Safety and Performance Study of the Harpoon Medical Transapical Suturing Device (TSD-5) in Subjects With Degenerative Mitral Regurgitation - EFS/CE Mark Study for the Harpoon Medical Device in Poland
Phase: NA
Conditions: Mitral Valve Regurgitation, Mitral Valve Prolapse, Mitral Valve Insufficiency
Sponsor: Edwards Lifesciences

 
 
 
 
EFS amended to CE for the Harpoon Medical Device 
 
 
  
Safety and Performance study of the Harpoon Medical Transapical 
Suturing Device (TSD-5) in subjects with degenerative mitral 
regurgitation - CE Mark Study for the Harpoon Medical Device 
in Poland 
 
NCT02771275 
August 07, 2019 

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Protocol Title: Safety and Performance study of the Harpoon Medical Transapical Suturing 
Device (TSD-5) in subjects with degenerative mitral regurgitation - CE Mark Study for the 
Harpoon Medical Device in Poland 
Protocol Number: 
HMFIM -1000-PL-04 
Revision: 
07 August 2019 
Sponsor: 
Edwards Lifesciences 
One Edwards Way 
Irvine, CA 92614, U.S.A. 
www.edwards.com 
 Monitor: 
 EAR: 
Edwards Lifesciences Services GmbH 
Edisonstrasse 6  
D-85716 Unterschleissheim
Germany
Tel: +49 89 95475-0
Protocol Signature pages are provided separate to this 
protocol  
Protocol Signature pages are provided separate to this 
protocol 
CONFIDENTIALITY 
STATEMENT 
This study is confidential in nature. All information related to this study is considered proprietary and should not be made 
available to those not directly involved in this study. Authorized recipients of this information include investigators and co- 
investigators, other health care personnel necessary to conduct the study and Institutional Review Boards / Ethical Committees 
The above personnel provided with data from this study are hereby informed of its confidential and proprietary nature. 
Release of this data to individuals other than those listed above requires the prior written permission of [Sponsor]. 

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TABLE OF CONTENTS 
Contents 
TABLE OF CONTENTS ................................................................................................. 2 
I.
DEFININTIONS AND ADVERSE EVENT REPORTING ........................................ 3 
II.
BACKGROUND SIGNIFICANCE ........................................................................... 3 
III.
STUDY OBJECTIVES ........................................................................................... 6 
Performance Goals: ....................................................................................................... 6 
Safety Goals: .................................................................................................................. 6 
IV.
SUBJECT SELECTION ......................................................................................... 6 
Intended Use: ................................................................................................................. 6 
Inclusion Criteria: ........................................................................................................... 7 
Exclusion Criteria: .......................................................................................................... 7 
V.
SUBJECT ENROLLMENT ..................................................................................... 8 
VI.
STUDY PROCEDURES ........................................................................................ 9 
Entry using the valved introducer ................................................................................... 9 
Conversion to Standard of Care ................................................................................... 10 
VII.
STATISTICAL ANALYSIS .................................................................................... 11 
VIII. RISKS AND DISCOMFORTS .............................................................................. 11 
IX.
POTENTIAL BENFITS ......................................................................................... 11 
X.
MONITORING AND QUALITY ASSURANCE ...................................................... 12 
a.
Appendix A: DATA COLLECTION SCHEDULE ................................................... 13 
b.
Appendix B: REFERENCES ................................................................................ 15 

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I.
DEFININTIONS AND ADVERSE EVENT REPORTING
Adverse Device Effect - Adverse Device Effects are adverse events that are device related.
Adverse Device Effects can be classified as either Serious or Unanticipated.
Adverse Event - any untoward medical occurrence in a subject (does not imply that there is a
relationship between the adverse event and the device under investigation) [equivalent to an
observation]
Serious Adverse Event (SAE) - adverse event that a) led to a death, b) led to a serious
deterioration in the health of the subject that
•
Resulted in a life-threatening illness or injury,
•
Resulted in a permanent impairment of a body structure or a body function,
•
Required hospitalization or prolongation of existing hospitalization,
•
Resulted in medical or surgical intervention to prevent permanent impairment to body
structure or a body function [equivalent to a complication]
SAEs must be reported via eCRF (electronic case report form) immediately but no later than 3 
calendar days upon site awareness. 
Subject - is a patient who meets the inclusion and exclusion criteria that elects to enroll in the 
study and provides informed consent 
Unanticipated Device Adverse Event (UDAE) – serious adverse device effect which, by its 
nature, incidence, severity or outcome has not been identified in the current version of the risk 
analysis report.. 
UADEs must be reported to MedPass International by telephone and/or email within 24 hours 
upon site awareness. 
II.
BACKGROUND SIGNIFICANCE
Mitral Regurgitation, Transapical mitral valve repair, and the TSD-5
Mitral valve disease is the most common valvular heart disorderi, with nearly 4 million
Americans estimated to have severe mitral valve regurgitation (“MR”).ii MR results in a volume
overload on the left ventricle which in turn leads to ventricular dilation, decreased ejection
performance, pulmonary hypertension, symptomatic congestive heart failure, atrial fibrillation,
right ventricular dysfunction and death. Successful surgical mitral valve repair restores mitral
valve competence, abolishes the volume overload on the left ventricle, improves symptom
status and prevents adverse left ventricular remodeling.
The large majority of mitral regurgitation results from either degenerative disease (caused by
elongated or ruptured native chords that fail to support the mitral valve leaflets) or functional
ischemic or idiopathic MR (the motion of the normal mitral valve leaflets is restricted by the
enlarged ventricle) both of which lead to ineffective valve closure and regurgitation.
At present 2/3rds of mitral valve procedures in North America are performed on subjects with
degenerative MR and the case mix is estimated to be similar in the European Union. A
common method of treating degenerative mitral valve regurgitation during open cardiac
surgery involves replacing and/or supplementing elongated or ruptured chords with artificial
chords made of ePTFE. While open cardiac surgery has a low mortality risk, it results in
substantial  disability  and  has  important  risks,  including  stroke,  bleeding,  infection,  and

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replacement rather than repair of the mitral valve. The ability to place ePTFE artificial cords 
on the mitral valve without a chest-splitting incision, cardiopulmonary bypass, or stopping the 
heart would represent a tremendous advance in decreasing the risk and invasiveness of mitral 
valve repair. 
While considerable efforts have been directed toward minimally invasive chordal replacement, 
the only commercially available option available in the EU is a device from NeoChord Inc. The 
chordae replacement surgical procedure is performed using the NeoChord DS1000 device. 
The procedure is performed on a beating heart through a 2 to 3 inch incision between the ribs. 
Echocardiographic guidance is used during the procedure to aid the surgeon in positioning the 
device on the mitral valve leaflets. The device enters the heart through the apex, extends into 
the left ventricle and between the mitral valve leaflets. When the echocardiographic guidance 
confirms the proper position on the valve leaflets, the ePTFE suture is deployed and attached 
to the leaflet. The suture is then pulled through the apex of the heart as the DS1000 is 
removed. The correct length of the suture is determined using the echocardiographic guidance 
and observing the improvement in the mitral valve regurgitation in the beating heart. 
Although this technology presents a minimally invasive solution for the replacement of chordae 
tendineae, the device requires the surgeon to enter the left ventricle with a large shaft (~10mm) 
for every suture. Additionally, the device limits suture placement to the free edge of the mitral 
leaflet and requires the operator to grasp the free edge of the moving mitral leaflet. Neochord 
has reported several instances of ePTFE suture tear-outs from the mitral valve leaflet. There 
is a need for a less invasive, beating heart cordal delivery device with more a more effective 
anchoring mechanism. 
To address this unmet need, Harpoon Medical has developed a novel small-diameter (<3mm) 
rigid linear device with a needle wrapped with ePTFE in a preformed knot configuration The 
device may be delivered via a purpose-designed valved introducer inserted a few centimeters 
“off apex” just below the papillary muscle to secure cords to the mitral leaflet with a “bulky 
knot” anchor or directly into the left ventricle using an entry point a similar entry point. This 
knot is housed inside the rigid metal shaft (<3mm) of the delivery device until proper positioning 
is achieved on the ventricular side of the mitral leaflet with transesophageal echocardiography 
(TEE). To deploy and form the knot on the atrial side, a handle mechanism is actuated which 
advances the needle and knot through the leaflet, withdraws the needle out of the knot, then 
pulls the ends of the suture to form/expand the bulky knot on the atrial side of the leaflet. The 
ends of the suture are then released from the delivery system which can then be withdrawn 
from the patient leaving the bulky knot in place. The process can be repeated with additional 
devices to deliver additional sutures in the prolapsed leaflet. The length of the ePTFE cords 
sutures can be adjusted in real-time under echo guidance to optimize the surface of coaptation 
between leaflets before they are secured to an ePTFE pledget on the epicardium. 
The Harpoon device will provide many significant advantages over current surgical 
interventions including: 1) a small minimally invasive incision, 2) no sternotomy, 3) no 
cardiopulmonary bypass, 4) no aortic manipulation, 5) a direct path to the valve plane, 6) 
performed on a beating heart, 7) real-time TEE-guided chordal length adjustment and 8) less 
complicated procedure that is teachable and adoptable. The only intracardiac implant is an 

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ePTFE suture which has a 25+ year history of safety in conventional mitral valve repair 
procedures. 
Importantly, the Harpoon approach will not compromise subsequent traditional open-heart 
mitral valve repair or replacement procedures. Collectively, these benefits should translate 
into dramatically less pain and disability, lower hospital lengths of stay, fewer strokes, less 
renal failure, fewer wound infections and lower peri-procedural mortality. 
Currently, mitral valve surgical procedures require a 3 to 6 hour procedure with 4 to 7 days of 
in hospital recovery (including at least a 1 day in the ICU) and a month or more of recovery 
before the subject can return to work. With the Harpoon device, the procedure will be 
transformed in to a 45 to 60 minute procedure where the subject can be discharged within 24 
hours and can return to work within a week. 
Treatments: At this time, there are treatments available to replace ruptured or elongated cords 
and result in the reduction of MR; however there is no currently effective medical therapy that 
treats or cures MR. The current technologies available to address the structural defects of 
mitral regurgitation include: 
•
Open heart operations to repair or replace the mitral valve. Open cardiac mitral valve
operations require either a sternotomy or a thoracotomy, cardiopulmonary bypass, aortic
manipulation and cardioplegic cardiac arrest. Mitral valve repair is carried out with leaflet
resectional techniques (Carpentier) or nonresectional techniques using ePTFE cords
placed under direct vision. Because the heart is flaccid and arrested, sizing the cords is
difficult. Improper sizing of the cords may result in a failed or ineffective mitral valve repair.
The success of mitral valve repair is significantly dependent on the expertise of the
operating surgeon. For patients with degenerative mitral valve disease, mitral valve
replacement is inferior to mitral valve repair (short-term higher perioperative mortality and
long term substantially higher risks of stroke and prosthetic valve endocarditis as well as
either the need for lifelong anticoagulation (mechanical valve) or the risk of repeat mitral
operation (bioprosthetic valve). Mitral valve replacement (compared to repair) is a risk of
open cardiac surgery. This procedure is also very invasive and not a feasible option for all
patients.
•
In 2008, Evalve received CE mark to market the MitraClip in the EU. Shortly thereafter,
the company was acquired by Abbott Labs. The implantation of MitraClip does not involve
open-heart surgery, but mimics the surgical method of edge-to-edge valve repair where
the mitral valve leaflets are clipped together with the device instead of being sutured
together. Extensive clinical experience with the MitraClip has been collected over the last
six years and the clinical efficacy has been mixed.
•
In 2013, Neochord released a CE marked, Class III medical device to the EU as a
minimally invasive procedure that is performed on a beating heart to replace cords that
have become elongated or ruptured. Neochord does not involve open-heart surgery, but
mimics the surgical method of suturing the free-edge of the mitral valve to install
replacement cords. The surgical entry point is through the apex of the heart for the
deployment of a suture by the Neochord device. Initial clinical results have been promising
but when the cordal suture is not properly anchored the procedure does not produce a
reliable repair.

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Although these procedures are available to a cardiothoracic surgeon in the EU, there is still a 
need for additional minimally invasive treatment options for patients suffering from mitral valve 
regurgitation. The MitraClip is limited to an edge-to-edge repair which is rarely used in isolation 
during open heart operations and has demonstrated mixed clinical efficacy. The large shaft of 
the NeoChord device creates significant trauma to the left ventricle and the device design 
limits the placement of the cordal suture to the free edge of the mitral valve leaflet which has 
impacted the durability of the repair. It is expected that the Harpoon Medical transapical 
suturing device will be a valuable treatment alternative for patients suffering from mitral valve 
regurgitation because it can access the left ventricle like the NeoChord device but with a 
smaller shaft or via a small valved introducer and has a more securing anchoring mechanism 
that can be deployed anywhere on the mitral valve leaflet. 
III.
STUDY OBJECTIVES
The purpose of this study is to evaluate the safety and performance of the Harpoon Medical
TSD-5. The data collected from this trial was used to support the design of the study to support
CE Mark of the TSD-5 Device.  The Harpoon Medical device received CE Mark in December
of 2017. Enrollment in this trial was completed as of November 2017. Follow-ups range from
12 to 36 months.  The purpose of this amendment is to increase the frequency of follow-up
and to extend the follow-up to 5 years post-implant.
Performance Goals:
Primary Performance Endpoints: To demonstrate that the TSD-5 performs as designed and
has the ability to successfully implant one or more ePTFE cords on the mitral valve via a small
left thoracotomy on the beating heart and reduce mitral regurgitation from severe  to </=
moderate at the conclusion of the procedure and at 30 days post-procedure.
Secondary Performance Endpoints: Severity of mitral regurgitation at 6 months, 12 months,
18 months, 24 months, 30 months, and 36 months follow-up shall be tracked and recorded.
Safety Goals:
Primary Safety Endpoints: Procedure freedom from Serious Adverse Events (SAEs) during
the ePTFE implantation procedure, at discharge, and at 30 days follow-up shall be tracked
and recorded.
Secondary Safety Endpoints Freedom from Serious Adverse Events (SAEs) at 6 months,
12 months, 18 months, 24 months, 30 months, and 36 months follow-up shall be tracked
and recorded.
IV.
SUBJECT SELECTION
Subjects will be screened, selected, and enrolled in this trial based on the inclusion and
exclusion criteria. Once enrollment has occurred, performance of the Harpoon transapical
mitral repair procedure will occur within 30 days.
Intended Use:
The TSD-5 is intended to secure ePTFE sutures on the mitral valve for the treatment of
mitral valve disease.

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Inclusion Criteria: 
•
All subjects referred for mitral valve surgery
•
Presence of severe mitral regurgitation as read on an echocardiographic study performed
within 60 days prior to procedure. Assessment of mitral regurgitation will be performed by
the investigational site echocardiography laboratory and confirmed by the Core
Echocardiography Laboratory using an integrative method.
•
Age > 18 years
•
Estimated post-ePTFE cordal implantation coaptation surface is adequate in the
judgment of the operating surgeon and the patient eligibility committee
•
Degenerative mitral valve disease
•
Subject is able to sign informed consent and able to return for follow-up and is capable of
participating in all testing associated with this clinical investigation
•
Women of child-bearing potential have a negative pregnancy test
•
Able to sign informed consent
Exclusion Criteria: 
•
Age < 18 years
•
Infective endocarditis
•
Anterior or bileaflet prolapse
•
Functional mitral regurgitation
•
History of Mediastinal Radiation
•
Inflammatory (rheumatic) valve disease
•
Requirement for concomitant cardiac surgery (e.g., coronary artery bypass grafting
(CABG), aortic valve surgery, etc.)
•
Symptomatic coronary artery disease
•
Cardiogenic shock at the time of enrollment
•
ST segment elevation myocardial infarction requiring intervention within 30 days prior to
enrollment
•
Evidence of cirrhosis or hepatic synthetic failure
•
Pregnancy at the time of enrollment (women of child bearing age should have negative
pregnancy within 14 days of surgery)
•
Severe pulmonary hypertension (PA systolic pressure > 70 mmHg)
•
Previous cardiac surgery, or surgery on the left pleural space
•
Left ventricular, atrial or appendage thrombus
•
Severely calcified mitral leaflets
•
Recent stroke (<  6 months) with permanent impairment
•
EuroScore (for mitral valve repair) > 8%
•
Subjects with contraindications to transesophageal echocardiography
•
Severe left or right ventricular dysfunction
•
NYHA Class IV
•
Renal insufficiency CKD stage 3b or worse (GFR < 45 ml/min/1.73 m2)
•
Patient is participating in another clinical study for which follow-up is currently ongoing.
(Co-enrollment in an investigational device or interventional study)
•
Patient with non-cardiac co-morbidities and life expectancy < 1 year

-HARPOON
-MEDICAL 
•
Patient has a condition or conditions that, in the opinion of the Investigator, preclude
participation, including willingness to comply with all follow-up procedures
V.
SUBJECT ENROLLMENT
This is a prospective, nonrandomized, single-centered European study designed single arm 
study to demonstrate the performance and safety of the Harpoon Medical TSD-5 in Subjects 
with degenerative mitral regurgitation. A maximum of fifty (50) subjects will be enrolled. The 
estimated enrollment period is 24 months, and all subjects shall be followed for 30 days, 6 
months, 12 months, 18 months, 24 months, 30 months, 36 months, 48 months and 60 months 
after ePTFE implantation in accordance with the Schedule of Clinical Investigations (see 
below). 
Subject wjthdrawal from the study: A withdrawal refers to a Subject who is determined to
be inactive in the study due to physician discretion, Subject choice (withdrawal of consent), 
and loss to follow-up or Subject death. Final status will be reported on all Subjects as per the 
informed consent. Three documented phone calls and a registered/certified letter will be used 
to assure that there is minimal loss to follow-up. If these efforts to contact the Subject are 
unsuccessful, the Subject will be considered lost to follow-up. 
Pre-procedure/baseline evaluations: All Subjects enrolled in the study will undergo
transthoracic echocardiography and transesophageal echocardiography prior to surgery. 
These are routine preoperative studies for Subjects undergoing heart valve surgery. 
Physical Assessment: All study Subjects will undergo a comprehensive history and physical 
examination. Once enrolled, a physical assessment must be completed within 30 days of the 
procedure and recorded on a Case Report Form (CRF). In addition to a physical examination 
and a comprehensive history, the physical assessment will include: 
•
Vital signs, 12-lead ECG, Laboratory assessment (including WBC count; Hemoglobin;
hematocrit; platelet count; creatinine Level, Total Albumin, Total Bilirubin; INR; BNP,
NTproBNP) and a chest radiograph (X-Ray)
•
A serum pregnancy test for females with childbearing potential (age < 50 years) will be
completed within 14 days prior to the procedure.
•
As per the standard of care for valve surgery, any subject with symptoms of coronary artery
disease and all subjects age >/= 45 years without risk factors shall undergo preoperative
diagnostic left heart catheterization ("LHC").
•
Pulmonary Function Tests, when clinically indicated
•
6 Minute Walk test
Standard 
transthoracic 
echocardiographic 
evaluation: 
Standard 
transthoracic 
echocardiographic assessment of the degree of mitral regurgitation will be performed as 
described in "Recommendations for evaluation of the severity of native valvular regurgitation 
with two-dimensional and Doppler echocardiography" (Zoghbi et al, J Am Soc 
Echocardiography 2003; 16:777-802) 
An integrative approach will be used, and Subjects will be categorized as having one of: 
1. None/trivial
2. Mild
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-HARPOON
-MEDICAL 
3. Moderate
4. Severe
Table 1 Qualitative and quantitative parameters useful in grading mitral regurgitation severity 
Uld 
Moderate 
Severe 
Strm'ctu.ral parameters 
LA s:iz.e 
Normal• 
Normal or dilated 
Usually dilated .. 
LV size 
Nonna!• 
Nonnal or dilated 
Usually dilated•• 
Mitral leaflets or 
Nom1al or abnormal 
Normal or abnormal 
Abno,mal/ 
support apparatus 
Flail leaflet/ 
Ruptured P"Pillary muscle 
Doppler parameters 
Color flow jct areal 
Small, central jct 
Variable 
Large central jet ( usually 
( usually < 4 cm2 or 
> 10 cm2 or> 40% of LA
< 20%ofLA area) 
area) or variable size wall-
impinging jet swirling in LA 
Mitral inflow -l'W 
A wave dominatlť 
Variable 
E wave dominanrl> 
(E usually 1.2 m/s) 
Jet density -CW 
Incomplete or faint 
Dense 
Dense 
Jee contour -CW 
Parabolic 
Usually parabolic 
Early pealing-triangular 
Pwmonary vein flow 
Syst01ic dominance§ 
Syst0lic blLUltin!f 
Syst01ic flow rcversalt 
Quantitati\'e par:tmeters"' 
VC width (cm) 
<0.3 
0.3-0.69 
.e: 0.7 
R Vol (ml/bear) 
<30 
30-44 
45.59 
,e: 60 
RF(%) 
<30 
30-39 
40-49 
ae: 50 
ERDA (cm2) 
<0.20 
0.20-0.29 
0.30-0.39 
,e: 0.40 
CW> Continuous wave; LA., left arrium; ERDA, effet..--r:ive regurgiranrorifice area; LV, left ventricle; PW, pulsed wa\•e.; RF regurgiranr fraetioo; R Vol, regurgitant 
v̍umc; VC, vena concracta. 
,. Unless tJicrcarc othcr reasons for LA or LV dilation. Normal 2D measurements: LV minora.,is :s:: 2.8 an/m2• LV end-diastolic volumes 82 ml/m2,maximal 
LA antcro·pos«:rior diameters 2 cm/m', maximal LA volumes 36 ml/m' (2,33,35). 
• • Exception; acut:e mitrJ.I regurgitation. 
'At a Nyquist limitof50-60 cm/<. 
t Pulmonary venous systolic Bow rcvcrsaJ is specific bot not sensitive for scwrc MR. 
♦ Usually above 50 years of agt or in condition.̎ of impaired relaxation, in the absence of miual stc110Si.s or Other causes of elevated LA pressure. 
s Unless other reasons for syst0lic blunting (eg. atrial fibrillation, elevated left atrial pressure). 
4' Quaotitati\'e parameters cao help sub-clas.̏fy the moderate regurgitation group imo mild-to-mode.rote and moder.1te-t0-se,•ere. 
VI.
STUDY PROCEDURES
The surgical procedure may be completed using the valved introducer. 
Entry using the valved introducer 
1. General (single lumen) endotracheal anesthesia with appropriate monitoring lines (e.g.
arterial line)
2. Supine position with elevation of the left hemithorax to 30 degrees
3.
Performance of a small left lateral thoracotomy.
4.
Placement of a purse string suture on the lateral wall of the left ventricle approximately 2
cm away from the apex.
5.
Administration of systemic heparin to maintain an activated clotting time (ACT) > 350
seconds throughout the procedure, with subsequent heparin administration as needed.
ACT will be checked every 20 minutes.
6.
Insertion and securing of the valved introducer under echocardiographic guidance.
7.
Insertion of the TSD-5 via the valved introducer.
8.
Navigation to the leaflet target zone
9.
Confirmation of limitation of motion of mitral valve leaflet and assurance of proper
targeting.
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10. Deployment of TSD-5 bulky knot suture
11. Withdrawal of the TSD-5 device through the valved introducer
12. Securing of the free ends of the bulky knot suture with a surgical snap with colored tape
on the handle. Repeat Steps 7 to 12 up to four times total per valved introducer
13. Removal of valved introducer and tighten  purse string suture
14. Adjust length of implanted ePTFE cords under echocardiographic guidance to
minimize/abrogate mitral regurgitation and maximize leaflet coaptation.
15. Tie the properly tensioned bulky knot sutures to an ePTFE pledget, one per suture set,
on the myocardium
16. Closure of thoracotomy, insertion of chest tube(s).
Conversion to Standard of Care 
If in the judgment of the operating surgeon, adequate MR reduction has not been achieved, 
or if for any other clinical reason, conversion to standard of care (SOC) mitral valve surgery 
via a median sternotomy will be performed.  Subjects who undergo a conversion to SOC mitral 
valve surgery via a median sternotomy will be followed up for 30 days. 
Post-procedure management: Standard hospital protocols for the management of subjects 
after mitral valve surgery shall be followed. Unless other indications for anticoagulation are 
present, all subjects shall receive only aspirin (325 mg/day, beginning on arrival to the 
intensive care unit). 

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Discharge: All subjects will be discharged from the hospital at the discretion of the attending 
cardiac surgeon. Prior to dismissal all Subjects will undergo a comprehensive predismissal 
echocardiogram, as well as a physical assessment (vide supra) in accordance with the 
schedule of Clinical Investigations. 
Subject follow-up: Subjects will be seen in the outpatient clinic 30 days (+10 days/-0 days) 
after the Harpoon procedure. A TTE and a clinical assessment shall be performed at that 
time (in accordance with the schedule of Clinical Investigations) to evaluate the TSD-5 device 
against the primary and secondary performance and safety endpoints. 
Additional clinical and echocardiographic follow-up in a registry fashion shall occur for all 
active subjects (in accordance with the Clinical Investigations defined in the table below) at 
the following intervals: 
•
6 months (+/- 30 days),
•
12 months (+/- 30 days)
•
18 months (+/- 30 days)
•
24 months (+/- 30 days)
•
30 months (+/- 30 days)
•
36 months (+/- 30 days)
•
48 months (+/- 30 days) and
•
60 months (+/- 30 days)
If due to an increase of MR, or due to any other medical circumstances, and a study patient 
has to undergo a Mitral Valve reoperation, this patient will be followed up by the study team for 
30 days and then will be exited from the study. 
VII.
STATISTICAL ANALYSIS
The sample size for this study was determined using outcomes from available peer-reviewed
literature, anticipated improvements in MR reduction at the conclusion of the procedure, at
the time of the hospital dismissal and at 30 days and one year. Specifically the percentage
of subjects that demonstrate MR reduction from severe to </+ moderate at the conclusion of
the procedure and at 30 days. These data will be used to assess the safety and performance
of the device when used on a human subject.  These data will be used to assess initial safety
and performance of the Harpoon Medical TSD-5, and are not designed to test a statistical
hypothesis, and therefore a formal sample size has not been calculated. All data will be
captured on an intent-to-treat basis.  Data will be reported as descriptive statistics.
VIII.
RISKS AND DISCOMFORTS
There are risks associated by our protocol. The Harpoon Medical TSD-5 device received
CE Mark in December 2017. The study uses minimally invasive surgical techniques to
repair/replace cords in a human heart. The discomforts we predict are equivalent to what is
expected from similar operative procedures (i.e., localized pain, discomfort at the incision
site(s)).  Should the Harpoon Mitral Valve Repair System not perform as designed,
conventional open-heart procedures will be used to facilitate the repair of the mitral valve.
IX.
POTENTIAL BENFITS
The Harpoon Medical TSD-5 will provide many significant advantages over current surgical
interventions including: 1) a small minimally invasive incision, 2) no sternotomy, 3) no
cardiopulmonary bypass, 4) no aortic manipulation, 5) a direct path to the valve plane, 6)
performed on a beating heart, 7) real-time TEE-guided chordal length adjustment and  8) less
complicated procedure that is teachable and adoptable.  The only intracardiac implant is an
ePTFE suture which has a 25+ year history of safety in mitral valve repair procedures.

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disclosed without written permission from Edwards Lifesciences LLC 
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Page 12 of 15 
 
Importantly, the Harpoon approach will not compromise subsequent traditional open-heart 
mitral valve repair or replacement procedures 
X.
MONITORING AND QUALITY ASSURANCE
The clinical trial site(s) will be monitored in accordance with policies at Harpoon Medical, Inc.
and those federal regulations that pertain to clinical research; namely, 21 CFR Parts 50, and
56; and others as applicable.
All SAEs (serious adverse events) and device deficiencies (reported by Investigators or identified
by Safety) will be adjudicated by an independent Clinical Endpoint Committee (CEC) through the
36 month follow-up, based on relevant source documents provided from the investigational sites.
The CEC will verify SAE criteria and code. For all confirmed SAEs, CEC will also conduct a
causality assessment in regards to the investigational Harpoon device and the index procedure.
All adjudication activities are managed by Sponsor’s Safety team according to the CEC Charter.
CLINCAL ENDPOINT COMMITTEE 
A Clinical Endpoint Committee (CEC) is responsible for adjudicating all SAEs including device 
deficiencies which may lead to SAE through the 36 month follow-up visit.  In addition, all 
confirmed SAEs are assessed in regards to relationship to the Harpoon device and Index 
procedure.   
The Sponsor’s Safety Department manages all CEC preparation activities according to an 
approved CEC Charter. 
Adjudicated data is used for a final analysis. If event is not adjudicated, site reported data is 
used. 

 
 
 
CONFIDENTIAL AND PROPRIETATARY DATA: This document and the information contained herein may not be reproduced, used, or 
disclosed without written permission from Edwards Lifesciences LLC 
Version: HMFIM -1000-PL-04, 07 August 2019  
 
Page 14 of 15 
 
Versions 03 or 04 are approved by the Ethic Committee (EC) and Competent Authority (CA).   
Once Protocol Version 04 has been approved by relevant EC and CA, subjects will be contacted 
and asked to consent to the additional visits and have their data collected. Patients who exited 
from the trial at 36 months as scheduled per protocol Version 03 will be contacted and 
requested to continue their follow-up up to 60 months as scheduled by Protocol Version 04.  
 
Two different versions of information letters (informed consent form) will be sent depending on 
patient status (already exited or not). Each patient will have to sign this letter (informed consent 
form) to approve collection of additional data.