Prospective REgistry to Study Clinical OutcomEs of Repair of Mitral ValvEs in South Asia
Conditions: Mitral Valve Disease
Sponsor: Medtronic Cardiac Surgery

PRESERVE-Mitral Clinical Investigation Plan  
 
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Clinical Investigation Plan 
Study Title  PRESERVE - MITRAL 
Prospective REgistry to Study Clinical OutcomEs of 
Repair of Mitral ValvEs in South Asia. 
Clinical Investigation Plan Identifier MDT16016SUR002 
Study Product Name Profile 3DTM, CG Future® annuloplasty systems 
Sponsor/Local Sponsor Medtronic plc. 
Clinical Research 
Mailstop: MVS66 
Mounds View South 
8200 Coral Sea St. NE 
Mounds View, MN 55112 
Regional Sponsor: 
Vinay Rajan, Ph.D 
India- Medtronic Pvt. Ltd. 
Solitaire Corporate Park, Bldg No. 12, 4th Floor, 
Andheri -Ghatkopar Link Road, Andheri-East 
Mumbai, Maharashtra 400 093 
INDIA 
Contact Number: +91-22-33074700 
Document Version 1.0 / 10-APR-2017 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. Any 
distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly 
prohibited. Persons to whom the information is disclosed must know that it is confidential and that it may 
not be further disclosed by them. 
 
 

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Study Sponsor Contact Information 
Medtronic contact information is provided below. This information is subject to change during the course 
of the clinical study. Periodic updates to study contact information will be sent to the centers as needed. 
 
Study Sponsors and Contacts 
Medical Advisor 
 
Dr. Sidney Cohen, Sr. Clinical Medical Advisor 
Direct Phone: +1 7072923164 
sidney.a.cohen@medtronic.com 
Clinical Study Manager 
 
Kritika Gupta, Principal Clinical Research Specialist 
Direct Phone: +91 8291182170 
Direct Fax: +91 2233074704 
kritika.gupta@medtronic.com 
Study Monitor 
 
Bankim Chauhan, Clinical Contingent 
Direct Phone: +91 9930270042  
bankim.chauhan@medtronic.com 
Clinical Leadership 
 
Vinay Rajan, Ph.D, Country Clinical Leader 
Direct Phone: +91 9619332703 
Direct Fax: +91 2233074704 
vinay.rajan@medtronic.com 
 
 
 

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1. Investigator Statement 
Study product Name 
Profile 3DTM, CG Future® 
Sponsor 
Medtronic plc 
Clinical Research 
Mailstop: MVS66 
Mounds View South 
8200 Coral Sea St. NE 
Mounds View, MN 55112 
Regional Sponsor: 
Vinay Rajan, Ph.D 
India- Medtronic Pvt. Ltd. 
Solitaire Corporate Park, Bldg No. 12, 4th Floor, 
Andheri -Ghatkopar Link Road, Andheri-East 
Mumbai, Maharashtra 400 093 
INDIA 
Clinical Investigation Plan Identifier 
MDT16016SUR002 
Version Number/Date  
1.0 / 10-APR-2017 
I have read the protocol, including all appendices, and I agree that it contains all necessary details for me 
and my staff to conduct this study as described. I will conduct this study as outlined herein and will make 
a reasonable effort to complete the study within the time designated. 
I agree to comply with  the  India Good Clinical Practice (India GCP). I agree to ensure that the 
confidential information contained in this document will not be used for any purpose other than the 
evaluation and conduct of the clinical investigation without the prior written consent of Medtronic. 
I will provide all study personnel under my supervision copies of the protocol and access to all 
information provided by Medtronic. I will discuss this material with them to ensure that they are fully 
informed about the products and the study. 
Investigator’s Signature: 
 
Investigator’s Name: 
 
Institution: 
 
Date:  
 
 
 

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Table of Contents  
 
1. 
Investigator Statement ...................................................................................................... 3 
Table of Contents ...................................................................................................................... 4 
2. 
Glossary .............................................................................................................................. 7 
3. 
Synopsis ............................................................................................................................. 9 
4. 
Introduction ..................................................................................................................... 11 
4.1. Background ........................................................................................................................... 11 
4.2. Purpose ................................................................................................................................. 15 
5. 
Objectives and Endpoints ................................................................................................. 15 
5.1. Objectives ............................................................................................................................. 15 
5.1.1. 
Primary Objective(s) .............................................................................................................. 15 
5.1.2. 
Secondary Objective(s).......................................................................................................... 15 
5.2. Endpoints .............................................................................................................................. 15 
5.2.1. 
Primary Endpoint .................................................................................................................. 15 
5.2.2. 
Secondary Endpoint(s) .......................................................................................................... 15 
6. 
Study Design .................................................................................................................... 17 
6.1. Duration ................................................................................................................................ 17 
6.2. Rationale ............................................................................................................................... 18 
7. 
Product Description.......................................................................................................... 18 
7.1. General ................................................................................................................................. 18 
7.2. Manufacturer ......................................................................................................................... 20 
7.3. Packaging .............................................................................................................................. 20 
7.4. Intended Population ............................................................................................................... 20 
7.5. Equipment ............................................................................................................................. 20 
7.6. Product Use ........................................................................................................................... 20 
7.7. Product Training Requirements ............................................................................................... 21 
7.8. Product Receipt and Tracking ................................................................................................. 21 
7.9. Product Storage ..................................................................................................................... 21 
7.10. 
Product Return ................................................................................................................. 21 

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7.11. 
Product Accountability ...................................................................................................... 21 
8. 
Selection of Subjects ........................................................................................................ 21 
8.1. Study Population .................................................................................................................... 21 
8.2. Subject Enrollment ................................................................................................................. 22 
8.3. Inclusion Criteria .................................................................................................................... 22 
8.4. Exclusion Criteria ................................................................................................................... 22 
9. 
Study Procedures ............................................................................................................. 22 
9.1. Schedule of Events ................................................................................................................. 22 
9.2. Subject Screening .................................................................................................................. 25 
9.3. Prior and Concomitant Medications ......................................................................................... 26 
9.4. Subject Consent ..................................................................................................................... 26 
9.5. Randomization and Treatment Assignment .............................................................................. 26 
9.6. Medication Compliance ........................................................................................................... 27 
9.7. Assessment of Efficacy ........................................................................................................... 27 
9.8. Assessment of Safety ............................................................................................................. 27 
9.9. Recording Data ...................................................................................................................... 27 
9.9.1. 
Enrollment (Baseline) Visit .................................................................................................... 28 
9.9.2. 
Implant Visit .......................................................................................................................... 29 
9.9.3. 
Discharge Visit ....................................................................................................................... 29 
9.9.4. 
3-6 month Follow Up ............................................................................................................. 29 
9.9.5. 
12 month Follow Up .............................................................................................................. 30 
9.9.6. 
Source documents ................................................................................................................. 30 
9.10. 
Deviation Handling ........................................................................................................... 31 
9.11. 
Subject Withdrawal or Discontinuation ............................................................................... 32 
10. 
Risks and Benefits ......................................................................................................... 32 
10.1. 
Potential Risks .................................................................................................................. 32 
10.2. 
Potential Benefits ............................................................................................................. 33 
10.3. 
Risk-Benefit Rationale ....................................................................................................... 33 
11. 
Adverse Events and Device Deficiencies ....................................................................... 34 
11.1. 
Definitions/Classifications .................................................................................................. 34 
11.2. 
Reporting of Adverse Events and Device Deficiencies .......................................................... 36 

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12. 
Data Review Committees .............................................................................................. 39 
13. 
Statistical Design and Methods ..................................................................................... 39 
13.1. 
Missing/Unused/Unauthentic Data ..................................................................................... 39 
13.2. 
Subgroup Analysis ............................................................................................................ 39 
13.3. 
Interim Analysis ............................................................................................................... 39 
13.4. 
Sample Size Determination ............................................................................................... 40 
13.5. 
Primary Endpoints ............................................................................................................ 40 
13.6. 
Secondary Endpoints ........................................................................................................ 40 
14. 
Ethics ............................................................................................................................. 41 
14.1. 
Statement(s) of Compliance .............................................................................................. 41 
15. 
Study Administration ..................................................................................................... 41 
15.1. 
Monitoring ....................................................................................................................... 41 
15.2. 
Data Management ............................................................................................................ 42 
15.2.1. 
Electronic Data Capture ..................................................................................................... 42 
15.2.2. 
Data Collection .................................................................................................................. 42 
15.2.3. 
Data Validation .................................................................................................................. 42 
15.3. 
Direct Access to Source Data/Documents ........................................................................... 43 
15.4. 
Confidentiality .................................................................................................................. 43 
15.5. 
Liability ............................................................................................................................ 43 
15.6. 
CIP Amendments ............................................................................................................. 43 
15.7. 
Record Retention ............................................................................................................. 43 
15.8. 
Publication and Use of Information .................................................................................... 44 
15.9. 
Suspension or Early Termination ....................................................................................... 45 
16. 
References ..................................................................................................................... 45 
17. 
Appendices  ................................................................................................................... 47 
18. 
Version History .............................................................................................................. 58 
 
 
 

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2. Glossary 
Term 
Definition 
ADE 
Adverse Device Effect 
AE   
 
Adverse Event 
AC 
Advisory Committee 
ASADE 
Anticipated Serious Adverse Device Effect 
CDSCO 
Central Drugs Standard Control Organization 
CIP 
Clinical Investigation Plan 
CMP 
Clinical Management Plan  
CRS 
Clinical Research Specialist 
CTA 
Clinical Trial Agreement 
CV 
Curriculum Vitae 
CVD 
Cardiovascular Disease 
DCGI 
Drug Controller General of India 
DD 
Device Deficiency 
DMC 
Data Monitoring Committee 
DRF 
Data Release Form 
DTL 
Delegated Task List  
EC 
Ethics Committee 
ECG 
Electrocardiogram/Electrocardiography 
eCRF   
Electronic Case Report Form 
EDC 
Electronic Data Capture 
FU 
Follow Up 
GCP 
Good Clinical Practice 

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Term 
Definition 
HF 
Heart Failure 
IRB 
Institutional Review Board 
LAD 
Left Atrial Diameter 
LVEDD 
Left Ventricular End Diastolic Diameter 
LVEF 
Left Ventricular Ejection Fraction 
LVOTO  
Left Ventricular Outflow Tract Obstruction  
MACCE  
Major Adverse Cardiac & Cerebrovascular Event 
MI 
Myocardial Infarction 
MR 
Mitral Regurgitation 
MS 
Mitral Stenosis 
MV 
Mitral Valve 
NYHA   
New York Heart Association 
PI 
Principal Investigator (one per site)  
PIC  
Patient Informed Consent 
RDC 
Remote Data Capture 
SADE  
Serious Adverse Device Effect 
SAE 
Serious Adverse Event 
SAM 
Systolic Anterior Motion 
SOP 
Standard Operating Procedure  
TEE 
Transoesophageal Echocardiograph 
TTE 
Transthoracic Echocardiograph 
UADE    
Unanticipated Adverse Device Effect 
USADE    
Unanticipated Serious Adverse Device Effect 

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3. Synopsis 
Title 
PRESERVE - MITRAL 
Prospective REgistry to Study Clinical OutcomEs of Repair of Mitral 
ValvEs in South Asia.  
Clinical Study Type 
Post Market Registry 
Product Name 
Profile 3DTM, CG Future® 
Sponsor  
Medtronic plc. 
Clinical Research 
Mailstop: MVS66 
Mounds View South 
8200 Coral Sea St. NE 
Mounds View, MN 55112 
Regional Sponsor 
Vinay Rajan, Ph.D 
India- Medtronic Pvt. Ltd. 
Solitaire Corporate Park, Bldg No. 12, 4th Floor, 
Andheri -Ghatkopar Link Road, Andheri-East 
Mumbai, Maharashtra 400 093 
INDIA 
Indication under 
investigation  
Patients suffering from mitral valve disease and indicated for a mitral 
valve repair procedure with Profile 3D™ and CG Future® annuloplasty 
system as part of standard of care, in accordance with the product label 
indications (instructions for use), contraindications, and warnings 
Investigation Purpose 
There is limited local evidence on mitral repair products in South Asia 
and a prospective post market registry will provide real world data on 
clinical outcomes 
Product Status 
Profile 3D™ and CG Future® annuloplasty systems are indicated for the 
reconstruction and/or remodeling of the pathological mitral valve. The 
devices are approved and commercially available in India and are 
commercially available in Bangladesh and Nepal. 
  
Primary Objective(s) 
The objective of this registry is to gather data on the clinical outcomes 
of Medtronic mitral repair products (Profile 3D™ and CG Future® 
annuloplasty systems) in the approved intended use up to 12 months 
from the day of procedure 
Secondary Objective(s) 
Characterize the demographics of the patients undergoing mitral valve 
repair using annuloplasty systems in India, and assess the functional 

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and procedural outcomes of the procedure.  
Study Design 
PRESERVE-Mitral Registry is a prospective non-randomized, non-
interventional, post-market registry. 
Sample Size 
200 
Inclusion/Exclusion 
Criteria 
Inclusion Criteria: 
1. Patients with valvular insufficiency and/or stenosis  and 
indicated for the reconstruction and/or remodeling of 
pathological mitral valves with Profile 3D™ and CG Future® 
annuloplasty systems 
2. Indications and contraindications provided in the product 
Instructions for Use 
3. Subject is 18 years of age or older 
4. The patient or his/her Legally Authorized Representative (LAR) 
has been informed about the nature of the registry and  the 
patient informed consent for study participation has been 
obtained prior to performing any study-related procedures from 
the subject or Legally Authorized Representative, as per 
applicable local requirements 
Exclusion Criteria: 
1. Contraindications as per IFU: 
a. Heavily calcified valves 
b. Valvular retraction with severely reduced mobility 
c. Active bacterial endocarditis 
2. Aortic valve replacement as concomitant procedure 
3. Already participating in another  clinical study, possibly leading 
to bias and jeopardizing the scientific appropriate assessment of 
the study endpoints 
Study Procedures and 
Assessments 
 
Baseline/Pre-Operative (data from most recent assessment before 
planned implant date preferred, not exceeding 60 days) 
 
Implant 
 
Discharge (date of discharge or 7 days post procedure, whichever 
comes first) 
 
3 to 6 months (data reported from 90 days up to 210 days post 
procedure, whichever comes later) 
 
12 months (data reported up to day 395 (365 +/- 30 days) post 
procedure date will be collected) 
Safety Assessments 
All relevant safety data will be collected and reported per local 
regulations and EC/IRB requirements 

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4. Introduction  
4.1. Background  
Cardiovascular diseases are the leading cause of mortality in India, contributing to 25% of all mortality in 
the country. The Global Burden of Disease study estimate of age-standardized CVD death rate of 272 per 
100,000 population in India is higher than the global average of 235 per 100,000 population [1]. 
 
Mitral valve regurgitation 
One of the important pathologies seen in patients with cardiovascular disease is mitral valve regurgitation 
and insufficiency. Patients might suffer from different types of mitral valve dysfunction leading to different 
levels of regurgitation. The following classification of dysfunctioning valves was introduced by 
Carpentier [2]: 
 Type I: the free edges of the leaflets remain below the plane of the annulus during systole 
and open normally during diastole; 
 Type II: the free edge of one or both leaflets overrides the plane of the annulus during systole; 
 Type III: one or both leaflets do not open fully during diastole or close fully during systole 
o 
IIIa: restricted leaflet motion during systole and diastole 
o 
IIIb: restricted leaflet closure during systole 
 
Type I dysfunction is the result of annular dilatation, often caused by myocardial infarction (MI). In most 
cases, type II dysfunction is a result from rupture or elongation of either the papillary muscles or the 
chordae tendinae, possibly as a result of MI. Type IIIa is mostly caused by 
leaflet 
thickening/retraction, chordal thickening/shortening/fusion or commissural fusion. Type IIIb dysfunction 
is the most common form of ischemic mitral regurgitation (IMR) [3]. 
 
Apart from the types of valve dysfunction, the severity of regurgitation can be gauged as per ASE 
guidelines [4] (see Table 1). 
 
 

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Table 1: ASE Guidelines for MR Severity Grading with  Echocardiography [4] 
 
 
 
MR Severity* 
 
Mild 
Moderate 
Severe 
Structural 
 
 
 
MV Morphology 
None or mild leaflet 
abnormality (e.g., mild 
thickening, calcifications or 
prolapse, mild tenting) 
Moderate leaflet abnormality or 
moderate tenting 
Severe valve lesions (primary: 
flail leaflet, ruptured papillary 
muscle, severe retraction, 
large perforation; secondary: 
severe tenting, poor leaflet 
coaptation) 
LV and LA size† 
Usually normal 
Normal or mild dilated 
Dilated‡ 
Qualitative Doppler 
 
 
 
Color flow jet 
area§ 
Small, central, narrow, often 
brief 
Variable 
Large central jet (>50% of LA) 
or eccentric wall-impinging jet 
of variable size 
Flow convergence|| 
Not visible, transient or small 
Intermediate in size and duration 
Large throughout systole 
CWD jet 
Faint/partial/parabolic 
Dense but partial or parabolic 
Holosystolic/dense/triangular 
Semiquantitative 
 
 
 
VCW (cm) 
<0.3 
Intermediate 
≥0.7 (>0.8 for biplane)¶ 
Pulmonary vein 
flow# 
Systolic dominance (may be 
blunted in LV dysfunction or 
AF) 
Normal or systolic blunting# 
Minimal 
to 
no 
systolic 
flow/systolic flow reversal 
Mitral inflow** 
A-wave dominant 
Variable 
E-wave dominant (>1.2 m/sec) 
Quantitative††,‡‡ 
 
 
 
EROA, 2D PISA 
(cm2) 
<0.20 
0.20-0.29 
0.30-0.39 
≥0.40 
(may be lower in 
secondary MR with 
elliptical ROA) 
RVol (mL) 
<30 
30-44 
45-59†† 
≥60 
(may be lower in low 
flow conditions) 
RF (%) 
<30 
30-39 
40-49 
≥50 
ROA, Regurgitant orifice area. 
Bolded qualitative and semiquantitative signs are considered specific for their MR grade. 
*All parameters have limitations, and an integrated approach must be used that weighs the strength of each echocardiographic 
measurement. All signs and measures should be interpreted in an individualized manner that accounts for body size, sex, and all 
other patient characteristics. 
†This pertains mostly to patients with primary MR. 
‡LV and LA can be within the ‘‘normal’’ range for patients with acute severe MR or with chronic severe MR who have small body size, 
particularly women, or with small LV size preceding the occurrence of MR. 
§With Nyquist limit 50-70 cm/sec. 
||Small flow convergence is usually <0.3 cm, and large is $ 1 cm at a Nyquist limit of 30-40 cm/sec. 
¶For average between apical two- and four-chamber views. 
#Influenced by many other factors (LV diastolic function, atrial fibrillation, LA pressure). 
**Most valid in patients >50 years old and is influenced by other causes of elevated LA pressure. 
††Discrepancies among EROA, RF, and RVol may arise in the setting of low or high flow states. 
‡‡Quantitative parameters can help subclassify the moderate regurgitation group. 

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Mitral valve repair – global perspective 
Mitral valve repair is established as a procedure to alleviate mitral valvular insufficiency/stenosis. The 
pathophysiology of mitral valve insufficiency can be ischemic, rheumatic, degenerative, congenital, 
infective, myxomatous, etc. 
Mitral valve repair may lead to better outcomes as compared to replacement. The overall survival of 
patients undergoing valve repair was found to be significantly superior to that of patients undergoing 
valve replacement, with 5- and 10-year survival rates, respectively, of 83±3% and 68±6% (repair, 
n=195) and 69±3%  and  52±4%  (replacement, n=214) [5].  
Western studies on mitral valve repair have typically focused on patients with ischemic pathophysiology. In 
a study of patients with chronic moderately severe to severe mitral regurgitation (grade 3-4) and 
ischemic or dilated cardiomyopathy, all 121 patients underwent mitral valve repair (8 with a flexible 
ring; 113 with a semi-rigid ring) with concomitant surgery. The 30-day mortality was 3.3% and 
survival rates at 3 and 30 months were 95% and 91% respectively. At discharge, all 117 patients had 
MR level of 2 or less. No difference was found between patients implanted with flexible and semi-rigid 
annuloplasty rings [6]. 
One group of researchers investigated leaflet curvature and stress distribution of the mitral valve 
using numerical and experimental data and found that "it seems reasonable to hypothesize that a 
saddle-shaped annuloplasty ring may increase mitral valve repair durability by reducing leaflet and 
chordal strain". The shape of Medtronic’s Profile 3D ring exactly matches the shape described by the 
authors [7]. 
Guidelines 
Current ACC/AHA guidelines [8] state that mitral valve repair is recommended in preference to mitral valve 
replacement in certain patients with chronic severe primary MR limited to posterior leaflet, or involving the 
anterior leaflet or both leaflets when a successful and durable repair can be accomplished. Concomitant 
repair is indicated for patients with chronic severe primary MR if they undergo cardiac surgery.  
Mitral valve repair is considered reasonable in asymptomatic patients with chronic severe primary MR with 
preserved LV function, and reasonable as a concomitant procedure in patients with chronic moderate 
primary MR when undergoing cardiac surgery for other indications. Mitral valve surgery (including either 
repair, commissurotomy or replacement) may be considered in patients with rheumatic mitral valve 
disease when surgical treatment is indicated. 
The guidelines also state that mitral valve surgery is indicated for severely symptomatic patients with 
severe mitral stenosis who are not at risk for surgery and who are not candidates for or have failed 
previous percutaneous mitral balloon commissurotomy. 
Regional perspective 
Despite the guidelines, there may be local and regional differences in the standard practice in different 
geographies. While there are some Indian studies that have looked into mitral valve repair [9], [10], [11], 
there is still a need to gather more local evidence on clinical outcomes at long term follow up (12 months).  
 
 
 

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Table 2: Indian studies on mitral valve repair procedures 
 
Gupta, et al (2010) 
[9] 
Choudhary, 
et 
al 
(2001) [10] 
Saravana, 
et 
al 
(2015) [11] 
Sample Size 
n = 44 
n = 818 
n = 163 
Prospective/Retrospective 
Prospective 
Retrospective 
Prospective 
Disease type 
100% rheumatic 
88% rheumatic 
6% congenital 
4% myxomatous 
1% infective 
1% ischemic 
43% rheumatic 
25% degenerative 
21% ischemic 
9% congenital 
1% subacute 
bacterial endocarditis 
1% other 
Lesion type 
45% pure MR 
39% MR+MS 
16% pure MS 
53% pure MR 
47% MR+MS 
94% >=grade 3 MR 
6% MR+MS 
NYHA class 
91% NYHA III/IV 
64% NYHA III/IV 
14% with congestive 
HF 
88% NYHA III/IV 
 
The significant proportion of mitral valve repair patients in India have rheumatic disease. Mitral valve 
repair is more technically challenging in this population, and is associated with higher failure rate. [10]. 
 
It is estimated that rheumatic heart disease prevalence is in the range of 1.5 to 2 per 1000 individuals (2–
2.5 million cases in absolute numbers) in India, with an estimated 88,674 deaths (7 per 100,000 
population) in the year 2010 [1]. 
 
The Global Rheumatic Heart Disease Registry (REMEDY study) enrolled patients presenting with rheumatic 
disease in 12 African countries, Yemen and India [12]. The patients with rheumatic heart disease were 
young (median age 28 years) and largely female (66.2%). The majority (63.9%) had multivalvular disease 
complicated by congestive heart failure. The majority of cases of mitral stenosis (72.9%) and mitral 
regurgitation (60.4%) had moderate-to-severe disease. A stark finding was that the utilization of valve 
surgery and valvuloplasty in patients with rheumatic heart disease in low-middle-income countries like 
India was 27.8%. Amongst the patients having native rheumatic valve disease with no percutaneous or 
surgical interventions, it was found that children in the first decade of life presented mostly with pure 
mitral regurgitation, and in the second decade of life, presented with mixed mitral and aortic valve disease 
with dominant mitral lesion [12]. 
 
Given this background, it is clear that the significant body of evidence for mitral valve annuloplasty from 
the west may not give a realistic picture of patients undergoing the same procedure in South Asia. Due to 
the difference in disease pathophysiology, the significant population of patients with rheumatic disease 
and differing surgical practice, there is a need to conduct a geography-specific study to understand the 
clinical outcome of patients undergoing mitral valve annuloplasty in the region. PRESERVE-Mitral, a 

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prospective registry to study long term performance of annuloplasty systems is thus proposed to 
document clinical outcomes, physician practice and report on outcomes in these patients.  
4.2. Purpose 
There is limited local evidence on mitral repair products in South Asia and a prospective post-market 
registry will provide real world data on clinical outcomes.  
5. Objectives and Endpoints 
5.1. Objectives 
5.1.1. 
Primary Objective(s) 
The objective of this registry is to gather data on the clinical outcomes of Medtronic mitral repair products 
(Profile 3D™ and CG Future® annuloplasty systems) in the approved intended use up to 12 months from 
the day of procedure.  
5.1.2. 
Secondary Objective(s)  
Characterize the demographics of the patients undergoing mitral valve repair using annuloplasty systems 
in South Asia, and assess the functional and procedural outcomes of the procedure.  
5.2. Endpoints 
5.2.1. 
Primary Endpoint 
To evaluate clinical outcomes at 12 months post procedure: 
1. Improvement in MR (grade) 
This will be determined by assessing the level of mitral valve regurgitation using echo, in subjects 
at 12 months post procedure compared to the level at baseline. The levels of regurgitation, level 
0-4, will correspond to the ASE guidelines ranging from no MR, Mild MR, Moderate MR, Moderate-
to-Severe MR and Severe MR, as described in Table 1 above. 
2. All cause mortality  
All deaths occurring from any cause post procedure. 
5.2.2. 
Secondary Endpoint(s)  
 
Characterization of patient demographics and pathophysiology of mitral valve disease 
The patients will be identified by collecting the following patient characteristics at baseline: age 
(in years), gender, previous cardiovascular surgery, symptoms of heart failure, cardiac rhythm, 

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New York Heart Association (NYHA) classification, risk factors, level of regurgitation, type of 
mitral valve deficiency, etc. 
 
Improvement in MR grade at discharge and first follow up (3-6 months)  
This will be determined by assessing the level of mitral valve regurgitation using echo, in subjects 
at discharge and 3-6 months post procedure compared to the level at baseline. The levels of 
regurgitation, level 0-4, will correspond to the ASE guidelines ranging from no MR, Mild MR, 
Moderate MR, Moderate-to-Severe MR and Severe MR, as described in Table 1 above. 
 
Improvement in NYHA functional class at discharge, first follow up (3-6 months) and second follow 
up (12 months) compared to baseline 
The New York Heart Association (NYHA) Functional Classification is a system for defining cardiac 
disease and related functional limitations into four broad categorizations as defined in Table 3 
below. 
Table 3: NYHA functional class definitions 
Classification 
Description 
Class I 
Patients with cardiac disease, but without resulting limitations of physical activity. 
Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or 
anginal pain. 
Class II 
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. 
Class 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. 
Class IV 
Patients with cardiac disease resulting in inability to perform any physical activity 
without discomfort. Symptoms of cardiac insufficiency or of the angina syndrome may 
be present even at rest. If any physical activity is undertaken, discomfort is increased. 
 
 
Hospitalization for Heart Failure at 6 months and at 12 months post procedure  
Hospitalizations for Heart Failure are defined as a non-elective hospital admission for signs and 
symptoms related to heart failure that results in a one-night stay (i.e., where the admission date 
and the discharge date differ by at least one calendar day).  For the purpose of the protocol, 
overnight stays at nursing home facilities or extended care facilities do not meet the protocol 
definition of hospitalization. The occurrence of hospitalization for heart failure will be evaluated at 
6 months and 12 months post procedure. 
 
Mitral valve re-intervention at discharge, 6 months and at 12 months post procedure  
Following the completion of the procedure, defined as the subject leaving the operating theater 
with an implanted Profile 3DTM or CG Future® annuloplasty system, any surgical or percutaneous 
interventional catheter procedure that repairs, otherwise alters or adjusts, or replaces the 
previously implanted annuloplasty system will be termed re-intervention. In addition to surgical 

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reoperations, enzymatic, balloon dilatation, interventional manipulation, repositioning, or 
retrieval, and other catheter-based interventions for valve-related complications are also 
considered re-interventions. The re-intervention rate will be evaluated at discharge, 6 months 
and 12 months post procedure. 
 
Stroke at 6 months and at 12 months post procedure  
Stroke is defined as an acute episode of focal or global neurological dysfunction caused by brain, 
spinal cord, or retinal vascular injury as a result of hemorrhage or infarction, where the 
neurological dysfunction lasts for greater than 24 hours. The occurrence of stroke will be 
evaluated at 6 months and 12 months post procedure. 
 
New onset of Atrial Fibrillation, as evaluated through follow up ECG at discharge, first follow up (3-6 
months) and at second follow up (12 months)  
New onset of AF is defined as when the subject did not present with prior history of AF at 
baseline nor was AF detected at baseline visit, but AF did manifest post procedure and was either 
diagnosed during the study visits (discharge, 3-6 months or 12 months visit) or was otherwise 
diagnosed during the duration of subject participation in the study. The incidence of new onset 
AF will be evaluated at discharge, first follow up (3-6 months) and at second follow up (12 
months). 
 
Number of attempts required for procedural success, and bypass time as a measure of procedural 
complexity, as measured by standard operating room procedures at the site. 
6. Study Design  
PRESERVE-Mitral is a prospective non-randomized non-interventional post-market registry. A total of 200 
patients who are eligible and who are intended to be implanted with a Profile 3DTM or CG Future® 
Annuloplasty system in the surgical repair procedure will be included in the study.  
The subjects will be evaluated at discharge for evaluation of procedural success and subsequently 
followed up as per standard-of-care at the site from 3-6 months (90 days to 210 days) post procedure 
and at 12 months (365 days +/- 30 days) post procedure for assessment of longer term outcome at 
which time subjects will also exit the study. Echo images will be evaluated pre-implant, intra-op, 
discharge and during follow ups, according to the standard routine in the center. 
Patients eligible for mitral valve repair and compliant with the enrollment criteria will be considered by the 
investigator for inclusion in the study. 
6.1. Duration 
The enrollment period is anticipated to take about 20 months. The study is expected to start enrolling in 
July 2017. With a maximum follow-up period of 12 months, the study is expected to last 32 months after 
the first patient enrollment. It is expected that an additional 4 months would be required for data 
analysis, and preparation of the publication. This study will be conducted in 10 centers in India, Nepal 

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and Bangladesh. Each center can include a maximum of 40 subjects in the study, which is 20% of the 
overall enrollment for the study. There is no minimum enrollment per site applicable for this study. 
A site may be selected for participation in the registry if the site complies with the following 
requirements: 
 
Sites are expected to adhere to Indian GCP and other local regulations as applicable. 
 
The site will appoint a Principal Investigator at the physician-in-charge level or above with 
appropriate experience and qualifications to oversee investigational procedures.  
 
The  PI  and  other  investigators  have  knowledge  and  experience  in  mitral  valve repair, e.g. 
implanting the Profile 3D or CG Future Annuloplasty systems. 
 
The site has the necessary facilities to conduct the registry (for example echocardiography). 
 
The site applies a 3-6 month and 12 month follow up as standard practice of care for these 
patients. 
 
Site is willing to comply with all requirements of the regulatory agency, Ethics Committees, or 
Institutional Review Boards, and the CIP. 
6.2. Rationale  
This study is a post-market registry, studying products that are already in the markets being studied. The 
study is designed to be observational, following the standard of care at each centre, in order to obtain 
real world data on the use of the products. The time period of the first follow up is kept flexible, in 
accordance with the variation in practice at different centres and in order to maximize compliance. The 
second follow up (12 month) is a standard timepoint for evaluation of longer term outcomes at all 
centres. All data collected in the study are as per the centre’s standard practice, and no interventional 
procedure will be added in the study. 
7. Product Description 
7.1. General 
The Medtronic Profile 3D™ Annuloplasty Ring (Figure 1), Model 680R, consists of a titanium core 
overmolded with silicone and covered with polyester fabric. The ring must be implanted in the mitral 
position. The ring is marked at three points by colored sutures; two markers correspond to the trigons of 
the mitral valve, and one identifies the midpoint of the device. The device size is identified by the inside 
diameter of the ring at its widest point. The titanium core enables radiographic visualization of the device. 
Non-clinical testing has demonstrated that the Profile 3D™ Ring is compatible with Magnetic Resonance 
Imaging (MRI) under normal Magnetic Resonance mode (additional information is provided in Appendix 
L.1. 

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Figure 1: Profile 3D™ Annuloplasty Ring 
 
 
The indications for use are to reconstruct and/or remodel the pathological mitral valve. Valvular 
insufficiency and/or stenosis may be corrected by appropriate repair and annular remodeling. The Profile 
3D product is contraindicated for use with highly calcified valves or in retracted valves with severely 
reduced leaflet mobility. It is also contraindicated for patients suffering from active bacterial endocarditis.  
The Medtronic Profile 3D™ Annuloplasty Ring is commercially released (CE-mark since 2008) and in this 
study, the Profile 3D ring will be applied only within the indications for use. At the time the protocol was 
finalized, the Medtronic Profile 3D™ Annuloplasty Ring was also approved in the additional geographies 
(Nepal) in which the study will be conducted. The technical aspects for the Profile 3D Annuloplasty Ring – 
Model 680R – are provided in Appendix L.1. 
The Medtronic Accessories, 768S Profile 3D™ Sizer Set including 9 Profile 3D™ sizers 24-40 mm, are used 
to identify the size of the ring. In addition, the Annuloplasty Handle Accessories (7686 Annuloplasty 
Handle (216 mm length) and/or 7686XL Annuloplasty Handle (373 mm length)) are used to be able to 
implant the profile ring. The T76880 Profile 3D™ Accessory Tray serves to organize and store the various 
accessories when not in use and may be used to hold the accessories during sterilization. All accessories 
are also commercially available in the countries/geographies in which the study will take place. 
Figure 2: The Medtronic CG Future® Annuloplasty System (Ring and Band) 
 
The Medtronic CG Future® Annuloplasty Ring Model 638R and the Medtronic CG Future® Annuloplasty 
Band Model 638B (hereafter referred to as CG Future® Annuloplasty Ring/Band) for mitral valve repair 
are designed to predictably remodel the annulus to maintain apposition of the anterior and posterior 
leaflets. Correct annuloplasty ring/band sizing is an important element to achieve a successful repair. 

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The CG Future® COMPOSITE Ring is the first composite ring to offer posterior remodeling while 
maintaining anterior flexibility. A flexible anterior segment seamlessly connects to the ring's semi-rigid 
posterior, providing the support needed to dynamically remodel the annulus, thereby allowing physiologic 
movement throughout the cardiac cycle. It has an unique eyelet design for easy anchoring to the 
trigones. Semi-rigid design offers enough flexibility to allow movement of the mitral annulus during the 
cardiac cycle. The band is ideal for small incisions and minimally invasive procedures where visibility and 
access to the anterior portion of the mitral annulus may be limited.  
The CG Future® Ring is available in eight sizes ranging from 24 mm to 38 mm. 
The CG Future® Band is available in seven sizes ranging from 26 mm to 38 mm. 
7.2. Manufacturer 
The products are manufactured by Medtronic, PLC. 
7.3. Packaging 
The PROFILE 3D™ and CG Future® annuloplasty systems are commercially available. Refer to IFU for 
packaging and storage information.  
7.4. Intended Population 
The PROFILE 3DTM and CG Future® systems are indicated for the reconstruction and/or remodeling of 
pathological mitral valves. Valvular insufficiency and/or stenosis may be corrected by appropriate repair 
and annular remodeling. 
CONTRAINDICATIONS 
 
Heavily calcified valves. 
 
Valvular retraction with severely reduced mobility. 
 
Active bacterial endocarditis. 
7.5. Equipment 
All equipment for collecting data will be as available at the site. 
7.6. Product Use 
The product should be used as per the Directions For Use outlined in the Instructions For Use insert that 
comes packaged with the products (Appendix L.1.). 

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7.7. Product Training Requirements 
This is a post-market registry, hence there is no requirement for specific product training. 
7.8. Product Receipt and Tracking 
All devices being used in this study are commercially available in the countries/geographies in which the 
study will be conducted. Therefore, the devices will be used off the shelf. The products are provided to 
the hospital with the appropriate language labeling. In this study, the Profile 3D and CG Future products 
will be applied only within the indications for use. Existing procedures for commercial product regarding 
distribution, shipment, receipt and tracking of these devices will be followed. Additional device traceability 
is not applicable for this study. 
7.9. Product Storage 
All devices being used in this study are commercially available in the selected countries/geographies in 
which this study will take place.  
Refer to the Instructions for Use for storage of the study device (Appendix L.1.).   
7.10. Product Return 
The study will follow the commercial process for explanted device to be properly retrieved, packaged and 
shipped to sponsor, which is the same as the process followed for the device in the market. 
7.11. Product Accountability  
Except documentation of serial numbers and model numbers of devices being used in this study, there 
are no device tracking requirements. The documentation of these numbers needs to be recorded on the 
eCRF. 
8. Selection of Subjects 
8.1. Study Population 
The patient population includes all patients suffering from mitral valve disease, indicated for a mitral 
valve repair procedure, either as a stand-alone procedure or concomitant to another procedure (for 
example, coronary artery bypass grafting, tricuspid valve repair, treatment of atrial fibrillation, etc. but 
excluding patients undergoing aortic valve replacement) and for which the surgeon considers the 
implantation of a Profile 3DTM or CG Future® annuloplasty system most appropriate to reconstruct the 
regurgitant valve. 

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8.2. Subject Enrollment 
A subject is considered enrolled in this study at the time at which he/she signed the Patient Informed 
Consent Form.  
The investigator will maintain a log of all subjects enrolled in the study assigning an identification code 
linked to their names, alternative subject identification or contact information. 
8.3. Inclusion Criteria 
1. Patients with valvular insufficiency and/or stenosis  and indicated for the reconstruction and/or 
remodeling of pathological mitral valves with Profile 3D™ and CG Future™ annuloplasty systems 
2. Indications and contraindications provided in the product Instructions for Use 
3. Subject is 18 years of age or older 
4. The patient or his/her Legally Authorized Representative (LAR) has been informed about the 
nature of the registry and  the patient informed consent for study participation has been obtained 
prior to performing any study-related procedures from the subject or Legally Authorized 
Representative, as per applicable local requirements  
8.4. Exclusion Criteria 
1. Contraindications as per IFU: 
a. Heavily calcified valves 
b. Valvular retraction with severely reduced mobility 
c. Active bacterial endocarditis 
2. Aortic valve replacement as concomitant procedure 
3. Already participating in another  clinical study, possibly leading to bias and jeopardizing the 
scientific appropriate assessment of the study endpoints 
9. Study Procedures  
9.1. Schedule of Events 
The following table (Table 1) lists the schedule of events for the study for each study related visit. 
 
Table 1: Schedule of Events 
Visit 
Procedure 
Data Collection 
Baseline/Pre-
Operative 
(data from 
most recent 
assessment 
Enrollment 
Consent 
Eligibility assessment (inclusion/exclusion criteria) 
 
Patient Data 
Patient Demographics 

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before 
planned 
implant date 
preferred, not 
exceeding 60 
days) 
Pre-Operative Clinical History (cardiac rhythm, previous procedures, 
symptoms, risk factors, lesion information, etc.) 
Medications 
Echo 
MR 
Mitral Gradient 
Leaflet coaptation 
Aortic and Tricuspid valves 
HF parameters (LVEF, LVEDD, LAD, etc.) 
Implant 
Implant Data 
Procedure Details 
Repair Details 
Concomitant Procedures 
Sizing 
Serious Adverse Events including major adverse cardiac or 
cerebrovascular events (MACCE) as defined in section 11.1 
Echo   
Intra-op echo 
Discharge 
(date of 
discharge or 
7 days post 
procedure, 
whichever 
comes first) 
Health 
Assessment 
Subject Assessment (Cardiac rhythm, NYHA, etc.) 
Serious Adverse Events including major adverse cardiac or 
cerebrovascular events (MACCE) as defined in section 11.1 
Medication 
Echo 
MR 
Mitral Gradient 
Leaflet coaptation 
Aortic and Tricuspid valves 
HF parameters (LVEF, LVEDD, LAD, etc.) 
3-6 Month 
Follow Up 
(data 
reported from 
90 days up to 
210 days post 
procedure, 
whichever 
comes later) 
Health 
Assessment 
Subject Assessment (Cardiac rhythm, NYHA, etc.) 
Serious Adverse Events including major adverse cardiac or 
cerebrovascular events (MACCE) as defined in section 11.1 
Medication 
Echo 
MR 
Mitral Gradient 
Leaflet coaptation 

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Aortic and Tricuspid valves 
HF parameters (LVEF, LVEDD, LAD, etc.) 
12 Month 
Follow Up 
(data 
reported up 
to day 395 
(365 +/- 30 
days) post 
procedure 
date will be 
collected) 
Health 
Assessment 
Subject Assessment (Cardiac rhythm, NYHA, etc.) 
Serious Adverse Events including major adverse cardiac or 
cerebrovascular events (MACCE) as defined in section 11.1 
Medication 
Echo 
MR 
Mitral Gradient 
Leaflet coaptation 
Aortic and Tricuspid valves 
HF parameters (LVEF, LVEDD, LAD, etc.) 
Study Exit 
Exit 
 
The following figure (Figure 3) is indicative of the study methods. 

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Figure 3: Study Methods 
 
9.2. Subject Screening  
Patients indicated for mitral repair procedure will be considered for enrollment in this study, and screened 
based on inclusion/exclusion criteria mentioned in Section 8. Site will maintain a Screening Log to 
maintain screening information. 
Patients with valvular insufficiency and/or stenosis  and indicated for the 
reconstruction and/or remodeling of pathological mitral valves with annuloplasty 
system 
Patient informed consent 
Enroll 
Eligibility 
Baseline: Demographics, clinical history, medications, Echo (MR grade and other 
parameters) 
Implant:  
Procedure and Repair Details, Concomitant Procedures, Sizing. Intra-op Echo 
Serious Adverse Events including MACCE (Section 11.1) 
Discharge:  
Subject Assessment (Cardiac rhythm, NYHA), Medications, Echo,  
Serious Adverse Events including MACCE (Section 11.1) 
3-6 month Follow Up:  
Subject Assessment (Cardiac rhythm, NYHA), Medications, Echo 
Serious Adverse Events including MACCE (Section 11.1) 
12 month Follow Up:  
Subject Assessment (Cardiac rhythm, NYHA), Medications, Echo 
Serious Adverse Events including MACCE (Section 11.1) 
Study Exit 

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9.3. Prior and Concomitant Medications 
During the course of the study, subjects will continue to take medication as advised by their physician per 
standard of care. The study does not advise or limit the subject from any particular medication. 
9.4. Subject Consent 
The investigator or authorized designee must obtain written informed consent before any study related 
activity takes place.  
Prior to the consent discussion, the patient should receive the EC/IRB approved Patient Information and 
Patient Informed Consent Form. During the consent discussion the investigator or his/her authorized 
designee must fully inform the patient of all aspects of the study that are relevant to the patient’s 
decision to participate in the study. If a patient is illiterate, an impartial witness must be present during 
the entire informed consent discussion. All items addressed in the Patient Information and the Patient 
Informed Consent Form must be explained. The language used shall be as non-technical as possible and 
must be understandable to the patient and the impartial witness, where applicable.  
The patient must have ample time and opportunity to read and understand the Patient Information and 
the Patient Informed Consent Form, to inquire about details of the study, and to decide whether or not to 
participate in the study. All questions about the study should be answered to the satisfaction of the 
patient. 
Neither the investigator, nor the investigation site staff shall coerce or unduly influence a patient to 
participate or to continue to participate in the study. The informed consent process shall not waive or 
appear to waive the patient’s rights. 
When the patient decides to participate in the study, the Patient Informed Consent Form must be signed 
and personally dated by the patient and investigator or authorized designee. If applicable, the witness 
shall also sign and personally date the consent form to attest that the information in the Patient 
Information and Patient Informed Consent Form was accurately explained and clearly understood by the 
patient, and that informed consent was freely given. 
After all persons have signed and dated the Patient Informed Consent Form, the investigator must 
provide the patient with a copy of the Patient Information and the signed and dated Patient Informed 
Consent Form. 
This study does not require any additional interventions other than the standard of care, and hence, the 
subject will be treated as per physician’s discretion in case of requirement of emergency treatments. 
It will be the investigator’s responsibility to fulfil any additional EC requirements, if any on the informed 
consent process.   
9.5. Randomization and Treatment Assignment 
PRESERVE-Mitral is a prospective non-randomized non-interventional post-market registry and does not 
involve randomization.   

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9.6. Medication Compliance 
The study will not be prescribing any particular medication, all subjects will continue on their medication 
as prescribed by their physicians per standard practice. 
9.7. Assessment of Efficacy 
This is a post-market registry assessing long term clinical outcomes. 
9.8. Assessment of Safety 
Serious Adverse Events and Device Deficiencies throughout the study will be collected and recorded in 
the AE and DD CRF’s. All Adverse Events and Device Deficiencies will be reviewed by Medtronic Safety 
Representative. Safety Representative will ensure the timely review and reporting of all events. Safety 
assessment will be documented in the safety database. The types of events and reporting requirements 
are described in section 11 below. 
Product Complaint:  
Any written, electronic or oral communication that alleges deficiencies related to the identity, quality, 
durability, reliability, safety, effectiveness or performance of a medical device that has been released for 
distribution. Any complaint involving the possible failure of a device, labeling or packaging to meet any of 
its specifications is subject to reporting. Devices/products used in this study are commercially available in 
the countries participating in the study. Product complaints are not within the scope of this CIP and 
should be reported in addition to the Adverse Event reporting requirements. It is the responsibility of the 
investigator to report all product complaint(s) associated with a medical device distributed by Medtronic, 
regardless whether they are related to intended use, misuse or abuse of the product, promptly.   
9.9. Recording Data 
The following table (Table 4) lists out the data collection requirements for each visit related to the study.  
Table 4. Data Collection Requirements 
 
Baseline / 
Pre-
Operative 
(data from most 
recent 
assessment 
from planned 
implant date 
preferred, not 
exceeding 60 
days) 
Implant 
Discharge 
(date of 
discharge or 7 
days post 
procedure, 
whichever 
comes first) 
3-6 month 
Follow Up  
(data reported 
from 90 days up 
to 210 days 
post procedure, 
whichever 
comes later) 
12 month 
Follow Up 
(data reported 
up to day 395 
(365 +/- 30 
days) post 
procedure date 
will be 
collected)  
Inclusion/Exclusion Criteria 
X 
 
 
 
 
PIC 
X 
 
 
 
 
Patient demographics 
X 
 
 
 
 
Pre-operative clinical 
history 
X 
 
 
 
 

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Baseline / 
Pre-
Operative 
(data from most 
recent 
assessment 
from planned 
implant date 
preferred, not 
exceeding 60 
days) 
Implant 
Discharge 
(date of 
discharge or 7 
days post 
procedure, 
whichever 
comes first) 
3-6 month 
Follow Up  
(data reported 
from 90 days up 
to 210 days 
post procedure, 
whichever 
comes later) 
12 month 
Follow Up 
(data reported 
up to day 395 
(365 +/- 30 
days) post 
procedure date 
will be 
collected)  
Mitral Valvular Lesion and 
Risk Factors 
X 
 
 
 
 
Cardiac Rhythm 
Assessment 
X 
 
X 
X 
X 
Heart Failure Symptoms 
X 
 
X 
X 
X 
NYHA Classification 
X 
 
X 
X 
X 
Medications 
X 
 
X 
X 
X 
Echocardiography including 
MR grade, mitral gradient, 
coaptation, LVEF, LVEDD, LAD 
and tricuspid and aortic valve 
assessments 
X 
X(1) 
X 
X 
X 
Implant Details 
 
X 
 
 
 
Concomitant Procedures 
 
X 
 
 
 
Re-operation 
 
 
X 
X 
X 
Serious Adverse Events 
including MACCE (as defined in 
section 11.1) 
 
X 
X 
X 
X 
Device Deficiency 
 
X 
X 
X 
X 
Death 
As they occur 
Protocol Deviation 
Study Exit 
 
 
 
 
X 
 
(1) TEE specific parameters will be collected for TEE done at implant  
9.9.1. 
Enrollment (Baseline) Visit 
Besides the PIC and the meeting of the in/exclusion criteria, the following information will be collected: 
 
Demographics such as age and gender will be collected after enrolling subject 
 
Medical History such as etiology and history of previous surgical intervention will be documented 
 
Cardiac rhythm will be documented, measured as per standard practice (ECG/Holter) 
 
Heart failure symptoms (such as dyspnea, persistent coughing, edema, fatigue, nausea, 
orthopnea, confusion, increased heart rate) will be collected and results of physical examination 
(such as systolic and diastolic blood pressure, NYHA class) will be documented 
 
Evaluation of the mitral valvular lesion will be done and documented (Rheumatic, Ischemic, etc) 
 
Medication – The drug therapy provided to the subject at the enrollment visit will be documented 

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 
Echocardiography – Transthoracic echo (TTE) data will be collected,  documenting  mitral valve 
regurgitation grade, mitral gradient and coaptation, right/left atrial, ventricular size and functional 
information (including aortic and tricuspid evaluation), etc. 
Data from the most recent assessment before the planned implant date will be preferred, not exceeding 
60 days.  
9.9.2. 
Implant Visit 
The implant will be performed as per surgeon’s discretion and standard practice. The following 
information will be collected during the implant procedure. 
 
Details of surgical approach and procedural complexity (cross-clamp time, concomitant 
procedures, etc) will be documented 
 
Mitral valve pathology (valve dilatation, calcification, prolapse, etc) and leaflet segments affected 
(A1, A2, A3, P1, P2, P3) will be documented 
 
Details of mitral repair along with the ring/band annuloplasty (papillary muscle repair, chordal 
replacement or shortening, etc) and sizing of mitral valve annulus will be documented 
 
Serious Adverse Events including MACCE (as defined in section 11.1) during the implant will be 
documented, and an Adverse Event form will also be filled out 
 
Echocardiography – Transoesophageal echo (TEE) data will be collected, documenting  various 
TEE parameters routinely evaluated during annuloplasty procedure. 
9.9.3. 
Discharge Visit 
This visit will be conducted at date of discharge or 7 days post procedure, whichever comes first. The 
following data are to be collected: 
 
Cardiac rhythm will be documented, measured as per standard practice (ECG/Holter) 
 
Heart failure symptoms (such as dyspnea, persistent coughing, edema, fatigue, nausea, 
orthopnea, confusion, increased heart rate) will be collected and results of physical examination 
(such as systolic and diastolic blood pressure, NYHA class) will be documented 
 
Medication – The drug therapy provided to the subject at discharge visit will be documented 
 
Serious Adverse Events including MACCE (as defined in section 11.1) since the implant will be 
documented, and an Adverse Event form will also be filled out  
 
Echocardiography – Transthoracic echo (TTE) data will be collected,  documenting  mitral valve 
regurgitation grade, mitral gradient and coaptation, right/left atrial, ventricular size and functional 
information (including aortic and tricuspid evaluation), etc. 
9.9.4. 
3-6 month Follow Up  
This visit will be conducted between 90 days up to 210 days post procedure, whichever comes later. The 
following data are to be collected: 
 
Cardiac rhythm will be documented, measured as per standard practice (ECG/Holter) 
 
Heart failure symptoms (such as dyspnea, persistent coughing, edema, fatigue, nausea, 
orthopnea, confusion, increased heart rate) will be collected and results of physical examination 
(such as systolic and diastolic blood pressure, NYHA class) will be documented 
 
Medication – The drug therapy provided to the subject since last visit will be documented 

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 
Serious Adverse Events including MACCE (as defined in section 11.1) since the implant will be 
documented, and an Adverse Event form will also be filled out 
 
Echocardiography – Transthoracic echo (TTE) data will be collected,  documenting  mitral valve 
regurgitation grade, mitral gradient and coaptation, right/left atrial, ventricular size and functional 
information (including aortic and tricuspid evaluation), etc. 
9.9.5. 
12 month Follow Up  
This visit will be conducted up to 395 days (365 days +/- 30 days) post procedure. The following data are 
to be collected: 
 
Cardiac rhythm will be documented, measured as per standard practice (ECG/Holter) 
 
Heart failure symptoms (such as dyspnea, persistent coughing, edema, fatigue, nausea, 
orthopnea, confusion, increased heart rate) will be collected and results of physical examination 
(such as systolic and diastolic blood pressure, NYHA class) will be documented 
 
Medication – The drug therapy provided to the subject since last  visit will be documented 
 
Adverse Events since last visit will be documented, and an Adverse Event form will also be filled 
out 
 
Echocardiography – Transthoracic echo (TTE) data will be collected,  documenting  mitral valve 
regurgitation grade, mitral gradient and coaptation, right/left atrial, ventricular size and functional 
information (including aortic and tricuspid evaluation), etc. 
9.9.6. 
Source documents  
Source data are all information, original records of clinical findings, observations, or other activities in a 
clinical trial necessary for the reconstruction and evaluation of the trial. Source data are contained in 
source documents. Examples of these original documents, and data records include but not limited to: 
hospital records, clinical and office charts, laboratory notes, memoranda, or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments such as hospital monitoring 
equipment, Holter portable document format (PDF) reports, copies or transcriptions certified after 
verification as being accurate and complete, microfiches, photographic negatives, microfilm or magnetic 
media, x-rays, subject files, and records kept at the pharmacy, at the laboratories, and at 
medicotechnical departments involved in the clinical trial. 
The investigator will clearly mark clinical records to indicate that the subject is enrolled in this clinical 
study.  
The site is responsible to record all trial related source data enabling the sponsor to reconstruct the 
complete course of the clinical trial. Source data will be transcribed to and reported through the CRF 
accordingly. A source data identification list will be provided to the sponsor for approval prior to 
commencing the clinical part of the trial. The list will be filed in the investigator site file. 
Where copies of the original source document as well as printouts of original electronic source documents 
are retained, these shall be signed and dated by a member of the investigation site team with a 
statement that it is a true reproduction of the original source document. 
 

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9.10. Deviation Handling 
A protocol deviation is defined as an event where the clinical investigator or site personnel did not 
conduct the study in accordance to the protocol or the Investigator agreement. The investigator is not 
allowed to deviate from these documents except with prior approval and under emergency 
circumstances. All deviations shall be documented and explained, regardless the reason for the deviation.  
Examples of protocol deviations include but are not limited to the following:  
 
Failure to obtain informed consent prior to participation 
 
Incorrect version of the informed consent form used 
 
Failure to obtain EC/IRB approval before the start of the study 
 
Subject did not meet inclusion/exclusion criteria 
 
Source data permanently lost 
 
Enrollment of subjects during lapse of EC/IRB approval  
Investigators should obtain prior approval from Medtronic before initiating any change or deviation from 
the CIP, except where necessary to protect the life or physical wellbeing of a subject in an emergency 
situation. Such approval shall be documented in writing and maintained in the investigator site files. Prior 
approval is generally not expected in situations where unforeseen circumstances are beyond the 
investigator’s control (eg. subject did not attend scheduled follow-up visit).  
Deviations will be reported to Medtronic regardless of whether medically justifiable, pre-approved by 
Medtronic, or taken to protect the subject in an emergency. Study deviations should be reported to 
Medtronic vide the study Deviation eCRF (1 eCRF for each protocol deviation). Relevant information for 
each deviation will be documented on a deviation form completed by site personnel and reviewed by the 
Investigator.  
Investigators should report the following deviations to Medtronic and their reviewing EC/IRB in 
accordance with reporting requirements of local EC/IRB: 
 
Failure to obtain written informed consent  
 
Deviations to protect the life or physical well-being of a subject in an emergency  
In addition, Investigators are required to adhere to local EC/IRB procedures for reporting deviations.  
Medtronic is responsible for analyzing deviations, assessing their significance, and identifying any 
corrective and/or preventive actions that may be warranted such as amending the CIP, in accordance 
with Medtronic SOPs. Repetitive or serious investigator non-compliance may represent a need to initiate a 
corrective action plan, which may include suspension of enrollment or termination of the investigator’s or 
site’s participation in the study. 
Request for approval of study deviations  
The investigator shall obtain documented approval from Medtronic, before implementation, for any 
change in- or deviation from the CIP. In case of any deviations that can affect the subject’s rights, safety 
and well-being or the scientific integrity of the clinical study, approval from the EC/IRB and regulatory 
authority must also be obtained before implementation. The investigator shall timely contact the Clinical 
Manager for review of the proposed change/deviation.  

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Prior approval is not always realistic in situations where unforeseen circumstances are beyond the 
investigator’s control. However, also in these cases, the event is considered a deviation, and shall be 
reported.  
In any emergency situation the investigator shall exercise his/her judgment to safeguard the subject’s 
interest. Such deviations from the CIP do not require the prior approval of Medtronic. The investigator 
shall report the deviation as soon as possible to Medtronic and the reviewing EC/IRB, if applicable. 
9.11. Subject Withdrawal or Discontinuation 
All subjects will be encouraged to remain in the registry through the last follow-up visit at 12 months. 
Subjects who discontinue participation prematurely after attempted implant will be included in the 
analysis of results (as appropriate) but they will not be replaced in the enrollment of total study subjects. 
If a study subject is discontinued from the study early, the reason for discontinuation should be 
documented in the subject file and a Study Exit eCRF must be completed. If discontinuation is because of 
safety concerns, the subject shall be asked to be followed for collection of ongoing safety data outside 
the study. Any data collected after the exit date will not be analyzed as part of the study. 
In case the subject undergoes device explant, the subject will be exited from the study. 
The subjects will be exited from the study following their 12 month follow up visit. This 12 month visit will 
be primarily conducted via in-office visit and has a window period of additional 1 month, up to day 395 
post implant. All adverse event information will be collected and reported during this follow up visit, as 
per timelines described above in section 11.2;  subjects will be considered exited from the study on 
completion of their 12 month visit or when they are considered lost to follow up (after three failed 
attempts are made to contact the subjects). 
The investigating site and Sponsor will make every effort to have all subjects complete the follow up visit 
schedule. A subject will not be considered lost-to-follow-up unless all efforts to obtain compliance are 
unsuccessful. At a minimum, the effort to obtain follow-up information must include three attempts to 
make contact via telephone and if contact via phone is not successful, a traceable letter from the 
Investigator must be sent to the subject’s last known address. Should both telephone and mail efforts to 
contact the subject be unsuccessful, the subject’s primary physician should be contacted.  Subjects will 
then be deemed lost to follow up. All contact efforts to obtain follow-up must be documented in the 
subject’s medical records. 
 If a subject discontinues the study at any time, is withdrawn from the study early, or completes all 
protocol required follow-up they should then be followed per the local standard of care for their 
condition. 
10. Risks and Benefits 
10.1. Potential Risks 
This study does not require any additional interventions other than the standard of care, therefore no 
risks other than the risks typically associated with a routine annuloplasty procedure and follow-ups are 
anticipated. All products in the study are commercially available when the study is in effect and will be 
used in accordance with approved labeling. 

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While infrequent, certain complications have been reported when using annuloplasty systems. As per the 
Instructions-For-Use of the product, these include the following: 
• 
Uncorrected or recurrent regurgitation 
• 
Stenosis 
• 
Dehiscence 
• 
Hemolysis (even with mild regurgitation) 
• 
Low cardiac output 
• 
Heart block 
• 
Systolic anterior motion (SAM) and left ventricular outflow tract obstruction (LVOTO) 
• 
Damage to coronary arteries 
• 
Endocarditis 
• 
Thrombosis 
• 
Thromboembolism 
• 
Anticoagulant-related bleeding or hemorrhage 
• 
Ring fracture 
• 
Leaflet perforation 
 
These complications could lead to: 

Reoperation 

Explant of the annuloplasty system 

Permanent disability 

Death  
There might be additional risks associated with any concomitant procedures as conducted per standard 
treatment of the subject which are not listed here. 
In case of occurrence of adverse events, the subjects will be treated and followed up as per standard of 
care, as mandated by the treating physician. 
10.2. Potential Benefits 
There is no immediate benefit associated with participating in the study. However, the evidence collected 
in this study may help to improve future care. 
10.3. Risk-Benefit Rationale 
This study is a non-interventional study, with no additional risks to the subject relative to participation in 
the study, and hence, the potential benefits outweigh the risks. 

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11. Adverse Events and Device Deficiencies 
11.1. Definitions/Classifications 
Adverse Event (AE) (ISO 14155:2011, 3.2) 
Any untoward medical occurrence, unintended disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in subjects, users or other persons, whether or not related 
to the investigational medical device. 
NOTE 1 This definition includes events related to the investigational medical device or the 
comparator.  
NOTE 2 This definition includes events related to the procedures involved. 
NOTE 3 For users or other persons, this definition is restricted to events related to investigational 
medical devices.  
Adverse Device Effect (ADE) (ISO14155:2011 3.1) 
Adverse event related to the use of an investigational medical device. 
NOTE 1 This definition includes adverse events resulting from insufficient or inadequate 
instructions for use, deployment, implantation, installation, or operation, or any malfunction of the 
investigational medical device 
NOTE 2 This definition includes any event resulting from use error or from intentional misuse of the 
investigational medical device 

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Serious Adverse Event (SAE) (ISO 14155:2011, 3.37) 
Adverse event that 
a) led to a death 
b) led to serious deterioration in the health of the subject, that either resulted in: 
1. a life-threatening illness or injury, or 
2. a permanent impairment of a body structure or a body function, or 
3. in-patient or prolonged hospitalization, or 
4. medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function 
c) led to fetal distress, fetal death or a congenital abnormality or birth defect 
NOTE Planned hospitalization for a pre-existing condition, or a procedure required by the CIP, 
without serious deterioration in health, is not considered a serious adverse event. 
Serious Adverse Device Effect (SADE) (ISO14155:2011 3.36) 
Adverse device effect that has resulted in any of the consequences characteristic of a serious 
adverse event 
Unanticipated serious adverse device effect (USADE)   (ISO14155:2011 3.42) 
Serious adverse device effect which by its nature, incidence, severity or outcome had not been 
identified in the current version of the risk analysis report 
NOTE Anticipated serious adverse device effect (ASADE) is an effect which by its nature, incidence, 
severity or outcome has been identified in the risk analysis report 
Major adverse cardiac and cerebrovascular events (MACCE) 
 
All-cause mortality 
 
Myocardial infarction 
 
Emergent cardiac surgery or re-intervention 
 
Stroke 
 
Hospitalization for Heart Failure 

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Device Deficiency (DD) (ISO14155:2011 3.15) 
Inadequacy of a medical device with respect to its identity, quality, durability, reliability, safety or 
performance  
NOTE Device deficiencies include malfunctions, use errors and inadequate labeling 
  
11.2. Reporting of Adverse Events and Device Deficiencies 
Investigator reporting requirement 
Report 
Submit to 
Description/Constraints 
All SAE,SADE, 
USADE 
Monitor and Sponsor 
Investigator shall report all SAEs, SADEs and USADEs to 
the Sponsor and monitor promptly of their occurrence. 
(Indian GCP section 3.3.4.3) 
It is recommended for investigator to report all SAEs, 
SADEs and USADEs to the sponsor within 24 hours.  
For reported deaths the investigator shall supply any 
additional information e.g. autopsy report and terminal 
medical reports. (Indian GCP section 3.3.4.5) 
All SAE, SADE, 
USADE  
EC 
Investigator shall report all SAEs, SADEs and USADEs to 
the EC promptly of their occurrence. (Indian GCP section 
3.3.4.3) 
For reported deaths the investigator shall supply any 
additional information e.g. autopsy report and terminal 
medical reports. (Indian GCP section 3.3.4.5)  
It is recommended for investigator to report all SAEs, 
SADEs and USADEs to EC within 7 working days unless a 
stricter timeline is required by the EC. 
All Device Deficiency Monitor and Sponsor 
Investigator shall report all DDs to the Sponsor and 
monitor promptly of their occurrence. 
It is recommended for investigator to report all DDs to the 
sponsor within 24 hours.  

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New information 
that may adversely 
affect safety of the 
subjects or the 
conduct of the study 
EC, monitor and 
sponsor 
Investigator shall promptly report new information that 
may adversely affect safety of the subject or the conduct 
of the study. (Indian GCP section 3.3.4.4)  
 
Sponsor reporting requirement 
Report 
Submit to 
Description/Constraints 
USADE  
DCGI , Chairman 
of the EC  
The report of the serious adverse event, after due analysis, shall 
be forwarded by the Sponsor to the Licensing Authority and 
Chairman of the Ethics Committee within 15 days the sponsor 
became aware of the serious adverse event. In case of the site 
directly reporting the USADE to EC, the Sponsor requirement to 
report to the EC is considered to be sufficiently met. 
 
 
Non reportable events 
The events listed in the table below are expected for patients undergoing cardiac surgery, and do not 
need to be reported as an AE, unless they occur outside of the stated timeframe, are otherwise 
considered to be an AE according to the investigator, or are suspected or confirmed to be device-related. 
Body Category 
Occurrence 
Timeframe (hours) 
post procedure 
Hematologic 
Blood transfusion and anemia occurring during the 
procedure within expected ranges (part of the regular 
hospital protocol) 
0 
Hematologic 
Any bleeding during the procedure 
0 
Hematologic 
Any bleeding after procedure with < 3 units blood 
transfusion, or < 1 liter blood loss 
24 
Cardiac 
Short transient episode of arrhythmia (including 
ventricular fibrillation) during procedure 
0 
Central Nervous 
System 
Confusion, anxiety and/or disorientation (other than 
TIA/stroke) starting within 48 hours with or without 
medical intervention 
120 (5 days) 
Central Nervous 
Temporary change in mental status (other than 
72 

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Body Category 
Occurrence 
Timeframe (hours) 
post procedure 
System 
TIA/stroke) not requiring additional medical 
interventions or new medical assessments (e.g. CT) 
Central Nervous 
System 
Dizziness and/or lightheadedness with or without 
treatment 
24 
Central Nervous 
System 
Headache with or without treatment 
72 
Central Nervous 
System 
Sleep problems or insomnia with or without treatment 
120 (5 days) 
Respiratory/Pulmonary 
Mild dyspnea or cough with or without treatment 
72 
Respiratory 
Oxygen supply after extubation / “forced breathing 
therapy” 
48 
Gastrointestinal 
Diarrhea with or without treatment 
48 
Gastrointestinal 
Obstipation / Constipation with or without treatment 
72 
Gastrointestinal 
Anesthesia-related nausea and/or vomiting with or 
without treatment 
24 
Body Temperature 
Low-grade fever (<101.3°F or <38.5°C) without 
confirmed infection 
48 
Body Temperature 
Low body temperature 
6 
Pain 
Pain (e.g. back, shoulder) related to laying on the 
procedure table with or without treatment 
72 
Pain 
Incisional pain (pain at access site) with or without 
standard treatment and patient not returning to clinic 
to have additional treatment 
No time limit 
Pain 
Pain in throat and/or trachea due to intubation 
72 
Skin and subcutaneous 
System 
Mild to moderate bruising or ecchymosis 
168 (7 days) 
Respiratory 
Atelectasis / Pleural Effusion not requiring punctuation 
168 (7 days) 
General 
Edema resulting in weight increase up to 4 kg / 9lbs 
from baseline 
168 (7 days) 
 

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12. Data Review Committees  
There will be no Data Monitoring Committee (DMC) or Clinical Events Committee (CEC) used in this 
study. There will be a Medical Advisor assigned to this study, who will provide guidance on safety issues 
when escalated from the safety representative and is consulted on planning and documentation for the 
study. The contact information will be kept in the study roster. 
13. Statistical Design and Methods 
The statistical analyses will be performed by Medtronic employed statisticians. Three study populations 
are defined: 
• 
Enrolled: Composed of all patients who signed the Patient Informed Consent Form. 
• 
Attempted Implant (AT): Composed of all enrolled subjects who are attempted for a Profile 3DTM or 
CG Future® Annuloplasty system implantation. Time zero begins at the date of attempted procedure.   
• 
Implanted (IMP): Composed of all AT subjects who had either a Profile 3DTM or CG Future® 
Annuloplasty system implanted. Time zero for implanted subjects begins at the date of implant 
procedure. 
All data collected from enrolled, attempted implant, and implanted subjects will be utilized in the analyses 
as appropriate. Analyses of the primary and secondary endpoints will be descriptive, and no statistical 
hypothesis tests will be performed.  
All continuous variables will be summarized as the number of subjects, means, standard deviations, 
medians, minimums, maximums, and interquartile ranges. Categorical variables will be summarized as 
frequencies and percentages.  
Additional details of planned statistical analysis will be specified in Statistical Analysis Plan (SAP). Any 
deviations from the original statistical plan will be summarized in the Clinical Study Report(s) (CSRs), 
along with the justification for the deviations.  
13.1. Missing/Unused/Unauthentic Data 
Every effort will be undertaken to minimize missing data, unused data and unauthentic data. Unless 
otherwise specified, no statistical techniques will be used to impute missing data. The number of subjects 
included in each analysis will be reported so that the reader can assess the potential impact of missing 
data. Data management procedures defined in Section 15.2 will be followed to minimize unauthentic data 
in the analysis datasets. Handling of unused data will be defined in the Statistical Analysis Plan. 
13.2. Subgroup Analysis 
Details of planned subgroup analysis will be specified in Statistical Analysis Plan (SAP). 
13.3. Interim Analysis 
An interim summary of the data is planned when all enrolled and implanted subjects have had the 
opportunity to be followed through (are eligible for) the discharge visit. This is an observational study, no 

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statistical hypothesis tests will be performed, and there are no pass/fail criteria for the results of this 
study. 
13.4. Sample Size Determination 
The sample size of 200 subjects who are eligible and intended to be implanted with a Profile 3DTM or CG 
Future® Annuloplasty system in the surgical repair procedure is adequate and appropriate for the 
evaluation of local evidence and obtaining real world data on clinical outcomes following implantation of 
these two products. This sample size was not statistically derived as this is not a hypothesis driven study.   
13.5. Primary Endpoints 
The primary endpoints are the following clinical outcomes at 12 months post procedure: 
1. Improvement in MR (grade) 
Mitral valve function will be based on site echocardiographic recordings. For each subject with paired 
data, the change from baseline (improved, no change, worsened) will be evaluated at 12 months. 
The primary endpoint of improvement in MR (grade) will be presented with frequencies and 
percentages of subjects with improved MR at 12 months. The two-sided 95% exact binomial 
confidence interval of the overall percent of subjects with improved MR at 12 months will also be 
reported.  
2. All-cause mortality 
A Kaplan-Meier analysis will be performed. The endpoint is descriptive and no statistical hypothesis 
test will be performed.   
13.6. Secondary Endpoints 
The secondary endpoints are as follows: 
1. Characterization of patient demographics and pathophysiology of mitral valve disease 
Baseline demographic and clinical variables will be summarized. Descriptive statistics will be provided. 
2. Improvement in MR grade at discharge and first follow up (3-6 months) 
Mitral valve function will be based on site echocardiographic recordings. For each subject with paired 
data, the change from baseline (improved, no change, worsened) will be evaluated at discharge and 
3-6 months. The secondary endpoint of improvement in MR (grade) will be presented with 
frequencies and percentages of subjects with improved MR at discharge and 3-6 months. The two-
sided 95% exact binomial confidence interval of the overall percent of subjects with improved MR at 
discharge and 3-6 months will also be reported. 
3. Improvement in NYHA functional class at discharge, first follow up (3-6 months) and second follow 
up (12 months) compared to baseline 
For each subject with paired data or who died prior to visit, the change from baseline (improved, no 
change, worsened or died) will be calculated at discharge, 3-6 months, and 12 months. The endpoint 
of improvement in NYHA class will be presented with frequencies and percentages of subjects with 
improved NYHA at discharge, 3-6 months, and 12 months. The two-sided 95% exact binomial 
confidence interval of the overall percent of subjects with improved NYHA class at these time 
intervals will also be reported.  
4. Hospitalization for Heart Failure at 6 months and at 12 months post procedure 

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A Kaplan-Meier analysis will be performed. The duration of hospitalization for heart failure will be 
summarized. The endpoint is descriptive and no statistical hypothesis test will be performed.  
5. Mitral valve re-intervention at discharge, 6 months and at 12 months post procedure 
A Kaplan-Meier analysis will be performed. The endpoint is descriptive and no statistical hypothesis 
test will be performed.  
6. Stroke at 6 months and at 12 months post procedure 
A Kaplan-Meier analysis will be performed. The endpoint is descriptive and no statistical hypothesis 
test will be performed.  
7. New onset of Atrial Fibrillation, as evaluated through follow up ECG at discharge, first follow up (3-6 
months) and at second follow up (12 months) 
The number (and percent) of subjects with new onset of Atrial Fibrillation will be evaluated at 
discharge, 3-6 months, and 12 months. Descriptive statistics will be provided.  
8. Number of attempts required for procedural success, and bypass time as a measure of procedural 
complexity 
The number of attempts (per subject) required for procedural success and the bypass time will be 
summarized. Descriptive statistics will be provided. 
14. Ethics 
14.1. Statement(s) of Compliance  
 
The study will be conducted in accordance with the protocol and ethical principles that have their 
origin in the Declaration of Helsinki, and India GCP. 
 
The study will not begin until EC/IRB approvals as required are received.  
 
Any special requirements imposed by EC/IRB will be followed for the respective sites.  
 
The Name(s), title(s), address(es), and contact numbers of the investigator(s) who are 
responsible for conducting the study, along with their consent letter(s) (Investigator 
Statement),will be listed and kept separate from the CIP and will be updated by the sponsor.  
 
The Name(s), address(es) and contact numbers of the institution(s) particulars of the head(s) of 
the institution(s), will be kept separate from the CIP. The sponsor will maintain an updated list.  
 
If any action is taken by an EC/IRB with respect to the investigation, that information should be 
forwarded to the sponsor.  
15. Study Administration 
15.1. Monitoring  
It is the responsibility of Medtronic to ensure proper monitoring of this clinical investigation per 
regulations. Trained Medtronic personnel or delegates appointed by Medtronic may perform study 
monitoring at the study site in order to ensure that the study is conducted in accordance with the CIP, 
the Clinical Trial Agreement, and applicable local regulatory requirements. Medtronic, or delegates, must 
therefore be allowed access to the subjects’ medical records (and other source data/documentation) 
upon request as per the Subject Informed Consent and Clinical Trial Agreement. 

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Monitoring Visits  
Frequency of monitoring visits will be based upon subject enrollment, duration of the study, study 
compliance, findings from previous monitoring visits and any suspected inconsistency in data that 
requires investigation. Monitoring for the study will be done in accordance to the study monitoring plan. 
Monitoring visits may be conducted to assess the investigator’s adherence to the CIP, including but not 
limited to Ethics Board approval and review of the study, maintenance of records and reports, and review 
of source documents against subject CRFs. Monitors review study compliance by identifying findings of 
non-compliance and communicating those findings along with recommendations for 
preventative/corrective actions to site personnel. Monitors may work with study personnel to determine 
appropriate corrective action recommendations and to identify trends within the study or at a particular 
site.     
15.2. Data Management 
15.2.1. 
Electronic Data Capture 
Medtronic will use the Oracle Clinical Remote Data Capture database system for data collection. The 
database is located on a secure server at a Medtronic facility located in the United States. All users will be 
trained on the use of the database prior to obtaining access. Once access is granted, users will have a 
unique User ID and will create their own password. Data stored electronically shall be maintained in 
compliance with 21CFR Part 11. The database for this trial will be maintained for life of the medical 
device plus one year, or 15 years, whichever is longer according to corporate policy and record retention 
schedule. 
15.2.2. 
Data Collection 
It is the responsibility of the participating Investigator to ensure the quality of the data being collected.  
Required data will be recorded on electronic case report forms (eCRFs) by authorized site personnel as 
indicated on the Delegation of Tasks List. The eCRFs must be completed and/or updated to reflect the 
latest observations on the subjects participating in the trial.  
The investigator will electronically sign each eCRF.  
The EDC system maintains an audit trail on entries, changes or corrections in eCRFs, once the eCRF is 
saved as complete. If changes are made to an already signed eCRF, the investigator shall re-sign this 
eCRF. 
15.2.3. 
Data Validation 
The sponsor and/or assigned designee will be responsible for the processing and quality control of the 
data (data management) per the Data Management Plan, which describes the procedures for data 
review, database cleaning and issue/resolution of data queries. Data will be collected and stored in a 
validated, password protected database. Data analysis will be conducted utilizing validated software and 
analysis programs by qualified biostatisticians. 

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Trial data collected will be monitored and verified against source documents in accordance with 
ISO14155:2011 guidelines and international standards. Any data discrepancies will be addressed through 
queries posted within the EDC system. 
15.3. Direct Access to Source Data/Documents  
The sponsor or a regulatory authority, may audit the study site to evaluate the conduct of the study and 
to ensure compliance to GCP, the CIP, and applicable local regulatory requirements. The clinical 
investigator(s)/institution(s) shall allow study related monitoring, audits, Ethics Board review and 
regulatory inspection(s) by providing direct access to source data/documents. 
15.4. Confidentiality 
All records and other information about subjects participating in this study will be treated as private and 
confidential, investigator will keep full patient lists or records.  
Medtronic will collect data in such a way that no subject can be identified. Participating subjects will not 
be identified by name in any published reports about the study. 
15.5. Liability 
Since this is a post market study with no investigational devices, no compensation will be provided to 
subjects for participating in the study or as part of the study.  
Medtronic maintains appropriate clinical trial liability insurance coverage as required under applicable laws 
and regulations and will comply with applicable local law and custom concerning specific insurance 
coverage. If required a Clinical Trial insurance statement/certificate will be provided to the Medical 
Institution and Ethics Committee.    
15.6. CIP Amendments 
Medtronic will submit any significant amendment to the Clinical Investigation Plan, including a justification 
for this amendment, to the investigators to obtain approval from their respective EC/IRB. Where 
applicable, minor administrative amendments to the Clinical Investigation Plan will also be submitted to 
the EC /IRB for notification or approval per EC requirements. 
15.7. Record Retention 
The site is responsible for the maintenance of the records listed below:  
 
All essential correspondence that pertains to the study, including the Ethics Committee, sponsor, 
monitor, or the investigator that pertains to the investigation, including required reports. 
 
Signed and dated original clinical trial agreement.  
 
Insurance documents.  
 
All approved versions of the Clinical investigational plan.  

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 
All original signed copies of the PIC’s along with all other essential documents as approved by the 
Ethics Committee.  
 
Site personnel training documentation and delegated task list.  
 
Ethics Committee approval/Notification documents, as applicable.  
 
Relevant Medical history towards subject eligibility.  
 
Current curriculum vitae (signed and dated) of investigators and other members of Investigation site 
team per the DTL.  
 
Records of AEs and ADEs reported to Sponsor. 
 
Final Clinical Study Report (CSR)  
Records are subject to be audited by Medtronic for compliance and all study related documents and 
material should be maintained for a period of three years after the completion of the study.   
Investigational sites are responsible for ensuring that the participating investigator and other site staff are 
appropriately licensed/qualified. Medtronic will review these records to assess compliance to institutional 
policy and required regulations   
15.8. Publication and Use of Information 
The Medtronic study team will collaborate to publish the results of the study in an appropriate/highest 
impact local (Indian) and global publications.  Medtronic may implement a publication committee to 
effectively manage and oversee the primary, secondary and ancillary publications generated from the 
study while complying with all applicable guidelines and policies. 
Publications and presentations referring to the PRESERVE-Mitral Study will be coordinated by Medtronic 
to allow the use of all available data. The following publication policy will have to be adhered to by all 
participating Investigational Centers:  
Authorship on any publication(s) resulting from this study will be assigned according to substantial 
contributions to conception and design, acquisition of data, or analysis and interpretation of data, drafting 
the article or revising it critically for important intellectual content and final approval of the version to be 
published. This is in accordance with the Vancouver principles (The Uniform Requirements for 
Manuscripts Submitted to Biomedical Journals: Writing and Editing for Biomedical Publication, ICMJE, 
October 2008), as agreed upon by the editors of all major medical journals.  
The number of authors will be dependent on the regulations of the concerning journal. Names of all 
participating investigators will appear in the Acknowledgment of the paper.  
Based on the principle that Medtronic owns the data of the PRESERVE-Mitral study, a single 
Investigational Center may access and use the data provided by itself for scientific publications following 
prior approval by Medtronic.  
Medtronic as the owner of the data can use the data and/or any results derived from the data or 
publications based on that data for marketing purposes, further research and development of devices or 
educational use.  
The study sponsor will collect data in such way that no subject can be identified, and monitor study 
records. Participating subjects will not be identified by name in any published reports about the study.  

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15.9. Suspension or Early Termination 
Medtronic may decide to suspend or prematurely terminate the study (eg, because of a business 
decision). If the study is terminated prematurely or suspended, Medtronic shall promptly inform the 
clinical investigators of the termination or suspension and the reason(s) for this. The investigator shall 
then promptly inform the reviewing EC/IRB and the study subjects or their legal representative. In case 
of early termination, subjects need to be followed until at least 30 days after the initial procedure. 
Medtronic may decide to suspend or prematurely terminate an Investigational Center (eg,  in case of 
expiring approval of the reviewing EC/IRB, non-compliance to the Clinical Investigation Plan or lack of 
enrollment). If an Investigational Center is suspended or prematurely terminated, Medtronic shall 
promptly inform the clinical investigator(s) of the termination or suspension and the reason(s) for this. 
The investigator shall then promptly inform the reviewing EC/IRB and the study subjects or their legal 
representative. In case of early termination, subjects need to be followed until at least 30 days after the 
initial procedure.  
16. References 
[1]  D. Prabhakaran, P. Jeemon and A. Roy, "Cardiovascular diseases in India: current epidemiology and 
future directions," Circulation, vol. 133, pp. 1605-1620, 2016.  
[2]  A. Carpentier, S. Chauvaud, J. N. Fabiani, A. Deloche, J. Relland, A. Lessana, C. D'Allaines, P. 
Blondeau, A. Piwnica and C. Dubost, "Reconstructive surgery of mitral valve incompetence: ten year 
appraisal," J Thorac Cardiovasc Surg, vol. 79, no. 3, pp. 338-348, 1980.  
[3]  F. Filsoufi, S. P. Salzberg and D. H. Adams, "Current management of ischemic mitral regurgitation," 
Mt Sinai J Med, vol. 72, no. 2, pp. 105-115, 2005.  
[4]  W. A. Zoghbi, D. Adams, R. O. Bonow, M. Enriquez-Sarano, E. Foster, P. A. Grayburn, R. T. Hahn, Y. 
Han, J. Hung, R. M. Lang, S. H. Little, D. Shah, S. Shernan, P. Thavendiranathan, J. D. Thomas and 
N. J. Weissman, "Recommendations for noninvasive evaluation of native valvular regurgitation: A 
report from the American Society of Echocardiography developed in collaboration with the Society 
for Cardiovascular Magnetic Resonance.," J Am Soc Echocardiogr, Vols. S0894-7317, no. 17, pp. 
30007-X, 2017.  
[5]  M. Enriquez-Sarano, H. V. Schaff, T. A. Orszulak, A. J. Tajik, K. R. Bailey and R. L. Frye, "Valve 
repair improves the outcome of surgery for mitral regurgitation," Circulation, vol. 91, pp. 1022-1028, 
1995.  
[6]  S. Geidel, M. Lass, K. Krause, C. Schneider, S. Boczor, K. H. Kuck and J. Ostermeyer, "Early and late 
results of restrictive mitral valve annuloplasty in 121 patients with cardiomyopathy and chronic mitral 
regurgitation," Thorac Cardiovasc Surg, vol. 56, no. 5, pp. 262-268, 2008.  
[7]  I. S. Salgo, J. H. Gorman III, R. C. Gorman, B. M. Jackson, F. W. Bowen, T. Plappert, M. G. St John 

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Sutton and L. H. Edmunds Jr., "Effect of annular shape on leaflet curvature in reducing mitral leaflet 
stress," Circulation, vol. 106, no. 6, pp. 711-717, 2002.  
[8]  R. Nishimura, C. M. Otto, R. O. Bonow, C. E. Ruiz, B. A. Carabello, N. J. Skubas, J. P. Erwin III, P. 
Sorajja, R. A. Guyton, T. M. Sundt III, P. T. O'Gara and J. D. Thomas, "2014 AHA/ACC guideline for 
the management of patients with valvular heart disease: executive summary," Circulation, vol. 129, 
pp. 000-000, 2014.  
[9]  A. Gupta, P. Gharde and A. Sampath Kumar, "Anterior mitral leaflet length: predictor for mitral valve 
repair in a rheumatic population," Ann Thorac Surg, vol. 90, pp. 1930-1933, 2010.  
[10] S. K. Choudhary, S. Talwar, B. Dubey, A. Chopra, A. Saxena and A. Sampath Kumar, "Mitral valve 
repair in a predominantly rheumatic population," Tex Heart Inst J, vol. 28, no. 1, pp. 8-15, 2001.  
[11] J. Saravana Ganesh, V. Arun, A. Raghuram and K. Subramanyan, "Mitral valve repair – Is 
replacement not an ideal operation anymore?," in Indian Heart Journal, 2015.  
[12] L. Zuhlke, M. E. Engel, G. Karthikeyan, S. Rangarajan, P. Mackie, B. Cupido, K. Mauff, S. Islam, A. 
Joachim, R. Daniels and V. Francis, "Characteristics, complications, and gaps in evidence-based 
interventions in rheumatic heart disease: the Global Rheumatic Heart Disease Registry (the REMEDY 
study)," Eur Heart J, vol. 36, pp. 1115-1122, 2015.  
[13] D. J. DiBardino, A. W. El-Bardissi, R. S. McClure, O. A. Razo-Vasquez, N. E. Kelly and L. H. Cohn, 
"Four decades of experience with mitral valve repair: analysis of differential indications, technical 
evolution, and long-term outcome," J Thorac Cardiovasc Surg, vol. 139, pp. 76-83, 2010.  
 
 
 
 

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17. Appendices    
Appendix L.1. 
Instructions-for-Use – Profile 3DTM Annuloplasty Ring
1 DEVICE DESCRIPTION 
The Medtronic PROFILE 3D™ Annuloplasty Ring, Model 680R 
(hereafter referred to as PROFILE 3D™ Ring) consists of a titanium 
core overmolded with silicone and covered with polyester fabric. The 
ring must be implanted in the mitral position. The ring is marked at 
three points by colored sutures; two markers correspond to the 
trigones of the mitral valve and one identifies the midpoint of the 
device. The device size is identified by the inside diameter of the ring 
at its widest point. The titanium core enables radiographic 
visualization of the device. 
Nonclinical testing has demonstrated the PROFILE 3D™ Ring is 
Magnetic Resonance (MR) Conditional. It can be scanned safely 
according to the conditions presented in Table 1. 
Patients with the PROFILE 3D™ Ring may safely undergo MRI for 
Normal Mode of the MR System as defined in the IEC Standard 
60601-2-33. MR image quality may be compromised if the area of 
interest is in the exact same area or relatively close to the position of 
the PROFILE 3D™ Ring. Therefore, it may be necessary to optimize 
MR imaging parameters for the presence of this implant. See Table 1 
for maximum distortion distances for spin echo and gradient echo 
sequences. These values are based upon nonclinical testing at 3T 
according to ASTM F2119-01. 
aIn nonclinical testing according to ASTM F2182-02a when the local 
SAR is normalized to 1 W/kg for 15 minutes of MR scanning in a GE 
64 MHz whole body transmit coil, and a Siemens TrioTim 3T whole 
body transmit coil. 
2 INDICATIONS 
The PROFILE 3D™ Ring is indicated for the reconstruction and/or 
remodeling of pathological mitral valves. Valvular insufficiency and/or 
stenosis may be corrected by appropriate repair and annular 
remodeling. 
3 CONTRAINDICATIONS 
Heavily calcified valves. 
Valvular retraction with severely reduced mobility. 
Active bacterial endocarditis. 
4 WARNINGS 
For single use only. 
Only surgeons who have received adequate training to determine 
whether incompetent,stenotic, or diseased heart valves are capable 
of being repaired or replaced should use this device. 
Only surgeons who have received appropriate training in valve 
repair, including ring implant and sizing techniques, should use this 
device. 
Correct annuloplasty ring sizing is an important element of a 
successful valve repair. Undersizing the ring can result in valve 
stenosis, ring dehiscence, and/or ring fracture. Oversizing the ring 
can result in valve regurgitation and/or ring fracture. 
Care should be taken that sutures are not placed in atrial tissue, as 
this may result in impairment of the cardiac conduction system. 
It is necessary to secure the ring into fibrous trigone tissue to 
maintain permanent attachment. 
Suture knots must be securely tied. Loose knots and long suture 
tails 
may 
be 
a 
source 
for 
hemolysis, 
thrombosis, 
or 
thromboembolism. 
Do not cut the ring. Resultant loose threads may be a source of 
hemolysis, thrombosis, and/or thromboembolism. 
In addition, 
resultant jagged edges of the stiffener may lead to tissue trauma. 
Do not alter or deform the ring to conform to annular anatomy as 
this could lead to ring fracture, possible valve regurgitation, or 
stenosis. 
Do not squeeze the ring with sharp instruments as this may damage 
the surface of the stiffener, which may result in ring fracture and 
possible mitral regurgitation. 
Intraoperative and/or postoperative echocardiography should be 
used to evaluate the effectiveness of the valve repair. Minimizing 
regurgitation and systolic anterior motion (SAM) are important 
elements of an effective repair. 
Surgeons who use annuloplasty rings should be current on all 
anticoagulation regimens. 
When postoperative anticoagulant therapy is used, the patient's 
anticoagulation status should be carefully monitored. 
Patients with intra-atrial thrombi or a giant left atrium may benefit 
from long-term anticoagulation therapy. 
The surgeon may desire that patients in atrial fibrillation remain on 
anticoagulation therapy until sinus rhythm is established. 
The ring is indicated for use in the mitral position only. Use in the 
tricuspid position may result in ring fracture, conduction system 
damage, tricuspid regurgitation, and/or ring dehiscence. 
5 PRECAUTIONS 
Do not use cutting edge needles, as they may damage the 
annuloplasty device potentially leading to ring dehiscence, ring 
fracture, and possible mitral regurgitation. 
6 POTENTIAL ADVERSE EVENTS 
While infrequent, certain complications have been reported when 
using annuloplasty rings. 
These include the following: 
Uncorrected or recurrent regurgitation 
Stenosis 
Ring dehiscence 
Hemolysis (even with mild regurgitation) 
Low cardiac output 
Heart block 
Systolic anterior motion (SAM) and left ventricular outflow tract 
obstruction (LVOTO) 
Damage to coronary arteries 
Endocarditis 
Thrombosis 
Thromboembolism 
Anticoagulant-related hemorrhage 
Ring fracture 
Leaflet perforation 
The potential for these complications should be considered when 
selecting the most beneficial surgical procedure for each patient. 
To avoid or minimize occurrence of these adverse events, the 
annuloplasty repair, including sizing and implantation, should be 
conducted in accordance with the methods prescribed in these 
Instructions for Use by surgeons with appropriate training and 
experience in valve repair. 

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7 INDIVIDUALIZATION OF TREATMENT 
To allow for healing and incorporation of the annuloplasty ring by host 
tissue, regardless of cardiac rhythm, postoperative anticoagulation 
therapy should be considered for at least six weeks following surgery. 
8 PATIENT COUNSELING INFORMATION 
Patients with annuloplasty rings who undergo dental or other 
potentially 
bacteremic 
procedures 
must 
be 
considered 
for 
prophylactic antibiotic therapy. 
9 HOW SUPPLIED 
9.1 Packaging 
The PROFILE 3D™ Ring is available in the following sizes for the 
mitral position: 24, 26, 28, 30, 32, 34, 36, 38, and 40 mm. The 
package contains a single annuloplasty ring assembly consisting of 
the device and holder (Figure 1) packaged in sterile, double-aseptic 
transfer trays. The packaging system is designed to ease placement 
of the device into the sterile field. The ring assembly is sterile if the 
trays are undamaged and unopened. The outer surfaces of the outer 
tray are NONSTERILE and must not be placed in the sterile field. 
9.2 Storage 
Store the product in its original packaging, including the outer shelf 
carton, in a clean, cool, and dry area to protect the product and 
minimize the potential for contamination. 
The sterility and nonpyrogenicity of the PROFILE 3D™ Ring are 
validated to remain unaffected until the Use By date identified on the 
shelf carton, provided the trays are not opened or damaged. 
10 DIRECTIONS FOR USE 
10.1 Sizing 
The Medtronic PROFILE 3D™ Ring Sizer Set, Model 7680S is used 
to select the proper 
PROFILE 3D™ Ring size for repair of the mitral valve. Sizers are 
reusable; however, they must be cleaned and sterilized by autoclave 
(steam) prior to each use. 
Proper ring size selection is an important part of valvular annuloplasty 
to help restore proper valve function. Use the PROFILE 3D™ Ring 
Sizer Set for size selection. The metal section of the sizer is 
malleable, allowing the surgeon to align the sizers with the valve 
annulus. 
Warning: 
Do not use other manufacturers’ annuloplasty sizers or sizers from 
other Medtronic annuloplasty products to size the PROFILE 3D™ 
Ring. Other annuloplasty sizers may not indicate the appropriate 
PROFILE 3D™ Ring size. 
The sizers are provided NONSTERILE; they must be cleaned and 
sterilized prior to use. 
Mitral Valve 
To determine the proper PROFILE 3D™ Ring size, both the distance 
between the annular trigones and the area of the anterior leaflet must 
be measured. First, lower the sizer onto the valve annulus and align 
the sizer notches with the annular trigones. Second, gently extend the 
anterior leaflet and cover its surface with the selected sizer. The sizer 
that has a notch spacing most nearly matching the intertrigonal 
distance (Figure 2) and a surface area most nearly matching that of 
the anterior leaflet corresponds to the size of the ring that should be 
selected. Either end of the sizer may be used for sizing. 
10.2 Handling and Preparation Instructions 
Open the box and remove the product literature and Patient 
Registration Form. 
Remove the double-aseptic transfer tray containing the ring 
mounted to the holder. 
Inspect the trays ensuring they have not been opened or damaged. 
The ring assembly is sterile as long as the inner tray has not been 
compromised. If the inner tray is damaged, do not implant the ring. 
If the outer tray is damaged, the exterior surface of the inner tray 
may not be sterile. 
Open the outer transfer tray, and while still holding the bottom of the 
outer tray, pass the inner tray into the sterile field. 
The inner tray should be opened only in the sterile field. 
10.3 Device Implantation 
The PROFILE 3D™ Ring assembly may be used with or without the 
Medtronic Annuloplasty Handle, Model 7686 (provided separately). 
Warning: The handle must be cleaned and sterilized prior to use. 
To use the handle, align and engage the sterile handle into the snap 
fit cavity of the holder (Figure 3). The thin section of the handle is 
malleable, allowing the surgeon to align the device with the annulus. 
Note: The handle must be inserted into the side of the holder with the 
snap fit cavity and the printed text. 
Remove the serial number identification tag (Figure 4) and record the 
serial number in the patient’s record. Verify that the serial number 
matches the serial number on the Patient Registration Form. 
Warning: The serial tag must be removed from the ring for proper 
function. Do not cut or tear the ring fabric during removal of the serial 
tag. 
Mitral Suture Placement 
Caution: The PROFILE 3D™ Ring is designed for implantation only 
with interrupted-suture techniques. 
Place sutures in each trigone, approximately 4 mm in width. Place 
additional interrupted sutures, approximately 4 mm in width, in the 
anterior and posterior portions of the mitral annulus (Figure 5). A total 
of approximately 10 to 14 sutures should be placed in the annulus. 
Warning: Avoid placing sutures in the circumflex coronary artery. 
Note: Pledgets may be used for trigone sutures and midposterior 
annulus suture to reduce the possibility of ring dehiscence. 
Ring Suture Placement 
Orient the ring assembly to the mitral annulus (Figure 6). 
Pass sutures through the ring, approximately 2 mm in width, entering 
at the bottom of the ring and exiting the periphery of the ring (Figure 
7). Pass only one suture through each trigonal marker on the ring. 
Holder/Handle Removal 
Use the holder/handle to push the ring down onto the valve annulus 
while pulling back on the sutures. Using a scalpel, cut the retention 
sutures on the holder in the areas indicated (Figure 8). Remove the 
disposable holder and handle from the valve annulus (Figure 9). 
Dispose of the holder. 
Warning: 
Do not cut the ring fabric while cutting the holder retention sutures. 
The PROFILE 3D™ Ring holder must be removed from the ring at 
the end of the procedure for proper function. Under no circumstances 
should the holder remain attached to the ring. 
Knots, Testing 
Tie all knots around the device securely (Figure 10a and 10b), trim all 
excess sutures, and test valvular competency after removing the 
holder. 
Warning: Suture knots must be securely tied. Loose knots and long 
suture tails may be a source of hemolysis, thrombosis, or 
thromboembolism. 
10.4 Accessories 
The PROFILE 3D™ Ring Sizer Set, Model 7680S is used to select 
the proper PROFILE 3D™ Ring size for repair of the mitral valve. 
Sizers are reusable; however, they must be cleaned and sterilized by 
autoclave (steam) prior to each use. Refer to the PROFILE 3D™ 
Ring Sizer Set Instructions for Use for detailed information on 
accessory use and sterilization. 

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Warning: 
Do not use other manufacturers’ annuloplasty sizers or sizers from 
other Medtronic annuloplasty products to size the PROFILE 3D™ 
Ring. Other annuloplasty sizers may not indicate the appropriate 
PROFILE 3D™ Ring size. 
The sizers are provided NONSTERILE; they must be cleaned and 
sterilized prior to use. 
Use only the Annuloplasty Handle, Model 7686 to interface with the 
holder. Refer to the Annuloplasty Handle Instructions for Use for 
detailed information on use and sterilization. 
Warning: The handle is provided NONSTERILE; it must be cleaned 
and sterilized prior to use. 
10.5 Sterilization 
The ring is provided sterile (steam) on the holder and must not be 
resterilized. Rings that have been damaged or contaminated from 
patient contact should not be used. 
11 REGISTRATION INFORMATION 
Note: Patient registration does not apply in countries where patient 
privacy laws conflict with providing patient information, including 
countries from the EU. 
A Patient Registration Form is included in each device package. After 
implantation, please complete all requested information. The serial 
number may be found on the package and on the identification tag 
attached to the device. Return the original form to the Medtronic 
address indicated on the form and provide the temporary 
identification card to the patient prior to discharge. 
12 DISCLAIMER OF WARRANTIES 
THE FOLLOWING DISCLAIMER OF WARRANTY APPLIES TO UNITED 
STATES CUSTOMERS ONLY: 
DISCLAIMER OF WARRANTY 
ALTHOUGH THE PROFILE 3D™ ANNULOPLASTY RING, MODEL 
680R, HEREAFTER REFERRED TO AS “PRODUCT,” HAS BEEN 
MANUFACTURED UNDER CAREFULLY CONTROLLED CONDITIONS, 
MEDTRONIC HAS NO CONTROL OVER THE CONDITIONS UNDER 
WHICH THIS PRODUCT IS USED. MEDTRONIC, THEREFORE, 
DISCLAIMS ALL WARRANTIES, BOTH EXPRESS AND IMPLIED, WITH 
RESPECT TO THE PRODUCT, INCLUDING, BUT NOT LIMITED TO, 
ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR 
A PARTICULAR PURPOSE. MEDTRONIC SHALL NOT BE LIABLE TO 
ANY PERSON OR ENTITY FOR ANY MEDICAL EXPENSES OR ANY 
DIRECT, INCIDENTAL, OR CONSEQUENTIAL DAMAGES CAUSED BY 
ANY USE, DEFECT, FAILURE, OR MALFUNCTION OF THE PRODUCT, 
WHETHER A CLAIM FOR SUCH DAMAGES IS BASED UPON 
WARRANTY, CONTRACT, TORT, OR OTHERWISE. NO PERSON HAS 
ANY AUTHORITY TO BIND MEDTRONIC TO ANY REPRESENTATION 
OR WARRANTY WITH RESPECT TO THE PRODUCT. 
The exclusions and limitations set out above are not intended to, and 
should not be construed so as to, contravene mandatory provisions of 
applicable law. If any part or term of this Disclaimer of 
Warranty is held by any court of competent jurisdiction to be illegal, 
unenforceable, or in conflict with applicable law, the validity of the 
remaining portion of the Disclaimer of Warranty shall not be affected, and 
all rights and obligations shall be construed and enforced as if this 
Disclaimer of Warranty did not contain the particular part or term held to be 
invalid. 
THE FOLLOWING DISCLAIMER OF WARRANTY APPLIES TO 
CUSTOMERS OUTSIDE THE UNITED STATES: 
DISCLAIMER OF WARRANTY ALTHOUGH THE PROFILE 3D™ 
ANNULOPLASTY RING, MODEL 680R, HEREAFTER 
REFERRED TO AS “PRODUCT,” HAS BEEN CAREFULLY DESIGNED, 
MANUFACTURED, AND TESTED PRIOR TO SALE, THE PRODUCT 
MAY 
FAIL 
TO 
PERFORM 
ITS 
INTENDED 
FUNCTION 
SATISFACTORILY FOR A VARIETY OF REASONS. THE WARNINGS 
CONTAINED 
IN 
THE 
PRODUCT 
LABELING 
PROVIDE 
MORE 
DETAILED INFORMATION AND ARE CONSIDERED AN INTEGRAL 
PART OF THIS DISCLAIMER OF WARRANTY. MEDTRONIC, 
THEREFORE, DISCLAIMS ALL WARRANTIES, BOTH EXPRESS AND 
IMPLIED, WITH RESPECT TO THE PRODUCT. MEDTRONIC SHALL 
NOT BE LIABLE FOR ANY INCIDENTAL OR CONSEQUENTIAL 
DAMAGES CAUSED BY ANY USE, DEFECT, OR FAILURE OF THE 
PRODUCT, WHETHER THE CLAIM IS BASED ON WARRANTY, 
CONTRACT, TORT, OR OTHERWISE. 
The exclusions and limitations set out above are not intended to, and 
should not be construed so as to, contravene mandatory provisions of 
applicable law. If any part or term of this Disclaimer of 
Warranty is held to be illegal, unenforceable, or in conflict with applicable 
law by a court of competent jurisdiction, the validity of the remaining 
portions of this Disclaimer of Warranty shall not be affected, and all rights 
and obligations shall be construed and enforced as if this Disclaimer of 
Warranty did not contain the particular part or term held to be invalid. 
 
Figure 1 
 
 
 
 
 
 
 

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Figure 2 
 
Figure 3 
 
 
 
 
 
Figure 4 
 
Figure 5 
 
 
 

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Figure 6 
 
 
 
Figure 7 
 
 
 
 
 
 
Figure 8 
 
 
Figure 9
 
 
 
 

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Figure 10a 
 
 
 
 
Figure 10b 
 
 
 
Instructions-for-Use – CG Future® Annuloplasty Ring/Band 
1 DEVICE DESCRIPTION 
The Medtronic CG Future® Annuloplasty Ring Model 638R and the 
Medtronic CG Future® Annuloplasty Band Model 638B (hereafter 
referred to as CG Future® Annuloplasty Ring/Band) consist of a 
MP35N wire overmolded with silicone and covered with polyester 
fabric. Both the ring and band must be implanted in the mitral 
position. The ring and band are marked at three points by colored 
sutures; two markers correspond to the trigones of the mitral valve 
and one identifies the midpoint of the device. The device size is 
identified by the inside diameter of the ring or band at its widest point. 
The MP35N wire allows radiographic visualization of the devices. The 
ring also includes a silicone marker, impregnated with barium sulfate, 
for radiographic visualization. 
Nonclinical testing has demonstrated that the CG Future® 
Annuloplasty Ring/Band is MR (magnetic resonance) Conditional. It 
can be scanned safely under the following conditions: 
Static magnetic field of 3.0 tesla 
Spatial gradient field of 3.9 T/m 
Maximum whole-body-averaged specific absorption rate (SAR) of 
1.1 W/kg for 20 minutes of scanning as read from equipment 
monitor 
In nonclinical testing the CG Future® Annuloplasty Ring/Band 
produced a temperature rise of 0.2°C at a maximum wholebody-
averaged specific absorption rate (SAR) of 1.1 W/kg for 20 minutes 
of MR scanning in a field strength of 3.0 tesla, GE Signa®1 LX 3.0 T 
MR System: multi-coil superconducting, actively shielded magnet 
housed in a 94 cm bore; gradient amplitude - 40 mT/m and slew rate 
- 150 T/m/s; VH3_M4 software. The maximum whole body SAR of 
1.1 W/kg for 20 minutes was read from the scanner console. 
2 INDICATIONS 
The CG Future® Annuloplasty Ring/Band are indicated for the 
reconstruction and/or remodeling of pathological mitral valves. 
Valvular insufficiency and/or stenosis may be corrected by 
appropriate repair and annular remodeling. 
3 CONTRAINDICATIONS 
Heavily calcified valves. 
Valvular retraction with severely reduced mobility. 
Active bacterial endocarditis. 
4 WARNINGS 
For single use only. 
Only surgeons who have received adequate training to determine 
whether incompetent, stenotic, or diseased heart valves are capable 
of being repaired or replaced should use this device. 
Only surgeons who have received appropriate training in valve 
repair, including ring and band implant and sizing techniques, should 
use this device. 
1 Signa® is a registered trademark of General Electric Corporation. 
Correct annuloplasty ring and band sizing is an important element of 
a successful valve repair. Undersizing the ring or band can result in 
valve stenosis, ring/band dehiscence, and/or ring/band fracture. 
Oversizing the ring or band can result in valve regurgitation and/or 
ring/band fracture. 
Care should be taken that sutures are not placed in atrial tissue, as 
this may result in impairment of the cardiac conduction system. 
It is necessary to secure the ends of the ring and band into fibrous 
trigone tissue to maintain permanent attachment. 
Suture knots must be securely tied. Loose knots and long suture 
tails 
may 
be 
a 
source 
for 
hemolysis, 
thrombosis, 
or 
thromboembolism. 
Do not cut the ring or band, as resultant loose threads may be a 
source of hemolysis, thrombosis, and/or thromboembolism. 
Intraoperative and/or postoperative echocardiography should be 
used to evaluate the effectiveness of the valve repair. 

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Minimizing regurgitation and systolic anterior motion (SAM) are 
important elements of an effective repair. 
Surgeons who use annuloplasty rings and bands should be current 
on all anticoagulation regimens. 
When postoperative anticoagulant therapy is used, the patient's 
anticoagulation status should be carefully monitored. 
Patients with intra-atrial thrombi or a giant left atrium may benefit 
from long-term anticoagulation therapy. 
The surgeon may desire that patients in atrial fibrillation remain on 
anticoagulation therapy until sinus rhythm is established. 
Do not alter or deform the ring or band to conform to annular 
anatomy as this could lead to ring/band fracture and possible mitral 
regurgitation. 
Do not squeeze the ring or band with sharp instruments as this may 
damage the surface of the stiffener, which may result in ring/band 
fracture and possible mitral regurgitation. 
The ring and band are indicated for use in the mitral position only. 
Use in the tricuspid position may result in ring/band fracture, 
conduction system damage, tricuspid regurgitation, and/or ring/band 
dehiscence. 
5 PRECAUTIONS 
Do not use cutting edge needles, as they may damage the 
annuloplasty device potentially leading to ring/band dehiscence, 
ring/band fracture, and possible mitral regurgitation. 
6 POTENTIAL ADVERSE EVENTS 
While infrequent, certain complications have been reported when 
using annuloplasty ring/bands. These include the following: 
Uncorrected or recurrent regurgitation 
Stenosis 
Ring/Band dehiscence 
Hemolysis (even with mild regurgitation) 
Low cardiac output 
Heart block 
Systolic anterior motion (SAM) and left ventricular outflow tract 
obstruction (LVOTO) 
Damage to coronary arteries 
Endocarditis 
Thrombosis 
Thromboembolism 
Anticoagulant-related hemorrhage 
Ring/Band fracture 
Leaflet perforation 
The potential for these complications should be considered when 
selecting the most beneficial surgical procedure for each patient. 
To avoid or minimize occurrence of these adverse events, the 
annuloplasty repair, including sizing and implantation, should be 
conducted in accordance with the methods described in these 
Instructions for Use by surgeons with appropriate training and 
experience in valve repair. 
7 INDIVIDUALIZATION OF TREATMENT 
To allow for healing and incorporation of the annuloplasty ring or 
band by host tissue, regardless of cardiac rhythm, postoperative 
anticoagulation therapy should be considered for at least six weeks 
following surgery. 
8 PATIENT COUNSELING INFORMATION 
Patients with annuloplasty rings or bands who undergo dental or 
other potentially bacteremic procedures must be considered for 
prophylactic antibiotic therapy. 
9 HOW SUPPLIED 
9.1 Packaging 
The CG Future® 638R Annuloplasty Ring is available in the following 
sizes for the mitral position: 24, 26, 28, 30, 32, 34, 36, and 38 mm. 
The CG Future® 638B Annuloplasty Band is available in the following 
sizes: 26, 28, 30, 32, 34, 36, and 38 mm. 
The package contains a single annuloplasty ring or band assembly 
consisting of the device and holder (Figure 1) packaged in sterile, 
double-aseptic transfer pouches. The packaging system is designed 
to ease placement of the device into the sterile field. The ring and 
band assemblies are sterile if the pouches are undamaged and 
unopened. The outer surfaces of the outer pouch are NONSTERILE 
and must not be placed in the sterile field. 
9.2 Storage 
Store the product in its original packaging, including the outer shelf 
carton, in a clean, cool, and dry area to protect the product and 
minimize the potential for contamination. 
The sterility and nonpyrogenicity of the CG Future® Annuloplasty 
Ring/Band are validated to remain unaffected until the Use By date 
identified on the shelf carton, provided the pouches are not opened or 
damaged. 
10 DIRECTIONS FOR USE 
10.1 Sizing 
The CG Future® 7638 Ring/Band Sizer Set is used to select the 
proper CG Future® Annuloplasty Ring/Band size for repair of the 
mitral valve. Sizers are reusable; however, they must be cleaned and 
sterilized by autoclave (steam) prior to each use. 
Proper ring/band size selection is an important part of valvular 
annuloplasty to help restore proper function. Use the CG Future® 
7638 Annuloplasty Ring/Band Sizer Set and Medtronic 7615 
Annuloplasty Handle for size selection. 
The handle and sizers are provided NONSTERILE; they must be 
cleaned and sterilized prior to use. Align and insert the handle into 
the snap cavity of the sizer (Figure 2). The thin section of the handle 
is malleable, allowing the surgeon to align the sizers with the valve 
annulus. 
Warning: Do not use other manufacturers’ annuloplasty sizers or 
sizers from other Medtronic annuloplasty products to size the CG 
Future® Annuloplasty Ring/Band. 
Mitral Valve 
To determine the proper ring or band size, both the distance between 
the annular trigones and the area of the anterior leaflet must be 
measured. First, lower the sizer onto the valve annulus and align the 
sizer notches with the annular trigones. Second, gently extend the 
anterior (A) leaflet and cover its surface with the selected sizer. The 
sizer that has a notch spacing most nearly matching the intertrigonal 
distance (Figure 3) and a surface area most nearly matching that of 
the anterior leaflet corresponds to the size of the ring or band that 
should be selected. 
10.2 Handling and Preparation Instructions 
Open the box and remove the product literature and Patient 
Registration Form. 
Remove the double-aseptic transfer pouch containing the device 
mounted to the holder. 
Inspect the pouches ensuring they have not been opened or 
damaged. The ring and band assemblies are sterile as long as the 
inner pouch has not been compromised. If the inner pouch is 
damaged, do not implant the device. 
If the outer pouch is damaged, the exterior surface of the inner 
pouch may not be sterile. 
Open the outer transfer pouch, and while still holding the bottom of 
the outer pouch, pass the inner pouch into the sterile field. 
The inner pouch should be opened only in the sterile field. 

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10.3 Device Implantation 
The CG Future® Annuloplasty Ring/Band assembly may be used with 
or without the handle (Medtronic 7615 Annuloplasty Handle, provided 
separately). 
Caution: The CG Future® Annuloplasty Ring/Band are designed for 
implantation only with interrupted-suture techniques. 
Warning: The handle must be cleaned and sterilized prior to use. 
To use the handle, align and engage the sterile handle into the snap 
fit cavity of the holder (Figure 4). The thin section of the handle is 
malleable, allowing the surgeon to align the device with the annulus. 
Note: The handle must be inserted into the side of the holder with the 
snap fit cavity and the printed text. 
Remove the serial number identification tag (Figure 5) and record the 
serial number in the patient's record. Verify that the serial number 
matches the serial number on the Patient Registration Form. 
Warning: The serial tag must be removed from the ring/band for 
proper function. Do not cut or tear the ring/band fabric during removal 
of the serial tag. 
Mitral Annulus Suture Placement 
Place sutures in each trigone, approximately 4 mm in width. 
Place additional interrupted sutures, approximately 4 mm in width, in 
the posterior portion of the mitral annulus following the line of cusp 
insertion (Figure 6). A total of approximately 10 to 14 sutures should 
be placed for the ring/band. 
Warning: Avoid placing sutures in the circumflex coronary artery. 
Note: Pledgets may be used for trigone sutures and mid-posterior 
annulus suture to reduce the possibility of ring/band dehiscence. 
Band Suture Placement 
Orient the band assembly on the mitral (M) annulus on the holder 
(Figure 7). 
Pass sutures through the band, approximately 2 mm in width, 
entering at the bottom of the band and exiting the periphery of the 
band (Figure 8). The sutures placed in the trigonal tissue should be 
passed through the eyelets of the band stiffener (Figure 9). 
Pass only one suture through the trigonal marker on the device. 
Ring Suture Placement 
Orient the ring assembly on the mitral (M) annulus on the holder 
(Figure 7). 
Pass sutures through the ring, approximately 2 mm in width, entering 
at the bottom of the ring and exiting the periphery of the ring (Figure 
8). Place sutures completely around the device, including the anterior 
mitral annulus region. The sutures placed in the trigonal tissue should 
be passed through the eyelets of the ring stiffener (Figure 9). Pass 
only one suture through the trigonal marker on the device. 
Caution: The ring/band must be sutured through the eyelets into the 
trigonal tissue to ensure secure attachment. 
Holder/Handle Removal 
Use the holder/handle to push the ring or band down onto the valve 
annulus while pulling back on the sutures. Using a scalpel, cut the 
retention sutures on the holder in the areas indicated (Figure 10). 
Remove the disposable holder and handle from the valve annulus 
(Figure 11). Dispose of the holder. 
Warning: Do not cut the ring or band fabric while cutting the holder 
retention sutures. 
Knots, Testing 
Tie all knots around the device securely (Figure 12), trim all excess 
sutures, and test valvular competency after removing the holder. 
Warning: The CG Future® Annuloplasty Ring/Band holder must be 
removed from the device at the end of the procedure for proper 
function. Under no circumstances should the holder remain attached 
to the ring or band. 
Warning: Suture knots must be securely tied. Loose knots and long 
suture tails may be a source of hemolysis, thrombosis, or 
thromboembolism. 
10.4 Accessories 
Use the CG Future® 7638 Annuloplasty Ring/Band Sizer Set to 
determine the appropriate device size. Refer to the CG Future® 
Annuloplasty Ring/Band Sizer Set Instructions for Use for detailed 
information on accessory use and sterilization. 
Warning: Do not use other manufacturers’ annuloplasty sizers or 
sizers from other Medtronic annuloplasty products to size the CG 
Future® Annuloplasty Ring/Band. 
Use only the Medtronic 7615 Annuloplasty Handle to interface with 
the holder and sizers. Refer to the Medtronic Annuloplasty 
Handle Instructions for Use for detailed information on use and 
sterilization. 
10.5 Sterilization 
10.5.1 Ring/Band (Model 638R/638B) 
The ring and band are provided sterile (ethylene oxide) on the holder 
and must not be resterilized. Rings and bands that have been 
damaged or contaminated from patient contact should not be used. 
11 REGISTRATION INFORMATION 
Note: Patient registration does not apply in countries where patient 
privacy laws conflict with providing patient information, including 
countries from the EU. 
A patient registration form is included in each device package. 
After implantation, please complete all requested information. 
The serial number may be found on the package and on the 
identification tag attached to the device. Return the original form 
to the Medtronic address indicated on the form and provide the 
temporary identification card to the patient prior to discharge. 
12 DISCLAIMER OF WARRANTIES 
THE FOLLOWING DISCLAIMER OF WARRANTY APPLIES TO 
UNITED STATES CUSTOMERS ONLY: 
The exclusions and limitations set out above are not intended to, and 
should not be construed so as to, contravene mandatory provisions of 
applicable law. If any part or term of this Disclaimer of Warranty is 
held by any court of competent jurisdiction to be illegal, 
unenforceable, or in conflict with applicable law, the validity of the 
remaining portion of the Disclaimer of Warranty shall not be affected, 
and all rights and obligations shall be construed and enforced as if 
this Disclaimer of Warranty did not contain the particular part or term 
held to be invalid. 
DISCLAIMER OF WARRANTY 
ALTHOUGH THE CG FUTURE® 638R/638B ANNULOPLASTY 
RING/BAND, THE CG FUTURE® 7638 RING/BAND SIZER SET, 
AND 
THE 
MEDTRONIC 
7615 
ANNULOPLASTY 
HANDLE, 
HEREAFTER REFERRED TO AS "PRODUCT," HAVE BEEN 
MANUFACTURED UNDER 
CAREFULLY CONTROLLED CONDITIONS, MEDTRONIC HAS NO 
CONTROL OVER THE CONDITIONS UNDER WHICH THIS 
PRODUCT IS USED. MEDTRONIC, THEREFORE, DISCLAIMS ALL 
WARRANTIES, BOTH EXPRESS AND IMPLIED, WITH RESPECT 
TO THE PRODUCT, INCLUDING, BUT NOT LIMITED TO, ANY 
IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR 
A PARTICULAR PURPOSE. MEDTRONIC SHALL NOT BE LIABLE 
TO ANY PERSON OR ENTITY FOR ANY MEDICAL EXPENSES 
OR ANY DIRECT, INCIDENTAL, OR 
CONSEQUENTIAL DAMAGES CAUSED BY ANY USE, DEFECT, 
FAILURE, OR MALFUNCTION OF THE PRODUCT, WHETHER A 
CLAIM FOR SUCH DAMAGES IS BASED UPON WARRANTY, 
CONTRACT, TORT, OR OTHERWISE. 
NO PERSON HAS ANY AUTHORITY TO BIND MEDTRONIC TO 
ANY REPRESENTATION OR WARRANTY WITH RESPECT TO 
THE PRODUCT. 
 
THE FOLLOWING DISCLAIMER OF WARRANTY APPLIES TO 
CUSTOMERS OUTSIDE THE UNITED STATES: 
The exclusions and limitations set out above are not intended to, and 
should not be construed so as to, contravene mandatory provisions of 
applicable law. If any part or term of this Disclaimer of Warranty is 
held to be illegal, unenforceable, or in conflict with applicable law by a 
court of competent jurisdiction, the validity of the remaining portions 
of this Disclaimer of Warranty shall not be affected, and all rights and 

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obligations shall be construed and enforced as if this Disclaimer of 
Warranty did not contain the particular part or term held to be invalid. 
DISCLAIMER OF WARRANTY 
ALTHOUGH THE CG FUTURE® 638R/638B ANNULOPLASTY 
RING/BAND, THE CG FUTURE® 7638 RING/BAND SIZER SET, 
AND 
THE 
MEDTRONIC 
7615 
ANNULOPLASTY 
HANDLE, 
HEREAFTER REFERRED TO AS "PRODUCT," HAVE BEEN 
CAREFULLY DESIGNED, 
MANUFACTURED, 
AND 
TESTED 
PRIOR 
TO 
SALE, 
THE 
PRODUCT MAY FAIL TO PERFORM ITS INTENDED FUNCTION 
SATISFACTORILY 
FOR 
A VARIETY OF REASONS. 
THE 
WARNINGS CONTAINED IN THE PRODUCT LABELING PROVIDE 
MORE DETAILED INFORMATION AND 
ARE CONSIDERED AN INTEGRAL PART OF THIS DISCLAIMER 
OF WARRANTY. MEDTRONIC, THEREFORE, DISCLAIMS ALL 
WARRANTIES, BOTH EXPRESS AND IMPLIED, WITH RESPECT 
TO THE PRODUCT. MEDTRONIC SHALL NOT BE LIABLE FOR 
ANY INCIDENTAL OR 
CONSEQUENTIAL DAMAGES CAUSED BY ANY USE, DEFECT, 
OR FAILURE OF THE PRODUCT, WHETHER THE CLAIM IS 
BASED ON WARRANTY, CONTRACT, TORT, OR OTHERWISE. 
 
Figure 1 
 
 
 
 
Figure 2 
 
Figure 3 
 
 
 

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Figure 4 
 
 
Figure 5 
 
 
 
 
 
Figure 6 
 
Figure 7 
 

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Figure 8 
 
Figure 9 
 
Figure 10 
 
Figure 11 
 

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Figure 12 
 
 
 
18. Version History 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
 
Not Applicable, New Document 
Kritika Gupta, Clinical Study Manager 
Aditya Chachad, Clinical Study 
Manager 
 

PRESERVE-Mitral Statistical Analysis Plan 
 
Form 
 
Revision 2.0 
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This document is electronically controlled Medtronic Controlled Information 056-F286, Statistical Analysis Plan Template 
Version A 
 
 
Statistical Analysis Plan 
Clinical Investigation Plan Title  PRESERVE - MITRAL 
Prospective REgistry to Study Clinical OutcomEs of 
Repair of Mitral ValvEs in South Asia. 
Clinical Investigation Plan Identifier MDT16016SUR002 
Clinical Investigation Plan Version Version 1.0, dated 10-APR-2017 
Sponsor/Local Sponsor Medtronic plc. 
Clinical Research 
Mailstop: MVS66 
Mounds View South 
8200 Coral Sea St. NE 
Mounds View, MN 55112 
Regional Sponsor: 
Vinay Rajan, Ph.D 
India- Medtronic Pvt. Ltd. 
Solitaire Corporate Park, Bldg No. 12, 4th Floor, 
Andheri -Ghatkopar Link Road, Andheri-East 
Mumbai, Maharashtra 400 093  
INDIA 
Contact Number: +91-22-33074700 
Document Version Version 2.0, dated 09-AUG-2019 
Confidentiality Statement 
The information contained in this document is confidential and the proprietary property of Medtronic. 
Any distribution, copying, or disclosure without the prior written authorization of Medtronic is strictly 
prohibited. Persons to whom the information is disclosed must know that it is confidential and that it 
may not be further disclosed by them. 
 
 
 

PRESERVE-Mitral Statistical Analysis Plan 
 
Form 
 
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Version A 
Table of Contents 
1. 
Version History ........................................................................................................................ 3 
2. 
List of Abbreviations and Definitions of Terms ............................................................................ 4 
3. 
Introduction............................................................................................................................. 4 
4. 
Study Objectives ...................................................................................................................... 5 
4.1 
Primary Objective(s) .................................................................................................................. 5 
4.2 
Secondary Objective(s) ............................................................................................................. 5 
5. 
Investigation Plan .................................................................................................................... 5 
5.1 
Study Design .............................................................................................................................. 5 
5.2 
Selection of Subjects ................................................................................................................. 6 
6. 
Determination of Sample Size ................................................................................................... 6 
7. 
Statistical Methods ................................................................................................................... 7 
7.1 
Study Subjects ........................................................................................................................... 7 
7.2 
General Methodology ............................................................................................................... 7 
7.3 
Center Pooling ........................................................................................................................... 8 
7.4 
Handling of Missing, Unused, and Spurious Data and Dropouts .............................................. 8 
7.5 
Adjustments for Multiple Comparisons .................................................................................... 8 
7.6 
Demographic and Other Baseline Characteristics .................................................................... 8 
7.7 
Treatment Characteristics ......................................................................................................... 8 
7.8 
Interim Analyses ........................................................................................................................ 8 
7.9 
Evaluation of Objectives ........................................................................................................... 8 
7.10 
Safety Evaluation..................................................................................................................... 14 
7.11 
Health Outcomes Analyses ..................................................................................................... 14 
7.12 
Changes to Planned Analysis................................................................................................... 14 
8. 
Validation Requirements ......................................................................................................... 14 
9. 
References ............................................................................................................................ 14 
10. Statistical Appendices ............................................................................................................. 15 
 
 

PRESERVE-Mitral Statistical Analysis Plan 
 
Form 
 
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This document is electronically controlled Medtronic Controlled Information 056-F286, Statistical Analysis Plan Template 
Version A 
1. 
Version History 
Version 
Summary of Changes 
Author(s)/Title 
1.0 
• 
Not Applicable, New Document 
Shuzhen Li, Principal Statistician 
2.0 
• 
Revised analysis set for primary and 
secondary endpoints to Successfully 
Implanted subjects. 
• 
Revised analysis method for new onset of 
atrial fibrillation to Kaplan-Meier analysis. 
• 
Added specification on the time point at 
which a subject is deemed to have an 
attempted implant. 
• 
Added specification on the standard error 
estimator for the Kaplan-Meier analyses. 
• 
Last follow-up date definition was revised 
for subjects with exit reason of lost to 
follow-up. 
• 
Revised Section 7.6 to include Enrolled and 
Successfully Implanted cohorts in reporting 
of demographic and other baseline 
characteristics. 
• 
Revised Section 7.7 to include Attempted 
Implant and Successfully Implanted 
cohorts in reporting of procedural 
characteristics. 
• 
Added subgroup analyses for the primary 
and selected secondary endpoints. 
Angie Zhang, Principal Statistician 

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2. 
List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
ACC 
American College of Cardiology 
AE 
Adverse Event 
AF 
Atrial Fibrillation 
AHA 
American Hospital Association 
ASE 
American Society of Echocardiography 
CIP 
Clinical Investigation Plan 
CRF 
Case Report Form 
CSH 
Medtronic Coronary and Structural Heart 
CVD 
Cardiovascular Disease 
ECG 
Electrocardiogram/Electrocardiography 
eCRF 
Electronic Case Report Form 
IFU 
Instructions For Use 
LAR 
Legally Authorized Representative 
MR 
Mitral Regurgitation 
NYHA 
New York Heart Association 
PRESERVE – MITRAL 
Prospective REgistry to Study Clinical OutcomEs of Repair of Mitral 
ValvEs in South Asia 
SAP 
Statistical Analysis Plan 
UADE 
Unanticipated Adverse Device Effect 
3. 
Introduction 
Cardiovascular Diseases (CVD) are the leading cause of mortality in India, contributing to 25% of all 
mortality in the country. The Global Burden of Disease study estimate of age-standardized CVD death 
rate of 272 per 100,000 population in India is higher than the global average of 235 per 100,000 
population [1]. 
 
One of the important pathologies seen in patients with cardiovascular disease is mitral valve 
regurgitation and insufficiency. Patients might suffer from different types of mitral valve dysfunction 
leading to different levels of regurgitation. 
 
Mitral valve repair is established as a procedure to alleviate mitral valvular insufficiency/stenosis. The 
pathophysiology of mitral valve insufficiency can be ischemic, rheumatic, degenerative, congenital, 
infective, myxomatous, etc. 
 
Mitral valve repair may lead to better outcomes as compared to replacement. Western studies on mitral 
valve repair have typically focused on patients with ischemic pathophysiology. Current ACC/AHA 
guidelines [2] state that mitral valve repair is recommended in preference to mitral valve replacement in 
certain patients with chronic severe primary MR limited to posterior leaflet, or involving the anterior 
leaflet or both leaflets when a successful and durable repair can be accomplished. Concomitant repair is 
indicated for patients with chronic severe primary MR if they undergo cardiac surgery. 

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Despite the guidelines, there may be local and regional differences in the standard practice in different 
geographies. While there are some Indian studies that have looked into mitral valve repair [3], [4], [5], 
there is still a need to gather more local evidence on clinical outcomes at long term follow up (12 
months). The significant proportion of mitral valve repair patients in India have rheumatic disease. 
Mitral valve repair is more technically challenging in this population, and is associated with higher failure 
rate. 
 
Given this background, it is clear that the significant body of evidence for mitral valve annuloplasty from 
the west may not give a realistic picture of patients undergoing the same procedure in South Asia. Due 
to the difference in disease pathophysiology, the significant population of patients with rheumatic 
disease and differing surgical practice, there is a need to conduct a geography-specific study to 
understand the clinical outcome of patients undergoing mitral valve annuloplasty in the region. 
PRESERVE-Mitral, a prospective registry to study long term performance of annuloplasty systems is thus 
proposed to document clinical outcomes, physician practice and report on outcomes in these patients. 
 
There is limited local evidence on mitral repair products in South Asia and a prospective post-market 
registry will provide real world data on clinical outcomes. 
4. 
Study Objectives 
4.1 Primary Objective(s) 
The objective of this registry is to gather data on the clinical outcomes of Medtronic mitral repair 
products (Profile 3DTM or CG Future® Annuloplasty systems, which include Profile 3D Ring, CG Future 
Ring and CG Future Band) in the approved intended use up to 12 months from the day of procedure.  
4.2 Secondary Objective(s) 
Characterize the demographics of the patients undergoing mitral valve repair using annuloplasty 
systems in South Asia, and assess the functional and procedural outcomes of the procedure. 
5. 
Investigation Plan 
5.1 Study Design 
PRESERVE-Mitral is a prospective non-randomized non-interventional post-market registry. A total of 
200 patients who are eligible and who are intended to be implanted with a Profile 3DTM or CG Future® 
Annuloplasty system in the surgical repair procedure will be included in the study. 
 
The subjects will be evaluated at discharge for evaluation of procedural success and subsequently 
followed up as per standard-of-care at the site from 3-6 months (90 days to 210 days) post procedure 
and at 12 months (365 days +/- 30 days) post procedure for assessment of longer-term outcome at 
which time subjects will also exit the study. Echo images will be evaluated pre-implant, intra-op, 
discharge and during follow ups, according to the standard routine in the center. 

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5.2 Selection of Subjects 
5.2.1 
Study Population 
The patient population includes all patients suffering from mitral valve disease, indicated for a mitral 
valve repair procedure, either as a stand-alone procedure or concomitant to another procedure (for 
example, coronary artery bypass grafting, tricuspid valve repair, treatment of atrial fibrillation, etc. but 
excluding patients undergoing aortic valve replacement) and for which the surgeon considers the 
implantation of a Profile 3DTM or CG Future® Annuloplasty system most appropriate to reconstruct the 
regurgitant valve. 
5.2.2 
Subject Enrollment 
A subject is considered enrolled in this study at the time at which he/she signed the Patient 
Informed Consent Form. 
5.2.3 
Inclusion Criteria 
1. Patients with valvular insufficiency and/or stenosis and indicated for the reconstruction and/or 
remodeling of pathological mitral valves with Profile 3DTM or CG Future® Annuloplasty systems. 
2. Indications and contraindications provided in the product Instructions for Use (IFU). 
3. Subject is 18 years of age or older. 
4. The patient or his/her Legally Authorized Representative (LAR) has been informed about the nature 
of the registry and the patient informed consent for study participation has been obtained prior to 
performing any study-related procedures from the subject or LAR, as per applicable local 
requirements. 
5.2.4 
Exclusion Criteria 
1. Contraindications as per IFU: 
a. Heavily calcified valves; 
b. Valvular retraction with severely reduced mobility; 
c. Active bacterial endocarditis. 
2. Aortic valve replacement as concomitant procedure. 
3. Already participating in another clinical study, possibly leading to bias and jeopardizing the scientific 
appropriate assessment of the study endpoints. 
6. 
Determination of Sample Size 
The sample size of 200 subjects who are eligible and intended to be implanted with a Profile 3DTM or CG 
Future® Annuloplasty system in the surgical repair procedure is adequate and appropriate for the 
evaluation of local evidence and obtaining real world data on clinical outcomes following implantation 
of these two products. This sample size was not statistically derived as this is not a hypothesis driven 
study. 

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7. 
Statistical Methods 
7.1 Study Subjects 
7.1.1 
Disposition of Subjects 
Subject disposition will be summarized, including the number of subjects enrolled, attempted implant, 
successfully implanted, died, explanted, withdrawn, lost to follow-up, and completed each visit during 
the study. 
7.1.2 
Clinical Investigation Plan (CIP) Deviations 
Protocol violations (study deviations) will be reported to Medtronic throughout the study by each site 
and identified through monitoring activities. CIP deviations will be summarized. 
7.1.3 
Analysis Sets 
There are three analysis sets defined for this study. Analysis sets used for each objective are defined in 
the corresponding objective section. The primary analysis set is the Successfully Implanted analysis set. 
• 
Enrolled analysis set: Composed of all subjects who signed the Patient Informed Consent Form. Time 
zero begins on the date of informed consent. 
• 
Attempted Implant analysis set (AT): Composed of all enrolled subjects who were attempted for a 
Profile 3DTM or CG Future® Annuloplasty system implantation. A subject with one or more attempts 
of the Medtronic study device recorded on the procedure case report form (CRF) is considered as 
implant attempted. Time zero begins on the date of the first attempted procedure. 
• 
Successfully Implanted analysis set (IMP): Composed of all AT subjects who had either a Profile 3DTM 
or CG Future® Annuloplasty system implanted successfully. Time zero begins on the date of implant 
procedure. 
 
All data collected from enrolled, attempted implant, and successfully implanted subjects will be utilized 
in the analyses as appropriate. Analyses of the primary and secondary endpoints will be descriptive, and 
no statistical hypothesis tests will be performed. 
7.2 General Methodology 
Descriptive statistics will be used to report study data. For continuous variables (e.g. age), the mean, 
median, standard deviation, minimum, maximum, and first and third quartiles will be presented. For 
categorical variables, the number and percentage of subjects in the category of interest will be 
presented. For time to event data, Kaplan-Meier analyses of event or event-free rates at discharge, 6 
and 12 months will be presented. For these analyses, the time points will correspond to 7 days, 183 days 
and 365 days post implantation respectively. At each time point with data, the product limit estimate of 
the event or event-free rates, and the loglog transformed 95% confidence interval using the Peto 
standard error will be presented. For subjects without an event, the date of censoring will be the latest 
date of all follow-up visits (including phone and/or mail correspondence), assessments, events (including 
death) and study exits. For subjects whose exit reason is lost to follow-up, the last follow-up date will be 
the latest date of the follow-up visits (including phone and/or mail correspondence), assessments and 
events. 

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7.3 Center Pooling 
Although data for this registry will be collected from multiple centers, no center pooling analyses are 
planned. 
7.4 Handling of Missing, Unused, and Spurious Data and Dropouts 
Every effort will be undertaken to minimize missing, unused and spurious data and dropouts. Unless 
otherwise specified, no statistical techniques will be used to impute missing data. The number of 
subjects included in each analysis will be reported so that the reader can assess the potential impact of 
missing data. 
 
In the case of partial dates, if only the month and year are known, the event or assessment will 
be analyzed as if it occurred on the 15th of that month. If only the year is known, the event or 
assessment will be analyzed as if it occurred on June 30th of that year. These resolutions of partial dates 
are subject to the restrictions that events must occur no earlier than the procedure date or after study 
exit. 
7.5 Adjustments for Multiple Comparisons 
No multiple comparisons/multiplicity adjustments will be made.  
7.6 Demographic and Other Baseline Characteristics 
Demographics and baseline characteristics will be summarized for the Enrolled and Successfully 
Implanted analysis sets. Continuous variables will be summarized with means, medians, standard 
deviations, minimums, maximums, and first and third quartiles. Categorical variables will be summarized 
with frequencies and percentages. 
7.7 Treatment Characteristics  
Procedural data will be summarized for the Attempted Implant and Successfully Implanted analysis sets. 
Continuous variables will be summarized with means, medians, standard deviations, minimums, 
maximums, and first and third quartiles. Categorical variables will be summarized with frequencies and 
percentages. 
7.8 Interim Analyses  
An interim summary of the data is planned when all enrolled and successfully implanted subjects have 
had the opportunity to be followed through the discharge visit. This is an observational study. No 
statistical hypothesis tests will be performed, and there are no pass/fail criteria for the results of this 
study. 
7.9 Evaluation of Objectives 
7.9.1 Primary Endpoint #1 
Improvement in mitral valve regurgitation (MR) (grade) at 12 months post procedure. 
 
Hypothesis/Decision criteria: 

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No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
Mitral valve function will be based on site echocardiographic recordings. The parameter to be estimated 
is the grade of mitral valve regurgitation using echo, in subjects at baseline and 12 months post 
procedure. The grades of MR, 0-4, will correspond to the ASE guidelines (as described in Table 1 in CIP) 
ranging from no MR, Mild MR, Moderate MR, Moderate-to-Severe MR and Severe MR. 
 
Data Collection and Analysis Dataset:  
Data will be collected on an ECHOCARDIOGRAM (CV) CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort, and for the IMP subjects with 
CG Future Band, CG Future Ring and Profile 3D Ring respectively. IMP subjects having available MR 
collection at both baseline and 12 months post procedure will be included in the analysis. 
 
Analysis Method: 
For each subject with paired data, the change from baseline (improved, no change, worsened) will be 
evaluated at 12 months. This primary endpoint of improvement in MR (grade) will be presented with 
frequencies and percentages of subjects with improved MR at 12 months. Two-sided 95% exact 
binomial confidence intervals of the percent of subjects overall and in each of the three subgroups with 
improved MR at 12 months will also be reported. 
7.9.2 Primary Endpoint #2 
All-cause mortality rate at 12 months post procedure. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
All-cause mortality event rate estimate will be provided at 12 months post procedure. 
 
Data Collection and Analysis Dataset:  
Data will be collected on an AE CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort, and for the IMP subjects with 
CG Future Band, CG Future Ring and Profile 3D Ring respectively.  
 
Analysis Method: 
A Kaplan-Meier analysis will be performed.  
7.9.3 Secondary Endpoint #1 
Characterization of subject demographics and pathophysiology of mitral valve disease. 
 
Hypothesis/Decision criteria: 

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No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
Baseline demographics and clinical variables will be summarized. The following subject characteristics at 
baseline will be reported: age (in years), gender, previous cardiovascular surgery, symptoms of heart 
failure, cardiac rhythm, New York Heart Association (NYHA) classification, risk factors, level of 
regurgitation, type of mitral valve deficiency, etc. 
 
Data Collection and Analysis Dataset:  
Data will be collected on a DEMOGRAPHICS (DM) or PRE-OPERATIVE CLINICAL HISTORY (MH) CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort.  
 
Analysis Method: 
Descriptive statistics will be provided. For continuous variables (e.g. age), the mean, median, standard 
deviation, minimum, maximum, and first and third quartiles will be presented. For categorical variables, 
the number and percentage of subjects in the category of interest will be presented, as described in 
section 7.2. 
7.9.4 Secondary Endpoint #2 
Improvement in mitral valve regurgitation (MR) (grade) at discharge and first follow up (3-6 months). 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
Mitral valve function will be based on site echocardiographic recordings. The parameter to be estimated 
is the grade of mitral valve regurgitation using echo, in subjects at discharge and 3-6 months post 
procedure. The grades of MR, 0-4, will correspond to the ASE guidelines (as described in Table 1 in CIP) 
ranging from no MR, Mild MR, Moderate MR, Moderate-to-Severe MR and Severe MR. 
 
Data Collection and Analysis Dataset:  
Data will be collected on an ECHOCARDIOGRAM (CV) CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort, and for the IMP subjects with 
CG Future Band, CG Future Ring and Profile 3D Ring respectively. IMP subjects having available MR 
collection at baseline, discharge and 3-6 months post procedure will be included in the analysis. 
 
Analysis Method: 
For each subject with paired data, the change from baseline (improved, no change, worsened) will be 
evaluated at discharge and 3-6 months follow up. This secondary endpoint of improvement in MR 
(grade) will be presented with frequencies and percentages of subjects with improved MR at discharge 
and 3-6 months. Two-sided 95% exact binomial confidence intervals of the percent of subjects overall 
and in each of the three subgroups with improved MR at discharge and 3-6 months will also be 
reported. 

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7.9.5 Secondary Endpoint #3 
Improvement in New York Heart Association (NYHA) functional class at discharge, first follow up (3-6 
months) and second follow up (12 months) compared to baseline. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
The parameter to be estimated is NYHA classification at discharge, 3-6 months and 12 months follow-up. 
 
New York Heart Association (NYHA) classification and risk factors are defined as below: 
 
 
Data Collection and Analysis Dataset:  
Data will be collected on a DEMOGRAPHICS (DM) or DISCHARGE/FOLLOW UP (SV) CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort. All IMP subjects with 
available NYHA collections (I/II/III/IV) or died at baseline, discharge, 3-6 months and 12 months follow 
up visits will be included in the analysis. 
 
Analysis Method: 
For each subject with paired data or who died prior to a visit, the change from baseline (improved, no 
change, worsened or died) will be calculated at discharge, 3-6 months, and 12 months. The endpoint of 
improvement in NYHA class will be presented with frequencies and percentages of subjects with 
improved NYHA at discharge, 3-6 months, and 12 months. The two-sided 95% exact binomial confidence 
interval of the overall percent of subjects with improved NYHA class at discharge, 3-6 months, and 12 
months will also be reported. 

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7.9.6 Secondary Endpoint #4 
Hospitalization for Heart Failure at 6 and 12 months post procedure. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
Hospitalization for Heart Failure event rate estimate will be provided at 6 and 12 months post 
procedure. 
 
Data Collection and Analysis Dataset:  
Data will be collected on an AE CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort.  
 
Analysis Method: 
A Kaplan-Meier analysis will be performed.  
7.9.7 Secondary Endpoint #5 
Mitral valve re-intervention at discharge, 6 and 12 months post procedure. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
Mitral valve re-intervention event rate estimate will be provided at discharge, 6 and 12 months post 
procedure. 
 
Data Collection and Analysis Dataset:  
Data will be collected on a RE-INTERVENTION (RE-OP) CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort.  
 
Analysis Method: 
A Kaplan-Meier analysis will be performed.  
The number and percentage of subjects with mitral valve re-intervention post implant on or prior to 
discharge will also be presented, as described in section 7.2. 
7.9.8 Secondary Endpoint #6 
Stroke at 6 and 12 months post procedure. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 

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Endpoint Definition/Parameters to Be Estimated: 
Stroke event rate estimate will be provided at 6 and 12 months post procedure. 
 
Data Collection and Analysis Dataset:  
Data will be collected on an AE CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort.  
 
Analysis Method: 
A Kaplan-Meier analysis will be performed.  
7.9.9 Secondary Endpoint #7 
New onset of atrial fibrillation (AF), as evaluated through follow up ECG at discharge, first follow up (3-6 
months) and at second follow up (12 months), as well as on the AE form. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
New onset of AF is defined as when the subject did not present with prior history of AF at baseline nor 
was AF detected at baseline visit, but AF did manifest post procedure and was either diagnosed during 
the study visits (discharge, 3-6 months or 12 months visit) or was otherwise diagnosed during the 
duration of subject participation in the study. 
 
Data Collection and Analysis Dataset:  
Data will be collected on a DISCHARGE/FOLLOW UP (SV) CRF or an AE CRF. 
This objective will be analyzed for the Successfully Implanted (IMP) cohort.  
 
Analysis Method: 
A Kaplan-Meier analysis will be performed. 
7.9.10 
Secondary Endpoint #8  
Number of attempts required for procedural success, and bypass time as a measure of procedural 
complexity, as measured by standard operating room procedures at the site. 
 
Hypothesis/Decision criteria: 
No specific hypotheses or pass/fail criteria have been set. The analysis will be descriptive and no 
statistical hypothesis test will be performed. 
 
Endpoint Definition/Parameters to Be Estimated: 
Number of attempts required for procedural success, and bypass time as a measure of procedural 
complexity. 
 
Data Collection and Analysis Dataset:  
Data will be collected on an IMPLANT (IMP) CRF. 

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This objective will be analyzed for the Successfully Implant (IMP) cohort.  
 
Analysis Method: 
The number of attempts (per subject) required for procedural success and the bypass time will be 
summarized. Descriptive statistics will be provided. 
7.10 Safety Evaluation  
Primary and secondary safety endpoints will be summarized as noted in Section 7.9 of this Statistical 
Analysis Plan (SAP). Adverse events will be provided in a listing for all attempted implant subjects. The 
proportion of subjects experiencing events will also be summarized by MEDDRA coding (System Organ 
Class and High Level Term) for successfully implanted and attempted but not successfully implanted 
subjects. 
 
7.11 Health Outcomes Analyses  
No health outcomes analyses are planned. 
7.12 Changes to Planned Analysis  
Analysis set defined in the CIP for the primary and secondary endpoints is changed to the Successfully 
Implanted set in order to align with other surgical valve studies.  
 
New onset of atrial fibrillation will be evaluated using Kaplan-Meier method instead of percent of 
subjects as described in the CIP in order to incorporate subject censoring in the course of the study. 
Atrial fibrillation identified on the post-procedural ECG or AE forms will be included in the analysis. 
 
Changes to V1.0 of the SAP include: Baseline data will be presented for the Enrolled and Successfully 
Implanted cohorts, and procedural data will be presented for the Attempted Implant and Successfully 
Implanted cohorts. As one of the objectives of the registry is to characterize subjects who are 
considered eligible for mitral valve repair in South Asia, analyzing baseline and procedural characteristics 
on these analysis cohorts will cover the populations of interest. 
 
Sub-group analyses will be performed on the Successfully Implanted subjects with CG Future Band, CG 
Future Ring and Profile 3D Ring respectively for the primary and selected secondary endpoints. 
8. 
Validation Requirements 
Level 1 validation (independent validation) will be used for the analysis datasets and the primary and 
secondary endpoints. Level 2 validation (peer review) will be used for additional analyses, data 
summaries, and listings. 
9. 
References  
[1] D. Prabhakaran, P. Jeemon and A. Roy, "Cardiovascular diseases in India: current epidemiology and 
future directions," Circulation, vol. 133, pp. 1605-1620, 2016. 
 

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[2] R. Nishimura, C. M. Otto, R. O. Bonow, C. E. Ruiz, B. A. Carabello, N. J. Skubas, J. P. Erwin III, P. Sorajja, 
R. A. Guyton, T. M. Sundt III, P. T. O'Gara and J. D. Thomas, "2014 AHA/ACC guideline for the 
management of patients with valvular heart disease: executive summary," Circulation, vol. 129, pp. 
000-000, 2014. 
 
[3] A. Gupta, P. Gharde and A. Sampath Kumar, "Anterior mitral leaflet length: predictor for mitral valve 
repair in a rheumatic population," Ann Thorac Surg, vol. 90, pp. 1930-1933, 2010. 
 
[4] S. K. Choudhary, S. Talwar, B. Dubey, A. Chopra, A. Saxena and A. Sampath Kumar, "Mitral valve 
repair in a predominantly rheumatic population," Tex Heart Inst J, vol. 28, no. 1, pp. 8-15, 2001. 
 
[5] J. Saravana Ganesh, V. Arun, A. Raghuram and K. Subramanyan, "Mitral valve repair – Is replacement 
not an ideal operation anymore?," in Indian Heart Journal, 2015.  
10. Statistical Appendices  
There are no statistical appendices for this study.