Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation
Phase: NA
Conditions: Mitral Regurgitation, Mitral Insufficiency, Mitral Valve Insufficiency, Cardiovascular Diseases, Valve Disease, Heart, Heart Valve Diseases, Functional Mitral Regurgitation, Degenerative Mitral Valve Disease
Sponsor: Abbott Medical Devices

 
Clinical Investigation Plan Cover Page 
 
 
 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the express written 
consent of Abbott. 
87173 CIP Posting Cover Page Ver C 
Template 
Page 1 of 1 
 
 
NCT Number: NCT03433274 
SUMMIT 
Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral 
Valve System for the Treatment of Symptomatic Mitral Regurgitation (SUMMIT) 
Study Document No:  ABT-CIP-10241 
Version E 
Date: 05-MAY-2022 
 
 
Sponsor  
 
 
Abbott Medical  
        
 
 
 
177 County Road B East 
      
  
 
 
St. Paul, MN 55117 
        
 
 
 
United States of America 
 
 
 
 
 
 
 
 
 
 
 

Abbott Medical 
 
CONFIDENTIAL 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 1 of 122 
 
 
 
 
SUMMIT 
 
 
 
 
 
 
 
CS0004-P 
SUMMIT 
Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter Mitral 
Valve System for the Treatment of Symptomatic Mitral Regurgitation 
IDE Number 
G140240 
Version Number 
Version E 
Date 
5 May 2022 
Study Principal Investigator  
(Cardiothoracic Surgeon)  
Gorav Ailawadi, M.D., M.B.A 
Chairman and Professor of Cardiac Surgery 
University of Michigan 
Study Principal Investigator  
(Interventional Cardiologist) 
Jason Rogers, M.D. 
Professor of Cardiovascular Medicine 
Director, Interventional Cardiology 
UC Davis Medical Center 
Co-Principal Investigator – 
Severe MAC Cohort 
(Cardiothoracic Surgeon) 
Vinod Thourani, M.D. 
Marcus Chief of Cardiovascular Surgery 
Piedmont Healthcare and the Marcus Heart Valve Center 
 
Co-Principal Investigator – 
Severe MAC Cohort 
(Interventional Cardiologist) 
Paul Sorajja, M.D. 
Director, Center for Valve and Structural Heart Disease 
Minneapolis Heart Institute 
Abbott Northwestern Hospital 
Trial Type 
Prospective, controlled, multicenter clinical investigation of the 
Tendyne™ Transcatheter Mitral Valve System for the treatment 
of eligible subjects with symptomatic, severe mitral regurgitation. 
Sponsor 
 
 
Abbott Medical  
177 County Road B East 
St. Paul, MN 55117 
United States of America 
Protocol Author 
Jeremy Glynn, PhD 
Principal Clinical Scientist, Abbott 
No use or disclosure of information contained within this document is permitted without prior written 
authorization from Abbott Medical 
 

Abbott Medical 
 
CONFIDENTIAL 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 2 of 122 
 
 
 
 
SUMMIT 
 
 
Tendyne™ Transcatheter Mitral Valve System 
CLINICAL INVESTIGATION PLAN 
SITE PRINCIPAL INVESTIGATOR (PI) SIGNATURE PAGE 
Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter 
Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation (SUMMIT) 
Clinical Investigation Plan No. CS0004-P (ABT-CIP-10241) 
 
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) / Ethics Committee (EC).  I will provide copies 
of this CIP and all pertinent information to the trial personnel under my supervision and my 
hospital IRB / EC.  I will discuss this material with them and ensure they are fully informed 
regarding the Tendyne™ Transcatheter Mitral Valve System and the conduct of the trial according 
to this CIP, applicable laws and regulatory regulations, including hospital IRB / EC requirements. 
 
 
Investigational Site Name 
 
 
_______________________________________________________________________ 
Site PI Signature 
 
 
 
 
 
Date 
 
 
_______________________________________________    
Site PI Printed Name                                                                     
 
 

Abbott Medical 
 
CONFIDENTIAL 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 3 of 122 
 
 
 
 
SUMMIT 
 
 
Tendyne™ Transcatheter Mitral Valve System 
CLINICAL INVESTIGATION PLAN 
STUDY PRINCIPAL INVESTIGATOR (PI) SIGNATURE PAGE 
Clinical Trial to Evaluate the Safety and Effectiveness of Using the Tendyne Transcatheter 
Mitral Valve System for the Treatment of Symptomatic Mitral Regurgitation (SUMMIT) 
Clinical Investigation Plan No. CS0004-P (ABT-CIP-10241) 
 
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) / Ethics Committee (EC).  I will provide copies 
of this CIP and all pertinent information to the trial personnel under my supervision and my 
hospital IRB / EC.  I will discuss this material with them and ensure they are fully informed 
regarding the Tendyne™ Transcatheter Mitral Valve System and the conduct of the trial according 
to this CIP, applicable laws and regulatory regulations, including hospital IRB / EC requirements. 
 
 
Investigational Site Name 
 
 
_______________________________________________________________________ 
Study PI Signature 
 
 
 
 
 
Date 
 
 
_______________________________________________    
Study PI Printed Name                                                                           
 

Abbott Medical 
 
CONFIDENTIAL 
This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 4 of 122 
 
 
 
 
SUMMIT 
 
Table of Contents 
TABLE OF CONTENTS ..............................................................................................................4 
TABLE OF FIGURES ...................................................................................................................9 
TABLE OF TABLES .....................................................................................................................9 
COMPLIANCE STATEMENT ..................................................................................................10 
CLINICAL INVESTIGATION PLAN SUMMARY ................................................................11 
1 
INTRODUCTION................................................................................................................20 
2 
BACKGROUND INFORMATION ...................................................................................20 
2.1 
Background and Rationale .............................................................................................20 
2.1.1 Clinical Need .............................................................................................................20 
2.1.2 Current Guidelines .....................................................................................................21 
2.1.3 Barriers to Guideline Adherence ...............................................................................24 
2.1.4 Treatment of Mitral Annular Calcification ................................................................24 
2.1.5 Transcatheter Edge-to-Edge Mitral Valve Repair (TEER) ........................................25 
2.1.6 Transcatheter Mitral Valve Replacement ..................................................................26 
2.1.7 Clinical Experience with the Tendyne Transcatheter Mitral Valve System ..............26 
2.1.8 Rationale for Conducting this Clinical Trial / Investigation ......................................27 
2.1.9 Severe MAC CAP Rationale .....................................................................................28 
2.2 
Summary of Investigational Device ...............................................................................29 
2.2.1 Name of the Investigational Device ...........................................................................29 
2.2.2 Intended Indication for Use .......................................................................................29 
2.2.3 Description of the Investigational Device (Tendyne Transcatheter Mitral Valve 
System) ..................................................................................................................................29 
2.2.4 Procedures Involved in the Use of the Device ...........................................................30 
2.2.5 Training Required for the Use of the Device .............................................................30 
2.2.6 Investigational Device Accountability .......................................................................30 
2.2.7 Description of the Control Group Device Used in the Randomized Cohort .............30 
3 
TRIAL OBJECTIVES / ENDPOINTS ..............................................................................31 
3.1 
Primary Endpoints .........................................................................................................31 
3.1.1 Primary Composite Endpoint - Randomized Cohort .................................................31 
3.1.2 Primary Composite Endpoint - Non-repairable Cohort .............................................31 
3.1.3 Primary Endpoint – Severe MAC Cohort ..................................................................31 
3.1.4 Primary Endpoint – Severe MAC CAP Cohort .........................................................31 
3.2 
Secondary Endpoints - Randomized Cohort ..................................................................31 
3.3 
Secondary Endpoints – Non-repairable Cohort .............................................................32 
3.4 
Secondary Endpoints – Severe MAC Cohort ................................................................32 
3.5 
Secondary Endpoints – Severe MAC CAP Cohort........................................................32 
3.6 
Descriptive Endpoints – Randomized, Non-repairable, Severe MAC and Severe MAC 
CAP Cohorts ..............................................................................................................................32 
3.6.1 Clinical Endpoints ......................................................................................................32 
3.6.2 MVARC Endpoints ....................................................................................................33 
3.6.3 Echocardiographic Endpoints ....................................................................................33 
3.6.4 Health Economic Data (U.S. Investigational Sites) ...................................................34 
4 
TRIAL DESIGN, SCOPE AND DURATION ...................................................................34 

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05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 5 of 122 
 
 
 
 
SUMMIT 
 
4.1 
Trial Design ...................................................................................................................34 
4.2 
Number of Subjects to be Registered.............................................................................36 
4.3 
Expected Duration of the Clinical Investigation ............................................................36 
4.4 
Number of Subjects and Expected Duration of the Severe MAC CAP Cohort .............36 
4.5 
Enrollment of Traditionally Underrepresented Demographic Subgroups .....................37 
4.5.1 Prevalence of Valvular Heart Disease, Diagnosis and Treatment Patterns ...............37 
4.5.2 Representation of Underrepresented Demographic Subgroups .................................38 
4.5.3 Subgroup Analysis for Underrepresented Demographic Subgroups .........................38 
5 
SUBJECT SELECTION AND WITHDRAWAL .............................................................38 
5.1 
Subject Screening and Informed Consent ......................................................................38 
5.1.1 Special Circumstances for Informed Consent ............................................................40 
5.1.2 Enrollment of Medicare Beneficiaries (U.S. Subjects Only) .....................................40 
5.2 
Eligibility Criteria ..........................................................................................................40 
5.2.1 General Eligibility Criteria ........................................................................................40 
5.2.2 Inclusion Criteria .......................................................................................................41 
5.2.3 Exclusion Criteria ......................................................................................................42 
5.3 
Subject Selection ............................................................................................................44 
5.4 
Subject Registration .......................................................................................................44 
5.5 
Subject Discontinuation .................................................................................................44 
5.5.1 Subject Lost to Follow-up ..........................................................................................45 
5.6 
Early Termination of the Clinical Trial .........................................................................45 
5.7 
Trial Completion ............................................................................................................46 
6 
SUBJECT SCREENING AND RANDOMIZATION ......................................................47 
6.1 
Pre-Randomization ........................................................................................................47 
6.1.1 Roll-in Subjects ..........................................................................................................47 
6.1.2 Screening and Baseline Assessments.........................................................................47 
6.2 
Randomization / Registration ........................................................................................50 
7 
TREATMENT AND PRE-DISCHARGE VISITS ...........................................................50 
7.1 
Concomitant Procedures ................................................................................................50 
7.2 
Tendyne Procedure ........................................................................................................50 
7.2.1 Tendyne Procedure - Access ......................................................................................51 
7.2.2 Tendyne Procedure - Valve Delivery ........................................................................51 
7.2.3 Tendyne Procedure - Tensioning ...............................................................................51 
7.2.4 Tendyne Implant Card ...............................................................................................51 
7.3 
Control Group Procedure ...............................................................................................51 
7.4 
Procedural Data Requirements (Tendyne and Control Group)......................................52 
7.4.1 12-Lead ECG .............................................................................................................52 
7.4.2 Intraoperative Hemodynamic Measurements (Tendyne Only) ..................................52 
7.4.3 Additional Procedural Data Collection ......................................................................52 
7.4.4 Immediate Post-Operative Care .................................................................................52 
7.4.5 Anticoagulation Regimen ..........................................................................................52 
7.4.6 Pre-Discharge .............................................................................................................53 
8 
FOLLOW-UP FOR EVALUATION OF SAFETY AND EFFECTIVENESS ..............53 
8.1 
Clinical Follow-up (All Registered / Roll-in Subjects) .................................................53 

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CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 6 of 122 
 
 
 
 
SUMMIT 
 
8.2 
30 Day, 3 Month, 6 Month, and Annual Visits ..............................................................54 
9 
ADVERSE EVENTS ...........................................................................................................56 
9.1 
Definitions / Types of Events ........................................................................................56 
9.1.1 Adverse Event ............................................................................................................56 
9.1.2 Serious Adverse Event ...............................................................................................56 
9.1.3 Anticipated Adverse Events .......................................................................................57 
9.1.4 Unanticipated Adverse Device Effect (UADE) .........................................................58 
9.2 
Device Deficiency ..........................................................................................................58 
9.3 
Device / Procedure Relationship ....................................................................................58 
9.4 
Adverse Event / Device Deficiency Reporting ..............................................................59 
9.4.1 AE Reporting .............................................................................................................59 
9.4.2 SAE Reporting to Sponsor and IRB / EC ..................................................................59 
9.4.3 UADE Reporting to Sponsor and IRB .......................................................................59 
9.4.4 Device Deficiency Reporting .....................................................................................59 
9.4.5 Investigational Site AE Reporting Requirements to Sponsor ....................................60 
9.4.6 AE Reporting to Country Regulatory Authorities by the Sponsor ............................60 
9.5 
Heart Transplants or Subject Death (Tendyne Only) ....................................................60 
10 STATISTICAL METHODS ...............................................................................................60 
10.1 
Analysis Populations ......................................................................................................61 
10.1.1 Randomized Cohort ...................................................................................................61 
10.1.2 Non-repairable, Severe MAC and Severe MAC CAP Cohorts .................................61 
10.2 
Statistical Analyses ........................................................................................................61 
10.2.1 Randomized Cohort ...................................................................................................61 
10.2.2 Non-Repairable Cohort ..............................................................................................64 
10.2.3 Severe MAC Cohort ..................................................................................................65 
10.2.4 Severe MAC CAP Cohort ..........................................................................................66 
10.3 
Sample Size Calculations and Assumptions ..................................................................66 
10.3.1 Randomized Cohort ...................................................................................................66 
10.3.2 Non-Repairable Cohort ..............................................................................................67 
10.3.3 Severe MAC Cohort ..................................................................................................67 
10.3.4 Severe MAC CAP Cohort ..........................................................................................67 
10.4 
Timing of Analysis ........................................................................................................67 
10.5 
Subgroup Analysis .........................................................................................................67 
10.6 
Multiplicity Adjustments ...............................................................................................67 
10.7 
Procedures for Accounting for Missing Data ................................................................68 
10.8 
Statistical Criteria for Termination ................................................................................68 
10.9 
Trial Success ..................................................................................................................68 
10.10 Deviations from Statistical Plan.....................................................................................68 
11 DIRECT ACCESS TO SOURCE DATA / DOCUMENTS .............................................68 
12 QUALITY CONTROL AND QUALITY ASSURANCE .................................................69 
12.1 
Selection of Clinical Sites and Investigators .................................................................69 
12.1.1 Investigator Experience Requirements ......................................................................69 
12.1 
Site Principal Investigator Responsibilities ...................................................................70 
12.2 
Clinical Investigation Plan Amendments.......................................................................70 

Abbott Medical 
 
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express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 7 of 122 
 
 
 
 
SUMMIT 
 
12.3 
Trial Training .................................................................................................................71 
12.3.1 Site Training...............................................................................................................71 
12.3.2 Training of Sponsor’s Designees or Vendors ............................................................71 
12.3.3 Training of Sponsor’s Monitors .................................................................................71 
12.4 
Monitoring .....................................................................................................................71 
12.5 
Deviations from Clinical Investigation Plan ..................................................................72 
12.5.1 Deviations with Expedited Reporting Requirements .................................................72 
12.5.2 Non-Critical Deviations .............................................................................................72 
12.6 
Measures Taken to Avoid and Minimize Bias ...............................................................72 
12.6.1 Subject Recruitment and Randomization...................................................................73 
12.6.2 Maintaining Similar Levels of Follow-up..................................................................73 
12.6.3 Review of Trial Imaging Assessments ......................................................................73 
12.6.4 Safety and Effectiveness Monitoring .........................................................................73 
12.6.5 Follow-up Compliance...............................................................................................73 
12.7 
Quality Assurance Audit ................................................................................................74 
12.8 
Sponsor Support for Regulatory Body Inspection .........................................................74 
12.9 
Sponsor Auditing ...........................................................................................................74 
12.10 Committees ....................................................................................................................75 
12.10.1 Steering Committee (SC) .......................................................................................75 
12.10.2 Subject Eligibility Committee (SEC).....................................................................75 
12.10.3 Publications Committee .........................................................................................75 
12.10.4 Data and Safety Monitoring Board (DSMB) .........................................................75 
12.10.5 Clinical Events Committee (CEC) .........................................................................75 
13 DATA HANDLING AND RECORD KEEPING ..............................................................76 
13.1 
Data Management ..........................................................................................................76 
13.2 
Protection of Personally Identifiable Information .........................................................76 
13.3 
Data Management Plan ..................................................................................................77 
13.4 
Source Documentation ...................................................................................................77 
13.5 
Electronic Case Report Form Completion .....................................................................78 
13.6 
Record Retention ...........................................................................................................78 
13.6.1 Investigator Records ..................................................................................................78 
13.6.2 Sponsor Records ........................................................................................................79 
14 ETHICAL CONSIDERATIONS ........................................................................................80 
15 CLINICAL INVESTIGATION CONCLUSION ..............................................................80 
16 PUBLICATION POLICY ...................................................................................................80 
17 RISK ANALYSIS.................................................................................................................81 
17.1 
Anticipated Clinical Benefits .........................................................................................81 
17.2 
Foreseeable Adverse Events and Anticipate Adverse Device Effects ...........................81 
17.3 
Residual Risks Associated with the Device Under Investigation, as Identified in the Risk 
Analysis Report ..........................................................................................................................81 
17.4 
Risks Associated with Participation in the Clinical Trial ..............................................81 
17.5 
Possible Interactions with CIP-Required Concomitant Medications .............................82 
17.6 
Steps Taken to Control or Mitigate the Risks ................................................................82 
17.7 
Risk to Benefit Rationale ...............................................................................................83 

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05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 8 of 122 
 
 
 
 
SUMMIT 
 
APPENDIX I:  ABBREVIATIONS AND ACRONYMS .........................................................84 
APPENDIX II:  DEFINITIONS .................................................................................................85 
APPENDIX III:  SUBJECT SCREENING FLOW CHART ................................................100 
APPENDIX IV:  TRIAL ASSESSMENT AND FOLLOW-UP SCHEDULE ......................101 
APPENDIX V:  ESSENTIAL FRAILTY TOOLSET ............................................................102 
APPENDIX VI:  CONTACT INFORMATION .....................................................................103 
APPENDIX VII: ACCOMPANYING INFORMATION.......................................................104 
APPENDIX VIII: NON-SUITABILITY CRITERIA FOR TEER .......................................105 
APPENDIX IX:  CLINICAL INVESTIGATION PLAN REVISIONS ...............................106 
APPENDIX X MITRACLIP INDICATION FOR USE.........................................................113 
APPENDIX XI:  BIBLIOGRAPHY.........................................................................................114 
 

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This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 9 of 122 
 
 
 
 
SUMMIT 
 
TABLE OF FIGURES 
Figure 1. SUMMIT Trial Design .................................................................................................. 35 
Figure 2.  Decision Tree for Determining MR Etiology ............................................................... 92 
TABLE OF TABLES 
Table 1.  ACC/AHA 2017 Recommendations for Secondary MR Intervention .......................... 21 
Table 2: ACC/AHA 2020 Recommendations for Mitral Stenosis Intervention ........................... 23 
Table 3.  Follow-up Schedule* and Windows for Trial Subjects ................................................. 55 
Table 4.  Anticipated Adverse Events (Tendyne Transcatheter Mitral Valve System) ................ 57 
Table 5.  Investigational Site AE Reporting Requirements to Sponsor ........................................ 60 
Table 6.  Investigator Responsibilities .......................................................................................... 69 
Table 7.  Trial Procedure-Related Risks ....................................................................................... 82 
 
 
 
 
 
 
 

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This confidential document is the property of Abbott and shall not be reproduced, distributed, disclosed or used without the 
express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 10 of 122 
 
 
 
 
SUMMIT 
 
COMPLIANCE STATEMENT 
This trial will be conducted in accordance with this Clinical Investigation Plan, the Declaration of 
Helsinki, applicable Good Clinical Practices and regulations (e.g., US 21 CFR Part 50, 21 CFR 
Part 56, 21 CFR Part 812 and OUS ISO 14155:2020) and the appropriate local legislation(s). The 
most stringent requirements, guidelines or regulations will always be followed.  The conduct of 
the trial will be approved by the appropriate IRB/EC of the respective investigational site and by 
the applicable regulatory/competent authorities (e.g. FDA, PMDA, Health Canada, etc.). 
 
                                                                                                                                                                                    
 
 

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express written consent of Abbott 
05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 11 of 122 
 
 
 
 
SUMMIT 
 
CLINICAL INVESTIGATION PLAN SUMMARY 
Trial Name and 
Number 
SUMMIT (CS0004-P) 
Title 
Clinical Trial to Evaluate the Safety and Effectiveness of Using the 
Tendyne Transcatheter Mitral Valve System for the Treatment of 
Symptomatic Mitral Regurgitation 
Objectives 
To evaluate the safety and effectiveness of the Tendyne™ Transcatheter 
Mitral Valve System for the treatment of patients with symptomatic, 
moderate-to-severe or severe mitral regurgitation or for patients with 
symptomatic mitral valve disease due to severe mitral annular 
calcification. 
Investigational 
Device 
Tendyne Transcatheter Mitral Valve System 
Clinical Trial / 
Investigation 
Design 
Prospective, controlled, multicenter clinical investigation of the 
Tendyne Transcatheter Mitral Valve System (Tendyne) for the treatment 
of eligible subjects with symptomatic, moderate-to-severe or severe MR 
(≥ Grade III per American Society of Echocardiography criteria), or 
severe mitral annular calcification (MAC) for whom the site heart team 
deems transcatheter treatment is more appropriate than conventional 
mitral valve surgery. 
SUMMIT is a pre-market, interventional, pivotal investigation of the 
Tendyne Transcatheter Mitral Valve System. 
Subjects will be assigned to a cohort of the study at the discretion of the 
local site heart team. Subjects must satisfy the trial inclusion/exclusion 
criteria and be approved by the Subject Eligibility Committee (SEC), 
prior to treatment in the trial.  
Randomized Cohort: Subjects suitable for transcatheter mitral valve 
replacement (TMVR) with Tendyne and indicated for transcatheter 
edge-to-edge repair (TEER) with the MitraClip™ will be randomized in 
a 1:1 ratio to receive either Tendyne (Treatment) or MitraClip (Control). 
Subjects with primary MR must be at prohibitive surgical risk, while 
subjects with secondary MR must be symptomatic despite maximally-
tolerated guideline-directed medical therapy in accordance with the 
MitraClip Indications for Use. Randomization will be stratified by 
investigational site. 
Non-repairable Cohort: Subjects with valve anatomies appropriate for 
Tendyne TMVR but not suitable for TEER will be eligible to enroll in 
the Non-repairable cohort, in which all subjects will receive treatment 
with the Tendyne system. 

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05MAY2022 
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 ABT-CIP-10241 Rev. E  
Page 12 of 122 
 
 
 
 
SUMMIT 
 
Severe MAC Cohort: Subjects who have severe MAC resulting in 
symptomatic mitral valve disease (MR ≥ Grade III, or severe mitral 
stenosis (MS), or both moderate MR and moderate MS in the assessment 
of the Echocardiographic Core Laboratory) rendering the subject 
unsuitable for mitral valve surgery will be eligible to enroll in the MAC 
cohort, in which all subjects will receive treatment with the Tendyne 
system.  
Severe MAC Continued Access Plan (CAP) Cohort: After 
completion of enrollment in the Severe MAC cohort, up to 150 subjects 
(upon FDA approval) who have severe MAC rendering the subject 
unsuitable for mitral valve surgery may be eligible to enroll in the Severe 
MAC CAP Cohort, in which all subjects will receive treatment with the 
Tendyne system.  
Planned Sample 
Size / 
Investigational 
Sites 
Approximately 382 subjects will be included in the Randomized cohort, 
with approximately 191 subjects targeted to receive the investigational 
device, at up to 80 sites in United States, Canada, Europe, and Japan.  
In the Non-repairable cohort, approximately 325 subjects will be 
targeted to receive the investigational device. 
In the Severe MAC cohort, approximately 103 subjects will be targeted 
to receive the investigational device. 
Note: No site may enroll more than 20% of the total number of subjects 
in any cohort. 
Note: Up to 150 additional subjects (upon FDA approval) may be 
enrolled in the Severe MAC CAP Cohort 
Note: An additional 160 roll-in subjects (up to 2 per site) may be treated 
by operators without prior or recent experience using the Tendyne 
system to gain hands-on experience before registering subjects in a study 
cohort. 
Randomized Cohort - Primary Composite Endpoint (Non-Inferiority) 
Primary 
Composite 
Endpoint 
Freedom from all-cause mortality and heart failure hospitalization at 12 
months post index procedure 
Randomized Cohort – Secondary Endpoints 
Secondary 
Endpoints 
• Effectiveness: Freedom from MR > mild at 30 days post index 
procedure among survivors  
• Safety: Freedom from all-cause mortality and mitral valve 
reintervention at 12 months post index procedure 

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 ABT-CIP-10241 Rev. E  
Page 13 of 122 
 
 
 
 
SUMMIT 
 
• Improvement in Quality of Life (QoL), as measured by the Kansas 
City Cardiomyopathy Questionnaire (KCCQ) by at least 10 points 
at 12 months from baseline compared between treatment and 
control 
• Proportion of New York Heart Association (NYHA) Functional 
Classification I or II at 12 months compared between treatment and 
control 
• Improvement in distance walked on the 6 Minute Walk Test 
(6MWT distance or 6MWD) by at least 50 meters at 12 months 
from baseline compared between treatment and control 
Non-repairable Cohort - Primary Composite Endpoint (Performance goal) 
Primary 
Composite 
Endpoint 
Freedom from all-cause mortality and heart failure hospitalization at 12 
months post index procedure  
 
Non- repairable Cohort – Secondary Endpoints 
Secondary 
Endpoints 
• Change in Quality of Life (QoL), as measured by the Kansas City 
Cardiomyopathy Questionnaire (KCCQ) at 6 months and 12 months 
• Improvement of New York Heart Association (NYHA) Functional 
Classification I or II at 12 months 
• Change in distance walked on the 6 Minute Walk Test (6MWT 
distance or 6MWD) at 6 months and 12 months 
Severe MAC Cohort - Primary Endpoint (Performance goal) 
Primary Endpoint 
Freedom from all-cause mortality and heart failure hospitalization at 12 
months post index procedure 
Severe MAC Cohort - Secondary Endpoints (Performance goals) 
Secondary 
Endpoints 
• Freedom from MR > mild in severity at 30 days post index 
procedure among survivors 
• Change in Quality of Life (QoL), as measured by the Kansas City 
Cardiomyopathy Questionnaire (KCCQ) at 6 months and 12 months 
• Improvement of New York Heart Association (NYHA) Functional 
Classification I or II at 12 months 
• Change in distance walked on the 6 Minute Walk Test (6MWT 
distance or 6MWD) at 6 months and 12 months 
Severe MAC CAP Cohort - Primary Endpoint (Descriptive) 

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SUMMIT 
 
Primary Endpoint 
Freedom from all-cause mortality and heart failure hospitalization at 12 
months post index procedure 
Secondary 
Endpoints 
• Freedom from MR > mild in severity at 30 days post index 
procedure among survivors 
• Change in Quality of Life (QoL), as measured by the Kansas City 
Cardiomyopathy Questionnaire (KCCQ) at 6 months and 12 months 
• Improvement of New York Heart Association (NYHA) Functional 
Classification I or II at 12 months 
• Change in distance walked on the 6 Minute Walk Test (6MWT 
distance or 6MWD) at 6 months and 12 months 
Descriptive Endpoints – All cohorts 
Clinical Endpoints 
• All-cause mortality, CV hospitalizations, all stroke or MV 
reintervention or reoperation, at 2 years post index procedure and 
then yearly through 5 years 
• Change from baseline in distance walked on the 6MWT at each 
follow-up visit 
• Change from baseline in QoL, as measured by the KCCQ at each 
follow-up visit 
• Change from baseline in health outcomes, as measured by the EQ-
5D questionnaire, at each follow-up visit 
• Change from baseline in health outcomes, as measured by the 12-
item Short Form Health Survey (SF-12), at each follow-up visit 
• NYHA Functional Classification at each follow-up visit 
• Number of days alive and out of hospital from the time of the index 
procedure to 12 months, and then yearly through 5 years 
• Length of index hospitalization for procedure  
• Annualized rate of heart failure hospitalization 
• Change from baseline in BNP or NT pro-BNP levels, at all follow-
up visits 
• All-cause mortality at 30 days, 1 year, and then yearly through 5 
years 
MVARC 
Endpoints 
The following Mitral Valve Academic Research Consortium (MVARC) 
measures of success will be captured: 
• Technical Success (measured at exit from procedure room) 
• Device Success (measured at 30 days and at all later post-procedural 
intervals) 
• Procedural Success (measured at 30 days) 

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SUMMIT 
 
• Patient Success (measured at 12 months) 
Echocardiographic 
Endpoints 
The following echocardiographic endpoints, as adjudicated by the 
Echocardiography Core Laboratory, will be reported at baseline, 
discharge, 1 month, 6 months, 12 months, and then annually through 5 
years.  For continuous variables, change from baseline to each follow-
up will also be reported:  
• MR severity grade 
• Effective Regurgitant Orifice Area (EROA) 
• Regurgitant Volume 
• Regurgitant Fraction 
• Left Ventricle End Diastolic Volume (LVEDV) 
• Left Ventricular End Systolic Volume (LVESV) 
• Left Ventricular End Diastolic Dimension (LVEDD) 
• Left Ventricular End Systolic Dimension (LVESD) 
• Left Ventricular Ejection Fraction (LVEF) 
• Right Ventricular Systolic Pressure (RVSP) 
• Mitral Valve Area  
• Mean Mitral Valve Gradient 
• Mean Left Ventricular Outflow Tract Gradient 
• Cardiac Output  
• Forward Stroke Volume 
Subject Follow-up 
Subjects will be evaluated at the following trial 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 / End of Trial 

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SUMMIT 
 
Planned Duration 
of Trial 
Approximately 108 months.  This includes a 48-month recruitment 
period, with subject follow-up continuing for an additional 60 months. 
Trial 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. Symptomatic, moderate-to-severe or severe mitral regurgitation 
(MR ≥ Grade III per American Society of Echocardiography 
criteria), or severe mitral annular calcification (MAC), where a 
transcatheter therapy is deemed more appropriate than conventional 
mitral valve surgery by the local site heart team.  
Note: MR and MS severity must be determined by assessment of a 
qualifying 
transesophageal 
echocardiogram 
(TEE) 
and 
transthoracic echocardiogram (TTE), obtained within 120 days 
prior to subject consent, and must be confirmed by the 
Echocardiography Core Laboratory. 
Note: Patients with severe MAC must have symptomatic mitral 
valve disease associated with MR ≥ Grade III, or severe mitral 
stenosis (MS), or both moderate MR and moderate MS as assessed 
by the Echocardiography Core Laboratory. 
2. NYHA Functional Classification ≥ II (if Class IV, patient must be 
ambulatory). 
3. The local site heart team determines that the subject has been 
adequately treated per applicable standards for coronary artery 
disease (e.g., revascularization), left ventricular dysfunction (e.g., 
cardiac resynchronization therapy) and heart failure (e.g., GDMT).  
The SEC must concur that the subject has been adequately treated. 
4. The local site heart team and the SEC concur on the intended study 
cohort for the subject. 
Randomized cohort:   Eligibility for this cohort is limited to 
subjects where the local site heart team deems the mitral valve 
anatomy is suitable for TEER and are within approved MitraClip 
indications, which must be confirmed by experienced MitraClip 
operators from the SEC. Subjects with primary MR must be at 
prohibitive surgical risk, while subjects with secondary MR must be 
symptomatic 
despite 
maximally-tolerated 
guideline-directed 
medical therapy and meet the MitraClip Indications for Use.  
Non-repairable cohort:   Eligibility for this cohort is limited to 
subjects where the local site heart team deems the mitral valve 
anatomy is not suitable for TEER with MitraClip or does not meet 
MitraClip indications, which must be confirmed by experienced 
MitraClip operators from the SEC. 

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SUMMIT 
 
Severe MAC cohort: Eligibility for this cohort is limited to subjects 
where the local site heart team deems the degree of MAC renders 
the subject unsuitable for mitral valve surgery. 
Severe MAC CAP cohort: Eligibility for this cohort is identical to 
the pivotal SUMMIT Severe MAC cohort.   
5. Age 18 years or older at time of consent. 
6. Subject has been informed of the nature of the trial and agrees to its 
provisions, including the possibility of randomization to the Control 
group, complying with trial required testing, medications, and 
follow-up visits, and has provided written informed consent. 
Exclusion Criteria 
1. Mitral valvular vegetation or mass. 
2. Left Ventricle (LV) or Left Atrium (LA) thrombus. 
3. Chest condition that prevents transapical access. 
4. Left Ventricular Ejection Fraction (LVEF) less than 25% assessed 
by the site based on a TTE obtained within 120 days prior to subject 
consent. 
Note:  LVEF will be principally based on TTE and must be 
confirmed by the Echocardiography Core Laboratory. 
5. Left Ventricular End Diastolic Diameter (LVEDD) > 7.0 cm 
assessed by the site based on a TTE obtained within 120 days prior 
to subject consent. 
Note:  A qualifying LVEDD must be confirmed by the 
Echocardiography Core Laboratory. 
6. Prior surgical or interventional treatment of mitral valve involving 
implantation of prosthetic material (e.g. valve repair or 
replacement, or MitraClip). 
7. Mitral pathoanatomy and Left Ventricular Outflow Tract (LVOT) 
anatomy deemed not suitable for Tendyne transcatheter mitral valve 
implantation. 
8. Aortic valve disease requiring surgery or transcatheter intervention. 
9. Tricuspid valve disease requiring surgery or transcatheter 
intervention. 
10. Severe tricuspid regurgitation or severe right ventricular 
dysfunction. 
11. Any surgical or interventional procedure within the period of 60 
days prior to or planned procedure 60 days following subject 
registration.   
12. Implant or revision of Cardiac Resynchronization Therapy (CRT) 
device within 90 days prior to intended subject registration. 

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SUMMIT 
 
13. Myocardial Infarction (MI) within 30 days prior to intended subject 
registration. 
14. Symptomatic, unresolved multi-vessel or unprotected left main 
coronary artery disease (e.g., active ischemia) requiring stenting or 
Coronary Artery Bypass Grafting (CABG). 
15. Cerebrovascular accident (CVA) within 6 months prior to intended 
subject registration. 
16. Unresolved severe symptomatic carotid stenosis (> 70% by 
ultrasound).  
17. Cardiogenic shock or hemodynamic instability requiring inotropes 
or mechanical support devices at the time of planned implant 
procedure. 
18. Hypertrophic or restrictive cardiomyopathy, or constrictive 
pericarditis. 
19. Any 
of 
the 
following: 
 
leukopenia, 
acute 
anemia, 
thrombocytopenia, history of bleeding diathesis, or coagulopathy if 
cannot be adequately treated.  
20. History of endocarditis within 6 months of planned implant 
procedure. 
21. Active systemic infection requiring antibiotic therapy.  
22. Known hypersensitivity or contraindication to procedural or post-
procedural medications (e.g., contrast solution, anti-coagulation and 
antiplatelet therapy) that cannot be adequately managed medically. 
23. Subjects in whom TEE is contraindicated or high risk. 
24. Known hypersensitivity to nickel or titanium. 
25. Subject is undergoing hemodialysis due to chronic renal failure. 
26. 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. 
27. Subject has Chronic Obstructive Pulmonary Disease (COPD) 
requiring continuous home oxygen therapy or chronic outpatient 
oral steroid use. 
28. Subjects with non-cardiac comorbidities that are likely to result in 
a life expectancy of less than 12 months. 
29. Modified Rankin Scale ≥ 4 disability. 
30. Status 1 heart transplant or prior orthotopic heart transplantation. 
31. Pregnant, lactating, or planning pregnancy during the clinical 
investigation follow-up period. 
Note:  Female subjects of childbearing age should be instructed to 
use safe contraception (e.g. intrauterine devices, hormonal 

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SUMMIT 
 
contraceptives: contraceptive pills, implants, transdermal patches 
hormonal vaginal devices, injections with prolonged release). 
32. 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. 
33. Presence of other anatomic or comorbid conditions, or other 
medical, social, or psychological conditions that, in the 
investigator’s opinion, could limit the subject’s ability to participate 
in the clinical investigation or to comply with follow-up 
requirements, or impact the scientific soundness of the clinical 
investigation results.  

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1 
INTRODUCTION 
SUMMIT is a pre-market, interventional, pivotal investigation of the Tendyne Transcatheter 
Mitral Valve System. The objective of SUMMIT (Clinical Trial to Evaluate the Safety and 
Effectiveness of Using the Tendyne Transcatheter Mitral Valve System for the Treatment of 
Symptomatic Mitral Regurgitation) is to evaluate the safety and effectiveness of the Tendyne 
Transcatheter Mitral Valve System in eligible subjects with symptomatic, moderate-to-severe or 
severe mitral regurgitation (MR ≥ Grade III per American Society of Echocardiography criteria), 
or severe mitral annular calcification, where the site heart team deems a transcatheter approach is 
more appropriate than conventional mitral valve surgery. 
The SUMMIT Severe MAC Continued Access Plan (CAP) is an expansion of the SUMMIT 
pivotal study designed to collect additional safety and clinical effectiveness data on the Tendyne 
Transcatheter Mitral Valve System in patients with severe MAC following completion of 
enrollment of subjects in the primary analysis population of the severe MAC cohort. The Severe 
MAC CAP cohort will allow additional patients to enroll in SUMMIT after completion of 
enrollment in the pivotal cohort. Conduct of the Severe MAC CAP cohort will follow the same 
protocol outlined for the pivotal IDE trial. 
 
As the Sponsor, Abbott Medical (“Abbott”) has the overall responsibility for the conduct of the 
trial, including assurance that the trial will be performed according to this Clinical Investigation 
Plan (CIP) and U.S. Food and Drug Administration (FDA) and any other applicable country’s 
regulations.  The Sponsor will have direct and indirect responsibilities for day-to-day trial 
management and may delegate responsibilities for some trial management activities to a Contract 
Research Organization (CRO). 
This clinical investigation will be conducted in accordance with this CIP. All investigators 
involved in the conduct of the clinical investigation will be qualified by education, training, or 
experience to perform their tasks and this training will be documented appropriately.   
This CIP describes the requirements for the SUMMIT trial. 
2 
BACKGROUND INFORMATION 
2.1 
Background and Rationale 
2.1.1 Clinical Need  
Symptomatic, moderate-to severe and severe MR are associated with high morbidity and mortality 
[1]–[5].  This is particularly true of MR that results from myocardial dysfunction and adverse left 
ventricular (LV) remodeling (secondary or functional MR) [2]–[4], as opposed to MR arising from 
mitral leaflet pathology (primary or degenerative MR )[5]. Mitral annular calcification (MAC) is 
a degenerative process that can result in either mitral stenosis or MR, or a combination of both 
disorders. 
Although medical therapies, such as beta-blockers and inhibitors of the renin-angiotensin-
aldosterone pathways have been associated with reverse LV remodeling [6], and in some cases, a 
reduction in the severity of MR [7], the outlook for patients whose MR persists in spite of optimal 
medical therapy remains poor [2].  For these patients, surgical valve repair or replacement is an 

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SUMMIT 
 
option described in the current recommendations to guide management decisions [8]–[10]. 
Transcatheter mitral valve repair systems have also been evaluated for the treatment of MR. The 
most widely-used transcatheter mitral valve repair system is the MitraClip, which is based on the 
edge-to-edge repair technique [11]–[19]. However, to date, no transcatheter mitral valve 
implantation system is approved by the FDA for use, demonstrating a clinical need for additional 
transcatheter therapeutic options, in particular to treat patients with anatomies not suitable for 
transcatheter repair. 
2.1.2 Current Guidelines 
The American College of Cardiology/American Heart Association (ACC/AHA) have published 
guidelines for the management of valvular heart disease in 2017 [9], updated in 2020 [10].  
Recommendations for intervention in secondary MR are in Class IIa or IIb, are included in Table 
1. Note that management of patients with severe MAC is not addressed in the current guidelines. 
These patients do not have treatment options currently available except for continuation of medical 
care.  
Table 1.  ACC/AHA 2017 Recommendations for Secondary MR Intervention 
COR 
LOE  Recommendations 
Comment/Rationale 
IIa  
C 
Mitral valve surgery is reasonable for patients 
with chronic severe secondary MR (stages C 
and D) who are undergoing CABG or AVR. 
2014 recommendation remains 
current. 
IIa  
B-R 
It is reasonable to choose chordal-sparing 
MVR over downsized annuloplasty repair if 
operation 
is 
considered 
for 
severely 
symptomatic patients (NYHA class III to IV) 
with chronic severe ischemic MR (stage D) 
and persistent symptoms despite GDMT for 
HF [3], [4], [28]–[31], [20]–[27] 
NEW: An RCT has shown that 
mitral valve repair is associated 
with a higher rate of recurrence of 
moderate or severe MR than that 
associated with mitral valve 
replacement (MVR) in patients 
with 
severe, 
symptomatic, 
ischemic 
MR, 
without 
a 
difference in mortality rate at 2 
years’ follow-up. 
 
IIb  
B 
Mitral valve repair or replacement may be 
considered for severely symptomatic patients 
(NYHA class III to IV) with chronic severe 
secondary MR (stage D) who have persistent 
symptoms despite optimal GDMT for HF [3], 
[4], [30]–[32], [20]–[23], [26]–[29]. 
2014 recommendation remains 
current. 
IIb  
B-R 
In patients with chronic, moderate, ischemic 
MR (stage B) undergoing CABG, the 
usefulness of mitral valve repair is uncertain 
[32,33]. MODIFIED: LOE updated from C to 
B-R. 
The 
2014 
recommendation 
supported mitral valve repair in 
this group of patients. An RCT 
showed no clinical benefit of 
mitral repair in this population of 
patients, with increased risk of 
postoperative complications. 
The ACC/AHA recommendations are based on the following studies:  
In a randomized control trial (RCT) of surgical mitral valve repair versus MVR in 251 patients 
with severe ischemic MR (IMR), mortality rate at 2 years was 19.0% in the repair group and 23.2% 

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in the replacement group (p=0.39) [25]. There was no difference between repair and MVR in LV 
remodeling.  The rate of recurrence of moderate or severe MR over 2 years was higher in the repair 
group than in the replacement group (58.8% versus 3.8%, p<0.001), leading to a higher incidence 
of heart failure (HF) and repeat hospitalizations in the repair group.  The high mortality rate at 2 
years in both groups emphasizes the poor prognosis of secondary MR. 
The lack of apparent benefit of surgical valve repair over valve replacement in secondary MR 
versus primary MR highlights that primary and secondary MR are two different disease etiologies 
[4], [30]–[32], [20]–[27]. 
The most recent guidelines concluded that the best mitral valve intervention for chronic secondary 
MR (beyond guideline directed medical therapy and cardiac resynchronization therapy) is unclear 
due to the limited evidence in the published literature.  Consequently, there are no Class I 
recommendations for surgical mitral valve intervention (repair or replacement), and only a single 
IIa recommendation if surgical intervention is performed concomitant to other surgical 
interventions.  
If left untreated, however, secondary MR will likely progress due to the associated progressive LV 
systolic dysfunction and adverse remodeling.  Despite this, approximately half the patients with 
indications for correction of MR are not treated surgically due to advanced age, comorbidities, 
surgical contraindications, or a perception of low likelihood of benefit [33].  For these patients, 
less invasive transcatheter therapies have been evaluated as an adjunct to optimal medical therapy 
[34].  These therapies include strategies directed at leaflet repair [35], [36], annular reduction[37], 
or valve replacement[38]. 
As an alternative to conventional mitral valve surgery, two RCTs recently evaluated transcatheter 
mitral valve repair with the MitraClip system in conjunction with GDMT vs. GDMT alone in 
patients with secondary MR [39], [40]. The COAPT trial found a significant reduction in the 
annualized rate of all hospitalizations for heart failure within 24 months in the MitraClip + GDMT 
group vs. GDMT alone (35.8% per patient-year vs. 67.9% per patient-year) [39]. Additionally, 2-
year mortality was also significantly reduced in the MitraClip + GDMT group compared to GDMT 
control (29.1% vs. 46.1%), demonstrating that treating moderate-to-severe or severe secondary 
MR improves outcomes in patients with advanced heart failure. Unlike COAPT, the MITRA-FR 
trial failed to demonstrate any benefit over GDMT [40]. Differences in outcomes between these 
trials are likely due to differences in the patients enrolled, i.e., COAPT enrolled patients with more 
severe MR that was disproportionate to the degree of LV dilatation compared to MITRA-FR [41]. 
These two complementary trials indicate that patients with moderate-to-severe or severe secondary 
MR benefit from valvular intervention and associated reduction in MR severity. Based on the 
results of these trials, the FDA recently approved an expanded indication for the MitraClip system 
to include secondary MR. Subsequently, TEER was recently added as a Class IIa recommendation 
in the ACC/AHA guidelines for patients who have chronic severe secondary MR, persistent 
symptoms (NYHA class II, III or IV) while on GDMT, appropriate valvular anatomy, LVEF 
between 20% and 50%, LVESD ≤ 70 mm, and pulmonary artery systolic pressure ≤ 70 mmHg 
[10].  
Mitral stenosis (MS) is the most frequent valvular disorder caused by rheumatic fever [42]. While 
the prevalence of MS has overall decreased, rheumatic MS still accounts for approximately 10% 
of left-sided valve diseases in Europe, with a higher frequency observed in developing 

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countries[43], [44]. Interventional procedures are performed in over half of patients diagnosed 
with MS [43]. Recommendations for intervention in MS are in Class I, IIa or IIb, are included in 
Table 2. 
Table 2: ACC/AHA 2020 Recommendations for Mitral Stenosis Intervention 
COR 
LOE  Recommendations 
I 
A 
In symptomatic patients (NYHA class II, III, or IV) with severe 
rheumatic MS (mitral valve 
area ≤1.5 cm2, Stage D) and favorable valve 
morphology with less than moderate (2+) 
MR* in the absence of LA thrombus, percutaneous mitral balloon 
commissurotomy (PMBC) is recommended if it can be performed 
at a Comprehensive Valve Center 
I 
B-NR 
In severely symptomatic patients (NYHA class III or IV) with 
severe rheumatic MS (mitral valve area ≤1.5 cm2, Stage D) who 
1) are not candidates for PMBC, 2) have failed a previous PMBC, 
3) require other cardiac procedures, or 4) do not have access to 
PMBC, mitral valve surgery (repair, commissurotomy, or valve 
replacement) is indicated. 
IIa  
B-NR 
In asymptomatic patients with severe rheumatic MS (mitral valve 
area ≤1.5 cm2, Stage C) and favorable valve morphology with less 
than 2+ MR in the absence of LA thrombus who have elevated 
pulmonary pressures (pulmonary artery systolic pressure >50 
mm Hg), PMBC is reasonable if it can be performed at a 
Comprehensive Valve Center. 
IIb  
C-LD 
In asymptomatic patients with severe rheumatic MS (mitral valve 
area ≤1.5 cm2, Stage C) and favorable valve morphology with less 
than 2+/ MR* in the absence of LA thrombus who have new onset 
of AF, PMBC may be considered if it can be performed at a 
Comprehensive Valve Center. 
IIb 
C-LD 
In symptomatic patients (NYHA class II, III, or IV) with 
rheumatic MS and an mitral valve area >1.5 cm2, if there is 
evidence of hemodynamically significant rheumatic MS on the 
basis of a pulmonary artery wedge pressure >25 mm Hg or a 
mean mitral valve gradient >15 mm Hg during exercise, PMBC 
may be considered if it can be performed at a Comprehensive 
Valve Center. 
IIb 
B-NR 
In severely symptomatic patients (NYHA class III or IV) with 
severe rheumatic MS (mitral valve area ≤1.5 cm2, Stage D) who 
have a suboptimal valve anatomy and who are not candidates 
for surgery or are at high risk for surgery, PMBC may be 
considered if it can be performed at a Comprehensive Valve 
Center. 
 
Of patients receiving treatment for MS, over half of patients in developed nations undergo surgical 
valve replacement, which was attributed to more advanced valve deformities that could not be 
addressed with commissurotomy [43]. In such patients with significant valve deformation, if they 

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SUMMIT 
 
are unable to undergo surgery, a transcatheter mitral valve replacement (TMVR) may be the only 
option to effectively treat their valve disease. 
2.1.3 Barriers to Guideline Adherence 
Despite the existence of well-defined guidelines and the abundant literature that indicates the 10 
year survival rate for medically managed patients ranges from 20 to 60% [45]–[49], several studies 
have shown that guideline adherence is poor, and many patients go without recommended surgical 
treatment [33], [50]–[52].  
An evaluation of surgical interventions in the Euro Heart Survey showed that only 193 of 396 
(48.7%) patients with symptomatic, severe MR had a surgical valve procedure [33].  Multivariate 
analysis identified five factors that led to the decision not to operate: LV dysfunction, non-ischemic 
etiology, patient age, comorbidities, and grade 3 versus more severe grades of MR.   
Specifically, these data showed that patients with LVEF between 30 and 60% accounted for 53% 
of the population that did not receive surgery, despite this level of LV dysfunction being a Class I 
recommendation in both the ACC/AHA and European Society of Cardiology (ESC) / European 
Association for Cardio-Thoracic Surgery (EACTS) guidelines [33]. Of the patients who do 
undergo surgery, an analysis of the STS Adult Cardiac Surgery Database found that secondary MR 
accounts for only 4.3% of isolated mitral valve surgeries [53].  
Toledano et al. published on the results of a questionnaire mailed to all cardiologists in Canada to 
identify causes of non-compliance to the published guidelines [52].  They found that only 57% of 
responding cardiologists correctly identified that an LVEF of 50 to 60% should trigger a referral 
for surgery.   Further, only 16% would appropriately refer an NYHA Class II patient with severe 
MR and an LVEF >60%. Together, these studies demonstrate that mitral valve surgery is often not 
performed in the majority of patients with severe MR, motivating alternative treatment options. 
2.1.4 Treatment of Mitral Annular Calcification 
Patients with MAC are a unique subgroup of patients due to their marked increased surgical risk. 
In these patients, there is a high risk of atrioventricular groove disruption, a complication that is 
nearly universally fatal [54], [55]. 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 [56]. In addition, MAC is typically accompanied by severe morbidities that 
significantly increase surgical risk, such as coronary atherosclerosis, vascular disease, and renal 
failure. Operative mortality for patients with severe MAC at a single center was 9.3%, compared 
to 1.5% for other mitral procedures over the same time period [57]. 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 
technical refinements to the surgical procedure 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 [58]–[60]. 

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SUMMIT 
 
Transcatheter techniques for treatment of MAC using balloon-expandable aortic prostheses 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 designed for treatment of calcific aortic stenosis. 
In the largest registry of transcatheter implantation of valve prostheses for the treatment of MAC 
(n=116), initial technical success was achieved in 89 patients (76.7%) [61]. While this registry 
demonstrates the feasibility of employing balloon-expandable aortic prostheses in patients with 
MAC, there were significant procedure-related complications including valve embolization in 
4.3% of patients, left ventricular outflow tract obstruction with hemodynamic compromise in 
11.2%, conversion to open heart surgery in 3.4%, and valve embolization in 4.3%. MR was 
reduced to trace or none in 51 patients (62.2%), highlighting the challenge of effective MR 
elimination in anatomies with significant MAC. The 30-day mortality observed was 25%, with a 
1-year mortality of 53.7%. While these results represent an important advance in transcatheter 
therapies for patients not suitable for surgery, the rate of procedural complications and subsequent 
mortality observed in follow-up highlight the challenges of treating patients with severe MAC, 
motivating the study of novel transcatheter therapeutic options that may provide more effective 
MR reduction or an improved safety profile. 
2.1.5 Transcatheter Edge-to-Edge Mitral Valve Repair (TEER) 
Transcatheter mitral valve repair techniques have been developed with the aim of providing lower-
risk therapies to improve MR-related mortality and morbidity, and to expand treatment options for 
patients who are not good surgical candidates. The leading system for transcatheter mitral valve 
repair is the MitraClip, which performs edge-to-edge repair. The MitraClip device has been 
evaluated in multiple feasibility studies in various patient cohorts [13], [16], [18], [62], in RCTs 
against MV repair surgery [12], [15] and guideline-directed medical therapy (GDMT) [39], [40], 
and in several registry studies [36], [63]–[65]. Compared to conventional mitral valve surgery, 
MitraClip treatment was less effective at reducing mitral regurgitation; however, MitraClip 
treatment was associated with fewer major adverse events at 30 days, and demonstrated sustained 
improvements in quality of life and heart failure symptoms [12]. Registry data has also 
demonstrated that while transcatheter repair can be safely performed in patients at prohibitive 
surgical risk and result in significant MR reduction, rates of death and heart failure hospitalization 
following treatment with MitraClip remain higher in patients with secondary MR than primary 
MR [36]. 
The outcomes from the Cardiovascular Outcomes Assessment of the Percutaneous Therapy for 
Heart Failure Patients with Functional Mitral Regurgitation (COAPT) trial were recently published, 
which compared MitraClip + GDMT to GDMT alone in patients with moderate-to-severe or severe 
secondary MR [40]. The outcomes showed that MitraClip repair resulted in a significantly greater 
number of patients with sustained reduction of MR to Grade ≤ 2+ (p < 0.004), significantly 
improved quality of life (KCCQ; p <0.001) and functional capacity (NYHA Class I/II; p < 0.001) 
at 12-months compared to GDMT treatment alone. At 24 months of follow-up, the MitraClip group 
also had a lower rate of hospitalization for heart failure (p < 0.001), and lower mortality (p < 0.001) 
versus GDMT treatment alone. These outcomes strongly suggest that there is a significant clinical 
benefit from transcatheter intervention in patients with severe secondary MR who may not be 
candidates for surgery. 

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Although the MitraClip system has demonstrated good procedural safety and clinical benefit from 
MR reduction, there is a population of patients with cardiac anatomies that are not suitable for the 
MitraClip procedure. A recent publication from the Heart Valve Collaboratory identified specific 
criteria that render patients as unsuitable TEER [66].  For these patient populations who are not 
candidates for open heart surgery and not suitable for transcatheter repair, including those with 
severe MAC, a transcatheter mitral valve replacement system may be the only option for treating 
their mitral valve disease. 
2.1.6 Transcatheter Mitral Valve Replacement 
Transcatheter mitral valve replacement (TMVR) has recently emerged as an exciting new frontier 
in the field of cardiac structural interventions. Although transcatheter aortic valve replacement 
(TAVR) is a well-established treatment option for patients with symptomatic severe calcific aortic 
stenosis, the experience with transcatheter mitral valve implantation remains at an earlier stage.  
There have been important challenges in the development of this technology, including the 
complexity of the mitral valve anatomy involving a saddle-shaped elliptical annulus, the 
subvalvular apparatus, the interaction with the left ventricular outflow tract (LVOT) and the aortic 
valve, as well as the large size of TMVR devices and catheters for implantation [67]. 
Furthermore, the patients being considered for TMVR are usually high risk with multiple 
comorbidities, including frailty, pulmonary hypertension, or severe left ventricular systolic 
dysfunction, each of which negatively impact the overall clinical outcome.  Despite these technical, 
anatomic, and clinical limitations, there has been significant progress in recent years. 
2.1.7 Clinical Experience with the Tendyne Transcatheter Mitral Valve System 
The Expanded Clinical Study of the Tendyne Transcatheter Mitral Valve System (NCT02321514), 
prospectively evaluated the use of the Tendyne Transcatheter Mitral Valve System, deployed using 
a transapical approach without cardiopulmonary bypass, in patients with severe native valve MR.  
The results of the first 30 patients through 30-day follow-up as well as the results of the first 100 
patients through 1-year follow-up have been published in the Journal of the American College of 
Cardiology [68], [69].   
The first 100 patients were enrolled between November 2014 and November 2017 at 24 sites (3 in 
Australia, 8 in Europe, and 13 in the United States) [69].  The MR etiology for these patients was 
secondary or mixed in 89 subjects, and primary in 11. The Tendyne Transcatheter Mitral Valve 
System had a high implantation success rate (97%) and a low procedural adverse event rate, with 
no operative deaths, strokes, or conversions to open heart surgery. 
In two cases, a there was an attempted implant of the prosthesis, but the valve was ultimately 
retrieved and the patient did not receive an implant.  The first case was due to dynamic LVOT 
obstruction caused by systolic anterior motion (SAM) of the anterior mitral leaflet, with the other 
was due to the inability to seat the device in a stable position following an incorrect ventricular 
access site. 
TTE at one-month follow-up showed no more than trace residual MR in 98.8% of patients, and 
98.4% of patients having trace or less MR at one year, demonstrating sustained MR elimination.  
The majority (88.5%) of surviving patients reported mild or no symptoms at one-year follow-up 
(NYHA Class I or II). Improved quality of life was also observed, where 73.4% of surviving 
patients had >10-point improvement in their Kansas City Cardiomyopathy Questionnaire score.  

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The Tendyne Transcatheter Mitral Valve System has also been successfully implanted in nine 
patients with severe MAC under compassionate use [70]. Device implantation with complete relief 
of MR occurred in all patients, and there were no instances of device embolization, significant 
mitral stenosis, or need for cardiopulmonary bypass or hemodynamic support. Technical success 
was achieved in eight of the nine patients.  One patient without technical success had LVOT 
obstruction (peak gradient = 60 mmHg) due to inadvertent rotation of the prosthesis. While this 
patient had no residual MR, the LVOT obstruction was recognized only after surgical closure, and 
successful alcohol septal ablation (final peak LVOT gradient, 10 mmHg) was performed. Median 
follow-up for the study was 12.0 months (range, 1 to 28 months). One patient died in hospice on 
post-operative day 41. One patient, who had uncomplicated TMVR, normal prosthetic function, 
no recurrent MR, and no cardiac symptoms, committed suicide eight months after the procedure. 
All other patients survived to the end of follow-up.  MR remained absent in all treated patients. 
There was no evidence of prosthesis dysfunction, including no significant mitral stenosis (mean 
gradient, 3.4 ±1.8 mmHg), hemolysis, thrombosis, as well as no major adverse clinical events in 
follow-up. The positive experience in these patients motivated Abbott to develop a formal 
Feasibility Study of up to 30 patients that is ongoing in the US. Eleven patients were treated in this 
study, which is now closed for enrollment. To date, there has been one death within 30 days of the 
procedure in the combined compassionate use and MAC feasibility study experience (1/20, 5%). 
Though the current experience in patients with severe MAC is limited, these early outcomes 
compare extremely favorably to those reported with off-label use of balloon-expandable aortic 
prostheses in MAC, where 30-day mortality was 25% [61]. 
To date, Abbott has implanted more than 400 TMVR prostheses in the context of clinical trials, 
representing one of the largest datasets in this field.  The SUMMIT trial will continue to help 
define the role of TMVR in the array of management options for patients with symptomatic, 
moderate-to-severe or severe MR or severe MAC. 
2.1.8 Rationale for Conducting this Clinical Trial / Investigation 
The SUMMIT trial is designed to compare the Tendyne Transcatheter Mitral Valve System to the 
current standard of care for patients with mitral regurgitation.  The objective of this trial is to 
investigate whether this technology holds promise for the large number of patients suffering from 
the debilitating symptoms of moderate-to-severe or severe mitral regurgitation and compare the 
outcomes to TEER with the MitraClip system.  In addition, for patients who are not appropriate 
for mitral valve surgery and whose valve anatomy is not suitable for transcatheter repair or do not 
meet the MitraClip indications, including patients with severe MAC, the trial will offer the 
opportunity of treatment with the Tendyne system when patients are symptomatic in spite of 
pharmacologic management.  
Based on the results of the Expanded Clinical Study of the Tendyne Transcatheter Mitral Valve 
System, the majority of patients enrolled in the randomized cohort are expected to have secondary 
MR. Therefore, MitraClip is the appropriate comparative treatment for this trial due to the 
significant reduction in mortality and HF hospitalization demonstrated by COAPT compared to 
GDMT alone, as well as the lack of strong guideline recommendations for mitral valve surgery [9] 
and the low rate of surgical corrections performed [33], [50]–[52] for patients with secondary MR. 
The MitraClip system has demonstrated an excellent procedural safety profile [36], even in high-
risk surgical patients [19], [71]. However, certain patients indicated for MitraClip have cardiac 

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anatomies that are less likely to experience effective MR reduction with MitraClip. Recurrent MR 
>1+ at 12-month follow-up was observed in 31% of subjects studied in COAPT and in 38% of 
patients in the TVT registry [36], [39]. In comparison, <2% of patients treated with Tendyne had 
more than trace MR at 1 year of follow-up, demonstrating the consistent MR reduction achieved 
with transcatheter replacement compared to repair [69]. This study will examine if more effective 
MR elimination achieved via transcatheter replacement is associated with improved clinical 
outcomes despite the increased invasiveness of the procedure. The higher likelihood of detrimental, 
residual MR following MitraClip treatment supports clinical equipoise between Tendyne and 
MitraClip treatment, balancing the greater likelihood of MR elimination with the Tendyne system 
that is achieved by a more invasive transapical procedure. 
Additionally, the SUMMIT study will collect detailed clinical and anatomic data on patients in 
both the Randomized and Non-repairable cohorts. These data will be used to identify criteria 
predictive of outcomes for repair and replacement. Furthermore, these data will describe clinical 
and anatomic features used by the local site heart team to determine eligibility for either study 
cohort as part of the therapy selection process. 
Patients who are not appropriate for MV surgery and whose valve anatomy is deemed not suitable 
for transcatheter repair by the local site heart team have limited treatment options. Patients with 
severe MAC are included in this category, as severe MAC often precludes both surgical treatment 
and MitraClip implantation. For these patients, medical management is the only therapeutic option. 
These patients will undergo the Tendyne procedure in the Non-repairable and Severe MAC cohorts. 
Potential benefits of the use of the Tendyne device include, but may not be limited to, the 
following: 
• Reduction in hospitalization rate due to complete elimination of MR 
• Improved symptomatic status and quality of life  
• Reduced mortality 
• Reduced rates of recurrent MR 
• Mitral valve replacement with avoidance of risks associated with cardiopulmonary bypass 
(CPB) 
Early data obtained from the Expanded Clinical Study of the Tendyne Transcatheter Mitral Valve 
System demonstrated that patients experience (post-procedure) reductions in MR severity and 
heart failure symptoms, along with improvements in quality of life and functional capacity, with 
relatively low mortality and rehospitalization rates (Section 2.1.7). These clinical benefits were 
also observed in patients with severe MAC. In consideration of the potential benefits and the risk 
profile of the Tendyne device, this clinical trial is scientifically and clinically justified. 
2.1.9 Severe MAC CAP Rationale 
The rationale for the Severe MAC CAP is to allow current study implanters to maintain their 
technical proficiency in Tendyne device implantation in the Severe MAC population, and to 
continue to collect safety and effectiveness data in this patient population. Data from the Severe 
MAC CAP cohort may be used to support the Pre-Market Approval (PMA) application for the 
Tendyne Transcatheter Mitral Valve system in patients with severe MAC.  

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2.2 
Summary of Investigational Device 
2.2.1 Name of the Investigational Device 
The investigational device to be used in this trial is the Tendyne Transcatheter Mitral Valve System, 
which consists of the Tendyne Transcatheter Mitral Valve and an instrument set to facilitate 
placement of the valve.  In this CIP, the investigational device is referred to as the “Tendyne 
Transcatheter Mitral Valve System” or the “Tendyne device.”  
2.2.2 Intended Indication for Use 
The Tendyne Transcatheter Mitral Valve System is indicated for patients with symptomatic, 
moderate-to-severe or severe MR (MR ≥ Grade III per American Society of Echocardiography 
criteria), severe mitral stenosis, or both moderate MR and moderate MS, for whom a transcatheter 
therapy is deemed more appropriate than conventional mitral valve surgery by the local site heart 
team, whose valve and ventricular anatomies are suitable for Tendyne transcatheter mitral valve 
implantation and whose symptoms persist despite maximally-tolerated GDMT. 
2.2.3 Description of the Investigational Device (Tendyne Transcatheter Mitral Valve System) 
The Tendyne Transcatheter Mitral Valve System consists of the Tendyne Transcatheter Mitral 
Valve with Apical Pad and a Tendyne Transcatheter Mitral Valve Delivery System that facilitates 
placement of the valve. The Tendyne Transcatheter Mitral Valve is a bioprosthesis intended for 
transapical implantation within the native mitral valve. The valve includes two parts; a porcine 
pericardial bioprosthetic valve and an Apical Pad (connected by a braided tether). The valve has 
three porcine pericardial tissue leaflets sewn onto a circular, self-expanding frame made of nitinol. 
The inner frame is sewn inside a self-expanding nitinol outer frame. The outer frame helps orient 
the prosthesis inside the native mitral valve. There is a radiopaque marker at A1 that can be 
visualized under fluoroscopy to confirm orientation of the valve. The outer frame cuff is raised 
along the anterior aspect and is referred to as the A2 region. The valve is designed for radial 
orientation such that the anterior aspect of the cuff rests upon the aortomitral continuity. This 
orientation aligns the cuff with the anterior portion of the native mitral valve. 
The frame is covered with a PET (polyethylene terephthalate) fabric cuff that provides the sealing 
surface within the native annulus. The self-expanding prosthesis is connected to a braided fiber 
tether made of polyethylene, intended to stabilize the valve by passing through the left ventricular 
myocardium near the apex, where it is fastened to an Apical Pad on the epicardium. 
The Tendyne 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 perform adequately. 
The Tendyne valve is available in several sizes to accommodate differing cardiac anatomies. The 
valve size should be selected to provide proper fit for paravalvular sealing, device stability and 
LVOT area. Standard imaging techniques should be used to assess the native mitral valve 
dimensions and left ventricular dimensions for valve sizing. 
The Tendyne Transcatheter Mitral Valve Delivery System consists of a Tendyne Loading System, 
Tendyne Delivery System, and Tendyne Pad Positioning System. The Tendyne Retrieval System 
is also available to retrieve the valve intraoperatively, in the event the valve implant is suboptimal. 

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For a more detailed description of the Tendyne Transcatheter Mitral Valve System refer to the 
Instructions for Use (IFU). 
2.2.4 Procedures Involved in the Use of the Device 
 
The procedures outlined in the approved Tendyne Transcatheter Mitral Valve System IFU must 
be followed in the use of this device under this CIP. 
2.2.5 Training Required for the Use of the Device 
 
Investigators will be trained in accordance with the approved Tendyne Transcatheter 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 Transcatheter 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. 
2.2.6 Investigational Device Accountability 
The Sponsor is responsible for the availability and distribution of all investigational products.  
Product will only be distributed to trial sites when the Sponsor has provided written documentation 
of investigational site readiness.  The Sponsor will ship and/or hand-carry devices (the Tendyne 
device) to the Principal Investigator or his/her designee at each site, after sites receive 
documentation of site activation and shipping authorization is complete.  The Tendyne device must 
be stored according to the labeling and Instructions for Use in a secure location to prevent 
unauthorized access or use. 
The investigator, or designee, will maintain adequate records of the receipt and disposition of the 
investigational device, 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. The Sponsor requires clinical sites to store all investigational products according to the 
labeling and Instructions for Use in a secure area to prevent unauthorized access or use. Storage 
locations for the devices at investigational sites must be locked with access restricted to only the 
investigators and authorized personnel. All unused investigational devices must be returned to the 
Sponsor when trial 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. 
2.2.7 Description of the Control Group Device Used in the Randomized Cohort 
Subjects randomized to the Control group in the randomized cohort will receive TEER with the 
commercially-approved MitraClip system.  Prior to randomization, the anatomic suitability for 
using MitraClip will be initially proposed by the local site heart team with the final determination 
made by the SEC in order to ensure concordance with the recently published criteria by the Heart 
Valve Collaboratory [66]. 

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3 
TRIAL OBJECTIVES / ENDPOINTS 
The objective of the SUMMIT trial is to evaluate the safety and effectiveness of the Tendyne 
Transcatheter Mitral Valve System for the treatment of symptomatic, moderate-to-severe or severe 
mitral regurgitation, severe mitral stenosis, with or without severe MAC in subjects who are treated 
per standard of care and meet trial eligibility criteria. 
The Randomized, Non-Repairable and Severe-MAC cohorts each have one primary composite 
endpoint. The primary endpoint is the same across all 3 cohorts. The trial has several secondary 
safety, effectiveness and descriptive endpoints. 
3.1 
Primary Endpoints 
3.1.1 Primary Composite Endpoint - Randomized Cohort 
The primary composite endpoint is: freedom from all-cause mortality and heart failure 
hospitalization at 12 months post index procedure. The composite endpoint will evaluate whether 
the Tendyne device is non-inferior to TEER with MitraClip.   
3.1.2 Primary Composite Endpoint - Non-repairable Cohort 
The primary composite endpoint is: freedom from all-cause mortality and heart failure 
hospitalization at 12 months post index procedure.  The composite endpoint will be evaluated 
based on a performance goal.  
3.1.3 Primary Endpoint – Severe MAC Cohort 
The primary composite endpoint is: freedom from all-cause mortality and heart failure 
hospitalization at 12 months post index procedure. The composite endpoint will be evaluated based 
on a performance goal.   
3.1.4 Primary Endpoint – Severe MAC CAP Cohort  
The primary composite endpoint is: freedom from all-cause mortality and heart failure 
hospitalization at 12 months post index procedure. The endpoint will be descriptively summarized 
and compared to the results in the Severe MAC Cohort primary analysis population.   
 
3.2 
Secondary Endpoints - Randomized Cohort 
The following secondary endpoints will be evaluated: 
• Effectiveness: Freedom from MR > mild in severity at 30 days post index procedure among 
survivors (superiority) 
• Safety: Freedom from all-cause mortality and MV reintervention at 12 months (non-
inferiority) 
• Improvement in Quality of Life (QoL), as measured by the Kansas City Cardiomyopathy 
Questionnaire (KCCQ) by at least 10 points at 12 months from baseline 
• Proportion of New York Heart Association (NYHA) Functional Classification I or II at 12 
months 

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• Improvement in distance walked on the 6 Minute Walk Test (6MWT distance or 6MWD) 
by at least 50 meters at 12 months from baseline 
Additionally, if non-inferiority is demonstrated, superiority of Treatment over Control for the 
primary composite endpoint will also be tested. 
3.3 
Secondary Endpoints – Non-repairable Cohort 
The following secondary endpoints will be evaluated: 
• Change in QoL as measured by the KCCQ from baseline to 6 months and 12 months 
• Improvement of NYHA Functional Classification I and II at 12 months 
• Change in distance walked on the 6MWT from baseline to 6 months and 12 months 
3.4 
Secondary Endpoints – Severe MAC Cohort 
The following secondary endpoints will be evaluated: 
• Freedom from MR > mild in severity at 30 days post index procedure among survivors 
(performance goal) 
• Change in QoL as measured by the KCCQ from baseline to 6 months and 12 months 
• Change in proportion of NYHA Functional Classification I and II at 12 months 
• Change in distance walked on the 6MWT from baseline to 6 months and 12 months 
3.5 
Secondary Endpoints – Severe MAC CAP Cohort 
The following secondary endpoints will be evaluated descriptively: 
• Freedom from MR > mild in severity at 30 days post index procedure among survivors  
• Change in QoL as measured by the KCCQ from baseline to 6 months and 12 months 
• Change in proportion of NYHA Functional Classification I and II at 12 months 
• Change in distance walked on the 6MWT from baseline to 6 months and 12 months 
 
3.6 
Descriptive Endpoints – Randomized, Non-repairable, Severe MAC and Severe MAC 
CAP Cohorts 
3.6.1 Clinical Endpoints 
The following clinical endpoints will be reported: 
• All-cause mortality, CV hospitalizations, all stroke or MV reintervention or reoperation, at 
2 years post index procedure and then yearly through 5 years 
• Distance walked on the 6MWT at baseline, 30 days, 6 months, 12 months and then yearly 
through 5 years (change from baseline to follow-up). 
• KCCQ QoL scores at baseline, 30 days, 6 months, 12 months and then yearly through 5 
years (change from baseline to follow-up). 

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• EQ-5D index scores at baseline, 30 days, 6 months, 12 months and then yearly through 5 
years (change from baseline to follow-up). 
• SF-12 QoL scores at baseline, 30 days, 6 months, 12 months and then yearly through 5 
years (change from baseline to follow-up). 
• NYHA Functional Classification at baseline, 30 days, 6 months, 12 months and then yearly 
through 5 years. 
• Number of days alive and out of hospital from the time of index procedure to 12 months, 
and then yearly through 5 years. 
• Annualized rate of heart failure hospitalization 
• Change from baseline in BNP or NT pro-BNP levels, at all follow-up visits. 
• All-cause mortality at 30 days, 1 year, and then yearly through 5 years 
3.6.2 MVARC Endpoints 
The following MVARC endpoints will be captured for the Tendyne device and Control group in 
the Randomized, Non-repairable and Severe MAC cohorts (see Appendix II:  Definitions) [72]: 
• Technical Success 
• Device Success 
• Procedural Success 
• Patient Success 
3.6.3 Echocardiographic Endpoints 
The following echocardiographic data will be reported, as adjudicated by the Echocardiography 
Core Laboratory, at baseline, discharge, 1 month, 6 months, 12 months, and then yearly through 5 
years.  For continuous variables, change from baseline to each follow-up will also be reported:  
• MR severity grade 
• Effective Regurgitant Orifice Area 
• Regurgitant Volume 
• Regurgitant Fraction 
• Left Ventricle End Diastolic Volume 
• Left Ventricular End Systolic Volume 
• Left Ventricular End Diastolic Dimension 
• Left Ventricular End Systolic Dimension 
• Left Ventricular Ejection Fraction 
• Right Ventricular Systolic Pressure 
• Mitral Valve Area  
• Mean Mitral Valve Gradient 

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• Mean Left Ventricular Outflow Tract Gradient 
• Cardiac Output  
• Forward Stroke Volume 
3.6.4 Health Economic Data (U.S. Investigational Sites) 
During the course of the trial, the Sponsor (or third-party designee) will collect health economic 
data from investigational sites located in the United States.  This includes gathering information 
regarding hospitalizations for initial treatment and throughout the follow-up period.   The data 
collected may include billing information (provided as a UB-04 form or equivalent and itemized 
hospital bills, where applicable) for items such as hospital care, physician services, laboratory tests 
and diagnostic procedures.   
These data will be used as part of a dedicated health economic study in order to evaluate the cost-
effectiveness of alternative therapies for mitral valve disease and potentially to support coverage 
and reimbursement policy. All information collected for the purposes of the heath economic 
evaluation will be stored in a HIPAA-compliant secure database and will be appropriately de-
identified for analytic purposes.  
4 
TRIAL DESIGN, SCOPE AND DURATION 
4.1 
Trial Design 
SUMMIT is a pre-market, interventional, pivotal investigation of the Tendyne Transcatheter 
Mitral Valve System. This trial is a prospective, controlled, multicenter clinical investigation of 
the Tendyne Transcatheter Mitral Valve System for the treatment of symptomatic, moderate-to-
severe or severe mitral regurgitation or severe MAC, for whom the site heart team deems 
transcatheter treatment is more appropriate than conventional mitral valve surgery. The clinical 
investigation has been designed to involve as little pain, discomfort, fear, and any other foreseeable 
risk as possible for subjects. Refer to the Risk Analysis section of this clinical investigation plan 
for details. Figure 1 provides an overview of the SUMMIT trial design. 
 

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SUMMIT 
 
    
  
Figure 1. SUMMIT Trial Design 
Participating sites may initially propose the study cohorts in accordance with the trial content. The 
final determination of the study cohorts will be made by the SEC.  Subjects must satisfy the trial 
inclusion/exclusion criteria and be approved by the SEC, prior to inclusion in the trial.  
Randomized cohort: Subjects suitable for TMVR with Tendyne and indicated for TEER with the 
MitraClip will be randomized in a 1:1 ratio to receive either Tendyne (Treatment) or MitraClip 
(Control). Subjects with primary MR must be at prohibitive surgical risk, while subjects with 
secondary MR must be symptomatic despite maximally-tolerated guideline-directed medical 
therapy in accordance with the MitraClip Indications for Use. Randomization will be stratified by 
investigational site. See Appendix X for the FDA-approved MitraClip indication for use. 
Non-repairable cohort: Subjects with valve anatomies appropriate for Tendyne TMVR but not 
suitable for TEER will be eligible to enroll in the Non-repairable cohort, in which all subjects will 
receive treatment with the Tendyne system.  
Severe MAC cohort: Subjects who have severe MAC rendering the subject unsuitable for mitral 
valve surgery will be eligible to enroll in the Severe MAC cohort, in which all subjects will receive 
treatment with the Tendyne system. 
Severe MAC CAP cohort: After completion of enrollment in the Severe MAC Cohort, up to an 
additional 150 subjects (upon FDA approval) with severe MAC rendering the subject unsuitable 
for mitral valve surgery may enroll in the Severe MAC CAP cohort, in which all subjects will 
receive treatment with the Tendyne system.   
A recent publication from the Heart Valve Collaboratory (HVC, which includes the FDA, 
academic leaders, and industry representatives) has identified specific criteria that render potential 

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SUMMIT 
 
subjects as unsuitable for MitraClip™ [66]. Only subjects satisfying these criteria are eligible for 
enrollment into the non-randomized (Non-Repairable and Severe MAC) cohorts. The SUMMIT 
SEC will ensure that MitraClip suitability is evaluated in concordance with the guidance published 
by the HVC. The HVC criteria for MitraClip non-suitability described by Lim et al. is outlined in 
Appendix VIII. 
4.2 
Number of Subjects to be Registered 
This trial will enroll male and female subjects who satisfy the inclusion and exclusion criteria and 
provide written informed consent.  Investigational sites will attempt to recruit consecutive subjects 
who must meet all eligibility criteria.  Subjects are considered registered for the SUMMIT trial 
upon Tendyne procedure attempt (subjects in the Non-repairable and Severe MAC cohorts) or 
upon randomization (subjects in the Randomized cohort).   
This trial will register approximately 382 subjects within the Randomized cohort, approximately 
325 subjects within the Non-repairable cohort, and approximately 103 subjects in the Severe MAC 
cohorts, at up to 80 investigational sites in the U.S., Canada, Europe and Japan. No site may enroll 
more than 20% of the total number of subjects in any cohort.  
Up to an additional 160 roll-in subjects may be treated by operators without recent or prior 
experience with the Tendyne device to gain hands-on experience before registering subjects in the 
trial cohorts (see Section 6.1.1 Roll-in Subjects for further details).  Once the site completes the 
roll-in phase, all subsequent subjects must be registered in either the Randomized, Non-repairable 
or Severe MAC cohorts.  Roll-in subjects will not count toward the subject caps in the Randomized 
(382 subjects), Non-repairable (325 subjects) or MAC (103 subjects) cohorts. Additionally, 
subjects enrolled in the Non-randomized cohort prior to publication of the criteria by Lim et al. 
will be re-evaluated by the SEC to determine if they satisfy the revised criteria for the Non-
repairable cohort [66]. Any subject who does not satisfy the revised criteria by Lim et al. will be 
excluded from the Non-repairable cohort for analysis. Subjects who are excluded in this regard 
from the primary analysis population will be followed-up as per the protocol through 60 months 
and reported separately. It is anticipated that less than 20% of the approximately 95 subjects 
enrolled will be excluded (<20 subjects). 
4.3 
Expected Duration of the Clinical Investigation 
The total duration of the trial is estimated as 108 months.  This includes a 48-month subject 
recruitment 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, 
12 months, and annually thereafter through 60 months (see Table 3 for visit windows).  When all 
registered subjects have been followed for 60 months, or have exited the trial, the trial will be 
closed. 
 
4.4 
Number of Subjects and Expected Duration of the Severe MAC CAP Cohort 
Enrollment in the Severe MAC CAP cohort will be initiated following completion of enrollment 
of the Severe MAC Cohort. The Severe MAC CAP cohort is anticipated to have a 24-month 
enrollment duration, which is based on a 12-month follow-up requirement for the primary analysis 
of the Severe MAC cohort followed by a 12-month duration for PMA submission and review.  

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SUMMIT 
 
 
Subjects will have required follow-up evaluations at pre-discharge, 30 days, 3 months, 6 months, 
12 months, and annually thereafter through 60 months (see Table 3 for visit windows).  When all 
registered subjects have been followed for 60 months, or have exited the trial, the Severe MAC 
CAP will be closed. 
 
4.5 
Enrollment of Traditionally Underrepresented Demographic Subgroups 
Historically, specific demographic subgroups such as women and racial or ethnic minorities have 
been under-represented in or excluded from many clinical trials.  This has led to a lack of 
information on these subgroups for many medical treatments.  Therefore, it is important to ensure 
there is an adequate representation of such demographic subgroups and to assess if there is a 
difference in treatment response between these subgroups.   
The Sponsor intends to implement FDA's guidance on the evaluation of sex-specific data in 
medical device clinical studies [73], to ensure adequate representation of women and other 
traditionally under-represented demographic subgroups in the SUMMIT trial. 
As noted in the guidance, some barriers to participation of women and ethnic minorities in clinical 
investigations have traditionally been: 
• Lack of understanding about main obstacles to participation of such subgroups in clinical 
research  
• Inclusion/exclusion criteria potentially not needed to define the clinical investigation 
population may unintentionally exclude specific subgroups  
• Under diagnosis of disease etiologies and pathophysiology leading to under referral of 
demographic subgroups  
• Avoidance of specific subgroups by investigators and Sponsors due to the perception that 
it takes more time and resources to recruit them  
• Fear of fetal consequences (for female participants)  
• Family responsibilities limiting women's ability to commit time for follow-up requirements 
The Sponsor will take steps, including the following, to ensure adequate representation of women 
and racial or ethnic minorities in this clinical investigation:  
• The Sponsor will approach sites without bias or consideration for specific demographic 
subgroups  
• The Sponsor will have informed consent materials in alternative languages at the request 
of the site    
4.5.1 Prevalence of Valvular Heart Disease, Diagnosis and Treatment Patterns 
Population-based studies demonstrate no difference in the prevalence of valvular heart disease in 
men and women and that the population is diverse (40% black, 59% white, and 1% other) [74], 
[75].  These studies also report that in the community setting, women are diagnosed with valvular 
heart disease less often than men. 

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In another study, which looks at data from the STS database between the years 2000 and 2007, 
women and men had a nearly equal representation for having mitral valve surgery.  However, 
women underwent mitral valve replacement at a higher rate than men (65% women; 35% men) 
and mitral valve repair at a lower rate than men (44% women; 56% men) [76]. An additional study 
of the TVT registry data between October 2013 and September 2015 identified 2,952 patients 
treated with the MitraClip system, of which 55.8% were male, demonstrating similar rates of 
transcatheter mitral interventions between genders [36]. 
4.5.2 Representation of Underrepresented Demographic Subgroups 
The traditional barriers to enrollment of women (such as fear of fetal consequences, family 
responsibilities that may limit the ability for time commitment to trial follow-up) are not expected 
to occur in this trial.  Furthermore, valvular heart disease is also prevalent in traditionally 
underrepresented non-white subgroups.   
In the Tendyne CE Mark Study, which was a global study that enrolled throughout Europe, the 
U.S. and Australia, women represent 31% (31/100) and non-whites represent 5% (5/100) of treated 
subjects.  As the SUMMIT trial will primarily enroll subjects in the U.S., which has a diverse 
population, a high proportion of non-white subjects are expected to enroll.  Furthermore, the 
Sponsor will take the following actions in this trial: 
• Provide training to investigational site personnel to ensure adequate representation of these 
demographic subgroups.  
• Regularly review enrollment/registration demographics to investigate whether there is 
under-representation of these subgroups.  
• Regularly review withdrawal rates for under-represented subgroups and compare these 
rates to the overall trial population. 
• Select sites that have experience performing mitral valve surgery and transcatheter mitral 
valve repair without consideration for racial or ethnic minorities.  
• Provide informed consent materials in alternative languages and will work with sites and 
IRBs/ECs on recruitment materials. 
• As appropriate and necessary, re-train sites on the importance of recruiting and retaining 
subjects in the trial. 
4.5.3 Subgroup Analysis for Underrepresented Demographic Subgroups 
The Statistical Analysis Plan (SAP) pre-specifies analyses to assess heterogeneity of safety and 
effectiveness endpoints across demographic subgroups.  
5 
SUBJECT SELECTION AND WITHDRAWAL   
5.1 
Subject Screening and Informed Consent 
This clinical investigation will enroll male and female subjects with symptomatic, moderate-to-
severe or severe mitral regurgitation (MR; MR ≥ Grade III per American Society of 
Echocardiography criteria), or severe mitral annular calcification. Subjects must meet all eligibility 
criteria and provide written informed consent prior to conducting any investigation-specific 
procedures not considered standard of care. A patient who does not satisfy all general eligibility 

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SUMMIT 
 
criteria prior to informed consent is considered a recruitment failure and should not be enrolled in 
the clinical investigation. 
The Investigator or his/her authorized designee (if applicable) will conduct the Informed Consent 
process, as required by applicable regulations and the center’s IRB/EC. This process will include 
a verbal discussion with the subject on all aspects of the clinical investigation that are relevant to 
the subject’s decision to participate, such as details of clinical investigation procedures, anticipated 
benefits, and potential risks of clinical investigation participation. Subjects must be informed about 
their right to withdraw from the clinical investigation at any time and for any reason without 
sanction, penalty or loss of benefits to which the subject is otherwise entitled. Withdrawal from 
the clinical investigation will not jeopardize their future medical care or relationship with the 
investigator.  
During the discussion, the Principal Investigator or his/her authorized designee will avoid any 
improper influence on the subject and will respect subject’s legal rights. Financial incentives will 
not be given to the subject. Subjects may be compensated for time and travel directly related to the 
participation in the clinical investigation. The subject shall be provided with the Informed Consent 
form written in a language that is understandable to the subject and has been approved by the 
center’s IRB/EC. The subject shall have adequate time to review, ask questions, and consider 
participation. The Principal Investigator or his/her authorized designee will make efforts to ensure 
that the subject understands the information provided. If the subject agrees to participate, the 
Informed Consent form must be signed and dated by the subject and thereafter by the person 
obtaining the consent prior to any clinical investigation-specific procedures. The signed original 
will be filed in the subject’s hospital or research charts, and a copy will be provided to the subject. 
The dated signatures can be electronic. The site will follow local hospital and local EC/IRB 
provisions for documenting electronic ICF signature 
Failure to obtain informed consent from a subject prior to clinical investigation enrollment should 
be reported to Sponsor within 5 working days and to the reviewing center’s IRB/EC according to 
the IRB’s/ EC’s reporting requirements. 
If, during the clinical investigation, new information becomes available that can significantly 
affect a subject’s future health and medical care, the Principal Investigator or his/her authorized 
designee (if applicable) will provide this information to the subject. If relevant, the subject will be 
asked to confirm their continuing informed consent in writing. 
All subjects must be screened by the site’s investigator and clinical research staff, who have been 
trained to the CIP and delegated to screen subjects, to determine if the potential subject is eligible 
for trial registration.  Subjects will be assigned a unique subject identifier through the electronic 
data capture (EDC) system. All consented subjects considered for the trial must be reported to the 
Sponsor on a frequent basis during the trial registration period.  The result of the subject screening 
process should be documented within the baseline screening eCRF to include: whether the subject 
met eligibility criteria (and if not, which eligibility criteria were not met) and whether the subject 
was subsequently registered (and if not, the reason for not registering).   
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 trial, potential risks and benefits of participation, and 
answer questions from potential subjects.  All subjects must sign and date the IRB/EC approved 

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SUMMIT 
 
ICF prior to any clinical trial-specific procedures. Subjects who are not subsequently registered 
will be withdrawn from the clinical investigation.   
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 subject has provided informed consent.  
For sites in the United States, 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. 
For live cases at congresses, subjects need to sign a specific Live Case ICF, approved by the 
IRB/EC and by the Sponsor, as well as by the applicable regulatory/competent authorities (e.g., 
U.S. FDA, Health Canada).  The investigator must request the Sponsor approval prior to 
performing a Live Case. 
5.1.1 Special Circumstances for Informed Consent 
Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or 
individuals without legal authority, are excluded from the study population. Individuals under the 
age of 18 or age of legal consent are excluded from the study population. Pregnant or breastfeeding 
women are excluded from the study population. 
Individuals unable to read or write may be enrolled in this clinical investigation. Informed 
consent will be obtained through a supervised oral process. An independent witness will be 
present throughout the Informed Consent process. The written Informed Consent form and any 
other information will be read aloud and explained to the prospective subject or his/her legally 
acceptable representative and either will sign and personally date the Informed Consent form. 
The witness will also sign and personally date the Informed Consent form attesting that the 
information was accurately explained and that informed consent was freely given. 
5.1.2 Enrollment of Medicare Beneficiaries (U.S. Subjects Only) 
This clinical investigation will enroll appropriate Medicare beneficiaries that qualify based on the 
inclusion and exclusion criteria set forth in the trial. 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 17) 
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.  

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 ABT-CIP-10241 Rev. E  
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SUMMIT 
 
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.  
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 has consented to participate in the trial.  
Subjects must meet all of the inclusion criteria to be considered for the clinical trial.  If any of the 
exclusion criteria are met, the subject is excluded from the clinical trial and cannot be registered. 
If subjects are registered into the clinical investigation and are later found to have met exclusion 
criteria or not all inclusion criteria, these subjects will continue follow-up in the clinical 
investigation and will be included in the analysis population. 
Note: Roll-in subjects must also meet the eligibility criteria listed below. 
5.2.2 Inclusion Criteria 
Subjects must meet all of the following inclusion criteria to participate in the trial: 
1. Symptomatic, moderate-to-severe or severe mitral regurgitation (MR ≥ Grade III per 
American Society of Echocardiography criteria), or severe mitral annular calcification 
(MAC), where a transcatheter therapy is deemed more appropriate than open surgery by 
the local site heart team.  
Note: MR and MS severity must be determined by assessment of a qualifying 
transesophageal echocardiogram (TEE) and transthoracic echocardiogram (TTE), obtained 
within 120 days prior to subject consent, and must be confirmed by the Echocardiography 
Core Laboratory. 
Note: Patients with severe MAC must have symptomatic mitral valve disease associated 
with MR≥ Grade III, or severe mitral stenosis (MS), or both moderate MR and moderate 
MS as assessed by the Echocardiography Core Laboratory. 
2. NYHA Functional Classification ≥ II (if Class IV, patient must be ambulatory). 
3. The local site heart team determines that the subject has been adequately treated per 
applicable standards for coronary artery disease (e.g., revascularization), left ventricular 
dysfunction (e.g., cardiac resynchronization therapy) and heart failure (e.g., GDMT).  The 
SEC must concur that the subject has been adequately treated. 
4. The local site heart team and the SEC concur on the intended study cohort for the subject. 
Randomized cohort:   Eligibility for this cohort is limited to subjects where the local site 
heart team deems the mitral valve anatomy is suitable for TEER and are within approved 
MitraClip indications, which must be confirmed by experienced MitraClip operators within 
the SEC. Subjects with primary MR must be at prohibitive surgical risk, while subjects 
with secondary MR must be symptomatic despite maximally-tolerated guideline-directed 
medical therapy and meet the MitraClip Indications for Use.  
Non-repairable cohort:   Eligibility for this cohort is limited to subjects where the local 
site heart team deems the mitral valve anatomy is not suitable for TEER with MitraClip or 
does not meet MitraClip indications, which must be confirmed by experienced MitraClip 
operators from the SEC. 

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Severe MAC cohort: Eligibility for this cohort is limited to subjects where the local site 
heart team deems the degree of MAC renders the subject unsuitable for mitral valve surgery. 
Severe MAC CAP cohort: Eligibility for this cohort is identical to the original Severe 
MAC cohort.   
5. Age 18 years or older at time of consent.  
6. Subject has been informed of the nature of the trial and agrees to its provisions, including 
the possibility of randomization to the Control group, complying with trial required testing, 
medications, and follow-up visits, and has provided written informed consent. 
5.2.3 Exclusion Criteria 
Subjects must not meet any of the following exclusion criteria to participate in the trial: 
1. Mitral valvular vegetation or mass. 
2. Left Ventricle or Left Atrium thrombus. 
3. Chest condition that prevents transapical access. 
4. LVEF less than 25% assessed by the site based on a TTE obtained within 120 days prior 
to subject consent. 
Note: LVEF will be principally based on TTE and confirmed by the Echocardiography 
Core Laboratory. 
5. LVEDD > 7.0 cm assessed by the site based on a TTE obtained within 120 days prior to 
subject consent. 
Note:  A qualifying LVEDD must be confirmed by the Echocardiography Core Laboratory. 
6. Prior surgical or interventional treatment of mitral valve involving implantation of 
prosthetic material (e.g. valve repair or replacement, or MitraClip). 
7. Mitral pathoanatomy and LVOT anatomy deemed not suitable for Tendyne transcatheter 
mitral valve implantation. 
8. Aortic valve disease requiring surgery or transcatheter intervention. 
9. Tricuspid valve disease requiring surgery or transcatheter intervention. 
10. Severe tricuspid regurgitation or severe right ventricular dysfunction. 
11. Any surgical or interventional procedure within the period of 60 days prior to or planned 
procedure 60 days following subject registration. 
12. Implant or revision of CRT device within 90 days prior to intended subject registration. 
13. Myocardial infarction within 30 days prior to intended subject registration. 
14. Symptomatic, unresolved multi-vessel or unprotected left main coronary artery disease 
(e.g., active ischemia) requiring stenting or CABG. 
15. CVA within 6 months prior to intended subject registration. 
16. Unresolved severe symptomatic carotid stenosis (> 70% by ultrasound). 

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SUMMIT 
 
17. Cardiogenic shock or hemodynamic instability requiring inotropes or mechanical support 
devices at the time of planned implant procedure. 
18. Hypertrophic or restrictive cardiomyopathy, or constrictive pericarditis. 
19. Any of the following:  leukopenia, acute anemia, thrombocytopenia, history of bleeding 
diathesis, or coagulopathy if cannot be adequately treated. 
20. History of endocarditis within 6 months of planned implant procedure. 
21. Active systemic infection requiring antibiotic therapy. 
22. Known hypersensitivity or contraindication to procedural or post-procedural medications 
(e.g., contrast solution, anti-coagulation or antiplatelet therapy) that cannot be adequately 
managed medically. 
23. Subjects in whom TEE is contraindicated or high risk. 
24. Known hypersensitivity to nickel or titanium. 
25. Subject is undergoing hemodialysis due to chronic renal failure. 
26. 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. 
27. Subject has COPD requiring continuous home oxygen therapy or chronic outpatient oral 
steroid use. 
28. Subjects with non-cardiac comorbidities that are likely to result in a life expectancy of less 
than 12 months. 
29. Modified Rankin Scale ≥ 4 disability. 
30. Status 1 heart transplant or prior orthotopic heart transplantation. 
31. Pregnant, lactating, or planning pregnancy during the clinical investigation follow-up 
period. 
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). 
32. 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. 
33. Presence of other anatomic or comorbid conditions, or other medical, social, or 
psychological conditions that, in the investigator’s opinion, could limit the subject’s ability 
to participate in the clinical investigation or to comply with follow-up requirements, or 
impact the scientific soundness of the clinical investigation results.  

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5.3 
Subject Selection 
Subjects in this trial must have symptomatic, moderate-to-severe or severe mitral regurgitation or 
severe MAC.  Subjects must be treated per standard of care, meet trial eligibility criteria, and 
have been assessed by the local site heart team for suitability for mitral valve surgery (see 
Section 6 - Subject Screening and Randomization).  Several mechanisms will be employed in 
this trial to ensure appropriate subjects are registered in the trial:  
• Subjects will be selected for inclusion in the SUMMIT trial by a multidisciplinary team at 
each investigational site involving interventional cardiology, cardiac surgery, imaging 
(echocardiography and CT) and heart failure personnel, as appropriate. 
• All imaging (TEE, TTE, and Cardiac CT) will be submitted to the Sponsor and assessed 
by independent Echocardiography/CT Core Laboratories.  The Sponsor (or imaging core 
laboratory) may provide echocardiographic and/or cardiac CT training/guidance to sites 
and assist in the review of screening images to ensure conformance to trial eligibility 
requirements.   
• The SEC must concur with the local site heart team that subjects have been treated per 
standard of care, meet trial eligibility criteria, and can be treated in the Randomized, 
Non-repairable, Severe MAC or Severe MAC CAP cohorts of the trial (see Section 
12.11.2 -  Subject Eligibility Committee for more details). 
5.4 
Subject Registration 
Subjects are enrolled in the trial upon providing written informed consent.  For the Randomized 
cohort, subjects will be considered registered in the trial at the time of subject randomization. Sites 
may not register more than 20% of the total of 382 subjects in the randomized cohort. 
For the Non-repairable, Severe MAC and Severe MAC CAP cohorts, subjects are considered 
registered in the trial upon Tendyne procedure attempt (initial incision for the Tendyne procedure).  
Sites may not register more than 20% of the total subjects in the Non-repairable (325) or Severe 
MAC (103) cohorts.   
There is no minimum number of subjects to be registered at any site.   
5.5 
Subject Discontinuation 
Each registered subject shall remain in the trial until completion of the required follow-up period, 
however, a subject’s participation in any clinical trial 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  5.6 - Early Termination of the 
Clinical Trial 

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SUMMIT 
 
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/EC as 
defined by their institution’s procedure(s).  
No additional follow–up will be required or data recorded from subjects once withdrawn from the 
trial, except for the status (deceased/alive), which will be obtained from the Social Security Death 
Index. 
However, if a subject withdraws from the trial due to problems related to the safety or effectiveness 
of the investigational device, the investigator shall ask for the subject's permission to follow his/her 
status/condition outside of the clinical investigation. 
In case of subject withdrawal of consent, the site should make attempts to schedule the subject for 
a final clinical investigation visit. At this final follow-up visit, the subject will undergo the 
following assessments: 
• Transthoracic echocardiogram 
• Six-minute walk test 
• Kansas City Cardiomyopathy Questionnaire 
• Any assessments required to complete the Follow Up eCRF 
• Any assessments required to complete the Adverse Event or Device Deficiency eCRFs, if 
applicable 
5.5.1 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 shall be recorded in the source documentation, 
including date, time and initials of site personnel trying to make contact. 
• If these attempts are unsuccessful, a letter (certified if applicable) will 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-trial cardiologist or relative will be 
considered subject contact for the purpose of collecting vital status information. The center 
shall retain records of the contact. 
5.6 
Early Termination of the Clinical Trial 
No formal statistical rule for early termination of the trial for insufficient effectiveness of the 
investigational device is defined.  

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SUMMIT 
 
The Sponsor reserves the right to discontinue the clinical trial/investigation at any stage or reduce 
the follow up period with suitable written notice to the investigators. 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 and Safety Monitoring Board and Steering Committee 
decision to terminate the trial  
• Further product development is cancelled 
• Decision by a regulatory body   
Should the clinical trial be discontinued by the Sponsor, subjects will be followed per routine 
hospital practice, with device-related SAEs being reported to the Sponsor as per 
vigilance/commercial reporting requirements. The investigator shall return all clinical 
trial/investigational materials (including devices) to the Sponsor, and provide written notification 
to the overseeing IRB/EC (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.  
A Principal Investigator, IRB/EC or regulatory authority may suspend or prematurely terminate 
participation in the clinical investigation at the investigational site(s) for which they are responsible. 
The investigators will follow the requirements specified in the Clinical Trial Agreement.  
If the Sponsor suspends or prematurely terminates the clinical investigation at an individual site in 
the interest of safety, the Sponsor will inform all other Principal Investigators. 
If suspension or premature termination occurs, the Sponsor will remain responsible for providing 
resources to fulfill the obligations from the CIP and existing agreements for following the subjects 
enrolled in the clinical investigation, and the Principal Investigator or authorized designee will 
promptly inform the enrolled subjects at his/her site, if appropriate.  Details for such subjects 
follow up will be provided. The investigator will be requested to return all clinical investigation 
materials (including devices) to the Sponsor and provide a written statement to the IRB/EC. 
If a suspended investigation is to be resumed, approval will be obtained from the EC/IRB and a 
notification should be sent to the regulatory body or bodies, as applicable, and if subjects were 
informed of suspension, they shall be informed of the resumption of the clinical investigation. 
5.7 
Trial Completion 
The trial will be completed when all roll-in and registered subjects have either completed a 5-year 
follow-up visit, have reached a clinical outcome or have withdrawn from the trial.  Upon trial 
completion, the Sponsor and/or its designees will notify the sites and perform trial closeout visits.  
All unused devices and any unused trial 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.   

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Other items that will be reviewed during the trial closeout visit may include: discussing record 
retention requirements, device accountability, the possibility of site audits, publication policy, and 
notifying the IRB/EC of trial closure. 
Upon completion of the clinical investigation, specific follow-up (regardless of how follow-up was 
completed, e.g. withdrawal, completion of scheduled follow-ups), subjects should be followed per 
standard of care for subjects with symptomatic mitral valve disease. Previous participation in this 
investigation does not require subjects to have any unique follow-up requirements once 
participation is complete. Investigational device traceability and identification requirements for 
such follow-up are the same as for commercially approved implants. 
6 
SUBJECT SCREENING AND RANDOMIZATION 
Potential patients presenting at the clinical sites will be fully informed about the clinical 
investigation, following the established Informed Consent process (described in Section 5.1). 
Once a duly dated and signed Informed Consent form is obtained, the clinical investigation-
specific screening procedures may begin. Section 6.1.2 describes the assessments performed as 
part of the screening process: 
Subjects must be screened for clinical investigation eligibility by a member of the site’s clinical 
investigation team previously trained to the CIP. 
If the subject does not meet all inclusion criteria or meets any of the exclusion criteria, the subject 
is considered a screening failure. The Principal Investigator or the delegated clinical investigation 
personnel will record the screening failure in the hospital records. 
Patients meeting general inclusion criteria and no exclusion criteria will be asked to sign an 
Informed Consent form if they wish to participate in the clinical investigation. These patients will 
also be entered into the study electronic database (EDC) system. 
Subject data will be collected following enrollment into the clinical investigation. 
6.1 
Pre-Randomization 
6.1.1 Roll-in Subjects 
The decision to identify a subject as a roll-in will depend on the level of experience of the 
investigator with the device.  Sites may perform up to two (2) roll-in procedures prior to beginning 
the registration phase for the trial and subjects will be designated as roll-ins prior to undergoing 
the procedure.  Consideration of roll-ins will be based on the following criteria: 
• Investigator does not have prior experience with the Tendyne device; or  
• Investigator has not performed a recent Tendyne procedure 
The site must receive authorization from the Sponsor for each roll-in case.  Each roll-in case must 
also be presented by the local site heart team to the SEC, and the SEC must confirm subject 
eligibility. 
6.1.2 Screening and Baseline Assessments 
Screening of a subject for possible inclusion in the trial may commence once a subject has been 
identified as potentially having symptomatic, moderate-to-severe or severe mitral regurgitation or 
severe MAC.  Subject’s general medical eligibility must be assessed via subject interview and 

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medical record review prior to subject registration and within the windows stipulated in Table 3.  
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 trial and are within the screening 
window.  
Outlined below is the schedule of tests and assessments that need to be completed prior to 
registration.  For a summary of the screening process, refer to Appendix III:  Subject Screening 
Flow Chart.  
Baseline Imaging up to 120 Days Prior to Subject Consent 
Cardiac CT images obtained within 120 days prior to subject consent or anytime thereafter must 
be captured per the Cardiac CT Core Laboratory imaging protocol.  Similarly, TTE and TEE 
images must be obtained up to 120 days prior to subject consent or anytime thereafter and must be 
captured per the Echocardiography Core Laboratory imaging protocol. If any imaging is not 
standard of care, the subject must provide informed consent prior to obtaining any trial imaging. 
Once obtained, Cardiac CT, TTE and TEE images will be submitted to the Sponsor.  Both the 
Sponsor and either the CT Core Laboratory or Echocardiography Core Laboratory will review the 
images and assess subject’s anatomical suitability relevant to valve sizing and to perform 
procedural planning. The Echocardiography Core Laboratory will confirm the subject’s MR 
severity, LVEF and LVEDD meet eligibility criteria. 
If clinically indicated, subject’s coronary artery disease status should be assessed via a routine 
diagnostic coronary angiogram within 60 days prior to subject registration.  Any revascularization 
treatment should be administered prior to subject registration as outlined in the subject eligibility 
criteria in Section 5.2. 
Screening Assessments within 90 Days Prior to Registration 
Subjects must complete all trial required assessments prior to registration in the randomized cohort 
and prior to the procedure in roll-in subjects and the non-repairable or severe MAC cohorts. 
• Medical history must be obtained, including review of subject’s medical records.  This 
review will include history of comorbidities and pre-existing medical conditions; previous 
cardiovascular and peripheral vascular interventions; symptoms and diagnosis of mitral 
insufficiency; history of hospitalizations (related to heart failure and mitral valve 
insufficiency) within the past 12 months. 
• A physical exam including an assessment of subject’s cardiac status and sitting vital signs 
(heart rate and blood pressure). 
• Blood tests performed, including: BNP or NT-proBNP, plasma free hemoglobin, serum 
creatinine, serum albumin, International Normalized Ratio (INR), Creatine kinase-MB 
(CK-MB) if indicated or Troponin (Type I or T) if indicated. 
• A 12-lead electrocardiogram (ECG) must be performed. 
• Concomitant chronic 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 

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SUMMIT 
 
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, SF-12, and EQ-5D questionnaires must be completed by the subject;  
o Note: To minimize bias and undue influence, the QoL questionnaires 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). 
• The 6MWT must be administered according to the ATS Statement  [77] 
• The following assessments will be captured to assist the local site heart team and SEC in 
determining a subject’s risk profile.  These assessments include, but are not limited to: 
o STS Predicted Risk of Mortality (PROM) score for both mitral valve replacement 
and repair 
o Essential Frailty Toolset (see 
o Appendix V:  Essential Frailty Toolset 
o Major Organ System Compromise (evaluated on review of subject’s medical 
history) 
• 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), 
and heart failure (e.g., guideline directed medical therapy). 
o Subjects with current or prior symptoms of heart failure and reduced LVEF must 
be symptomatic, despite being on stable GDMT. 
o GDMT must be documented for a minimum of 30 days prior to intended trial 
registration and subject must be on appropriate class of medications (per the 
ACC/AHA/HSFA Heart Failure Guidelines), which typically include: ACE 
Inhibitor or Angiotensin II Receptor Blocker, Beta-Blocker, and a diuretic as 
appropriate.  
If at any time during the screening process there has been a significant change in the subject’s 
overall condition (e.g., due to recent MI, stroke or worsening heart failure) or the subject has 
undergone a recent intervention that may impact mitral regurgitation severity (e.g., CRT implant, 
CABG, PCI), it may be necessary to repeat eligibility assessments and/or imaging to confirm that 
the subject still meets the eligibility criteria. Subjects with significant changes in condition after 
approval by the SEC must be re-evaluated by the Committee. 

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6.2 
Randomization / Registration 
Prior to a subject being designated to a study cohort, or assigned as a roll-in, the following must 
be confirmed: 
• Echocardiography Core Laboratory must confirm MR severity, LVEF and LVEDD; 
• Sponsor must confirm anatomical suitability of subject for the Tendyne device; and 
• SEC must concur with local site heart team that the subject has been treated per standard 
of care, meets trial eligibility criteria, and can be treated in the Randomized, Non-repairable 
or Severe MAC cohorts of the trial (see 12.11.2 -  Subject Eligibility Committee for more 
details). 
If the screening images are inadequate or the SEC determines a subject requires additional 
treatment before consideration for the trial, the subject may be deferred and reconsidered for the 
trial.  If a subject is deferred, trial required imaging or assessments may need to be repeated. 
Subjects will be assigned to a study cohort, or designated as a roll-in, through the EDC system.  If 
assigned to the randomized cohort, randomization will also occur via the EDC system. 
7 
TREATMENT AND PRE-DISCHARGE VISITS  
For subjects assigned to the Tendyne device (including the Treatment group in the Randomized 
cohort, any subject in the Non-repairable or Severe MAC cohorts, and all roll-ins), the Tendyne 
procedure will be performed.  For the Control group, TEER with the MitraClip system will be 
performed.   
For subjects in the randomized cohort (Treatment and Control group) the procedure must occur 
within 14 days from the date of randomization. 
7.1 
Concomitant Procedures 
Concomitant interventional (ex. percutaneous coronary intervention) or surgical procedures are 
not allowed during implant of the Tendyne device or the Control device in any study cohort, with 
the exception of balloon mitral valvuloplasty if deemed necessary for device implantation. 
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.  The surgeon may perform the 
procedure jointly with an experienced interventional cardiologist.  Sponsor personnel will be 
available for procedural support for all Tendyne cases.  For a comprehensive description of the 
Tendyne procedure, refer to the Tendyne Transcatheter Mitral Valve System IFU. If the devices 
were not used according to the IFU or other instructions in this CIP, complete a Protocol Deviation 
form. 
Note:  Prior to performing the procedure, all investigators must undergo training by the 
Sponsor on the Tendyne device and on the CIP.  In addition, all investigators must 
read and understand the IFU that accompanies the device. 

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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 predetermined by CT.  A 
balloon tip catheter is then inserted, leading with the inflated balloon tip to establish an 
entanglement free pathway from the ventricular access site to the left atrium.  A 0.035 standard J 
wire is then advanced into either a pulmonary vein or coiled in the atrium.   
  Once an entanglement free pathway has been achieved, the balloon tip catheter is deflated and 
removed.  The 8 Fr. sheath is also removed and the Tendyne sheath is inserted. 
7.2.2 Tendyne Procedure - Valve Delivery 
The delivery system is advanced using echocardiography and fluoroscopy guidance to maintain 
proper trajectory and to confirm final sheath depth is above the mitral annulus. 
Radial orientation of the valve is primarily performed using TEE.  The valve is positioned such 
that the raised anterior aspect is radially oriented toward the aortomitral continuity. 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 paravalvular leak, 
LVOT obstruction and MR resolution.  At this point, the valve can be recaptured and can be re-
positioned if needed.  When valve position has been optimized, the delivery system is removed. 
7.2.3 Tendyne Procedure - Tensioning 
Tether tension is adjusted using the pad positioning system 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 apical pad is fastened to the tether and the instrument 
is removed. 
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 Card 
At discharge, each subject implanted with a Tendyne device must be provided an Implant Card.  
An Implant Card is included in the package with each Tendyne Transcatheter Mitral Valve System.  
The subject should be instructed to keep this Implant Card on their person at all times.  The serial 
number of the implanted Tendyne device and lot number of the apical pad should be recorded on 
the Implant Card. 
7.3 
Control Group Procedure 
Implantation of the Control device will be performed by site investigators (from the local site heart 
team) that have been trained to perform the Tendyne procedure.  Refer to the IFU associated with 
the Control device (MitraClip) for device implantation. 

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7.4 
Procedural Data Requirements (Tendyne and Control Group) 
The following procedural information shall be recorded on the appropriate eCRF(s) after implant 
or attempted implant of the Tendyne or Control group device. 
7.4.1 12-Lead ECG 
A 12-lead ECG will be performed pre- and post-implant.   
7.4.2 Intraoperative Hemodynamic Measurements (Tendyne Only) 
Subjects who receive a Tendyne device (including the Treatment group in the Randomized cohort, 
any subject in the Non-repairable or Severe MAC cohorts, and all roll-ins) will undergo right-heart 
catheterization to measure hemodynamics intraoperatively.  Cardiac output (CO), pulmonary 
arterial (PA), aortic, and right atrial (RA) pressures will be measured before and after the valve 
placement.  LV pressures should be measured via a pigtail catheter or similar.   
7.4.3 Additional Procedural Data Collection 
In addition to the intraoperative imaging and hemodynamic measurements, the following Tendyne 
device and Control group procedural information shall be recorded: 
• General procedure information  
• Treatment and Control group implant information 
• Clinical tests 
• Changes in concomitant cardiovascular medications (e.g., heart failure, hypertension, 
antithrombotic medications) 
• Fluoroscopy duration  
• Adverse events, if applicable 
• Protocol deviations, if applicable 
• Device deficiency, if applicable 
7.4.4 Immediate Post-Operative Care 
Subjects 
will 
receive 
standard 
post-cardiac 
transapical 
(Tendyne 
device) 
or 
transfemoral/transseptal (Control group) care as judged appropriate by the investigator. The 
subject’s ACT should also be monitored in accordance with hospital protocols.    
7.4.5 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. 
For subjects in the Control group, anticoagulation (warfarin) and antiplatelet therapy (aspirin or 
alternate agent) shall be maintained per the MitraClip IFU. 
Notes:  

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• During the period of CIP required anticoagulation, 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 implanted with the Tendyne device, a TTE must be conducted between 60 and 
120 days after anticoagulation stoppage.  
o If the TTE identifies evidence of increased gradient or concerns with leaflet 
mobility (e.g., mitral valve gradient ≥ 6 mmHg), a cardiac CT must be conducted 
to evaluate hypoattenuated leaflet thickening or motion.  If renal insufficiency 
precludes a cardiac CT, a TEE must be performed instead. 
7.4.6 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 
(heart rate and blood pressure). 
• Changes in concomitant cardiovascular medications (e.g., heart failure, hypertension, 
antithrombotic medications) 
• 12-lead ECG  
• TTE 
• Laboratory and clinical tests: serum creatinine, International Normalized Ratio (INR), 
Creatine Kinase-MB (CK-MB) if indicated, or Troponin (Type I or T) if indicated 
• Adverse events, if applicable 
• Protocol deviations, if applicable 
• Device deficiency (Tendyne device only), if applicable 
8 
FOLLOW-UP FOR EVALUATION OF SAFETY AND EFFECTIVENESS  
8.1 
Clinical Follow-up (All Registered / Roll-in Subjects) 
Follow-up evaluations are required at 30 days, 3 months, 6 months, 12 months, and annually 
thereafter through 5 years (Table 3).  For all registered and roll-in subjects, follow-up visits will 
be calculated from the date of the index procedure, or the date of registration if a subject is 
registered but does not undergo a 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 trial assessments occurring at each visit, 
refer to Appendix IV:  Trial Assessment and Follow-up Schedule.   
Subjects shall be followed at the investigational site where the subject was registered (or 
designated as a roll-in), 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 and roll-in 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 

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investigators at all scheduled follow-up visits.  Subjects implanted with the Tendyne or Control 
device must also be evaluated for device function.   
During follow-up, the site Principal Investigator should collaborate with the other site investigators, 
as applicable, in determining the treatment strategy for all roll-in and registered subjects at their 
site.  Any treatment during follow-up (e.g., due to an adverse event or a change in the subject’s 
condition) should be reported on the appropriate eCRFs. 
Note: If a subject has an unsuccessful Tendyne or Control device implant, they should remain in 
the trial and continue to be followed per the trial follow-up schedule.  Additionally, if a subject is 
randomized to receive either the Treatment or Control device but does not undergo the implant 
procedure, they should remain in the trial and continue to be followed per the trial follow-up 
schedule (calculated from the date of randomization).  
8.2 
30 Day, 3 Month, 6 Month, and Annual Visits 
Follow-up visits are required at 30 days, 3 months (phone contact), 6 months, and annually 
thereafter through 5 years.  Subjects must continue to take baseline medications without change 
during follow-up, unless clinically (medically) necessary.  If there are any cardiovascular 
medication changes, these changes, and the reason for change must be documented on the eCRF.  
Required tests and procedures are outlined in Appendix IV:  Trial Assessment and Follow-up 
Schedule.  All visits and tests must be completed within the visit window specified in Table 3, 
even if the subject is in hospital.  The following data will be collected for site visits:   
• A physical exam including an assessment of subject’s cardiac status and sitting vital signs 
(heart rate and blood pressure). 
• Changes in concomitant cardiovascular medications (e.g., heart failure, hypertension, 
antithrombotic medications) 
• NYHA Functional Classification assessment 
• Blood tests performed, including: BNP or NT-proBNP, plasma free hemoglobin, serum 
creatinine, INR, CK-MB if indicated or Troponin (Type I or T) if indicated 
• TTE  
• 12-lead ECG 
• Cardiac CT (Note: Only required at 30-day visit) 
• KCCQ, SF-12, and EQ-5D questionnaires 
• 6-Minute Walk Test 
• Modified Rankin Scale (Assessment to be completed after suspected onset of stroke) 
• Assess and record adverse events, if applicable  
• Assess and record protocol deviations, if applicable 
• COVID-19 assessment, if applicable 
Note:  The 3-month visit will be conducted via telephone.  This visit will assess potential 
adverse events and changes to concomitant cardiovascular medications. 

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Echocardiography images (TTE) obtained at each follow-up visit should be submitted in a timely 
manner.  Throughout the course of the trial, the Echocardiography Core Laboratory may provide 
feedback to sites regarding quality of images obtained. 
During the follow-up period, if a subject requires a cardiac procedure (i.e., MV surgery, permanent 
LVAD, heart transplant), which may or may not result in explant of the Tendyne or Control device, 
the subject will remain in the trial and continue to be followed. 
Every attempt must be made to ensure trial 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 trial questionnaires (KCCQ, SF-12, and EQ-5D).  This 
should only be performed in rare instances and the Sponsor should be notified of such instances in 
advance. 
Subjects who do not have a scheduled follow-up visit will be documented as having a missed visit 
and a protocol deviation (refer to Section 12.6 - 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 3.  Follow-up Schedule* and Windows for Trial Subjects 
Follow-Up Visit 
Window Start 
Day 
Target Day 
Window Close 
Day 
Follow up 
Method 
Pre-Discharge 
(Registered and 
roll-in subjects)  
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 
Phone Call 
6 Months 
(±30 days) 
152 
182 
212 
Site visit 
12 Months 
(±30 days) 
335 
365 
395 
Site visit 
2 years 
(±30 days) 
701 
731 
761 
Site visit 
3 years 
(±45 days) 
1051 
1096 
1141 
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 for registered and 
roll-in subjects.  If a subject in the Randomized cohort does not undergo a Treatment or 
Control group procedure, follow-up visit dates are calculated from the date of randomization. 

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9 
ADVERSE EVENTS  
To comply with worldwide standards and guidelines on clinical investigation adverse event 
reporting, the Sponsor has adopted uniform and worldwide applicable standard definitions and 
reporting timelines to be used and adhered to by the investigators. 
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, 
in the context of a clinical investigation, whether or not related to the investigational medical 
device. 
This definition includes events related to the investigational medical device or comparator and/or 
the procedures involved. This definition includes events related to the procedures involved. For 
users or other persons, this definition is restricted to events related to the use of investigational 
medical devices or comparators. 
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 
Serious Adverse Event (SAE) is an AE that led to any of the following.  
a) death, 
b) a serious deterioration in the health of the subject, that resulted in any of the following: 
1) life-threatening illness or injury 
2) permanent impairment of a body structure or a body function 
3) hospitalization or prolongation of patient hospitalization 
4) medical or surgical intervention to prevent life threatening illness or injury or permanent 
impairment to a body structure or a body function 
5) chronic disease 
c) fetal distress, fetal death or a congenital physical or mental impairment 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.  

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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 4 summarizes the anticipated events that have been identified as possible complications 
from the Tendyne Transcatheter Mitral Valve System.  Please also refer to the list of anticipated 
events in the Tendyne Transcatheter Mitral Valve System IFU and package insert for the Control 
device therapies required per protocol. 
Table 4.  Anticipated Adverse Events (Tendyne Transcatheter Mitral Valve System) 
Normal postoperative sequelae or expected postoperative events during the acute perioperative 
period (72 hours) should not be recorded as SAEs unless they meet the seriousness criteria defined 
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)  
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 
Pain 
Cardiac perforation 
Pleural effusion 
Conduction defect, with or without need for 
pacemaker  
Pulmonary embolism 
Damage to cardiac tissue and/or structures 
Pulmonary hypertension 
Death 
Paravalvular leak 
Decreased LV function and/or cardiac output 
Pericardial effusion / tamponade 
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, calcium, tissue, 
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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in Section 9.1.2. A few common examples of normal post-operative sequelae or expected 
postoperative 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 
Transcatheter Mitral Valve 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 any inadequacy in the identity, quality, durability, reliability, 
usability, safety or performance of an investigational device, including malfunction, use errors or 
inadequacy in the information supplied by the manufacturer including labeling. 
Note: This definition includes device deficiencies related to the investigational medical device or 
the device comparator 
Note: Cybersecurity incidents related to the investigational product, shall be reported as device 
deficiencies 
A device malfunction is the failure of an investigational medical device to perform in accordance 
with its intended purpose when used in accordance with the instructions for use or CIP, or IB 
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 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 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. 
 
 

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9.4 
Adverse Event / Device Deficiency Reporting 
9.4.1 AE Reporting 
The investigator will monitor the occurrence of adverse events for each subject during the course 
of the trial.  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 valve, a TTE must be conducted if signs or symptoms 
suggestive of valve dysfunction are exhibited.  If the TTE indicates evidence of valve dysfunction, 
a cardiac CT must be performed.  If renal insufficiency precludes a cardiac CT, a TEE must be 
performed instead. 
For this clinical investigation, only SAEs, regardless of device and/or procedural relatedness, will 
be collected on each subject from the time of trial registration through trial completion.  A 
summary of AE reporting requirements is further described in this section and summarized in  
Table 5. 
Unchanged, chronic, non-worsening or pre-existing conditions are not AEs and should not be 
reported. 
The Sponsor will provide an offline form to allow the investigator to report SAEs in the event 
entry cannot be made in the EDC. This does not replace the EDC reporting system and sites must 
still enter all information in the EDC system as soon as feasible. 
9.4.2 SAE Reporting to Sponsor and IRB / EC 
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 three 
(3) calendar days from the day the trial 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 date the site staff became aware the event met the criteria of an SAE must be recorded in the 
source document.  The investigator will further report the SAE to the local IRB/EC according to 
the institution’s IRB/EC reporting requirements.    
9.4.3 UADE Reporting to Sponsor and IRB 
The Sponsor requires the investigator to report any UADE to the sponsor within three (3) calendar 
days of the investigator’s knowledge of the event, unless local requirements are more stringent, 
and to the IRB/EC per requirements.   
9.4.4 Device Deficiency Reporting 
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 trial 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 also be reported to the IRB/EC 
per the investigative site’s local requirements. 

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The device, if not successfully implanted in the subject, should be returned to the Sponsor. Device 
deficiencies/malfunctions should be reported to the IRB/EC per the investigative site’s local 
requirements. 
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 5.  All reports are subject to inspection and to the retention requirements described in 
13.6.1 Investigator Records. 
Table 5.  Investigational Site AE Reporting Requirements to Sponsor 
Event 
Investigational 
Site 
Reporting timelines 
SAE 
All Sites 
SAEs must be reported no later than three (3) calendar days 
from the day the trial 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 three (3) calendar days 
from the day the trial 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 three (3) calendar days 
from the day the trial 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 AE Reporting to Country Regulatory Authorities by the Sponsor  
The Sponsor will report SAEs, UADEs, and DDs to the country regulatory authority, per local 
requirements.  
Note: Reportable device deficiencies include those that might have led to an SAE 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. 
9.5 
Heart Transplants or Subject Death (Tendyne Only) 
In the event of heart transplant or subject death, histological and engineering analyses of the in situ 
valve would provide valuable information. The Sponsor must be contacted for shipping and 
packaging materials and to arrange for transport.  
10 STATISTICAL METHODS 
The following section describes the statistical methods for the clinical investigation. Additional 
details are provided in a Statistical Analysis Plan (SAP). 

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10.1 Analysis Populations 
10.1.1 Randomized Cohort 
The Intention-to-Treat, modified Intention-to-Treat and Per-Protocol are defined below. For all the 
analyses, the duration of follow-up will be calculated from the date of registration. 
Intention-to-Treat (ITT) Population 
The ITT population will consist of all subjects randomized in the cohort. All subjects will be 
analyzed in the group randomized regardless of the treatment received.  
Modified Intention-to-Treat (mITT) Population 
The mITT population will consist of all subjects in the ITT population (Tendyne and Control 
groups) with an attempted index procedure. Subjects will be analyzed in the actual attempted index 
procedure. Subjects who are randomized but did not have any procedure attempted will be 
excluded from the mITT population.  
Per-Protocol (PP) Population 
The Per-Protocol population will consist of all subjects who meet all major study inclusion criteria 
and none of the major exclusion criteria for the trial and have a successfully implanted Tendyne 
or MitraClip (control device) at the end of the index procedure per the randomization. Subjects 
who are randomized but did not have a device implanted at the end of index procedure will be 
excluded from the PP population. 
10.1.2 Non-repairable, Severe MAC and Severe MAC CAP Cohorts 
Attempted Procedure (AP) Population 
The Attempted Procedure population for the Non-repairable and Severe MAC cohorts will consist 
of subjects in whom a Tendyne procedure is attempted. 
Additionally, subjects that were enrolled with an attempted Tendyne procedure in the Non-
randomized cohort, as defined in the CIP version C, prior to publication of the criteria by Lim et 
al., but do not satisfy the revised criteria, will be excluded from the Non-repairable cohort AP 
population. Subjects who are excluded in this regard and had an attempted Tendyne procedure will 
be reported descriptively and separately. 
  
10.2 Statistical Analyses 
10.2.1 Randomized Cohort 
Randomized Cohort – Primary Composite Endpoint 
The primary endpoint for the Randomized cohort is freedom from all-cause mortality and heart 
failure hospitalization (HFH) at 12-months post index procedure.  The trial is intended to 
demonstrate non-inferiority of the Tendyne Transcatheter Mitral Valve System to TEER with 
MitraClip for the treatment of moderate-to-severe or severe MR. 
The null (H0) and alternative (H1) hypotheses are: 
H0: πD - πC ≤ -d  

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H1: πD - πC > -d  
where πD and πC are the true event rates for the composite of freedom from all-cause mortality and 
HFH at 12 months in the Treatment and Control group, respectively, and d is the non-inferiority 
margin.  The non-inferiority margin is set at 12.5%.   
The primary analysis for the primary endpoint will be performed on the ITT population. The 
analysis will also be performed on the mITT and PP populations. The non-inferiority test of the 
primary endpoint is based on the event rates estimated by Kaplan-Meier method using the Com-
Nougue [78] method employing a one-sided test with 5% significance level.  
The assumed event rates were established using published rates of death and HFH in the MitraClip 
+ medical therapy groups in two recent randomized control trials: COAPT and MITRA-FR. The 
12.5% non-inferiority margin was determined to be less than the reduction in a composite of death 
and HFH by MitraClip therapy over GDMT-only in a COAPT sub-group analysis reflective of 
patients to be enrolled in the SUMMIT randomized cohort. Details are provided in the Statistical 
Analysis Plan (SAP). 
Randomized Cohort – Secondary Endpoints 
The following secondary endpoints will be evaluated.  These endpoints will be evaluated for 
labeling claims if the primary endpoint for the randomized cohort is met.  
Effectiveness: Freedom from MR > mild in severity at 30 days post index procedure among 
survivors 
Subjects treated with the Tendyne device are expected to experience greater reduction in MR 
severity than subjects in the Control group.  The proportion of subjects with MR ≤ mild (1+) at 30 
days will be compared between the Treatment and Control groups.  
The null and alternative hypotheses are stated as:  
 H0: PD - PC ≤ 0    
 H1: PD - PC > 0 
where PD and PC represent the proportion of subjects with MR ≤ 1+ at 30 days in the Treatment 
and Control groups, respectively. The hypothesis will be tested using Fisher’s exact test at one-
sided 2.5% significance level. The primary analysis for this secondary endpoint will be performed 
on the ITT population.       
Safety: Freedom from all-cause mortality and MV reintervention at 12 months 
The Tendyne device may reduce the risk for surgical reintervention and subjects in the Treatment 
group are expected to experience greater reduction in MR severity than subjects in the Control 
group. The proportion of subjects alive and without MV reintervention at 12 months will be 
compared between the Treatment and Control groups.  
The null and alternative hypotheses are stated as:  
H0: πD - πC ≤ -d  
H1: πD - πC > -d  

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where πD and πC are the true event rates for the composite of freedom from all-cause mortality and 
MV reintervention or reoperation at 12 months in the Treatment and Control group, respectively, 
and d is the non-inferiority margin of 10%. This non-inferiority test of the endpoint will be based 
on the event free rates estimated by Kaplan-Meier method using the Com-Nougue method 
employing a one-sided test with 2.5% significance level. The justification of the non-inferiority 
margin d of 10% is provided in the SAP.   
Improvement in KCCQ by at least 10 points at 12 months from baseline  
To evaluate the benefit of the Tendyne device, the change from baseline in Quality of Life as 
measured by the KCCQ score will be compared between Tendyne and MitraClip groups at 12 
months for non-inferiority. 
The null and alternative hypotheses are stated as:  
 H0: PD - PC ≤ -d    
 H1: PD - PC > -d 
where PD and PC represent the proportion of subjects who improved at least 10 points in KCCQ 
score at 12 months from baseline in the Treatment and Control groups, respectively, and d is the 
non-inferiority margin of 15%. The hypothesis will be tested using Farrington-Manning score test 
at one-sided 2.5% significance level. The justification of the non-inferiority margin d of 15% is 
provided in the SAP.  
Proportion of Patients with NYHA Functional Classification I or II at 12 months 
To evaluate improvement in heart failure symptoms, the proportion of NYHA Functional 
Classification I or II at 12 months between Tendyne and MitraClip groups will be tested for non-
inferiority. 
The null and alternative hypotheses are stated as:  
 H0: PD - PC ≤ -d    
 H1: PD - PC > -d 
where PD and PC represent the proportion of subjects who have NYHA Functional Classification 
I/II at 12 months in the Treatment and Control groups, respectively, and d is the non-inferiority 
margin of 15%. The hypothesis will be tested using Farrington-Manning score test at one-sided 
2.5% significance level. The justification of the non-inferiority margin d of 15% is provided in the 
SAP. 
Improvement in Six-Minute Walk Test Distance by at least 50 meters at 12 months from baseline  
To evaluate the benefit of the Tendyne device, the change from baseline in distance walked as 
measured by the 6MWT will be compared between Tendyne and MitraClip groups at 12 months 
for non-inferiority.  
The null and alternative hypotheses are stated as:  
 H0: PD - PC ≤ -d    
 H1: PD - PC > -d 

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where PD and PC represent the proportion of subjects who improved at least 50 meters in 6MWT 
distance at 12 months from baseline in the Treatment and Control groups, respectively, and d is 
the non-inferiority margin of 15%. The hypothesis will be tested using Farrington-Manning 
score test at one-sided 2.5% significance level. The justification of the non-inferiority margin d of 
15% is provided in the SAP. 
10.2.2 Non-Repairable Cohort 
Non-Repairable Cohort – Primary Endpoint 
The primary endpoint for the Non-repairable cohort is freedom from all-cause mortality and heart 
failure hospitalization at 12 months post index procedure.  The trial is intended to demonstrate that 
the primary endpoint event rate in subjects treated with the Tendyne Transcatheter Mitral Valve 
System is greater than a pre-specified performance goal (PG). 
The null and alternative hypotheses are: 
H0: πD   ≤   πPG 
H1: πD   >   πPG 
where πD is the true rate of freedom from all-cause mortality and heart failure hospitalization at 12 
months post index procedure, and πPG is the performance goal.  The PG is set at 45% (justification 
of the PG is provided in the SAP).  The Kaplan-Meier analysis will be used to compute the 
composite event free rate at 12 months; the standard error and confidence limits will be computed 
using Greenwood’s method. The null hypothesis will be tested at the one-sided 2.5% level of 
significance using asymptotic normal distribution. 
Subjects who have not experienced mortality or heart failure hospitalization, within 12 months, 
will be censored at the date of last information available. 
The PG was established using published rates of death and HFH in recent randomized control trials 
of the MitraClip system. Details are provided in the SAP.  
Non-Repairable Cohort – Secondary Endpoints 
The following secondary endpoints will be evaluated in the Non-repairable cohort.  These 
endpoints will be evaluated for labeling claims if the primary endpoint for the Non-repairable 
cohort is met. Details about statistical methods are described in the SAP. 
Change in Quality of Life, as measured by the KCCQ through 12 months 
To evaluate the benefit of the Tendyne device, the change in Quality of Life as measured by the 
KCCQ scores at 6-month and 12-month follow-up visits from baseline will be tested separately. 
Details about hypotheses, statistical methods, and the significance level are described in the SAP.  
Improvement of NYHA Functional Classification I or II at 12 months 
To evaluate improvement in heart failure symptoms, the proportion of NYHA Functional 
Classification I or II at 12 months will be compared with that at baseline. 
The null and alternative hypotheses are stated as:  
H0: PM12, NYHA I/II ≤ PB, NYHA I/II vs.  
H1: PM12, NYHA I/II > PB, NYHA I/II    

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where PM12, NYHA I/II and PB, NYHA I/II represent the proportion of subjects with NYHA Classification 
I/II at 12 months and baseline, respectively. 
Change in Six Minute Walk Test Distance through 12 Months 
To evaluate the long-term benefit of the Tendyne device, the change in distance walked as 
measured by the 6MWT at 6-month and 12-month follow-up visits from baseline will be tested 
separately. Details about hypotheses, statistical methods, and the significance level are described 
in the SAP. 
10.2.3 Severe MAC Cohort 
Severe MAC Cohort – Primary Endpoint 
The primary endpoint for the Severe MAC cohort is freedom from all-cause mortality and heart 
failure hospitalization at 12 months post index procedure. 
The null and alternative hypotheses are: 
H0: πD   ≤   πPG 
H1: πD   >   πPG 
where πD is the true event rate for the composite of freedom from all-cause mortality and heart 
failure hospitalization at 12 months and πPG is the performance goal.  The PG is set at 43% 
(justification of the PG is provided in the SAP). The Kaplan-Meier analysis will be used to 
compute the composite event free rate at 12 months; the standard error and confidence limits will 
be computed using Greenwood’s method. The null hypothesis will be tested at the one-sided 2.5% 
level of significance using asymptotic normal distribution. 
Subjects who have not experienced mortality or heart failure hospitalization within 12 months, 
will be censored at the date of last information available. 
The PG was established using published rates of death and HFH in recent randomized control trials 
of the MitraClip system. Details are provided in the Statistical Analysis Plan (SAP). 
Severe MAC Cohort – Secondary Endpoints 
The following secondary endpoints will be evaluated in the Severe MAC cohort.  These endpoints 
will be evaluated for labeling claims if the primary endpoint for the Severe MAC cohort is met. 
Freedom from MR > mild in severity at 30 days post index procedure 
To evaluate whether the Tendyne system is more effective at reducing MR than a pre-specified 
performance goal derived from literature, freedom from MR > mild (1+) at 30 days post index 
procedure will be tested against a PG. 
The null and alternative hypotheses are stated as: 
H0: PMR ≤ 1+   ≤   PPG 
H1: P MR ≤ 1+   >   PPG 
where P MR ≤ 1+ is the proportion of subjects who have MR ≤ 1+ at 30 days post index procedure. 
PPG is set at 75%. 

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The hypothesis will be tested by comparing the one-sided 97.5% exact lower confidence bound of 
the observed MR ≤ 1+ rate at 30 days to the performance goal of 75% (details provided in the 
SAP).  The null hypothesis will be rejected at the one-sided 2.5% significance level using Binomial 
exact test. 
Change in Quality of Life, as measured by the KCCQ through 12 months 
To evaluate the benefit of the Tendyne device, the change in Quality of Life as measured by the 
KCCQ scores at 6-month and 12-month follow-up visits from baseline will be tested separately. 
Details about hypotheses, statistical methods, and the significance level are described in the SAP. 
Improvement of NYHA Functional Classification I or II at 12 months 
To evaluate improvement in heart failure symptoms, the proportion of NYHA Functional 
Classification I or II at 12 months will be compared with that at baseline. 
The null and alternative hypotheses are stated as:  
H0: PM12, NYHA I/II ≤ PB, NYHA I/II  
H1: PM12, NYHA I/II > PB, NYHA I/II    
where PM12, NYHA I/II and PB, NYHA I/II represent the proportion of subjects with NYHA Classification 
I/II at 12 months and baseline, respectively. The SAP specifies the details of this hypothesis test. 
Change in Six Minute Walk Test Distance through 12 Months 
To evaluate the long-term benefit of the Tendyne device, the change in distance walked as 
measured by the 6MWT at 6-month and 12-month follow-up visits from baseline will be tested 
separately. Details about hypotheses, statistical methods, and the significance level are described 
in the SAP. 
10.2.4 Severe MAC CAP Cohort  
Endpoints will be descriptively summarized and compared to the results in the Severe MAC 
primary analysis cohort. Data from the Severe MAC CAP Cohort may be used to support the PMA 
application for Severe MAC.  
 
10.3 Sample Size Calculations and Assumptions 
10.3.1 Randomized Cohort 
The sample size for the Randomized cohort is determined based on the primary endpoint of 
freedom from all-cause mortality and heart failure hospitalizations (HFH) at 12 months. The 
primary endpoint will be analyzed based on the ITT population in which the Tendyne group is 
tested against the MitraClip group for non-inferiority. The null and alternative hypotheses are 
stated in Section 10.2.1. Assuming the rate of freedom from events at 12 months for both the 
Tendyne group and the MitraClip group is 65%, a non-inferiority margin of 12.5%, and a 1:1 
randomization ratio (Tendyne vs. MitraClip), a simulation was performed employing the Com-
Nougue method with a one-side 5% significance level. Based on an overall expected attrition rate 
of up to 15% at 12 months (details described in the SAP), a total sample size of 382 (191 per 
group) subjects will provide approximately 80% power.  

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SUMMIT 
 
10.3.2 Non-Repairable Cohort 
The sample size for the Non-repairable cohort is determined based on the primary endpoint of 
freedom from all-cause mortality and HFH at 12 months. The primary endpoint will be analyzed 
based on the AP Population and tested against a pre-specified performance goal of 45%. The null 
and alternative hypotheses are stated in Section 10.2.2. Assuming the freedom from event rate at 
12 months for the Tendyne Transcatheter Mitral Valve System is 54%, and based on asymptotic 
normality of KM survival estimates with Greenwood variance estimates, a simulation was 
performed with a one-side 2.5% significance level. Based on an overall expected attrition rate of 
up to 15% at 12 months (details described in the SAP) and accounting for approximately 20 
subjects being excluded from the cohort due to not meeting the criteria from Lim, et al. [66], a 
total sample size of 325 subjects will provide approximately 85% power.  
10.3.3 Severe MAC Cohort 
The sample size for the Severe MAC cohort is determined based on the primary endpoint of 
freedom from all-cause mortality and heart failure hospitalizations (HFH) at 12 months. The 
primary endpoint will be analyzed based on the AP Population and tested against a pre-specified 
performance goal of 43%. The null and alternative hypotheses are stated in Section 10.2.3. 
Assuming the rate of freedom from events at 12 months for the Tendyne Transcatheter Mitral 
Valve System is 60%, and based on asymptotic normality of KM survival estimates with 
Greenwood variance estimates, a simulation was performed with a one-side 2.5% significance 
level. Based on an overall expected attrition rate of up to 15% at 12 months (details described in 
the SAP), a total sample size of 103 subjects will provide approximately 90% power. 
10.3.4 Severe MAC CAP Cohort 
After enrollment has been completed for the Severe MAC Cohort, additional patients with severe 
MAC will be enrolled in the Severe MAC CAP. Up to an additional 150 subjects upon FDA 
approval may be enrolled into the Severe MAC CAP, until the PMA review is complete for the 
Tendyne system. The sample size of 150 subjects is based on the assumption of approximately 6-
7 subjects being enrolled per month into the CAP, which is in accordance with the historical 
enrollment in the original Severe MAC cohort.  
10.4 Timing of Analysis 
The primary and secondary endpoints in the Randomized, Non-repairable and Severe MAC 
cohorts will be analyzed when all registered subjects in the corresponding cohorts complete 12 
months of follow-up. 
10.5 Subgroup Analysis 
Subgroup analysis will be provided for the primary endpoint of the Randomized, Non-repairable 
and Severe MAC cohorts. Details about subgroup analysis are provided in the SAP. 
10.6 Multiplicity Adjustments 
Since the three cohorts (Randomized, Non-repairable and Severe MAC) are independent and 
mutually exclusive, the primary and secondary endpoints for the three cohorts will be evaluated 
separately and need no multiplicity adjustment among the cohorts. Data from subjects enrolled in 
the Severe MAC CAP will be independently analyzed from the primary study cohorts. 

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SUMMIT 
 
The primary endpoint of each cohort must be met for individual cohort success. The secondary 
endpoints for each cohort will be evaluated for labeling claims if the primary endpoint of that 
cohort is met.  Appropriate multiplicity adjustments will be applied to the analysis of the secondary 
endpoints within each cohort. Details about multiplicity adjustments are provided in the SAP.   
10.7 Procedures for Accounting for Missing Data 
Analyses will be performed on all evaluable data. Missing 12-month KCCQ scores, 6MWD and 
NYHA Classifications will be imputed from the nearest post 12-month value, within 365 days of 
the scheduled 12-month visit, if applicable.  Missing 30-day MR measurements will be imputed 
from the nearest post-procedure MR measurement obtained from the core lab, within 365 days of 
the scheduled 1-month follow-up visit, if applicable. Sensitivity to missing primary endpoint data 
is described in the SAP.  
10.8 Statistical Criteria for Termination 
There are no statistical criteria for termination of this clinical investigation. 
10.9 Trial Success 
Randomized Cohort 
The Randomized cohort will be considered successful if the primary endpoint is met.  Additional 
labeling claims may be made based on the secondary endpoints. 
Non-Repairable Cohort 
The Non-repairable cohort will be considered successful if the primary endpoint is met.  Additional 
labeling claims may be made based on the secondary endpoints. 
Severe MAC Cohort 
The Severe MAC cohort will be considered successful if the primary endpoint is met.  Additional 
labeling claims may be made based on the secondary endpoints. 
 
Severe MAC CAP Cohort 
No pre-specified success criteria will be set for the Severe MAC CAP; the primary and secondary 
endpoints will be descriptively summarized. 
10.10 Deviations from Statistical Plan 
Any major changes to the statistical plan will be documented in an amendment to the statistical 
plan. Less significant changes to the planned analyses will be documented in the final report.   
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/EC review and regulatory inspections to be 
performed. 
Subjects providing informed consent are agreeing to allow clinical investigation monitors or 
regulatory agencies, including foreign countries, to review, in confidence, any records identifying 
the subjects in this clinical investigation. This information may be shared with regulatory agencies; 

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however, Sponsor undertakes not to otherwise release the subject’s personal and private 
information.  
12 QUALITY CONTROL AND QUALITY ASSURANCE 
To ensure the trial 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 trial.  These controls include the establishment of training, monitoring, support of 
quality audits and trial 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 representatives (see Appendix 
II:  Definitions for a full description): 
• 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/EC, and 
regulatory/competent authorities. 
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 trial, investigators are 
responsible for ensuring that investigational site resources are available and that the appropriate 
population of subjects can be identified/treated.   
12.1.1 Investigator Experience Requirements 
Implantation of the Tendyne device must include an operator (e.g., cardiothoracic surgeon) who is 
experienced in transapical access.  
Implantation of the Control device will be performed by the same site investigators that have been 
trained to perform the Tendyne procedure.   
The responsibilities of the various roles/specialties on the multidisciplinary team at the site are 
summarized in Table 6 below: 
Table 6.  Investigator Responsibilities 
Role / Specialty 
Responsibility 
Interventional 
Cardiologist 
• Evaluates all potential subjects 
• Performs Tendyne and Control group procedure* 
• May present potential subjects to SEC 

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Role / Specialty 
Responsibility 
Cardiothoracic Surgeon 
• Evaluates all potential subjects 
• Performs Tendyne and Control group procedure* 
• May present potential subjects to SEC 
Echocardiographer 
• Evaluates potential subjects for echocardiographic eligibility 
criteria 
• Participates in the Tendyne procedure 
Note: Interventional Cardiologists or Cardiothoracic Surgeons can be Tendyne implanters as 
long as they have undergone the Tendyne Transcatheter Mitral Valve System training and are 
authorized by the Sponsor to perform the procedure. A total of three operators are required to 
complete the implant procedure; however, only the primary two operators require prior 
authorization by the sponsor. Training of the third operator can occur at, or just prior to, the 
day of the procedure and does not require pre-authorization from Abbott. 
12.1 Clinical Investigation Finances and Agreements 
The clinical investigation will be financed by Abbott.  Investigational sites will be compensated 
by Abbott for participation in the clinical investigation per the conditions of agreement between 
the Sponsor and the Investigational site. 
 
12.2 Site Principal Investigator Responsibilities 
The role of the Site Principal Investigator is to implement, oversee the management of the day-to-
day conduct of the clinical investigation as well as ensure data integrity and the rights, safety and 
well-being of the subjects involved in the clinical investigation. The principal investigator shall 
support monitoring and reporting to IRB/EC and local competent authorities as necessary, 
throughout the conduct of the clinical investigation. 
 
The principal investigator is responsible for ensuring adequate training and qualification of the 
investigation site team and for maintaining oversight of their activities. The Principal Investigator 
may delegate tasks to members of the investigation site team but retains responsibility for the 
clinical investigation. This also applies when activities are outsourced to an external organization 
by the principal investigator in which case he/she shall exercise oversight to ensure the integrity 
of all tasks performed and any data generated by this external organization. 
 
12.3 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/EC of the 
amendment (administrative changes) or obtaining IRB’s/EC’s approval of the amendment 
(changes in subject care or safety), according to the instructions provided by the Sponsor. 
The Sponsor will submit the CIP Amendment to regulatory bodies per applicable regulation and 
await regulatory approval before implementing the CIP amendment. 
 

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Acknowledgement/approval by the IRB/EC of the CIP amendment must be documented in writing 
prior to implementation.  Copies of this documentation must also be provided to the Sponsor. 
12.4 Trial Training  
12.4.1 Site Training 
Investigators and site clinical trial 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 trial personnel will include, but is not limited to, the CIP 
requirements, investigational device usage, eCRF completion and trial personnel responsibilities.  
All investigators and site clinical trial personnel that are trained must sign a training log (or an 
equivalent) upon completion of the training.  Investigator/trial personnel must not perform any 
trial-related activities that are not considered standard of care at the site prior to being trained.  
12.4.2 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 trial will be trained to the CIP and other 
trial documents (as appropriate). 
12.4.3 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. 
12.5 Monitoring 
The Sponsor and/or designee will monitor the trial over its duration according to the CIP-specific 
Monitoring Plan, which will include the planned extent of source data verification.  
Prior to initiating any procedure, the Sponsor monitor (or delegate) will ensure that the following 
criteria are met:  
• 
The investigator understands and accepts the obligation to conduct the clinical investigation 
according to the CIP and applicable regulations, and has signed the Investigator Agreement.  
• 
The Investigator and his/her staff should have sufficient time and facilities to conduct the 
clinical investigation and should have access to an adequate number of appropriate subjects 
to conduct the clinical investigation.  
• 
Source documentation (including original medical records) must be available to substantiate 
proper informed consent procedures, adherence to CIP procedures, adequate reporting and 
follow-up of adverse events, accuracy of data collected on case report forms, and device 
information.  
• 
The Investigator/site will permit access to such records. A monitoring visit sign-in log will 
be maintained at the site. The Investigator will agree to dedicate an adequate amount of time 
to the monitoring process. The Investigator and/or research coordinator will be available for 
monitoring visits. It is expected that the Investigator will provide the monitor with a suitable 
working environment for review of clinical investigation-related documents 

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12.6 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. No waivers for CIP deviations will be granted by 
Sponsor. All deviations must be reported to the Sponsor using the Deviation CRF. 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 determine the cause of deviations, implement corrective actions and inform their IRB/EC or 
equivalent committee of CIP deviations in accordance with their specific IRB/EC or equivalent 
committee 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 trial 
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 trial.  
12.6.1 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/EC 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/EC shall be documented and maintained in the clinical 
trial file at the site and by the Sponsor.  
12.6.2 Non-Critical Deviations  
Protocol deviations that do not have the urgency associated with expedited notification or prior 
Tendyne/IRB/EC approval (as discussed in the above paragraphs) will be reported upon discovery, 
such as during completion of eCRFs or during a monitoring visit. 
12.7 Measures Taken to Avoid and Minimize Bias 
Due to the nature of the treatment in the Treatment and Control groups, site personnel and some 
Sponsor personnel will be aware of treatment assignment.  The following steps will be taken to 
minimize bias in the conduct of the trial and analyses of clinical data. 

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SUMMIT 
 
12.7.1 Subject Recruitment and Randomization 
Investigational sites will attempt to recruit consecutive subjects who meet trial eligibility criteria, 
with the following considerations: 
• Candidates will be considered for the trial after they have been informed of trial 
requirements and have signed the informed consent form.  See Section 5 - Subject 
Selection and Withdrawal for additional details on subject screening and informed 
consent process.  
• Imaging (TEE, TTE, and Cardiac CT) for trial eligibility will be confirmed by an 
independent core laboratory. 
• All baseline tests and assessments must be completed prior to registration. 
• Subjects will be randomized or treated only after the investigational site personnel have 
confirmed and documented that the subject has met all eligibility criteria, the imaging core 
labs have confirmed eligibility, and the SEC has concurred with the local site heart team 
that the subject has been treated per applicable standards and can be treated in either the 
Randomized, Non-repairable or Severe MAC cohorts of the trial. 
• Randomization will be stratified by site, assigned in permuted block sizes, and block sizes 
will not be disclosed to the sites.  
12.7.2 Maintaining Similar Levels of Follow-up 
The follow-up schedule for all registered subjects (Treatment and Control groups), including those 
that have been designated as a roll-in subject, is identical.  Subjects will be followed by the local 
site heart team and will continue to be treated per standard of care consistent with the subject’s 
condition prior to trial registration. 
12.7.3 Review of Trial Imaging Assessments 
MR severity, MR etiology, left ventricular dimensions, along with other measures, will be assessed 
by Echocardiography and Cardiac CT Core Laboratories at baseline and during follow-up.  
12.7.4 Safety and Effectiveness Monitoring 
All SAEs will be reviewed by the Sponsor (and/or designee).  SAEs requiring adjudication will be 
submitted to an independent CEC.  Every effort will be made to keep the CEC blinded to the 
subject’s treatment assignment. 
12.7.5 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: 

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SUMMIT 
 
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 trial to provide the reason 
for withdrawal and ask them if the investigator may contact them at the end of the trial 
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 survival status (only the status will be sent to 
Sponsor, not any subject identifying information). 
In addition to aforementioned steps, investigational sites will be educated on the importance of 
maintaining low rates of withdrawals for all registered subjects, including those that have been 
designated as a roll-in, and will be expected to make every effort to maintain low withdrawals 
during trial conduct.  Withdrawals from the trial will require discussion between the investigator 
and the Sponsor.  
12.8 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 trial 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.  
12.9 Sponsor Support for Regulatory Body Inspection 
In the event an investigator is contacted by a Regulatory Agency regarding this clinical trial, the 
Investigator shall 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 clinical trial (e.g., Form FDA 483, Inspectional Observations, and 
warning letters).  As necessary, the Sponsor may provide any assistance in preparing and/or 
responding to regulatory inspections. 
12.10   Sponsor Auditing 
The Sponsor may conduct periodic Quality Assurance audits (on-site audits) at various 
investigational sites.  These audits will be conducted as follows: 
• The Sponsor shall prepare an audit plan as well as the operating procedures for the related 
duties, and conduct audits in accordance with the audit plan and the operating procedures. 
• Individual engaged in auditing (hereinafter referred to as "auditor") shall be different than 
those in charge of medical device development or monitoring. 
• The auditor shall prepare an audit report documenting the matters confirmed in the audit 
to certify and verify that the audit has been conducted, and submit them to the Sponsor. 

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12.11 Committees 
12.11.1 Steering Committee (SC) 
The Steering Committee is responsible for providing trial leadership and overseeing the scientific 
and operational aspects of the trial. This committee will meet regularly to monitor subject 
enrollment and registration, general data collection and non-compliance with the CIP at individual 
sites, to review and act upon recommendations of the DSMB, to review operational issues that 
may arise and warrant a CIP amendment or other corrective action, and to determine policy 
regarding any publications arising from data generated from the performance of the trial. 
12.11.2 Subject Eligibility Committee (SEC) 
The SEC will confirm that each subject is symptomatic despite being on GDMT, has been 
adequately treated per applicable standards (e.g., coronary artery disease and left ventricular 
dysfunction), and meets trial entrance criteria.  The committee will also confirm whether the 
subject is appropriate for TEER as well as the appropriate cohort of the trial. 
The SEC will be comprised of, at a minimum, representatives from the following specialties:  
cardiothoracic surgery (with expertise in mitral valve surgery), interventional cardiology (with 
expertise in mitral valve therapies, including MitraClip) and may include cardiology (with 
expertise in heart failure).  The composition, guiding policies, and operating procedures governing 
the SEC are described in a separate SEC Charter. 
12.11.3 Publications Committee 
The Publication Committee will oversee and guide the ongoing scientific presentation and 
publication activities for the SUMMIT trial.  The Publication Committee will determine policies 
and strategies regarding presentations and/or publications arising from trial generated data.  The 
committee will also review and approve all external requests for accessing trial-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. 
12.11.4 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.   
The DSMB may consider a recommendation for modifications or termination of the clinical 
investigation based on any perceived safety concerns regardless of statistical significance. The 
recommendations of the DSMB are not binding, and all final decisions related to clinical 
investigations modifications rest with the Sponsor.  
12.11.5 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 trial.  The CEC will be responsible for adjudicating 
adverse events reported in the trial.  The composition, guiding policies, and operating procedures 
are defined in a separate CEC Charter. 

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13 DATA HANDLING AND RECORD KEEPING 
 
Sponsor and/or its affiliates will maintain documentation of the systems and procedures used in 
data collection for the duration of the clinical investigation. 
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 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 the Sponsor. 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 trial, 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 the Sponsor.  
For the clinical trial 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/EC and clinical 
trial monitor/Sponsor, AE reports, and information regarding subject discontinuation or 
completion of the clinical trial. 
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.   
13.2 Protection of Personally Identifiable Information 
The Sponsor respects and protects personally identifiable information collected or maintained for 
this clinical investigation.  
The Sponsor implements technical and physical access controls to ensure that Personal 
Information is accessible only to and processed only on a ‘need to know’ basis, including periodic 
review of access rights, and revocation of access when an individual’s employment is terminated 
or the individual transitions to a role that does not require access to Personal Information, and 
appropriate restrictions on physical access to premises, facilities, equipment, and records 
containing Personal Information. 
The Sponsor requires the investigational sites to transfer into Sponsor’s data management systems 
only pseudonymous Personal Information (key-coded) necessary to conduct the Clinical 
Investigation, such as the patient’s medical condition, treatment, dates of treatment, etc. The 
Sponsor discloses as part of the clinical investigation informed consent process that some Sponsor 
representatives still may see Personal Information at the participating sites for technical support of 

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the participating physicians on the device implant or procedures, monitoring and quality control 
purposes. Confidentiality of Personal Information will be observed by all parties involved at all 
times throughout the clinical investigation. The privacy of each subject and confidentiality of 
his/her information will be preserved in reports and when publishing any data. 
The Sponsor data management systems and processes were designed, developed, and tested 
according to industry standards to appropriately safeguard Confidential Information (including any 
Personal Information) against unauthorized access and/or interference by third parties, intrusion, 
theft, destruction, loss or alteration. Clinical Investigation data are encrypted in transit and at rest.  
The Sponsor maintains a Privacy Incident procedure that complies in all respects with Applicable 
Law and industry best practices. 
13.3 Data Management Plan 
A Data Management Plan (DMP) will describe procedures used for data review, data cleaning, 
and issuing and resolving data discrepancies. If appropriate, the DMP may be updated throughout 
the duration of the clinical investigation. All revisions will be tracked and document controlled. 
13.4 Source Documentation 
 
Regulations and GCPs require that the investigator maintain information in the subject’s medical 
records that corroborates data collected on the eCRFs.   Throughout the clinical trial 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 trial 
progress records, laboratory reports, eCRFs, signed ICFs, device accountability records, 
correspondence with the IRB/EC and clinical trial monitor or Sponsor, AE reports, and information 
regarding subject discontinuation or completion of the clinical trial.  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 trial sufficient 
to verify CIP entry criteria. 
• Dated and signed notes on the day of entry into the trial 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. 
• Trial required laboratory reports and 12-lead ECGs, signed and dated for review and 
annotated for clinical significance of out of range results.  

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Note: With electronic medical records some clinical sites may be able to annotate that the 
labs or ECG have been reviewed in the system. For those sites that do not have such 
capability, the labs or ECG may be able to be printed or signed. 
• Notes regarding CIP required and/or prescription medications taken during the trial 
(including start and stop dates). 
• Subject’s condition upon completion of or withdrawal from the trial. 
• Patient reported outcome measures may be completed using CRF worksheets. These serve 
as the source documentation. 
• Any other data required to substantiate data entered into the eCRF. 
13.5 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 trial. The investigator will ensure 
the accuracy, completeness, legibility, and timeliness of the data reported to the Sponsor on the 
CRFs and in all required reports. 
Only authorized site personnel will be permitted to enter the CRF data through the EDC system 
deployed by the Sponsor. An electronic audit trail will be used to track any subsequent changes of 
the entered data. 
13.6 Record Retention 
 
The Sponsor will archive and retain all documents pertaining to the trial as per the applicable 
regulatory record retention requirements. 
The investigator will maintain all CRFs, essential trial documents, and any source documentation 
that supports data collected on trial subjects, in compliance with regulations and their local IRB/EC 
requirements.   The Investigator must obtain permission from Sponsor in writing before destroying 
or transferring control of any clinical investigation records.  
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.    
13.6.1 Investigator Records 
Investigators will maintain the following complete, accurate, and current records relating to the 
investigator’s participation in this trial including, but not limited to: 
• Trial-related correspondence with another investigator, an IRB/EC, the Sponsor, monitors, 
subjects, or regulatory agencies, including required reports that relate to this trial 
• Device Accountability log 
• Delegation of Authority log 
• Subject’s case history records 

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• 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 trial deviation 
• Clinical investigation plan and amendments 
• Trial personnel training records 
• Signed investigator agreement and clinical trial reimbursement agreement 
• Current curriculum vitae (current by address) 
• Current medical license (current by date) 
• 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. 
13.6.2 Sponsor Records 
The Sponsor will maintain the following records:  
• Trial-related correspondence (including correspondence with regulatory/competent 
authorities and IRB/EC) that pertains to the investigation, including IRB/EC 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 trial 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 trial 
personnel 
• eCRFs submitted by investigator and center-specific samples of ICFs and protocols 
• Progress reports 
• Final clinical trial report 
• Records of adverse device effects (anticipated and unanticipated) and device deficiencies 
• All other records required by applicable regulations and any other regulatory/competent 
authority requirements. 

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14 ETHICAL CONSIDERATIONS 
 
IRB/EC 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 
clinical trial.  The approval letter must be received prior to the start of the trial 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/EC, the Sponsor, and/or the 
regulatory agencies/competent authorities. Any amendments to the CIP as well as associated ICF 
changes will be submitted to the IRB/EC and written approval obtained prior to implementation, 
according to each institution’s IRB/EC requirements. No changes will be made to the CIP or ICF 
or other written information provided to the patient without appropriate approvals, including 
IRB/EC, the Sponsor, and the regulatory agencies (if applicable). 
Until the clinical trial is completed, the investigator will update the IRB/EC of the progress of this 
clinical trial, per IRB/EC requirements.  Written approval must be obtained from the IRB/EC 
annually to continue the clinical trial, or according to each institution’s IRB/EC requirements.  
Further, any amendments to the CIP as well as associated ICF changes will be submitted to the 
IRB/EC and written approval obtained prior to implementation, according to each institution’s 
IRB/EC 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 CLINICAL INVESTIGATION CONCLUSION 
The clinical investigation will be concluded when: 
• All sites are closed AND 
• The final report has been provided to investigators or the Sponsor has provided formal 
documentation of clinical investigation closure. The final report will be submitted within 
six months of the end of the investigation. 
16 PUBLICATION POLICY 
 
The data and results from this trial are the sole property of the Sponsor.  The Sponsor shall have 
the right to access and use all data and results generated during the trial.  The investigators will not 
use trial-related data without the written consent of the Sponsor for any other purpose than for trial 
completion or for generation of publication material, as referenced in the clinical trial 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 trial 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 trial site agreement. 
The Sponsor will register the clinical trial 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 

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ClinicalTrials.gov.  Investigational sites shall not take any action to register the trial.  A full report 
of the pre-specified outcomes, including any negative outcomes, will be made public through 
www.clinicaltrials.gov 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 www.clinicaltrials.gov. 
17 RISK ANALYSIS 
 
Risk evaluation was conducted in accordance with EN ISO 14971:2012: Medical Devices - 
Application of Risk Management to Medical Devices.   
17.1 Anticipated Clinical Benefits 
Data obtained from an ongoing clinical trial with the Tendyne device appears to show that subjects 
experience (post-procedure) reductions in MR severity, along with improvements in Quality of 
Life, functional capacity and left ventricular volumes and dimensions[65,66].  Additional potential 
benefits of the use of the Tendyne device may include, but are not limited to, the following: 
• Reduction in hospitalization rate due to complete elimination of MR 
• Improved symptomatic status and quality of life  
• Reduced mortality 
• Reduced rates of recurrent MR 
• Mitral valve replacement with avoidance of risks associated with cardiopulmonary bypass 
(CPB)  
17.2 Foreseeable Adverse Events and Anticipate Adverse Device Effects 
As previously described, Table 4 indicates all anticipated AEs/risks associated with the use of the 
Tendyne Transcatheter Mitral Valve System.  Risks associated with the specified device and 
procedure are described in the Instructions for Use.  There may be risks related to the device under 
investigation that are unknown at present.  Likewise, the exact frequency of the risk may be 
unknown. 
17.3 Residual Risks Associated with the Device Under Investigation, as Identified in the 
Risk Analysis Report 
Risk analysis of the Tendyne Transcatheter Mitral Valve has been performed in accordance with 
the risk management plant and Failure Mode Effect Analysis (FMEA) (Ref: RM0004) to 
systemically identify potential hazards associated with the design and use of this device. Based 
upon bench testing and prior clinical studies data, all risks have been identified and determined to 
be within acceptable levels. 
17.4 Risks Associated with Participation in the Clinical Trial 
The risk associated with trial-required testing and assessments are summarized in Table 7.  
Although routine, these tests and assessments may be performed at greater frequency than standard 
of care practices.  

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Table 7.  Trial Procedure-Related Risks 
Trial 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 trial  
Hemodynamics 
A separate written informed consent process consistent 
with clinic policies and practices will occur outside of trial 
Computed tomography angiography 
(CTA) 
A separate written informed consent process consistent 
with clinic policies and practices will occur outside of trial 
Surgical valve replacement 
procedure or surgical repair 
procedure  
A separate written informed consent process consistent 
with clinic policies and practices will occur outside of trial  
17.5 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 
17.6 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. 

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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 trial are minimized through device 
design, investigator selection and training, pre-specified subject eligibility requirements, trial 
monitoring to ensure adherence to the CIP and the use of a DSMB.  Stopping rules will be 
discussed with the DSMB and applied for subject safety through enrollment.  A steering committee 
will provide operational and scientific oversight. All SAEs and device deficiencies will be reported 
to the Sponsor and will be monitored internally for safety surveillance purposes. 
17.7 Risk to Benefit Rationale  
The Tendyne Transcatheter Mitral Valve System represents a novel, state-of-the-art technology 
that provides the unique benefit of treatment of mitral regurgitation. The potential risks are well 
tolerated when compared with other treatment options for symptomatic, severe MR.  Therefore, 
the incremental benefits of the Tendyne Transcatheter Mitral Valve System outweigh the risks 
associated with this product.  

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APPENDIX I:  ABBREVIATIONS AND ACRONYMS 
Acronym 
Definition 
Acronym 
Definition 
6MWD/T 
Six Minute Walk Distance/Test 
IFU 
Instructions for Use 
ACC 
American College of Cardiology 
IMR 
Ischemic Mitral Regurgitation 
AE 
Adverse Event 
INR 
International Normalized Ratio 
AHA 
American Heart Association 
IRB 
Institutional Review Board 
CABG 
Coronary Artery Bypass Grafting 
KCCQ 
Kansas City Cardiomyopathy Questionnaire 
CAP 
Continued Access Plan 
LV 
Left Ventricle 
CCS 
Canadian Cardiovascular Society 
LVEDD 
Left Ventricular End Diastolic Dimension 
CEC 
Clinical Events Committee 
LVEDV 
LVEDV Left Ventricle End Diastolic Volume 
CFR 
Code of Federal Regulations 
LVEF 
Left Ventricular Ejection Fraction 
CIP 
Clinical Investigational Plan 
LVESD 
Left Ventricular End Systolic Dimension 
COPD 
Chronic Obstructive Pulmonary Disease 
LVESV 
Left Ventricular End Systolic Volume 
CRO 
Contract Research Organization 
LVOT 
Left Ventricular Outflow Tract 
CRT 
Cardiac Resynchronization Therapy 
MAC 
Mitral Annular Calcification 
CT 
Computerized Tomography 
MI 
Myocardial Infarction 
CV 
Cardiovascular 
MR 
Mitral Regurgitation 
CVA  
Cerebrovascular Accident 
MS 
Mitral Stenosis 
DD 
Device Deficiency 
MV 
Mitral Valve 
DAOH 
Days Alive and Out of Hospital 
MVARC 
Mitral Valve Academic Research Consortium 
DSMB 
Data and Safety Monitoring Board 
MVR 
Mitral Valve Replacement 
EACTS 
European Association for Cardio-
Thoracic Surgery 
NYHA 
New York Heart Association 
EC 
Ethics Committee 
PAS 
Pulmonary Artery Systolic pressure 
ECG 
Electrocardiogram 
PCI 
Percutaneous Coronary Intervention 
EDC 
Electronic Data Capture 
PG 
Performance Goal 
EFT 
Essential Frailty Toolset 
PROM 
Predicted Risk of Mortality 
EROA 
Effective Regurgitant Orifice Area 
QoL 
Quality of Life 
ESC 
European Society of Cardiology 
RCT 
Randomized Control Trial 
FDA  
U.S. Food and Drug Administration 
RVSP 
Right Ventricular Systolic Pressure 
GCP  
Good Clinical Practices 
SAE 
Serious Adverse Event 
GDMT 
Guideline Directed Medical Therapy 
SEC 
Subject Eligibility Committee 
HF 
Heart Failure 
SF-12 
Short Form Health Survey 
HFH 
Heart Failure Hospitalization 
STS 
Society of Cardiothoracic Surgeons 
HIPAA 
Health Insurance Portability and 
Accountability Act 
TEE 
Transesophageal Echocardiogram 
ICD 
Implantable Cardioverter Defibrillator 
TEER 
Transcatheter Edge-to-Edge Repair 
ICF 
Informed Consent Form 
TTE 
Transthoracic Echocardiogram 
ICH 
International Council for Harmonization 
TMVR 
Transcatheter Mitral Valve Replacement 
IDE 
Investigational Device Exemption 
UADE 
Unanticipated Adverse Device Effect 
 
 

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APPENDIX II:  DEFINITIONS 
The following definitions will be used in the SUMMIT trial Clinical Investigational Plan.  All 
events constituting primary or secondary endpoints will be adjudicated by the independent Clinical 
Events Committee, along with relationship to the Treatment or Control group device and/or 
procedure. 
Bleeding 
Bleeding is defined per MVARC, which is based on the modified VARC-2 and modified Bleeding 
Academic Research Consortium (BARC) [69].  For this trial, the CEC will adjudicate bleeding 
events based on the tables below.  
MVARC Primary Bleeding Scale (Modified VARC-2) 
I.  Minor 
Any overt, actionable sign of hemorrhage (e.g., more bleeding than would be expected for a 
clinical circumstance, including bleeding found by imaging alone) that meets ≥1 of the 
following: 
• requiring nonsurgical medical intervention by a health care professional 
• leading to hospitalization or increased level of care 
• prompting evaluation; or requires 1 or 2 U of whole blood or packed RBC 
transfusion; and 
• does not meet criteria for major, extensive, or life-threatening bleeding. 
II. Major 
Overt bleeding either associated with: 
• a drop in the hemoglobin of ≥3.0 g/dl or requiring transfusion of ≥3 U of whole blood 
or packed RBCs, and  
• does not meet criteria of life-threatening or extensive bleeding. 
III. Extensive 
Overt source of bleeding with: 
• a drop in hemoglobin of ≥4 g/dl or whole blood or packed RBC transfusion ≥4 U 
within any 24-h period, or 
• drop in hemoglobin of ≥6 g/dl or whole blood or packed RBC transfusion ≥4 U 
(BARC type 3b) within 30 days of the procedure. 
IV. Life-threatening 
Bleeding in a critical organ, such as intracranial, intraspinal, intraocular, or pericardial 
necessitating surgery or intervention, or intramuscular with compartment syndrome OR 
bleeding causing hypovolemic shock or hypotension (systolic blood pressure <90 mm Hg 
lasting >30 min and not responding to volume resuscitation) or requiring significant doses 
of vasopressors or surgery. 
V. Fatal 
Bleeding adjudicated by the CEC as being a proximate cause of death. Severe bleeding 
adjudicated as being a major contributing cause of a subsequent fatal complication, such as 
MI or cardiac arrest, is also considered fatal bleeding. 
Modified BARC Bleeding Scale (Secondary Use) 
Type 0 

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No bleeding. 
Type 1 
Bleeding that is not actionable and does not cause the patient to seek unscheduled performance of 
studies, hospitalization, or treatment by a health care professional.  May include episodes leading to 
self-discontinuation of medical therapy by the patient without consulting a health care professional 
Type 2 
Any overt, actionable sign of hemorrhage (e.g., more bleeding than would be expected for a clinical 
circumstance, including bleeding found by imaging alone) that does not fit the criteria for type 3, 4, 
or 5 but does meet at least one of the following criteria:  
• 
requiring nonsurgical, medical intervention by a healthcare professional 
• 
leading to hospitalization or increased level of care, or  
• 
prompting evaluation 
Type 3 
Type 3a  
• 
Overt bleeding plus hemoglobin drop of 3 to <5 g/dL* (provided  hemoglobin drop is related to 
bleed)  
• 
Any transfusion with overt bleeding 
Type 3b  
• 
Overt bleeding plus hemoglobin drop ≥5 g/dL* (provided hemoglobin drop is related to bleed)  
• 
Cardiac tamponade 
• 
Bleeding requiring surgical intervention for control (excluding dental/nasal/skin/hemorrhoid) 
• 
Bleeding requiring intravenous vasoactive agents 
Type 3c  
• 
Intracranial hemorrhage (does not include microbleeds or hemorrhagic transformation, does 
include intraspinal) 
• 
Subcategories confirmed by autopsy or imaging or lumbar puncture 
• 
Intraocular bleed compromising vision 
Type 4 (periprocedural) 
• 
Perioperative intracranial bleeding within 48 h 
• 
Reoperation after closure of sternotomy for the purpose of controlling bleeding 
• 
Transfusion of ≥5 U whole blood or packed red blood cells within a 48-h period† 
• 
Chest tube output ≥2L within a 24-h period 
Type 5 (fatal bleeding) 
Type 5a  
• 
Probable fatal bleeding; no autopsy or imaging confirmation but clinically suspicious 
Type 5b 
• 
Definite fatal bleeding; overt bleeding or autopsy or imaging confirmation 
 
 
 
 

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Canadian Cardiovascular Society Grading of Angina Pectoris (CCS Angina Classification) 
CCS Angina Classification is defined by the Canadian Cardiovascular Society [79] as: 
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. 
Cardiovascular Death 
Cardiovascular death is defined by VARC II [80], as any one of the following: 
• Death due to proximate cardiac cause (e.g., myocardial infarction, cardiac tamponade, 
worsening heart failure) 
• Death caused by non-coronary vascular conditions such as neurological events, pulmonary 
embolism, ruptured aortic aneurysm, dissecting aneurysm, or other vascular disease 
• All procedure-related deaths, including those related to a complication of the procedure or 
treatment for a complication of the procedure 
• All valve-related deaths including structural or non-structural valve dysfunction or other 
valve-related adverse events 
• Sudden or unwitnessed death 
• Death of unknown cause 
Non-cardiovascular death is any death in which the primary cause of death is clearly related to 
another condition (e.g., trauma, cancer, suicide). 
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. 

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Relatedness 
Definition 
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. 
Chronic Kidney Disease 
The following definitions of Chronic Kidney Disease will be utilized in the trial, as stated from 
National Institute for Health & Clinical Excellence [81]: 
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 SUMMIT trial, 
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 trial, as applicable. 

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Endocarditis 
Defined as a diagnosis of endocarditis based on the following Duke criteria [82]: 
Criteria 
Definition 
Pathological Criteria • Microorganisms: culture or histology in a vegetation, in a vegetation 
that has embolized, or in an intracardiac abscess, or  
• Pathological lesions: vegetation or intracardiac abscess present, 
confirmed by histology showing active endocarditis; or 
Major Clinical 
Criteria 
• Persistently positive blood cultures: 
o Typical organisms for endocarditis: Streptococcus viridans, S 
bovis, “HACEK” group, community acquired Staphylococcus 
aureus or enterococci, in the absence of a primary focus  
• Persistent bacteremia:  
o ≥ 2 positive cultures separated by ≥12 hours or ≥ 3 positive cultures 
≥ 1 h apart or 70% blood culture samples positive if ≥ 4 are drawn 
• Evidence of endocardial involvement 
o Positive echocardiogram 
▪ Oscillating vegetation 
▪ Abscesses 
▪ Valve perforation 
▪ New partial dehiscence of prosthetic valve 
o New valvular regurgitation 
Minor Clinical 
Criteria 
• Predisposing heart condition:  MVP, bicuspid aortic valve, rheumatic 
or congenital heart disease, intravenous drug use  
• Fever 
• Vascular phenomena:  Major arterial emboli, septic pulmonary 
emboli, mycotic aneurysm, intracranial hemorrhage, Janeway lesions 
• Immunologic phenomena:  Glomerulonephritis, Osler's nodes, Roth 
spots, and rheumatoid factor 
• Positive blood culture: not meeting major criteria  
• Echocardiogram: positive but not meeting major criteria 
Note:  Clinical Diagnosis of Endocarditis is based on: 
• 2 major criteria; or 
• 1 major + 3 minor criteria; or 
• 5 minor criteria 
Guideline Directed Medical Therapy (GDMT) 
Guideline Directed Medical Therapy (GDMT) is defined per the ACC/AHA/HFSA Heart Failure 
Guidelines [83].  GDMT must be documented for a minimum of 30 days prior to intended trial 
registration and subject must be on appropriate class of medications, which typically include: ACE 
Inhibitor or Angiotensin II Receptor Blocker, Beta-Blocker, and diuretic as appropriate. 
 

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Hospitalization (All-cause) 
Admission to inpatient unit or ward in the hospital for at least 24 hours, including emergency 
department stay.  Excludes the index procedure hospitalization as well as 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: 
Hospitalization (Cardiovascular):  Treatment in any inpatient unit or ward in the hospital for at 
least 24 hours, including emergency department stay for cardiovascular 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 unit or ward hospitalization for at least 24 hours 
including emergency stay that requires treatment for 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 (MitraClip) device implant is first attempted. 
Left Ventricular Dysfunction 
Subjects enrolled in the SUMMIT trial 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  

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• 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  
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 (e.g., CT), heart failure specialists, cardiac anesthesiologists, 
intensivists, nurses, and social workers. 
Mitral Regurgitation Etiology 
Defined in Figure 2, adapted from the 2017 ACC Expert Consensus Decision Pathway for MR 
[84]. 
 

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Figure 2.  Decision Tree for Determining MR Etiology 
 

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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 
Mitral Valve Academic Research Consortium (MVARC) 
The following MVARC endpoints will be captured for the Tendyne device and Control group in 
the study cohorts [72]. 
MVARC (Tendyne) 
MVARC (Control Group) 
Technical Success 
Measured at exit from procedure room: 
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 
reintervention related to the device or 
access procedure 
Note: Criterion #3 above has been 
modified from the MVARC guidelines 
since the Tendyne device is designed to be 
fully retrievable, and thus allows the use of 
Technical Success  
Measured at exit from operating room:  
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 
reintervention related to the device or 
access procedure 
Note: Criterion #3 above has been 
modified from the MVARC guidelines as 
either a single or multiple MitraClip 
devices 
may 
be 
attempted 
and/or 

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SUMMIT 
 
MVARC (Tendyne) 
MVARC (Control Group) 
additional devices during the index 
procedure. 
ultimately implanted, and thus allows the 
use of additional devices during the index 
procedure. 
Device Success 
Measured at 30 days and at all later post-
procedural intervals: 
1) Absence of procedural mortality or stroke; 
and 
2) Proper placement and positioning of the 
device 
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 structural 
valve dysfunction (see Appendix II:  
Definitions), and with no greater than 
mild (1+) paravalvular MR (and 
without associated hemolysis). 
Note: Criterion #4c above has been 
modified from the MVARC guidelines, to 
align with the structural valve dysfunction 
definition used in this CIP. 
Device Success  
Measured at 30 days and at all later post-
procedural intervals:  
1) Absence of procedural mortality or stroke; 
and  
2) Proper placement and positioning of the 
device 
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 
mitral stenosis (i.e., post-procedure 
EOA is >1.5 cm2) with a transmitral 
gradient <5 mm Hg). 
Note: Criterion #4c above has been 
modified from the MVARC guidelines, as 
paravalvular leak is not applicable to 
MitraClip. 
Procedural Success 
All of the following must be present (measured 
at 30 days): 
1) Device 
success 
(either 
optimal 
or 
acceptable*); and 
2) Absence of major device or procedure 
related serious adverse events, including: 
a) Death 
b) Stroke 
c) Life-threatening bleeding (MVARC 
scale) 
 Procedural Success  
All of the following must be present 
(measured at 30 days):  
1) Device 
success 
(either 
optimal 
or 
acceptable*); and  
2) Absence of major device or procedure 
related serious adverse events, including: 
a) Death  
b) Stroke  
c) Life-threatening bleeding (MVARC 
scale)  

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SUMMIT 
 
MVARC (Tendyne) 
MVARC (Control Group) 
d) Major vascular complications 
e) Major cardiac structural complications 
f) Stage 2 or 3 acute kidney injury 
(includes new dialysis) 
g) Myocardial infarction or coronary 
ischemia requiring PCI or CABG 
h) Severe hypotension, heart failure, or 
respiratory 
failure 
requiring 
intravenous pressors or invasive or 
mechanical heart failure treatments 
such as ultrafiltration or hemodynamic 
assist devices, including intra-aortic 
balloon pumps or left ventricular or 
biventricular 
assist 
devices, 
or 
prolonged intubation for ≥ 48 hours. 
i) Any structural valve dysfunction, 
migration, 
thrombosis, 
or 
other 
complication requiring surgery or 
repeat intervention. 
d) Major vascular complications  
e) Major cardiac structural complications  
f) Stage 2 or 3 acute kidney injury 
(including new dialysis)  
g) Myocardial infarction or coronary 
ischemia requiring PCI or CABG  
h) Severe hypotension, heart failure, or 
respiratory 
failure 
requiring 
intravenous pressors or invasive or 
mechanical heart failure treatments 
such as ultrafiltration or hemodynamic 
assist devices, including intra-aortic 
balloon pumps or left ventricular or 
biventricular 
assist 
devices, 
or 
prolonged intubation for ≥ 48 hours  
i) Any device detachment, migration, 
thrombosis, or other complication 
requiring 
surgery 
or 
repeat 
intervention. 
Note: Criterion #2i above has been 
modified from the MVARC guidelines as 
structural 
valve 
dysfunction 
is 
not 
applicable to MitraClip. 
Patient Success 
All of the following must be present (measured 
at 12 months): 
1) Device 
success 
(either 
optimal 
or 
acceptable*); and 
2) Subject returned to the pre-procedural 
setting; and 
3) No re-hospitalizations or reinterventions 
for the underlying condition (e.g., mitral 
regurgitation, heart failure); 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). 
Patient Success  
All of the following must be present measured 
at 12 months):  
1) Device 
success 
(either 
optimal 
or 
acceptable*); and  
2) Subject returned to the pre-procedural 
setting; and  
3) No re-hospitalizations or reinterventions 
for the underlying condition (e.g., mitral 
regurgitation, heart failure); 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).  

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SUMMIT 
 
MVARC (Tendyne) 
MVARC (Control Group) 
*MR reduction is considered optimal when post-procedure MR is reduced to trace or absent. 
MR reduction is considered acceptable when post-procedure MR is reduced by at least 1 class 
or grade from baseline and to no more than moderate (2+) in severity. 
Myocardial Infarction 
Myocardial infarction (MI) classification and criteria for diagnosis is defined by MVARC, which 
incorporates elements of the Third Universal definition of MI [72], [85]. 
MI Type 
Definition 
Periprocedural 
MI 
(≤48 hours after the 
index procedure) 
• New ischemic symptoms (e.g., chest pain or shortness of breath), 
or new ischemic signs (e.g., ventricular arrhythmias, new or 
worsening heart failure, new ST-segment changes, hemodynamic 
instability, new pathological Q-waves in at least two contiguous 
leads, imaging evidence of new loss of viable myocardium or 
new wall motion abnormality) AND 
• The peak CK-MB measured within 48 h of the procedure rises to 
≥ 10x the local laboratory ULN plus new ST-segment elevation 
or depression of  ≥1 mm in ≥2 contiguous leads (measured 80 ms 
after the J-point), or to ≥5x ULN with new pathological Q waves 
in ≥2 contiguous leads or new persistent LBBB, OR in the 
absence of CK-MB measurements and a normal baseline cTn, a 
cTn (I or T) level measured within 48 h of the PCI rises to ≥70x 
the local laboratory ULN plus new ST-segment elevation or 
depression of ≥1 mm in ≥2 contiguous leads (measured 80 ms 
after the J-point), or ≥35x ULN with new pathological Q waves 
in ≥2 contiguous leads or new persistent LBBB. 
Spontaneous MI (>48 
hours after the index 
procedure) 
• Detection of rise and/or fall of cardiac biomarkers (preferably 
troponin) with at least one value above the 99th percentile URL, 
together with the evidence of myocardial ischemia with at least 
one of the following: 
o ECG changes indicative of new ischemia (new ST-T 
changes or new left bundle branch block (LBBB)) 
o New pathological Q-waves in at least two contiguous leads 
o Imaging evidence of a new loss of viable myocardium or 
new wall motion abnormality 
o Sudden, unexpected cardiac death, involving cardiac arrest, 
often with symptoms suggestive of myocardial ischemia, 
and accompanied by presumable new ST elevation, or new 
LBBB, and/or evidence of fresh thrombus by coronary 
angiography and/or at autopsy, but death occurring before 
blood samples could be obtained, or at a time before the 
appearance of cardiac biomarkers in the blood. 

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SUMMIT 
 
 
 
 
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. 
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. 
Randomization (from ISO 14155) 
Process of assigning subjects to the investigational medical device or comparator groups using an 
established, recognized statistical methodology to determine the assignment in order to reduce bias. 
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. 
Single Leaflet Device Attachment (SLDA) 
The loss of insertion of a single leaflet from the MitraClip device with ongoing insertion of the 
opposing leaflet [65]. 
Stroke and TIA (from VARC II) 
The following stroke and TIA diagnostic criteria will be used in this trial, per VARC II [80]: 
• 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 
MI Type 
Definition 
o Pathological findings of an acute myocardial infarction. 

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SUMMIT 
 
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 [77]. 
• 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. 
Structural Valve Dysfunction 
Structural valve dysfunction will apply to Tendyne only, and will be defined as hemodynamic 
dysfunction (moderate or severe) in the presence of morphologic dysfunction. These definitions 
were adapted based on the EAPCI Consensus Statement [86] and the ASE Guidelines [87]: 
Type of Valve Dysfunction 
Definition 
Moderate hemodynamic dysfunction • Mean transvalvular gradient 6-10 mmHg OR 
• Moderate transvalvular regurgitation (grade 2-3+)  
Severe hemodynamic dysfunction 
• Mean transvalvular gradient >10 mmHg OR 
• Severe transvalvular regurgitation (grade 4+) 
Morphologic dysfunction 
• Leaflet abnormalities resulting in stenosis and/or 
central regurgitation, including: 
o Integrity – torn or flail 
o Structure – thickening or calcification 
o Function – impaired mobility 

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SUMMIT 
 
Type of Valve Dysfunction 
Definition 
• Strut/frame fracture 
• Tether rupture 
• Apical pad deterioration 
 
 
 
 
Society of Thoracic Surgeons (STS) Predicted Risk of Mortality (PROM) Score 
STS PROM scores for both “MV Replacement Only” and “MV Repair” will be calculated in the 
trial for the Tendyne device and Control group subjects.  The risk calculators can be completed 
online at http://riskcalc.sts.org/. 
 
 

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SUMMIT 
 
APPENDIX III:  SUBJECT SCREENING FLOW CHART 
 

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SUMMIT 
 
APPENDIX IV:  TRIAL 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 
 
X 
X 
 
X 
X 
X 
Cardiovascular Medications 
X 
X 
X 
X 
X 
X 
X 
X 
Essential Frailty Toolset (EFT) 
X 
 
 
 
 
 
 
 
STS PROM Risk Score 
X 
 
 
 
 
 
 
 
CCS Angina Classification 
X 
 
 
 
 
 
 
 
NYHA Classification 
X 
 
 
X 
 
X 
X 
X 
Modified Rankin Scale (mRS‡) 
X 
 
 
 
 
 
 
 
Six Minute Hall Walk Test 
X 
 
 
X 
 
X 
X 
X 
KCCQ 
X 
 
 
X 
 
X 
X 
X 
EQ-5D 
X 
 
 
X 
 
X 
X 
X 
SF-12 
X 
 
 
X 
 
X 
X 
X 
CLINICAL LABORATORY TESTS 
Pregnancy Test 
X 
 
 
 
 
 
 
 
Creatinine 
X 
 
X 
X 
 
X 
X 
X 
Plasma–free Hemoglobin 
X 
 
 
X 
 
X 
X 
X 
BNP or NT pro-BNP 
X 
 
 
X 
 
X 
X 
X 
International Normalized Ratio 
(INR) 
X 
 
X 
X 
 
X 
X 
X 
Creatine Kinase-MB (CK-MB) if 
indicated 
X 
 
X 
X 
 
X 
X 
X 
Troponin (Type I or T) if 
indicated  
X 
 
X 
X 
 
X 
X 
X 
Serum albumin 
X 
 
 
 
 
 
 
 
INTRAOPERATIVE HEMODYNAMICS – (Tendyne Only) 
Cardiac Output 
 
X 
 
 
 
 
 
 
PA Pressures 
 
X 
 
 
 
 
 
 
RA Pressures 
 
X 
 
 
 
 
 
 
Aortic 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 
TEE 
X 
X 
 
 
 
 
 
 
TTE^ 
X 
 
X 
X 
 
X 
X 
X 
OTHER 
Device Deficiencies 
 
X 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
Protocol Deviations 
X 
X 
X 
X 
X 
X 
X 
X 
COVID-19 Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
*The 3 month visit will be conducted via telephone. 
‡Modified Rankin Scale is also to be completed after suspected onset of stroke^ 
^TTE imaging must be conducted between 60 and 120 days after anticoagulation stoppage for subjects implanted with the Tendyne valve. If the TTE 
identifies suspected valve dysfunction, contrast-enhanced cardiac CT imaging is also required. If renal insufficiency precludes a cardiac CT, a TEE must 
be performed instead. 
Note: Baseline imaging for Cardiac CT, TEE and TTE must be acquired no earlier than 120 days prior to subject consent.  

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SUMMIT 
 
 
APPENDIX V:  ESSENTIAL FRAILTY TOOLSET 
The Essential Frailty Toolset (EFT) will be used to assist the local site heart team and SEC in 
determining whether a subject is suitable for mitral valve surgery, as previously outlined in Section 
6.1.2.  The following figure describes the components and scoring method for this test [86].   
Additional instructions for conducting the five chair raises, assessing cognitive impairment (using 
the Mini-CogTM), and obtaining laboratory values will be provided as part of trial training.  
 

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SUMMIT 
 
APPENDIX VI:  CONTACT INFORMATION 
Any questions, including requests for a list of investigational sites, can be obtained upon request 
to the Clinical Project Manager (or designee) for the trial. 
Abbott Medical 
177 County Road B East 
St. Paul, MN 55117 
United States 
Phone: +1 (651) 289-5500 
E-mail:  Summit.Trial@abbott.com 
 
 
 

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SUMMIT 
 
APPENDIX VII: ACCOMPANYING INFORMATION 
Investigational device labels, case report forms, and informed consent form template have all been 
provided under separate cover and are available on request from the Sponsor. 
 
A copy of the monitoring plan can be obtained on request from the Sponsor clinical project 
manager. 
 
See Appendix VI: Contact Information.   
 
 

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SUMMIT 
 
APPENDIX VIII: NON-SUITABILITY CRITERIA FOR TEER  
Inability to perform TEER 
• Intracardiac thrombus* 
• Imaging limitations precluding TEER* 
• Not suitable for transfemoral/transseptal procedure 
Risk of stenosis following TEER 
• Carpentier Class IIIa (e.g., Rheumatic, radiation, chronic inflammatory condition) 
• Severe Mitral annular calcification with MS  
• Calcified or fibrotic leaflets with restricted leaflet motion 
• Prior surgical annuloplasty or ring with potential for stenosis* 
• Prohibitively small mitral valve area (e.g., MVA < 3.5 cm2) or pre-existing mitral gradient 
Risk of inadequate MR reduction with TEER 
• Post endocarditis, leaflet tissue loss/perforation 
• Active endocarditis* 
• Short (<5 mm in grasping zone) or restricted posterior leaflet 
• MR primarily due to clefts 
• Extreme mitral valve complexity precluding successful TEER 
o Severe Barlow’s disease / multiple significant regurgitant jets 
o Excessive redundancy 
o Leaflet calcification 
o Poor coaptation reserve inhibiting restoration of coaptation 
Futility 
• Life expectancy <12 months, insufficient MR, inotropic support not related to MV disease* 
• Less than 3+/4+ MR by quantitative echo assessment* 
• Patients with inotropic requirement not thought to be related to mitral valve disease* 
Summarized from DS Lim, et al (2021). “Consensus Document on Non-Suitability for 
Transcatheter Mitral Valve Repair by Edge-to-edge Therapy [66]. Criteria marked with a “*” are 
not applicable to the review of TEER suitability within SUMMIT as these are trial exclusion 
criteria. 
 

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SUMMIT 
 
APPENDIX IX:  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/EC 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 
12Feb2018 
Not Applicable 
First release of CIP 
02P 
13Mar2018 
• 
Updated indications for use statement and trial 
eligibility criteria to include an estimated 
surgical mortality risk of ≥ 3%. 
• 
Updated 
the 
minimum 
anticoagulation 
requirement for subjects receiving the Tendyne 
device to 6 months. 
• 
Added imaging requirement of having a TTE 
conducted between 60 and 120 days after 
stoppage of anticoagulation in subjects who 
received a bioprosthetic replacement valve 
(Tendyne or Control).  If TEE indicates signs of 
leaflet thrombosis, a cardiac CT must be 
conducted. 
• 
Added TTE imaging requirement for subjects 
implanted with a bioprosthetic mitral valve 
(Tendyne or Control device) who exhibit signs 
or symptoms of leaflet thrombosis.  If 
thrombosis is suspected, then a cardiac CT must 
be conducted to evaluate hypoattenuated leaflet 
thickening or motion. 
• 
Updated Periprocedural MI definition to be 
consistent with MVARC. 
Revision based on FDA 
feedback from 03Mar2018 
e-mail. 
A 
04Apr2018 
• 
Updated CIP to clarify Surgical and Non-
surgical primary endpoints will be measured 
using “completers”. 
• 
Updated secondary endpoint analysis details for 
Surgical and Non-surgical arms will be 
included within the SAP. 
• 
Added “CIP Revisions” appendix to CIP. 
• 
Updated TTE/CT imaging requirements for 
suspected leaflet thrombosis to cover a broader 
“valve dysfunction” category. 
• 
Updated imaging requirements for suspected 
valve dysfunction to allow a TEE, if subject has 
renal insufficiency and cannot undergo a CT. 
Revision based on FDA 
statistical recommendations 
from 16Mar2018 letter. 

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SUMMIT 
 
• 
Updated MVARC endpoints to be assessed for 
Control group and moved endpoint definitions 
to Appendix. 
B 
05Aug2019 
• 
Updated “Surgical Arm” to “Randomized 
Cohort” and “Non-Surgical Arm” to “Non-
Randomized Cohort” 
• 
Changed control therapy of Randomized cohort 
from mitral valve Surgery to MitraClip 
• 
Added MAC cohort for subjects with severe 
mitral annular calcification that renders them 
unsuitable candidates for conventional mitral 
valve surgery. Primary and secondary endpoint 
definitions and statistical analysis plan for these 
endpoints were also added. 
• 
Updated Exclusion criteria 1 to no longer 
exclude severe MAC or stenosis as these can be 
treated within the MAC cohort 
• 
Clarified exclusion criteria 18 to exclude 
“Hypertrophic or restrictive cardiomyopathy, 
or constrictive pericarditis” 
• 
Added exclusion criteria “33. Presence 
of 
other anatomic or comorbid conditions, or other 
medical, social, or psychological conditions 
that, in the investigator’s opinion, could limit 
the subject’s ability to participate in the clinical 
investigation or to comply with follow-up 
requirements, 
or 
impact 
the 
scientific 
soundness of the clinical investigation results.” 
• 
Update Primary Composite Endpoint for 
Randomized Cohort to Survival free of heart 
failure hospitalization at 12 months and 
adjusted sample size based on new event rate 
assumptions. 
• 
Modified 
Secondary 
Endpoints 
for 
Randomized Cohort to add survival free of MV 
reintervention and remove days in hospital 
post-index 
procedure 
and 
STS 
morbidity/mortality at 30 days 
• 
Added Secondary Endpoints to Randomized 
arm to include change in NYHA, KCCQ, and 
6MWD at 12 months, testing treatment vs. 
control for non-inferiority 
• 
Added Clinical Endpoint of All-cause mortality 
at 30 days, 1 year, and then yearly thorough 5 
years 
• 
Specified MR inclusion of moderate-to-severe 
or severe MR (MR ≥ Grade III per ASE 
guidelines) 
• 
Specified MAC cohort inclusion to be MR ≥ 
Grade III, severe MS or moderate MR and 
moderate or greater MS 
Study re-design required 
due to results from COAPT 
clinical trial and MitraClip 
indication expansion that 
will result in a new standard 
of care for secondary MR  
 
Added MAC cohort to 
initiate prospective single-
arm study in patients with 
severe mitral annular 
calcification within 
SUMMIT 
 
Assessments specific to 
surgical mortality/morbidity 
removed as surgery is no 
longer control therapy 
 
Standard language 
added/modified to align 
with Abbott structural heart 
standards 
 
The MAC primary endpoint 
was adjusted to incorporate 
feedback from FDA 
reviewers. The performance 
goal was established based 
on data from the GDMT-
only group within the 
COAPT study, as this 
population resembles the 
standard of care for patients 
with severe MAC 
 
Clarified patients in the 
randomized cohort would 
need to meet MitraClip 
indications 
 
Instituted limit that sites 
may not enroll more than 
20% of the total number of 
patients for a cohort 
 
Added former PIs of MAC 
study to be co-PIs of MAC 
cohort within SUMMIT 

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Page 108 of 122 
 
 
 
 
SUMMIT 
 
• 
Removed trial eligibility criteria of an estimated 
surgical mortality risk of ≥ 3%. 
• 
Changed baseline imaging windows to ≤120 
days prior to consent 
• 
Added rationale for randomizing to MitraClip 
rather than surgery 
• 
Updated Tendyne results to align with 100 
patients at 1 yr manuscript (Sorajja, et al. 2019) 
• 
Applied standard MVARC endpoint definitions 
for MitraClip group 
• 
Updated 
Structural 
Valve 
Dysfunction 
definition to be hemodynamic dysfunction in 
the presence of morphologic dysfunction. 
• 
Changed 
definition 
of 
heart 
failure 
hospitalization to only include inpatient events 
(>24 hrs) 
• 
Removed references to a subject’s authorized 
representative as subjects need to be able to 
provide written consent 
• 
Citation indices updated to incorporate new 
works cited 
• 
Updated Study Design and Subject Screening 
flow charts to align with new study design 
• 
Added Clinical Endpoint of annualized rate of 
heart failure hospitalization 
• 
Changed Primary endpoint of MAC cohort to 
survival free of heart failure hospitalization at 
one year post index procedure. The endpoint 
will be evaluated based on a performance goal. 
• 
Removed the MAC cohort Secondary safety 
endpoint (all-cause mortality at one year) due to 
redundancy with the new Primary endpoint 
• 
Updated statistical analysis section to reflect 
revised MAC cohort endpoint design and 
sample size calculations. 
• 
Corrected typographical errors 
• 
Clarified Randomized cohort is limited to 
subjects at prohibitive surgical risk (primary 
MR) or are symptomatic despite being on 
maximally-tolerated GDMT (secondary MR) 
• 
Added Paul Sorajja, M.D. and Vinod Thourani, 
M.D. as Co-Principal Investigators for the 
MAC cohort 
• 
Changed name of Safety Analysis population 
(MAC and Non-randomized cohorts) to 
Attempted Procedure population. 
• 
Updated nomenclature from transcatheter 
mitral 
valve 
replacement 
(TMVR) 
to 
transcatheter mitral valve intervention (TMVI) 
 
Changed the name of the 
Safety Analysis population 
because population will be 
used for more than safety 
analyses. 
C 
30Jun2020 
• 
Updated the Sponsor to Abbott Medical to 
reflect current filing status 
The COVID-19 pandemic 
was not accounted for in the 
statistical analyses proposed 

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05MAY2022 
CIP Template 86357 Rev. J 
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Page 109 of 122 
 
 
 
 
SUMMIT 
 
• 
Removed Josh Schumacher from authorship as 
he is no longer employed by the Sponsor 
• 
Added FDA-approved MitraClip Indication for 
Use (Appendix IX) 
• 
Corrected instances of “Transcatheter Mitral 
Valve 
Replacement 
(TMVR)” 
to 
“Transcatheter Mitral Valve Implantation 
(TMVI)”  
• 
Aligned with current SAP that no site may 
enroll more than 20% of the total number of 
subjects in any cohort 
• 
Re-phrased all endpoints to be described as 
“Freedom from” events for consistency across 
trial cohorts 
• 
Updated section describing outcomes in 
patients with severe MAC and cited publication 
on this patient population by Sorajja et al. in the 
Journal of the American College of Cardiology 
• 
Replaced “Global Feasibility Study” with 
“Expanded Clinical Study of the Tendyne 
Mitral 
Valve 
System” 
to 
align 
with 
ClinicalTrials.gov listing, and clarified that this 
study is now closed to enrollment 
• 
Updated Device Description to align with the 
current IFU 
• 
Updated 
physician 
affiliations 
when 
appropriate 
• 
Clarified CK-MB testing is only performed if 
indicated 
• 
Clarified that subjects with significant changes 
in condition after approval by the Subject 
Eligibility Committee should be re-evaluated 
by the Committee 
• 
Removed reference to specific Fogarty balloon 
catheter for alignment with current IFU 
• 
Removed requirement for systolic blood 
pressure to be maintained below 135 mmHg 
post-Tendyne procedure as this may conflict 
with hospital procedure 
• 
Added COVID-19 assessment to follow-up 
data collection list 
• 
Revised Statistical Methods to reflect change 
from binomial to Kaplan-Meier rate calculation 
to account for censoring prior to 12 months 
• 
Clarified analysis method for KCCQ and 
6MWT secondary endpoint analyses  
• 
Updated procedures to account for missing data 
to align with current SAP 
• 
Clarified that Control procedures should be 
performed by physicians on the Tendyne 
implant team, but not necessarily requiring all 
Tendyne-trained physicians 
at the initiation of the trial. 
Some underlying 
assumptions were 
challenged by the impact of 
COVID-19 on trial conduct 
and outcomes. Therefore, in 
accordance with guidance 
documents from FDA and 
EU, the statistical analysis 
plan was updated to account 
for the anticipated impact of 
COVID-19. Section 10 
describing the statistical 
analysis methods was 
updated accordingly to 
align with the SAP. 
 
References to the Expanded 
Clinical Study and the 
MAC Feasibility Study 
were updated to reflect 
current study status and 
provide updated results, if 
applicable. 
 
Additional edits were 
performed for clarification 
and to align with the current 
versions of the IFU and 
SAP. 

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05MAY2022 
CIP Template 86357 Rev. J 
Clinical Investigation Plan (CS0004-P) 
 ABT-CIP-10241 Rev. E  
Page 110 of 122 
 
 
 
 
SUMMIT 
 
• 
Updated Appendix IV to align with assessment 
requirements described in the body of the CIP 
• 
Added 
Appendix 
VII 
to 
clarify 
study 
documents that could be obtained on request 
from the Sponsor 
• 
Clarified imaging timelines from the point of 
consent 
• 
Corrected typographical errors 
D 
08SEPT2021 
• 
Primary endpoint for the Non-repairable Cohort 
was changed to freedom from all-cause 
mortality or heart failure hospitalization, 
evaluated at 12 months post index procedure 
• 
Performance goal changed from 44% to 48% 
freedom from death/HFH 
• 
Changed the definition of “registration” for 
Non-repairable and MAC patients to the point 
of initial incision rather that the induction of 
anesthesia.  
• 
Added Appendix VII summarizing the criteria 
from the Heart Valve Collaboratory that will be 
used by the SEC members to determine if a 
patient is suitable for TEER or not 
• 
Added ACC/AHA guidelines for intervention 
in patients with mitral stenosis 
• 
Changed TMVI (transcatheter mitral valve 
implantation) to TMVR (transcatheter mitral 
valve replacement) 
• 
Changed the names of the Non-randomized 
cohort to Non-repairable, and the MAC cohort 
to severe MAC cohort 
• 
Clarified that CK-MB or troponin tests are 
acceptable for diagnosing potential myocardial 
infarction, in alignment with the definition of 
myocardial infarction defined by MVARC 
• 
Specified that heart rate and blood pressure are 
mandatory components of the vital signs 
assessment 
• 
Changed the name of the investigational device 
from “Tendyne Mitral Valve System” to 
“Tendyne Transcatheter Mitral Valve System” 
• 
Sample size for the Non-repairable cohort is 
increased to 325 to account for subjects (~20) 
enrolled and treated under the Non-randomized 
cohort definition, but do not meet the new 
criteria of Lim et al., that will be excluded from 
the Non-repairable cohort analysis.   
The Primary Endpoint for 
the Non-repairable cohort 
was changed to freedom 
from death and HFH, in 
alignment with the other 
cohorts of the trial. The 
original endpoint was 
designed when SUMMIT 
had a Surgical and Non-
surgical arm. However, 
with most patients having 
secondary MR and heart 
failure, this endpoint is 
considered to be appropriate 
and aligns with the other 2 
study cohorts. The 
performance goal and 
sample size calculations has 
been updated from 44% to 
45% based on data from the 
COAPT GDMT-only 
population, similar to the 
method used for the severe 
MAC cohort. 
 
The definition of 
“registration” for Non-
repairable and MAC 
patients was changed to the 
point of initial incision as 
some patients are 
anesthetized and found to 
have a change in their 
condition such that they are 
no longer eligible for the 
study (ex. developed severe 
TR). These patients are not 
intended to be registered 
and followed per protocol. 
 
A recent publication from 
the Heart Valve 
Collaboratory specified 
criteria that would render a 

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SUMMIT 
 
subject as not suitable for 
TEER. The Non-repairable 
cohort now requires 
subjects must meet these 
criteria to be eligible for the 
Non randomized cohort, 
and that any subject deemed 
not suitable for TEER to be 
eligible for the trial in the 
Non randomized cohort. 
These criteria are now 
summarized in Appendix 
VII.  
 
Additionally, subjects 
previously enrolled that do 
not meet these criteria will 
be replaced with additional 
subjects. The sample size 
for this cohort has been 
updated to 325 patients to 
account for these patients 
being removed from the 
analysis cohort. 
 
The Non-randomized 
cohort was changed to Non-
repairable to avoid 
confusion as MAC is also a 
single-arm, non-randomized 
cohort. The MAC cohort 
was renamed to Severe 
MAC as only patients 
where the MAC is 
precluding mitral valve 
surgery are eligible; others 
will go in the Non-
repairable cohort 
E 
05May2022 
• 
Added Severe MAC Continued Access Plan 
(CAP) 
• 
Aligned to most recent Abbott CIP template for 
compliance with ISO14155:2020 
• 
Clarified protocol requirements for Troponin 
testing and medication logging 
The SUMMIT Severe MAC 
Continued Access Plan 
(CAP) is an expansion of 
the SUMMIT pivotal study 
designed to collect 
additional safety and 
clinical effectiveness data 
on the Tendyne 
Transcatheter Mitral Valve 
System in patients with 
severe MAC following 
completion of enrollment of 
subjects in the primary 
analysis population of the 

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Page 112 of 122 
 
 
 
 
SUMMIT 
 
severe MAC cohort. The 
Severe MAC CAP will 
allow additional patients to 
enroll in SUMMIT while 
under PMA review. 
Conduct of the SUMMIT 
MAC CAP will follow the 
same protocol outlined for 
the pivotal IDE trial. 
 
As of 5 Jan 2022, Abbott 
has implemented quality 
system changes to execute 
clinical investigations in 
compliance to ISO 
14155:2020. All relevant 
principles of Good Clinical 
Practice have been applied 
to this ongoing study. 
 
Clarified that Troponin 
testing is only required if 
indicated (i.e. in setting of 
suspected myocardial 
infarction) and that the 
medication log is designed 
to capture usage of chronic 
cardiovascular medications 
and any changes to those 
medication post-procedure. 
Acute treatments are 
captured within the 
procedure or adverse event 
case report forms. 
 
 
 

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SUMMIT 
 
APPENDIX X MITRACLIP INDICATION FOR USE 
• The MitraClip™ NTR/XTR Clip Delivery System is indicated for the percutaneous reduction 
of significant symptomatic mitral regurgitation (MR ≥ 3+) due to primary abnormality of the 
mitral apparatus [degenerative MR] in patients who have been determined to be at prohibitive 
risk for mitral valve surgery by a heart team, which includes a cardiac surgeon experienced in 
mitral valve surgery and a cardiologist experienced in mitral valve disease, and in whom 
existing comorbidities would not preclude the expected benefit from reduction of the mitral 
regurgitation. 
• The MitraClip™ NTR/XTR Clip Delivery System, when used with maximally tolerated 
guideline-directed medical therapy (GDMT), is indicated for the treatment of symptomatic, 
moderate-to-severe or severe secondary (or functional) mitral regurgitation (MR; MR ≥ Grade 
III per American Society of Echocardiography criteria) in patients with a left ventricular 
ejection fraction (LVEF) ≥ 20% and ≤ 50%, and a left ventricular end systolic diameter 
(LVESD) ≤ 70 mm whose symptoms and MR severity persist despite maximally tolerated 
GDMT as determined by a multidisciplinary heart team experienced in the evaluation and 
treatment of heart failure and mitral valve disease. 
 
 

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SUMMIT 
 
APPENDIX XI:  BIBLIOGRAPHY 
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A. W. Asgar, M. J. Mack, and G. W. Stone, “Secondary mitral regurgitation in heart failure: 
Pathophysiology, prognosis, and therapeutic considerations,” J. Am. Coll. Cardiol., vol. 65, 
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[2] 
R. Nasser et al., “Evolution of Functional Mitral Regurgitation and Prognosis in 
Medically Managed Heart Failure Patients With Reduced Ejection Fraction,” JACC Hear. 
Fail., vol. 5, no. 9, pp. 652–659, 2017, doi: 10.1016/j.jchf.2017.06.015. 
[3] 
A. Rossi et al., “Independent prognostic value of functional mitral regurgitation in patients 
with heart failure. A quantitative analysis of 1256 patients with ischaemic and non-
ischaemic dilated cardiomyopathy,” Heart, vol. 97, no. 20, pp. 1675–1680, 2011, doi: 
10.1136/hrt.2011.225789. 
[4] 
F. Grigioni, M. Enriquez-Sarano, K. J. Zehr, K. R. Bailey, and A. J. Tajik, “Ischemic mitral 
regurgitation: Long-term outcome and prognostic implications with quantitative Doppler 
assessment,” 
Circulation, 
vol. 
103, 
no. 
13, 
pp. 
1759–1764, 
2001, 
doi: 
10.1161/01.CIR.103.13.1759. 
[5] 
C. Tribouilloy et al., “Long-term mortality associated with left ventricular dysfunction in 
mitral regurgitation due to flail leaflets: A multicenter analysis,” Circ. Cardiovasc. Imaging, 
vol. 7, no. 2, pp. 363–370, 2014, doi: 10.1161/CIRCIMAGING.113.001251. 
[6] 
G. Cioffi et al., “Pharmacological left ventricular reverse remodeling in elderly patients 
receiving optimal therapy for chronic heart failure,” Eur. J. Heart Fail., vol. 7, no. 6, pp. 
1040–1048, 2005, doi: 10.1016/j.ejheart.2004.11.003. 
[7] 
B. Seneviratne, G. A. Moore, and P. D. West, “Effect of captopril on functional mitral 
regurgitation in dilated heart failure: a randomised double blind placebo controlled trial.,” 
Heart, vol. 72, no. 1, pp. 63–68, 2007, doi: 10.1136/hrt.72.1.63. 
[8] 
H. Baumgartner et al., “2017 ESC/EACTS Guidelines for the management of valvular heart 
disease,” Eur. Heart J., vol. 38, no. 36, pp. 2739–2786, 2017, doi: 10.1093/eurheartj/ehx391. 
[9] 
R. A. Nishimura et al., “2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline 
for the Management of Patients with Valvular Heart Disease: A Report of the American 
College of Cardiology/American Heart Association Task Force on Clinical Practice 
Guidelines,” Circulation, vol. 135, no. 25, pp. e1159–e1195, Jun. 2017, doi: 
10.1161/CIR.0000000000000503. 
[10] C. M. Otto et al., 2020 ACC/AHA Guideline for the Management of Patients With Valvular 
Heart Disease: A Report of the American College of Cardiology/American Heart 
Association Joint Committee on Clinical Practice Guidelines, vol. 143, no. 5. 2021. 
[11] T. Feldman et al., “Randomized Comparison of Percutaneous Repair and Surgery for Mitral 
Regurgitation 5-Year Results of EVEREST II,” J. Am. Coll. Cardiol., vol. 66, no. 25, pp. 
2844–2854, 2015, doi: 10.1016/j.jacc.2015.10.018. 
[12] T. Feldman et al., “Percutaneous Repair or Surgery for Mitral Regurgitation,” N. Engl. J. 
Med., vol. 364, no. 15, pp. 1395–1406, Apr. 2011, doi: 10.1056/NEJMoa1009355. 
[13] O. Franzen et al., “Acute outcomes of MitraClip therapy for mitral regurgitation in high-

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Page 115 of 122 
 
 
 
 
SUMMIT 
 
surgical-risk patients: Emphasis on adverse valve morphology and severe left ventricular 
dysfunction,” Eur. Heart J., vol. 31, no. 11, pp. 1373–1381, 2010, doi: 
10.1093/eurheartj/ehq050. 
[14] O. Franzen et al., “MitraClip® therapy in patients with end-stage systolic heart failure,” 
Eur. J. Heart Fail., vol. 13, no. 5, pp. 569–576, 2011, doi: 10.1093/eurjhf/hfr029. 
[15] L. Mauri et al., “4-Year results of a randomized controlled trial of percutaneous repair 
versus surgery for mitral regurgitation,” J. Am. Coll. Cardiol., vol. 62, no. 4, pp. 317–328, 
2013, doi: 10.1016/j.jacc.2013.04.030. 
[16] L. Paranskaya et al., “Early and mid-term outcomes of percutaneous mitral valve repair with 
the MitraClip®: comparative analysis of different EuroSCORE strata,” EuroIntervention, 
vol. 8, no. 5, pp. 571–578, Sep. 2012, doi: 10.4244/EIJV8I5A88. 
[17] W. Schillinger, M. Hünlich, S. Baldus, and T. Ouarrak, “Acute outcomes after MitraClip 
therapy in highly aged patients: Results from the German TRAnscatheter mitral valve 
interventions (TRAMI) registry.,” pp. 1–7. 
[18] C. Tamburino et al., “Percutaneous mitral valve repair with the MitraClip system: Acute 
results from a real world setting,” Eur. Heart J., vol. 31, no. 11, pp. 1382–1389, 2010, doi: 
10.1093/eurheartj/ehq051. 
[19] P. L. Whitlow et al., “Acute and 12-month results with catheter-based mitral valve leaflet 
repair: The EVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study,” J. 
Am. Coll. Cardiol., vol. 59, no. 2, pp. 130–139, 2012, doi: 10.1016/j.jacc.2011.08.067. 
[20] P. Lancellotti, P. L. Gérard, and L. A. Piérard, “Long-term outcome of patients with heart 
failure and dynamic functional mitral regurgitation,” Eur. Heart J., vol. 26, no. 15, pp. 
1528–1532, 2005, doi: 10.1093/eurheartj/ehi189. 
[21] B. H. Trichon, G. M. M. Felker, L. K. Shaw, C. H. Cabell, C. M. O’Connor, and C. M. 
O’Connor, “Relation of frequency and severity of mitral regurgitation to survival among 
patients with left ventricular systolic dysfunction and heart failure,” Am. J. Cardiol., vol. 
91, no. 5, pp. 538–543, 2003, doi: 10.1016/S0002-9149(02)03301-5. 
[22] T. Mihaljevic et al., “Impact of Mitral Valve Annuloplasty Combined With 
Revascularization in Patients With Functional Ischemic Mitral Regurgitation,” J. Am. Coll. 
Cardiol., vol. 49, no. 22, pp. 2191–2201, 2007, doi: 10.1016/j.jacc.2007.02.043. 
[23] K. M. Harris, T. M. Sundt, D. Aeppli, R. Sharma, and B. Barzilai, “Can late survival of 
patients with moderate ischemic mitral regurgitation be impacted by intervention on the 
valve?,” Ann. Thorac. Surg., vol. 74, no. 5, pp. 1468–1475, 2002, doi: 10.1016/S0003-
4975(02)03920-6. 
[24] U. Benedetto et al., “Does combined mitral valve surgery improve survival when compared 
to revascularization alone in patients with ischemic mitral regurgitation? A meta-analysis 
on 2479 patients,” J. Cardiovasc. Med., vol. 10, no. 2, pp. 109–114, 2009, doi: 
10.2459/JCM.0b013e32831c84b0. 
[25] M. A. Deja et al., “Influence of mitral regurgitation repair on survival in the surgical 
treatment for ischemic heart failure trial,” Circulation, vol. 125, no. 21, pp. 2639–2648, 

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Page 116 of 122 
 
 
 
 
SUMMIT 
 
2012, doi: 10.1161/CIRCULATIONAHA.111.072256. 
[26] L. H. Cohn et al., “The effect of pathophysiology on the surgical treatment of ischemic 
mitral regurgitation: operative and late risks of repair versus replacement.,” Eur. J. 
Cardiothorac. Surg., vol. 9, no. 10, pp. 568–74, 1995, Accessed: Apr. 10, 2019. [Online]. 
Available: http://www.ncbi.nlm.nih.gov/pubmed/8562102. 
[27] K. M. J. Chan et al., “Coronary Artery Bypass Surgery With or Without Mitral Valve 
Annuloplasty in Moderate Functional Ischemic Mitral Regurgitation,” Circulation, vol. 126, 
no. 21, pp. 2502–2510, 2012, doi: 10.1161/circulationaha.112.143818. 
[28] M. A. Acker et al., “Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral 
Regurgitation,” N. Engl. J. Med., vol. 370, no. 1, pp. 23–32, Jan. 2013, doi: 
10.1056/nejmoa1312808. 
[29] D. Goldstein et al., “Two-Year Outcomes of Surgical Treatment of Severe Ischemic Mitral 
Regurgitation,” N. Engl. J. Med., vol. 374, no. 4, pp. 344–353, 2016, doi: 
10.1056/nejmoa1512913. 
[30] K. Fattouch et al., “POINT: Efficacy of adding mitral valve restrictive annuloplasty to 
coronary artery bypass grafting in patients with moderate ischemic mitral valve 
regurgitation: A randomized trial,” J. Thorac. Cardiovasc. Surg., vol. 138, no. 2, pp. 278–
285, 2009, doi: 10.1016/j.jtcvs.2008.11.010. 
[31] A. H. Wu, K. D. Aaronson, S. F. Bolling, F. D. Pagani, K. Welch, and T. M. Koelling, 
“Impact of mitral valve annuloplasty on mortality risk in patients with mitral regurgitation 
and left ventricular systolic dysfunction,” J. Am. Coll. Cardiol., vol. 45, no. 3, pp. 381–387, 
2005, doi: 10.1016/j.jacc.2004.09.073. 
[32] D. S. Lim et al., “Improved functional status and quality of life in prohibitive surgical risk 
patients with degenerative mitral regurgitation after transcatheter mitral valve repair,” J. Am. 
Coll. Cardiol., vol. 64, no. 2, pp. 182–192, 2014, doi: 10.1016/j.jacc.2013.10.021. 
[33] M. Mirabel et al., “What are the characteristics of patients with severe, symptomatic, mitral 
regurgitation who are denied surgery?,” Eur. Heart J., vol. 28, no. 11, pp. 1358–1365, 2007, 
doi: 10.1093/eurheartj/ehm001. 
[34] P. Sorajja, M. B. Leon, D. H. Adams, J. G. Webb, and R. S. Farivar, “Transcatheter therapy 
for mitral regurgitation clinical challenges and potential solutions,” Circulation, vol. 136, 
no. 4, pp. 404–417, 2017, doi: 10.1161/CIRCULATIONAHA.117.025264. 
[35] J. S. Gammie et al., “Beating-Heart Mitral Valve Repair Using a Novel ePTFE Cordal 
Implantation Device: A Prospective Trial,” J. Am. Coll. Cardiol., vol. 71, no. 1, pp. 25–36, 
2018, doi: 10.1016/j.jacc.2017.10.062. 
[36] P. Sorajja et al., “Outcomes With Transcatheter Mitral Valve Repair in the United States,” 
J. Am. Coll. Cardiol., vol. 70, no. 19, pp. 2315–2327, Nov. 2017, doi: 
10.1016/j.jacc.2017.09.015. 
[37] G. Nickenig et al., “Transcatheter Mitral Annuloplasty in Chronic Functional Mitral 
Regurgitation,” JACC Cardiovasc. Interv., vol. 9, no. 19, pp. 2039–2047, 2016, doi: 
10.1016/j.jcin.2016.07.005. 

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SUMMIT 
 
[38] A. Regueiro, J. F. Granada, F. Dagenais, and J. Rodés-Cabau, “Transcatheter Mitral Valve 
Replacement: Insights From Early Clinical Experience and Future Challenges,” J. Am. Coll. 
Cardiol., vol. 69, no. 17, pp. 2175–2192, 2017, doi: 10.1016/j.jacc.2017.02.045. 
[39] G. W. Stone et al., “Transcatheter Mitral-Valve Repair in Patients with Heart Failure,” N. 
Engl. J. Med., pp. 1–12, Sep. 2018, doi: 10.1056/NEJMoa1806640. 
[40] J.-F. Obadia et al., “Percutaneous Repair or Medical Treatment for Secondary Mitral 
Regurgitation,” 
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[41] P. A. Grayburn, A. Sannino, and M. Packer, “Proportionate and Disproportionate 
Functional Mitral Regurgitation: A New Conceptual Framework That Reconciles the 
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