Harmony™
TPV 22 and TPV 25 Transcatheter Pulmonary Valves and
Delivery Catheter System
Instructions for Use
Caution: Federal law (USA) restricts this device to sale by or on the order of a physician.
Medtronic, Medtronic with rising man logo, and Medtronic logo are trademarks of
Medtronic. Third-party trademarks (“TM*”) belong to their respective owners. The following
list includes trademarks or registered trademarks of a Medtronic entity in the United States
and/or in other countries.
AOA™, Harmony™
Explanation of symbols on package labeling
MR Conditional
For US audiences only
Model
Size
Serial number
Consult instructions for use at this website
Catalog number
Lot number
Manufacturer
Do not resterilize
Do not reuse
Do not use if package is damaged
Sterilized using ethylene oxide
Sterile LC: Device has been sterilized using liquid chemical sterilants according to EN/ISO 14160
Use-by date
Quantity
Temperature limit
Nonpyrogenic
Keep dry
Do not freeze
Fragile, handle with care
Keep away from sunlight
Maximum guidewire diameter
3
Temperature limit maintained
Temperature limit exceeded
Date of manufacture
Manufactured in
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Device
Model
TPV 22
HARMONY-22
TPV 25
HARMONY-25
Delivery catheter system
HARMONY-DCS
1.0 Device description
The Harmony TPV system consists of a self-expanding transcatheter pulmonary valve and a
delivery catheter system.
Table 1: Model numbers
1.1 Transcatheter pulmonary valve (TPV)
The TPV consists of a porcine pericardial valve that is preserved in buffered 0.2%
glutaraldehyde and sutured within a Nitinol frame that is sewn onto a polyester knit fabric. The
inflow end of the TPV features an attachment suture loop on each crown to thread onto the
delivery catheter system coil during loading. The TPV is treated with an alpha amino oleic acid
antimineralization process (AOA), which has been shown to mitigate leaflet calcification in
animal studies. A final sterilization step is performed using a 0.2% glutaraldehyde sterilant in
which the TPV is preserved and packaged until used.
1.2 Patient anatomical criteria
Caution: The Harmony TPV bioprosthesis size must be appropriate to fit the patient’s anatomy
measured using a perimeter base framework. Proper sizing of the device is the responsibility of
the physician. Failure to implant a device within the sizing matrix could lead to adverse effects
such as those listed in Chapter 5.
Caution: The Harmony device is not intended for patients previously treated with an RV-PA
conduit or previously implanted bioprosthesis.
The Harmony TPV bioprosthesis is available in two sizes (TPV 22, model number HARMONY22 and TPV 25, model number HARMONY-25), and each is appropriate for a range of patient
main pulmonary artery (PA) sizes (measured with ECG-gated CTA at the end of the diastolic
phase, i.e. 90% time point in the cardiac cycle) as shown in Figure 1 and Figure 2 respectively.
Please also note the following points:
• this device is intended to be implanted in a section of the main PA (between the RVOT and
main PA bifurcation) with proper distal, proximal and axial dimensions to ensure sufficient
oversizing of the device with respect to the anatomy
• the perimeter values along the main PA should be compared to those of the device at all
possible implant locations or in all possible implant scenarios within the implant zone (i.e.,
within the main PA and between the RVOT and main PA bifurcation)
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Harmony TPV22
Anatomical Size (perimeter-derived
Harmony TPV25
Anatomical Size (perimeter-derived
• the patient’s main PA should have cross-sectional perimeters described in Figure 1 or Figure
2 on the distal and proximal parts of the PA within the implant zone of the main PA
• the combined RVOT and overall PA length should be longer than or equal to the device
length
• The patient’s venous anatomy should accommodate an 8.33 mm (25Fr) delivery catheter
system
PA section
diameter)
(1) Outflow
Distal PA/Bifurcation
(2) Valve Housing >22 mm
(3) Inflow
Proximal PA/RVOT
Figure 1: TPV 22 (Nitinol frame profile) with dimensions and HARMONY-22 sizing matrix
PA section
22 mm - 28 mm
23 mm - 39 mm
diameter)
Figure 2: TPV 25 (Nitinol frame profile) with dimensions and HARMONY-25 sizing matrix
(1) Outflow
Distal PA/Bifurcation
(2) Valve Housing >25 mm
(3) Inflow
Proximal PA/RVOT
25 mm - 38 mm
32 mm - 48 mm
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1.3 Delivery catheter system (DCS)
The delivery catheter system (DCS) has a braided outer shaft with a polytetrafluoroethylene
(PTFE) lined capsule in which the TPV is housed. The DCS has a soft, tapered distal tip. The
TPV is attached to the distal end of the DCS by the DCS coil and is protected by the capsule
during delivery. The deployment of the self-expanding TPV is controlled by pulling back the
outer shaft, allowing the TPV to open. Rotating the proximal handle on the proximal end of the
DCS rotates the DCS coil and releases the TPV for final deployment.
The DCS has a nominal outside diameter of 8.33 mm (25 Fr) and a nominal effective length of
101 cm. The DCS is compatible with an 0.889 mm (0.035 in) intravascular guidewire.
1. Distal tip
2. Guidewire lumen
3. Delivery catheter system coil
4. Capsule
5. Outer shaft
Figure 3: Delivery catheter system
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6. Hemostasis sleeve
7. Stopcock
8. Hemostasis valve body
9. Hemostasis actuator
10. Proximal handle
11. Proximal handle actuator
12. Guidewire luer
13. Loading funnel halves (packaged with delivery catheter system)
14. Capsule support tube (preloaded on the delivery catheter system)
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2.0 Indications
The Harmony Transcatheter Pulmonary Valve (TPV) System is indicated for use in the
management of pediatric and adult patients with severe pulmonary regurgitation (i.e., severe
pulmonary regurgitation as determined by echocardiography and/or pulmonary regurgitant
fraction ≥ 30% as determined by cardiac magnetic resonance imaging) who have a native or
surgically-repaired right ventricular outflow tract and are clinically indicated for surgical
pulmonary valve replacement.
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3.0 Contraindications
The following are contraindications for the use of this device:
• Active bacterial endocarditis or other active infections
• Known intolerance to Nitinol (titanium or nickel) or an anticoagulation/antiplatelet regimen
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4.0 Warnings and precautions
Carefully read all warnings, precautions, and instructions for use for all components of the
system before use. Failure to read and follow all instructions or failure to observe all stated
warnings could cause serious injury or death to the patient.
4.1 Warnings
4.1.1 General
• Implantation of the Harmony TPV system should be performed only by physicians who have
received Harmony TPV system training.
• The transcatheter pulmonary valve (TPV) is to be used only in conjunction with the Harmony
delivery catheter system (DCS).
• This procedure should only be performed where emergency pulmonary valve surgery can be
performed promptly.
• Do not use any of the Harmony TPV system components if any of the following has
occurred:
• It has been dropped, damaged, or mishandled in any way
• The Use By date has elapsed
4.1.2 Transcatheter pulmonary valve (TPV)
• This device was designed for single use only. Do not reuse, reprocess, or resterilize the TPV.
Reuse, reprocessing, or resterilization may compromise the structural integrity of the device
and/or create a risk of contamination of the device, which could result in patient injury,
illness, or death.
• Do not resterilize the TPV by any method. Exposure of the device and container to
irradiation, steam, ethylene oxide, or other chemical sterilants renders the device unfit for
use.
• The device is packaged with a temperature sensor. Do not freeze the device. Do not expose
the device to extreme temperatures. Do not use the device if the arrow on the sensor points to
the symbol that indicates that the temperature limit has been exceeded.
• Do not use the device if any of the following have occurred:
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• The tamper-evident seal is broken.
• The serial number tag does not match the container label.
• The arrow on the sensor points to the symbol that indicates that the temperature limit
has been exceeded.
• The device is not completely covered by the storage solution.
• Do not contact any of the Harmony TPV system components with cotton or cotton swabs.
• Do not expose any of the Harmony TPV system components to organic solvents, such as
alcohol.
• Do not introduce air into the catheter.
• Do not expose the device to solutions other than the storage and rinse solutions.
• Do not add or apply antibiotics to the device, the storage solution, or the rinse solution.
• Do not allow the device to dry. Maintain tissue moisture with irrigation or immersion.
• Do not attempt to repair a damaged device.
• Do not handle the valve leaflet tissue or use forceps to manipulate the valve leaflet tissue.
• Do not attempt to recapture the device once deployment has begun.
• Do not attempt to retrieve the TPV if any one of the outflow TPV struts is protruding from
the capsule. If any one of the outflow TPV struts has deployed from the capsule,
the TPV must be released from the catheter before the catheter can be withdrawn.
• Do not attempt post-implant balloon dilatation (PID) of the TPV during the procedure, which
may cause damage to or failure of the TPV leading to injury to the patient resulting in
reintervention.
4.1.3 Delivery catheter system (DCS)
• This device was designed for single use only. Do not reuse, reprocess, or resterilize the DCS.
Reuse, reprocessing, or resterilization may compromise the structural integrity of the device
and/or create a risk of contamination of the device, which could result in patient injury,
illness, or death.
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• Do not reuse or resterilize the DCS.
• If resistance is met, do not advance the guidewire, DCS, or any other component without
first determining the cause and taking remedial action.
• Do not remove the guidewire from the DCS at any time during the procedure.
4.2 Precautions
4.2.1 General
• Clinical long-term durability has not been established for the Harmony TPV. Evaluate the
TPV performance as needed during patient follow-up.
• The safety and effectiveness of Harmony TPV implantation in patients with pre-existing
prosthetic heart valve or prosthetic ring in any position has not been demonstrated.
• The Harmony TPV system has not been studied in female patients of child-bearing potential
with positive pregnancy.
4.2.2 Before Use
• Exposure to glutaraldehyde may cause irritation of the skin, eyes, nose, and throat. Avoid
prolonged or repeated exposure to the chemical vapor. Use only with adequate ventilation. If
skin contact occurs, immediately flush the affected area with water (for a minimum of 15
minutes) and seek medical attention immediately.
• The TPV and the glutaraldehyde storage solution are sterile. The outside of the TPV
container is nonsterile and must not be placed in the sterile field.
• The TPV and DCS should be used only in a sterile catheterization laboratory (cath lab)
environment. Ensure that sterile technique is used at all times.
• Strictly follow the TPV rinsing procedure.
• For TPV 25: Ensure that all green sutures have been removed from the attachment suture
loops on the TPV before loading onto the DCS.
• Prevent contamination of the TPV, its storage solution, and the DCS with glove powder.
• Verify the orientation of the TPV before loading it onto the DCS. The inflow end of the TPV
with attachment suture loops must be loaded first.
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• Do not place excessive pressure on the TPV during loading.
• Inspect the sealed DCS packaging before opening. If the seal is broken or the packaging has
been damaged, sterility cannot be assured.
• Proper functioning of the DCS depends on its integrity. Use caution when handling the DCS.
Damage may result from kinking, stretching, or forceful wiping of the DCS.
• This DCS is not recommended to be used for pressure measurement or delivery of fluids.
• Carefully flush the DCS and maintain tight DCS connections to avoid the introduction of air
bubbles.
4.2.3 During Use
• The TPV segment is rigid and may make navigation through vessels difficult.
• Do not advance any portion of the DCS under resistance. Identify the cause of resistance
using fluoroscopy and take appropriate action to remedy the problem before continuing to
advance the DCS.
• Careful management of the guidewire is recommended to avoid dislodgement of the TPV
during DCS removal.
• Once deployment is initiated, retrieval of the TPV from the patient is not recommended.
Retrieval of a partially deployed valve may cause mechanical failure of the delivery catheter
system or may cause injury to the patient. Refer to Section 5.0 for a list of potential adverse
events associated with the Harmony TPV implantation.
• During deployment, the DCS can be advanced or withdrawn prior to the outflow struts
protruding from the capsule. Once the TPV struts contact the anatomy during deployment, it
is not recommended to reposition the device. Advancing the catheter forward once the TPV
struts make contact with the anatomy may lead to an undesired deployment or may cause
damage to or failure of the TPV and injury to the patient. Refer to Section 5.0 for a list of
potential adverse events associated with the Harmony TPV implantation.
• Physicians should use judgment when considering repositioning of the TPV (for example,
using a snare or forceps) once deployment is complete. Repositioning the bioprosthesis is not
recommended, except in cases where imminent serious harm or death is possible (for
example, occlusion of the main, left, or right pulmonary artery). Repositioning of a deployed
valve may cause damage to or failure of the TPV and injury to the patient. Refer to Section
5.0 for a list of potential adverse events associated with the Harmony TPV implantation.
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• Ensure the capsule is closed before DCS removal. If increased resistance is encountered
when removing the DCS through the introducer sheath, do not force passage. Increased
resistance may indicate a problem and forced passage may result in damage to the device and
harm to the patient. If the cause of resistance cannot be determined or corrected, remove the
DCS and introducer sheath as a single unit over the guidewire, and inspect the DCS and
confirm that it is complete.
• If there is a risk of coronary artery compression, assess the risk and take the necessary
precautions.
• Endocarditis is a potential adverse event associated with all bioprosthetic valves (Chapter 5).
Patients should make their health care providers aware that they have a bioprosthetic valve
before any procedure. Postprocedure, administer appropriate antibiotic prophylaxis as needed
for patients at risk for prosthetic valve infection and endocarditis.
• Prophylactic antibiotic therapy is recommended for patients receiving a TPV before
undergoing dental procedures.
• Postprocedure, administer anticoagulation and/or antiplatelet therapy per physician/clinical
judgment and/or institutional protocol.
• Excessive contrast media may cause renal failure. Preprocedure, measure the patient’s
creatinine level. During the procedure, monitor contrast media usage.
• Conduct the procedure under fluoroscopy. Fluoroscopic procedures are associated with the
risk of radiation damage to the skin, which may be painful, disfiguring, and long-term.
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5.0 Potential complications/adverse events
Potential risks associated with the implantation of the Harmony TPV may include, but are not limited
to, the following:
• Death
• Valve dysfunction
• Tissue deterioration
• Hematoma
• Heart failure
• Cerebrovascular incident
• Perforation
• Rupture of the RVOT
• Compression of the aortic root
• Compression of the coronary arteries
• Sepsis
• Pseudoaneurysm
• Erosion
• Stent fracture
• Arrhythmias
• Device embolization or migration
• Pulmonary embolism
• Occlusion of a pulmonary artery
• Laceration or rupture of blood vessels
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• Device misorientation or misplacement
• Valve deterioration
• Regurgitation through an incompetent valve
• Physical or chemical implant deterioration
• Paravalvular leak
• Valve dysfunction leading to hemodynamic compromise
• Residual or increasing transvalvular gradients
• Progressive stenosis and obstruction of the implant
• Hemorrhage
• Endocarditis
• Thromboembolism
• Thrombosis
• Thrombus
• Intrinsic and extrinsic calcification
• Bleeding
• Bleeding diathesis due to anticoagulant use
• Fever
• Pain at the catheterization site
• Allergic reaction to contrast agents
• Infection
• Progressive pulmonary hypertension
• Progressive neointimal thickening and peeling
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• Leaflet thickening
• Hemolysis
General surgical risks applicable to transcatheter pulmonary valve implantation:
• Abnormal lab values (including electrolyte imbalance and elevated creatinine)
• Allergic reaction to antiplatelet agents, contrast medium, or anesthesia
• Exposure to radiation through fluoroscopy and angiography
• Permanent disability
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6.0 Patient information
6.1 Registration information
A patient registration form is included in each bioprosthesis package. After implantation, please
complete all requested information. The serial number is located on both the package and the
identification tag attached to the bioprosthesis. Return the original form to the Medtronic address
indicated on the form and provide the temporary identification card to the patient prior to
discharge.
Medtronic will provide an Implanted Device Identification Card to the patient. The card contains
the name and telephone number of the patient’s physician as well as information that medical
personnel would require in the event of an emergency. Patients should be encouraged to carry
this card with them at all times.
6.2 MRI safety information
Nonclinical testing and modeling have demonstrated that the TPV is MR Conditional. A patient
with this device can be safely scanned in an MR system meeting the following conditions:
• Static magnetic field of 1.5 T or 3.0 T
• Maximum spatial field gradient of 2500 gauss/cm (25 T/m)
• Maximum MR system reported, whole body averaged specific absorption rate (SAR) of
4.0 W/kg (First Level Controlled Operating Mode)
Under the scan conditions defined above, the TPV is expected to produce a maximum in vivo
temperature rise of less than 3°C after 15 minutes of continuous scanning.
In nonclinical testing, the image artifact caused by the device extends approximately 3 mm from
the TPV when imaged with a spin echo pulse sequence and 5 mm when imaged with a gradient
echo pulse sequence and a 3.0 T MRI system. The lumen of the device was clear for the spin
echo images and only partially obscured for the gradient echo images.
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7.0 How supplied
7.1 Packaging
7.1.1 TPV
The TPV is chemically sterilized and provided sterile and nonpyrogenic in a sealed glass
container filled with a buffered 0.2% glutaraldehyde solution. If the jar is undamaged and
unopened, the TPV is sterile. The outer surfaces of the jar are nonsterile and must not be placed
in the sterile field.
7.1.2 Delivery catheter system (DCS) and loading system (LS)
The DCS and the LS are sterilized with ethylene oxide gas and packaged in a double-pouch
configuration. The packaging is designed to ease placement of the DCS and the LS in the sterile
field. If the pouches are undamaged and unopened, the DCS and the LS are sterile. The outer
surfaces of the outer pouch are nonsterile and must not be placed in the sterile field.
7.2 Storage
Store the TPV at room temperature (5°C to 25°C [41°F to 77°F]). Store the DCS at room
temperature in a dry environment and away from direct sunlight.
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8.0 Instructions for use
The following is a sequential outline of the implant procedure. The type of diagnostic catheters,
guidewires, and other tools needed are at the discretion of the operator.
Note: See Figure 1, Figure 2, and Figure 3 for TPV and DCS components.
8.1 Access site preparation and preimplantation imaging
Sterilize the access site before implanting the TPV; maintain sterile techniques throughout the
procedure. Obtain preimplantation imaging of the anatomy to confirm that the anatomy is
suitable for successful implantation of the TPV.
Note: Periprocedural antibiotics may be administered according to institutional policy.
1. Prepare the venous access site using aseptic techniques and drape to provide a sterile
field.
2. Gain venous and arterial access.
3. Administer heparin to achieve a target ACT of >250 seconds.
4. Use an end-hole catheter through the venous introducer to obtain pressure measurements
in the right atrium, right ventricle (RV), and pulmonary artery.
5. Obtain right ventricular angiography in lateral and cranial projections, if necessary. A
right or left anterior oblique projection (RAO or LAO) may also be required.
6. Using direct measurement of the intended implantation site, obtain dimensions to confirm
that morphology is an acceptable size for implantation.
7. Place a pigtail catheter through the arterial introducer and advance to the aorta to obtain
systemic pressures. Perform an aortic root angiography to show the coronary anatomy
relative to the implantation site.
8. Simultaneously record the aortic and RV pressures to obtain an RV-to-systemic systolic
pressure ratio.
9. Advance an end-hole catheter to the distal pulmonary artery for secure guidewire
placement through the venous access site.
10. Deploy a 0.889 mm (0.035 in) ultra-stiff guidewire to the most distal position possible in
the pulmonary artery through the end-hole catheter.
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11. Remove the end-hole catheter; leave the guidewire in place.
8.2 Preparation of the DCS
1. Carefully inspect the package before opening.
Caution: Do not use after the Use By date or if the integrity of the sterile package has
been compromised (for example, damaged package).
2. Verify that the outer shelf carton label matches the outer pouch label.
3. Using aseptic technique, remove the product from the protective package. Discard the
protective packaging.
4. Visually check that the product is free of defects and that the LS components are present.
Do not use if any defects are noted.
5. Remove the loading funnel halves from the tray. Rinse in a clean saline bowl and leave in
the bowl until required for loading.
6. Remove the DCS (including the capsule support tube) from the tray by gripping the DCS
appropriately and overcoming the packaging snap features. Lay the DCS on the sterile
bench in a straight configuration and discard the tray.
8.3 Preparation of the TPV
The TPV is packaged sterile in a jar with a hermetic seal and a tamper-evident seal. Before
opening, carefully examine the jar and lid for damage, leakage, or broken seals. The jar should
contain enough sterilant to cover the TPV completely.
The following steps must be followed in correct sequence to ensure adequate rinsing of the
sterilant from the TPV:
1. Using aseptic technique, prepare 3 sterile bowls: 2 containing isotonic saline solution
(500 mL, enough to cover the TPV completely) for rinsing and 1 remaining empty.
2. Remove the TPV from the jar, following the steps for either TPV 22 or TPV 25.
For TPV 22: remove the TPV by grasping the fabric with atraumatic forceps and lifting
the TPV from the jar.
For TPV 25: remove the TPV by grasping the serial number tag, which is attached to the
inflow end of the TPV, with atraumatic forceps and lifting the TPV from the jar. If the
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serial number tag is not accessible, it is acceptable to remove the TPV by grasping the
fabric with atraumatic forceps and lifting the TPV from the jar.
The outside of the jar is nonsterile. Do not allow the TPV to come into contact with the
outside of the jar.
Note: On TPV 22, the serial number tag is sutured end-to-end around the center TPV
segment. On TPV 25, the serial number tag is attached to the inflow end of the TPV.
3. Verify that the serial number on the tag matches the jar label serial number. If any
difference is noted, do not use the TPV.
4. To detach the serial number tag, follow the steps for either TPV 22 or TPV 25.
For TPV 22: Hold the TPV over the empty sterile bowl. Use scissors to clip the single
suture line between the 2 ends of the tag. Do not cut the knots that secure the tag. Do not
cut or clip the polyester knit fabric or Nitinol struts. Once the suture is clipped, the tag
and suture fall away from the TPV. Verify that no tag-attachment suture remains on the
TPV.
For TPV 25: Hold the TPV over the empty sterile bowl. Use scissors to clip the green
suture lines at one location between the attachment suture loops. Do not cut the
attachment suture loops or the knots that secure the tag. Do not cut or clip the polyester
knit fabric or Nitinol struts. Once the suture is clipped, manually pull the serial tag to
remove the tag and green suture away from the TPV. Verify that no green suture remains
on the TPV.
5. Drain the residual storage solution from the TPV into the empty discard bowl (bowl 1) by
holding the TPV outflow end downward.
6. Transfer the TPV to the first rinse bowl (bowl 2). Rinse the TPV by emptying, filling,
inverting, and swirling the TPV for a minimum of 1 minute. Empty the rinse solution
from the TPV into the bowl.
7. Transfer the empty TPV to the second rinse bowl (bowl 3) and repeat Step 6 for a
minimum of 1 minute. Leave the TPV in the rinse bowl until needed for loading to
prevent the tissue from drying.
8. Empty any rinse solution from the TPV before loading the TPV onto the DCS. Ensure
that the valve is in the open position before loading the TPV onto the DCS.
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8.4 DCS loading
1. Before beginning the loading sequence, flush through the hemostasis valve body to wet
the internal seal.
2. Position the pre-mounted capsule support tube over the DCS capsule. Ensure the flared
end is facing the distal tip of the DCS.
3. Advance the distal tip until the luer touches the proximal handle edge.
4. Retract the outer shaft to expose the holding coil by pulling the hemostasis valve body
proximally, while holding the proximal handle stationary.
5. Lock the hemostasis valve body by rotating the actuator clockwise. Flush with sterile
saline through the hemostasis valve body. Unlock the hemostasis valve body by rotating
the actuator counter-clockwise
6. Slide the TPV over the distal tip of the DCS, with the TPV’s inflow end first. Take care
not to puncture the valve’s leaflets with the pointed distal tip of the DCS.
7. Thread each attachment suture loop onto the DCS coil in sequence. Rotate the TPV 2 full
turns onto the DCS coil so that the TPV is securely attached to the DCS. Ensure that the
attachment suture loops do not become entangled at the proximal collar of the DCS coil.
Note: During loading of the suture loops, if there is any observation of infolding, reload
the attachment suture loops.
8. Assemble the 2 loading funnel halves over the inflow end of the TPV. Carefully connect
the 2 halves. Do not catch the TPV or the capsule’s distal edge in the process.
9. Hold the loading funnel stationary and rotate the capsule support tube clockwise until
reaching a full stop to assemble the loading tools. Retract the assembled loading tool until
the funnel shoulder engages with the distal end of the capsule.
10. Keep both the assembled loading tools and the outer shaft stationary. Pull the proximal
handle in the proximal direction to load the TPV into the capsule. Continue to flush the
DCS while loading the TPV.
Caution: Do not place excessive pressure on the TPV or DCS during loading.
11. Adjust the position of the valve within the capsule so there is an approximately 1 cm gap
between the distal end of the capsule and the distal end of the frame.
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12. Once the TPV is fully enclosed in the capsule, lock the hemostasis valve body by rotating
the actuator clockwise.
13. Disassemble the loading tools by rotating the capsule support tube counter-clockwise and
taking the loading funnel halves apart. Slide the capsule support tube over the distal tip to
remove it from the DCS.
14. Hold the DCS with its distal tip pointed upward. Flush the DCS with normal saline,
taking care not to rotate the DCS coil (which would release the TPV prematurely).
15. To close the tip into the capsule, push the tip proximally until the max tip outer diameter
is flush with the capsule distal edge.
Note: Do not pull the tip into the DCS by pulling on the guidewire luer.
16. If there is a gap between the tip and the TPV in the capsule, unlock the hemostasis valve
body by rotating the actuator counter-clockwise. Adjust the position of the crimped TPV
to minimize the gap. Lock the hemostasis valve body by rotating the actuator clockwise.
17. Lock the proximal handle by rotating the actuator clockwise.
18. Flush the DCS through the guidewire luer.
19. Advance the hemostasis sleeve until it is flush with the proximal end of the capsule.
Caution: Do not load or re-load the TPV onto the DCS after the TPV or the DCS has
been inserted into a patient. A second attempt may be made to load an undamaged TPV
onto the DCS but only if neither the TPV nor the DCS has entered the body. Do not load
the TPV onto the DCS more than 2 times.
8.5 TPV implantation
1. Dilate the vein using a venous dilator, being careful not to displace the guidewire.
2. Remove the venous dilator from the vein and advance the DCS over the guidewire until
the hemostasis sleeve working length is fully inserted.
3. Carefully advance the DCS through the sleeve towards the intended implant zone. This
action requires manipulation of the DCS and the guidewire.
Note: Attention must be paid to maintain adequate guidewire position at all times.
4. Once the TPV has reached the implant zone, ensure the proper TPV position using
angiography.
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Caution: Ensure careful consideration to position the TPV within the target implant
zone. TPV implantation outside of target implant zone may lead to an undesired
deployment or sub-optimal placement requiring manipulations that may cause damage to
or failure of the TPV and injury to the patient.
5. Unlock the proximal handle by rotating the actuator counter-clockwise, and advance the
distal tip forward.
6. Unlock the hemostasis valve body by turning the actuator counter-clockwise. While
holding the proximal handle stationary with one hand to control TPV position, slowly
pull back the hemostasis valve body to retract the outer shaft. Expose the first 2 Nitinol
struts and ensure correct TPV expansion and position using angiography.
7. Once correct expansion is confirmed, continue to slowly pull back the hemostasis valve
body while holding the proximal handle stationary to retract the outer shaft and maintain
TPV position at the intended site. Continue to deploy the TPV while maintaining TPV
position until the TPV frame is fully exposed in the RVOT. Ensure that the capsule is
fully retracted under fluoroscopy with the aid of the capsule marker band.
8. While maintaining the TPV position, gradually rotate the proximal handle counter-
clockwise, releasing the TPV crown by crown. If heart rhythm disturbance is detected,
maintain the catheter position and do not release the TPV further until the disturbance
resolves. Resume gradually rotating the proximal handle counter-clockwise until all the
inflow sutures on the TPV are released from the DCS coil.
9. Retract the outer shaft while maintaining the position of the distal tip of the DCS in
relation to the TPV.
10. Carefully retract the DCS coil into the capsule.
11. With careful manipulation of the guidewire and inner shaft, remove the distal tip of the
DCS back through the TPV.
Caution: Use careful management of the guidewire to avoid dislodgement or movement
of the TPV.
12. Using fluoroscopy and guidewire manipulation, pull on the inner shaft to center the distal
tip back into the DCS. Lock the proximal handle by rotating the actuator clockwise.
Remove the DCS from the patient.
Note: Take care not to overcapture the tip by using too much force on the inner shaft.
13. Valve function can be verified at this point by repeating pressure measurements.
Compare the RV pressure to the systemic pressure measured through the arterial
approach.
26
14. Inject contrast media into the main pulmonary artery to aid in demonstrating valve
function and position. Ensure that the valve is not held open by the guidewire, which may
give the false impression of pulmonary regurgitation.
15. Perform an RV angiogram to assess the TPV position and paravalvular leakage (if any).
16. Remove the guidewire and introducer sheath while maintaining hemostasis.
Caution: Dispose of the DCS in accordance with applicable laws, regulations, and
hospital procedures, including those regarding biohazards, microbial hazards, and
infectious substances.
27
9.0 Return of explanted TPV
Medtronic is interested in obtaining explanted TPVs. Specific pathological studies of the
explanted TPV will be conducted under the direction of a consulting pathologist. A written
summary of the findings will be returned to the physician. Contact a Medtronic representative to
request a product return kit to return explanted TPV for analysis and disposal. If a kit is not
available, place the explanted TPV in a container filled with glutaraldehyde or 10% buffered
formalin immediately after explantation. For further return instructions, contact a Medtronic
representative.
28
10.0 Summary of clinical studies
10.1 The Medtronic Harmony Transcatheter Pulmonary Valve Clinical Study
The Harmony clinical study was a prospective, non-randomized, multi-center study and included
two phases, i.e., the early feasibility study (EFS) phase and the pivotal study phase. The EFS
treated (i.e., catheterized) 21 patients between May 30, 2013, and May 13, 2015, at 3
investigational sites in the U.S. and Canada. The pivotal study treated 50 patients between March
14, 2017, and November 8, 2019, at 13 investigational sites in the U.S., Canada, and Japan.
Clinical data from the EFS phase and the pivotal study phase were pooled because largely
similar clinical protocols were followed in the two phases.
The study utilized an independent Data Safety Monitoring Board (DSMB), a Clinical Events
Committee (CEC), and MRI/echocardiography/explant pathology core laboratories.
At the time of database lock, a total of 340 patients had enrolled in the clinical study of the
Harmony TPV System, 71 of which were catheterized (“Catheterized Cohort”) and the
remainder were not treated due to various reasons, such as screen failures and enrollment
completion. Seventy (70) of the 71 catheterized patients received a Harmony TPV implant
(“Implanted Cohort”), including 20 EFS patients with a Harmony TPV 22 implant, 31 pivotal
study patients with a TPV 22 or TPV 25 and 19 pivotal study patients with an earlier clinical
design iteration of the TPV 25 (designated as “cTPV 25” 1) implant. One EFS patient did not
receive a Harmony TPV implant after catheterization due to high pulmonary artery pressure. Of
the 70 patients in the Implanted Cohort, two originally implanted with a cTPV 25 valve were
explanted within 24 hours post implant due to valve migration and subsequently received a
surgical valve: one on the day of the index procedure and the other the following day. The
remaining 68 patients constitutes the “Implanted > 24 Hours Cohort.”
Refer to Table 2 below for additional details. The data in this IFU represents data through 6
months of follow-up for these 70 patients. Medtronic intends to commercialize the Harmony
TPV 22 and the Harmony TPV 25. From the data represented on this IFU, it is inclusive of data
from the earlier clinical design iteration of the Harmony TPV 25 (cTPV 25) which was later
modified (TPV 25) during the study.
1
The cTPV 25 implant was modified to become the TPV 25 implant due to it not deploying as intended in some
cases with challenging anatomies.
29
Implanted >24
Table 2. Studies and Valve Sizes
Catheterized
Cohort
Attempted
Implant Cohort
Implanted
Cohort
Hours Cohort
All Patients 71 70 70 68
Feasibility Phase (TPV 22
only) 21 20 20 20
Pivotal Phase 50 50 50 50
TPV 22 21 21 21 21
cTPV 251 19 19 19 17
TPV 25
1
Earlier clinical design iteration used in the Pivotal study
2
Modified version in the Pivotal study, Commercial version
2
10 10 10 10
10.1.1 Patient Population
The demographics and baseline characteristics of the study population are typical for a
transcatheter pulmonary valve replacement study performed in the U.S., as summarized in Table
3. Of the 71 catheterized patients with medical history data available, 63 included Tetralogy of
Fallot as their original diagnosis while the remaining patients had other diagnoses, the most
common of which was pulmonary stenosis. All patients presented with moderate or severe
pulmonary regurgitation.
Table 3. Patient Demographics and Baseline Characteristics - Catheterized Cohort
Summary Statistics*
Assessment
(N= 71)
Sex
Female 40.8% (29/71)
Male 59.2% (42/71)
Age at baseline (years) 28.5 ± 12.0 (71)
<22 38.0% (27/71)
12 to <18 19.7% (14/71)
18 to <22 18.3% (13/71)
≥22 62.0% (44/71)
Original Diagnosis
30
Summary Statistics*
Assessment
Tetralogy of Fallot 88.7% (63/71)
With pulmonary stenosis 60.6% (43/71)
With pulmonary atresia 7.0% (5/71)
Absent pulmonary valve 0.0% (0/71)
Sub-type not indicated 21.1% (15/71)
Pulmonary stenosis‡ 6.0% (3/50)
Pulmonary atresia with intact ventricular septum‡ 2.0% (1/50)
Transposition of the Great Arteries 0.0% (0/71)
Truncus arteriosus 0.0% (0/71)
Branch Pulmonary Artery Stenosis§ 0.0% (0/21)
Other diagnosis† 8.5% (6/71)
Type of Surgical Patch Material
None 11.3% (8/71)
Dacron 2.8% (2/71)
(N= 71)
Gore-Tex 4.2% (3/71)
Autologous pericardium 11.3% (8/71)
Bovine pericardium 2.8% (2/71)
Unknown/not available 47.9% (34/71)
Other 19.7% (14/71)
Pacemaker or ICD Implant 9.9% (7/71)
Pulmonary regurgitation by echocardiography
None - Mild 0.0% (0/71)
Moderate 4.2% (3/71)
Severe 95.8% (68/71)
Mean RVOT gradient (mmHg) by echocardiogramǁ 9.7 ± 5.3 (56)
Number of previous open heart surgeries 1.3 ± 0.5 (71)
Previous history of endocarditis‡ 2.0% (1/50)
31
Summary Statistics*
Assessment
(N= 71)
* Continuous measures - Mean ± SD (Total no.); categorical measures - % (no./Total no.)
†
Patients with “Other diagnosis” as Original Diagnosis had: double outlet right ventricle
(DORV), atrial septal defect, DORV with pulmonary stenosis, “absent” left pulmonary artery,
Noonan syndrome and dysplastic pulmonary valve stenosis, and variant of Tetralogy of Fallot
(DORV with pulmonary stenosis, secundum atrial septal defect and patent ductus arteriosus).
‡
Information only collected in the 50 patients catheterized in the pivotal study phase.
§
Information only collected in the 21 patients catheterized in the EFS phase.
ǁ
Fifty-six (56) of the 71 patients had available core laboratory echocardiography data.
10.1.2 Procedure Data
Seventy-one patients were catheterized and 70 were implanted with the Harmony TPV. One
Native EFS patient was catheterized with the intent to implant; however, upon further
assessment, the investigator elected not to proceed with implant due to high pulmonary artery
(PA) pressures. The Harmony TPV 22 implant was not attempted in this patient.
General anesthesia was utilized for all patients and venous access was achieved by the femoral
vein in 67 patients and jugular vein for 4 patients. Mean total procedure time was 142.5 ± 62.9
minutes and mean fluoroscopic time was 37.5 ± 20.1 minutes, as shown in Table 4.
Table 4. Procedural Data - Catheterized Cohort
Summary Statistics*
Assessment
(N= 71)
Anesthesia
General 100.0% (71/71)
Local 0.0% (0/71)
Venous access site for valve delivery
Femoral vein 94.4% (67/71)
Jugular vein 5.6% (4/71)
Total fluoroscopic time (min) 37.5 ± 20.1 (69)
Total procedural time (min) 142.5 ± 62.9 (70)
Total intubation time (min) 213.6 ± 129.0 (50)
* Continuous measures - Mean ± SD (Total no.); categorical measures - % (no./Total no.)
32
10.1.3 Safety and Effectiveness Results
10.1.3.1 Primary Safety Endpoint
The primary safety endpoint is freedom from procedure or device-related mortality at 30 days
post implant, for patients in the catheterized cohort.
There were no procedure- or device-related deaths reported at 30 days post implant, as
summarized in Table 5.
Table 5. Summary of Procedure or Device-related Mortality at 30 Days Post Implant -
Catheterized Cohort
Summary Statistics*
(N= 71)
Mortality
Procedure or Device-related 0.0% (0)
Procedure-related 0.0% (0)
Device-related 0.0% (0)
* Event Rate (number of patients)
% (n)
10.1.3.2 Primary Effectiveness Endpoint
• The primary effectiveness endpoint was percentage of patients with no Harmony valve
reinterventions and acceptable hemodynamic function at 6 months as defined by: Mean
RVOT gradient as measured by continuous-wave Doppler ≤40 mmHg
o If a catheterization was performed for clinical purposes, the catheterization peak
gradient measurement superseded the continuous-wave Doppler measurement and
was used to support the primary effectiveness endpoint. A peak gradient of ≤40
mmHg as measured by catheterization was considered acceptable hemodynamic
function
-AND-
• Pulmonary regurgitant fraction <20% as measured by MRI
o If MRI was contraindicated, a continuous-wave Doppler measurement was used
to support the primary effectiveness endpoint. Less than moderate pulmonary
regurgitation as measured by continuous-wave Doppler was considered
acceptable hemodynamic function.
33
Of the 68 patients in the Implanted > 24 Hours Cohort, three patients had missing
echocardiography data due to COVID-19 impact or non-evaluable echocardiography per the
imaging core laboratory. A summary of patients with acceptable TPV hemodynamic function at
6 months without reintervention on the Harmony TPV within the Implanted > 24 Hours Cohort
is provided in Table 6, which showed that 58 (89.2%) of the 65 patients with evaluable
echocardiography data achieved the primary effectiveness endpoint.
Table 6: Patients with Acceptable TPV Hemodynamic Function at 6 Months without
Reintervention on the Harmony TPV – Implanted > 24 Hours Cohort
Summary Statistics
Primary Effectiveness Endpoint Analysis
Number of evaluable patients* 65
Number of patients with reintervention 5
Number of patients with mean gradient > 40 mmHg 0
Number of patients with pulmonary regurgitation ≥ moderate 2
(N=68)
Number and percentage of patients with acceptable TPV
hemodynamic function without reintervention
Standard error for percentage 3.8%
Two-sided 95% confidence interval† 79.1% - 95.6%
*Three patients implanted with a TPV 25 whose echocardiography data were either missing
due to COVID-19 impact or not evaluable per the imaging core laboratory were excluded.
†
Two-sided Clopper-Pearson interval
58 (89.2%)
10.1.3.3 Additional Outcome Measures
Technical Success at Exit from Catheterization Laboratory/Operating Room
The technical success rate at exit from the catheterization laboratory/operating room is
summarized in Table 7 for the Implanted Cohort. Technical success was achieved in 92.9% of
the patients.
34
Table 7: Technical Success Rate at Exit from Catheterization Laboratory/
Operating Room - Implanted Cohort
Technical Success
Overall technical success 92.9% (65/70)
No device- or procedural-related mortality 100.0% (70/70)
Successful access, delivery, and retrieval of the delivery
system
Deployment and correct positioning (including minor
repositioning if needed) of the single intended device
No unplanned or emergency surgery or reintervention related
to the device or access procedure
*Event rate (no./Total no.)
Summary Statistics*
(N=70)
100.0% (70/70)
95.7% (67/70)
95.7% (67/70)
Device Success (or Freedom from Device Failure)
The Kaplan-Meier rate of freedom from device failure through 6 months for the Implanted
Cohort is summarized in Figure 4. At 6 months post implant, 84.3% of the patients were free
from device failure.
35
Number of subjects at risk:
90.0%
70
85.7%
60
84.3%
59
Freedom from Device Failure
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Months Post-Implant
All Subjects
Figure 4: Freedom from Device Failure through 6 Months - Implanted Cohort
Note: The confidence intervals were calculated without multiplicity adjustment. The
adjusted confidence intervals could be wider than presented here. As such, confidence
intervals are provided to illustrate the variability only and should not be used to draw
any statistical conclusion.
Eleven (11) patients in the Implanted Cohort met the device failure criteria, as summarized in
Table 8.
Table 8: Device Failure - Implanted Cohort
Reasons for Device Failure
Device failure* 11/70
Device- or procedural-related mortality 0
Original intended device not in place 6
Mean RVOT gradient > 40 mmHg 1
Pulmonary regurgitation ≥ moderate 4
Surgical reoperation or catheter reintervention 7
Structural performance (migration, embolization, detachment, major
stent fracture, hemolysis, thrombosis, endocarditis)
Erosion or RVOT/PA rupture 1
36
Summary Statistics
(N= 70)
6
Reasons for Device Failure
Paravalvular leak ≥ moderate 4
*
Eleven patients included 3 patients from the EFS phase and 8 from the pivotal study phase.
The reasons listed for device failure are not mutually exclusive (a given patient could have
more than one device failure reasons).
Summary Statistics
(N= 70)
Procedural Success
Procedural success was evaluated for the pivotal phase only because not all components per
definition of the endpoint were captured in the feasibility phase of the study. The pivotal phase
included 50 patients in the Implanted Cohort. The rate of procedural success at 30 days is
summarized in Table 9 for the Implanted Cohort of the pivotal phase, which showed an overall
procedural success rate of 84.0%.
Table 9: Procedural Success at 30 Days - Implanted Cohort (Pivotal Phase)
Procedural Success
Summary Statistics*
(N= 50)
Overall procedure success 84.0% (42/50)
No device failure 84.0% (42/50)
No life-threatening major bleed†
No major vascular or cardiac structural complications required
unplanned reintervention or surgery†
No stage 2 or 3 acute kidney injury (including new dialysis) †
No pulmonary embolism†
No severe heart failure or hypotension requiring intravenous
inotrope, ultrafiltration, or mechanical circulatory support†
Prolonged intubation ≤ 48 hours 100.0% (50/50)
*Event rate (no./Total no.)
†
Information not available for 2 of the 50 patients.
100.0% (48/48)
97.9% (47/48)
100.0% (48/48)
100.0% (48/48)
100.0% (48/48)
Freedom from TPV Dysfunction
The Kaplan-Meier rate of freedom from TPV dysfunction through 6 months for the Implanted >
24 Hours Cohort is shown in Figure 5. At 6 months post implant, 89.7% of the patients were
37
Figure 5: Freedom from TPV Dysfunction through 6 Months
– Implanted >24 Hours Cohort
Number of subjects at risk:
97.1%
68
92.6%
63
89.7%
61
Freedom from TPV Dysfunction
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Months Post-Implant
All Subjects
free from TPV dysfunction.
Note: The confidence intervals were calculated without multiplicity
adjustment. The adjusted confidence intervals could be wider than presented
here. As such, confidence intervals are provided to illustrate the variability
only and should not be used to draw any statistical conclusion.
All-cause Mortality
The Kaplan-Meier rate of freedom from all-cause mortality through 6 months for the
Catheterized Cohort is shown in Figure 6. There was no death reported in the catheterized
patients at 6 months.
38
Number of subjects at risk:
100%
71
100%
67
100%
66
Freedom from All-cause Mort alit y
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Months Post-Implant
All Subjects
Figure 6: Freedom from All-Cause Mortality – Catheterized Cohort
Characterization of Right Ventricle Remodeling
Right ventricular remodeling post Harmony TPV implant was characterized via cardiovascular
magnetic resonance (CMR) imaging, where not contraindicated. There were a significant number
of patients with CMR contraindication, such as pacemaker implantation. The paired right
ventricular end diastolic volume (RVEDV) and RVEDV index, pulmonary regurgitation fraction
(PRF), and net right ventricular stroke volume pre- and post-implant are shown in Figure 7
through Figure 9, respectively. The post-implant timepoint was 6 months for patients implanted
in the pivotal stage and 12 months for patients implanted in the feasibility stage (CMR was not
performed at 6 months in the feasibility stage). The RVEDV decreased from 287.5 ± 61.9 to
210.3 ± 56.7 ml, with the corresponding RVEDV index decreasing from 159.4 ± 28.9 to 115.0 ±
29.9 ml/m2; the net right ventricular stroke volume increased from 79.5 ± 26.2 to 91.0 ± 24.2
ml/beat); and the pulmonary regurgitant fraction decreased from 40.5 ± 11.6% to 2.4 ± 3.3%.
39
Figure 7: Right Ventricular End Diastolic Volume (RVEDV) and RVEDV Index
Pre- and Post-Implant – Implanted Cohort
(a) RVEDV (b) RVEDV Index
Figure 8: Pulmonary Regurgitation Fraction (PRF) Pre- and Post-Implant
– Implanted Cohort
50
100
150
200
250
300
350
400
450
500
RVEDV (ml)
Pre-Implant (N=37) Post-I mplant ( N =37)
50
100
150
200
250
300
RV ED V I nd ex ( ml/ m²)
Pre-Implant (N=37)
Post-I mpl ant ( N =37)
0
10
20
30
40
50
60
PRF(%)
Pre-Implant (N=30) Post-I mpl ant (N=30)
40
Figure 9: Net Right Ventricular Stroke Volume Pre- and Post-Implant
– Implanted Cohort
30
60
90
120
150
180
Net Right Ventricular Stroke Volume (ml/beat)
Pre-Implant (N=30) Post-I mplant (N =30)
Pulmonary Regurgitation
Pulmonary regurgitation through 6 months assessed by echocardiography is shown in Figure 10.
The proportion of patients with severe pulmonary regurgitation was 1.7% at 6 months compared
to 84.4% at baseline.
Figure 10: Pulmonary Regurgitation by Visit – Implanted Cohort
41
RVOT Gradient
The RVOT gradient over time post implant is shown in Figure 11. At discharge the mean RVOT
gradient was 13.5 ± 6.3 mmHg and remained stable through 6 months (14.0 ± 5.3 mmHg).
Figure 11: Mean RVOT Gradient by Visit – Implanted Cohort
Quality of Life
Quality of life over time was assessed in the Implanted > 24 Hours Cohort using the 36-Item
Short Form Survey (SF-36). The SF-36 scores through 6 months for patients implanted in the
pivotal stage are shown in Figure 12. Gains were observed across the mean scores of all eight
scales at 6 months post-implant, with the most gain in the areas of physical functioning (80.5 ±
25.6 at baseline vs. 94.6 ± 8.8 at 6 months) and role limitations due to physical health (79.2 ±
33.9 at baseline vs. 95.6 ± 18.7 at 6 months). The assessment was not performed in patients
implanted in the feasibility stage.
42
Figure 12: SF-36 Score by Visit – Implanted > 24 Hours Cohort (Pivotal Phase)
Adverse Events
The CEC-adjudicated adverse events at 6 months are summarized in Table 10 for the for
Catheterized Cohort, stratified by the study phase and implant model.
Table 10: CEC-Adjudicated Adverse Events at 6 Months – Catheterized Cohort
Summary Statistics*
Feasibility
Phase
Adverse Events
All-cause mortality 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Embolization of the TPV 2.8% (2) 0.0% (0) 0.0% (0) 10.5% (2)
Migration of the TPV 4.2% (3) 9.5% (2) 3.2% (1) 0.0% (0)
All Patients
(N=71)
TPV 22
(N=21)
Pivotal Phase
TPV 22 &
TPV 25
(N=31)
cTPV 25
(N=19)
Misorientation of the TPV 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Misplacement of the TPV 1.4% (1) 0.0% (0) 0.0% (0) 5.3% (1)
43
Summary Statistics*
Feasibility
Phase
Adverse Events
Other device related AE† 7.0% (5) 4.8% (1) 0.0% (0) 21.1% (4)
Collapse of valve frame 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Endocarditis 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Erosion 1.4% (1) 4.8% (1) 0.0% (0) 0.0% (0)
Stent fracture: major 1.4% (1) 4.8% (1) 0.0% (0) 0.0% (0)
Thrombosis of the TPV 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Structural deterioration 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Valve dysfunction 4.2% (3) 14.3% (3) 0.0% (0) 0.0% (0)
Stenosis 4.2% (3) 14.3% (3) 0.0% (0) 0.0% (0)
All Patients
(N=71)
TPV 22
(N=21)
Pivotal Phase
TPV 22 &
TPV 25
(N=31)
cTPV 25
(N=19)
Regurgitation 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Stenosis & regurgitation 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Paravalvular leak 8.5% (6)‡ 4.8% (1)‡ 3.2% (1) 21.1% (4)
Major 1.4% (1) 4.8% (1) 0.0% (0) 0.0% (0)
Minor 7.0% (5) 0.0% (0) 3.2% (1) 21.1% (4)
Coronary compression causing
myocardial ischemia
Perforation of the heart 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Perforation of the vessel 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
RVOT rupture or dissection 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Congestive heart failure 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Cardiac arrest 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Myocardial infarction 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
44
Summary Statistics*
Feasibility
Phase
Adverse Events
Hemorrhage 7.0% (5) 0.0% (0) 9.7% (3) 10.5% (2)
Major or life threatening 0/0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Minor 7.0% (5) 0.0% (0) 9.7% (3) 10.5% (2)
Pulmonary thromboembolism 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Pseudoaneurysm 1.4% (1) 0.0% (0) 3.2% (1) 0.0% (0)
Brachial plexus injury 1.4% (1) 0.0% (0) 3.2% (1) 0.0% (0)
Arrhythmia 23.9% (17) 4.8% (1) 25.8% (8) 42.1% (8)
Heart block, 3rd degree 1.4% (1) 0.0% (0) 0.0% (0) 5.3% (1)
Supraventricular tachycardia 2.8% (2) 0.0% (0) 6.5% (2) 0.0% (0)
All Patients
(N=71)
TPV 22
(N=21)
Pivotal Phase
TPV 22 &
TPV 25
(N=31)
cTPV 25
(N=19)
Ventricular premature beats 5.6% (4) 0.0% (0) 6.5% (2) 10.5% (2)
Ventricular tachycardia 14.1% (10) 4.8% (1) 12.9% (4) 26.3% (5)
*Event rate (number of patients)
†
Other device-related adverse events included four TPV maldeployments with the cTPV 25
implant and one frame collapse.
‡
One patient had a minor paravalvular leak reported followed by a major paravalvular leak
reported, which resulted in the Harmony valve being explanted. This is reported as one major
paravalvular leak event.
Surgical Reintervention
The results of surgical reinterventions at 6 months post implant are summarized in Table 11,
stratified by the study phase and implant model. Four patients had their Harmony TPV explanted
and a surgical valve placed by 6 months.
45
Table 11: Surgical Reinterventions at 6 Months – Implanted Cohort
Summary Statistics*
Feasibility
Phase
Surgical Reintervention
Explant of the TPV 5.7% (4) 10.0% (2) 0.0% (0) 10.0% (2)
Repair or alteration of RVOT, TPV
conserved
*Event rate (number of patients)
All Patients
(N= 70)
0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
TPV 22
(N=20)
Pivotal Phase
TPV 22 &
TPV 25
(N=31)
cTPV 25
(N=19)
Catheter Reintervention
The results of catheter reinterventions at 6 months post implant are summarized in Table 12,
stratified by the study phase and implant model. Three patients had 6 total catheter
reinterventions performed through 6-month follow-up, with some patients having more than one
type of catheter reintervention.
Table 12: Catheter Reinterventions at 6 Months – Implanted Cohort
Summary Statistics*
Feasibility
Phase
Catheter Reintervention
Implantation of another TPV 2.9% (2) 0.0% (0) 0.0% (0) 10.5% (2)
All
Patients
TPV 22
(N= 70)
(N=20)
Pivotal Phase
TPV 22 &
cTPV 25
TPV 25
(N=20)
(N=31)
46
Summary Statistics*
Catheter Reintervention
Feasibility
Phase
All
Patients
TPV 22
(N= 70)
(N=20)
Pivotal Phase
TPV 22 &
cTPV 25
TPV 25
(N=20)
(N=31)
Stent placement, Branch PA 2.9% (2) 0.0% (0) 0.0% (0) 10.5% (2)
Stent placement, other 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Balloon angioplasty of the TPV 0.0% (0) 0.0% (0) 0.0% (0) 0.0% (0)
Other† 2.9% (2) 0.0% (0) 0.0% (0) 10.5% (2)
*Event rate (number of patients)
†
Reinterventions classified by sites as “other” included balloon angioplasty and balloon
inflation.
47
10.1.3.4 Subgroup Analyses
Acceptable Hemodynamic Performance Stratified by Age
The number of patients in the Implanted >24 Hours Cohort with acceptable TPV
hemodynamic function at 6 months without reintervention post implant stratified by age (“<
22 years” vs. “≥ 22 years”) is shown in Table 13. The results are comparable between the “<
22 years” subgroup and the “≥ 22 years” subgroup.
Table 13. Patients with Acceptable TPV Hemodynamic Function at 6 Stratified By Age
– Implanted > 24 Hours Cohort
Summary Statistics (N=68)
Patients with Acceptable TPV
Hemodynamic Function at 6 Months
< 22 years
≥ 22 years
(N=27)
Number of evaluable patients 27 38
Number and percentage of patients with
acceptable TPV hemodynamic function
without reintervention
Standard error for percentage 6.0% 5.0%
Two-sided 95% confidence interval* 70.8% - 97.6% 75.2% - 97.1%
*Two-sided Clopper-Pearson interval
24 (88.9%) 34 (89.5%)
(N=41)
Acceptable Hemodynamic Performance Stratified by Gender
The number of patients in the Implanted >24 Hours Cohort with acceptable TPV
hemodynamic function at 6 months without reintervention post implant stratified by gender
is shown in Table 14. The results are comparable between the female and male subgroups.
48
Table 14. Patients with Acceptable TPV Hemodynamic Function at 6 Months Stratified
By Gender – Implanted > 24 Hours Cohort
Summary Statistics (N=68)
Patients with Acceptable TPV
Hemodynamic Function at 6 Months
Female
Male
(N=28)
(N=40)
Number of evaluable patients 26 39
Number and percentage of patients with
acceptable TPV hemodynamic function
23 (88.5%) 35 (89.7%)
without reintervention
Standard error for percentage 6.3% 4.9%
Two-sided 95% confidence interval* 69.8% - 97.6% 75.8% - 97.1%
*Two-sided Clopper-Pearson interval.
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50
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