The AMPLATZER® Septal Occluder System

**Summary of Safety and Effectiveness Data**

Table of Contents

1\. General Information [1](#general-information)

2\. Indications And Usage [1](#indications-and-usage)

3\. Contraindications [2](#contraindications)

4\. Warnings and Precautions [2](#warnings-and-precautions)

5\. Device Description [2](#device-description)

6\. Alternative Practices or Procedures
[4](#alternative-practices-or-procedures)

7\. Marketing History [5](#marketing-history)

8\. Adverse Events [6](#adverse-events)

8.1 Adverse Events of the Device on Health
[6](#adverse-events-of-the-device-on-health)

8.2 Potential Adverse Events [7](#potential-adverse-events)

9\. Summary Of Preclinical Studies [8](#summary-of-preclinical-studies)

9.1 Bench Testing [8](#bench-testing)

9.2 MRI Compatibility [10](#mri-compatibility)

9.3 Corrosion Testing [10](#corrosion-testing)

9.3.1 Corrosion -- Bench Testing [10](#corrosion-bench-testing)

9.3.2 Corrosion -- Animal Testing [11](#corrosion-animal-testing)

9.3.3 Abrasion [11](#abrasion)

9.4 Biocompatibility Tests [11](#biocompatibility-tests)

9.5 Useful Life (Sterilization/Shelf Life)
[12](#useful-life-sterilizationshelf-life)

9.6 Animal Testing [12](#animal-testing)

10\. Summary Of Clinical Studies [13](#summary-of-clinical-studies)

10.1 Objective [13](#objective)

10.2 Study Design [13](#study-design)

10.3 Patient Description and Accountability
[14](#patient-description-and-accountability)

11\. Data Analysis and Results [15](#data-analysis-and-results)

12\. Device Failures and Replacements
[17](#device-failures-and-replacements)

13\. Conclusions Drawn From The Studies
[17](#conclusions-drawn-from-the-studies)

13.1 Atrial Septal Defects [17](#atrial-septal-defects)

13.2 Fenestrated Fontan [18](#fenestrated-fontan)

14\. Panel Recommendation [**Error! Bookmark not
defined.**](#__RefHeading___Toc531596113)

15\. CDRH Decision [**Error! Bookmark not
defined.**](#__RefHeading___Toc531596114)

16\. Approval Specifications [**Error! Bookmark not
defined.**](#__RefHeading___Toc531596115)

# General Information

> Device Generic Name: Transcatheter Atrial Septal Defect Occlusion
> Device
>
> Device Trade Name: AMPLATZER® Septal Occluder and
>
> AMPLATZER® Delivery System
>
> Applicant\'s Name and Address: AGA Medical Corporation
>
> 682 Mendelssohn Avenue
>
> Golden Valley, MN 55427
>
> USA
>
> Date(s) of Panel Recommendation: September 10, 2001
>
> Premarket Approval Application (PMA) Number: P000039
>
> Date of Good Manufacturing Practice Inspection: October 2000
>
> Date of Notice of Approval to Applicant:

# Indications And Usage

The AMPLATZER® Septal Occluder (ASO) device is indicated for the
occlusion of atrial septal defects (ASD) in secundum position. The ASO
device is also indicated in patients who have undergone a fenestrated
Fontan procedure and who now require closure of the fenestration.

Patients indicated for ASD closure have echocardiographic evidence of
ostium secundum atrial septal defect and clinical evidence of right
ventricular volume overload (i.e., 1.5:1 degree of left to right shunt
or RV enlargement).

# Contraindications

3.1 Any patient known to have extensive congenital cardiac anomaly which
can only be adequately repaired by way of cardiac surgery.

3.2 Any patient known to have sepsis within one month prior to
implantation, or any systemic infection that cannot be successfully
treated prior to device placement.

3.3 Any patient known to have a bleeding disorder, untreated ulcer or
any other contraindications to aspirin therapy, unless another
anti-platelet agent can be administered for 6 months.

3.4 Any patient known to have a demonstrated intracardiac thrombi on
echocardiography (especially left atrial or left atrial appendage
thrombi).

3.5 Any patient whose size (i.e., too small for TEE probe, catheter
size, etc) or condition (active infection, etc) would cause the patient
to be a poor candidate for cardiac catheterization.

3.6 Any patient with the margins of the defect \<5mm to the coronary
sinus, AV valves or right upper lobe pulmonary vein.

# Warnings and Precautions 

> The warnings and precautions can be found in the AMPLATZER Septal
> Occluder final labeling (Instructions for Use).

# Device Description

The AMPLATZER® Septal Occluder is a self-expandable, double disc device
made from a Nitinol wire mesh. The two discs are linked together by a
short connecting waist corresponding to the size of the ASD. In order to
increase its closing ability, the discs and the waist are filled with
polyester fabric. The polyester fabric is securely sewn to each disc by
a polyester thread.

**Device Specifications**

![](media/image1.png){width="1.3854166666666667in"
height="1.238888888888889in"}

Table 1 - Device Specifications / Recommended sheath sizes

+----------+----------+----------+----------+---------+-------------+
| Order    | A        | B        | Width Of | C       | SMALLEST    |
|          |          |          |          |         |             |
| Number   | Device   | LA Disc  | Co       | RA Disc | recommended |
|          | Size     | Diameter | nnecting | D       | sheath size |
|          |          |          | Waist    | iameter |             |
|          | (=S      |          |          |         |             |
|          | tretched |          |          |         |             |
|          | ASD)     |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 4 mm     | 16 mm    | 3 mm     | 12 mm   | 6-7 French  |
| -ASD-004 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 5 mm     | 17 mm    | 3 mm     | 13 mm   | 6-7 French  |
| -ASD-005 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 6 mm     | 18 mm    | 3 mm     | 14 mm   | 6-7 French  |
| -ASD-006 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 7 mm     | 19 mm    | 3 mm     | 15 mm   | 6-7 French  |
| -ASD-007 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 8 mm     | 20 mm    | 3 mm     | 16 mm   | 6-7 French  |
| -ASD-008 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 9 mm     | 21 mm    | 3 mm     | 17 mm   | 6-7 French  |
| -ASD-009 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 10 mm    | 22 mm    | 3 mm     | 18 mm   | 6-7 French  |
| -ASD-010 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 11 mm    | 25 mm    | 4 mm     | 21 mm   | 7 French    |
| -ASD-011 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 12 mm    | 26 mm    | 4 mm     | 22 mm   | 7 French    |
| -ASD-012 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 13 mm    | 27 mm    | 4 mm     | 23 mm   | 7 French    |
| -ASD-013 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 14 mm    | 28 mm    | 4 mm     | 24 mm   | 7 French    |
| -ASD-014 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 15 mm    | 29 mm    | 4 mm     | 25 mm   | 7 French    |
| -ASD-015 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 16 mm    | 30 mm    | 4 mm     | 26 mm   | 7 French    |
| -ASD-016 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 17 mm    | 31 mm    | 4 mm     | 27 mm   | 7 French    |
| -ASD-017 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 18 mm    | 32 mm    | 4 mm     | 28 mm   | 8-9 French  |
| -ASD-018 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 19 mm    | 33 mm    | 4 mm     | 29 mm   | 8-9 French  |
| -ASD-019 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 20 mm    | 34 mm    | 4 mm     | 30 mm   | 8-9 French  |
| -ASD-020 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 22 mm    | 36 mm    | 4 mm     | 32 mm   | 9 French    |
| -ASD-022 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 24 mm    | 38 mm    | 4 mm     | 34 mm   | 9 French    |
| -ASD-024 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 26 mm    | 40 mm    | 4 mm     | 36 mm   | 10 French   |
| -ASD-026 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 28 mm    | 42 mm    | 4 mm     | 38 mm   | 10 French   |
| -ASD-028 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 30 mm    | 44 mm    | 4 mm     | 40 mm   | 10 French   |
| -ASD-030 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 32 mm    | 46 mm    | 4 mm     | 42 mm   | 10 French   |
| -ASD-032 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 34 mm    | 50 mm    | 4 mm     | 44 mm   | 12 French   |
| -ASD-034 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 36 mm    | 52 mm    | 4 mm     | 46 mm   | 12 French   |
| -ASD-036 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+
| 9        | 38 mm    | 54 mm    | 4 mm     | 48 mm   | 12 French   |
| -ASD-038 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+

The AMPLATZER® Delivery System includes:

-   **Delivery Sheath** with Touhy-Borst Adapter - used to deliver the
    device.

-   **Dilator** -- used to ease penetration of tissue.

-   **Loading Device** -- used to introduce the AMPLATZER Septal
    Occluder into the delivery sheath.

-   **Plastic Vise** -- facilitates directional control and serves as
    the "handle" for disconnecting (unscrewing) the delivery cable from
    the device.

-   **Delivery Cable** -- the device is screwed onto the distal tip of
    the delivery cable, which allows for placement (and if necessary,
    retrieval) of the device.

![](media/image2.png){width="5.553472222222222in"
height="3.071527777777778in"}

Figure 1 AMPLATZER Septal Occluder Device and Delivery System

# Alternative Practices or Procedures

The only alternative to device closure of an ASD is open-heart surgery.
Cardiac surgery that is required for closure of such defects is a major
procedure that requires cardiopulmonary bypass. Surgery is relatively
safe with a mortality of less than 1%. If the patient suffers from
coexistent medical illnesses such as pulmonary disease, diabetes, renal
failure, etc., the risks of surgery are higher.

# Marketing History

These devices have not been marketed in the United States. The AMPLATZER
Septal Occluder and Delivery System received the CE Mark in 1998.
Additionally the AMPLATZER Septal Occluder and Delivery System has been
marketed in the following countries:

Africa

Argentina

Australia

Austria

Belgium

Brazil

Canada

Chile

China

Colombia

Costa Rica

Czech Republic

Denmark

Finland

France

Germany

Greece

Hong Kong

India

Israel

Italy

Jordan

Korea

Kuwait

Lebanon

Malaysia

Mexico

Monaco

New Zealand

Norway

Pakistan

Poland

Portugal

Russia

Saudi Arabia

Singapore

Slovakia

Spain

Sweden

Switzerland

Taiwan

Thailand

The Netherlands

Tunisia

Turkey

United Kingdom

Uruguay

Venezuela

The AMPLATZER Septal Occluder has not been withdrawn from marketing for
any reason relating to the safety and effectiveness of the device. The
AMPLATZER Delivery Systems were voluntarily recalled by AGA Medical due
to reports of dislodgment and embolization of the delivery sheath distal
tip marker band. The sheaths are no longer manufactured with marker
bands.

# Adverse Events

## 8.1 Adverse Events of the Device on Health {#adverse-events-of-the-device-on-health .unnumbered}

The AMPLATZER Septal Occluder was evaluated in a multi-center,
non-randomized, pivotal study comparing the device to surgical closure
of atrial septal defects; 423 patients received 433 devices with a total
device exposure of 911.5 years. Individual patient exposure to the
device averaged 25.6 months (ranging from 0 to 38.9).

A Registry group was also studied to evaluate the device in patients
with other conditions appropriate for device closure. Forty-eight (48)
patients with Fenestrated Fontan (FF) (communication in the baffle with
at least 5mm distance from the free atrial wall and central venous
pressure less than 15Hg) were enrolled in the study.

There was one death reported in the pivotal study (device group) and no
deaths were reported in the Fenestrated Fontan Registry Group. The Data
Safety Monitoring Board determined that the death was not device or
procedure related.

**Table 1 Adverse Events -- Pivotal Study**

+-----------------------------------+-----------+------------+--------+
| Major Adverse Events              | AMPLATZER | Surgical   | p      |
|                                   |           | Control    | -value |
|                                   | Patients  |            |        |
|                                   |           | Patients   |        |
+-----------------------------------+-----------+------------+--------+
| Cardiac Arrhythmia requiring      | 2/442     | 0/154      | 1.00   |
| major treatment                   | (0.5%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Device Embolization with surgical | 3/442     | 0/154      | 0.57   |
| removal                           | (0.7%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Device Embolization with          | 1/442     | 0/154      | 1.00   |
| percutaneous removal              | (0.2%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Delivery System Failure           | 1/442     | 0/154      | 1.00   |
|                                   | (0.2%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Pericardial Effusion with         | 0/442     | 3/154      | 0.017  |
| tamponade                         | (0.0%)    | (1.9%)     |        |
+-----------------------------------+-----------+------------+--------+
| Pulmonary Edema                   | 0/442     | 1/154      | 0.26   |
|                                   | (0.0%)    | (0.6%)     |        |
+-----------------------------------+-----------+------------+--------+
| Repeat Surgery                    | 0/442     | 2/154      | 0.066  |
|                                   | (0.0%)    | (1.3%)     |        |
+-----------------------------------+-----------+------------+--------+
| Surgical Wound Adverse Event      | 0/442     | 2/154      | 0.066  |
|                                   | (0.0%)    | (1.3%)     |        |
+-----------------------------------+-----------+------------+--------+
| Total Major Adverse Events        | 7/442     | 8/154      | 0.030  |
| Patients                          | (1.6%)    | (5.2%)     |        |
+-----------------------------------+-----------+------------+--------+

**Table 1 Adverse Events -- Pivotal Study (continued)**

+-----------------------------------+-----------+------------+--------+
| Minor Adverse Events              | AMPLATZER | Surgical   | p      |
|                                   |           | Control    | -value |
|                                   | Patients  |            |        |
|                                   |           | Patients   |        |
+-----------------------------------+-----------+------------+--------+
| Anemia                            | 0/442     | 1/154      | 0.26   |
|                                   | (0.0%)    | (0.6%)     |        |
+-----------------------------------+-----------+------------+--------+
| Allergic reaction (drug)          | 2/442     | 0/154      | 1.00   |
|                                   | (0.5%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Atelectasis                       | 0/442     | 1/154      | 0.26   |
|                                   | (0.0%)    | (0.6%)     |        |
+-----------------------------------+-----------+------------+--------+
| Cardiac Arrhythmias Minor         | 15/442    | 9/154      | 0.23   |
| Treatment                         | (3.4%)    | (5.8%)     |        |
+-----------------------------------+-----------+------------+--------+
| Device Embolization with          | 1/442     | 0/154      | 1.00   |
| percutaneous removal              | (0.2%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Extremity Tingling/Numbness       | 1/442     | 0/154      | 1.00   |
|                                   | (0.2%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Headaches/Possible TIA            | 2/442     | 0/154      | 1.00   |
|                                   | (0.5%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Delivery System Failure           | 2/442     | 0/154      | 1.00   |
|                                   | (0.5%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Pericardiotomy Syndrome           | 0/442     | 2/154      | 0.066  |
|                                   | (0.0%)    | (1.3%)     |        |
+-----------------------------------+-----------+------------+--------+
| Pericardial effusion              | 0/442     | 6/154      | \      |
|                                   | (0.0%     | (3.9%)     | <0.001 |
+-----------------------------------+-----------+------------+--------+
| Pleural Effusion                  | 0/442     | 1/154      | 0.26   |
|                                   | (0.0%)    | (0.6%)     |        |
+-----------------------------------+-----------+------------+--------+
| Pneumothorax                      | 0/442     | 3/154      | 0.017  |
|                                   | (0.0%)    | (1.9%)     |        |
+-----------------------------------+-----------+------------+--------+
| Staph Infection                   | 0/442     | 1/154      | 0.26   |
|                                   | (0.0%)    | (0.6%)     |        |
+-----------------------------------+-----------+------------+--------+
| Surgical Wound Adverse Events     | 0/442     | 1/154      | 0.26   |
|                                   | (0.0%)    | (0.6%)     |        |
+-----------------------------------+-----------+------------+--------+
| Thrombus formation                | 3/442     | 0/154      | 0.56   |
|                                   | (0.7%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Transfusions                      | 0/442     | 2/154      | 0.066  |
|                                   | (0.0%)    | (1.3%)     |        |
+-----------------------------------+-----------+------------+--------+
| Upper Respiratory Infection/Fever | 0/442     | 2/154      | 0.066  |
|                                   | (0.0%)    | (1.3%)     |        |
+-----------------------------------+-----------+------------+--------+
| Urinary Tract Disturbance         | 1/424     | 0/154      | 1.00   |
|                                   | (0.2%)    | (0.0%)     |        |
+-----------------------------------+-----------+------------+--------+
| Total Minor Adverse Events        | 27/442    | 29/154     | \      |
| (Patients)                        | (6.1%)    | (18.8%)    | <0.001 |
+-----------------------------------+-----------+------------+--------+

Table 2: Adverse Events -FF

+-------------------------------+----------------+--------------------+
|                               | AMPLATZER      | Upper 95%          |
|                               |                | Confidence         |
|                               | Patients       |                    |
|                               |                | Bound              |
+-------------------------------+----------------+--------------------+
| Major Adverse Events          |                |                    |
+-------------------------------+----------------+--------------------+
| Repeat Surgery                | 1/48 (2.1%)    | 0.095              |
+-------------------------------+----------------+--------------------+
| Hemothorax                    | 1/48(2.1%)     | 0.095              |
+-------------------------------+----------------+--------------------+
| Minor Adverse Events          |                |                    |
+-------------------------------+----------------+--------------------+
| Vomiting (required 2 nights   | 1/48 (2.1%)    | 0.095              |
| in hospital)                  |                |                    |
+-------------------------------+----------------+--------------------+
| Atrial                        | 1/48 (2.1%)    | 0.095              |
| fibrillation/cardioversion    |                |                    |
+-------------------------------+----------------+--------------------+
| Total Adverse Events          | 4/48 (8.3%)    | 0.181              |
+-------------------------------+----------------+--------------------+

## 8.2 Potential Adverse Events {#potential-adverse-events .unnumbered}

Placement of the AMPLATZER Septal Occluder involves using standard
interventional cardiac catheterization techniques. The following adverse
events (listed in alphabetical order) might be expected from
interventional cardiac catheterization techniques.

-   Air embolus

-   Allergic dye reaction

-   Anesthesia reactions

-   Apnea

-   Fever

-   Hypertension/hypotension

-   Infection including endocarditis

-   Perforation of vessel or myocardium

-   Pseudoaneurysm including blood loss requiring transfusion

-   Valvular regurgitation

# Summary Of Preclinical Studies

## 9.1 Bench Testing {#bench-testing .unnumbered}

Bench testing was done to ensure that all initial design requirements
were met. Bench testing has demonstrated the strength and reliability of
the device. Design verification of the device and its components has
been conducted to verify that the device is safe for its intended use.

Table 3 Summary of AMPLATZER Septal Occluder Testing

+-------------+----+----+-------------------+---+---+---+----+---------+
| **Test**    | *  |    | **Specification** | * |   |   |    |         |
|             | *S |    |                   | * |   |   |    |         |
|             | am |    |                   | R |   |   |    |         |
|             | pl |    |                   | e |   |   |    |         |
|             | es |    |                   | s |   |   |    |         |
|             | ** |    |                   | u |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | * |   |   |    |         |
|             |    |    |                   | * |   |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
| Pull Test   | ** | *  | [.004 - .006"     | * |   | * |    |         |
|             | Wi | *N | diameter          | * |   | * |    |         |
| Laser Weld  | re | ** | wire]{.underline} | W |   | M |    |         |
| -- Marker   | ** |    |                   | i |   | e |    |         |
| Bands to    |    |    | \>12 lbs          | r |   | a |    |         |
| Wire Braid  | ** |    |                   | e |   | n |    |         |
|             | Di |    | [.007" diameter   | * |   | [ |    |         |
|             | a. |    | wire]{.underline} | * |   | + |    |         |
|             | ** |    |                   |   |   | ] |    |         |
|             |    |    | \>24 lbs          | * |   | { |    |         |
|             |    |    |                   | * |   | . |    |         |
|             |    |    | [.008" diameter   | d |   | u |    |         |
|             |    |    | wire]{.underline} | i |   | n |    |         |
|             |    |    |                   | a |   | d |    |         |
|             |    |    | \> 32.2 lbs       | m |   | e |    |         |
|             |    |    |                   | e |   | r |    |         |
|             |    |    |                   | t |   | l |    |         |
|             |    |    |                   | e |   | i |    |         |
|             |    |    |                   | r |   | n |    |         |
|             |    |    |                   | * |   | e |    |         |
|             |    |    |                   | * |   | } |    |         |
|             |    |    |                   |   |   | S |    |         |
|             |    |    |                   |   |   | D |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | a |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | g |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | ) |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | b |    |         |
|             |    |    |                   |   |   | s |    |         |
|             |    |    |                   |   |   | * |    |         |
|             |    |    |                   |   |   | * |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 9  |                   | . |   | 3 |    |         |
|             | 00 |    |                   | 0 |   | 0 |    |         |
|             | 4" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 4 |   | 3 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 6 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | 6 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 10 |                   | . |   | 3 |    |         |
|             | 00 |    |                   | 0 |   | 6 |    |         |
|             | 5" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 5 |   | 7 |    |         |
|             |    |    |                   | " |   | 9 |    |         |
|             |    |    |                   |   |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 9 |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | 0 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 11 |                   | . |   | 3 |    |         |
|             | 00 |    |                   | 0 |   | 7 |    |         |
|             | 6" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 6 |   | 6 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 8 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | 9 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 9 |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 6 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 5  |                   | . |   | 4 |    |         |
|             | 00 |    |                   | 0 |   | 9 |    |         |
|             | 7" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 7 |   | 8 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 6 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | 1 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | \ |    |         |
|             |    |    |                   |   |   | > |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 5  |                   | . |   | A |    |         |
|             | 00 |    |                   | 0 |   | l |    |         |
|             | 8" |    |                   | 0 |   | l |    |         |
|             |    |    |                   | 8 |   | s |    |         |
|             |    |    |                   | " |   | a |    |         |
|             |    |    |                   |   |   | m |    |         |
|             |    |    |                   |   |   | p |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | s |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | x |    |         |
|             |    |    |                   |   |   | c |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | b |    |         |
|             |    |    |                   |   |   | s |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
| Pull Test   | ** | *  | [.004 - .006"     | * |   | * |    |         |
|             | Wi | *N | diameter          | * |   | * |    |         |
| Laser Weld- | re | ** | wire]{.underline} | W |   | M |    |         |
|             | ** |    |                   | i |   | e |    |         |
| Screw       |    |    | \>12 lbs          | r |   | a |    |         |
| Attachment  | ** |    |                   | e |   | n |    |         |
| to Marker   | Di |    | [.007" diameter   | * |   | [ |    |         |
| Bands       | a. |    | wire]{.underline} | * |   | + |    |         |
|             | ** |    |                   |   |   | ] |    |         |
|             |    |    | \>24 lbs          | * |   | { |    |         |
|             |    |    |                   | * |   | . |    |         |
|             |    |    | [.008" diameter   | D |   | u |    |         |
|             |    |    | wire]{.underline} | i |   | n |    |         |
|             |    |    |                   | a |   | d |    |         |
|             |    |    | \> 32.2 lbs       | m |   | e |    |         |
|             |    |    |                   | e |   | r |    |         |
|             |    |    |                   | t |   | l |    |         |
|             |    |    |                   | e |   | i |    |         |
|             |    |    |                   | r |   | n |    |         |
|             |    |    |                   | * |   | e |    |         |
|             |    |    |                   | * |   | } |    |         |
|             |    |    |                   |   |   | S |    |         |
|             |    |    |                   |   |   | D |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | a |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | g |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | ) |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | b |    |         |
|             |    |    |                   |   |   | s |    |         |
|             |    |    |                   |   |   | * |    |         |
|             |    |    |                   |   |   | * |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 5  |                   | . |   | 3 |    |         |
|             | 00 |    |                   | 0 |   | 4 |    |         |
|             | 4" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 4 |   | 8 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 7 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 6 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | 8 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 7  |                   | . |   | 3 |    |         |
|             | 00 |    |                   | 0 |   | 8 |    |         |
|             | 5" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 5 |   | 3 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 8 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | 1 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 1 |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | 7 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 10 |                   | . |   | 4 |    |         |
|             | 00 |    |                   | 0 |   | 7 |    |         |
|             | 6" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 6 |   | 9 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 9 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 3 |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 9 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | \ |    |         |
|             |    |    |                   |   |   | > |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | 0 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 5  |                   | . |   | 4 |    |         |
|             | 00 |    |                   | 0 |   | 9 |    |         |
|             | 7" |    |                   | 0 |   | . |    |         |
|             |    |    |                   | 7 |   | 8 |    |         |
|             |    |    |                   | " |   | [ |    |         |
|             |    |    |                   |   |   | + |    |         |
|             |    |    |                   |   |   | ] |    |         |
|             |    |    |                   |   |   | { |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | u |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | r |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | i |    |         |
|             |    |    |                   |   |   | n |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | } |    |         |
|             |    |    |                   |   |   | 6 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   | ( |    |         |
|             |    |    |                   |   |   | 4 |    |         |
|             |    |    |                   |   |   | 1 |    |         |
|             |    |    |                   |   |   | . |    |         |
|             |    |    |                   |   |   | 2 |    |         |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   | - |    |         |
|             |    |    |                   |   |   | \ |    |         |
|             |    |    |                   |   |   | > |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | ) |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             | .  | 5  |                   | . |   | A |    |         |
|             | 00 |    |                   | 0 |   | l |    |         |
|             | 8" |    |                   | 0 |   | l |    |         |
|             |    |    |                   | 8 |   | s |    |         |
|             |    |    |                   | " |   | a |    |         |
|             |    |    |                   |   |   | m |    |         |
|             |    |    |                   |   |   | p |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | s |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | x |    |         |
|             |    |    |                   |   |   | c |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | e |    |         |
|             |    |    |                   |   |   | d |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | 5 |    |         |
|             |    |    |                   |   |   | l |    |         |
|             |    |    |                   |   |   | b |    |         |
|             |    |    |                   |   |   | s |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
| Pull Test   | 5  |    | 12 lbs            | * |   |   |    |         |
|             |    |    |                   | * |   |   |    |         |
| Delivery    |    |    |                   | M |   |   |    |         |
| Cable screw |    |    |                   | e |   |   |    |         |
| and device  |    |    |                   | a |   |   |    |         |
| end screw   |    |    |                   | n |   |   |    |         |
|             |    |    |                   | [ |   |   |    |         |
|             |    |    |                   | + |   |   |    |         |
|             |    |    |                   | ] |   |   |    |         |
|             |    |    |                   | { |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | d |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | } |   |   |    |         |
|             |    |    |                   | S |   |   |    |         |
|             |    |    |                   | D |   |   |    |         |
|             |    |    |                   | ( |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | g |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | ) |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | b |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | * |   |   |    |         |
|             |    |    |                   | * |   |   |    |         |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   | 2 |   |   |    |         |
|             |    |    |                   | 6 |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
|             |    |    |                   | 4 |   |   |    |         |
|             |    |    |                   | [ |   |   |    |         |
|             |    |    |                   | + |   |   |    |         |
|             |    |    |                   | ] |   |   |    |         |
|             |    |    |                   | { |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | d |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | } |   |   |    |         |
|             |    |    |                   | 2 |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
|             |    |    |                   | 3 |   |   |    |         |
|             |    |    |                   | ( |   |   |    |         |
|             |    |    |                   | 2 |   |   |    |         |
|             |    |    |                   | 3 |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
|             |    |    |                   | 4 |   |   |    |         |
|             |    |    |                   | - |   |   |    |         |
|             |    |    |                   | - |   |   |    |         |
|             |    |    |                   | 2 |   |   |    |         |
|             |    |    |                   | 9 |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
|             |    |    |                   | 1 |   |   |    |         |
|             |    |    |                   | 5 |   |   |    |         |
|             |    |    |                   | ) |   |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
| Device      | 1  |    | Structural        | S |   |   |    |         |
| Integrity   |    |    | Integrity must    | t |   |   |    |         |
|             |    |    | remain intact.    | r |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | c |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | g |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | y |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | m |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | d |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | c |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | w |   |   |    |         |
|             |    |    |                   | h |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | g |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | d |   |   |    |         |
|             |    |    |                   | m |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | p |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | w |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | w |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | c |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | , |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | w |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | w |   |   |    |         |
|             |    |    |                   | h |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | n |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | h |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | e |   |   |    |         |
|             |    |    |                   | f |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | r |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | l |   |   |    |         |
|             |    |    |                   | d |   |   |    |         |
|             |    |    |                   | i |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | c |   |   |    |         |
|             |    |    |                   | p |   |   |    |         |
|             |    |    |                   | o |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | w |   |   |    |         |
|             |    |    |                   | a |   |   |    |         |
|             |    |    |                   | s |   |   |    |         |
|             |    |    |                   | c |   |   |    |         |
|             |    |    |                   | u |   |   |    |         |
|             |    |    |                   | t |   |   |    |         |
|             |    |    |                   | . |   |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
| Life Cycle  | 3  |    | Structural        | S | W |   | \# | Desc    |
|             | 00 |    | integrity must    | i | i |   |    | ription |
|             |    |    | remain intact     | z | r |   | Fa | of      |
|             | (  |    | after 400 million | e | e |   | il | f       |
|             | 30 |    | cycles            |   | d |   |    | indings |
|             | ea |    |                   |   | i |   |    |         |
|             | ch |    |                   |   | a |   |    |         |
|             | of |    |                   |   | . |   |    |         |
|             | t  |    |                   |   |   |   |    |         |
|             | he |    |                   |   |   |   |    |         |
|             | sm |    |                   |   |   |   |    |         |
|             | al |    |                   |   |   |   |    |         |
|             | le |    |                   |   |   |   |    |         |
|             | st |    |                   |   |   |   |    |         |
|             | &  |    |                   |   |   |   |    |         |
|             | l  |    |                   |   |   |   |    |         |
|             | ar |    |                   |   |   |   |    |         |
|             | ge |    |                   |   |   |   |    |         |
|             | st |    |                   |   |   |   |    |         |
|             | de |    |                   |   |   |   |    |         |
|             | vi |    |                   |   |   |   |    |         |
|             | ce |    |                   |   |   |   |    |         |
|             | in |    |                   |   |   |   |    |         |
|             | ea |    |                   |   |   |   |    |         |
|             | ch |    |                   |   |   |   |    |         |
|             | of |    |                   |   |   |   |    |         |
|             | t  |    |                   |   |   |   |    |         |
|             | he |    |                   |   |   |   |    |         |
|             | wi |    |                   |   |   |   |    |         |
|             | re |    |                   |   |   |   |    |         |
|             | di |    |                   |   |   |   |    |         |
|             | am |    |                   |   |   |   |    |         |
|             | et |    |                   |   |   |   |    |         |
|             | er |    |                   |   |   |   |    |         |
|             | s) |    |                   |   |   |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 4 | . |   | 0  |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 4 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 1 | . |   | 0  |         |
|             |    |    |                   | 0 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 4 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 1 | . |   | 0  |         |
|             |    |    |                   | 1 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 5 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 1 | . |   | 2  | 1)  1   |
|             |    |    |                   | 7 | 0 |   | [^ |         |
|             |    |    |                   |   | 0 |   | 1] |  broken |
|             |    |    |                   |   | 5 |   |    |         |
|             |    |    |                   |   | " |   |    |    wire |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |    near |
|             |    |    |                   |   |   |   |    |     end |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |   screw |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    | 2)  1   |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |  broken |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |    wire |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |    near |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |  marker |
|             |    |    |                   |   |   |   |    |         |
|             |    |    |                   |   |   |   |    |    band |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 1 | . |   | 0  |         |
|             |    |    |                   | 8 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 6 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 2 | . |   | 1  | Broken  |
|             |    |    |                   | 4 | 0 |   |    | wires   |
|             |    |    |                   |   | 0 |   |    | in      |
|             |    |    |                   |   | 6 |   |    | waist.  |
|             |    |    |                   |   | " |   |    | Brass   |
|             |    |    |                   |   |   |   |    | metal   |
|             |    |    |                   |   |   |   |    | shaving |
|             |    |    |                   |   |   |   |    | found   |
|             |    |    |                   |   |   |   |    | san     |
|             |    |    |                   |   |   |   |    | dwiched |
|             |    |    |                   |   |   |   |    | between |
|             |    |    |                   |   |   |   |    | the two |
|             |    |    |                   |   |   |   |    | device  |
|             |    |    |                   |   |   |   |    | discs   |
|             |    |    |                   |   |   |   |    | during  |
|             |    |    |                   |   |   |   |    | removal |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 2 | . |   | 0  |         |
|             |    |    |                   | 6 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 7 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 3 | . |   | 0  |         |
|             |    |    |                   | 4 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 7 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
|             |    |    |                   |   | [ |   |    |         |
|             |    |    |                   |   | ^ |   |    |         |
|             |    |    |                   |   | 2 |   |    |         |
|             |    |    |                   |   | ] |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 3 | . |   | 0  |         |
|             |    |    |                   | 4 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 8 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+
|             |    |    |                   | 4 | . |   | 0  |         |
|             |    |    |                   | 0 | 0 |   |    |         |
|             |    |    |                   |   | 0 |   |    |         |
|             |    |    |                   |   | 8 |   |    |         |
|             |    |    |                   |   | " |   |    |         |
+-------------+----+----+-------------------+---+---+---+----+---------+

Table 4 Summary of AMPLATZER Delivery System Testing

+---------------+----+-----+-----------+-------+---------------------+
| **Test**      | *  |     | **Specif  | *     |                     |
|               | *S |     | ication** | *Resu |                     |
|               | am |     |           | lts** |                     |
|               | pl |     |           |       |                     |
|               | es |     |           |       |                     |
|               | ** |     |           |       |                     |
+---------------+----+-----+-----------+-------+---------------------+
| Delivery      | ** | **  | The       | **S   | **Mean              |
| Sheath        | Si | N** | sheath    | ize** | [+]{.underline} SD  |
|               | ze |     | must not  |       | (range) degrees**   |
| Kink          | ** |     | kink      |       |                     |
| Resistance    |    |     | during    |       |                     |
|               |    |     | normal    |       |                     |
|               |    |     | clinical  |       |                     |
|               |    |     | use.      |       |                     |
+---------------+----+-----+-----------+-------+---------------------+
|               | 6F | 4   |           | 6F    | 131.3               |
|               |    |     |           |       | [+]{.underline} 4.8 |
|               |    |     |           |       | (125 -- 135)        |
+---------------+----+-----+-----------+-------+---------------------+
|               | 7F | 4   |           | 7F    | 118.8               |
|               |    |     |           |       | [+]{.underline} 2.5 |
|               |    |     |           |       | (115 -- 120)        |
+---------------+----+-----+-----------+-------+---------------------+
|               | 8F | 4   |           | 8F    | 112.5               |
|               |    |     |           |       | [+]{.underline} 6.5 |
|               |    |     |           |       | (105 -- 120)        |
+---------------+----+-----+-----------+-------+---------------------+
|               | 9F | 4   |           | 9F    | 112.5               |
|               |    |     |           |       | [+]{.underline} 2.9 |
|               |    |     |           |       | (110 -- 115)        |
+---------------+----+-----+-----------+-------+---------------------+
|               | 1  | 5   |           | 10F   | 106 [+]{.underline} |
|               | 0F |     |           |       | 5.5 (100 -- 110)    |
+---------------+----+-----+-----------+-------+---------------------+
|               | 1  | 5   |           | 12F   | 129 [+]{.underline} |
|               | 2F |     |           |       | 4.2 (125 -- 135)    |
+---------------+----+-----+-----------+-------+---------------------+
| Delivery      | 10 |     | The cable | *     |                     |
| Cable         |    |     | must not  | *Mean |                     |
|               |    |     | kink      | [+]{. |                     |
| Kink          |    |     | during    | under |                     |
| Resistance    |    |     | normal    | line} |                     |
|               |    |     | clinical  | SD    |                     |
|               |    |     | use.      | (r    |                     |
|               |    |     |           | ange) |                     |
|               |    |     |           | degr  |                     |
|               |    |     |           | ees** |                     |
|               |    |     |           |       |                     |
|               |    |     |           | 128.5 |                     |
|               |    |     |           | [+]{. |                     |
|               |    |     |           | under |                     |
|               |    |     |           | line} |                     |
|               |    |     |           | 7.8   |                     |
|               |    |     |           | (120  |                     |
|               |    |     |           | -145) |                     |
+---------------+----+-----+-----------+-------+---------------------+
| Pull Tests -  | ** | **  | Pull      | **S   | **Mean              |
|               | Si | N** | strength  | ize** | [+]{.underline} SD  |
| Delivery      | ze |     | must not  |       | (range) lbs**       |
| Sheath        | ** |     | be        |       |                     |
|               |    |     | \<3lbs.   |       |                     |
| Hub to Tubing |    |     |           |       |                     |
+---------------+----+-----+-----------+-------+---------------------+
|               | 6F | 4   |           | 6F    | 8 [+]{.underline}   |
|               |    |     |           |       | 1.3 (6.85 -- 9.25)  |
+---------------+----+-----+-----------+-------+---------------------+
|               | 7F | 4   |           | 7F    | 10.5                |
|               |    |     |           |       | [+]{.underline} 0.1 |
|               |    |     |           |       | (10.3 -- 10.7)      |
+---------------+----+-----+-----------+-------+---------------------+
|               | 8F | 4   |           | 8F    | 11.3                |
|               |    |     |           |       | [+]{.underline} 0.1 |
|               |    |     |           |       | (11.3 -- 11.5)      |
+---------------+----+-----+-----------+-------+---------------------+
|               | 9F | 4   |           | 9F    | 11.6                |
|               |    |     |           |       | [+]{.underline} 0.1 |
|               |    |     |           |       | (11.5 -- 11.8)      |
+---------------+----+-----+-----------+-------+---------------------+
|               | 1  | 5   |           | 10F   | 14.3                |
|               | 0F |     |           |       | [+]{.underline} 0.1 |
|               |    |     |           |       | (14.2 -- 14.4)      |
+---------------+----+-----+-----------+-------+---------------------+
|               | 1  | 5   |           | 12F   | 17.3                |
|               | 2F |     |           |       | [+]{.underline} 1.0 |
|               |    |     |           |       | (16.2 -- 18.7)      |
+---------------+----+-----+-----------+-------+---------------------+
| Pull Test --  | 10 |     | 12 pounds | *     |                     |
| Delivery      |    |     |           | *Mean |                     |
| Cable --      |    |     |           | [+]{. |                     |
| Cable to      |    |     |           | under |                     |
| Cable Screw   |    |     |           | line} |                     |
| Weld Joint    |    |     |           | SD    |                     |
|               |    |     |           | (r    |                     |
|               |    |     |           | ange) |                     |
|               |    |     |           | lbs** |                     |
|               |    |     |           |       |                     |
|               |    |     |           | 46.1  |                     |
|               |    |     |           | [+]{. |                     |
|               |    |     |           | under |                     |
|               |    |     |           | line} |                     |
|               |    |     |           | 5.5   |                     |
|               |    |     |           | (37 - |                     |
|               |    |     |           | \>50) |                     |
+---------------+----+-----+-----------+-------+---------------------+

## 9.2 MRI Compatibility {#mri-compatibility .unnumbered}

Two AMPLATZER Septal Occluders were placed in a water phantom, fixed
with adhesive tape, and examined by a Siemens 1.5 Tesla MRI apparatus.
Various imaging modalities were used and minimal artifacts were only
observed in the object vicinity. The device is MRI safe up to 1.5 Tesla.

## 9.3 Corrosion Testing {#corrosion-testing .unnumbered}

### 9.3.1 Corrosion -- Bench Testing {#corrosion-bench-testing .unnumbered}

The device was tested per ASTM F746. The Nitinol sample did not display
the general pitting found on the 316SS sample. In addition, there was no
indication of crevice corrosion on the nickel-titanium sample as was
seen on the 316 SS samples.

Eight devices were tested for corrosion potential. The devices were
degreased, rinsed with deionized water and blown with dry air. The
electrolyte was prepared by dissolving 36.9g reagent grade sodium
chloride in deionized water. After transfer to the corrosion cell, the
electrolyte was deoxygenated by sparging with zero grade nitrogen for a
minimum of 60 minutes.

The devices were suspended in the corrosion cell and maintained in the
electrolyte at open circuit for 60 minutes before beginning the
polarization scan (0.6 V/h). The electrochemistry was performed with a
PAR 263 Potentiosatat.

In all devices the onset of corrosion occurred ca. 0.08 V from the open
circuit potential. The corrosion potential (E~CORR~) for the samples
tested varied by ca. 0.08 V. The shape of the hysteresis curve indicates
that localized corrosion may occur.

### 9.3.2 Corrosion -- Animal Testing {#corrosion-animal-testing .unnumbered}

Post mortem examination was conducted in an animal specimen wherein two
devices were implanted (device #1 -- implanted 18 months and device #2
implanted 14 months). Although the animal was implanted with the
AMPLATZER Muscular Ventricular Septal Occluder device, materials and
methods are identical to the AMPLATZER Septal Occluder.

Analysis revealed both devices were nearly covered by neoendocardium.
Gross inspection revealed no wire breakage. Light microscopy at 40x
revealed a smooth surface. Scanning electron microscopy was carried out
and compared to a new control wire. Both surfaces appear identical. The
wire surface appearance was typical of oxidized Nitinol wire.

Both devices were weighed (275 mg and 156 mg). No evidence of corrosion
was observed for either device.

### 9.3.3 Abrasion {#abrasion .unnumbered}

A device was explanted from a swine after 3 months (at least 26 million
cycles). A biopsy was taken from the neo-endocardium for histologic
examination. The device was examined grossly, by light microscopy and by
scanning electron microscopy (SEM). No broken wires were detected.

SEM examination was made at randomly selected wire intersection on both
the large and small discs. The typical condition of the wires at the
intersections was photographed. Results indicate that there are no signs
of intersecting wires abrading each other.

## 9.4 Biocompatibility Tests {#biocompatibility-tests .unnumbered}

The AMPLATZER Septal Occluder is constructed of Nitinol (a
nickel-titanium alloy) and polyester. Sufficient information from the
literature exists to demonstrate biocompatibility of the Nitinol for use
in an implantable device.[^3]^,^[^4]^,^[^5].

The polyester fabric and the patient contacting components of the
delivery system underwent biocompatibility testing in accordance with
FDA General Program Memorandum G95-1, which provides an FDA-modified
matrix of International Standard ISO 10993, "Biological Evaluation of
Medical Devices Part 1: Evaluation and Testing."

**Table 5 -- Summary of Biocompatibility Testing**

  ----------------------------- -------------------- --------------------
  ***Test***                    ***Result***         

                                ***Polyester         ***Delivery
                                Fabric***            System***

  Cytotoxicity                  Pass                 Pass

  Sensitization                 Non-sensitizer       Non-sensitizer

  Hemolysis                     Non hemolytic        Non-hemolytic

  Intracutaneous Injection      Pass                 Pass
  (Irritation)                                       

  Toxicity                      Pass (Subchronic)    Pass (Systemic)

  Acute Systemic Injection      Pass                 *Not required*

  Ames Salmonella Mutagenicity  No mutagenic         *Not required*
                                activity             

  Implantation                  Moderate reaction\*  *Not required*

  Chronic Toxicity              Pass                 *Not required*
  ----------------------------- -------------------- --------------------

\*A "moderate reaction" is exactly what is expected when tissue ingrowth
is the desired result.

## 9.5 Useful Life (Sterilization/Shelf Life)  {#useful-life-sterilizationshelf-life .unnumbered}

The AMPLATZER Septal Occluder and Delivery System are single-use devices
which are provided sterile (via ethylene oxide) to the user. The
sterilization cycle was validated to ensure successful sterilization to
a Sterility Assurance Level (SAL) of 10^-6^ .

Product and package stability testing of the AMPLATZER Septal Occluder
and Delivery System was performed. Visual inspection and physical
testing indicated that the device performed within product specification
for up to 3 years. Based upon these results, an expiration date of 3
years has been established.

## 9.6 Animal Testing {#animal-testing .unnumbered}

Animal studies were conducted to evaluate the device design and to
demonstrate that the AMPLATZER Septal Occluder was capable of providing
rapid closure and endothelialization of atrial septal defects without
evidence of residual shunting. Twelve (12) Yucatan minipigs underwent
surgical creation of an atrial septal defect and were allowed to recover
for 10 -- 14 days. The animals were then implanted with the AMPLATZER
Septal Occluder.

Sequential angiographic studies and blood gas measurements were repeated
at one week, one month and three month intervals. The animals were then
euthanized with removal of the heart and lungs for gross and histologic
examination.

At 3 months all animals studied exhibited complete endothelialization by
neoendothelium. This tissue in-growth demonstrated that the device was
firmly fixed into position and was covered by a glistening
non-thrombogenic layer of cells. In this final state, it was apparent
that no thrombosis, shunting or dislodgment occurred.

# Summary Of Clinical Studies

## 10.1 Objective  {#objective .unnumbered}

> The objective of the study was to compare the clinical performance of
> the AMPLATZER Septal Occluder device for atrial septal defect (ASD)
> closure with that documented for the ASD Surgical Repair Procedure. A
> Registry Group was also studied to evaluate the device in patients
> with Fenestrated Fontan.

## 10.2 Study Design {#study-design .unnumbered}

> A multi-center, non-randomized, controlled clinical study was
> performed to evaluate the safety (incidence of major adverse events)
> and effectiveness (closure of the defect defined as [\<]{.underline}
> 2mm shunt) of the AMPLATZER Septal Occluder.
>
> [Pivotal Study]{.underline}
>
> Enrolled patients had echocardiographic evidence of ostium secundum
> atrial septal defect (device group: defect size [\<]{.underline} 38mm)
> and clinical evidence of right ventricular volume overload or had
> clinical symptoms such as paradoxical embolism or atrial dysrhythmia
> in the presence of a minimal shunt. Exclusion criteria included:

-   Patients with multiple defects that could not be adequately covered
    by the device (device group only).

-   Associated congenital cardiac anomalies requiring surgery.

-   Ostium primum or sinus venosus atrial septal defects.

-   Partial anomalous pulmonary venous drainage.

-   Pulmonary vascular resistance above 7 Woods units or a right-to-left
    shunt at the atrial level with a peripheral arterial saturation \<
    94%.

-   Patients with recent myocardial infarction, unstable angina and
    decompensated congestive heart failure.

-   Patient with right and/or left ventricular decompensation with
    ejection fraction \< 30%.

-   Sepsis.

-   History of repeated pulmonary infection.

-   Any type of serious infection \< 1 month prior to procedure.

-   Malignancy where life expectancy was \< 2 years.

-   Demonstrated intracardiac thrombi on echocardiography.

-   Weight \< 8 Kilograms.

-   Inability to obtain informed consent.

```{=html}
<!-- -->
```
-   Patients with gastritis, gastric ulcer, duodenal ulcer, bleeding
    disorders etc. and other contraindications to aspirin therapy unless
    other anti-platelet agents can be administered for 6 months.

[Registry Group]{.underline}

The inclusion criteria for the Registry group were:

-   **Fenestrated Fontan** (communication in the baffle with at least
    5mm distance from the free atrial wall and central venous pressure
    less than 15Hg).

## 10.3 Patient Description and Accountability {#patient-description-and-accountability .unnumbered}

> Patients were enrolled into the pivotal study from March 1998 through
> March 2000 at 29 centers in the United States. Device placement was
> attempted in 442 patients. In 18 patients the device was recaptured
> prior to releasing from the delivery cable due to anatomical
> conditions. There was one acute embolization. Thus 423 patients
> received 433 devices. ASD surgical data was collected prospectively in
> 117 patients and retrospectively in 37 patients.

Table 6: Patient Baseline Demographics

+------------------------+---------------+-------------------+---------+
| Variable               | AMPLATZER     | Surgical Control  | p-value |
|                        |               |                   |         |
|                        | Patients      | Patients          |         |
+------------------------+---------------+-------------------+---------+
| Age (years)            | 18.1 ± 19.3   | 5.9 ± 6.2 (154)   | \<0.001 |
| Mean±s.d.(N)           | (442)         |                   |         |
|                        |               | \[0.6, 38.2\]     |         |
| \[range\]              | \[0.6, 82.0\] |                   |         |
+------------------------+---------------+-------------------+---------+
| Gender                 |               |                   |         |
+------------------------+---------------+-------------------+---------+
| Female                 | 299/442       | 94/154 (61.0%)    | 0.14    |
|                        | (67.6%)       |                   |         |
+------------------------+---------------+-------------------+---------+
| Male                   | 143/442       | 60/154 (39.0%)    |         |
|                        | (32.4%)       |                   |         |
+------------------------+---------------+-------------------+---------+
| Height (cm)            | 134.6 ± 32.0  | 105.5 ± 26.9      | \<0.001 |
| Mean±s.d.(N)           | (440)         | (151)             |         |
|                        |               |                   |         |
| \[range\]              | \[58,188\]    | \[60,178\]        |         |
+------------------------+---------------+-------------------+---------+
| Weight (kg) Mean±s.d   | 42.3 ±27.3    | 20.6 ± 15.2 (153) | \<0.001 |
| (N)                    | (440)         |                   |         |
|                        |               | \[4.8,78.4\]      |         |
| \[range\]              | \[6.3,130\]   |                   |         |
+------------------------+---------------+-------------------+---------+
| Medical History        |               |                   |         |
+------------------------+---------------+-------------------+---------+
| CHF                    | 11/442 (2.5%) | 7/154 (4.5%)      | 0.27    |
+------------------------+---------------+-------------------+---------+
| Failure to Thrive      | 14/442 (3.2%) | 13/154 (8.4%)     | 0.012   |
+------------------------+---------------+-------------------+---------+
| CAD                    | 9/442 (2.0%)  | 0/154 (0%)        | 0.12    |
+------------------------+---------------+-------------------+---------+
| Respiratory Infections | 7/442 (1.6%)  | 13/154 (8.4%)     | \<0.001 |
+------------------------+---------------+-------------------+---------+
| TIA                    | 6/442 (1.4%)  | 1/154 (0.6%)      | 0.68    |
+------------------------+---------------+-------------------+---------+
| COPD                   | 1/442 (0.2%)  | 0/154 (0%)        | 1.00    |
+------------------------+---------------+-------------------+---------+
| Hypertension           | 16/442 (3.6%) | 0/154 (0%)        | 0.016   |
+------------------------+---------------+-------------------+---------+
| Stroke                 | 13/442 (2.9%) | 0/154 (0%)        | 0.026   |
+------------------------+---------------+-------------------+---------+
| Recurrent              | 5/442 (1.1%)  | 1/154 (0.6%)      | 1.00    |
| Strokes/TIA's          |               |                   |         |
+------------------------+---------------+-------------------+---------+
| Diabetes               | 4/442 (0.9%)  | 0/154 (0%)        | 0.58    |
+------------------------+---------------+-------------------+---------+

Table 7: Pre-Closure --Fenestrated Fontan

+------------------------------------------+---------------------------+
| Age (years) Mean±s.d (N)                 | 7.8 ± 6.9 (48)            |
|                                          |                           |
| \[range\]                                | \[1.6, 44.9\]             |
+------------------------------------------+---------------------------+
| Gender: Female                           | 29/48 (60.4%)             |
+------------------------------------------+---------------------------+
| Height (cm) Mean±s.d.(N)                 | 114.5 ± 25.2 (46)         |
|                                          |                           |
| \[range\]                                | \[78,168\]                |
+------------------------------------------+---------------------------+
| Weight (kg) Mean±s.d (N)                 | 22.4 ± 13.5 (48)          |
|                                          |                           |
| \[range\]                                | \[9.7, 68.7\]             |
+------------------------------------------+---------------------------+
| Medical History:                         |                           |
+------------------------------------------+---------------------------+
| CHF                                      | 1/48 (2.1%)               |
+------------------------------------------+---------------------------+
| Failure to thrive                        | 1/48 (2.1%)               |
+------------------------------------------+---------------------------+
| Stroke                                   | 2/48 (4.2%)               |
+------------------------------------------+---------------------------+
| Heart Murmur                             | 26/47 (55.3%)             |
+------------------------------------------+---------------------------+
| Pulmonary Ejection Murmur                | 2/47 (4.3%)               |
+------------------------------------------+---------------------------+
| Mid Diastolic Murmur                     | 1/47 (2.1%)               |
+------------------------------------------+---------------------------+
| Right axis deviation                     | 11/45 (24.4%)             |
+------------------------------------------+---------------------------+
| Peaked p waves                           | 1/45 (2.2%)               |
+------------------------------------------+---------------------------+
| Cardiomegaly                             | 20/45 (44.4%)             |
+------------------------------------------+---------------------------+

# Data Analysis and Results

Patients with ostium secundum atrial septal defects and clinical
evidence of right ventricular volume overload who were being evaluated
for ASD closure underwent physical examination which included: heart
murmur classification; an electrocardiogram (EKG) to document cardiac
electrical characteristics; a chest x-ray to evaluate heart size and
pulmonary vasculature; a detailed 2D Color Doppler Transthoracic Echo
(TTE) to evaluate the atrial septal defect location, number of ASD's,
size of the ASD's, and distance from the ASD to the coronary sinus,
pulmonary vein, and AV valves.

The patients were instructed to avoid strenuous activity for a period of
one month. and to take aspirin for 6 months post placement
(3-5mg/kg/day). Additionally, patients were examined and a transthoracic
Echocardiogram (TTE) was conducted at 24 hours, 6 months and 1 year.
Post-discharge data was collected in surgical patients when available.
Ninety-four (94) surgical repair patients were confirmed to be closed by
echo at 12 months. All were assumed closed at 12 months. Trivial and
small shunts were considered hemodynamically insignificant.

An independent core lab assessed a subset of echo videotapes for
12-month shunt status; a Data Safety Monitoring Board adjudicated all
adverse events.

**Table 8: Principal Effectiveness and Safety Results - Pivotal Study**

+---------------------------+------------+--------------+-------------+
|                           | AMPLATZER  | Surgical     | 90%         |
|                           |            | Control      | Confidence  |
|                           | P          | Patients     | Interval    |
|                           | atients^1^ |              |             |
+---------------------------+------------+--------------+-------------+
| Technical Success         | 423/442    | 154/154      | (-0.        |
|                           | (95.7%)    | (100.0%)     | 084,-0.010) |
+---------------------------+------------+--------------+-------------+
| Procedure Success         | 413/423    | 154/154      | (-0.059,    |
|                           | (97.6%)    | (100.0%)     | +0.008)     |
+---------------------------+------------+--------------+-------------+
| Early ([\<]{.underline}   | 401/442    | 148/154      | (-0.111,    |
| 30 days) Composite        | (90.7%)    | (96.1%)      | -0.005)     |
| Success                   |            |              |             |
+---------------------------+------------+--------------+-------------+
| 12-month Composite        | 331/362    | 146/154      | (-0.096,    |
| Success                   | (91.4%)    | (94.8%)      | +0.019)     |
+---------------------------+------------+--------------+-------------+
| 24-hour Closure Success   | 404/418    | 154/154      | (-0.073,    |
|                           | (96.7%)    | (100%)       | -0.001)     |
+---------------------------+------------+--------------+-------------+
| 6-month Closure Success   | 376/387    | 154/154      | (-0.068,    |
|                           | (97.2%)    | (100%)       | +0.003)     |
+---------------------------+------------+--------------+-------------+
| 12-month Closure Success  | 326/331    | 149/149      | (-1.052,    |
|                           | (98.5%)    | (100%)       | 0.017)      |
+---------------------------+------------+--------------+-------------+
|                           |            |              |             |
+---------------------------+------------+--------------+-------------+
| **Principal Safety        |            |              |             |
| Measures**                |            |              |             |
+---------------------------+------------+--------------+-------------+
| Major Adverse Events      | 7/442      | 8/154 (5.2%) | (-0.090,    |
| 12-months                 | (1.6%)     |              | -0.002)     |
+---------------------------+------------+--------------+-------------+
| Minor Adverse Events      | 27/442     | 29/154       | (-0.200,    |
| 12-months                 | (6.1%)     | (18.8%)      | -0.070)     |
+---------------------------+------------+--------------+-------------+
| 12-month Composite        | 0.934      | 0.938        | \[-0.077,   |
| Success (K-M)             |            |              | +0.036\]    |
+---------------------------+------------+--------------+-------------+
| Survival at 30 days (K-M) | 0.939      | 0.956        | \[-0.052,   |
|                           |            |              | +0.018\]    |
+---------------------------+------------+--------------+-------------+
| Survival at 180 days      | 0.936      | 0.947        | \[-0.048,   |
| (K-M)                     |            |              | +0.026\]    |
+---------------------------+------------+--------------+-------------+

**Table 9: Principal Effectiveness and Safety Results - Pivotal Study**

**Patient Age \< 20 years**

+---------------------------+--------------+-------------+-------------+
|                           | AMPLATZER    | Surgical    | 90%         |
|                           |              | Control     | Confidence  |
|                           | Patients     | Patients    | Interval    |
+---------------------------+--------------+-------------+-------------+
| Technical Success         | 315/328      | 149/149     | (-0.086,    |
|                           | (96.0%)      | (100%)      | -0.005)     |
+---------------------------+--------------+-------------+-------------+
| Procedure Success         | 306/315      | 149/149     | (0.074,     |
|                           | (97.1%)      | (100%)      | +0.005)     |
+---------------------------+--------------+-------------+-------------+
| Early ([\<]{.underline}   | 295/328      | 143/149     | (-0.124,    |
| 30 days) Composite        | (89.9%)      | (95.9%)     | -0.007)     |
| Success                   |              |             |             |
+---------------------------+--------------+-------------+-------------+
| 12-month Composite        | 256/281      | 142/149     | (-0.108,    |
| Success                   | (91.1%)      | (95.3%)     | +0.013)     |
+---------------------------+--------------+-------------+-------------+
| 24-hour Closure Success   | 301/310      | 149/149     | (-0.075,    |
|                           | (97.1%)      | (100%)      | +0.005)     |
+---------------------------+--------------+-------------+-------------+
| 6-month Closure Success   | 270/278      | 149/149     | (-0.077,    |
|                           | (97.1%)      | (100%)      | +0.006)     |
+---------------------------+--------------+-------------+-------------+
| 12-month Closure Success  | 246/251      | 149/149     | (-0.068,    |
|                           | (98.0%)      | (100%)      | +0.014)     |
+---------------------------+--------------+-------------+-------------+
|                           |              |             |             |
+---------------------------+--------------+-------------+-------------+
| **Principal Safety        |              |             |             |
| Measures**                |              |             |             |
+---------------------------+--------------+-------------+-------------+
| Major Adverse Events      | 6/328 (1.8%) | 7/149       | (-0.086,    |
| 12-months                 |              | (4.7%)      | +0.008)     |
+---------------------------+--------------+-------------+-------------+
| Minor Adverse Events      | 16/328       | 29/149      | (-0.221,    |
| 12-months                 | (4.9%)       | (19.5%)     | -0.085)     |
+---------------------------+--------------+-------------+-------------+
| 12-month Composite        | 0.930        | 0.944       | \[-0.055,   |
| Success (K-M)             |              |             | +0.027\]    |
+---------------------------+--------------+-------------+-------------+
| Survival at 30 days (K-M) | 0.933        | 0.954       | \[-0.059,   |
|                           |              |             | +0.017\]    |
+---------------------------+--------------+-------------+-------------+
| Survival at 180 days      | 0.930        | 0.954       | \[-0.062,   |
| (K-M)                     |              |             | +0.014\]    |
+---------------------------+--------------+-------------+-------------+

^1^Unit of analysis = Patient. Although 10 patients had 2 defects each
treated with an AMPLATZER Septal Occluder; all patients with multiple
AMPLATZER implants were successfully treated.

Technical Success: successful deployment of the device, or the
successful completion of the surgical procedure.

Procedure Success: successful closure of the defect as measured
immediately following the procedure

([\<]{.underline} 2 mm residual shunt)

Composite Success: All device placement attempts without a major adverse
event, surgical reintervention, embolization, technical failure or major
shunt (defined as \> 2 mm).

Closure Success: among patients that were technical successes, closure
of the atrial septal defect (defined as a shunt [\<]{.underline} 2mm)
without the need for surgical repair.

Major Adverse Events: Events that are life threatening, prolong
hospitalization or have long-term consequences or need for ongoing
therapy. These include but are not limited to cerebral embolism, cardiac
perforation with tamponade, endocarditis, pericardial effusion with
tamponade, repeat surgery, death, cardiac arrhythmias requiring
permanent pacemaker placement or long term anti-arrhythmic medication
and device embolizations requiring immediate surgical removal.

Minor Adverse Events: Device embolization with percutaneous retrieval,
cardiac arrhythmia with treatment, phrenic nerve injury, hematoma, other
vascular access site adverse events, retroperitoneal hematoma, surgical
wound adverse events, other procedural adverse events, pericardial
effusion requiring medical management, evidence of device associated
thrombus formation without embolization (with or without treatment) and
marker band embolization without known sequelae.

Table 9: Principal Efficacy Results---FF

+---------------------------------+-----------------+-----------------+
| PRINCIPAL EFFECTIVENESS RESULTS | AMPLATZER       | Lower 95%       |
|                                 |                 | Confidence      |
|                                 | Patients        | Bound           |
+---------------------------------+-----------------+-----------------+
| Technical Success               | 46/48 (95.8%)   | 0.875           |
+---------------------------------+-----------------+-----------------+
| Procedure Success               | 46/46 (100.0%)  | 0.937           |
+---------------------------------+-----------------+-----------------+
| Early Composite Success         | 44/48 (91.7%)   | 0.819           |
+---------------------------------+-----------------+-----------------+
| 6 month Success                 | 38/38 (100.0%)  | 0.924           |
+---------------------------------+-----------------+-----------------+
| Primary Efficacy Outcome (12    | 32/32 (100.0%)  | 0.911           |
| month Success)                  |                 |                 |
+---------------------------------+-----------------+-----------------+
| Hospital days Mean±s.d. (N)     | 1.2± 0.7 (39)   | (0.95, 1.41)    |
|                                 |                 |                 |
| \[range\]                       | \[0.0, 4.0\]    |                 |
+---------------------------------+-----------------+-----------------+

Table 10: Principal Safety Results -- FF

+--------------------------------+--------------+----------------------+
| PRINCIPAL EFFECTIVENESS        | AMPLATZER    | Upper 95% Confidence |
| RESULTS                        |              | Bound                |
|                                | Patients^1^  |                      |
+--------------------------------+--------------+----------------------+
| Major Adverse Events           | 2/48 (4.2%)  | 0.125                |
+--------------------------------+--------------+----------------------+
| Minor Adverse Events           | 2/48 (4.2%)  | 0.125                |
+--------------------------------+--------------+----------------------+
| Total Adverse Events           | 4/48 (8.3%)  | 0.181                |
+--------------------------------+--------------+----------------------+

^1^Unit of analysis = patient

#  Device Failures and Replacements

**Device:** Reported device failures include deformed upon deployment
("cobra") and immediate device embolization

**Delivery System:** Marker band embolization, sheath kink/accordion,
and leaking hubs have been reported for the delivery system.

# Conclusions Drawn From The Studies

## 13.1 Atrial Septal Defects {#atrial-septal-defects .unnumbered}

Effectiveness of the AMPLATZER Septal Occluder for treatment of atrial
septal defects has been demonstrated by:

-   Successful closure of ASD's at 12-month follow-up without the need
    for additional surgical repair in 326 out of 331 patients.

-   These results are statistically equivalent to the 100% rate reported
    for the ASD Surgical Repair Control group. The Lower 95% confidence
    bound for the difference in 12-month success rate is -1.052, which
    is greater than the protocol specified requirement of -.08.

-   The adverse event rates associated with the use of the AMPLATZER
    device at 12 months are within the protocol-defined acceptable
    limits. The mortality rate for the device cohort was 0%, which is
    less than the proposed 2%; the major adverse event rate for
    AMPLATZER patients was 1.6%, which is less than the proposed 10%
    rate. The overall AMPLATZER adverse event rate (7.2%) was
    statistically significantly lower than that reported for the control
    group (24.0%) (p = \<0.001).

-   In addition to a high rate of effectiveness and a low risk of major
    adverse events, the mean length of hospital stay for AMPLATZER
    patients of 1 day is statistically significantly lower than the mean
    of 3.4 days documented for the ASD Surgical Repair control group (p
    \<0.001).

## 13.2 Fenestrated Fontan {#fenestrated-fontan .unnumbered}

Effectiveness of the AMPLATZER Septal Occluder for treatment of
Fenestrated Fontans has been demonstrated by:

-   Results consistent with those obtained for treatment of ASD.

-   Primary Efficacy Outcome at 12 months follow-up without the need for
    additional surgical repair in 32 of 32 patients, obviates the need
    for a second surgical procedure in this patient population.

-   The adverse event rates associated with the use of the AMPLATZER
    device at 12 months are within the protocol-defined acceptable
    limits. The mortality rate for the device cohort was 0%, which is
    less than the proposed 2%; the major adverse event rate for
    AMPLATZER patients was 4.2%, which is less than the proposed 10%
    rate.

In conclusion, the AMPLATZER® device operates as designed and is safe
and effective in the clinical environment in the intended patient
population and is appropriate for market release.

#  Panel Recommendation

At an advisory meeting held on September 10, 2001, the Circulatory
System Devices recommended that Amplatzer® ASO System be approved
subject to the submission to, and approval by, the Center for Devices
and Radiological Health (CDRH) the following:

-   changes to the labeling for the Amplatzer® ASO System;

-   items to be incorporated into the training program; and

```{=html}
<!-- -->
```
-   collection of 5-year follow-up data for patients enrolled in the
    clinical investigations contained in the PMA.

#  CDRH Decision

####  {#section .Style1 .unnumbered}

#### CDRH concurred with the Circulatory System Devices Panel recommendation of September 10, 2001, and conveyed the Conditions of Approval in a facsimile dated November 11, 2001. AGA Medical indicated concurrence with those Conditions of Approval.  {#cdrh-concurred-with-the-circulatory-system-devices-panel-recommendation-of-september-10-2001-and-conveyed-the-conditions-of-approval-in-a-facsimile-dated-november-11-2001.-aga-medical-indicated-concurrence-with-those-conditions-of-approval. .Style1 .unnumbered}

#### FDA issued an approval order on \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. The applicant's manufacturing facility was inspected on October 30, 2000 and contract sterilization facility was inspected on May 1, 2001. These facilities were found to be in compliance with the device Good Manufacturing Practice regulations. {#fda-issued-an-approval-order-on-____________________________.-the-applicants-manufacturing-facility-was-inspected-on-october-30-2000-and-contract-sterilization-facility-was-inspected-on-may-1-2001.-these-facilities-were-found-to-be-in-compliance-with-the-device-good-manufacturing-practice-regulations. .Style1 .unnumbered}

#  Approval Specifications

> Indications for Use: See the Instructions for Use (Attachment 1)

####  {#section-1 .Style1 .unnumbered}

#### Hazards to Health from use of the Device: See CONTRAINDICATIONS, WARNINGS and PRECAUTIONS, and ADVERSE EVENTS in the Instructions for Use (Attachment 1). {#hazards-to-health-from-use-of-the-device-see-contraindications-warnings-and-precautions-and-adverse-events-in-the-instructions-for-use-attachment-1. .Style1 .unnumbered}

> Postapproval requirements and restrictions: See approval order.

#### The Approval Order, Summary of Safety and Effectiveness Data, and labeling can be found on the Internet at address \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_. {#the-approval-order-summary-of-safety-and-effectiveness-data-and-labeling-can-be-found-on-the-internet-at-address-_________________________________. .Style1 .unnumbered}

[^1]: In both cases, the devices had retained their preset shape and had
    to be compressed several times to detect the broken wires. If a wire
    were to fracture in the clinical setting, it would not protrude due
    to the shape memory property of Nitinol.

[^2]: Initially, the 34mm device was manufactured with .007" wire. It
    was later changed to .008" wire.

[^3]: Castleman LS, Motzkin SM, Alicandri FP, et al. Biocompatibility of
    Nitinol Alloy as an Implant Material. *J of Biomedical Materials
    Research* 1976; 10:695-731.

[^4]: Cragg AH, De Jong SC, Barnhardt WH, et al: Nitinol Intravascular
    Stent: Results of Preclinical Evaluation. *Radiology* 1993; 189-775.

[^5]: Prince MR, Salzman EW, Schoen, FJ, et al: Local Intravascular
    Effects of the Nitinol Blood Clot Filter. *Investigative Radiology*
    1998; 23:294-300.