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

**Instructions for Use**

Table of Contents

> [Section]{.underline} [Page]{.underline}

1.  Brief Device Description 1

2.  Indications & Usage 1

3.  Contraindications 1

4.  Warnings 2

5.  Precautions 2

6.  Adverse Events 3

7.  Clinical Studies 5

8.  Individualization of Treatment 9

9.  Patient Information 10

10. How Supplied 10

11. Directions for Use 10

**AMPLATZER® Septal Occluder and Delivery System**

Caution: Federal law (USA) restricts this device to sale by or on the
order of a physician (or properly licensed practitioner).

1.  **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.

2.  **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.

3.  **CONTRAINDICATIONS**

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

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

    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.

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

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

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

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4.  **WARNINGS**

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

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

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        be withdrawn through intracardiac structures unless they have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

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

5.  **PRECAUTIONS**

    1.  Handling

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

    1.  Sizing

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-   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.

    1.  Procedural

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

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-   Transesophogeal 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.

    1.  Post-Implant

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-   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.

6.  **ADVERSE EVENTS**

    1.  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.

##  {#section .unnumbered}

2.  Deaths

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

3.  Observed Adverse Events

    1.  Pivotal Clinical Study

**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 |
+-----------------------------------+-----------+------------+--------+

2.  Registry Group -- Fenestrated Fontan

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              |
+-------------------------------+----------------+--------------------+

4.  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

1.  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    |
+------------------------+---------------+-------------------+---------+

1.  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%)             |
+------------------------------------------+---------------------------+

7.2 Methods

7.2.1 Device Patients

> 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.

2.  Surgical Control Group

> 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.

3.  Results

**Table 5: 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        | 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      | 8/154 (5.2%) | (-0.090,    |
| 12-months                 | (1.6%)     |              | -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 (K-M) | 0.909      | 0.956        | \[-0.091,   |
|                           |            |              | -0.003\]    |
+---------------------------+------------+--------------+-------------+
| 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.

2.  Registry Group -- Fenestrated Fontan

    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"

7.  **INDIVIDUALIZATION OF TREATMENT**

8.1 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.

8.2 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.

8.  **PATIENT INFORMATION**

> Refer to the *Patient's Guide to Transcatheter Closure of an Atrial
> Septal Defect Using the AMPLATZER® Septal Occluder System*.

9.  **HOW SUPPLIED**

> The AMPLATZER Septal Occluder is packaged separately from the
> AMPLATZER Delivery System. Refer to Table 8 in the following section
> for the recommended Delivery System sizes.

10. **DIRECTIONS FOR USE**

11.1 Maintaining Device Effectiveness

Store in a cool dry place.

11.2 Complete Device Description

11.2.1 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/image1.png){width="1.3854166666666667in"
height="1.238888888888889in"}

Table 8 - Device Specifications/Recommended sheath sizes

+----------+----------+----------+----------+---------+-------------+
| Order    | A        | B        | Width Of | C       | recommended |
|          |          |          |          |         | sheath size |
| ## Numb  | Device   | LA Disc  | Co       | RA Disc |             |
| er {#num | Size     | Diameter | nnecting | D       |             |
| ber .unn |          |          | Waist    | iameter |             |
| umbered} | (=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 |          |          |          |         |             |
+----------+----------+----------+----------+---------+-------------+

11.2.2 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.

![](media/image2.png){width="6.0in" height="3.7194444444444446in"}

11.3 Directions for Use

-   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 ON PAGE 15*

-   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)