................................................................................37 
10.2.2  Subject Disposition ....................................................................................................37 
10.2.3  Study Conduct ............................................................................................................38 
10.2.4  Analysis Samples .......................................................................................................38 
10.2.5  Analysis of Population Demographics, Baseline and Procedural Characteristics .....38 
10.2.6  Analysis of Primary Safety Endpoint ........................................................................38 
10.2.7  Analysis of Clinical Endpoints ..................................................................................38 

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10.2.8  Subgroup Analysis .....................................................................................................38 
10.2.9  Handling of Missing Data ..........................................................................................38 
11  DIRECT ACCESS TO SOURCE DATA / DOCUMENTS .............................................39 
12  QUALITY CONTROL AND QUALITY ASSURANCE .................................................39 
12.1 
Selection of Clinical Sites and Investigators .................................................................39 
12.2 
Clinical Investigation Plan Amendments .......................................................................40 
12.3 
Study Training ...............................................................................................................40 
12.3.1  Site Training...............................................................................................................40 
12.3.2  Training of Sponsor’s Designees or Vendors ............................................................40 
12.3.3  Training of Sponsor’s Monitors .................................................................................40 
12.4 
Monitoring .....................................................................................................................40 
12.4.1  Designated Monitors ..................................................................................................40 
12.4.2  Monitoring Visits .......................................................................................................41 
12.5 
Deviations from Clinical Investigation Plan ..................................................................41 
12.5.1  Deviations with Expedited Reporting Requirements .................................................41 
12.5.2  Non-Critical Deviations .............................................................................................41 
12.6 
Review of Study Imaging Assessments .........................................................................42 
12.7 
Safety and Effectiveness Monitoring .............................................................................42 
12.8 
Follow-up Compliance...................................................................................................42 
12.9 
Quality Assurance Audit ................................................................................................42 
12.10  Sponsor Support for Regulatory Body Inspection .........................................................42 
12.11  Committees ....................................................................................................................43 
12.11.1  Publications Committee .........................................................................................43 
12.11.2  Data and Safety Monitoring Board (DSMB) .........................................................43 
12.11.3  Clinical Events Committee (CEC) .........................................................................43 
13  DATA HANDLING AND RECORD KEEPING ..............................................................43 
13.1 
Data Management ..........................................................................................................44 
13.2 
Source Documentation ...................................................................................................44 
13.3 
Electronic Case Report Form Completion .....................................................................45 
13.4 
Record Retention ...........................................................................................................45 
13.4.1  Investigator Records ..................................................................................................45 
13.4.2  Sponsor Records ........................................................................................................46 
14  ETHICAL CONSIDERATIONS ........................................................................................47 
15  PUBLICATION POLICY ...................................................................................................48 
16  RISK ANALYSIS.................................................................................................................48 
16.1 
Anticipated Clinical Benefits .........................................................................................48 
16.2 
Risks Associated with Participation in the Clinical Study .............................................49 
16.3 
Possible Interactions with CIP-Required Concomitant Medications .............................49 
16.4 
Steps Taken to Control or Mitigate the Risks ................................................................50 
16.5 
Risk to Benefit Rationale ...............................................................................................50 
APPENDIX I:  ABBREVIATIONS AND ACRONYMS .........................................................51 
APPENDIX II:  DEFINITIONS .................................................................................................52 
APPENDIX III: STUDY ASSESSMENT AND FOLLOW-UP SCHEDULE........................59 
APPENDIX IV:  CONTACT INFORMATION .......................................................................60 
APPENDIX V: CLINICAL INVESTIGATION PLAN REVISIONS ....................................61 
APPENDIX VI:  BIBLIOGRAPHY...........................................................................................62 

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TABLE OF FIGURES 
Figure 1.  Mitral Regurgitation Severity ....................................................................................... 55 
TABLE OF TABLES 
Table 1. MAC Compassionate Use Implants ................................................................................ 16 
Table 2.  Follow-up Schedule and Windows for Study Subjects ................................................. 32 
Table 3.  Anticipated Adverse Events ........................................................................................... 33 
Table 4.  Investigational Site AE Reporting Requirements to Sponsor ........................................ 36 
Table 5.  Description and Submission Requirements of Sponsor Reports ................................... 47 
Table 6.  Study Procedure-Related Risks ..................................................................................... 49 
 
 
 
 
 
 
 

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25APR2018 
Clinical Investigation Plan 
CS0005-P Version A 
Page 7 of 64 
COMPLIANCE STATEMENT 
This study will be conducted in accordance with this Protocol, the Declaration of Helsinki and US 
Good Clinical Practice and the applicable regulatory requirements (such as, 21 CFR Part 50, 21 
CFR Part 56,21 CFR Part 812, 21 CFR Part 54, and 21 CFR Part 11and 45 CFR part 46). The 
conduct of the study will be approved by the Food and Drug Administration (FDA) and the 
appropriate Institutional Review Board (IRB) of the respective investigational site.  
                                                                                                                                                                                    
 
 

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Clinical Investigation Plan 
CS0005-P Version A 
Page 8 of 64 
CLINICAL INVESTIGATION PLAN SUMMARY 
Study Name and 
Number 
MAC Feasibility Study (CS0005-P) 
Title 
Feasibility study of the Tendyne Mitral Valve System for use in 
subjects with Mitral Annular Calcification 
Objectives 
To evaluate the feasibility of using the Tendyne Mitral Valve System 
in the treatment of mitral valve regurgitation in patients with severe 
mitral annular calcification.   
Investigational 
Device 
Tendyne Mitral Valve System 
Clinical Study / 
Investigation Design 
This study is a prospective, single-arm, multicenter feasibility clinical 
study of the Tendyne Mitral Valve System for the treatment of eligible 
subjects with symptomatic, severe mitral regurgitation and severe 
mitral 
annular 
calcification. 
Subjects 
satisfying 
the 
study 
inclusion/exclusion will undergo a procedure to implant the Tendyne 
device. 
Planned Sample Size 
/ Investigational Sites 
Up to 30 subjects will be registered in the study to receive the Tendyne 
device at up to 10 sites in the United States.  
Primary Safety 
Endpoint 
Composite endpoint of Device Success and freedom from device or 
procedure related serious adverse events (SAEs) at 30 days post 
implant, as classified by the Clinical Events Committee (CEC).  
Definition of Device Success:  
All of the following must be present: 
1) Absence of procedural mortality or stroke; and 
2) Proper placement and positioning of the device; and 
3) Freedom from unplanned surgical or interventional procedures 
related to the device or access procedure; and 
4) 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 or 
complications 
c) Reduction of MR to either optimal or acceptable levels 
without significant structural valve dysfunction and with 
no greater than mild (1+) paravalvular MR (and without 
associated hemolysis) 
 

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Clinical Endpoints 
The following clinical endpoints will be assessed as part of this 
feasibility study 
1) Technical Success as measured at exit from the procedure 
Definition of Technical success: 
a) 
Absence of procedural mortality; and 
b) Successful access, delivery and retrieval of the device 
delivery system; and 
c) 
Successful deployment and correct positioning of the 
intended device; and 
d) Freedom from emergency surgery or re-intervention related 
to the device or access procedure 
 
2) Patient Success at 1, 2, 3, 4, and 5 years post index procedure 
Definition of Patient Success: 
a) Device Success (either optimal or acceptable); and 
b) Subject returned to the pre-procedural setting (e.g. home, 
assisted living facility); and 
c) No transcatheter or surgical re-interventions for mitral 
valvular disease (modified from MVARC guidelines); and 
d) Improvement 
from 
baseline 
symptoms 
(NYHA 
improvement by ≥ 1 Functional Classification); and 
e) Improvement from baseline in functional status (6MWD 
improvement by ≥ 50 meters); and 
f) Improvement from baseline in Quality of Life (KCCQ 
improvement by ≥ 10 points) 
 
3) Device Success as measured at 30 days and at all post-procedural 
intervals 
4) Freedom from all-cause mortality at 3 months, 6 months, 1 year  
and then annually through 5 years post index procedure  
5) Change from baseline in distanced walked on the 6MWT at each 
follow-up visit 
6) Change from baseline in QoL, as measured by the KCCQ at each 
follow-up visit 
7) NYHA Functional Classification at each follow-up visit  

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Subject Follow-up 
Subjects will be seen at the following study intervals: 
Visit 1 – Screening / Baseline  
Visit 2 – Procedure 
Visit 3 – Pre-discharge 
Visit 4 – Follow up 30 days post procedure 
Visit 5 – Follow-up 90 days post procedure 
Visit 6 – Follow-up 182 days post procedure 
Visit 7 – Follow-up 365 days post procedure  
Visit 8 – Follow-up 731 days post procedure 
Visit 9 – Follow-up 1096 days post procedure 
Visit 10 – Follow-up 1461 days post procedure 
Visit 11 – Follow-up 1826 days post procedure  
Planned Duration of 
Study 
Approximately 76 months. This includes a 16-month subject 
enrollment phase period, with subject follow-up continuing for an 
additional 60 months.  
Study reports will be completed annually with a final report estimated 
for completion within 3 months of the last subject visit. 
Eligibility Criteria 
Inclusion Criteria 
1. Heart Team determines subject is not a suitable candidate for 
conventional surgical treatment due to degree of MAC present 
and, the subject will likely benefit from transcatheter valve 
implantation 
2. Severe, symptomatic mitral regurgitation (as defined in the 2017 
ACC expert Consensus Decision Pathway on the Management of 
MR)  
3. NYHA Functional Classification ≥ II (if Class IV, patient must be 
ambulatory) 
4. Age 18 years or older at time of consent  
5. Not a member of a vulnerable population per the investigator’s 
judgment 
6. The subject or the subject’s legal representative has been 
informed of the nature of the study and agrees to its provisions, 
including complying with study required testing and follow-up 
visits, and has provided written informed consent 
Exclusion Criteria 
1. Presence of Left Ventricle or Left Atrium thrombus 
2. Subject has a chest condition that prevents transapical access 

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3. Left Ventricular Ejection Fraction (LVEF) less than 25% assessed 
by echocardiogram 
4. Left Ventricular End Diastolic Dimension (LVEDD) > 7.0 cm  
5. Severe mitral stenosis not amenable to balloon valvuloplasty or 
transcatheter therapy 
6. Prior intervention with permanently implanted mitral device (e.g. 
MitraClip) 
7. Mitral pathoanatomy and Left Ventricular Outflow tract (LVOT) 
anatomy deemed not suitable for Tendyne mitral valve 
implantation 
8. Any planned cardiac surgery or intervention that is 30 days prior 
and 30 days post that is not concomitant with the Tendyne 
procedure 
9. Cardiac resynchronization therapy (CRT) device or implantable 
pulse generator (IPG) implanted within three months of planned 
implant procedure  
10. Myocardial Infarction (MI) within 30 days prior to the planned 
implant procedure 
11. Symptomatic, or ischemia-associated coronary artery disease 
(e.g., active ischemia) amenable to revascularization and thus 
requiring stenting or Coronary Artery Bypass Grafting (CABG) 
12. Cerebrovascular accident (CVA) within six months prior to the 
planned implant procedure 
13. Unresolved severe symptomatic carotid stenosis (>70% by 
ultrasound) 
14. Cardiogenic shock or hemodynamic instability requiring 
inotropes or mechanical support devices within 1 month prior to 
planned implant procedure 
15. Severe tricuspid regurgitation or severe right ventricular 
dysfunction 
16. Hypertrophic 
or 
restrictive 
cardiomyopathy, 
constrictive 
pericarditis or any other structural heart disease causing heart 
failure other than dilated cardiomyopathy of either ischemic or 
non-ischemic etiology 
17. Any 
of 
the 
following: 
leukopenia, 
acute 
anemia, 
thrombocytopenia, history of bleeding diathesis, or coagulopathy 
if cannot be adequately treated 

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18. History of endocarditis within 6 months of planned implant 
procedure 
19. Active systemic infection requiring antibiotic therapy 
20. Known hypersensitivity or contraindication to procedural or post-
procedural medications (e.g., contrast solution, anti-coagulation 
therapy) which cannot be adequately managed medically 
21. Subject unable or unwilling to take anticoagulation with warfarin 
for a minimum of 6 months following Tendyne valve implantation 
22. Known hypersensitivity to nickel or titanium 
23. Subject is undergoing hemodialysis due to chronic renal failure 
( > Stage 4 CKD) 
24. Subject has pulmonary arterial hypertension (fixed PAS 
>70mmHg) 
Note: If PAS > 70mmHg, site must provide documentation PAS 
is not fixed in order to be eligible 
25. FEV1 < 50% of predicted or < 1L 
26. Subject refuses blood transfusions 
27. Subject has COPD requiring continuous home oxygen therapy or 
chronic outpatient oral steroid use 
28. Pregnant, lactating, or planning pregnancy within next 12 months 
Note:  Female subjects of childbearing age should be instructed 
to use safe contraception (e.g. intrauterine devices, hormonal 
contraceptives: contraceptive pills, implants, transdermal patches 
hormonal vaginal devices, injections with prolonged release) 
29. Currently participating in an investigational drug or another 
device trial that has not reached its primary endpoint   
Note: Trials requiring extended follow-up for products that were 
investigational, but have since become commercially available, 
are not considered investigational trials 
30. Subjects with non-cardiac co-morbidities that are likely to result 
in a life expectancy of less than 12 months 

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1 
INTRODUCTION 
The objective of this feasibility study is to provide preliminary information on the safety and 
effectiveness of the Tendyne Mitral Valve System for the treatment of symptomatic, severe mitral 
regurgitation in patients with severe mitral annular calcification (MAC). 
  
As the Sponsor, Tendyne Holdings, Inc. (“Tendyne”) has the overall responsibility for the conduct 
of the study including assurance that the study will be performed according to this CIP as per the 
U.S. Food and Drug Administration (FDA) and any other applicable regulations. Tendyne will 
have direct responsibilities for day-to-day study management, and may delegate responsibilities 
for some study management activities to a Contract Research Organization (CRO), if needed.   
2 
BACKGROUND INFORMATION 
2.1 
Mitral Valve Disease  
2.1.1 Mitral Regurgitation  
Two population-based studies in the US showed that mitral regurgitation (MR) is the most 
common heart valve disease [1,2]. The Framingham Offspring Study used color Doppler 
echocardiography to assess for MR, which was detected in 90% of the subjects, albeit trace or mild 
in severity (not clinically significant) in the majority of cases.  However, 1.6% of subjects had 
moderate to severe MR [2]. The most common factors associated with the presence of MR were 
older age, lower body mass index, heart failure, myocardial infarction (MI) and hypertension.   
Similarly, a population-based study by Nkomo et al. found moderate to severe MR occurring in 
approximately 1.7% of the US population with increasing prevalence among older individuals 
(7.3% of those ≥65 years of age).   The authors estimated that in the year 2000 approximately 2 to 
2.5 million people were affected by moderate to severe MR. With current US demographic trends 
toward increasing population growth and increasing numbers of older Americans, the number of 
people with MR is expected to double by 2030 [1].   
Referral and treatment patterns for valvular heart disease were evaluated in the Euro Heart Survey 
of 92 centers over a 3 month period in 2001 [3,4]. Mitral regurgitation was identified as the second 
most common form of valvular heart disease after aortic stenosis.  The authors noted that the 
difference compared to the US studies may have been due to the nature of the survey, in which 
only those patients referred for at least moderate valve disease to tertiary centers were included 
[4].  This suggests that patients with moderate or severe MR are not being properly referred for 
treatment, and important interventions are being delayed. 
2.1.2 Mitral Annular Calcification 
Mitral annular calcification is a chronic degenerative process in the fibrous base of the mitral valve 
which can result in either MS or MR, or a combination of both disorders.  The prevalence of MAC 
is age-dependent, with 15% to 30% of those older than 70 years affected.  MAC is more common 
in patients with kidney disease, fibrous skeletal abnormalities (e.g., Marfan syndrome), 
atherosclerosis, hypertension, and chronic inflammatory disorders.  MAC causes significant mitral 
stenosis or regurgitation by impairing diastolic annular dilation and restriction of mitral leaflet 

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motion. These changes typically progress over time with secondary calcification of the valvular 
apparatus.    
The pathophysiology of the disease is variable depending on the severity of the valve lesion, and 
whether the lesion is predominantly stenosis, regurgitation, or both. In predominant MR, there is 
a volume overload of the left ventricle that results in (LV) hypertrophy to compensate for both the 
metabolic demands of the body (forward stroke volume) and regurgitant volume with each 
heartbeat.  There is also a compensatory gradual enlargement of the left atrium (LA) and increase 
in LA compliance.  The chronic, compensated phase of the disease may consist of asymptomatic 
patients with normal exercise tolerances.   
Compensated MR may persist for many years.  At some point, however, the LV myocardium is 
no longer able to contract adequately to overcome the volume overload caused by MR. The 
reduced ability of the LV to contract results in a decreased stroke volume, which leads to decreased 
cardiac output, an increase in end systolic volume, increased LV filling pressures and increased 
pulmonary congestion.  In this stage, the patient displays signs of heart failure and exercise 
intolerance.  In an attempt to increase cardiac output, there is further dilatation of the LV, which 
leads to increasing dilatation of the MV annulus and increasingly more severe MR. 
2.2 
Treatment of Mitral Valve Disease  
2.2.1 Current Guidelines 
The American College of Cardiology/American Heart Association (ACC/AHA) and the European 
Society of Cardiology/European Association for Cardio-Thoracic Surgery (ESC/EACTS) have 
published guidelines for the management of mitral disease [5,6]. In summary, the guidelines advise 
surgical treatment of primary MR when the lesion is severe and with symptoms, left ventricular 
dysfunction, or when cardiac surgery is being undertaken for other indications. Surgical 
intervention also should be considered when patients have secondary, severe MR and are 
undergoing coronary artery bypass grafting. For mitral stenosis (MS), percutaneous mitral balloon 
commissurotomy is recommended for symptomatic patients with severe MS (valve area <1.5 cm2) 
and favorable valve morphology.  Characteristics of valve morphology that are favorable include 
pliability of the leaflets and sub-chordal apparatus, and the absence of grade 3 or 4 MR.  When the 
valve morphology is not favorable for percutaneous mitral balloon commissurotomy, surgery for 
severe MS is advised when the patient has severe symptoms (class III or IV). Some reports 
indicated that medical therapies directed at the underlying heart failure and LV dysfunction may 
have a beneficial effect on secondary MR in some patients.  Specifically, maximal therapy beta 
adrenergic blockers or angiotensin-converting enzyme inhibitors and cardiac resynchronization 
therapy have been shown to reduce MR severity [7-11].  The general belief has been that early 
reperfusion with percutaneous coronary intervention (PCI) or coronary artery bypass grafts 
(CABG) would reduce ischemic damage to the heart muscle and retard the process of LV 
remodeling, thereby preventing the development of MR [12].  However, treatment of the ischemia 
with PCI or CABG did not improve survival or result in the short-term or long-term improvement 
in the IMR severity [11-13]. Some data suggest that MV repair or reduction of annular diameter 
with an annuloplasty ring concomitant with a CABG procedure may provide benefit [14-17].  It 
should be noted; however, that surgical treatment of secondary MR is evolving such that many 
patients will not receive repair or replacement unless the patient has concomitant surgical 
indications for revascularization or aortic valve replacement. 

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2.2.2 Treatment of Mitral Annular Calcification  
Patients with MAC are a unique subgroup of patients due to their marked surgical risk.  In these 
patients, there is a high risk of atrioventricular groove disruption, a complication that is nearly 
universally fatal [18,19]. Other potential complications that can occur with open surgical treatment 
of MAC include ventricular rupture and injury to the left circumflex coronary artery.  The presence 
of MAC is associated with increased intraoperative conversion from valve repair to replacement 
[20]. In addition, MAC will be accompanied by severe morbidities that significantly increase 
surgical risk, such as coronary atherosclerosis, vascular disease, and renal failure. Thus, mitral 
valve surgery for treatment of MAC is reserved only for select patients. 
In order to avoid or minimize the risk of surgical complications with treatment of MAC, several 
approaches have been developed.  Mitral valve replacement without debridement of the mitral 
annulus has been utilized, though paravalvular regurgitation may occur due to the non-uniform 
sewing borders.  In other instances, an edge-to-edge repair has been employed; the main limitation 
with this approach is worsening of pre-existing mitral stenosis that is common in these patients.  
Success with surgical dissection and reconstruction of the calcified annulus with suturing, a 
pericardial patch, or an atrial flap, followed by mitral repair or replacement also has been reported 
[21-23].  
Transcatheter techniques for treatment of MAC have been developed to obviate the need for open 
surgical correction and minimize the procedural risk.  These off-label techniques have utilized 
direct atrial access, transseptal puncture, and transapical approaches for implanting transcatheter 
valves that were initially designed for treatment of calcific aortic stenosis. In the largest registry 
of transcatheter implantation of valve prostheses for the treatment of MAC (n=64), initial technical 
success was achieved in 46 patients (or 72%); additional valves were needed in 11 patients, leading 
to an overall procedural success rate of 89.2% [24]. Complications included left ventricular 
outflow tract obstruction with hemodynamic compromise (9.3%) and valve embolization (6.5%).  
Periprocedural death, owing to technical failures as well as high patient co-morbidity, occurred in 
19 of 64 cases (29.7%).  Importantly, there were no incidences of annular rupture.  All patients 
had mild or no residual MR after transcatheter valve implantation.  These results, which mirror 
what has also been described multiple case reports and series, are important advances as 1) the 
operators had utilized circular valve prostheses (Sapien, Sapien XT, Sapien 3, Inovare) in off-label 
fashion for the treatment of rigid, irregularly shaped annuli; 2) the high success rates occurred 
among operators  who were new to the procedure with very limited experience (64 patients treated 
at 32 sites); and 3) the valve prostheses utilized were neither retrievable nor repositionable, and 
thus create challenges for instances where there is device malpositioning. 
2.3 
Therapeutic Need 
2.3.1 Mitral Regurgitation  
Although the guidelines for management of valvular heart disease suggest that surgical repair of 
symptomatic MR is preferred over surgical replacement, more recent evidence indicates that 
replacement is not inferior and represents a viable first line treatment option for many patients.  
Additionally, there is a large patient population that has limited treatment options.  Specific 
populations of patients with limited options include those who are not suitable surgical candidates, 

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because they considered high risk for peri-procedural morbidity and mortality and those with 
secondary MR.   
These populations could benefit from a less invasive approach that does not require an open-heart 
procedure nor cardiopulmonary bypass.  Therefore, transcatheter mitral valve implantation has the 
potential to be a viable alternative to traditional mitral valve surgery.  
2.3.2 Mitral Annular Calcification 
Although the practice guidelines for the management of valvular heart disease recommend 
treatment of symptomatic mitral disease, patients with MAC have limited surgical and 
transcatheter options.  The surgical risk is markedly elevated in these patients due to technical 
challenges, as well as the severe morbidities (e.g., renal failure, atherosclerosis, inflammatory 
disorders) that frequently are present in patients with MAC.  While transcatheter therapy is 
routinely employed for the treatment of valvular disease in high or prohibitive risk patients, no 
technology has been designed specifically for patients with mitral disease due to MAC.  The use 
of available transcatheter therapy, while feasible in these patients, remains technically challenging 
with complications that, in part, are attributable to the off-label nature of employed devices. Thus, 
patients with MAC who are at high or prohibitive surgical risk could benefit from a less invasive 
approach designed for the mitral valve that does not require an open-heart procedure or 
cardiopulmonary bypass.  If successful, transcatheter mitral valve implantation with such devices 
would help to address a large unmet clinical need.  
2.4 
Compassionate Use Experience with the Tendyne Mitral Valve System 
The Tendyne Mitral Valve System is only available for use under clinical investigational settings.  
For patients who do not meet entry criteria for the current ongoing clinical study (ClinialTrials.gov 
identifier: NCT02321514 Expanded Clinical Study of the Tendyne Mitral Valve System), they 
may receive the device under expanded access mechanisms such as compassionate use. As of 
February 12, 2018, the Tendyne valve has been successfully implanted in twenty patients under 
compassionate use including six patients with MAC (Table 1).   
 
Table 1. MAC Compassionate Use Implants  
Site Name 
City, State 
Implanted 
Abbott Northwestern Hospital 
Minneapolis, MN 
5 
Emory University Hospital 
Atlanta, GA 
1 
 
2.4.1 Rationale for Conducting this Clinical Study / Investigation 
This feasibility study is designed to capture clinical and outcomes data to investigate whether the 
Tendyne Mitral Valve System holds promise for the treatment of patients suffering from the 
debilitating symptoms of symptomatic, severe mitral regurgitation associated with severe MAC. 
Information garnered from this study may be used to refine the patient population for whom the 
device is intended and/or form the basis for the development of subsequent clinical protocols. 
Patients who are not appropriate for MV surgery due to the increased procedural risk associated 
with the presence of MAC and history of comorbidities will undergo the Tendyne procedure. 

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Potential benefits of the use of the Tendyne device include, but may not be limited to, the 
following: 
 Improved symptomatic status and quality of life  
 Reduced mortality  
 Avoidance of procedural risks such as: cardiopulmonary bypass (CPB); atrioventricular 
groove disruption; ventricular rupture; and injury to the left circumflex coronary artery 
Early data obtained from the compassionate use experiences with the Tendyne device in patients 
with severe MR and severe MAC demonstrate that the Tendyne device can be successfully 
implanted. Patients experience post-procedure improvement in NYHA functional status and the 
device remains in place without paravalvular leak. In consideration of the potential benefits and 
the favorable risk profile of the Tendyne device, this feasibility study is clinically justified.   
2.5 
Summary of Investigational Device 
2.5.1 Name of the Investigational Device 
The investigational device to be used in this study is the Tendyne Mitral Valve System, which 
consists of the Tendyne Mitral Valve and an instrument to facilitate placement of the valve.  In 
this CIP, the investigational device is referred to as the “Tendyne Mitral Valve System” or the 
“Tendyne device”.  
2.5.2 Intended Use 
The Tendyne Mitral Valve System is intended for transapical, beating heart, mitral valve 
replacement in patients with a diseased, damaged, or malfunctioning mitral valve. 
2.5.3 Indications for Use 
The Tendyne Mitral Valve System is indicated for transapical delivery via a sheath in patients with 
symptomatic, severe mitral valve regurgitation with severe mitral annular calcification, who are 
not suitable for surgical treatment and in whom existing co-morbidities would not preclude the 
expected benefit from reduction of the mitral regurgitation. 
2.5.4 Description of the Investigational Device (Tendyne Mitral Valve System) 
The Tendyne Mitral Valve is a bioprosthetic valve, which consists of a porcine pericardial tri-
leaflet valve attached to an inner frame.  This inner valve is then attached to an outer frame and a 
tether.  During the implantation procedure, the tether is secured to an apical pad on the epicardial 
surface of the heart.  
The inner valve is comprised of three (3) identical, porcine leaflets assembled onto a circular, self-
expanding inner frame.  The outer valve assembly is intended to provide sealing and conform to 
the native mitral annulus.  It is made from the same super-elastic nickel-titanium alloy (Nitinol) as 
the inner frame.  The outer surface of the outer-frame is covered with a porous polyester material.  
The atrial surface of the outer-frame is covered in fixed porcine pericardial tissue.  The inner 
porcine and outer polyester materials are sutured to the outer frame with braided ultra-high 
molecular weight polyethylene suture.  

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A radiopaque marker at A1 can be visualized under fluoroscopy to confirm orientation of the valve.  
The outer-frame cuff is raised along the straight leg of the D-shape frame and is referred to as the 
A2 region or the “proud cuff” as it is the tallest section of the outer frame.  The proud cuff of the 
outer-frame is also used to orient the prosthesis inside the native mitral valve. 
The valve is fully repositionable and retrievable intraoperatively. Repositioning allows 
optimization of the valve position following deployment, and retrieval allows use of an alternative 
valve size if the initial valve does not have adequate performance. 
The inner valve is assembled into various sizes of outer frames to give the valve the ability to 
conform to a wide range of patient geometries.  The size of the valve is defined by the anterior-
posterior (AP) length, inter-commissural diameter (IC), the perimeter (PER) of the outer-frame 
and the effective orifice area (EOA). Imaging techniques are used to determine valve size based 
on the subject’s mitral annulus dimensions.  The valve size is chosen to provide the proper fit for 
paravalvular sealing and device stability.  The decision regarding which valve size to implant may 
be influenced by the simulated area of the LVOT created following implantation of the valve.  This 
modeling 
is 
performed 
using 
software 
(Circle 
cardiovascular 
imaging 
software, 
www.circlecvi.com; and Mimics medical image segmentation for engineering on anatomy, 
biomedical.materialise.com/mimics). 
The Instrument Set used in the transapical implantation of the valve includes the following 
components: 1) Tendyne Loading System, 2) Tendyne Delivery System and 3) Tendyne Pad 
Positioning System.  An additional instrument 4) Tendyne Retrieval System, is also available, 
which can be used to retrieve the valve intraoperatively, should the valve implant be suboptimal.  
All of the components of these systems are provided sterile via ethylene oxide (EO) sterilization.  
All components of these systems that come in contact with the subject are also provided non-
pyrogenic. 
For a more detailed description of the Tendyne Mitral Valve System refer to the Instructions for 
Use (IFU). 
2.5.5 Procedures Involved in the Use of the Device 
 
The procedures outlined in the approved Tendyne Mitral Valve System IFU must be followed in 
the use of this device under this CIP. 
2.5.6 Training Required for the Use of the Device 
 
Investigators will be trained in accordance with the approved Tendyne Mitral Valve System IFU.  
Investigator training will include, but will not be limited to, the use of a bench top model and 
demonstration unit to ensure that investigators understand the mechanics and characteristics of the 
Tendyne Mitral Valve System.  Sponsor staff will conduct this training and a training log will be 
used for documentation.  Only physicians who receive all required device training and have 
documentation that training was completed can perform the Tendyne procedure under this CIP. 
2.5.7 Investigational Device Accountability 
The Sponsor is responsible for the availability and distribution of all investigational products.  
Product will only be distributed to study sites when the Sponsor has provided written 
documentation of investigational site readiness.  The Sponsor will ship and/or hand-carry devices 

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(the Tendyne System) to the Principal Investigator or his/her designee at each site.  The Tendyne 
System must be stored in a secured location separate from market-released products. 
The investigator, or designee, will maintain adequate records of the receipt and disposition of the 
investigational device system, including reference/serial/lot numbers (as appropriate), date of use, 
subject number and implanting physician(s).  A Device Accountability Log supplied by the 
Sponsor will be used.  All unused investigational devices must be returned to the Sponsor when 
study registration is complete (completed device accountability reports will be generated for the 
site) or as otherwise deemed necessary (e.g., expired devices). 
Any investigational devices that are associated with a device failure or device deficiency (and were 
not successfully implanted) should be returned immediately to the Sponsor. 
3 
STUDY OBJECTIVES / ENDPOINTS 
The objective of this study is to capture preliminary information regarding the safety and 
effectiveness of the Tendyne Mitral Valve System. There are no pre-defined pass or fail criteria 
for evaluating the study objectives. Endpoints were selected to help determine the feasibility of 
the Tendyne Mitral Valve System in the treatment for mitral regurgitation in subjects with MAC. 
3.1 
Primary Safety Endpoint 
The primary safety endpoint will evaluate the procedural and device safety of the Tendyne Mitral 
Valve System. The composite endpoint is: Device Success (defined below) and freedom from 
device or procedure related serious adverse events (SAEs) at 30 days post implant, as classified by 
the Clinical Events Committee (CEC).  
Definition of Device Success:  
All of the following must be present: 
1) Absence of procedural mortality or stroke; and 
2) Proper placement and positioning of the device, and 
3) Freedom from unplanned surgical or interventional procedures related to the device or 
access procedure; and 
4) 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 or complications 
c) Reduction of MR to either optimal or acceptable levels without significant structural 
valve dysfunction and with no greater than mild (1+) paravalvular MR (and without 
associated hemolysis). 
 
Structural failure is when the valve fails to perform as intended due to a complication related 
the valve, such as: fracture, migration or embolization. Functional failure is when the valve 
performs as intended without complication but does not adequately reduce the degree of MR 
or results in new, significant mitral stenosis. 
 
Post-procedure MR reduction is considered optimal when reduced to trace or absent and 
acceptable when reduced by at least 1 class or grade from baseline and to no more than 
moderate (2+) residual MR in severity [25].  
 

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Note: Criterion #4c above has been modified from the MVARC guidelines [25], to align with 
the structural valve dysfunction definition used in this CIP. 
3.2 
Clinical Endpoints 
The following clinical endpoints will be evaluated: 
 Technical success evaluated upon exit from procedure room, defined as: 
1) Absence of procedural mortality; and 
2) Successful access, delivery and retrieval of the device delivery system; and 
3) Successful deployment and correct positioning of the intended device; and 
4) Freedom from emergency surgery or re-intervention related to the device or access 
procedure 
 Patient Success evaluated at 1, 2, 3, 4, and 5 years post index procedure, defined as: 
1) Device Success (either optimal or acceptable); and 
2) Subject returned to the pre-procedural setting (e.g. home, assisted living facility); and 
3) No transcatheter or surgical re-interventions for mitral valvular disease (modified from 
MVARC guidelines); and 
4) Improvement from baseline symptoms (NYHA improvement by ≥ 1 Functional 
Classification); and 
5) Improvement from baseline in functional status (6MWD improvement by ≥ 50 meters); 
and 
6) Improvement from baseline in Quality of Life (KCCQ improvement by ≥ 10 points) 
 Device Success as measured at 30 days and at all post-procedural intervals 
 Freedom from all-cause mortality at 3 months, 6 months, 1 year, and then annually through 5 
years post index procedure 
 Distance walked on the 6MWT at baseline, 30 days, 3 months, 6 months, 1 year, and then 
annually through 5 years post index procedure (change from baseline to follow-up) 
 KCCQ QoL scores at baseline, 30 days, 3 months, 6 months, 1 year, and then annually through 
5  years post index procedure (change from baseline to follow-up) 
 NYHA Functional Classification at baseline, 30 days, 3 months, 6 months, 1 year, and then 
annually through 5 years post index procedure  
4 
STUDY DESIGN, SCOPE AND DURATION 
4.1 
Study Design 
This study is a prospective, single-arm, multicenter feasibility clinical study of the Tendyne Mitral 
Valve System for the treatment of eligible subjects with symptomatic, severe mitral regurgitation 
and severe mitral annular calcification (MAC). 
Subjects whom the local site heart team determines: (a) are not suitable candidates for conventional 
mitral valve surgery due to the degree of MAC present; (b) will likely benefit from transcatheter 
valve implantation; and (c) meet study entrance criteria will receive the Tendyne device.  
4.2 
Number of Subjects to be Registered 
This study will enroll male and female subjects who satisfy the inclusion and exclusion criteria 
and provide written informed consent. This study will register up to 30 subjects at up to 10 
investigational sites in the U.S. 

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Subjects are enrolled in the study upon signing the informed consent form.  Subjects are considered 
registered in the study upon attempt of the implant procedure.     
There is no minimum number of subjects to be registered at any site.   
4.3 
Total Expected Duration of the Clinical Investigation 
The total duration of the study is estimated as 76 months. This includes a 16-month subject 
enrollment phase period, with subject follow-up continuing for an additional 60 months.  
Subjects will have required follow-up evaluations at pre-discharge, 30 days, 3 months, 6 months, 
1 year, and then annually through 5 years post index procedure (see Table 2 for visit windows).  
When all registered subjects have been followed for 5 years, or have exited the study, the study 
will be closed. 
5 
SUBJECT SELECTION AND WITHDRAWAL   
5.1 
Subject Screening and Informed Consent 
All subjects must be screened by the site’s investigator and clinical research staff, who have been 
trained to the CIP, to determine if the potential subject is eligible for study registration.  Potential 
subjects will be assigned a unique subject identifier through the electronic Case Report Form 
(eCRF) database.     
Patients are enrolled (i.e., become “subjects”) after they sign the Informed Consent Form (ICF).  
During the informed consent process, the investigator or designee, who has been trained on the 
CIP, will explain the nature and scope of the study, potential risks and benefits of participation, 
and answer questions from potential subjects.  All subjects (or subjects’ legally authorized 
representatives, if applicable) must sign and date the IRB approved informed consent form prior 
to any clinical study-specific procedures.  No subjects belonging to a vulnerable population (see 
Appendix II:  Definitions) will be enrolled.  
Obtaining the consent, and provision of a copy of the consent to the subject, along with date and 
time must be documented in the subject’s medical records.  The informed consent form must be 
signed by the investigator (or designee).  In addition, the signed informed consent must be kept in 
the subjects medical records.  The investigator, or designee, is responsible for advising the subject 
of any new information about the investigation or the Tendyne device that may become known 
during the study.   
If a specific test required to determine a subject’s eligibility is not standard of care, the test must 
be performed after written informed consent has been obtained.  If any of the required screening 
assessments are conducted as part of standard of care prior to obtaining written informed consent, 
it is acceptable to provide the results of these previously performed tests for purposes of screening 
after the subject (or subject’s legally authorized representative) has provided informed consent.  
An authorization for use and disclosure of the subject’s protected health information, in accordance 
with the Health Insurance Portability and Accountability Act (HIPAA), must be obtained from the 
subject or the subject’s legally authorized representative. 
For live cases at congresses, subjects need to sign a specific Live Case ICF, approved by the IRB 
and by Tendyne Holdings, Inc., as well as by the regulatory authorities (e.g. FDA), as applicable.  
The investigator must request Tendyne Holdings, Inc. approval prior to performing a Live Case. 

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5.1.1 Enrollment of Medicare Beneficiaries 
This clinical investigation will enroll appropriate Medicare beneficiaries that qualify based on the 
inclusion and exclusion criteria set forth in the study. The investigational device exemption (IDE) 
clinical trial adheres to all standards of Medicare coverage requirements set forth by CMS’s IDE 
and clinical trial coverage policies. The Risk Analysis section of this CIP (see Section 16) 
describes how all enrolled subjects, including Medicare beneficiaries, may be affected by the 
device under investigation. 
Subjects enrolled in the clinical investigation are expected to be consistent with the Medicare 
population based on demographic characteristics and cardiovascular risk factors, therefore, the 
clinical investigation results are expected to be generalizable to the Medicare population. 
5.2 
Eligibility Criteria 
5.2.1 General Eligibility Criteria 
Assessment for general eligibility criteria is based on medical records at the site and interview with 
a potential subject.  Clinical and laboratory tests used to assess eligibility shall be per site standard.  
If a specific test required to determine subject’s eligibility is not included in a site’s standard tests, 
the test must be performed after written informed consent has been obtained from the subject (or 
the subject’s legally authorized representative, if applicable).  
If any of the required screening assessments are conducted as part of standard of care prior to 
obtaining written informed consent, it is acceptable to provide the results of these previously 
performed tests for purposes of screening after the subject (or subject’s legally authorized 
representative) has consented to participate in the study.  Subjects must meet all of the inclusion 
criteria to be considered for the clinical study.  If any of the exclusion criteria are met, the subject 
is excluded from the clinical study and cannot be registered. 
5.2.2 Inclusion Criteria 
Patients must meet all of the following inclusion criteria to participate in the study: 
1. Heart Team determines subject is not a suitable candidate for conventional surgical 
treatment due to degree of MAC present and the subject will likely benefit from 
transcatheter valve implantation 
2. Symptomatic, severe mitral regurgitation, as defined in the 2017 ACC expert Consensus 
Decision Pathway on the Management of MR (see Figure 1 in the Appendix II) 
3. NYHA Functional Classification ≥ II (if Class IV, patient must be ambulatory) 
4. Age 18 years or older at time of consent  
5. Not a member of a vulnerable population per the investigator’s judgment 
6. The subject or the subject’s legal representative has been informed of the nature of the 
study and agrees to its provisions, including complying with study required testing and 
follow-up visits, and has provided written informed consent 

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5.2.3 Exclusion Criteria 
Subjects must not meet any of the following exclusion criteria to participate in the study: 
1. Presence of Left Ventricle or Left Atrium thrombus 
2. Chest condition that prevents transapical access 
3. Left Ventricular Ejection Fraction (LVEF) less than 25% assessed by echocardiogram 
4. Left Ventricular End Diastolic Dimension (LVEDD) > 7.0 cm  
5. Severe mitral stenosis not amenable to balloon valvuloplasty or transcatheter therapy 
6. Prior intervention with permanently implanted mitral device (e.g. MitraClip) 
7. Mitral pathoanatomy and Left Ventricular Outflow tract (LVOT) anatomy deemed not 
suitable for Tendyne mitral valve implantation 
8. Any planned cardiac surgery or intervention that is 30 days prior and 30 days post that is 
not concomitant with the Tendyne procedure 
9. Cardiac resynchronization therapy (CRT) device or implantable pulse generator (IPG) 
implanted within three months of planned implant procedure  
10. Myocardial Infarction (MI) within 30 days of the planned implant procedure 
11. Symptomatic, or ischemia-associated coronary artery disease (e.g., active ischemia) 
amenable to revascularization and thus requiring stenting or CABG 
12. Cerebrovascular accident (CVA) within six months of planned implant procedure 
13. Unresolved severe symptomatic carotid stenosis (> 70% by ultrasound) 
14. Cardiogenic shock or hemodynamic instability requiring inotropes or mechanical support 
devices within 1 month prior to planned implant procedure 
15. Severe tricuspid regurgitation or severe right ventricular dysfunction 
16. Hypertrophic or restrictive cardiomyopathy, constrictive pericarditis or any other structural 
heart disease causing heart failure other than dilated cardiomyopathy of either ischemic or 
non-ischemic etiology 
17. Any of the following:  leukopenia, acute anemia, thrombocytopenia, history of bleeding 
diathesis, or coagulopathy if cannot be adequately treated 
18. History of endocarditis within 6 months of planned implant procedure 
19. Active systemic infection requiring antibiotic therapy 
20. Known hypersensitivity or contraindication to procedural or post-procedural medications 
(e.g., contrast solution, anti-coagulation therapy) which cannot be adequately managed 
medically 
21. Subject unable or unwilling to take anticoagulation with warfarin for a minimum of 6 
months following Tendyne valve implantation  
22. Known hypersensitivity to nickel or titanium 

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23. Subject is undergoing hemodialysis due to chronic renal failure ( > Stage 4 CKD) 
24. Subject has pulmonary arterial hypertension (fixed PAS >70mmHg) 
a. Note: If PAS > 70mmHg, site must provide documentation PAS is not fixed in 
order to be eligible 
25. FEV1 < 50% of predicted or < 1L 
26. Subject refuses blood transfusions 
27. Subject has COPD requiring continuous home oxygen therapy or chronic outpatient oral 
steroid use 
28. Pregnant, lactating, or planning pregnancy within next 12 months 
a. Note:  Female subjects of childbearing age should be instructed to use safe 
contraception (e.g. intrauterine devices, hormonal contraceptives: contraceptive 
pills, implants, transdermal patches hormonal vaginal devices, injections with 
prolonged release). 
29. Currently participating in an investigational drug or another device trial that has not 
reached its primary endpoint  
a. Note: Trials requiring extended follow-up for products that were investigational, 
but have since become commercially available, are not considered investigational 
trials. 
30. Subjects with non-cardiac co-morbidities that are likely to result in a life expectancy of less 
than 12 months  
5.3 
Subject Discontinuation 
Each registered subject shall remain in the study until completion of the required follow-up period, 
however, a subject’s participation in any clinical study is voluntary and the subject has the right to 
withdraw at any time without penalty or loss of benefit. Conceivable reasons for discontinuation 
may include, but not be limited to, the following: 
 Subject death 
 Subject voluntary withdrawal  
 Subject lost-to-follow-up as described below  
 Subject’s follow-up is terminated according to Section  5.4 - Early Termination of the 
Clinical  
The Sponsor must be notified of the reason(s) for subject discontinuation. The site will provide 
this information to the Sponsor.  Investigators must also report this to their respective IRB as 
defined by their institution’s procedure(s).  
No additional follow–up will be required or data recorded from subjects once withdrawn from the 
study, except for the status (deceased/alive), which will be obtained from the Social Security Death 
Index. 
However, if a subject withdraws from the study due to problems related to the safety or 
performance of the investigational device, the investigator shall ask for the subject's permission to 
follow his/her status/condition outside of the clinical investigation. 

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5.3.1 Subject Lost-to-Follow-up 
If a subject misses two consecutive required follow up visits and attempts to contact the subject as 
detailed below are unsuccessful, then the subject is considered lost to follow-up. Site personnel 
shall make all reasonable efforts to locate and communicate with the subject (and document these 
efforts in the source documents), including the following: 
 A minimum of two (2) telephone calls, or e-mails, on different days over the specified 
follow-up window to contact the subject should be recorded in the source documentation, 
including date, time and initials of site personnel trying to make contact. 
 If these attempts are unsuccessful, a certified letter should be sent to the subject. 
 If a subject misses one or more non-consecutive follow-up visits it will be considered a 
missed visit. The subject may then return for subsequent visits. If the subject misses two 
consecutive time points and the above-mentioned attempts at communicating with the 
subject are unsuccessful, the subject will be considered lost-to-follow-up.  
Note: Contact with a general practitioner, non-study cardiologist or relative without presence of 
subject, or indirect documentation obtained via discharge letters will not be considered subject 
contact. 
5.4 
Early Termination of the Clinical Study 
No formal statistical rule for early termination of the study for insufficient effectiveness of the 
investigational device is defined.  
The Sponsor reserves the right to discontinue the clinical study/investigation at any stage or reduce 
the follow up period with suitable written notice to the investigator.  Possible reason(s) may include, 
but are not limited to: 
 Unanticipated adverse device effect (UADE) occurs and it presents an unreasonable risk 
to the participating subjects 
 Recommendation from the Data Safety Monitoring Board (DSMB) and Steering 
Committee decision to terminate the study  
 Further product development is cancelled 
 Decision by a regulatory body   
Should the clinical study be discontinued by the Sponsor, subjects will be followed per routine 
hospital practice, with device-related AEs being reported to the Sponsor.  The investigator shall 
return all clinical study/investigational materials (including devices) to the Sponsor, and provide 
written notification to the overseeing IRB (if applicable) regarding reasons for premature 
termination.  All applicable Clinical Investigation documents shall be subject to the same retention 
policy as detailed in Section 13 – Data Handling and Record Keeping.  
5.5 
Study Completion 
The study will be completed when all registered subjects have either completed a 5 year follow-
up visit, have reached a clinical outcome or have withdrawn from the study.  Upon study 
completion, the Sponsor and/or its designees will notify the sites and perform study closeout visits.  

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All unused devices and any unused study materials and equipment will be collected and returned 
to the Sponsor and/or its designees.  The Sponsor and/or its designees will ensure that the 
investigator’s regulatory files are up to date and complete, that database queries are resolved, and 
that any outstanding issues from previous monitoring visits have been resolved.   
Other items that will be reviewed during the study closeout visit may include: discussing record 
retention requirements, device accountability, the possibility of site audits, publication policy, and 
notifying the IRB of study closure. 
6 
SUBJECT SCREENING 
6.1 
Screening and Baseline Assessments 
Once a patient has signed the IRB approved informed consent form, screening of a subject for 
possible inclusion in the study may commence. The subject’s general medical eligibility must be 
assessed via interview and medical record review prior to subject registration, all screening and 
baseline assessments shall be within the windows stipulated in Table 2.  Standard of care tests that 
are performed prior to obtaining informed consent can be used to determine eligibility if those tests 
meet the requirements of this study and are within the screening window.  
The following screening/baseline imaging and assessments are to be completed prior to 
registration:  
Images must be captured per the core lab imaging protocols for TEE, TTE, and Cardiac CT.  If 
any imaging is not standard of care, the subject (or subject’s legally authorized representative) 
must provide informed consent prior to obtaining any study imaging. 
 TEE and TTE images to be obtained and submitted to the Sponsor within 60 days prior 
to registration.  The Echocardiography Core Laboratory will review the images and 
confirm the subject’s MR etiology, MR severity, and LVEF.  
 Cardiac CT images to be obtained and submitted to Sponsor within 120 days prior to 
registration.  Both the CT core laboratory and the Sponsor will review the cardiac CT 
images and assess annular calcification, assess subject’s anatomical suitability relevant to 
valve sizing, and to perform procedural planning. 
 Subject’s coronary artery disease status should be assessed via a routine diagnostic 
coronary angiogram, if clinically indicated.  Any revascularization treatment should be 
administered prior to subject registration as outlined in the subject eligibility criteria in 
Section 5.2. 
 
Screening/Baseline Assessments within 90 Days Prior to Registration 
 Medical history must be obtained, including review of subject’s medical records.  This 
review will include history of co-morbidities and co-existing medical conditions; previous 
cardiovascular and peripheral vascular interventions; symptoms and diagnosis of mitral 
insufficiency. 
 A physical exam including an assessment of subject’s cardiac status and sitting vital signs. 

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 Blood tests performed, including: BNP or NT-proBNP, plasma free hemoglobin, serum 
creatinine, International Normalized Ratio (INR), Creatine kinase-MB (CK-MB) and 
Troponin (Type I or T) 
 A 12-lead electrocardiogram (ECG) 
 Concomitant cardiovascular medications must be documented and may include the 
following: anticoagulants, antiplatelet agents, ACE inhibitors, angiotensin II receptor 
blockers or inhibitors, angiotensin receptor-neprilysin inhibitor, If channel inhibitor, beta 
blockers, calcium channel blockers, diuretics, digitalis preparations, and any medication 
that may increase the risk of bleeding 
 Modified Rankin Scale must be assessed 
 NYHA Functional Classification must be assessed 
 Canadian Cardiovascular Society (CCS) grading of angina pectoris must be assessed 
 KCCQ questionnaire must be completed by the subject;  
o Note: To minimize bias and undue influence, the QoL questionnaire will be 
completed by the subject, unless the subject is unable to complete the questionnaire 
on their own (in such cases a note to file must be completed to document the 
inability of subject to complete the questionnaire on their own). 
 Administer the 6MWT 
 Subject is evaluated by the local site heart team to confirm they have been adequately 
treated per applicable standards, including for coronary artery disease (e.g., 
revascularization), left ventricular dysfunction (e.g., cardiac resynchronization therapy) 
 Surgical risk assessment - the local site heart team shall review subject’s medical 
information to determine if subject is not a suitable candidate for conventional surgical 
treatment due to degree of MAC present and will likely benefit from transcatheter valve 
implantation  
6.2 
Notification by Sponsor of Subject Screening Pass or Fail  
Prior to subject being scheduled for the procedure, the Sponsor will review submitted screening 
and baseline medical information, TTE, TEE, and CT images to confirm anatomic and procedural 
suitability of the subject for the Tendyne device. Sponsor will notify Investigator when subject 
passes or fails the screening review.  
7 
TREATMENT AND PRE-DISCHARGE VISITS  
Subjects that pass the screening review will undergo a procedure to implant the Tendyne device.  
7.1 
Concomitant Procedures 
Pre-procedural planning and assessment of MAC may determine that concomitant mitral annulus 
valvuloplasty is required to ensure mobility of calcification prior to Tendyne valve implantation. 
In such cases, standard institutional techniques may be used.  

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7.2 
Tendyne Procedure 
The valve should be implanted with sterile techniques using primarily TEE guidance.  In addition, 
TTE and fluoroscopic imaging modalities may be used. 
Implantation of the valve will be performed by the local site heart team, with an experienced 
cardiac surgeon trained to perform transapical procedures and jointly with an experienced 
interventional cardiologist and echocardiographer.  Sponsor personnel will be available for 
procedural support for all Tendyne cases.  For a comprehensive description of the Tendyne 
procedure, refer to the Tendyne Mitral Valve System IFU. 
Note:  Prior to performing the procedure, all investigators must undergo training by the 
Sponsor on the Tendyne System and on the CIP.  In addition, all investigators must 
read and understand the IFU that accompanies the device. 
Subjects will be prepared for the procedure as per the institution’s standard practice for a 
transapical therapeutic intervention and TEE. 
The subject must be on anticoagulant/antiplatelet therapy appropriate for transapical therapeutic 
interventions.  Activated clotting time (ACT) is to be maintained at >300 seconds for the duration 
of the procedure. 
7.2.1 Tendyne Procedure - Access 
An 8 Fr. sheath is placed in the apex at the orthogonal access location determined by CT.  A 7 Fr. 
Fogarty catheter is then inserted, leading with the balloon until the mitral annulus is crossed.  A 
0.035 standard J wire is then advanced into either a pulmonary vein or coiled in the atrium.   
Once the J wire is in place, the Fogarty catheter is used to determine a chord-free path has been 
achieved by retracting/advancing over the wire.  Once an entanglement free pathway has been 
achieved, the Fogarty balloon is deflated and removed.  The 8 Fr. sheath is also removed and the 
Tendyne sheath is inserted. 
7.2.2 Tendyne Procedure - Device Delivery 
The delivery system is inserted into the Tendyne sheath and aligned for pre-planned rotation of 
the valve.  Both the sheath side port and the delivery system are de-aired and the flush is open until 
the valve is advanced to the tip of the delivery sheath.   
Clocking is performed in the 3D enface view.  The valve is then incrementally advanced until the 
A2 portion of the Tendyne valve is clocked to the center of the “D” shape of the mitral annulus.  
Using an X-plane echo image, the Tendyne valve is seated intra-annularly and the deployment of 
the valve is completed.   
When the valve is fully deployed, a full echo assessment is made to evaluate PVL, LVOT 
obstruction and MR resolution.  At this point, the valve can be recaptured and can be adjusted if 
needed.  When valve position has been optimized, the delivery system is removed. 
7.2.3 Tendyne Procedure - Tensioning 
Tension is adjusted using the apical pad tool to attain proper seating of the valve for mechanical 
stability and optimal paravalvular sealing. Once stability is achieved and valve function is 
determined to be acceptable, the instrument is removed and the apical pad is fastened to the tether. 

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Note:  The valve can be retrieved at any point during delivery and tensioning up to the point 
when the tether is cut just prior to surgical site closure. 
7.2.4 Tendyne Implant Identification Card 
At discharge, each subject implanted with a Tendyne device must be provided with an Implant 
Identification Card.  An Implant Identification Card is included in the package with each Tendyne 
Mitral Valve System.  The subject should be instructed to keep this Implant Identification Card on 
their person at all times.  The serial number of the implanted Tendyne device should be recorded 
on the Implant Identification Card. 
7.3 
Procedural Data Requirements 
The following procedural information should be recorded on the appropriate eCRF(s) after implant 
or attempted implant of the Tendyne device. 
7.3.1 12-Lead ECG 
A 12-lead ECG will be performed pre- and post-valve implant.  If prolonged hospitalization occurs 
after the procedure, the ECG may be collected within 10 days after the index procedure. 
7.3.2 Intraoperative Hemodynamic Measurement 
During the procedure to implant the Tendyne device, subjects will undergo right-heart 
catheterization to measure hemodynamics intraoperatively.  Cardiac output (CO), pulmonary 
arterial (PA), aortic and right arterial (RA) pressures will be measured before and after the valve 
placement via the right heart catheter.  LV pressures should be measured via a pigtail catheter.   
7.3.3 Intraoperative Angiography  
Per investigator discretion, subjects may undergo left-heart catheterization with radiographic 
imaging before and after the Tendyne valve placement to assess the LV and mitral valve 
competence.  Care must be taken to minimize the amount of contrast media injected into subjects 
with compromised renal function.  Therefore, left ventriculogram procedures described in this 
protocol are optional. 
Tendyne will provide specific instruction on intraoperative imaging requirements as part of 
investigator training. 
7.3.4 Additional Procedural Data Collection 
In addition to the intraoperative imaging and hemodynamic measurements, the following 
procedural information should be recorded: 
 General procedure information  
 Treatment and Control group implant information 
 Laboratory and clinical tests 
 Antiplatelet/Anticoagulation medications  
 Concomitant cardiovascular medications  
 Fluoroscopy duration 
 Adverse events, if applicable 

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 Protocol deviations, if applicable 
 Device deficiency, if applicable 
7.3.5 Immediate Post-Operative Care 
Blood pressure is to be closely monitored and maintained below 135 mmHg systolic during the 
immediate post-operative period, if possible.  The subject’s ACT should also be monitored in 
accordance with hospital protocols. 
Subjects will receive standard post-cardiac transapical care as judged appropriate by the 
investigator.     
7.3.6 Anticoagulation Regimen 
Subjects receiving the Tendyne device are required to be on anticoagulation therapy, warfarin, 
with a target INR range of 2.5 to 3.5, for a minimum of six months.  A single antiplatelet therapy 
(aspirin or alternate agent) should also be administered immediately after the procedure and may 
be continued indefinitely. 
Notes:  
 During the period of required anticoagulation as stated above, a subject’s anticoagulation 
regimen may be altered or stopped only if medically indicated, however, it should be 
restarted as soon as possible per physician’s discretion.  
 For subjects who receive the Tendyne device, a TTE must be performed between 60 and 
120 days after anticoagulation stoppage.  
o If the TTE indicates increased gradients (e.g. mitral valve gradient > 6mmHg) or 
leaflet mobility concerns are identified, a gated CT (4D with contrast) must be 
performed to evaluate leaflet thrombosis resulting in hypoattenuated leaflet 
thickening or motion.  
 For subjects with renal insufficiency, a TEE must be performed  
  
7.3.7 Pre-Discharge 
Pre-discharge data collection is to be performed within 72 hours prior to discharge from implanting 
hospital.  Pre-discharge data requirements include: 
 A physical exam including an assessment of subject’s cardiac status and sitting vital signs 
 Concomitant cardiovascular medications 
 12-lead ECG  
 Laboratory and clinical tests 
 Adverse events, if applicable 
 Protocol deviations, if applicable 
 Device deficiency, if applicable 

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8 
FOLLOW-UP FOR EVALUATION OF SAFETY AND EFFECTIVENESS  
8.1 
Clinical Follow-up 
Follow-up visits are required at 30 days, 3 months, 6 months, 1 year, and then annually through 5 
years (Table 2); visits will be calculated from the date of the index procedure.  Follow-up 
assessments can be performed at any point in the window, and should be conducted, whenever 
possible, by the same individual who performed the baseline tests.  For a complete schedule of 
study assessments occurring at each visit, refer to Appendix III: STUDY Assessment and 
Follow-up Schedule.   
Subjects should be followed at the investigational site where the subject was registered, and may 
be followed at another investigational site only with prior agreement from both the new site’s 
Principal Investigator and approval from the Sponsor. 
All registered subjects should continue to be monitored and treated per applicable standards of 
care consistent with the subject’s condition.  Subjects should be followed by the site investigators 
at all scheduled follow-up visits and be evaluated for device function.   
Note: If a subject has an unsuccessful Tendyne device implant, they should remain in the study 
and continue to be followed per the study follow-up schedule.   
8.2 
30 Day, 3 Month, 6 Month, and Annual Visits 
Subjects should continue to take baseline medications as clinically (medically) necessary.  
Required tests and procedures outlined below must be completed. All visits and tests must be 
completed within the visit window specified in Table 2, even if the subject is in hospital.   
 A physical exam including an assessment of subject’s cardiac status and sitting vital signs 
 Concomitant cardiovascular medications assessment 
 NYHA Functional Classification assessment 
 Blood tests performed, including: BNP or NT-proBNP, plasma free hemoglobin, serum 
creatinine, INR, CK-MB and Troponin (Type I or T) 
 TTE  
 12-lead ECG 
 Cardiac CT (Note: Required at 30 day visit – an additional CT may be required if 
anticoagulation regime is stopped, refer to Section 7.3.5 - Immediate Post-Operative 
Care) 
 KCCQ questionnaire 
 6-Minute Walk Test 
 Modified Rankin Scale (Assessment to be completed after onset of stroke) 
 Assess and record adverse events  
 Assess and record protocol deviations  
Echocardiography images (TTE) obtained at each follow-up visit should be submitted in a timely 
manner.  Throughout the course of the study, the Echocardiography Core Lab may provide 
feedback to sites regarding quality of images obtained. 

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During the follow-up period, if a subject requires a cardiac procedure (e.g. MV surgery, permanent 
LVAD, heart transplant) which may or may not result in explant of the Tendyne device, the subject 
will remain in the study and continue to be followed. 
Every attempt must be made to ensure study subjects do not miss a scheduled follow-up visit.  If 
a subject is unable to complete a visit, the site may attempt to contact them remotely to document 
their status (e.g., alive) and to administer study questionnaire (KCCQ).  This should only be 
performed in rare instances and the Sponsor should be notified of such instances in advance. 
Subjects who do not complete a required follow-up visit will be documented as having a missed 
visit and a protocol deviation (refer to Section 12.5 - Deviations from Clinical Investigation 
Plan) will be completed.  The investigator will keep a record of documented follow-up attempts 
in the subject’s file. 
Table 2.  Follow-up Schedule and Windows for Study Subjects 
Follow-Up Visit 
Window Start 
Day 
Target Day 
Window Close 
Day 
Follow up 
Method 
Pre-Discharge  
Within 72 hours 
of discharge 
Discharge date 
N/A 
In hospital or 
Site visit
30 Days 
(-3 /+14 days) 
27 
30 
44 
Site visit 
3 Months 
(±30 days) 
60 
90 
120 
Site visit 
6 Months 
(±30 days) 
152 
182 
212 
Site visit 
1 year 
(±30 days) 
335 
365 
395 
Site visit 
2 years 
(±30 days) 
701 
731 
761 
Site visit 
3 years 
(±45 days) 
1051 
1096 
1506 
Site visit 
4 years 
(±45 days) 
1416 
1461 
1506 
Site visit 
5 years 
(±45 days) 
1781 
1826 
1871 
Site visit 
Follow-up visit dates are calculated from the date of the index procedure  
9 
ADVERSE EVENTS  
9.1 
Definitions / Types of Events 
9.1.1 Adverse Event 
An adverse event (AE) is 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. 

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This definition includes events related to the investigational medical device and the procedures 
involved.  For users or other persons, this definition is restricted to events related to the 
investigational medical device. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease temporally associated with the use of a medicinal (investigational) 
product, whether or not related to the medicinal (investigational) product. 
Note:  
Unchanged, chronic conditions are not adverse events and should not be recorded on 
the eCRF Adverse Event form.  Pre-existing conditions that have not worsened are not 
considered AEs.  
9.1.2 Serious Adverse Event 
If the AE meets any of the criteria below, it is regarded as a serious adverse event (SAE).  
a) Death, 
b) Serious deterioration in health that either: 
1) Resulted in a life-threatening illness or injury, or 
2) Resulted in a permanent impairment of a body structure or a body function, or 
3) Required in-patient hospitalization or prolongation of existing hospitalization, or 
4) Resulted in medical or surgical intervention to prevent life threatening illness or Injury 
or permanent impairment to a body structure or a body function 
c) Fetal distress, fetal death or a congenital abnormality or birth defect 
Note 1:  
This includes device deficiencies that might have led to a serious adverse event if a) 
suitable action had not been taken or b) intervention had not been made or c) if 
circumstances had been less fortunate. These are handled under the SAE reporting 
system.  
Note 2:  
A planned hospitalization for pre-existing condition, or a procedure required by the 
CIP, without a serious deterioration in health, is not considered to be a SAE.  Such 
events will not count toward the primary endpoint.  
9.1.3 Anticipated Adverse Events 
Table 3 summarizes the anticipated events that have been identified as possible complications 
from the Tendyne Mitral Valve System.  Please also refer to the list of anticipated events in the 
Tendyne Mitral Valve System IFU. 
 
Table 3.  Anticipated Adverse Events 
Adverse foreign body response 
Foreign body response  
Adverse reaction to anesthesia 
Heart Failure, new or worsening 
Allergic reaction 
Hematoma
Anemia 
Hemolysis
Annular dissection 
Hypotension
Aortic insufficiency 
Infection / Sepsis
Atrial or ventricular injury 
Leaflet, chordal, papillary or ventricular rupture 
(resulting from mitral valvuloplasty, if performed)

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Normal post-operative sequelae or expected post-operative events do not need to be recorded as 
AEs unless they require physician prescribed pharmacologic and/or surgical intervention outside 
of the acute peri-operative period.   A few common examples of normal post-operative sequelae 
or expected post-operative events include access-site pain, bruising, and events related to general 
anesthesia. 
9.1.4 Unanticipated Adverse Device Effect (UADE) 
Unanticipated Adverse Device Effect (UADE) refers to any serious adverse effect on health or 
safety or any life-threatening problem or death caused by, or associated with, the Tendyne System, 
if that effect, problem, or death was not previously identified in nature, severity, or degree of 
incidence in the CIP, 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. 
9.2 
Device Deficiency 
Device deficiency (DD) is defined as an inadequacy of a medical device related to its identity, 
quality, durability, reliability, safety or performance, such as malfunction, misuse or use error and 
inadequate labeling. This includes the failure of the device to meet its performance specifications 
or otherwise perform as intended. 
9.3 
Device / Procedure Relationship 
Determination of whether there is a reasonable possibility that the device, the implant procedure, 
or the patient condition (pre-existing condition) caused or contributed to an AE is to be assessed 
by the investigator and recorded on the appropriate eCRF.  Additionally, the probability of 
relationship to the device or procedure should also be categorized.  This determination should be 
based on assessment of temporal relationships, evidence of alternative etiology and 
Atrial Septal Defect (resulting from mitral 
valvuloplasty, if performed) 
Liver failure 
Bioprosthetic valve dysfunction 
Mitral valve injury
Bleeding complications 
Mitral valve prolapse / stenosis 
Blood loss which may require transfusion
Myocardial infarction
Cardiac arrest 
Obstruction
Cardiac arrhythmia, atrial or ventricular 
Paravalvular leak
Cardiac perforation 
Pain
Conduction defect with or without need for 
pacemaker 
Pericardial effusion / tamponade 
Damage to cardiac tissue and/or structures
Pleural effusion
Death 
Pulmonary embolism
Decreased LV function and/or cardiac output
Pulmonary hypertension
Device embolism 
Renal insufficiency or failure 
Device erosion, migration or malposition
Respiratory difficulty, insufficiency, or failure
Device thrombosis 
Stroke or transient ischemic attack 
Embolism (air, blood clot, tissue, calcium, etc.)
Tear or damage to device
Endocarditis 
Vascular and access-related complications
Esophageal irritation, stricture, or perforation
Worsening of mitral regurgitation  
Fever  

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medical/biologic plausibility.  Definitions for the determination of device- and/or procedure-
relatedness include: 
Not Related:  
Exposure to the device/procedure has not occurred (no temporal relationship), 
or the occurrence of the adverse event is not reasonably related in time, or 
there is a definite alternative etiology, or it is biologically implausible for the 
adverse event to be related to the use of the device.  
Possibly Related:   Exposure to the device/procedure has occurred; and it cannot be ruled out that 
the device/procedure is not responsible for the adverse event. 
Definitely Related: Exposure to the device/procedure has occurred or the adverse event is related 
in time; and the device/procedure is definitely responsible for the adverse 
event. 
9.4 
Adverse Event / Device Deficiency Reporting 
9.4.1 AE Monitoring 
The investigator will monitor the occurrence of adverse events for each subject during the course 
of the study.  Event description, date of onset, severity, duration, and relationship to device and/or 
procedure will be recorded on the appropriate eCRF by the investigator or designee.   
For subjects implanted with the Tendyne device who exhibit signs or symptoms suggestive of 
valve dysfunction, a TTE must be performed. If evidence of valve dysfunction is detected via TTE, 
a CT (or TEE) must be performed. 
For this clinical investigation, all AEs will be collected on each subject from the time of study 
registration through study completion.  A summary of AE reporting requirements is further 
described in this section and summarized in Table 4. 
9.4.2 SAE Reporting to Sponsor and IRB 
SAEs may be reported by the subject, observed by the investigator, or documented in medical 
records and must be reported to the Sponsor on the Adverse Event eCRF.  Additional information 
related to previously reported SAEs should be updated within the eCRF as soon as the information 
has been reviewed and verified by the investigator. 
The investigator should report all SAEs to the Sponsor as soon as possible but no later than 3 
calendar days from the day the study personnel became aware of the event or as per the 
investigational site’s local requirements, if the requirement is more stringent than those outlined.   
The investigator will further report the SAE to the local IRB according to the institution’s IRB 
reporting requirements.    
9.4.3 UADE Reporting to Sponsor and IRB 
Tendyne Holdings, Inc., requires the investigator to report any UADE to the sponsor within 3 
calendar days of the investigator’s knowledge of the event, unless local requirements are more 
stringent, and to the IRB per requirements.   
The Sponsor is required to report the findings of the investigation of any UADE to the FDA and 
the IRB as soon as possible, but in no event later than 10 working days after knowledge of the 
event. 

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9.4.4 Device Deficiency  
The investigator should report all device deficiencies related to the Tendyne device to the Sponsor 
as soon as possible but no later than three (3) calendar days from the day the study personnel 
becomes aware of the event or as per the investigative site’s local requirements if the requirement 
is more stringent than those outlined. Device deficiencies should be reported to the IRB per the 
investigative site’s local requirements. 
The device, if not successfully implanted in the subject, should be returned to Tendyne Holdings, 
Inc. 
9.4.5 Investigational Site AE Reporting Requirements to Sponsor 
Investigators are responsible for preparation and submission to the Sponsor of all reportable AEs 
and DDs identified in the CIP.  Adverse event reporting requirements are included in Table 4.  All 
reports are subject to inspection and to the retention requirements described in Section 13.4.1 
Investigator Records. 
 
Table 4.  Investigational Site AE Reporting Requirements to Sponsor 
Event 
Investigational 
Site 
Reporting timelines 
AE 
All Sites 
AEs (not including normal or expected post-operative 
sequelae) must be reported as soon as possible after study 
personnel becoming aware of the event or as per the 
investigative site’s local requirements, if the requirement is 
more stringent than those outlined.
SAE 
All Sites 
SAEs must be reported no later than 3 calendar days from the 
day the study personnel became aware of the event or as per 
the investigative site’s local requirements, if the requirement 
is more stringent than those outlined.
UADE 
All Sites 
UADEs must be reported no later than 3 calendar days from 
the day the study personnel became aware of the event or as 
per the investigative site’s local requirements, if the 
requirement is more stringent than those outlined. 
Device 
Deficiency  
All Sites 
DDs must be reported no later than 3 calendar days from the 
day the study personnel became aware of the event or as per 
the investigative site’s local requirements, if the requirement 
is more stringent than those outlined.
9.4.6 UADE Reporting to FDA by the Sponsor  
The Sponsor will report UADEs to the FDA per IDE regulations (21 CRF 812.150(b)(1)).  
9.5 
Adjudication of AEs 
All SAEs and device or procedure related AEs reported during the study will be reviewed and 
adjudicated by the CEC.  Once adjudicated, final reporting of adverse events will be based upon 

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CEC adjudication.  Refer to section 12.11.3  Clinical Events Committee for the CEC’s role and 
responsibility.  
10 STATISTICAL METHODS 
10.1 Sample Size Considerations 
This is a feasibility study and no formal statistical hypotheses are to be tested for any of the study 
endpoints. Data collected from this study will provide preliminary device safety and effectiveness 
data for the use of the Tendyne Mitral Valve System in subjects with mitral regurgitation and 
mitral annular calcification.  Descriptive statistics will be reported for the study data primarily.  
Inferential statistical analysis will be conducted in an exploratory manner. The sample size for this 
study is planned to be up to 30 at up to 10 investigational sites.   
 
Statistical methods for the study are outlined below. Additional details will be provided in a 
Statistical Analysis Plan (SAP). 
10.2 Data Analysis Plan 
10.2.1 General Principles  
All statistical analyses will be performed using Statistical Analysis System (SAS) for Windows 
(version 9.4, SAS Institute Inc. Cary, NC) or other widely accepted statistical or graphical 
software.   
Descriptive statistics will be used to present the data and to summarize the results.  Discrete 
variables will be presented using frequency distributions and cross tabulations.  Continuous 
variables will be summarized by presenting the number of observations (N), mean, standard 
deviation, median, minimum, and maximum values.    
In general, data for all study subjects combined will be presented.  The primary analysis for all 
baseline characteristics and study outcomes will include all available data for all enrolled subjects.  
Individual data will be presented in subject listings. 
Summaries of the following endpoints present the number and percentage of unique subjects with 
an event, unless specified otherwise: protocol deviations; subject status; study medications; 
adverse events.   Thus, multiple occurrences of the same event are counted only once per subject, 
unless specified otherwise. 
10.2.2 Subject Disposition  
The number and percentage of subjects screened, screen failure, enrolled, treated, and completed 
will be summarized. Screen failure percentage is calculated from number of screened subjects and 
other percentages are calculated among number of enrolled subjects. A subject will be considered 
enrolled once they have signed the study patient informed consent form.  Subjects who discontinue 
from the study will be summarized with reason and listed by their primary reason for 
discontinuation.    
 

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10.2.3 Study Conduct  
Protocol deviations from the investigation plan will be summarized by deviation type as well as 
total.  Protocol deviations by investigational site will also be provided. 
 
10.2.4 Analysis Samples  
The primary analysis sample will be based on the principle of intention-to-treat (ITT).  All 
statistical analyses in this study will be “intent to treat” with enrolled subjects with attempted 
device implant included in the analysis.  As-treated analysis will also be conducted, which includes 
subjects with study device remain implanted. 
 
10.2.5 Analysis of Population Demographics, Baseline and Procedural Characteristics  
Descriptive statistics will be summarized for baseline demographics, medical history, baseline 
disease characteristics, echocardiography core laboratory data, and procedural characteristics. 
10.2.6 Analysis of Primary Safety Endpoint        
For the composite primary safety endpoint, the proportion of subjects with device success and free 
from device- and/or procedure-related SAEs (per CEC adjudication) at 30 days, along with exact 
95% confidence interval (CI), will be summarized.  The summaries for each individual safety data 
point will also be provided. 
10.2.7    Analysis of Clinical Endpoints 
Definition of clinical endpoints are described in Section 3.2. 
For composite endpoints, i.e., technical success, patient success, and device success, the number 
and percentage of subjects with success will be summarized.  Descriptive statistics for components 
of each endpoint will also be provided. 
For continuous variables (e.g., KCCQ scores and 6MWT distances), results will be summarized 
with the numbers of observations, means, standard deviations, minimums, maximums, and 95% 
confidence intervals.  Change from baseline will be included using these same descriptive 
statistics.    
For categorical variables such as mortality and NYHA classification, results will be summarized 
with subject counts and percentages/rates, and with 95% confidence intervals.    
10.2.8 Subgroup Analysis 
Sub-group analyses on performance, effectiveness, and safety endpoints are planned.  These 
analyses are exploratory in nature and may include certain baseline demographics, disease 
characteristics, echocardiography parameters, and procedural characteristics selected by 
investigators and sponsor aimed at a comprehensive understanding of device performance and 
safety profile. 
10.2.9 Handling of Missing Data 
Primary analyses will consist of all available data evaluated under ITT principles, referred to in 
International Conference on Harmonization module E9 (Statistical Principles for Clinical Trials) 

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as the full analysis set.  Consequently, data will only be absent from analyses of study outcomes 
in the event that they were not available for collection. 
In general, missing values in any of the endpoints will not be inputted when summarizing these 
endpoints using descriptive statistics. 
11 DIRECT ACCESS TO SOURCE DATA / DOCUMENTS 
The investigator/institution will permit and assure direct access to source data/documents (e.g., 
hospital/clinic/office charts, catheterization reports, laboratory results) in order for clinical 
investigation-related monitoring, audits, IRB review and regulatory inspections to be performed. 
Subjects providing informed consent are agreeing to allow Sponsor and/or its designee access and 
copying rights to pertinent information in their medical records concerning their participation in 
this feasibility study.  
The investigator will obtain, as part of the informed consent, permission for Sponsor monitors and 
designees, including auditors, or regulatory authorities to review, in confidence, any records 
identifying the subjects in this study. This information may be shared with regulatory agencies; 
however, per relevant confidentiality and privacy rules (HIPAA), the Sponsor and its designees 
will not otherwise release the subject's personal, private and protected health information. 
12 QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure the study is conducted in accordance with the CIP and that both the Sponsor and 
investigational sites are in compliance, proper quality control and assurance procedures will be 
followed in this study. These controls include the establishment of training, monitoring, support 
of quality audits and study committees. 
12.1 Selection of Clinical Sites and Investigators 
The Sponsor will select investigational sites after review of a site assessment and the qualifications 
of the proposed investigators at the site.  Each site will be required to have a Principal Investigator 
(either an interventional cardiologist or cardiothoracic surgeon) and a multidisciplinary team.  The 
multidisciplinary team will consist of a minimum of the following: 
 One (1) Interventional Cardiologist 
 One (1) Cardiothoracic Surgeon 
 One (1) Echocardiographer 
Investigators must be qualified by education, training, and experience to assume responsibility for 
the proper conduct of human subject research.  Investigators must use best practice guidelines to 
guide the management of subjects.    Investigators must provide evidence of such qualifications 
through current CVs and other relevant documentation requested by the Sponsor, IRB, and 
regulatory agencies. 
Investigators at the site are responsible for being familiar with the use of proposed investigational 
procedures, techniques and products, as described in current literature, product information, and 
other available sources.  As part of their qualification to conduct the study, investigators are 
responsible for ensuring that investigational site resources are available and that the appropriate 
population of subjects can be identified/treated.   

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12.2 Clinical Investigation Plan Amendments  
Approved CIP amendments will be provided to the investigators by the Sponsor prior to 
implementation. The Principal Investigator is responsible for notifying the IRB of the amendment 
(administrative changes) or obtaining IRB’s approval of the amendment (changes in subject care 
or safety), according to the instructions provided by the Sponsor.   
Acknowledgement/approval by the IRB of the CIP amendment must be documented in writing 
prior to implementation.  Copies of this documentation must also be provided to the Sponsor. 
12.3 Study Training 
12.3.1 Site Training 
Investigators and site clinical study personnel are required to attend Sponsor training sessions, 
which may be conducted at an investigator's meeting, a Site Initiation Visit (SIV) or other 
appropriate training sessions. Over-the-phone or self-training may take place as required.  Training 
of investigators or site clinical study personnel will include, but is not limited to, the CIP 
requirements, investigational device usage, eCRF completion and study personnel responsibilities.  
All investigators and site clinical study personnel that are trained must sign a training log (or an 
equivalent) upon completion of the training.  Investigator/study personnel must not perform any 
study-related activities that are not considered standard of care at the site prior to signing the 
training log.  
12.3.2 Training of Sponsor’s Designees or Vendors 
All Sponsor partners and/or designated vendors (e.g., Echocardiography Core Laboratory) 
responsible for any function in the conduct of the clinical study will be trained to the CIP and other 
study documents (as appropriate). 
12.3.3 Training of Sponsor’s Monitors 
Sponsor and/or designated monitors will be trained to the CIP, eCRFs and investigational device 
usage (as appropriate).  Documentation of this training will be according to written procedures. 
12.4 Monitoring 
The Sponsor and/or designee will monitor the study over its duration according to the monitoring 
plan and relevant standard operating procedures.  
12.4.1 Designated Monitors 
Study monitors are individuals who are designated to oversee the progress of a study.  These 
individuals are appropriately trained and qualified to monitor the progress of a clinical study.  
The study Sponsor may designate additional monitors at any time during the study.  To request 
information on the person(s) responsible for monitoring activities, contact the Sponsor at the 
following address: 
Abbott Global Clinical Operations  
5050 Nathan Lane North 
Plymouth, MN 55442 USA 

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12.4.2 Monitoring Visits 
Scheduled visits to an investigational site may occur at the following times: prior to the start of the 
clinical study (pre-site qualification visit), at initiation of the study (at first implant or shortly 
thereafter), interim visits throughout the clinical study as required, and upon completion of the 
clinical study as outlined in the study monitoring plan. 
12.5 Deviations from Clinical Investigation Plan 
The investigator will not deviate from the CIP for any reason without prior written approval from 
Sponsor except in cases of medical emergencies, when the deviation is necessary to protect the 
rights, safety and well-being of the subject or eliminate an apparent immediate hazard to the subject.  
In that event, the Investigator will notify Sponsor immediately by phone or in writing.  All 
deviations must be reported to the Sponsor.  For subject-specific deviations from the CIP, a 
deviation eCRF will be completed.  The occurrence of CIP deviations will be monitored by the 
Sponsor for evaluation of investigator compliance to the CIP and regulatory requirements and dealt 
with according to written procedures. Investigators will inform their IRB of deviations in 
accordance with their specific reporting policies and procedures.  
In the event of repeated non-compliance, the Sponsor, or designee, will attempt to secure 
compliance by one or more of the following (and not limited to):  
 Visiting the investigator and/or delegate 
 Telephoning the investigator and/or delegate 
 Corresponding with the investigator and/or delegate 
Repeated non-compliance with the signed agreement, the CIP or any other conditions of the study 
may result in further escalation in accordance with the Sponsor’s written procedures including 
securing compliance or, at its sole discretion; Sponsor may terminate the investigator's 
participation in the study.  
12.5.1 Deviations with Expedited Reporting Requirements  
For the following types of protocol deviations (per 21 CRF 812.150), an investigator is required 
to notify the Sponsor and the IRB within five (5) business days of the deviation. 
 Emergency deviation from the CIP (a deviation to protect the life or physical well-being 
of a subject in an emergency). 
 Failure to obtain informed consent.  
Notification to the Sponsor and/or the IRB should be documented and maintained in the clinical 
trial file at the site and at Tendyne Holdings, Inc.  
12.5.2 Non-Critical Deviations  
Protocol deviations which do not have the urgency associated with expedited notification or prior 
Tendyne/IRB approval (as discussed in the above paragraphs) will be reported upon discovery, 
such as during completion of eCRFs or during a monitoring visit. 

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12.6 Review of Study Imaging Assessments 
MR severity, MR etiology, localization of MAC, left ventricular dimensions, along with other 
measures, will be assessed by Echocardiography and Cardiac CT Core Labs at baseline and during 
follow-up.  
12.7 Safety and Effectiveness Monitoring 
All AEs will be reviewed by Tendyne Holdings, Inc., (and/or designee).  SAEs and all device or 
procedure related AEs will be adjudicated by an independent CEC.   
12.8 Follow-up Compliance 
The Sponsor will work with investigational sites to maintain high follow-up compliance. The 
following strategies may be used for increasing compliance: 
 During site initiation and training, the Sponsor will emphasize the importance of subject 
follow-up to the site, and that the site should communicate this importance to each subject. 
 Sites will be informed to promptly reschedule any missed subject visits, and to reinforce 
the necessity of a follow-up visit. 
 If a scheduled visit is missed due to subject illness, transportation issues, or travel, the site 
will be advised to: 
o Reinforce the necessity of follow-up visits; 
o Identify alternate transportation sources, and involve the Sponsor if necessary 
 Sites will be instructed to ask subjects who withdraw during the study to provide the reason 
for withdrawal and ask them if the investigator may contact them at the end of the study 
follow-up.   
 Subject follow-up rates will be monitored closely so that problems may be identified and 
addressed as soon as possible.   
 For subjects who are lost-to-follow-up, sites may be requested to examine the Social 
Security Death Index to determine subject status (only the status will be sent to Sponsor, 
not any subject identifying information). 
12.9 Quality Assurance Audit 
 
The Sponsor may conduct periodic Quality Assurance audits (on-site audits) at various 
investigational sites.  A sponsor representative, or designee, may request access to all study 
records, including source documentation, for inspection and duplication during a Quality 
Assurance audit.  The investigator and research coordinator must be available to respond to 
reasonable requests and queries made during the audit process.  
12.10 Sponsor Support for Regulatory Body Inspection 
In the event that an investigator is contacted by a Regulatory Agency regarding this feasibility 
study, the Investigator will notify the Sponsor immediately.  The investigator and research 
coordinator must be available to respond to reasonable requests and inspection queries made 
during the inspection process.  The investigator must provide the Sponsor with copies of all 
correspondence that may affect the review of the current study (e.g., Form FDA 483, Inspectional 

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Observations, and warning letters).  As necessary, the Sponsor may provide any assistance in 
preparing and/or responding to regulatory inspections. 
12.11 Committees 
12.11.1 Publications Committee 
 
The Publication Committee will oversee and guide the ongoing scientific presentation and 
publication activities for the MAC feasibility study.  The Publication Committee will determine 
policies and strategies regarding presentations and/or publications arising from study generated 
data.  The committee will also review and approve all external requests for accessing study-related 
data and strategies for presentation and publication. The composition, guiding policies, and 
operating procedures governing the Publication Committee are described in detail in a separate 
Publication Committee Charter. 
12.11.2 Data and Safety Monitoring Board (DSMB) 
The DSMB is an independent multidisciplinary group that is restricted to individuals free of 
apparent significant conflicts of interest. The source of these conflicts may be financial, scientific, 
or regulatory in nature.  The composition of the DSMB, guiding policies, and operating procedures 
are described in detail in a separate DSMB Charter.   
12.11.3 Clinical Events Committee (CEC) 
The CEC is an independent adjudication body comprised of a multi-disciplinary team of qualified 
physicians who are not investigators in the study.  The CEC will be responsible for adjudicating 
serious adverse events and device or procedure related adverse events reported in the study.  The 
composition, guiding policies, and operating procedures are defined in a separate CEC Charter. 
13 DATA HANDLING AND RECORD KEEPING 
 
Clinical data will be collected pre-registration during the screening period to establish subject 
eligibility at baseline, during the pre- and post- procedural hospital stay, and during the follow-up 
period for all subjects. 
All eCRF data collection will be performed through a secure web portal and all authorized 
personnel with access to the electronic data capture (EDC) system must use an electronic signature 
access method to enter, review or correct data. Electronic signature procedures shall comply with 
the CFR Title 21 Part 11 and the ICH Guidelines for Good Clinical Practice.  Passwords and 
electronic signatures will be strictly confidential.    
All eCRF data will be downloaded from the EDC system and reformatted for analysis into a data 
structure acceptable to Tendyne. The data will be subject to consistency and validation checks 
within the EDC system and to supplemental validation following download.  
At the conclusion of the study, completed eCRF images with the date-and-time stamped electronic 
audit trail indicating the user, the data entered, and any reason for change (if applicable) will be 
archived for each investigational site and a backup copy archived with Tendyne.  
For the study duration, the investigator will maintain complete and accurate documentation 
including, but not limited to, medical records, clinical trial progress records, laboratory reports, 
eCRFs, signed ICFs, device accountability records, correspondence with the IRB and study 

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monitor/Sponsor, AE reports, and information regarding subject discontinuation or completion of 
the study. 
13.1 Data Management 
The Sponsor’s data management group (or designee) will perform all data management activities, 
including data review, database cleaning, and issuing and resolving data queries, and 
documentation of the systems and procedures to be used.  The majority of these activities will 
occur at the following locations: 
Tendyne Holdings, Inc.  
177 County Road B East 
St. Paul, MN 55117 
13.2 Source Documentation 
 
IDE regulations (21 CFR 812) and GCPs require that the investigator maintain information in the 
subject’s medical records that corroborates data collected on the eCRFs.   Throughout the clinical 
study duration, the sites’ investigators (or designees as indicated on the delegation of authority 
log) will maintain complete and accurate documentation including but not limited to medical 
records, clinical study progress records, laboratory reports, eCRFs, signed ICFs, device 
accountability records, correspondence with the IRB and clinical study monitor or Sponsor, AE 
reports, and information regarding subject discontinuation or completion of the study.  Any source 
documentation (procedure reports, imaging studies, lab reports, death certificates, etc.) that is sent 
to the Sponsor, reviewing committees, or the core lab, should have all subject identifiers removed 
and replaced with the subject number.  In order to comply with GCP and regulatory requirements, 
the following information should be included in the subject record, at a minimum, and if applicable 
to the investigation: 
 Medical history/physical condition of the subject before involvement in the study sufficient 
to verify CIP entry criteria. 
 Dated and signed notes on the day of entry into the study referencing the Sponsor, CIP 
number, subject ID number and a statement that informed consent was obtained. 
 Dated and signed notes from each subject visit (for specific results of procedures and 
exams). 
 Adverse events reported and their resolution including supporting documents such as 
discharge summaries, imaging, ECGs, and lab results; including documentation of site 
awareness of SAEs and of investigator assessment of device/procedure relationship. 
 Study required laboratory reports and 12-lead ECGs, signed and dated for review and 
annotated for clinical significance of out of range results.  
 Notes regarding CIP required and/or prescription medications taken during the study 
(including start and stop dates). 
 Subject’s condition upon completion of or withdrawal from the study. 
 Any other data required to substantiate data entered into the eCRF. 

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13.3 Electronic Case Report Form Completion  
Primary data collection based on source-documented hospital and/or clinic chart reviews will be 
performed clearly and accurately by site personnel trained on the CIP and eCRF completion.  eCRF 
data will be collected for all subjects that are enrolled into the study. 
13.4 Record Retention 
 
The Sponsor will archive and retain all documents pertaining to the study as per the applicable 
regulatory record retention requirements. 
The investigator will maintain all CRFs, essential study documents, and any source documentation 
that supports data collected on study subjects, in compliance with ICH/GCP guidelines and their 
local IRB requirements.  Documents must be retained for at least two (2) years after the last 
approval of marketing application, or until at least two (2) years have elapsed since the formal 
discontinuation of the clinical investigation of the product.  These documents will be retained for 
a longer period of time by agreement with the Sponsor or in compliance with other regulatory 
requirements.  
The investigator will take measures to ensure essential documents are not accidentally damaged 
or destroyed.  If for any reason the investigator withdraws responsibility for maintaining these 
essential documents, custody must be transferred to an individual who will assume responsibility.  
In such an event, the Sponsor must receive written notification of this custodial change.  When 
these documents no longer need to be maintained, it is the Sponsor’s responsibility to inform the 
investigator.  
13.4.1 Investigator Records 
Investigators will maintain the following complete, accurate, and current records relating to the 
investigator’s participation in this study including, but not limited to: 
 Study-related correspondence with another investigator, an IRB, the Sponsor, monitors, 
subjects, or regulatory agencies, including required reports that relate to this study 
 Device Accountability log 
 Delegation of Authority log 
 Subject’s case history records 
 Signed informed consent form 
 Signed HIPAA authorization (if separate from the consent form) 
 Relevant subject complaints 
 Protocol required CRFs and data sets 
 Documentation of the dates and reasons for any study deviation 
 Clinical investigation plan and amendments 
 Study personnel training records 
 Signed investigator agreement and clinical study reimbursement agreement 
 Current curriculum vitae (current by address) 
 Current medical license (current by date) 

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 Financial disclosure 
 IRB approvals, renewals and correspondence 
If records are stored elsewhere, a pointer will be placed in the investigational site file explaining 
where the records are located. 
13.4.2 Sponsor Records 
The Sponsor will maintain the following records:  
 Study-related correspondence (including correspondence with regulatory authorities and 
IRBs) that pertains to the investigation, including IRB approval letters 
 Records of device shipment and device disposition (e.g., shipping receipts, materials 
destruct records) 
 Report of prior investigations summary 
 Copy of signed investigator agreement, clinical study reimbursement agreement, financial 
disclosure information, medical license and curriculum vitae (CV) of investigators 
 Training documentation of all research center staff personnel as well as Sponsor study 
personnel 
 eCRFs submitted by investigator and center-specific samples of ICFs and protocols 
 Progress reports 
 Final clinical study report 
 Records of adverse device effects (anticipated and unanticipated) and device deficiencies 
 All other records required by FDA according to 21CFR812.140(b)(4), and any other 
regulatory/competent authority requirements. 
 
 

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Sponsor Reports 
Sponsor is responsible for preparation and submission of the following reports as identified in 
Table 5. 
Table 5.  Description and Submission Requirements of Sponsor Reports 
Report 
Submit to 
Description 
UADE 
FDA, IRB, 
PIs 
Notification within 10 working days (21CFR 
812.150(b)(1)) 
Withdrawal of 
IRB approval 
FDA, IRB, 
PIs 
Notification within 5 working days (21CFR 
812.150(b)(2)) 
Withdrawal of 
FDA approval 
IRB, PIs 
Notification within 5 working days (21CFR 
812.150(b)(3)) 
Current 
investigator list 
FDA 
Submitted at 6 month intervals, a current list of the 
names and addresses of all investigators participating in 
the investigation (21CFR 812.150(b)(4)) 
Progress reports 
FDA, IRB 
Progress reports will be submitted at least annually or as 
stipulated by the FDA (21CFR 812.150(b)(5)) 
Recall and device 
disposition 
FDA, IRB 
Notification within 30 working days and will include the 
reasons for any request that an investigator return, repair 
or otherwise dispose of any devices (21CFR 
812.150(b)(6)) 
Final report 
FDA, IRB, 
PIs 
Sponsor will notify the FDA within 30 working days of 
the completion, termination of the investigation. A final 
report will be submitted to the FDA, investigators and 
IRBs within 6 months after completion or termination of 
this study.  (21CFR 812.150(b)(7)) 
Failure to obtain 
informed consent 
form 
FDA 
Sponsor will submit to the FDA a copy of any report by 
an investigator under paragraph (a)(5) of this section of 
use of a device without obtaining informed consent form, 
within 5 working days of receipt of notice of such use. 
(21 CFR 812.150(b)(8)) 
14 ETHICAL CONSIDERATIONS 
 
IRB approval for the CIP and ICF or other written information provided to the subject will be 
obtained by the Principal Investigator at each investigational site prior to participation in this 
feasibility study. The approval letter must be received prior to the start of the study and a copy 
must be provided to the Sponsor. No changes will be made to the CIP or ICF or other written 
information provided to the subject without appropriate approvals, including IRB, the Sponsor, 
and/or the regulatory agencies.  
Until the study is completed, the investigator will update the IRB of the progress of this study, per 
IRB requirements.  Written approval must be obtained from the IRB annually to continue the study, 

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or according to each institution’s IRB requirements. Further, any amendments to the CIP as well 
as associated ICF changes will be submitted to the IRB and written approval obtained prior to 
implementation, according to each institution’s IRB requirements. 
No investigative procedures other than those defined in this CIP will be undertaken on enrolled 
subjects without the written agreement of the IRB and the Sponsor. 
15 PUBLICATION POLICY 
 
The data and results from this study are the sole property of the Sponsor.  The Sponsor shall have 
the right to access and use all data and results generated during the study.  The investigators will 
not use study-related data without the written consent of the Sponsor for any other purpose than 
for study completion or for generation of publication material, as referenced in the clinical study 
agreement.  The publication or presentation of results from a single investigational site are not 
allowed until publication or presentation of the multi-center results.  The Sponsor acknowledges 
that the Publication Committee intends to publish a multi-center publication regarding the study 
results. The Sponsor must receive any proposed publication or presentation materials at least 60 
days prior to the proposed date of the presentation or the initial submission of the proposed 
publication in order for the materials to be reviewed by the Sponsor in compliance with the 
Sponsor’s publication policy set forth in the clinical study site agreement. 
The Sponsor will register the feasibility study on www.clinicaltrials.gov, in accordance with the 
International Committee of Medical Journal Editors guidelines, or any other applicable guidelines.  
The Sponsor shall be responsible for any such registration and results posting as required by 
ClinicalTrials.gov.  Investigational sites shall not take any action to register the study.  A full report 
of the pre-specified outcomes, including any negative outcomes, will be made public through the  
ClinicalTrials.gov  website  according  to  the  requirements  of  Section  801  of  the  FDA 
Amendments Act.  If this clinical investigation is terminated early, the Sponsor will make every 
effort to hasten the release of the pre-specified outcomes through ClinicalTrials.gov website. 
16 RISK ANALYSIS 
 
Risk evaluation was conducted in accordance with EN ISO 14971:2012: Medical Devices - 
Application of Risk Management to Medical Devices.   
16.1 Anticipated Clinical Benefits 
Potential benefits of the use of the Tendyne System may include, but are not limited to, the 
following: 
 Improved symptomatic status and quality of life  
 Reduced mortality  
 Avoidance of procedural risks such as: cardiopulmonary bypass (CPB); atrioventricular 
groove disruption; ventricular rupture; and injury to the left circumflex coronary artery 
  
 
 

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16.2 Risks Associated with Participation in the Clinical Study 
As previously described, Table 3 indicates all anticipated AEs/risks associated with the use of the 
Tendyne Mitral Valve System.  The risk associated with study-required testing and assessments 
are summarized in Table 6.  Although routine, these tests and assessments may be performed at 
greater frequency than standard of care practices.  
Table 6.  Study Procedure-Related Risks 
Study Procedures 
Risks 
History, Clinical Status, QOL 
Surveys, 6-Minute Walk & Physical 
Exam 
None, Minimal 
Laboratory testing 
Minimal. Usual risks associated with phlebotomy 
ECG 
None, Minimal 
Echocardiography: TTE 
None, Minimal 
Echocardiography: TEE 
A separate written informed consent process consistent 
with clinic policies and practices will occur outside of 
study 
Hemodynamics 
A separate written informed consent process consistent 
with clinic policies and practices will occur outside of 
study 
Computerized tomography 
angiography (CTA) 
A separate written informed consent process consistent 
with clinic policies and practices will occur outside of 
study
Angiography (LV Ventriculogram) / 
Hemodynamics 
Written informed consent consistent with institutional 
policy
16.3 Possible Interactions with CIP-Required Concomitant Medications 
Potential risks associated with warfarin may include, but are not limited to (refer to the product 
insert for a complete listing):  
 Bruising 
 Decrease in white blood cell count 
 Diarrhea 
 Fever 
 Headache 
 Inability to tolerate the medication 
 Increased risk of internal bleeding 
 Major bleeding which may result in death  
 Nose bleeds 
 Skin Rash 
 Upset Stomach 
 Vomiting 

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16.4 Steps Taken to Control or Mitigate the Risks 
In-depth recommendations, special precautions and instructions regarding patient selection, device 
handling, device placement and system removal are included in the IFU. 
The IFU also states that the devices can only be used by physicians who have received appropriate 
training on how to use the device.  This statement is interpreted to mean physician users are 
expected to be aware of the known and foreseeable safety risks associated with the use of the 
device, including the surgical and/or non-surgical treatment of these conditions. 
Risks associated with the use of the device during this clinical study are minimized through device 
design, investigator selection and training, pre-specified patient eligibility requirements, study 
monitoring to ensure adherence to the CIP and the use of a DSMB. Investigational sites will be 
notified of unexpected adverse device effects and other safety concerns that could negatively 
impact the safety of the subjects if such issues arise. Stopping rules will be discussed with the 
DSMB and applied for subject safety through enrollment.  All SAEs and device deficiencies will 
be reported to the Sponsor and will be monitored internally for safety surveillance purposes. 
16.5 Risk to Benefit Rationale  
The Tendyne Mitral Valve System represents a novel, state-of-the-art technology for the treatment 
of Mitral Regurgitation. Residual risks are well tolerated when compared with other mitral 
regurgitation treatment options. The potential hazards associated with the design and use of the 
Tendyne Mitral Valve System for use in patients with Mitral Valve Regurgitation and Mitral 
Annulus Calcification do not outweigh the potential benefits to the subject.  
 
 
 

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APPENDIX I:  ABBREVIATIONS AND ACRONYMS 
Acronym 
Definition 
Acronym 
Definition 
6MWD/T 
Six Minute Walk Distance/Test 
IDE 
Investigational Device Exemption 
ACC 
American College of Cardiology 
IFU 
Instructions for Use 
AE 
Adverse Event 
INR 
International Normalized Ratio 
AHA 
American Heart Association 
IPG 
Implantable Pulse Generator 
CABG 
Coronary Artery Bypass Grafting 
IRB 
Institutional Review Board 
CCS 
Canadian Cardiovascular Society 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
CEC 
Clinical Events Committee 
LV 
Left Ventricle 
CFR 
Code of Federal Regulations 
LVEDD 
Left Ventricular End Diastolic Dimension 
CIP 
Clinical Investigational Plan 
LVEF 
Left Ventricular Ejection Fraction 
COPD 
Chronic Obstructive Pulmonary Disease 
LVOT 
Left Ventricular Outflow Tract 
CRO 
Contract Research Organization 
MI 
Myocardial Infarction 
CRT 
Cardiac Resynchronization Therapy 
MR 
Mitral Regurgitation 
CT 
Computerized Tomography 
MV 
Mitral Valve 
DD 
Device Deficiency 
MVARC 
Mitral Valve Academic Research Consortium 
DSMB 
Data and Safety Monitoring Board 
NYHA 
New York Heart Association 
ECG 
Electrocardiogram 
PAS 
Pulmonary Artery Systolic pressure 
EDC 
Electronic Data Capture 
PCI 
Percutaneous Coronary Intervention 
EROA 
Effective Regurgitant Orifice Area 
PROM 
Predicted Risk of Mortality 
ESC 
European Society of Cardiology 
QoL 
Quality of Life 
FDA  
U.S. Food and Drug Administration 
RVSP 
Right Ventricular Systolic Pressure 
GCP  
Good Clinical Practices 
SAE 
Serious Adverse Event 
HIPAA 
Health Insurance Portability and 
Accountability Act 
STS 
Society of Cardiothoracic Surgeons 
ICD 
Implantable Cardioverter Defibrillator 
TEE 
Transesophageal Echocardiogram 
ICF 
Informed Consent Form 
TTE 
Transthoracic Echocardiogram 
ICH 
International Council for Harmonization 
UADE 
Unanticipated Adverse Device Effect 
 
 
 

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APPENDIX II:  DEFINITIONS 
The following definitions will be used in the MAC Feasibility Clinical Investigational Plan.  All 
serious adverse events and device or procedure related events will be adjudicated by the 
independent Clinical Events Committee, along with relationship to the Tendyne device and/or 
procedure. 
Canadian Cardiovascular Society Grading of Angina Pectoris (CCS Angina Classification) 
CCS Angina Classification is defined by the Canadian Cardiovascular Society as [26]: 
Grade 
Definition 
I 
Ordinary physical activity does not cause angina, such as walking and climbing 
stairs. Angina with strenuous or rapid or prolonged exertion at work or recreation 
II 
Slight limitation of ordinary activity. Walking or climbing stairs rapidly, walking 
uphill, walking or stair climbing after meals, or in cold, or in wind, or under 
emotional stress, or only during the few hours after awakening. Walking more than 
two blocks on the level and climbing more than one flight of ordinary stairs at a 
normal pace and in normal conditions. 
III 
Marked limitation of ordinary physical activity. Walking one or two blocks on the 
level and climbing on flight of stairs in normal conditions and at normal pace. 
IV 
Inability to carry on any physical activity without discomfort, anginal syndrome may 
be present at rest. 
 
Causal Relationship (from ISO 5840-3) 
Causal relationship is the relationship of the AE to the device, the implant procedure or the 
patient’s condition.  It should be established for both the Tendyne and Control device, based on 
the following categories: 
 
Relatedness 
Definition 
Device-related 
Any AE involving the function of the device, or the presence of the device 
in the body.  Included in this category are events that are directly attributed 
to the device or the use of the device system. 
Procedure-related Any AE that results from the implant procedure.  Events in this category are 
directly related to the general procedural sequelae. 
Patient condition-
related 
Any AE that results from the worsening of a pre-existing condition or 
cannot be attributed to the device procedure. 
 
 
 
 

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Chronic Kidney Disease 
The following definitions of Chronic Kidney Disease will be utilized in the study, as stated from 
National Institute for Health & Clinical Excellence [27]: 
Stage 
Definition 
1 
Slightly diminished function; kidney damage with normal or relatively high GFR 
(≥90 mL/min/1.73 m2). Kidney damage is defined as pathological abnormalities 
or markers of damage, including abnormalities in blood or urine test or imaging 
studies. 
2 
Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney damage. Kidney 
damage is defined as pathological abnormalities or markers of damage, including 
abnormalities in blood or urine test or imaging studies. 
3 
Moderate reduction in GFR (30–59 mL/min/1.73 m2). British guidelines 
distinguish between stage 3A (GFR 45–59) and stage 3B (GFR 30–44) for 
purposes of screening and referral. 
4 
Severe reduction in GFR (15–29 mL/min/1.73 m2) Preparation for renal 
replacement therapy. 
5 
Established kidney failure (GFR <15 mL/min/1.73 m2), permanent renal 
replacement therapy, or end stage renal disease. 
 
Coronary Artery Disease 
Approximately two-thirds of patients with HF have underlying CAD (ischemic cardiomyopathy).  
Therefore, it is imperative that appropriate treatment for CAD be used in the MAC feasibility study, 
according to the ACC/AHA/HSFA Guidelines for Heart Failure.  Specific recommendations listed 
in those guidelines are listed as follows: 
 Use of nitrates and beta blockers for the treatment of angina,  
 Coronary revascularization according to recommended guidelines in patients who have 
both HF and angina,  
 Patients with coronary artery disease and HF should be treated in accordance with 
recommended guidelines for chronic stable angina,    
 Use of antiplatelet agents for prevention of MI and death in patients with HF who have 
underlying coronary artery disease  
In addition, revascularization (i.e., percutaneous coronary intervention, etc.) should occur prior to 
subject registration in the study, as applicable. 
 
Hospitalization (All-cause) 
Admission to inpatient unit or ward in the hospital for at least 24 hours, including emergency 
department stay.  Excludes hospitalizations planned for pre-existing conditions, unless there is 
worsening in the baseline condition.   
For the purpose of the CIP, overnight stays at nursing home facilities, physical rehab or extended 
care facilities, including hospice, do not meet the protocol definition of hospitalization.  
Hospitalizations will be adjudicated by the CEC per the following: 

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Hospitalization (Cardiovascular):  Treatment in any inpatient unit or ward in the hospital for at 
least 24 hours, including emergency department stay for conditions such as heart failure (as defined 
below), coronary artery disease, acute myocardial infarction, stroke, hypertension, cardiac 
arrhythmias, cardiomegaly, pericardial effusion, atherosclerosis, peripheral vascular disease and 
mitral valve reintervention or reoperation. 
Hospitalization (Heart Failure):  Any inpatient or outpatient visit that requires IV (e.g., diuretics 
or inotropes) for the treatment of heart failure.  This definition also includes any event that meets 
all of the following criteria:  
 Subject has clinical signs and/or symptoms of heart failure, including new or worsening 
dyspnea, orthopnea, paroxysmal nocturnal dyspnea, increasing fatigue, worsening 
functional capacity or activity intolerance, or signs and/or symptoms of volume overload. 
 Results in intravenous (e.g., diuretic or vasoactive therapy) or invasive (e.g., ultrafiltration, 
IABP, mechanical assistance) treatment for heart failure.  
Hospitalization (Non-Cardiovascular):  Hospitalizations that are not heart failure or other 
cardiovascular hospitalizations, as defined in this CIP, will be categorized as non-cardiovascular 
hospitalizations. 
 
Index Procedure 
The procedure in which the Tendyne or Control (repair with remodeling annuloplasty or total 
chordal-sparing replacement) device implant is first attempted. 
 
Left Ventricular Dysfunction 
Subjects enrolled in the MAC feasibility study should be treated with ICD and/or CRT, as per the 
following guidelines, prior to subject enrollment in the trial: 
 An implantable cardioverter-defibrillator is recommended as secondary prevention to 
prolong survival in subjects with current or prior symptoms of HF and reduced LVEF who 
have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing 
ventricular tachycardia.  
 Implantable cardioverter-defibrillator therapy is recommended for primary prevention of 
sudden cardiac death to reduce total mortality in subjects with non-ischemic dilated 
cardiomyopathy or ischemic heart disease at least 40 days post-MI, a LVEF less than or 
equal to 35%, and NYHA Functional Class II or III symptoms while receiving chronic 
optimal medical therapy, and who have reasonable expectation of survival with a good 
functional status for more than 1 year  
 Subjects with LVEF of less than or equal to 35%, sinus rhythm, left bundle-branch block 
(LBBB), a QRS duration of ≥ 150 ms, and NYHA Functional Class III or ambulatory class 
IV symptoms despite recommended optimal medical therapy, should receive cardiac 
resynchronization therapy, with or without an ICD, unless contraindicated  
 
 
 

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Local Site Heart Team 
The Local Site Heart Team must consist of, at a minimum, the cardiothoracic surgeon, 
interventional cardiologist, and an echocardiographer.  Additional members of the heart team may 
include: other imaging specialists (CT), heart failure specialists, cardiac anesthesiologists, 
intensivists, nurses, and social workers. 
 
Mitral Regurgitation Severity  
Defined in Figure 1, adapted from the 2017 ACC Expert Consensus Decision Pathway on the 
Management of MR [28]  
 
 
Figure 1.  Mitral Regurgitation Severity 
 
 
 
 
 
 
Subjects included in the MAC feasibility study  

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Modified Rankin Scale Score 
The modified Rankin Scale (mRS) will be used to classify strokes as “disabling” or “non-
disabling” and should be assessed at the following time intervals: ≤ 7 days following an event, at 
30 days, and at 90 days. 
 
Score 
Definition 
0 
No symptoms at all 
1 
No significant disability despite symptoms; able to carry out all usual duties and 
activities 
2 
Slight disability; unable to carry out all previous activities, but able to look after 
own affairs without assistance 
3 
Moderate disability; requiring some help, but able to walk without assistance 
4 
Moderately severe disability; unable to walk without assistance and unable to 
attend to own bodily needs without assistance 
5 
Severe disability; bedridden, incontinent and requiring constant nursing care and 
attention 
6 
Dead 
Disabling stroke: an mRS score ≥2 with an increase in ≥1 mRS category from a subject’s pre-
stroke baseline at 90 days. 
Non-disabling stroke: an mRS score of < 2 at 90 days or one that does not result in an increase 
in at least one mRS category from an individual’s pre-stroke baseline 
 
New York Heart Association Classification (NYHA Class): 
Class 
Definition 
I 
Patients with cardiac disease but without resulting limitations of physical activity.
II 
Patients with cardiac disease resulting in slight limitation of physical activity.  Patients 
are comfortable at rest.  Ordinary physical activity results in fatigue, palpitation, 
dyspnea, or anginal pain. 
III 
Patients with cardiac disease resulting in marked limitation of physical activity.  
Patients are comfortable at rest.  Less than ordinary physical activity causes fatigue, 
palpitation dyspnea, or anginal pain.
IV 
Patients with cardiac disease resulting in inability to carry on any physical activity 
without discomfort.  Symptoms of cardiac insufficiency or of the anginal syndrome 
may be present even at rest.  If any physical activity is undertaken, discomfort is 
increased. 
 
 

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Principal Investigator (from ISO 14155) 
Qualified person responsible for conducting the clinical investigation at an investigation site.  If a 
clinical investigation is conducted by a team of individuals at an investigation site, the principal 
investigator is responsible for leading the team. 
 
Repositioning (from ISO 5840-3) 
Change in implant position of a partially or fully deployed transcatheter heart valve substitute via 
a transcatheter technique, possibly requiring full or partial recapturing of the device. 
 
Retrieval (from ISO 5840-3) 
Removal of a partially or fully deployed transcatheter heart valve substitute via a transcatheter 
technique. 
 
Stroke and TIA (from VARC II) 
The following stroke and TIA diagnostic criteria will be used in this study, per VARC II [29]: 
 Acute episode of a focal or global neurological deficit with at least one of the following:  
change in the level of consciousness, hemiplegia, hemiparesis, numbness, or sensory loss 
affecting one side of the body, dysphasia or aphasia, hemianopia, amaurosis fugax, or other 
neurological signs or symptoms consistent with stroke. 
 Stroke:  Duration of a focal or global neurological deficit ≥24 hours; OR <24 hours if 
available neuroimaging documents a new hemorrhage or infarct; OR the neurological 
deficit results in death. 
 TIA:  Duration of a focal or global neurological deficit <24 hours, any variable 
neuroimaging does not demonstrate a new hemorrhage or infarct. 
 No other readily identifiable non-stroke cause for the clinical presentation (e.g., brain 
tumor, trauma, infection, hypoglycemia, peripheral lesion, pharmacological influences), to 
be determined by or in conjunction with the designated neurologist. 
 Confirmation of the diagnosis by one of the following: 
o Neurologist or neurosurgical specialist 
o Neuroimaging procedure (CT scan or brain MRI), but stroke may be diagnosed on 
clinical grounds alone. 
 
Stroke Classification 
The following stroke definitions will be used, per VARC II [29]. 
 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. 
Note: A stroke may be classified as undetermined if there is insufficient information to 
allow categorization as ischemic or hemorrhagic. 
 

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Vulnerable Population (from ISO 14155) 
Individuals with mental disability, persons in nursing homes, children, impoverished persons, 
persons in emergency situations, homeless persons, nomads, refugees, and those permanently 
incapable of giving informed consent.  Vulnerable populations also may include members of a 
group with a hierarchical structure such as university students, subordinate hospital and laboratory 
personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.

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APPENDIX III: STUDY ASSESSMENT AND FOLLOW-UP SCHEDULE 
 
 
 
Exams, Tests and Data Collection 
Screening
/ Baseline 
Procedure 
Pre-
discharge 
1 Month 
3 Months 
6 Months 
1 and 2 
years 
Annual visits 
(3-5 years) 
Visit Window 
 
Before 
and After 
Implant
72 hours 
prior to 
discharge
-3 days 
+14 days 
±30 days 
±30 days 
±30 
days 
±45 days 
Informed Consent 
X 
 
 
 
 
 
 
 
Inclusion/Exclusion Screening 
X 
 
 
 
 
 
 
 
Medical history with Demographics 
X 
 
 
 
 
 
 
 
Physical Exam including Vital Signs while sitting  
X 
 
 
 
 
 
 
 
Cardiovascular Medications 
X 
X 
X 
X 
X 
X 
X 
X 
STS PROM Risk Score 
X 
 
 
 
 
 
 
 
CCS Angina class 
X 
 
 
 
 
 
 
 
NYHA Classification  
X 
 
 
X 
X 
X 
X 
X 
Six Minute Hall Walk Test 
X 
 
 
X 
X 
X 
X 
X 
KCCQ 
X 
 
 
X 
X 
X 
X 
X 
CLINICAL LABORATORY TESTS 
Pregnancy Test 
X 
 
 
 
 
 
 
 
Creatinine 
X 
 
X 
X 
X 
X 
X 
X 
Plasma–free Hemoglobin 
X 
 
 
X 
X 
X 
X 
X 
BNP or NT pro-BNP 
X 
 
 
X 
X 
X 
X 
X 
International Normalized Ratio (INR) 
X 
 
X 
X 
X 
X 
X 
X 
Creatine Kinase-MB (CK-MB) 
X 
 
X 
X 
X 
X 
X 
X 
Troponin (Type I or T) 
X 
 
X 
X 
X 
X 
X 
X 
HEMODYNAMICS 
Cardiac Output 
 
X 
 
 
 
 
 
 
PA Pressures 
 
X 
 
 
 
 
 
 
RA Pressures  
 
X 
 
 
 
 
 
 
LV Pressures 
 
X 
 
 
 
 
 
 
EXAMS AND TESTS 
Coronary Angiogram (if clinically indicated)  
X 
 
 
 
 
 
 
 
Cardiac CT# 
X 
 
 
X 
 
 
 
 
ECG (12-Lead) 
X 
X
X
X
X
X 
X 
X
TEE 
X 
X 
 
 
 
 
 
 
TTE^ 
X 
 
X 
X 
X 
X 
X 
X 
Angiography: LV Gram (Optional) 
 
X 
 
 
 
 
 
 
OTHER 
Device Deficiencies 
 
X 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
#Cardiac CT imaging (4D with contrast) is required for suspected thrombosis events in subjects implanted with the Tendyne device. 
^TTE imaging must be conducted between 60 and 120 days after anticoagulation stoppage for subjects who receive the Tendyne device.  
Note:  
Baseline imaging for Cardiac CT must be acquired < 120 days, and TEE / TTE echocardiograms must be acquired < 60 days from intended subject registration. All other screening 
assessments must be completed 90 days prior to registration.    
LV Gram is optional – only per investigator discretion.   
  

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APPENDIX IV:  CONTACT INFORMATION 
Any questions, including requests for a list of investigational sites, can be obtained upon request 
by contacting. 
Tendyne Holdings, Inc. 
(A subsidiary of Abbott Vascular, Inc) 
177 County Road B East 
St. Paul, MN 55117 
United States 
Phone: +1 651-289-5500 
 
 
 

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APPENDIX V: CLINICAL INVESTIGATION PLAN REVISIONS  
This CIP may be revised as appropriate by the Sponsor. Rationale will be included with each 
version in the revision history table below. The version number and date of revision will be 
documented.  
 
The acknowledgement of the revised CIP by the Coordinating Investigator (if applicable) and the 
Principal Investigators will be collected on the signature pages.  
 
IRB and relevant Regulatory Authorities, if applicable, will be notified of revisions to the CIP. As 
necessary, approval will also be obtained prior to implementation of the CIP.  
 
Revision History  
 
Ver 
Date 
Details 
Rationale 
01P 
28Mar2018 
Not applicable
Initial release of CIP
02P 
18Apr2018 
Extended study follow-up period from 2 
years to 5 years post procedure 
Revision based on 
FDA feedback. Email 
dated 18Apr2018.
A 
25Apr2018 
 Versioning & date change to Rev. A 
dated 25Apr2018 
 Correction to Sec. 6.1 – removed 
reference to EQ-5D and SF-12 QoL - 
not required for study
Administrative 
revision for Tendyne 
Quality System 
purposes 
 
 
 

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Iung B, Baron G, Tornos P, Gohlke-Bärwolf C, Butchart EG, Vahanian A. Valvular heart 
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Iung B. A prospective survey of patients with valvular heart disease in Europe: The Euro 
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