**AGA MEDICAL CORPORATION**

**AMPLATZER® Septal Occluder**

***and* Delivery System**

**Physician Manual**

**The AMPLATZER® Septal Occluder and Delivery System**

**Physician's Manual**

**Contents**

Overview of Manual [1](#overview-of-manual)

Brief Device Description [2](#brief-device-description)

Indications and Usage [3](#indications-and-usage)

Contraindications [3](#contraindications)

Warnings [4](#warnings)

Precautions [4](#precautions)

Sizing [4](#sizing)

Procedural [4](#procedural)

Post-Implant [5](#post-implant)

Adverse Events [5](#adverse-events)

Deaths [5](#deaths)

Observed Adverse Events [5](#observed-adverse-events)

Potential Adverse Events [6](#potential-adverse-events)

Clinical Studies [7](#clinical-studies)

Patients Studied [7](#patients-studied)

Methods [9](#methods)

Results [9](#results)

Individualization Of Treatment [11](#individualization-of-treatment)

Patient Selection [11](#patient-selection)

Use in Specific Populations [11](#use-in-specific-populations)

Directions For Use [12](#directions-for-use)

Patient Counseling Information [16](#patient-counseling-information)

Patient Registration [16](#patient-registration)

Physician Training [17](#physician-training)

How Supplied [18](#how-supplied)

Detailed Device Description [18](#detailed-device-description)

AMPLATZER Septal Occluder [18](#amplatzer-septal-occluder)

AMPLATZER Delivery System [19](#amplatzer-delivery-system)

AMPLATZER Exchange System [19](#__RefHeading___Toc520251705)

Glossary [20](#glossary)

Warranty Information [21](#warranty-information)

# Overview of Manual

This manual provides information on the AMPLATZER® Septal Occluder,
Delivery System and Exchange System. This manual describes some items to
discuss with your patient (and their parents) and explains how to
register the patient's device. You will also find instructions for
handling, storing, implanting, retrieving the device, as well as
instructions for exchanging the delivery system if necessary during a
procedure.

The manual is divided into the following sections:

-   Brief Device Description

-   Indications and Usage

-   Contraindications

-   Warnings

-   Precautions

-   Adverse Events

-   Clinical Studies

-   Individualization of Treatment

-   Directions for Use

-   

-   Patient Information

-   Physician Training Information

-   How Supplied

-   Detailed Device Description

-   

-   Glossary

-   Warranty Information

# Brief 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 patches. The polyester patches are securely sewn to each disc
by a polyester thread.

The AMPLATZER Delivery System was designed specifically to facilitate
attachment, loading, delivery and deployment of the AMPLATZER Septal
Occluder and is comprised of a delivery sheath, dilator, loading device,
plastic vise and delivery cable.

The AMPLATZER Exchange System is intended for removal of an AMPLATZER
Delivery Sheath and subsequent exchange for a sheath of equal or larger
diameter. The components are identical to the Delivery System.

For a complete list of model numbers, refer to the Detailed Device
Description section of this manual.

#### ![](media/image1.png){width="6.0in" height="3.7194444444444446in"}

#### Figure 1. The AMPLATZER Septal Occluder and Delivery System 

# Indications and Usage

The AMPLATZER Septal Occluder is a percutaneous, transcatheter, atrial
septal defect closure device intended for the occlusion of atrial septal
defects (ASD) in secundum position. Patients indicated for ASD closure
have echocardiographic evidence of ostium secundum atrial septal defect
and clinical evidence of right ventricular volume overload (ie, 1.5:1
degree of left to right shunt [or]{.underline} RV enlargement) or
clinical symptoms such as paradoxical embolism or atrial dysrhythmia in
the presence of a minimal shunt.

The device is also indicated in those patients who have undergone a
fenestrated Fontan procedure and who now require closure of the
fenestration.

# Contraindications

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

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-   Any patient known to have local or generalized sepsis, or any
    systemic infection that cannot be successfully treated prior to
    device placement.

-   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.

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

-   Any patient whose size or condition would cause the patient to be a
    poor candidate for cardiac catheterization.

-   Any patient where the margins of the defect are \<5mm to the
    coronary sinus, AV valves and right upper lobe pulmonary vein.

# Warnings 

-   The AMPLATZER Septal Occluder and Delivery System should only be
    used by those physicians trained in transcatheter defect closure
    techniques.

-   Physicians must be prepared to deal with urgent situations which
    require removal of embolized devices that result in critical
    hemodynamic compromise.

-   Embolized devices must be removed. Embolized devices should not be
    withdrawn through intracardiac structures unless they have been
    adequately collapsed within a sheath.

-   Do not use if the sterile barrier has been compromised in any way.

# Precautions

Handling

-   The AMPLATZER Septal Occluder and Delivery System are for single use
    only. Do not reuse or resterilize.

## Sizing

-   Accurate defect sizing is crucial to AMPLATZER Septal Occluder
    device selection. The use of a compliant balloon catheter to
    determine defect size is recommended. Device selection should be
    equal to, or slightly larger than, the balloon stretched diameter of
    the defect.

## Procedural 

-   Aspirin (3-5 mg/kg/day) is to be started at least 24 hours prior to
    the procedure. In the rare case of aspirin intolerance, two times
    200 mg of Ticlopidin are given. Cephalosporin therapy is optional.

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-   Patient should fully heparinized throughout the procedure with a
    minimum active clotting time (ACT) of 200 seconds prior to device
    insertion.

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-   Transesophageal echocardiography (TEE) or similar imaging equipment
    is recommended as an aid in placing the AMPLATZER Septal Occluder.
    If used, the patient's esophogeal anatomy must be adequate for
    placement and manipulation of the TEE probe.

-   Do not release the AMPLATZER Septal Occluder from the delivery cable
    if the device does not conform to its original configuration or if
    the device position is unstable. Recapture the device and redeploy.
    If still unsatisfactory, recapture the device and replace with a new
    device.

## Post-Implant

-   Patients should take appropriate endocarditis prophylaxis for 6
    months following device implantation. The decision to continue
    endocarditis prophylaxis beyond 6 months is at the discretion of the
    physician.

-   Patients should be treated with antiplatelet/anticoagulation therapy
    (such as aspirin) for 6 months post implant. The decision to
    continue antiplatelet/-anticoagulation therapy beyond 6 months is at
    the discretion of the physician.

# Adverse Events

Clinical Summary

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 (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.

## 

## Deaths 

There was one non device or procedure related death reported in the
pivotal study and no deaths reported in the Fenestrated Fontan Registry
Group.

## Observed Adverse Events

[Pivotal Clinical Study]{.underline}

**Table 1 Complications -- Pivotal Study**

+-----------------------------------+-----------+------------+--------+
| Major Complication                | 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 Complication       | 0/442     | 2/154      | 0.066  |
|                                   | (0.0%)    | (1.3%)     |        |
+-----------------------------------+-----------+------------+--------+
| Total Major Complications         | 7/442     | 8/154      | 0.030  |
| Patients                          | (1.6%)    | (5.2%)     |        |
+-----------------------------------+-----------+------------+--------+

**Table 1 Complications -- Pivotal Study (continued)**

+-----------------------------------+-----------+------------+--------+
| Minor Complications               | 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 Complications      | 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 Complications         | 27/442    | 29/154     | \      |
| (Patients)                        | (6.1%)    | (18.8%)    | <0.001 |
+-----------------------------------+-----------+------------+--------+

[Registry Group -- Fenestrated Fontan]{.underline}

Table 2: Complications -FF

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

## Potential Adverse Events

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

# Clinical Studies

The AMPLATZER Septal Occluder was evaluated in a multi-center,
non-randomized controlled study to compare the clinical performance of
the device for ASD closure with that documented for the ASD Surgical
repair procedure. Additionally, the device was studied in patients with
uncommon conditions wherein transcatheter closure with the device may
also be beneficial (Registry Group).

## Patients Studied

-   Pivotal study -- Atrial Septal Defects

Attempt to treat was initiated in 442 device patients and 154 surgical
patients. 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 (local/generalized).

-   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.

-   Patient with gastritis, gastric ulcer, duodenal ulcer, bleeding
    disorders etc and other contraindications to aspirin therapy unless
    other anti-platelet agents could not be administered for 6 months.

Patients underwent physical examination which included: heart murmur
classification; an electrocardiogram, chest x-ray, and 2D Color Doppler
Transthoracic Echo (TTE).

Table 3: 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    |
+------------------------+---------------+-------------------+---------+

-   Registry Group - Fenestrated Fontan

    Table 4: 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%)             |
+------------------------------------------+---------------------------+

##  

## Methods

[Device Patients]{.underline}

Device placement was attempted in 442 patients. The patients underwent
cardiac catheterization. Position and size of the defect were confirmed
by angiography. The size of the defect was determined by obtaining the
"stretched" diameter of the defect with a compliant balloon catheter. If
the size and position of the defect were determined to be feasible for
transcatheter closure, device placement was attempted. Nineteen (19)
patients did not receive the device (anatomical, defect too large, etc);
and an acute embolization occurred in another. Thus 423 patients
received 433 devices..

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.

[Surgical Control Group]{.underline}

Surgical repair of an atrial septal defect requires sternotomy,
cardiopulmonary bypass, aortic cross clamp and right atriotomy. If the
defect is small, primary repair by suturing the defect is feasible,
however, if the defect is large, then patch closure is the preferred
method. Different surgeons use different material for the patch. Most
surgeons use pericardium, however, some surgeons use Goretex® to repair
the ASD. At the end of the operation, the surgeon inserts chest tubes to
drain any blood. The chest tubes last for 24-48 hours after which they
are removed. The patient spends 3-5 days at the hospital after which
they go home.. A total of 154 patients underwent surgical closure of
their ASD. The surgical group required a 12 month visit.

## Results

**Table 5: Principal Effectiveness and Safety Results - Pivotal Study**

+--------------------------+--------------+-------------+------------+
|                          | AMPLATZER    | Surgical    | 90%        |
|                          |              | Control     | Confidence |
|                          | Patients^1^  | Patients    | Interval   |
+--------------------------+--------------+-------------+------------+
| Technical Success        | 423/442      | 154/154     | (-0.0      |
|                          | (95.7%)      | (100.0%)    | 84,-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       | 311/362      | 146/154     | (-0.153,   |
| Success                  | (85.9%)      | (94.8%)     | -0.033)    |
+--------------------------+--------------+-------------+------------+
| 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 Complications      | 7/442 (1.6%) | 8/154       | (-0.090,   |
| 12-months                |              | (5.2%)      | -0.002)    |
+--------------------------+--------------+-------------+------------+
| Minor Complications      | 27/442       | 29/154      | (-0.200,   |
| 12-months                | (6.1%)       | (18.8%)     | -0.070)    |
+--------------------------+--------------+-------------+------------+
| 12-month Composite       | 0.889        | 0.938       | \[-0.101,  |
| Success (K-M)            |              |             | +0.003\]   |
+--------------------------+--------------+-------------+------------+
| Survival at 30 days      | 0.909        | 0.956       | \[-0.091,  |
| (K-M)                    |              |             | -0.003\]   |
+--------------------------+--------------+-------------+------------+
| Survival at 180 days     | 0.902        | 0.947       | \[-0.092,  |
| (K-M)                    |              |             | +0.002\]   |
+--------------------------+--------------+-------------+------------+

^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
complication, 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 Complications: 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 Complications: Device embolization with percutaneous retrieval,
cardiac arrhythmia with treatment, phrenic nerve injury, hematoma, other
vascular access site complications, retroperitoneal hematoma, surgical
wound complications, other procedural complications, 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 6: Principal Efficacy Results---FF

+---------------------------------+-----------------+-----------------+
|                                 | 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 7: Principal Safety Results -- FF

+-------------------------+------------------+------------------------+
|                         | AMPLATZER        | Upper 95% Confidence   |
|                         |                  | Bound                  |
|                         | Patients^1^      |                        |
+-------------------------+------------------+------------------------+
| Major complications     | 2/48 (4.2%)      | 0.125                  |
+-------------------------+------------------+------------------------+
| Minor Complications     | 2/48 (4.2%)      | 0.125                  |
+-------------------------+------------------+------------------------+
| Total complications     | 4/48 (8.3%)      | 0.181                  |
+-------------------------+------------------+------------------------+

^1^Unit of analysis = "patient"

# Individualization Of Treatment

## Patient Selection

-   Device placement should only be attempted in those patients with
    sufficient rim around the defect to allow stable seating of the
    device.

-   Device placement should only be done with the assistance of TEE or
    similar imaging equipment.

-   Device size selection should be the same size (or slightly larger
    than) the stretched diameter of the defect.

## Use in Specific Populations

-   **Pregnancy** -- care should be taken to minimize the radiation
    exposure to the fetus and the mother.

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```
-   **Nursing Mothers** -- Although appropriate biocompatibility testing
    has been conducted for this implant device, there has been no
    quantitative assessment of the presence of leachables in breast
    milk.

# Directions For Use

This section outlines the basic steps of the suggested procedure for
implanting an AMPLATZER Septal Occluder.

-   Following percutaneous puncture of the femoral vein, perform a
    standard right heart catheterization.

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```
-   Perform an angiogram in order to demonstrate the atrial
    communication. Catheterize the left atrium using a 45° LAO position
    and with cranial angulation, inject contrast medium into the left
    atrium or into the right upper lobe pulmonary vein.

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```
-   Introduce a .035" exchange "J" tip guidewire into the left atrium.
    Insert a compliant balloon catheter over the exchange wire into the
    left atrium and determine the stretched diameter of the defect.

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```
-   [Sizing the defect]{.underline} -- Two methods can be used:

a)  Pull technique: Using a round compliant balloon, inflate the
    catheter with various increments of carbon dioxide or contrast
    medium (for patients not allergic to contrast media) and pull across
    the atrial communication. There should be only a slight deformity of
    the sizing balloon to determine the stretched diameter. If using a
    sizing plate, remove the sizing balloon and reinflate with the
    identical amount of CO~2~ or contrast medium. Pass the inflated
    balloon through various openings of the sizing plate to determine
    the stretched diameter of the defect. Sizing of the defect is very
    important for appropriate selection of the occlusion device,
    therefore repeat sizing of the defect is encouraged. Alternatively,
    determination of the balloon can also be established using
    echocardiographic or radiographic measurements.

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```
a)  Static technique: Using a balloon specifically designed for sizing
    atrial communications (i.e. AMPLATZER Sizing Balloon) the catheter
    is passed over the exchange guidewire directly through the skin. To
    facilitate this percutaneous entry, an assistant should apply
    forceful negative pressure with an attached syringe. Under
    fluoroscopic and echocardiographic guidance, the balloon catheter is
    placed across the defect and inflated with diluted contrast medium
    until the left-to-right shunt ceases as observed by
    echocardiography. Measurements can then be made identical to the
    pull technique.

> **NOTE:** *Always refer to the Instructions for use that accompany
> each balloon catheter to insure that the recommendations of the
> manufacturer are followed.*

-   Once the stretched diameter of the defect has been determined,
    select an occlusion device equal or, if the identical size is not
    available, slightly larger than the defect. Therefore, the device
    should be [stenting]{.underline} the defect.

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```
-   Remove the balloon catheter leaving the .035" exchange guidewire in
    place.

-   Pass the delivery cable through the loader and screw the device to
    the tip of the delivery cable. Once securely attached, immerse the
    device and loader in saline solution and pull the device into the
    loader with a jerking motion.

-   Insert the dilator into the delivery sheath and secure to the sheath
    with the locking mechanism. Introduce the dilator/delivery sheath
    assembly through the groin. Once the delivery sheath has reached the
    inferior vena cava, remove the dilator to allow back bleeding to
    purge all air from the system then connect the hemostasis valve and
    flush with a syringe before the left atrium is entered. Advance the
    sheath over the guidewire through the communication into the left
    upper pulmonary vein. Verify the correct position of the delivery
    sheath by a test injection of contrast medium. Remove the exchange
    wire and flush the sheath with saline.

-   Attach the loading device to the delivery sheath. Advance the device
    into the sheath by pushing ([not]{.underline} rotating) the delivery
    cable.

**NOTE:** *REFER TO DIAGRAMS FOLLOWING THIS SECTION*

-   Under fluoroscopic and echocardiographic guidance, deploy the left
    atrial disc and waist and pull the device [gently]{.underline}
    against the atrial septum, which can be felt and also observed by
    ultrasonography. With tension on the delivery cable, pull [the
    sheath]{.underline} back and deploy the right atrial disk. Pull the
    sheath back by approximately 15 cm. A [gentle]{.underline} "to and
    fro" motion with the delivery cable assures a secure position across
    the atrial septal defect, which can also be observed by ultrasound.

> ***WARNING:* Do not release the device from the delivery cable if the
> device does not conform to its original configuration or if device
> position is unstable. Recapture the device and redeploy. If still
> unsatisfactory, recapture the device and replace with a new device.**

-   [Confirm correct placement]{.underline}. If device placement is
    unsatisfactory or if the device does not reconfigure to its original
    shape, retract the device into the sheath and redeploy or replace
    with a new device.

-   [Release the device]{.underline}. Attach the plastic vise to the
    delivery cable by tightening the screw on the vise. Release the
    device by rotating the vise counterclockwise as indicated by the
    arrow. In the unlikely event that this should not be possible,
    advance the sheath against the right atrial disc to secure the
    device, which will facilitate detachment.

![](media/image2.wmf)

**To exchange the delivery sheath**

The AMPLATZER Exchange System is a delivery system especially adapted
for use in conjunction with the AMPLATZER family of occlusion devices.
The system components are identical to the AMPLATZER Delivery System,
with the exception of the dilator, which incorporates an enlarged inner
lumen for passage over an AMPLATZER delivery cable.

The AMPLATZER Exchange system is used to exchange the delivery sheath
during a procedure. It may become necessary to exchange the sheath for a
larger size.

\`

-   Peel open the package and flush the delivery sheath, dilator and
    loader using sterile heparinized normal saline or a similar isotonic
    solution by connecting a syringe to the luer hub of each component.

-   Insert the dilator into the delivery sheath and secure with the
    locking mechanism

-   Screw the delivery cable to the capsule located on the proximal end
    of the original delivery cable thus doubling its length.

    ![](media/image3.png){width="3.7465277777777777in"
    height="0.5916666666666667in"}

-   Once securely attached, remove the original delivery sheath from the
    patient and discard.

-   Introduce the dilator/delivery sheath exchange assembly over the
    lengthened cable assembly through the groin. Once the delivery
    sheath has reached the inferior vena cava, remove the dilator to
    allow back bleeding to purge all air from the system.

-   Advance the delivery sheath over the cable through the communication
    and disconnect the secondary cable.

-   Proceed with device recapture and/or deployment according to the
    instructions provided with the AMPLATZER Occlusion device.

# Patient Counseling Information

The patient and family should be advised of the known risks of the
implantation procedure and follow-up as discussed in other sections of
this manual, as well as the potential benefits. The patient should also
be advised to read *A Patient's Guide to Transcatheter closure of an
Atrial Septal Defect Using the AMPLATZER® Septal Occluder System.*

# Patient Registration

Inside the shipping container for each AMPLATZER Septal Occluder is an
implant registration form that creates a permanent record of your
patient's implant. It is important that you complete the form and
promptly return the original to AGA Medical Corporation. Copies are
provided for the patient's medical records.

AGA Medical will transfer vital information to a wallet-sized laminated
identification card and will mail it directly to the patient. A
temporary identification card provided on the form for the patient's use
until the permanent card arrives.

# Physician Training

Proctoring is required prior to implanting the device for the first
time. Physicians are required to contact AGA Medical Corporation and
request a referral to a physician experienced in the implantation
techniques of the AMPLATZER Septal Occluder. A minimum of three patients
are required for the proctoring session. A copy of the patients'
echocardiograms and any other pertinent information must be sent to the
proctor prior to the proctoring session to verify patient suitability
for the procedure.

Physicians should be thoroughly familiar with the AMPLATZER System
supporting material including all product labeling and education and
training materials.

# How Supplied

The AMPLATZER Septal Occluder, Delivery System and Exchange System are
all packaged separately from the AMPLATZER Delivery System.

NOTE: The contents of the inner package are **STERILE**.

# Detailed Device Description

## AMPLATZER Septal Occluder

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

![](media/image4.png){width="1.3854166666666667in"
height="1.238888888888889in"}

Table 8 - Device Specifications/Recommended sheath sizes

+----------+----------+----------+----------+---------+-------------+
| ORDER    | A        | B        | Width Of | C       | recommended |
|          |          |          |          |         | sheath size |
| NUMBER   | Device   | LA Disc  | Co       | RA Disc |             |
|          | Size     | Diameter | nnecting | D       |             |
|          |          |          | 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 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+

## AMPLATZER Delivery System

The AMPLATZER Delivery System was designed specifically to facilitate
attachment, loading, delivery and deployment of the AMPLATZER Septal
Occluder and is comprised of:

-   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 direction 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.

+----------------------------+---------------+-----------+------------+
| ORDER NUMBER               | SHEATH        | TIP       | USABLE     |
|                            |               |           | LENGTH     |
|                            | SIZE          | ANGLE     |            |
+============================+===============+===========+============+
| ![](media/image5.png)      |               |           |            |
+----------------------------+---------------+-----------+------------+
| 9-DEL-6F-45/60             | 6 French      | 45°       | 60         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-7F-45/60             | 7 French      | 45°       | 60         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-7F-45/80             | 7 French      | 45°       | 80         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-8F-45/60             | 8 French      | 45°       | 60         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-8F-45/80             | 8 French      | 45°       | 80         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-9F-45/80             | 9 French      | 45°       | 80         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-10F-45/80            | 10 French     | 45°       | 80         |
+----------------------------+---------------+-----------+------------+
| 9-DEL-12F-45/80            | 12 French     | 45°       | 80         |
+----------------------------+---------------+-----------+------------+

## AMPLATZER Exchange System

The AMPLATZER Exchange System is comprised of the identical components
as the Delivery System, and is available in the following
configurations:

  ------------------------------ ------------- ----------- ---------------
  **Order \#**                   **French**    **Curve**   **Length**

  9-EXCH-9F-45/80                9             45°         80 cm

  9-EXCH-12F-45/80               12            45°         80 cm
  ------------------------------ ------------- ----------- ---------------

# Glossary

ASD - Atrial Septal Defect

CAD - Coronary Artery Disease

CHF - Congestive Heart Failure

Closure Success - The successful closure of the atrial septal defect
(defined as \< 3mm residual shunt)

Composite Success- Closure (either device placement or surgery) without
a major complication, surgical reintervention, embolization or
significant shunt

COPD - Chronic Obstructive Pulmonary Disease

Fenestrated Fontan - Procedure performed to allow right to left shunting
in patients with complex congenital heart disease to reduce right sided
cardiac failure and pleural effusion

Hemodynamically insignificant shunts- Those shunts that are trivial
(\<1mm) and small ( [\<]{.underline} 2 mm)

Hemodynamically significant shunts- Those shunts that are moderate (
\>2 - 4mm) and large (\> 4 mm)

Large Shunt - Echocardiographic evidence of residual shunt measuring
more than 4mm. This is hemodynamically significant

Moderate Shunt - Echocardiographic evidence of residual shunt measuring
between 3 and 4mm. This is hemodynamically significant

Multiple Devices - Patients who currently have more than one device

Small shunt - Echocardiographic evidence of residual shunt measuring
between 1 and 2 mm. This is not hemodynamically significant

Qp/Qs - The ratio of pulmonary to systemic flow

TEE - Transesophageal echocardiogram

TIA - Transient Ischemic Attack

Trivial Shunt - Echocardiographic evidence of residual shunt measuring
less than 1mm. This is not hemodynamically significant

TTE - Transthoracic echocardiogram

# Warranty Information

The AMPLATZER Septal Occluder and Delivery System may be damaged by
improper handling or use. AGA Medical Corporation disclaims all
warranties, both express and implied, including, but not limited to, any
implied warranty of merchantability or fitness for a particular purpose.
AGA Medical Corporation shall not be liable to any person for entity for
any medical expenses or any direct, incidental or consequential damages
caused by any defect, failure or malfunction of the system, whether a
claim for such damage is based upon warranty, contract, tort or
otherwise.