Training Manual - Gore Medical
Training Manual - Gore Medical Training Manual - Gore Medical
TRAINING MANUAL P E R F O R M A N C E b y d e s i g n
- Page 2 and 3: Contents HISTORY...................
- Page 4 and 5: Features SIMPLICITY OF DESIGN • C
- Page 6 and 7: Product Components Tan Mandrel and
- Page 8 and 9: Occluder HYDROPHILIC TREATMENT Stan
- Page 10 and 11: Delivery System Complete delivery s
- Page 12 and 13: Delivery System TAN MANDREL • Con
- Page 14 and 15: Delivery System A firm and quick pu
- Page 16 and 17: Warnings WARNINGS • The GORE HELE
- Page 18 and 19: Precautions PRECAUTIONS (continued)
- Page 20 and 21: Choosing the Optimal Size Evaluate
- Page 22 and 23: deployment instructions D-1
- Page 24 and 25: Loading / Flushing Figure D-1 - The
- Page 26 and 27: Loading / Flushing • Once the Tan
- Page 28 and 29: Deployment When ready to deploy, co
- Page 30 and 31: Left Atrial Disc Deployment PUSH PI
- Page 32 and 33: Right Atrial Disc Deployment To del
- Page 34 and 35: Post-Lock Considerations The Occlud
- Page 36 and 37: Delivery System Removal When satisf
- Page 38 and 39: tips for success E-1
- Page 40 and 41: Premature Lock Release When the pro
- Page 42 and 43: “Missed” Right Atrial Eyelet In
- Page 44 and 45: Broken Retrieval Cord If, prior to
- Page 46 and 47: Excessive Force Encountered During
- Page 48 and 49: Fluoroscopic Appearance When deploy
- Page 50 and 51: Suggested Reading Patent Foramen Ov
TRAINING MANUAL<br />
P E R F O R M A N C E b y d e s i g n
Contents<br />
HISTORY.................................................................................Page A-1<br />
FEATURES.............................................................................. Page B-1<br />
PRODUCT...............................................................................Page C-1<br />
The GORE HELEX Septal Occluder.........................................Page C-2<br />
Delivery System...................................................................Page C-5<br />
Indications / Contraindications..........................................Page C-11<br />
Warnings...........................................................................Page C-12<br />
Precautions.......................................................................Page C-13<br />
Equipment Considerations.................................................Page C-15<br />
Choosing the Optimal Size................................................Page C-16<br />
Patient Considerations......................................................Page C-17<br />
DEPLOYMENT INSTRUCTIONS................................................ Page D-1<br />
Loading / Flushing.............................................................. Page D-3<br />
Advancing the System to Defect......................................... Page D-6<br />
Deployment........................................................................ Page D-7<br />
Left Atrial Disc Deployment................................................. Page D-8<br />
Transition — Left-to-Right................................................. Page D-10<br />
Right Atrial Disc Deployment............................................ Page D-11<br />
Lock Release.................................................................... Page D-12<br />
Post-Lock Considerations................................................. Page D-13<br />
Device Retrieval................................................................ Page D-14<br />
Delivery System Removal.................................................. Page D-15<br />
Review.............................................................................Page D-16<br />
Preparation, Deployment, and Sizing Guide Summary..............Insert<br />
TIPS FOR SUCCESS................................................................Page E-1<br />
Premature Lock Release......................................................Page E-3<br />
Kinked Tan Mandrel.............................................................Page E-4<br />
“Missed” Right Atrial Eyelet.................................................Page E-5<br />
Uneven Deployment............................................................Page E-6<br />
Broken Retrieval Cord..........................................................Page E-7<br />
Improper “Feel”...................................................................Page E-8<br />
Excessive Force Encountered During Unlocking.....................Page E-9<br />
Embolization / Emergency Recapture.................................Page E-10<br />
Fluoroscopic Appearance...................................................Page E-11<br />
REFERENCES........................................................................... Page F-1<br />
SELECTED DATA FROM THE FDA CLINICAL TRIAL..................... Page G-1<br />
Special thanks to the following cardiologists for input and guidance in the use of the<br />
GORE HELEX Septal Occluder:<br />
Sarah Badran, MD<br />
Lee Benson, MD<br />
Felix Berger, MD<br />
Philippe Bonhoeffer, MD<br />
Mario Carminati, MD<br />
John Cheatham, MD<br />
Kak Chen-Chan, MD<br />
Collin Crowley, MD<br />
Joseph V. De Giovanni, MD<br />
Michael deMoor, MD<br />
Peter Ewert, MD<br />
Thomas Fagan, MD<br />
John Hess, MD<br />
Frank Ing, MD<br />
Thomas Jones, MD<br />
Larry Latson, MD<br />
Fernando A. Maymone-.<br />
Martins, MD<br />
Chuck Mullins, MD<br />
Shakeel A. Qureshi, MD<br />
Jonathan Rome, MD<br />
Anthony P. Salmon, MD<br />
Ziad Saba, MD<br />
Martin Schneider, MD<br />
Horst Sievert, MD<br />
Robert Vincent, MD<br />
Neil Wilson, MD<br />
Evan Zahn, MD<br />
Thomas Zellers, MD
History<br />
Since the early 1980s, experience in the transcatheter closure of atrial septal defects has demonstrated .<br />
the importance of several features for an ideal closure device. Our research showed cardiologists felt that an<br />
Occluder should be quick and easy to deploy, visible under echocardiography, forgiving of errors, and readily<br />
removable even when partially or fully deployed. From a patient safety perspective, the device should present<br />
minimal risk of thrombosis, trauma or late erosion or penetration of any cardiovascular structures.<br />
The GORE HELEX Septal Occluder is one of a family of <strong>Gore</strong> interventional products recently designed for<br />
transcatheter implantation. These endovascular and cardiac products represent a new era in treatment of<br />
vascular and cardiac diseases.<br />
W. L. <strong>Gore</strong> & Associates (<strong>Gore</strong>) has been manufacturing high value expanded polytetrafluoroethylene (ePTFE)<br />
products for the cardiac, vascular, general, orthopedic and oral surgical markets for more than 30 years, with<br />
more than 25 million clinical implants. <strong>Gore</strong> ePTFE has been used in cardiovascular surgery in atrial septal defect<br />
(ASD) closure since 1982. In 1996, <strong>Gore</strong> began development of an interventional septal defect closure device.<br />
As development progressed, the company sought the advice and consultation of leading pediatric interventional<br />
cardiologists and cardiac surgeons.<br />
“The GORE HELEX Septal Occluder (W. L. <strong>Gore</strong> & Associates, Flagstaff, Arizona) is a new device with many<br />
desirable characteristics. These include direct placement of the delivery catheter across the septal defect without<br />
the need for a long sheath: rounded, flexible and atraumatic shape; easy deployment while maintaining the ability<br />
to withdraw the device back into the delivery system at any time prior to release; safety cord to allow for removal<br />
of the device even after release from the formed elements of the delivery system; and highly biocompatible<br />
expanded polytetrafluoroethylene (ePTFE) covering. The design of the device has been thoroughly tested by<br />
computer modeling in vitro testing and in vivo evaluations in an animal model of atrial septal defect (ASD). Early<br />
human experience in Europe for ASD and patent foramen ovale (PFO) indications has been encouraging...” 1<br />
1995-96 Prototype development<br />
1997-98 Pre-clinical testing<br />
1999 CE marked in June<br />
2000 US Feasibility Study initiated<br />
. . in April<br />
2001 US Pivotal Study initiated<br />
. . in March<br />
2003 US Continued Access Study<br />
. . with hydrophilic-coated ePTFE .<br />
. . initiated in May<br />
2006 FDA Approval of<br />
. . GORE HELEX Septal Occluder 1.1<br />
2007 FDA Approval of GORE HELEX..<br />
. . Septal Occluder with 1.5 .<br />
. . Delivery System<br />
2010 FDA Approval of GORE HELEX<br />
. . Septal Occluder with the 2.0.<br />
. . Delivery System<br />
Latson LA, Zahn EM, Wilson N...Helex Septal Occluder for closure of atrial septal defects...Current Interventional Cardiology Reports 2000;2(3):268-273.<br />
A-1
Features<br />
SIMPLICITY OF DESIGN<br />
• Compliant circular shape.<br />
• Flat profile.<br />
• ePTFE occlusion membrane..<br />
— Hydrophilic coating to enhance ultrasound visibility.<br />
• Circumferential Nitinol support frame, completely contained within ePTFE..<br />
— Low metal mass..<br />
— Minimal nickel leaching.<br />
SIMPLICITY OF OPERATION<br />
• Utilizes standard interventional techniques.<br />
• Universal sheathless delivery system (10 Fr). .<br />
— Pre-formed catheter for direct access to the septal defect..<br />
— Optional guidewire port.<br />
• Easily repositioned.<br />
• Easily retrieved using delivery system.<br />
• Allows accurate assessment of septal occlusion prior to final release from the delivery system.<br />
ePTFE MEMBRANE MATERIAL<br />
• ePTFE material performance is proven in more than 25 million clinical implants.<br />
• Reduced thrombogenicity.<br />
• Controlled tissue response: microporous surface allows thin and firm tissue attachment without<br />
exuberant tissue formation.<br />
• Biocompatible ePTFE material supports the formation of a functional intimal cell lining.<br />
B-1
product<br />
C-1
Product Components<br />
Tan Mandrel and Luer<br />
Green Delivery Catheter<br />
The Occluder<br />
Red Retrieval<br />
Cord Cap<br />
Gray Control<br />
Catheter and<br />
Luer<br />
Retrieval Cord<br />
C-2
Occluder<br />
The GORE HELEX Septal Occluder consists of compliant discs of ePTFE, circumferentially supported by Nitinol wire. The entire Occluder frame is<br />
constructed from a single Nitinol wire (Fig. C-2). Microporous ePTFE material, bonded to the Nitinol frame, is designed to encourage early tissue<br />
attachment, improving the security of the Occluder and reducing the potential for residual leakage. Perforations along the central edge of the<br />
ePTFE membrane are provided to align the material on the delivery system and are captured by the locking loop (Fig. C-1).<br />
The GORE HELEX Septal Occluder is supplied in diameters of 15, 20, 25, 30, and 35 mm.<br />
Mandrel<br />
ePTFE<br />
Right Atrial<br />
Disc<br />
Locking Loop<br />
Left Atrial<br />
Eyelet<br />
Nitinol Wire Frame<br />
Right Atrial<br />
Eyelet<br />
Left Atrial<br />
Disc<br />
Figure C-1<br />
Center Eyelet<br />
Figure C-2 – Nitinol Wire Frame Design<br />
C-3
Occluder<br />
HYDROPHILIC TREATMENT<br />
Standard microporous ePTFE membrane is hydrophobic and can interfere with echocardiographic evaluation.<br />
Since ultrasound assessment is essential to evaluation of appropriate Occluder placement, the membrane has<br />
been treated to render it hydrophilic and enhance ultrasound visibility.<br />
When placed in heparinized saline during the loading procedure described in the deployment section of this<br />
manual, the membrane will absorb the liquid and become transparent.<br />
GORE HELEX<br />
Septal Occluder<br />
Left Disc<br />
Right Disc<br />
Figure C-3 – Hydrophilic-treated ePTFE membrane<br />
Figure C-4 – Hydrophilic-treated GORE HELEX Septal Occluder<br />
implant from ultrasound<br />
C-4
Delivery System<br />
Y-ARM<br />
The "Y-Arm" of the GORE HELEX Septal Occluder simplifies deployment (Fig. C-5). The Gray Control<br />
Catheter and Tan Mandrel have only limited movement and must be locked in place at certain steps<br />
during device deployment.<br />
At the distal end of the delivery system, the Tan Mandrel is co-axial within the Green Delivery Catheter<br />
and the Gray Control Catheter (Fig. C-6). Additionally, a stiffening wire runs co-axial within the Tan<br />
Mandrel. Midway along the delivery system, the Tan Mandrel bifurcates out at the Gray Control Catheter<br />
lumen, to provide separate control "handles” for the operator.<br />
Steel Mandrel .<br />
Stiffener (Red in<br />
Illustration)<br />
Figure C-5 – "Y-Arm"<br />
Gray<br />
Tan<br />
Figure C-7<br />
Steel Mandrel .<br />
Stiffener (Red in<br />
Illustration)<br />
Green Delivery<br />
Catheter<br />
Bifurcation Slot<br />
Tan Mandrel<br />
Gray Control Catheter<br />
Figure C-6 – Longitudinal section of component bifurcation<br />
C-5
Delivery System<br />
Complete delivery system is used for deployment, repositioning and retrieval.<br />
GREEN DELIVERY CATHETER<br />
• Contains elongated Occluder<br />
• 10 Fr diameter<br />
• Perforated to allow delivery over 0.035" wire (Fig. C-8)<br />
• Pre-shaped catheter positions the Occluder across the defect (Fig. C-9)<br />
• Working length – 75 cm<br />
Figure C-8 – Guidewire slot with 0.035" guidewire<br />
in place<br />
Figure C-9 – GORE HELEX Septal Occluder<br />
C-6
Delivery System<br />
GRAY CONTROL CATHETER<br />
• Includes Retrieval Cord and Red Retrieval Cord Cap (Fig. C-10)..<br />
— Retrieval Cord holds Occluder to delivery system after lock release.. .<br />
(Fig. C-11)..<br />
— Can be used to unlock and retrieve Occluder after lock release if.. .<br />
necessary (Fig. C-11).<br />
• "D" shaped Gray Control Catheter and Tan Mandrel lumen prevents rotation of<br />
components (Fig. C-12)..<br />
— Separate Tan Mandrel and Retrieval Cord lumens to prevent entanglement..<br />
— Slotted tip allows lock loop to consistently deploy through the side of the..<br />
catheter, reducing disc separation during lock release.<br />
Figure C-10 – Red Retrieval Cord Cap secures end of<br />
Retrieval Cord to Gray Control Catheter<br />
Figure C-11 – Retrieval Cord looped<br />
through the proximal eyelet<br />
Figure C-12 – Occluder and<br />
cross-section of Gray Control Catheter<br />
C-7
Delivery System<br />
TAN MANDREL<br />
• Controls configuration of the Occluder<br />
• Retains the integral locking mechanism until release<br />
• Pulling gently on the Tan Mandrel configures the Occluder into a circular shape<br />
During assembly, the three eyelets and the ePTFE membrane perforations are threaded onto the Tan Mandrel. The locking loop is<br />
straightened and placed within the lumen of the Tan Mandrel. The Tan Mandrel tip is flared to retain the eyelets until lock release (Fig. C-13).<br />
Lock Loop<br />
Flared Region<br />
Left Atrial Eyelet<br />
Tan Mandrel<br />
Figure C-13 – Tan Mandrel with flared tip<br />
C-8
Delivery System<br />
In Figure C-14, the Occluder is shown as it would appear prior to lock release and prior to loading the<br />
Occluder into the delivery system. The Retrieval Cord holds the right atrial eyelet of the Occluder to the<br />
tip of the Gray Control Catheter. The locking loop is held straight within the Tan Mandrel. The Mandrel<br />
Stiffener runs along a portion of the length of the lock loop within the Tan Mandrel.<br />
Extended Lock Loop<br />
(in Tan Mandrel)<br />
Green<br />
Left Atrial Eyelet<br />
Tan Mandrel Flare<br />
Steel Mandrel .<br />
Stiffener (Red in<br />
Illustration)<br />
Tan<br />
Radiopaque Tip<br />
Gray<br />
Right Atrial<br />
Eyelet<br />
Center<br />
Eyelet<br />
Figure C-14 – Cross-section view — pre-lock release<br />
C-9
Delivery System<br />
A firm and quick pull on the Mandrel Luer pulls<br />
the Tan Mandrel tip through the three eyelets<br />
and allows the locking loop to deploy through .<br />
the slot in the Gray Control Catheter (Figs C-14<br />
and C-15).<br />
Right Atrial Eyelet<br />
Retrieval Cord<br />
In Figure C-15, the Occluder is shown following .<br />
lock release. The three eyelets are held closely<br />
together. The Tan Mandrel has been withdrawn<br />
into the Gray Control Catheter, allowing the lock<br />
loop to form through the slot at the tip of the Gray<br />
Control Catheter.<br />
Green Delivery<br />
Catheter<br />
Tan Mandrel<br />
Left Atrial Eyelet<br />
Once locked, the Occluder is still attached to the<br />
tip of the Gray Control Catheter by the Retrieval<br />
Cord.<br />
Radiopaque Tip<br />
Lock Loop<br />
Gray Control Catheter<br />
Center Eyelet<br />
Figure C-15 – Cross-section view — locked<br />
C-10
Indications / Contraindications<br />
INDICATIONS / INTENDED USE<br />
The GORE HELEX Septal Occluder is a permanently implanted prosthesis indicated for the percutaneous, transcatheter closure<br />
of atrial septal defects (ASDs), such as ostium secundum and patent foramen ovale.<br />
CONTRAINDICATIONS<br />
The GORE HELEX Septal Occluder is contraindicated for use in patients:<br />
• With extensive congenital cardiac anomalies that can only be adequately repaired by cardiac surgery<br />
• Unable to take anti-platelet or anticoagulant medications such as aspirin, heparin, or warfarin<br />
• With anatomy where the GORE HELEX Septal Occluder size or position would interfere with other intracardiac or intravascular structures,<br />
such as cardiac valves or pulmonary veins<br />
• With active endocarditis, or other infections producing bacteremia, or patients with known sepsis within one month of planned<br />
implantation, or any other infection that cannot be treated successfully prior to device placement<br />
• Whose vasculature is inadequate to accommodate one of the GORE HELEX Septal Occluder Recommended Introducer Sheaths (Table 1)<br />
• With known intracardiac thrombi<br />
C-11
Warnings<br />
WARNINGS<br />
• The GORE HELEX Septal Occluder is not recommended for defects larger than 18 mm.<br />
• The GORE HELEX Septal Occluder is not recommended for patients with a septal thickness of greater than 8 mm in the area of the occluder placement.<br />
• The GORE HELEX Septal Occluder has not been studied in patients known to have multiple defects requiring placement of more than one device.<br />
• The GORE HELEX Septal Occluder is not recommended for, and has not been studied in, patients with other anatomical types of ASDs that are<br />
eccentrically located on the septum (examples include sinus venosus ASD and ostium primum ASD), or fenestrated Fontan.<br />
• The GORE HELEX Septal Occluder has not been studied in patients with significant atrial septal aneurysm.<br />
• Regarding device deployment:.<br />
- The defect and atrial chamber size should be evaluated by Transesophageal / Transoesophageal Echocardiography (TEE / TOE) or Intracardiac Echo.<br />
(ICE) with color flow Doppler measurement to confirm that there is adequate space to accommodate the selected occluder size without impinging.<br />
on adjacent cardiac structures (e.g., A-V valves, ostia of the pulmonary veins, coronary sinus, or other critical features). .<br />
- There must be adequate room in the atrial chambers to allow the right and left atrial discs to lie flat against the septum with disc spacing equal to.<br />
the septal thickness, and without interference with critical cardiac structures or the free wall of the atria..<br />
- The defect should be evaluated to ensure there is an adequate rim to retain the device in ≥ 75% of the circumference of the defect.<br />
- The selected occluder diameter should be at least two times the diameter of the defect (i.e., a 2:1 ratio of device diameter-to-defect diameter)..<br />
Deploying the occluder in cases where the occluder diameter-to-defect diameter ratio is below 2:1 increases the risk of unsuccessful device.<br />
placement and device embolization..<br />
- An occluder that pulls through the defect during disc confirmation may be too small and should be removed and replaced with a larger size.<br />
• Embolized devices must be removed. An embolized device should not be withdrawn through intracardiac structures unless the occluder has been<br />
adequately collapsed within a sheath.<br />
• If successful deployment cannot be achieved after two attempts, an alternative treatment for ASD closure should be considered. Consideration<br />
should be given to the patient’s total exposure to radiation if prolonged or multiple attempts are required for the placement of the GORE HELEX Septal<br />
Occluder.<br />
• The GORE HELEX Septal Occluder should be used only by physicians trained in its use, and in transcatheter defect closure techniques. The procedure<br />
should be performed only at facilities where surgical expertise is available.<br />
• Patients allergic to nickel may suffer an allergic reaction to this device.<br />
C-12
Precautions<br />
PRECAUTIONS<br />
Handling<br />
• The GORE HELEX Septal Occluder is intended for single use only. An unlocked and removed occluder cannot be reused.<br />
• The GORE HELEX Device is designed for single use only; do not reuse device. <strong>Gore</strong> does not have data regarding reuse of this device. Reuse may cause<br />
device failure or procedural complications including device damage, compromised device biocompatibility, and device contamination. Reuse may<br />
result in infection, serious injury, or patient death.<br />
• Inspect the package before opening. If seal is broken, contents may not be sterile.<br />
• Inspect the product prior to use in the patient. Do not use if the product has been damaged.<br />
• Do not use after the labeled “use by” (expiration) date.<br />
• Do not resterilize.<br />
Procedural<br />
• Patients should be heparinized sufficiently to maintain an Activated Clotting Time (ACT) greater than 200 seconds throughout the procedure.<br />
• The GORE HELEX Septal Occluder should be used only in conjunction with appropriate imaging techniques to assess the septal anatomy and to<br />
visualize the wire frame. These techniques include multiplanar TEE / TOE or ICE, both with color flow Doppler, and fluoroscopy with real-time image<br />
magnification.<br />
• Retrieval equipment such as large diameter sheaths, loop snares, and retrieval baskets should be available for emergency or elective removal of the<br />
occluder.<br />
• Removal of an occluder should be considered if:.<br />
- The lock fails to capture all three eyelets<br />
- . The occluder will not come to rest in a planar position apposing the septal tissue<br />
- . The selected occluder is too small and allows excessive shunting<br />
- . There is impingement on adjacent cardiac structures<br />
C-13
Precautions<br />
PRECAUTIONS (continued)<br />
Post-Implant<br />
• Patients should take appropriate prophylactic antibiotic therapy consistent with the physician’s routine procedures following device implantation.<br />
• Patients should be treated with antiplatelet therapy, such as aspirin or clopridogrel bisulfate, for six months post-implant...The decision to continue<br />
antiplatelet therapy beyond six months is at the discretion of the physician.<br />
• In patients sensitive to antiplatelet therapy, alternative therapies, such as anticoagulants, should be considered.<br />
• Patients should be advised to avoid strenuous physical activity for a period of at least two weeks after occluder placement.<br />
• Patients should have Transthoracic Echocardiographic (TTE) exams prior to discharge, and at 1, 6, and 12 months after occluder placement to assess<br />
defect closure.<br />
• Fluoroscopic examination without contrast is recommended at 12 months post-procedure for patients with a 35 mm device with attention directed<br />
toward possible wire frame fractures.<br />
C-14
Equipment Considerations<br />
Facilities implanting the GORE HELEX Septal Occluder should have an interventional cardiac catheterization laboratory equipped with:<br />
• High resolution fluoroscopic imaging equipment.<br />
• Transesophageal Echocardiography (TEE) or Intracardiac Echocardiography equipment with color flow Doppler capabilities.<br />
• A standard range of catheterization supplies including introducer sheaths (as noted below), guidewires, and sizing balloons.<br />
Table C-1: Recommended Introducer Sheath Sizes<br />
Without Guidewire With Guidewire<br />
10 Fr or greater.<br />
(I.D. 0.131 in. / 3.33 mm)<br />
13 Fr or greater .<br />
(I.D. 0.171 in. / 4.33 mm)<br />
9 Fr TERUMO PINNACLE ®<br />
12 Fr COOK CHECK-FLO ®<br />
Introducer Sheath 1 Introducer Sheath<br />
11 Fr TERUMO PINNACLE ®<br />
Introducer Sheath<br />
1<br />
Although the sheath is designed to accommodate catheters up to 9 Fr in diameter, internal testing has shown compatibility of the introducer<br />
sheath with the GORE HELEX Septal Occluder catheter delivery system.<br />
• Should the emergency retrieval of an embolized device become necessary, larger, Mullins-type sheaths, snare catheters (35 mm will capture all sizes)<br />
or retrieval baskets should be available.<br />
The procedure should be performed only at facilities where surgical expertise is available.<br />
This product is intended for use by physicians trained in the use of the GORE HELEX Septal Occluder and in transcatheter defect closure.<br />
C-15
Choosing the Optimal Size<br />
Evaluate the defect and the atrial dimensions using TEE and fluoroscopy:<br />
• Determine defect size using a low pressure sizing balloon inflated across the defect.<br />
• There should be sufficient rim to hold the device in place and adequate room in the atria<br />
to allow the device to lie apposed to the septal tissue.<br />
• Recommended device-to-defect ratio is 2:1. Deploying the Occluder in patients where the .<br />
device-to-defect ratio is less increases the risk for embolization and residual leaks.<br />
The GORE HELEX Septal Occluder is available in diameters of 15, 20, 25, 30, and 35 mm, allowing<br />
closure of defects up to 18 mm.<br />
Table C-2<br />
Labeled Occluder<br />
Diameter (mm)<br />
Nominal Defect<br />
Size (mm)<br />
15 7.5<br />
20 10<br />
25 12.5<br />
30 15<br />
35 17.5<br />
Figure C-16<br />
C-16
Patient Considerations<br />
• The patient whose vasculature is inadequate to accommodate one of the GORE HELEX Septal Occluder<br />
Recommended Introducer Sheaths (Page C-15).<br />
• Activated Clotting Time (ACT) should be maintained at 200 seconds or greater throughout the procedure.<br />
• Standard and accepted post-procedural antiplatelet and antibiotic therapy should be employed.<br />
• Refer to the GORE HELEX Septal Occluder Instructions for Use (IFU) for patient warnings and precautions.<br />
C-17
deployment instructions<br />
D-1
Deployment Instructions<br />
The following pages describe the deployment of the GORE HELEX Septal Occluder.<br />
Three major points are addressed:<br />
Loading / Flushing<br />
Disc Formation<br />
Lock Release<br />
The cardiologist is encouraged to practice deployments in a model, both on the tabletop and under<br />
fluoroscopy in order to become completely familiar with the appearance and behavior of the device.<br />
D-2
Loading / Flushing<br />
Figure D-1 – The GORE HELEX Septal Occluder Delivery System and Tray<br />
The GORE HELEX Septal Occluder is provided in a sterile package ready to load. Prior to loading, the disc is fully formed and both the Gray<br />
Control Catheter Luer and the Mandrel Luer are locked. The Retrieval Cord is held tightly by the Red Retrieval Cord Cap (Fig. D-1).<br />
To begin the loading process, submerge the GORE HELEX Septal Occluder in heparinized saline. Keep the delivery system straight during<br />
loading.<br />
Fill a syringe (12 – 30 cc) with heparinized saline, attach it to the Red Retrieval Cord Cap and flush to fill the system.<br />
D-3
Loading / Flushing<br />
To begin loading, assure the Mandrel Luer is locked. Grasp the “Y-Arm" and loosen the Gray Control Catheter Luer (Fig. D-2).<br />
With the right hand, gently pull (retract) the Gray Control Catheter (Fig. D-3). The Mandrel Luer is locked, holding the Tan<br />
Mandrel in place. The Occluder will be easily drawn into the Green Delivery Catheter.<br />
Figure D-2 Figure D-3<br />
D-4
Loading / Flushing<br />
• Once the Tan Mandrel tip and Occluder begin to bow, (Fig. D-4), loosen the Mandrel Luer.<br />
• Grasp the Gray Control Catheter and continue to pull until the entire Occluder is inside the Green<br />
Delivery Catheter (Fig. D-5).<br />
• Once the entire Occluder is loaded into the Green Delivery Catheter, reload the syringe with heparinized<br />
saline, and flush vigorously.<br />
• Leave the syringe attached as the delivery system is moved to the table; flush again just prior to<br />
inserting the catheter into the sheath.<br />
Figure D-4<br />
Figure D-5<br />
D-5
Advancing the System to the Defect<br />
The GORE HELEX Septal Occluder has been designed as a self-contained delivery system and may be advanced across many defects directly.<br />
Physicians may choose to access the defect with a guidewire or a long sheath in order to select a particular fenestration or save time<br />
accessing a small tunnel.<br />
The GORE HELEX Septal Occluder delivery system can be advanced over a wire using the Guidewire Slot at the distal end of the Green<br />
Delivery Catheter. In that case, a larger introducer sheath must be employed. These include an 11 Fr TERUMO PINNACLE ® Introducer Sheath,<br />
a 12 Fr COOK CHECK-FLO ® Introducer Sheath, or any introducer sheath that is labeled 13 Fr or greater.<br />
If a long sheath is employed, it must be at least 10 Fr and less than 75 cm in length.<br />
D-6
Deployment<br />
When ready to deploy, confirm by echocardiography that the tip of the catheter is across the defect. .<br />
The delivery system will appear as in the photo below (Fig. D-6).<br />
• Both Luers are unlocked.<br />
• The Gray Control Catheter is retracted sufficiently to bring the entire Occluder within the Green Delivery Catheter.<br />
• 3 to 4 cm of the Tan Mandrel is exposed between the Luer and hub.<br />
Figure D-6<br />
D-7
Left Atrial Disc Deployment<br />
To begin deployment of the left atrial disc, grasp the "Y-Arm" in the left hand. All delivery motions of the Occluder<br />
should be observed on fluoroscopy with the intra atrial position confirmed by echocardiography.<br />
• Push the Gray Control Catheter to advance (Fig. D-7a, next page).<br />
– Notice that the Tan Mandrel moves as the Gray Control Catheter is pushed.<br />
• Continue pushing lightly until the Mandrel Luer engages the "Y-Arm".<br />
• Pinch (hold) the Gray Control Catheter with the left thumb and forefinger .<br />
to hold Occluder in position (Fig. D-7b, next page).<br />
• Pull the Mandrel Luer gently to form the disc (Fig. D-7c, next page).<br />
– The operator will feel a light tactile “stopping” sensation.<br />
– Avoid pulling left atrial eyelet against the Green Delivery Catheter tip.<br />
• Repeat the “Push / Pinch / Pull” sequence until the left atrial disc is formed to complete the deployment.<br />
D-8
Left Atrial Disc Deployment<br />
PUSH PINCH PULL<br />
Figure D-7a<br />
Figure D-7b<br />
Figure D-7c<br />
D-9
Transition — Left-to-Right<br />
Once the central eyelet exits the catheter tip, the operator will prepare to appose the formed left atrial disc against the septum.<br />
• Pull lightly on Tan Mandrel to flatten left atrial disc (Fig. D-8a).<br />
• Pull entire delivery system gently to appose the left atrial disc to the septum (Fig. D-8b).<br />
– Confirm contact with the septum on echocardiography.<br />
– Do not pull firmly against the septum.<br />
• Hold Gray Control Catheter and pull the Green Delivery Catheter gently until the "Y-Arm" .<br />
contacts the Mandrel Luer to prepare for right atrial disc deployment.<br />
• Tighten the Mandrel Luer (Fig. D-8c).<br />
Figure D-8a – Left disc formation complete,<br />
formed left disc presented to septum<br />
Figure D-8b – Left hand pulls,<br />
right hand holds<br />
Figure D-8c – Tighten Tan Mandrel Luer<br />
D-10
Right Atrial Disc Deployment<br />
To deliver the right atrial disc:<br />
• Hold the Green Delivery Catheter in the left hand to stabilize the device against the septum.<br />
• Push the Gray Control Catheter smoothly with the right hand to form the right atrial disc (Fig. D-9).<br />
• Tighten the Gray Control Catheter Luer (Fig. D-10).<br />
The Occluder is now fully formed and prepared for lock release.<br />
Figure D-9 Figure D-10 –<br />
Right disc complete,<br />
tighten control Luer<br />
D-11
Lock Release<br />
Lock release is a critical step in Occluder deployment and should be performed under ciné to ensure accuracy. Tension on<br />
the septum, caused by failure to fix the Gray Control Catheter position, may pull the Occluder through the defect from leftto-right.<br />
Allowing the Gray Control Catheter to push against the right disc may dislodge the Occluder to the left.<br />
When appropriate, confirm position of the device on echocardiography.<br />
• Remove the Red Retrieval Cord Cap and assure that the Retrieval Cord is free (Fig. D-11).<br />
• Hold the "Y-Arm" with left hand to prepare for lock release.<br />
• Loosen Mandrel Luer (Fig. D-12).<br />
• Pull the Tan Mandrel firmly and quickly with right hand to release the lock (Fig. D-13).<br />
–.. Lock loop deploys through slotted tip while the Occluder is held in position between the tip .<br />
of the Gray Control Catheter and the flare on the Tan Mandrel tip.<br />
• Continue to the pull the entire length of the Tan Mandrel from the Green Delivery Catheter while holding the Green<br />
Delivery Catheter in a fixed position.<br />
Figure D-11 – Remove Red<br />
Retrieval Cord Cap<br />
Figure D-12 –<br />
Loosen Mandrel Luer<br />
Figure D-13 – Quick, firm pull on the<br />
Tan Mandrel to lock<br />
D-12
Post-Lock Considerations<br />
The Occluder may change shape abruptly as the lock is released and as the Occluder conforms to the shape of the septum. The Occluder is<br />
compliant and the left and right discs may not appear parallel; as an example in the closure of a defect with deficient anterior-superior rim,<br />
it may be seen to be “embracing” the aorta.<br />
Now that the Occluder is loosened from the delivery system, a final echocardiographic analysis can be performed. Remember, the Occluder<br />
is still tethered to the delivery system by the Retrieval Cord should removal be required.<br />
Trivial residual leaks are likely to close quickly, often within the first few days following the procedure. Clinical experience has shown that<br />
small to moderate residual leaks typically close within six months of implantation. It is unlikely that residual leaks of greater than 3 mm will<br />
close. If atrial dimensions allow, a larger device will likely improve defect closure.<br />
D-13
Device Retrieval<br />
In the event of sub-optimal deployment, the Occluder may be removed.<br />
• Gently pull on Retrieval Cord to bring delivery system back into contact with the Occluder.<br />
• Replace and tighten Red Retrieval Cord Cap to secure the Retrieval Cord...<br />
• Loosen Gray Control Catheter Luer.<br />
• Pull Gray Control Catheter back into the Green Delivery Catheter.<br />
– Keep tip of Green Delivery Catheter away from lock loop.<br />
• Continue to unlock the Occluder until free of the septum.<br />
• Once free, pull entire system to groin and complete removal by pulling through the sheath.<br />
As long as the Occluder remains seated in the septum, the device will unlock and can be drawn into the Green<br />
Delivery Catheter. The operator must exercise care that the Green Delivery Catheter is withdrawn sufficiently to<br />
allow the locking loop to fully extend (Fig. D-14).<br />
Figure D-14<br />
Once the Occluder is free of the septum, the locking loop will present higher resistance and could cause the<br />
Retrieval Cord to break. The operator is cautioned to draw the entire Occluder / delivery system assembly back to<br />
the introducer sheath before completing device retrieval.<br />
D-14
Delivery System Removal<br />
When satisfied with Occluder position, the delivery system can be removed.<br />
• Ensure that the Red Retrieval Cord Cap has been removed.<br />
– Retrieval Cord is free on one end and looped through the right atrial eyelet.<br />
• Unlock the Gray Control Catheter<br />
• While holding the Gray Control Catheter, advance the Green Delivery Catheter such<br />
that it abuts the Occluder.<br />
• Slowly pull the Gray Control Catheter until catheter and Retrieval Cord exit the<br />
delivery system.<br />
– Dedicated Retrieval Cord lumen prevents tangling with other components.<br />
• Pull the Green Delivery Catheter until it exits the introducer sheath.<br />
Figure D-15 — Retrieval Cord is free on one end and looped<br />
through the right atrial eyelet<br />
D-15
Review<br />
ALWAYS<br />
• Use a light touch.<br />
• Move one component at a time.<br />
• Lock the Mandrel Luer at completion of left atrial disc.<br />
• Lock Gray Control Catheter Luer at completion of right atrial disc.<br />
• Make smooth transition from left atrial disc to right atrial disc.<br />
– Appose left atrial disc gently to left septum.<br />
– Hold Gray Control Catheter.<br />
– Pull Green Delivery Catheter to prepare for right atrial disc deployment.<br />
NEVER<br />
• Never... Pull the left atrial eyelet against the Green Delivery Catheter.<br />
. . – Premature lock may result.<br />
• Never... Pull the left atrial disc firmly against the septum.<br />
– Premature lock may result.<br />
• Never... Push the Tan Mandrel.<br />
D-16
tips for success<br />
E-1
Tips for Success<br />
The GORE HELEX Septal Occluder is a compliant device that quickly forms to the shape of the heart, reducing the potential for erosion<br />
through delicate tissues. Consequently, the Occluder can be positioned to close some complex defects, such as those with deficient<br />
anterior-superior rims.<br />
Though the GORE HELEX Septal Occluder is easy to deploy, there is a learning curve associated with achieving successful deployment.<br />
The following sections elaborate on the Occluder design and describe some of the techniques that cardiologists have found useful to<br />
improve defect closure and take advantage of the unique characteristics of this device. These discussions will point out some of the more<br />
common issues a cardiologist may encounter during early use of the GORE HELEX Septal Occluder.<br />
E-2
Premature Lock Release<br />
When the product is assembled, the three eyelets are loaded onto the Tan Mandrel, the locking loop is straightened and placed within the lumen of<br />
the Tan Mandrel at the distal tip. The tip is then flared to hold the eyelets in position. Once the Occluder is fully deployed across the septal defect,<br />
the Tan Mandrel is withdrawn, pulling the Tan Mandrel’s flared tip through the three eyelets. Upon release from the Tan Mandrel, the wire forms a<br />
loop and prevents the eyelets from escaping. Refer to the drawings on pages C-8 and C-9 to review product construction.<br />
The distal eyelet could become dislodged during loading or during extended repositioning and lead to premature lock release. Inadvertent lock<br />
release during left atrial disc conformation can be prevented by maintaining 3 – 5 mm between the tip of the Green Delivery Catheter and the left<br />
atrial eyelet. Once the left atrial disc is formed and seated against the septum, only mild tension on the delivery system is necessary to keep the<br />
Occluder seated. Greater tension on the system may cause the disc to pull through the septum, or it may cause the lock mechanism to partially<br />
release.<br />
Under high resolution fluoroscopy, the clinician may detect that the locking loop is no longer straight within the Green Delivery Catheter (Fig. E-1).<br />
Under fluoroscopy, a device that has been released will appear out of position or “floppy.” The operator will notice that the device no longer responds<br />
to Tan Mandrel manipulation (Figs. E-2 and E-3). Further delivery system manipulation will eventually result in full lock release. A prematurely released<br />
device must be removed and replaced with a new device.<br />
Figure E-1<br />
Figure E-2<br />
Figure E-3<br />
E-3
Kinked Tan Mandrel<br />
The function of the Tan Mandrel is twofold; extension elongates the Occluder during loading or repositioning and withdrawal configures the discs. .<br />
The Tan Mandrel is not radiopaque, however the Mandrel Stinner within the Tan Mandrel is visible under fluoroscopy. If the Tan Mandrel becomes<br />
kinked, the device will appear “off-center” with respect to the delivery system. Ciné will reveal that the Mandrel Stiffener and the locking loop are no<br />
longer alligned with the delivery system.<br />
The kinked Tan Mandrel is corrected by withdrawing the Tan Mandrel until the device assumes normal configuration. Once the Tan Mandrel is<br />
straightened, the device should deploy normally. If deployment problems persist, the device and delivery system should be removed and a new .<br />
device selected for use.<br />
E-4
“Missed” Right Atrial Eyelet<br />
In an optimal deployment, the lock sets when the Tan Mandrel is removed, capturing all three eyelets. Inappropriate catheter manipulation<br />
or unexpected movement of the heart may result in failure to capture the right atrial eyelet. Ciné of the Occluder in side view will quickly<br />
reveal if all eyelets are captured (Fig. E-4). A slight tug on the Retrieval Cord will demonstrate whether the eyelet moves with the device or<br />
independent of the device.<br />
Figure E-4<br />
E-5
Uneven Deployment<br />
The Occluder is designed to provide one and one-quarter discs on each side of the defect, separated by the central (septal) eyelet. Inappropriate<br />
tension, improper sizing, or oddly shaped defects may cause more of the Occluder to be configured in either the left or the right atrium (note<br />
position of central eyelet). The Occluder may be easily repositioned to correct this problem by extending the Tan Mandrel and withdrawing the<br />
control catheter in small increments until sufficient device has been recovered to correct the deployment.<br />
If an Occluder pulls through the defect repeatedly, there is a risk of embolization. The chosen device may be too small for the defect, or too large to<br />
properly configure within the atrium. An alternative device size should be utilized.<br />
Figure E-5 — Deployment favors right<br />
atrium<br />
Figure E-6 — Deployment favors left<br />
atrium<br />
E-6
Broken Retrieval Cord<br />
If, prior to final lock release, the Gray Control Catheter can be withdrawn without any corresponding motion of the Occluder, the clinician should<br />
suspect a broken or lost Retrieval Cord. Once the Retrieval Cord is broken or lost, standard interventional retrieval techniques (snares, retrieval<br />
baskets, etc.) must be employed should emergency recapture become necessary (see Embolization / Emergency Recapture, page E-10).<br />
The simplest cause might be that the Red Retrieval Cord Cap has become loosened, allowing the cord to slip out of reach. The application of a<br />
Kelly forcep across the entire delivery system may allow the Retrieval Cord to be fixed and allow the unlocking and withdrawal of the Occluder to<br />
continue. Should the cord break during unlocking, the device is considered at risk for embolization; emergency recapture procedures should be<br />
prepared immediately. Replacement of the Red Retrieval Cord Cap following lock release will ensure that the Retrieval Cord is under control.<br />
E-7
Improper “Feel”<br />
Clinicians quickly become accustomed to the appropriate “feel” of the GORE HELEX Septal Occluder. Any significant change in the force required to<br />
manipulate the device should alert the operator to consider the following possibilities:<br />
Repositioning<br />
If the Occluder has been repositioned extensively during deployment or if the device was loaded using inappropriate force, the right atrial eyelet<br />
could have become elongated. Though mild elongation of the formed wire recovers without problem, the Retrieval Cord could become trapped or<br />
entangled within the windings. In that condition, the operator will feel greater than normal resistance when attempting to withdraw the Gray Control<br />
Catheter during final release. If such a condition is encountered, the operator should replace the Red Retrieval Cord Cap or otherwise gain control of<br />
the Retrieval Cord such that the Occluder can be retrieved using the delivery system.<br />
E-8
Excessive Force Encountered During Unlocking<br />
If an Occluder must be unlocked and removed, following either a successful lock release or one that failed to capture all eyelets, the Tan Mandrel can<br />
no longer provide alignment of the eyelets that would guide them back into the Green Delivery Catheter. The center eyelet may “snag” on the Green<br />
Delivery Catheter tip during recapture, and cannot be easily brought into the delivery catheter (Fig. E-7). Manipulation of the Green Delivery Catheter<br />
with mild tension on the septum may help bring the center eyelet into the Green Delivery Catheter. If the entire delivery system is withdrawn, the<br />
Occluder will continue to unlock, and can safely be withdrawn. It may be necessary to remove the device and the sheath together.<br />
The Green Delivery Catheter must be withdrawn sufficiently during unlocking to allow the lock to fully extend (Fig. E-8) at each perforation in the<br />
ePTFE membrane and at each eyelet. Unlocking should always be performed under fluoroscopy at full magnification. Any extension of the eyelets, as<br />
shown in the accompanying image (Fig. E-9), indicates that too much force has been applied.<br />
When excessive force is applied, the Retrieval Cord may break or the Occluder frame could fracture. In either case, embolization is possible.<br />
Figure E-7<br />
Figure E-8 Figure E-9<br />
E-9
Embolization / Emergency Recapture<br />
Should the Occluder embolize from the defect, or if control of the device is lost due to Retrieval Cord breakage or device fracture, it is<br />
recommended that a large diameter sheath (such as an 11 Fr Mullins-type sheath) be exchanged and brought as close to the device as possible.<br />
The Occluder can be snared easily and brought into a larger sheath. While snaring the right atrial eyelet would be optimal, snaring any portion of<br />
the device will likely result in successful recapture. It can be difficult to recapture an embolized device through the 10 Fr Green Delivery Catheter.<br />
E-10
Fluoroscopic Appearance<br />
When deployed in a model having uniform dimensions, the Occluder appears planar and parallel (Fig. E-10). Notice that from the center<br />
eyelet the two radial arms are placed on opposite sides of the septum, the lock mechanism is straight as it aligns the eyelets and the lock loop is<br />
fully curled, capturing all three eyelets and securely locking the device in place.<br />
Septal anatomy, however, seldom allows the Occluder to take on such a theoretically ideal shape after deployment. Variation in the<br />
thickness of the septum and the proximity of the defect to other cardiac structures may cause the two discs to appear distinctly<br />
non-parallel (Figs. E-11 thru E-13). Apposition to the septum is more important than fluoroscopic appearance. A successful implant<br />
should rest in a planar condition relative to the septum. The position can be confirmed by TEE / ICE or by angiography. A right<br />
atrial or pulmonary artery contrast injection with observation of the levophase is used to illustrate left and right septal planes and<br />
to confirm that the Occluder is well apposed.<br />
Devices should be removed if:<br />
• An excessive shunt persists<br />
• The discs are not apposed to the septum<br />
• The right atrial eyelet was not captured<br />
Figure E-10<br />
Keep in mind that the disc-to-disc spacing usually becomes smaller in the first 30 minutes following deployment as the Occluder<br />
“settles” into place and further conforms to the cardiac anatomy.<br />
Figure E-11 Figure E-12 Figure E-13<br />
E-11
Suggested Reading<br />
Atrial Septal Defect References<br />
1. Zahn EM, Wilson N, Cutright W, Latson LA. Development and testing of the Helex Septal Occluder, a new expanded polytetrafluoroethylene atrial septal<br />
defect occlusion system. Circulation 2001;104(6):711-716.<br />
2. Hein R, Büscheck F, Fischer E, et al. Atrial and ventricular septal defects can safely be closed by percutaneous intervention. Journal of Interventional<br />
Cardiology 2005;18(6):515-522.<br />
3. Latson LA, Jones TK, Jacobson J, Zahn E, Rhodes JF. Analysis of factors related to successful transcatheter closure of secundum atrial septal defects<br />
using the HELEX Septal Occluder. American Heart Journal 2006;151(5):1129.e7-1129.e11.<br />
4. Jones TK, Latson LA, Zahn E, et al; for the Multicenter Pivotal Study of the HELEX Septal Occluder Investigators. Results of the U.S. Multicenter<br />
Pivotal Study of the HELEX Septal Occluder for percutaneous closure of secundum atrial septal defects. Journal of the American College of Cardiology<br />
2007;49(22):2215-2221.<br />
5. Kozlik-Feldmann R, Dalla Pozza R, Römer U, et al. First experience with the 2005 modified <strong>Gore</strong> Helex ASD occluder system. Clinical Research in<br />
Cardiology 2006;95(9):468-473.<br />
6. Smith BG, Wilson N, Richens T, Knight WB. Midterm follow-up of percutaneous closure of secundum atrial septal defect with Helex Septal Occluder.<br />
Journal of Interventional Cardiology 2008;21(4):363-368.<br />
7. Fagan T, Dreher D, Cutright W, Jacobson J, Latson L; GORE HELEX Septal Occluder Working Group. Fracture of the GORE HELEX Septal Occluder:<br />
associated factors and clinical outcomes. Catheterization & Cardiovascular Interventions 2009;73(7):941-948.<br />
F-1
Suggested Reading<br />
Patent Foramen Ovale References<br />
1. Sievert H, Horvath K, Zadan E, et al. Patent foramen ovale closure in patients with transient ischemia attack/stroke. Journal of Interventional Cardiology<br />
2001;14(2): 261-266.<br />
2. Krumsdorf U, Ostermayer S, Billinger K, et al. Incidence and clinical course of thrombus formation on atrial septal defect and patient foramen ovale<br />
closure devices in 1,000 consecutive patients. Journal of the American College of Cardiology 2004;43(2):302-309.<br />
3. Billinger K, Ostermayer SH, Carminati M, et al. HELEX Septal Occluder for transcatheter closure of patent foramen ovale: multicentre experience.<br />
EuroIntervention 2006;1(4):465-471.<br />
4. Ponnuthurai FA, van Gaal WJ, Burchell A, Mitchell A, Wilson N, Ormerod O. Single centre experience with GORE-HELEX Septal Occluder for closure of<br />
PFO. Heart, Lung & Circulation 2008;18(2):140-142.<br />
5. von Bardeleben RS, Richter C, Otto J, et al. Long term follow up after percutaneous closure of PFO in 357 patients with paradoxical embolism: difference<br />
in occlusion systems and influence of atrial septum aneurysm. International Journal of Cardiology 2009;34(1):33-41.<br />
6. Staubach S, Steinberg DH, Zimmermann W, et al. New onset atrial fibrillation after patent foramen ovale closure. Catheterization & Cardiovascular<br />
Interventions 2009;74(6):889-895.<br />
2
selected data from<br />
the fda clinical trial<br />
G-1
Selected Data from the US Clinical Trial<br />
ADVERSE EVENTS<br />
Three US clinical studies were conducted to evaluate the GORE HELEX Septal Occluder. These studies were performed with the original delivery system.<br />
The product described in the Instructions for Use is the same Occluder with a modified delivery system. Please note that the modified delivery system<br />
was not evaluated under the original US clinical study.<br />
The GORE HELEX Septal Occluder was evaluated in a Feasibility Study (two center, single arm), a Pivotal Study (multi-center, non-randomized), and a<br />
Continued Access Study (multi-center, single arm, prospective). The Feasibility Study included 51 subjects treated with the device. The Pivotal Study<br />
compared the device to surgical closure of ostium secundum atrial septal defects. Investigators were required to complete three device training cases.<br />
The Pivotal Study included 119 non-training subjects treated with the device and 128 subjects treated with surgical closure. The Continued Access Study<br />
included 137 non-training subjects treated with the device as of August 1, 2006, of which 122 subjects completed the 12 month follow-up evaluation.<br />
These subjects form the basis of the observed adverse event data reported in the following section. An independent Data Safety Monitoring Board<br />
(DSMB) reviewed all reported adverse events to determine device / procedure relationship and event severity (major or minor). An event was considered<br />
major if it required reintervention, readmission to the hospital or resulted in permanent damage or deficit. For the GORE HELEX Septal Occluder studies,<br />
reintervention was defined as chronic medical, and acute surgical or interventional cardiology therapies.<br />
Deaths<br />
There was one post-operative death in the surgical control treatment arm of the Pivotal Study. Subject died of complications related to post-pericardiotomy<br />
syndrome on Day 10 post-surgery. No deaths have been reported in the device subjects in the Feasibility, Pivotal, or Continued Access Studies.<br />
Observed Adverse Events<br />
Major adverse events reported through the 12 month follow-up for the Feasibility, Pivotal and Continued Access Studies are presented in Table G-1.<br />
G-2
Major Adverse Events<br />
Table G-1<br />
Number of Subjects with Successful Device Delivery by Category of Major Adverse Events<br />
— GORE HELEX Septal Occluder Studies Events Reported Through 12 Month Follow-up<br />
Pivotal Study<br />
Continued<br />
Feasibility Study Device Arm Surgery Arm Difference (95% CI) 1 Access Study<br />
Subjects Evaluable for Safety 51 119 128 137<br />
Deaths (Any Cause) 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Subjects With One<br />
or More Major Adverse Events<br />
2 (3.9%) 7 (5.9%) 14 (10.9%) -5.1% (-12.1%, 1.9%) 3 (2.2%)<br />
Cardiac 1 (2.0%) 2 (1.7%) 10 (7.8%) -6.1% (-11.5%, -0.8%) 2 (1.5%)<br />
Arrhythmia 1 (2.0%) 0 0 0<br />
Bleeding (treatment required) 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Device Embolization (post-procedure) 2 0 2 (1.7%) n / a n / a 2 (1.5%)<br />
Pulmonary Edema 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Post-Pericardiotomy Syndrome n / a n / a 8 (6.3%) n / a<br />
Integument (Skin) 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Allergic Reaction 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Neurologic 1 (2.0%) 2 (1.7%) 0 1.7% (-0.6%, 3.9%) 0<br />
Migraine (new) 0 2 (1.7%) 0 1.7% (-0.6%, 3.9%) 0<br />
Paresthesia 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Seizure 1 (2.0%) 0 0 0<br />
Pulmonary (Respiratory) 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Stridor 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Vascular 0 1 (0.8%) 1 (0.8%) 0.1% (-2.2%, 2.3%) 0<br />
Hemorrhage.<br />
(treatment or intervention required)<br />
0 1 (0.8%) 1 (0.8%) 0.1% (-2.2%, 2.3%) 0<br />
Wound 0 0 2 (1.6%) -1.6% (-3.8%, 0.7%) 0<br />
Hernia 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Scarring or Scar Related 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Device (GORE HELEX Septal Occluder) 0 3 (2.5%) n / a n / a 1 (0.7%)<br />
Allergic Reaction 0 1 (0.8%) n / a n / a 0<br />
Device Size Inappropriate 0 2 (1.7%) n / a n / a 0<br />
Device Removal Due to Fracture 0 0 n / a n / a 1 (0.7%)<br />
Other 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Anemia 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
NOTE: Analysis includes all Feasibility<br />
subjects, non-training Pivotal subjects and<br />
Continued Access subjects enrolled as of<br />
08/01/2006 and evaluated through 12<br />
month follow-up.<br />
.<br />
n / a: Not applicable<br />
1<br />
Differences between Pivotal device and<br />
surgery groups and associated 95%<br />
confidence intervals.<br />
2<br />
The four embolized devices were removed<br />
by transcatheter technique.<br />
G-3
Minor Adverse Events<br />
Table G-2a<br />
Number of Subjects with Successful Device Delivery by Category of Minor Adverse Events<br />
— GORE HELEX Septal Occluder Studies Events Reported Through 12 Month Follow-up<br />
Pivotal Study<br />
Continued<br />
Feasibility Study Device Arm Surgery Arm Difference (95% CI) 1 Access Study<br />
Subjects Evaluable for Safety 51 119 128 137<br />
Subjects With One or<br />
More Minor Adverse Events<br />
19 (37.3%) 34 (28.6%) 36 (28.1%) 0.4% (-10.9%, 11.8%) 46 (33.6%)<br />
Cardiac 7 (13.7%) 14 (11.8%) 26 (20.3%) -8.5% (-17.8%, 0.7%) 7 (5.1%)<br />
Arrhythmia 3 (5.9%) 10 (8.4%) 5 (3.9%) 4.5% (-1.5%, 10.5%) 4 (2.9%)<br />
Chest Pain 1 (2.0%) 2 (1.7%) 0 1.7% (-0.6%, 3.9%) 0<br />
Embolus – Air 1 (2.0%) 0 2 (1.6%) -1.6% (-3.8%, 0.7%) 0<br />
Hemopericardium 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Hypotension 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Other – Cardiac Complication 0 0 0 1 (0.7%)<br />
Palpitations 1 (2.0%) 0 0 1 (0.7%)<br />
Pericardial Effusion 1 (2.0%) 1 (0.8%) 5 (3.9%) -3.1% (-6.9%, 0.8%) 1 (0.7%)<br />
Pneumopericardium 0 0 3 (2.3%) -2.3% (-5.1%, 0.4%) 0<br />
Post-Pericardiotomy Syndrome n / a n / a 10 (7.8%) n / a<br />
Syncope 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Vaso-Vagal Reaction 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Integument 0 0 0 1 (0.7%)<br />
Abrasion 0 0 0 1 (0.7%)<br />
Musculo-Skeletal 0 0 0 1 (0.7%)<br />
Chest Pain 0 0 0 1 (0.7%)<br />
Neurologic 7 (13.7%) 8 (6.7%) 0 6.7% (2.3%, 11.1%) 17 (12.4%)<br />
Dizziness 2 (3.9%) 0 0 0<br />
Headache 4 (7.8%) 5 (4.2%) 0 4.2% (0.7%, 7.7%) 15 (10.9%)<br />
Migraine (pre-existing) 0 0 0 2 (1.5%)<br />
Migraine (new) 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 1 (0.7%)<br />
Paresthesia 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Visual Field Disturbance or Defect 1 (2.0%) 2 (1.7%) 0 1.7% (-0.6%, 3.9%) 0<br />
Pulmonary (Respiratory) 0 1 (0.8%) 8 (6.3%) -5.4% (-10.1%, -0.7%) 1 (0.7%)<br />
Atelectasis 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Congestion 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Dyspnea 0 0 0 1 (0.7%)<br />
Pleural Effusion (not requiring drainage) 0 0 3 (2.3%) -2.3% (-5.1%, 0.4%) 0<br />
Pneumothorax 0 0 4 (3.1%) -3.1% (-6.3%, 0.0%) 0<br />
Pneumonia 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Minor adverse events<br />
reported through the<br />
12 month follow-up for<br />
the Feasibility, Pivotal<br />
and Continued Access<br />
Studies are presented<br />
in Table G-2a and .<br />
Table G-2b.<br />
NOTE: Analysis includes all Feasibility<br />
subjects, non-training Pivotal subjects and<br />
Continued Access subjects enrolled as of<br />
08/01/2006 and evaluated through 12<br />
month follow-up.<br />
.<br />
n / a: Not applicable<br />
1<br />
Differences between Pivotal device and<br />
surgery groups and associated 95%<br />
confidence intervals.<br />
G-4
Minor Adverse Events (continued)<br />
Table G-2b<br />
Number of Subjects with Successful Device Delivery by Category of Minor Adverse Events<br />
— GORE HELEX Septal Occluder Studies Events Reported Through 12 Month Follow-up<br />
Pivotal Study<br />
Continued<br />
Feasibility Study Device Arm Surgery Arm Difference (95% CI) 1 Access Study<br />
Renal and Uro-Genital 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Urinary Retention 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Anesthesia 1 (2.0%) 3 (2.5%) 1 (0.8%) 1.7% (-1.4%, 4.9%) 7 (5.1%)<br />
Abdominal Pain 0 0 0 1 (0.7%)<br />
Bleeding (no treatment required) 0 0 0 1 (0.7%)<br />
Corneal Abrasion 0 0 0 1 (0.7%)<br />
Emesis 0 1 (0.8%) 1 (0.8%) 0.1% (-2.2%, 2.3%) 1 (0.7%)<br />
Nausea 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Nausea with Emesis 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 4 (2.9%)<br />
Paresthesia 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Sore Throat 1 (2.0%) 0 0 0<br />
Drug-Related 5 (9.8%) 6 (5.0%) 2 (1.6%) 3.5% (-1.0%, 7.9%) 7 (5.1%)<br />
Allergic Response 1 (2.0%) 0 2 (1.6%) -1.6% (-3.8%, 0.7%) 0<br />
Bruising / Ecchymosis 2 (3.9%) 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 4 (2.9%)<br />
Gastric Irritation 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 0<br />
Nosebleed 1 (2.0%) 4 (3.4%) 0 3.4% (0.2%, 6.5%) 3 (2.2%)<br />
Rectal Bleeding 1 (2.0%) 0 0 0<br />
Wound 2 (3.9%) 1 (0.8%) 4 (3.1%) -2.3% (-5.8%, 1.3%) 3 (2.2%)<br />
Access Site Bleeding 0 1 (0.8%) 0 0.8% (-0.8%, 2.4%) 1 (0.7%)<br />
Access Site Pain 1 (2.0%) 0 0 0<br />
Hematoma<br />
(not requiring treatment or intervention)<br />
1 (2.0%) 0 0 2 (1.5%)<br />
Scarring or Scar Related 0 0 2 (1.6%) -1.6% (-3.8%, 0.7%) 0<br />
Suture Related 0 0 1 (0.8%) -0.8% (-2.4%, 0.8%) 0<br />
Sternal Wire n / a n / a 1 (0.8%) n /a<br />
Delivery System 2 (3.9%) 1 (0.8%) n / a n / a 0<br />
Tan Mandrel Kink 1 (2.0%) 0 n / a n / a 0<br />
Retrieval Cord Break 1 (2.0%) 0 n / a n / a 0<br />
Retrieval Cord Detachment 0 1 (0.8%) n / a n / a 0<br />
Device (GORE HELEX Septal Occluder) 3 (5.9%) 6 (5.0%) n / a n / a 10 (7.3%)<br />
Fracture-Wire Frame 3 (5.9%) 6 (5.0%) n / a n / a 10 (7.3%)<br />
Non-Investigational Device Related 0 0 0 1 (0.7%)<br />
Contrast Reaction 0 0 0 1 (0.7%)<br />
Other 0 0 0 3 (2.2%)<br />
Fever 0 0 0 1 (0.7%)<br />
Nosebleed 0 0 0 1 (0.7%)<br />
Other 0 0 0 1 (0.7%)<br />
Minor adverse events<br />
reported through the<br />
12 month follow-up for<br />
the Feasibility, Pivotal<br />
and Continued Access<br />
Studies are presented<br />
in Table G-2a and .<br />
Table G-2b.<br />
NOTE: Analysis includes all Feasibility<br />
subjects, non-training Pivotal subjects and<br />
Continued Access subjects enrolled as of<br />
08/01/2006 and evaluated through 12<br />
month follow-up.<br />
.<br />
n / a: Not applicable<br />
1<br />
Differences between Pivotal device and<br />
surgery groups and associated 95%<br />
confidence intervals.<br />
G-5
Clinical Summary<br />
Three US clinical studies were conducted to evaluate the GORE HELEX Septal Occluder. These studies were performed with the original<br />
delivery system. The product described in the Instructions for Use is the same Occluder with a modified delivery system. Please note that<br />
the modified delivery system was not evaluated under the original US clinical study.<br />
Feasibility Study<br />
The GORE HELEX Septal Occluder was evaluated in a single arm, prospective<br />
Feasibility Study intended to provide an initial evaluation of the safety and<br />
performance of the GORE HELEX Septal Occluder for closure of ostium secundum<br />
atrial septal defects (ASDs). Two US sites participated in the study and enrolled<br />
63 subjects. The median subject age was 11 years (range: 6 months to 65 years)<br />
and 65% of the subjects were female. The median estimated defect size was<br />
12 mm (range: 4.5 to 20 mm), in subjects with a delivery attempt (n = 59), the<br />
median stretched defect size was 18 mm (range 6 to 26 mm).<br />
The GORE HELEX Septal Occluder was successfully implanted in 86.4% (51 / 59)<br />
of subjects with a delivery attempt. Subjects with a successful device delivery<br />
were followed for 12 months. No deaths, device embolizations, thrombus on the<br />
device, or erosions requiring surgery were reported through the 12 month followup.<br />
There were no repeat procedures to the target ASD in the study population.<br />
Of subjects evaluated for 12 month ASD closure by independent<br />
echocardiography core laboratory review, 94.6% (35 / 37) had a successful<br />
defect closure (complete occlusion or clinically insignificant leak). Clinically<br />
significant leaks were present in two subjects (5.4%) at the 12 month follow-up<br />
evaluation. Clinical success, a composite of safety (no major adverse events or<br />
repeat procedure) and efficacy (clinical closure at 12 months), was achieved in .<br />
89.5% of subjects (34 / 38) available for evaluation.<br />
Table G-3<br />
GORE HELEX Septal Occluder Feasibility Study<br />
Principal Safety and Effectiveness Results<br />
Feasibility<br />
Technical Success 1 51 / 59 (86.4%)<br />
Clinical Closure Success 2<br />
Pre-Discharge 49 / 51 (96.1%)<br />
6 Months 30 / 31 (96.8%)<br />
12 Months 35 / 37 (94.6%)<br />
Principal Safety Measures<br />
Major Adverse Events 12 Months 2 / 51 (3.9%)<br />
Minor Adverse Events 12 Months 19 / 51 (37.3%)<br />
Survival at 365 Days (K-M) 100%<br />
Composite Clinical Success 12 Months 3 34 / 38 (89.5%)<br />
1 Technical Success defined as successful delivery of the device.<br />
2 Clinical Closure Success defined as defect that is either Completely Occluded or Clinically Insignificant Leak. Leak status was<br />
evaluated by the investigational sites at pre-discharge and 6 months and by the echocardiography core laboratory at 12 months.<br />
3 Composite Clinical Success defined as no major adverse event or repeated procedure and clinical closure success at 12 months.<br />
G-6
Pivotal and Continued Access Studies<br />
PURPOSE<br />
The purpose of the Pivotal Study was to evaluate the safety and effectiveness of the GORE HELEX Septal Occluder for the closure of ostium<br />
secundum atrial septal defects. The purpose of the Continued Access Study was to evaluate design modifications to the GORE HELEX Septal<br />
Occluder. The design modifications incorporated into the GORE HELEX Septal Occluder were implemented based on investigator input and feedback<br />
given during the Feasibility and Pivotal Trials.<br />
G-7
Patient Selection<br />
PIVOTAL STUDY<br />
The Pivotal Study enrolled 143 non-training subjects in the device treatment arm and 128 subjects in the surgical control arm at 14 clinical sites within<br />
the US. Investigators who did not participate in the Feasibility Study were required to complete three device training cases. Fifty subjects were enrolled as<br />
training cases and these subjects were excluded from the primary endpoint analyses.<br />
Enrolled patients had echocardiographic evidence of an ostium secundum atrial septal defect and right heart volume overload (or as indicated by a Q P :Q S<br />
ratio of ≥ 1.5:1 for the device treatment arm). Patients enrolled in the device treatment arm had a defect size of 22 mm or less as measured by balloon<br />
sizing and an adequate rim to retain the device present in ≥ 75% of the circumference of the defect. Patients enrolled in the surgical control arm had<br />
surgical intervention within 12 months of IRB approval for the study, a minimum body weight of 8 kg at the time of surgery, and a pre-operative, nonanesthesized<br />
echocardiogram performed within six months of the ASD surgery date. Exclusion criteria included:<br />
• Patient had concurrent cardiac defect(s) that were associated with potentially significant morbidity or mortality that could elevate morbidity / mortality<br />
beyond what is common for ASD or that is expected to require surgical treatment within two years for the device treatment group or five years for the<br />
surgical control group.<br />
• Patient had systemic or inherited conditions that would significantly increase patient risk of major morbidity and mortality during the term of the study.<br />
• Patient had an uncontrolled arryhthmia.<br />
• Patient had history of stroke.<br />
• Patient was pregnant or lactating.<br />
• Patient had contraindication to antiplatelet therapy (device treatment arm).<br />
• Patient had a pulmonary artery systolic pressure greater than half the systemic systolic arterial pressure unless the indexed pulmonary artery<br />
resistance was < 5 Woods units (device treatment arm).<br />
• Patient had significant atrial septal aneurysm (device treatment arm).<br />
• Patient had multiple defects that would require placement of greater than one device (device treatment arm).<br />
• Patient had an atrial septum > 8 mm thick (device treatment arm).<br />
• Patient had an attempted transcatheter septal defect closure device placement within one month of surgery.<br />
(surgical control arm).<br />
• Patient had significant pulmonary hypertension at the time of surgery (surgical control arm).<br />
• Patient had already completed a routine 12 month post-operative evaluation (surgical control arm).<br />
G-8
Continued Access Study<br />
The Continued Access Study enrolled 189 non-training subjects at 13 clinical sites within the US as of August 1, 2006. Investigators who did not<br />
participate in the Feasibility and Pivotal Studies were required to complete three device training cases and these cases were excluded from the<br />
primary analyses. Enrolled subjects met the same inclusion and exclusion criteria as the Pivotal Study subjects.<br />
G-9
Demographics<br />
The median age of the 143 subjects enrolled in the device treatment arm of the Pivotal Study was 6.5 years (range: 1.4 to 72.4 years) and 65.7%<br />
of the subjects were female. The median estimated defect size was 10 mm (range: 1.3 to 25 mm) and in subjects with a delivery attempt (n = 134),<br />
the median stretched defect size was 14 mm (range 5 to 24 mm).<br />
The median age of the 128 subjects enrolled in the surgical control arm of the Pivotal Study was 4.7 years (range: 0.6 to 70.4 years), and 63.3% of<br />
the subjects were female. The median estimated defect size was 15 mm (range: 1.5 to 42 mm).<br />
The median age of the 189 non-training subjects enrolled in the Continued Access Study was 5.4 years (range: 0.8 to 58.4 years) and 65.6% of the<br />
subjects were female. The median estimated defect size was 10.0 mm (range: 1.7 to 21.0 mm). In subjects with a delivery attempt (n = 160), the<br />
median stretched defect size was 14.0 mm (range: 4.5 to 22 mm).<br />
G-10
Subject Demographics<br />
Table G-4<br />
GORE HELEX Septal Occluder Studies — Subject Demographics<br />
Pivotal Study<br />
Continued<br />
Device Arm Surgery Arm Difference (95% CI) 1 Access Study<br />
Number of Subjects 143 128 189<br />
Gender<br />
Male 49 (34.3%) 47 (36.7%) -2.5% (-13.9%, 9.0%) 65 (34.4%)<br />
Female 94 (65.7%) 81 (63.3%) 2.5% (-9.0%, 13.9%) 124 (65.6%)<br />
Subject Ethnicity<br />
White or Caucasian 95 (66.4%) 84 (65.6%) 0.8% (-10.5%, 12.1%) 131 (69.3%)<br />
Black or African American 15 (10.5%) 9 (7.0%) 3.5% (-3.2%, 10.2%) 13 (6.9%)<br />
Hispanic or Latino 26 (18.2%) 23 (18.0%) 0.2% (-9.0%, 9.4%) 23 (12.2%)<br />
Asian 3 (2.1%) 7 (5.5%) -3.4% (-8.0%, 1.2%) 7 (3.7%)<br />
Other 3 (2.1%) 3 (2.3%) -0.2% (-3.8%, 3.3%) 11 (5.8%)<br />
Unknown 1 (0.7%) 2 (1.6%) -0.9% (-3.4%, 1.7%) 4 (2.1%)<br />
Subject Age (years)<br />
N 143 128 189<br />
Mean (Std Dev) 12.4 (14.0) 9.2 (12.2) 3.2 (0.1, 6.4) 8.9 (9.6)<br />
Median 6.5 4.7 5.4<br />
Range (1.4, 72.4) (0.6, 70.4) (0.8, 58.4)<br />
Weight (kg)<br />
N 143 128 189<br />
Mean (Std Dev) 35.6 (26.0) 27.5 (22.4) 8.2 (2.3, 14.0) 29.3 (22.3)<br />
Median 23.0 17.5 19.0<br />
Range (9.2, 132.5) (8.3, 135.0) (6.9, 114.0)<br />
Body Surface Area (BSA)<br />
N 143 128 189<br />
Mean (Std Dev) 1.08 (0.51) 0.91 (0.46) 0.2 (0.1, 0.3) 0.95 (0.47)<br />
Median 0.89 0.72 0.77<br />
Range (0.32, 2.61) (0.38, 2.01) (0.33, 2.40)<br />
Estimated ASD Size (mm)<br />
N 141 124 188<br />
Mean (Std Dev) 10.7 (3.8) 15.5 (6.3) -4.8 (-6.1, -3.6) 10.0 (3.2)<br />
Median 10.0 15.0 10.0<br />
Range (1.3, 25.0) (1.5, 42.0) (1.7, 21.0)<br />
NOTE: Analysis includes all Feasibility<br />
subjects, non-training Pivotal subjects and<br />
Continued Access subjects enrolled as of<br />
08/01/2006 and evaluated through 12<br />
month follow-up.<br />
1<br />
Differences between Pivotal device and<br />
surgery groups and associated 95%<br />
confidence intervals.<br />
G-11
Subject <strong>Medical</strong> History<br />
Table G-5<br />
GORE HELEX Septal Occluder Studies — Subject <strong>Medical</strong> History<br />
Pivotal Study<br />
Continued<br />
Device Arm Surgery Arm Difference (95% CI) 1 Access Study<br />
Subjects Enrolled 143 128 189<br />
General <strong>Medical</strong> History<br />
Previous Cardiac Surgery 8 (5.6%) 4 (3.1%) 2.5% (-2.4%, 7.3%) 9 (4.8%)<br />
ECG Abnormalities 72 (50.3%) 89 (69.5%) -19.2% (-30.6%, -7.7%) 109 (57.7%)<br />
Cardiac Arrhythmia(s) 12 (8.4%) 3 (2.3%) 6.0% (0.8%, 11.3%) 7 (3.7%)<br />
Chromosomal Abnormalities 4 (2.8%) 7 (5.5%) -2.7% (-7.4%, 2.1%) 16 (8.5%)<br />
Emotional or Psychiatric Problems 5 (3.5%) 0 (0.0%) 3.5% (0.5%, 6.5%) 7 (3.7%)<br />
Epilepsy 0 (0.0%) 0 (0.0%) 0.0% (0.0%, 0.0%) 2 (1.1%)<br />
Failure to Thrive 1 (0.7%) 5 (3.9%) -3.2% (-6.8%, 0.4%) 8 (4.2%)<br />
Migraines 3 (2.1%) 1 (0.8%) 1.3% (-1.5%, 4.1%) 3 (1.6%)<br />
Neurological Deficits / Symptoms 7 (4.9%) 5 (3.9%) 1.0% (-3.9%, 5.9%) 9 (4.8%)<br />
Other (non-ASD) Cardiac Disease 15 (10.5%) 5 (3.9%) 6.6% (0.5%, 12.6%) 22 (11.6%)<br />
Other Vascular Disease 2 (1.4%) 1 (0.8%) 0.6% (-1.8%, 3.1%) 3 (1.6%)<br />
Pre-Term Baby 6 (4.2%) 8 (6.3%) -2.1% (-7.4%, 3.3%) 15 (7.9%)<br />
Respiratory Difficulties 14 (9.8%) 13 (10.2%) -0.4% (-7.5%, 6.8%) 23 (12.2%)<br />
Hepatitis 0 (0.0%) 0 (0.0%) 0 (0.0%)<br />
Other 29 (20.3%) 43 (33.6%) -13.3% (-23.8%, -2.8%) 79 (41.8%)<br />
Current Medication<br />
Anti-Arrhythmic 7 (4.9%) 2 (1.6%) 3.3% (-0.8%, 7.5%) 0 (0.0%)<br />
Anti-Coagulant 2 (1.4%) 0 (0.0%) 1.4% (-0.5%, 3.3%) 2 (1.1%)<br />
Anti-Hypertensive 4 (2.8%) 2 (1.6%) 1.2% (-2.2%, 4.7%) 2 (1.1%)<br />
Anti-Platelet 10 (7.0%) 2 (1.6%) 5.4% (0.7%, 10.1%) 18 (9.5%)<br />
Diuretic 5 (3.5%) 5 (3.9%) -0.4% (-4.9%, 4.1%) 3 (1.6%)<br />
Other 36 (25.2%) 29 (22.7%) 2.5% (-7.6%, 12.7%) 55 (29.1%)<br />
NOTE: Analysis includes all Feasibility<br />
subjects, non-training Pivotal subjects and<br />
Continued Access subjects enrolled as of<br />
08/01/2006 and evaluated through 12<br />
month follow-up.<br />
1<br />
Differences between Pivotal device and<br />
surgery groups and associated 95%<br />
confidence intervals.<br />
G-12
Design<br />
PIVOTAL STUDY<br />
The Multicenter Pivotal Study of the GORE HELEX Septal Occluder was a non-randomized, controlled trial comparing safety and efficacy outcomes of<br />
the GORE HELEX Septal Occluder with traditional (open) surgical repair of atrial septal defects.<br />
The primary study endpoint was clinical success, a composite evaluation of safety and efficacy, which was evaluated at 12 months post-procedure.<br />
Clinical success was defined as: 1) A residual defect classified as either completely occluded or clinically insignificant leak as determined by<br />
echocardiography core lab assessment; 2) No repeat procedure to the target ASD; and 3) No major device- or procedure-related adverse events. The<br />
study was designed to demonstrate that the clinical success rate of the GORE HELEX Septal Occluder was not inferior to the clinical success rate for<br />
surgical closure of ASDs.<br />
Additional safety endpoints included the proportion of subjects experiencing one or more major and minor device-related and / or procedure-related<br />
adverse events through 12 months post-procedure. Additional efficacy endpoints included delivery (technical) success, defined as successful<br />
deployment and accurate placement of the GORE HELEX Septal Occluder to the target ASD, and treatment efficacy, defined as the proportion of<br />
subjects with a final residual defect assessment of clinically successful closure (completely occluded or clinically insignificant leak).<br />
CONTINUED ACCESS STUDY<br />
The Continued Access Study was a prospective, single-arm trial intended to evaluate design modifications to the GORE HELEX Septal Occluder. The<br />
design modifications incorporated into the GORE HELEX Septal Occluder were implemented based on investigator input and feedback given during the<br />
Feasibility and Pivotal Trials. The Continued Access Study endpoints were the same as those of the Pivotal Study and were evaluated at 12 months.<br />
G-13
Method<br />
PIVOTAL STUDY — DEVICE TREATMENT ARM<br />
For patients enrolled in the device treatment arm of the Pivotal Study, dimensional verification and characterization of the ASD and surrounding<br />
cardiac structures were performed per the investigator’s standard methods. An initial static measurement of the septal defect was obtained during<br />
echocardiographic visualization. A second measurement was taken utilizing a balloon to gently stretch the defect and measure the balloon’s<br />
waist (narrowest portion of the balloon), and the balloon stretched defect size was used to determine the optimal size of the GORE HELEX Septal<br />
Occluder per IFU recommendations. Fluoroscopic and echocardiographic guidance were used throughout the procedure for placement of, and at the<br />
completion of each procedure to assess the status of, the GORE HELEX Septal Occluder.<br />
There was no requirement for prior therapy or medical management. All subjects were placed on the investigator’s choice of antiplatelet therapy for<br />
six months following implantation of the GORE HELEX Septal Occluder, and on prophylactic, post-procedure antibiotic therapy consistent with the<br />
investigator’s routine procedure.<br />
Follow-up evaluations, which included a physical exam, ECG, and an assessment of the residual defect status by TTE, were performed at hospital<br />
discharge, and at 1, 6, and 12 months post-procedure. If the TTE was inconclusive, a TEE or angiography may have been performed. At the 6 and 12<br />
month follow-up visits, fluoroscopic examinations were performed to assess device integrity.<br />
G-14
Method<br />
PIVOTAL STUDY — SURGICAL CONTROL ARM<br />
Investigators identified surgical control subjects at their respective sites who had undergone an open-heart surgical ASD closure within 12 months<br />
of IRB approval of the Pivotal Study, and who also met the inclusion / exclusion criteria for the control arm. Open-heart surgical ASD repair was<br />
performed per the investigator’s standard procedure, and was achieved by suturing the defect edges or by implantation of autologous or synthetic<br />
patch materials over the defect.<br />
Subjects were placed on antiplatelet therapy and prophylactic, post-procedure antibiotic therapy at the investigator’s discretion and consistent<br />
with investigator’s standard method.<br />
Follow-up evaluations, which included a physical exam, ECG, and an assessment of the residual defect status by TTE, were performed at hospital<br />
discharge and at 12 months. If the TTE was inconclusive, a TEE or angiography may have been performed.<br />
CONTINUED ACCESS STUDY<br />
The methodology and follow-up of the Continued Access Study was the same as that of the device treatment arm of the Pivotal Study.<br />
G-15
Results<br />
PIVOTAL STUDY — DEVICE TREATMENT ARM<br />
The GORE HELEX Septal Occluder was successfully implanted in 88.1% (119 / 135) of subjects with a delivery attempt. No deaths, device-related<br />
thrombus, perforations, or erosions requiring surgery were reported. Major adverse events were reported in 5.9% of subjects with a successful<br />
delivery through the 12 month follow-up. Clinically successful closure (complete occlusion or clinically insignificant leak), as determined by<br />
echocardiographic core laboratory review, was achieved in 98.1% of subjects evaluated at 12 months post-procedure. The primary clinical<br />
success endpoint was achieved in 91.7% of subjects evaluated.<br />
PIVOTAL STUDY — SURGICAL CONTROL ARM<br />
Major adverse events were reported in 10.9% of control subjects. One death resulting from complications of post-pericardiotomy syndrome was<br />
reported. Clinically successful closure, as determined by echocardiographic core laboratory review, was achieved in 100% of subjects evaluated<br />
at 12 months post-procedure. Clinical success was achieved in 83.7% of subjects evaluated.<br />
CONTINUED ACCESS STUDY<br />
The GORE HELEX Septal Occluder was successfully implanted in 85.6% of subjects with an attempt. No deaths, device-related thrombus,<br />
perforations, or erosions requiring surgery were reported. Major adverse events were reported in 2.2% of subjects with a successful delivery who<br />
have been evaluated through 12 months. Clinically successful closure, as determined by echocardiographic core laboratory review, was achieved<br />
in 99.1% of subjects who have been evaluated at 12 months post-procedure. The primary clinical success endpoint was achieved in 96.7% of<br />
subjects evaluated.<br />
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Tables of Safety and Effectiveness Results<br />
The principal safety and effectiveness results through 12 months and the procedure outcomes for the Pivotal and Continued Access<br />
Studies are reported in Tables G-6 and G-7.<br />
Table G-6<br />
GORE HELEX Septal Occluder Studies — Principal Safety and Effectiveness Results<br />
Pivotal Study<br />
Study Outcomes Device Arm Surgery Arm Difference (95% CI) 4<br />
Continued<br />
Access Study<br />
Technical Success 1 119 / 135 (88.1%) n / a n / a 137 / 160 (85.6%)<br />
Clinical Closure Success 2<br />
Pre-Discharge 115 / 118 (97.5%) 128 / 128 (100%) -2.5% (-5.4%, 0.3%) 134 / 136 (98.5%)<br />
Month 6 99 / 101 (98.0%) n / a n / a 111 / 111 (100%)<br />
Month 12 103 / 105 (98.1%) 82 / 82 (100%) -1.9% (-4.5%, 0.7%) 116 / 117 (99.1%)<br />
Principal Safety Measures<br />
Major Adverse Events 12 Months 7 / 119 (5.9%) 14 / 128 (10.9%) -5.1% (-11.9%, 1.8%) 3 / 137 (2.2%)<br />
Minor Adverse Events 12 Months 34 / 119 (28.6%) 36 / 128 (28.1%) 0.4% (-10.8%, 11.7%) 46 / 137 (33.6%)<br />
Survival at 365 Days (K-M) 100% 99.2% -0.8% (-2.3%, 0.7%) 100%<br />
Composite Clinical Success 12 Months 3 100 / 109 (91.7%) 72 / 86 (83.7%) 8.0% (-1.3%, 17.2%) 116 / 120 (96.7%)<br />
NOTE: Analysis includes all non-training Pivotal subjects and Continued Access subjects enrolled as of 08/01/2006 and evaluated through 12 month follow-up.<br />
n / a: Not applicable.<br />
1<br />
Technical Success defined as successful delivery of the device in subjects with a delivery attempted.<br />
2<br />
Clinical Closure Success defined as residual defect that is either Completely Occluded or Clinically Insignificant Leak.<br />
Leak status was evaluated by the investigational sites at pre-discharge and six months and by the echocardiography core laboratory at 12 months.<br />
3<br />
Composite Clinical Success defined as no major adverse event or repeated procedure and clinical closure success at 12 months.<br />
4<br />
Differences between Pivotal device and surgery groups and associated 95% confidence intervals.<br />
G-17
Tables of Safety and Effectiveness Results<br />
Table G-7<br />
GORE HELEX Septal Occluder Studies — Procedural Outcomes<br />
Pivotal Study<br />
Device Arm Surgery Arm Difference (95% CI) 1<br />
Continued<br />
Access Study<br />
Subjects with Delivery Attempt / Surgery 135 128 160<br />
Total Time Under Fluoroscopy (minutes)<br />
N 134 n / a 155<br />
Mean (Std Dev) 28 (21) 23 (16)<br />
Median 22 19<br />
Range (6, 148) (5, 116)<br />
Total Time Under Anesthesia (minutes)<br />
N 133 128 155<br />
Mean (Std Dev) 168 (63) 205 (43) -37.1 (-50.3, -23.9) 153 (63)<br />
Median 160 202 150<br />
Range (55, 360) (30, 330) (0, 380)<br />
Days in Hospital for Procedure<br />
N 135 128 160<br />
Mean (Std Dev) 1 (0) 3 (1) -1.9 (-2.1, -1.7) 1 (0)<br />
Median 1 3 1<br />
Range (0, 4) (1,9) (0, 2)<br />
NOTE: Analysis includes all non-training Pivotal subjects and Continued Access subjects enrolled as of 08/01/2006.<br />
n / a: Not applicable.<br />
1<br />
Differences between Pivotal device and surgery groups and associated 95% confidence intervals.<br />
G-18
Attempted and Delivered<br />
Table G-8 presents the number of devices attempted and number of those successfully delivered for each device size<br />
overall and by subject age at procedure for combined device subjects from the Pivotal and Continued Access Studies.<br />
Table G-8<br />
GORE HELEX Septal Occluder Studies<br />
Number of Devices Attempted and Successfully Delivered By Device Size and Subject Age at Procedure<br />
GORE HELEX Septal<br />
Occluder Device Size<br />
15 mm 20 mm 25 mm 30 mm 35 mm Overall<br />
(N S<br />
/N A<br />
) 1 (N S<br />
/N A<br />
) 1 (N S<br />
/N A<br />
) 1 (N S<br />
/N A<br />
) 1 (N S<br />
/N A<br />
) 1 (N S<br />
/N A<br />
) 1<br />
Subject Age<br />
Infant (< 2 yrs) 1 / 1 3 / 3 3 / 9 0 0 7 / 13<br />
Child (2 – 5 yrs) 5 / 5 23 / 32 58 / 108 30 / 71 4 / 21 120 / 237<br />
Child (6 – 11 yrs) 3 / 3 11 / 13 17 / 24 23 / 42 4 / 16 58 / 98<br />
Adolescent (12 – 20 yrs) 2 / 2 8 / 11 13 / 18 11 / 16 13 / 24 47 / 71<br />
Adult (21+ yrs) 0 1 / 1 5 / 5 7 / 8 11 / 18 24 / 32<br />
Overall 11 / 11 46 / 60 96 / 164 71 / 137 32 / 79 256 / 451<br />
NOTE: Analysis includes all non-training Pivotal subjects and Continued Access subjects enrolled as of 08/01/2006.<br />
1 N S<br />
= Number of successful device deliveries. N A<br />
= Number of devices attempted.<br />
G-19
Summary of Reported Medications for Device Subjects<br />
Table G-9 presents the frequency of reported medications at follow-up visits for combined device subjects from<br />
the Pivotal and Continued Access Studies.<br />
Table G-9<br />
GORE HELEX Septal Occluder Studies Summary of Reported Medications for Device Subjects<br />
Medications Pre-Procedure Pre-Discharge 6 Months 12 Months<br />
Anti-Platelet 28 / 333 (8.4%) 224 / 255 (87.8%) 147 / 215 (68.4%) 21 / 236 (8.9%)<br />
Anti-Arrhythmic 7 / 333 (2.1%) 6 / 255 (2.4%) 5 / 215 (2.3%) 4 / 236 (1.7%)<br />
Anti-Hypertensive 6 / 333 (1.8%) 4 / 255 (1.6%) 3 / 215 (1.4%) 4 / 236 (1.7%)<br />
Anti-Coagulant 4 / 333 (1.2%) 13 / 255 (5.1%) 2 / 215 (0.9%) 4 / 236 (1.7%)<br />
Diuretic 8 / 333 (2.4%) 2 /255 (0.8%) 2/ 215 (0.9%) 2 / 236 (0.8%)<br />
NOTE: Analysis includes all non-training Pivotal subjects and Continued Access subjects enrolled as of 08/01/2006.<br />
G-20
Summary of Procedural Fluoroscopy Times<br />
Table G-10 presents a summary of procedural fluoroscopy time by device delivery success and number<br />
of devices attempted for combined device subjects from the Pivotal and Continued Access Studies.<br />
Table G-10<br />
GORE HELEX Septal Occluder Studies<br />
Summary of Procedural Fluoroscopy Times for Device Subjects<br />
N<br />
Median<br />
(minutes)<br />
Range<br />
(minutes)<br />
Subjects with Successful Delivery 256 18.6 (5.3, 92.1)<br />
One Device Attempted 178 15.1 (5.3, 46.6)<br />
Two Devices Attempted 54 28.9 (9.8, 76.1)<br />
Three or More Devices Attempted 24 39.7 (24.0, 92.1)<br />
Subjects with Unsuccessful Delivery 39 36.0 (13.4, 148.0)<br />
One Device Attempted 19 26.3 (13.4, 51.3)<br />
Two Devices Attempted 9 34.9 (31.3, 56.2)<br />
Three or More Devices Attempted 11 74.2 (41.5, 148.0)<br />
NOTE: Analysis includes all non-training Pivotal subjects and Continued Access subjects enrolled as of 08/01/2006.<br />
G-21
Conclusion<br />
The clinical success outcomes satisfied the primary, non-inferiority hypothesis for the Pivotal Study (p < 0.001 using two-sample binomial<br />
proportions test with non-inferiority margin of 10%) and indicated that the clinical success rate of the GORE HELEX Septal Occluder is not inferior<br />
to surgical closure.<br />
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