SynCardia Systems Inc.

CardioWest Total Artificial Heart (TAH)

DIRECTIONS FOR USE

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1992 E. Silverlake Road

Tucson, AZ 85713

520-545-1234

Table of Contents

Page

**1.0 Device
Description**.................................................\......\...
3

> 1.1 Implantable
> TAH..............................\............\......... 3

1.2 External
Console...........................................\...\...\.... 4

**2.0 Indications for
Use**.............................................\............ 4

**3.0
Contraindications**......................................................\...
4

**4.0 Warnings**
\...\...\...\...\...\...\...\...\.................................................
5

**5.0
Precautions**...................................................\...\........\.....
6

**6.0 Summary of Clinical
Study**............................................. 7

6.1 Trial
Success........................................................ . 7

6.2 Hemodynamics........................................................
7

6.3 Adverse
Events........................................................ 8

6.4 TAH
Reliability........................................................ 9

**7.0 Implant
Procedures**\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....
10

> 7.1
> Preparation\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...
> 10
>
> 7.2 Removal of Native Ventricl
>
> es\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.... 11
>
> 7.3 Preparing the
> Atria\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\....
> 13
>
> 7.4 Outflow
> Connectors\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...
> 14
>
> 7.5 Connect Artificial
> Ventricles\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\....
> 15

**8.0 Operator's Manual for
Console**....................................... 20

> 8.1 Warnings for Console
> Operation............\...\...\...\...\...\...\...\...\..... 20
>
> 8.2 Readying Console for Clinical
> Use\...\...\...\...\...\...\...\...\...\...\...\...\...\..... 21
>
> 8.3 TAH Startup
> Procedure\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\............
> 21

**9.0 Explant
Procedures**.......................................\.........\.........
23

**10.0 System
Components**\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\...\.....
24

**Appendix A: Patient Selection and
Management**...................................... 25

> Patient
> Selection\....................................\.......\............................
> 25

Anticoagulation.........................................\...\..................\........\...
25

Exit
Site..............................................................................
26

**Appendix B: Outline of Training
Program**............................................ 27

**Appendix C: Materials
Matrix**............................................................ 28

**1.0 Device Description**

The SynCardia CardioWest Total Artificial Heart (TAH) system is a
pulsatile biventricular device that replaces a patient\'s native
ventricles and valves and pumps blood to both the pulmonary and systemic
circulation. The system consists of the implantable CardioWest TAH and
an external console connected by drivelines (Figure 1).

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height="3.611111111111111in"}

**Figure 1: CardioWest TAH System**

1.  **The Implantable CardioWest TAH**

> The implantable CardioWest TAH consists two artificial ventricles,
> each made of a semi-rigid polyurethane housing with four flexible
> polyurethane diaphragms separating the blood chamber from the air
> chamber. The diaphragms allow the artificial ventricle to fill and
> then eject blood when compressed by air from the external console.
> Mechanical valves, mounted in the inflow (27mm) and outflow (25mm)
> ports of each artificial ventricle, control the direction of blood
> flow. The maximum dynamic stroke volume of each ventricle is 70 ml,
> which allows for generating a flow rate up to 9.5 liters per minute.
>
> The left artificial ventricle is connected via the left atrial inflow
> connector to the left atrium, and via the aortic outflow cannulae to
> the aorta. The right artificial ventricle is connected via the right
> atrial inflow connector to the right atrium and via the pulmonary
> artery outflow cannulae to the pulmonary artery. Each artificial
> ventricle's driveline conduit is tunneled through the chest wall. The
> right and left artificial ventricle's driveline conduits are attached
> to seven-foot pneumatic drivelines that connect to the back of the
> external console.

## **The External Console**

> The external console operates and monitors the CardioWest TAH. The
> console includes a monitoring computer that provides noninvasive
> diagnostic and monitoring information to the user. Device rate,
> dynamic stroke volumes, and calculated cardiac outputs are displayed
> on a beat-to-beat basis. Drive pressure and flow waveforms, along with
> cardiac output trends are provided. Patient related alarms (e.g., low
> cardiac output) are also displayed on the computer screen.
>
> A separate alarm panel on the console provides information on critical
> drive pressure and backup air and battery status. In addition, an
> alarm is generated if the computer is not monitoring the patient. All
> alarms generate audio and visual feedback to the user.
>
> A backup air supply (two air tanks) and electrical power (backup power
> supply and console battery) are automatically activated if the
> external compressed air and/or AC power are interrupted. This can
> occur during patient transport or in the event of a failure in the
> hospital's air or electrical supply.
>
> The controller is the major component of the external console, and
> supplies pulses of pneumatic pressure to the right and left
> drivelines, which connect into the air chambers of the respective
> implanted artificial ventricles. These pulses cause the diaphragms to
> distend and thereby eject blood from the right artificial ventricle
> into the pulmonary circulation (typically 50-70mmHg) and from the left
> artificial ventricle into the systemic circulation (typically
> 180-200mmHg).

**2.0** **Indications for Use**

> The SynCardia Systems, Inc., CardioWest Total Artificial Heart
> (hereinafter called the CardioWest TAH) System is indicated for use as
> a bridge to transplantation in cardiac transplant candidates at risk
> of imminent death from non-reversible biventricular failure.  The
> CardioWest TAH System is intended for use inside the hospital.

3.  **Contraindications**

The CardioWest TAH is contraindicated for us in patients with body
surface areas \< 1.7m².

4.  **Warnings**

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1)  Setup and operation of this device should only be undertaken by
    personnel trained in accordance with the SynCardia training program.
    A thorough understanding of the technical principles, clinical
    applications, and risks associated with the device is necessary.
    Prior to use, refer to this IFU and to the CardioWest TAH Operator's
    Manual for important operating instructions.

2)  Sterile components of the CardioWest TAH are intended for single use
    only. Do not use if package is damaged. Do not re-sterilize or
    reuse.

3)  Safe use of this system has not been established in pregnant
    patients.

4)  Do not subject patients implanted with the CardioWest TAH to
    magnetic resonance imaging (MRI) scans.

5)  Safety and effectiveness in populations other than those of
    idiopathic and ischemic cardiomyopathies has not been established.

6)  Do not use this device if the implantable artificial ventricles
    cannot fit in the chest area vacated by the natural ventricles.
    Inferior vena cava and left pulmonary venous compression are
    possible consequences.

7)  Do not allow any catheter to get near the inflow valves of the
    CardioWest TAH. If a catheter gets into an inflow valve, the valve
    could become stuck, limiting flow. Confirm by x-ray after catheter
    insertion. A percutaneously inserted central catheter may migrate
    into the inflow valve when the patient raises their arm.

8)  There is a potential for air embolism. De-air the artificial
    ventricles to minimize the possibility of air inadvertently entering
    the device.

9)  Do not allow the external drivelines to become kinked. If there is
    any low cardiac output alarm, inspect the external drivelines for
    kinking.

10) A reduction in the maximum stroke volume on the external console's
    monitoring computer to below 50 milliliters may indicate a failure
    of one of the diaphragms in an artificial ventricle of the
    CardioWest TAH.

**5.0 Precautions**

1)  Measures should be taken to prevent infection or sepsis. Use strict
    aseptic techniques during implantation.

2)  The outflow grafts must be pre-clotted before use.

3)  When closing the chest, a reduction in device output may indicate
    inflow obstruction. Reposition the artificial ventricles by
    anchoring to a rib or moving into the left plural space.

4)  Do not use an antifibinolitic agent like Aprotinine or Amicar with
    an active clotting agent like FEIBA.

5)  Use only water-soluble antiseptic cleaners around the exit site.
    Ointments may delay tissue in-growth into the driveline conduits.

6)  Each external console contains a primary and a backup controller. An
    additional external console should also be available for use.

7)  A sudden reduction in CardioWest TAH flow may be due to a kink in
    the pneumatic drivelines, or some inflow obstruction to the
    CardioWest TAH, such as tamponade. Defibrillation or CPR will not be
    effective.

**6.0 Summary of Clinical Study**

The multi-center clinical (5) study focused on use of the CardioWest TAH
as a bridge to cardiac transplantation in transplant eligible patients
at risk of imminent death from non-reversible biventricular failure.
Ninety-five patients (ages 16-67) were implanted with the CardioWest TAH
and 35 patients were controls. Of the 95 patients implanted, 81 (70
males, 11 females) met all inclusion/exclusion criteria and were
designated the *core implant group*. All patients were in NYHA Class IV
at time of enrollment. The *control group* did not receive the TAH but
met study inclusion/exclusion criteria. Both groups were on maximal
medical therapy and at imminent risk of death before a donor heart could
be obtained.

1.  **Trial Success**

> Treatment success was defined as patients who, at 30 days post
> transplant, were 1) alive; 2) NYHA Class I or II, 3) not bedridden; 4)
> not ventilator dependent; and 5) not requiring dialysis.
>
> Trial success was achieved in 56 (69%) of the 81 core patients and in
> 13 (37%) of the 35 control patients. *The difference was highly
> significant* (*p=0.0019*). Statistical significance was also found
> with respect to survival to transplant (p=0.0008) and survival to 30
> days post transplant (p=0.0018). Of the core patients, 64 of the 81
> (79%) reached transplant after an average of 79 days (range 1-414). 16
> of the 35 (46%) controls reached transplant after an average of 9 days
> (range 1-44). 58 (72%) core patients and 14 (40%) controls survived to
> 30 day post transplant.
>
> There are not data to document success of the device in patients with
> severe pulmonary edema.

2.  **Hemodynamics**

> The hemodynamic performance of the CardioWest TAH was assessed through
> a comparison of pre- and post-implant values of cardiac index,
> systolic arterial blood pressure, and central venous pressure.
> Hemodynamic indices were effectively restored to near normal values.
> Average cardiac index increased from 1.9 to 3.0 L/min/m², average
> systolic blood pressure increased from 93mmHg to 120mmHg, and average
> CVP decreased from 20mmHg to 14mmHg.
>
> The average perfusion pressure (mean aortic pressure minus CVP)
> increased from 49mmHg to 63mmHg, which was associated with recovery of
> renal and hepatic function.

3.  **Adverse Events**

> Adverse events collected for all 81 core patients while on the
> CardioWest TAH device are presented in descending order below. The
> adverse events represent 17.6 device years of experience for an
> overall event rate of 1.9 events per month while on the device
> awaiting transplant. By comparison, 89 events occurred in 31 of the
> control patients (88.9%) during a total of 299 days awaiting
> transplant, for an overall event rate of 3.6 events per month while
> waiting for transplant.

Table 1\
Incidence of Adverse Events in Core Patients During Device
Implantation,\
in Decreasing Order of Frequency\
(Represents 17.6 years or 6411 days on the device)

  ------------------------------- ----------------- ---------------------
  **Adverse Event**               **Number of       **Number (%) of
                                  Events**          Patients\
                                                    n=81**

  Any Adverse Event               400               76 (93.8%)

  Infection                       125               58 (71.6%)

  Bleeding                        55                34 (42.0%)

  Respiratory Dysfunction         44                24 (29.6%)

  Hepatic Dysfunction             30                29 (35.8%)

  Neurological Event              26                20 (24.7%)

  Renal Dysfunction               23                21 (25.9%)

  Reoperation                     18                17 (21.0%)

  Device Malfunction              18                15 (18.5%)

  Peripheral Thromboembolism      14                9 (11.1%)

  Reduced Blood Pressure          14                12 (14.8%)

  Cardiac Index                   11                7 (8.6%)

  Technical/Procedural            11                3 (3.7%)

  Fit Complication                5                 5 (6.2%)

  Hemolysis                       3                 3 (3.7%)

  Miscellaneous                   3                 3 (3.7%)
  ------------------------------- ----------------- ---------------------

4.  **CardioWest TAH Reliability:**

> Reliability testing was conducted to determine with reasonable
> assurance how long a device would perform as intended, without
> failure.
>
> Three separate sets of *in vitro* reliability testing were conducted.
> In one test, four TAH units were run for a period of 180 days. During
> this time there were no failures or abnormalities observed.
>
> In a second *in vitro* reliability trial, four TAH units were tested
> in a "run to failure" study design and are ongoing. After 35 months of
> testing, there were no failures or abnormalities observed.
>
> A third test was initiated using three TAH units which had expired
> their 3 year sterilization expiration date. This provided information
> about the effects of long-term storage on the fatigue resistance
> properties of the TAH. After 24 months of testing, there were no
> failures or abnormalities observed.
>
> In conclusion, a total of eleven units have been run for various
> lengths of time over the last six years with no device-related
> failures. The cumulative number of days used for calculation was 6715
> and there have been no failures or signs of appreciable wear observed.
> When the 11 units are used to calculate reliability with a 90%
> confidence, the reliability at 30, 60 and 365 days is as reported in
> the table below.

Table 2\
Reliability Test Results with 90% Confidence

  --------------- ---------------- -------------- ------------- -----------
  \# days run     MTBF\*           Reliability in               
                                   number of days               
                                   run                          

                                   30             60            365

  6715            2916             0.99           0.98          0.88
  --------------- ---------------- -------------- ------------- -----------

**7.0 Implant Procedures**

This section contains the Implant Procedures. Patients receiving the
CardioWest TAH are prepared for the implant per standard hospital
procedures for any cardiac surgery. An arterial line, a central line,
and standard artificial ventilation are required prior to the start of
surgery. Transesophogeal echocardiography is recommended.

**7.1 Preparation**

-   Pass the CardioWestTAH sterile components into the sterile field.

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-   After a standard median sternotomy is performed and before starting
    heparin, 1) prepare the arterial outflow connectors, 2) trim atrial
    inflow connectors to appropriate size, and 3) tunnel the artificial
    ventricle conduits through the skin.

-   Preclot the two arterial outflow connectors three times with the
    patient\'s blood before giving the heparin. After exposure to the
    blood (approx. 30 cc for each connector each time) stretch
    connector, let dry for about 5 minutes and preclot again. The
    connectors are coated on the outside with biologic glue
    (cryoprecipitate with calcium and topical thrombin). Stretch again
    and let dry. This is done before cannulation so there is plenty of
    time to obtain sufficient preclotting of the outflow connectors. If
    the patient has been heparinized before deciding to implant the
    CardioWest TAH, the arterial outflow connectors should be preclotted
    with a combination of heparinized blood, protamine, and thrombin.

-   Trim the two inflow connectors. Cut edges of the atrial quick
    connects for the atrial anastomoses to a radius extending out from
    the connector for 5-7 mm. Cut in a completely circular fashion. Then
    stretch and invert them.

-   Pass the drivelines conduits through their subcutaneous pathways
    before heparinization of the patient. Position the left-sided
    ventricle conduit in the epigastrium at the level of the
    midclavicular line and approximately 2 inches below the costal
    margin. Make a semicircular skin flap incision on the left
    midclavicular line approximately 5 to 10 cm below the costal margin.

-   Place a long clamp through the subcutaneous tissue, rectus fascia,
    rectus muscle, and into the chest as a chest tube would be placed.
    Use a similar approach to place the driveline conduit for the
    prosthetic right ventricle, approximately 4 to 5cm medial to the
    left ventricle conduit so that no necrosis between the two exit
    sites will result.

-   Enlarge pathway by opening the clamp and inserting a 1-inch Penrose
    drain through the pathway. Place the end of the conduit in the
    Penrose drain and advance approximately 8-10 cm. Pull Penrose drains
    through the pathway that delivers the driveline conduit. Position
    the artificial ventricles lateral to the wound and cover with a
    towel while the rest of the procedure takes place. This provides
    ample opportunity for small bleeders in the driveline pathway to
    clot.

> **7.2 Removal of the Native Ventricles**

-   Cannulation of the aorta and both superior and inferior vena cava is
    done in a standard fashion. Umbilical tape chokers are used on the
    cavae. Dissection around the aorta and pulmonary artery is limited
    to the proximal portion of the aorta in anticipation of
    transplantation, thus leaving some untouched areas that will not be
    very fibrotic. Cardiopulmonary bypass is instituted and the heart is
    fibrillated. Total bypass is instituted by pulling on the choker
    tapes.

-   The heart is fibrillated and excision of the heart begun. The
    excision is different from that used for transplantation. It seeks
    to preserve the annulus of both the tricuspid and mitral valves.
    Thus, an incision is made on the ventricular side of the AV groove
    of the right ventricle (Figure 2).

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**Figure 2: First Incision of Ventricle Excision**

-   Incision can be done with a knife and extended with a knife or
    scissors. It is extended anteriorly across the right ventricular
    outflow tract and just proximal to the pulmonary valve. Posteriorly,
    it is extended to the interventricular septum and across the septum,
    staying on the left side of the arterioventricular (AV) groove and
    preserving the entirety of the mitral annulus. The anterior and
    posterior lines of incision are dissected apart from each other out
    to the level of the pulmonary bifurcation.

-   Trim the excess muscle on the right and left sides down to near the
    AV valves. All chordae are trimmed away, and a 2 mm edge of valve
    tissue along with the annulus is left intact. The atrial cuff
    generally extends 1 cm beyond the AV valves and consists of residual
    ventricular muscle and fat in the AV groove. The portion of the cuff
    in the left ventricular outflow tract consists of the residual
    anterior leaflet of the mitral valve and some aortic tissue. Most of
    the aortic tissue is trimmed away; however, some is left intact
    because it is felt to present strong tissue for the sewing of the
    inflow connector. The great vessels are then separated from the
    remaining ventricular myocardium above the valvular level. The great
    vessels are separated from each other (Figure 3).

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**Figure 3: Ventricles Removed**

> Over-sew the coronary sinus entrance into the right atrium. This
> prevents backflow of blood through the coronary sinus and out to the
> cut vessels on the AV groove.

-   Three 15 by 20 centimeter sheets of membrane are used to create a
    neo-pericardium to prevent adhesions. On the right side a sheet is
    anchored with non-absorbable suture to the pericardial reflection at
    the level of the superior vena cava, pulmonary veins and inferior
    vena cava. On the left side, a second sheet is sutured to the
    pericardial reflection just anterior to the left pulmonary veins. On
    the diaphragmatic side, a third sheet is sutured so as to cover the
    entire diaphragmatic pericardial surface. The 3 sheets are then
    folded upon themselves to keep them out of the operative field while
    the CardioWest TAH is implanted.

**7.3 Preparing the Atria**

> The outer walls of the entire right and left atrial cuff complex are
> encircled with Teflon felt buttresses. These are placed in such a way
> that they can be used for strengthening the anastomosis to the inflow
> connector and also to tamponade and control all possible bleeding from
> the AV groove portion of the connector. These are cut to approximately
> 10-12 mm in width and are generally 10 cm in length. It most often
> takes at least two of these to extend around the entire atrial cuff.
> They are placed on the outer edge of the cuff and sewn in place with a
> running 3-0 polypropylene (Figure 4). A long needle is used to
> accomplish this (MH needle) and, after completing this, the left and
> right atrial cuffs are surrounded by Teflon felt buttresses.

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height="3.907638888888889in"}

> **Figure 4: Atrial Sutures**

-   The atrial inflow connector is sewn first. It is inverted and placed
    inside the left atrial cuff on the lateral wall. 3-0 polypropylene
    is used with an MH needle with a running stitch, taking care to
    tailor the atrial cuff and the inflow connector into a single
    hemostatic suture line. The suture line includes both free walls of
    the atrium, buttressed with Teflon felt in the atrial septum, which
    has no buttressing material. A similar procedure is done with the
    right inflow connector. The connector is inverted, placed in the
    atrium, the suture line is run, and after completing both suture
    lines, the inflow connectors are returned to their normal position
    (Figure 5).

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height="3.9770833333333333in"}

**Figure 5: Inflow connector inverted for suturing (left), finished
normal position (right)**

-   Check for hemostasis with the plastic leak tester made to fit within
    the inflow connector. A syringe (60-100 cc) is used to inject into a
    three-way stopcock connected with the tester to test the left atrial
    suture line. The surgeon places his hand posterior to the left
    atrium and compresses the right and left pulmonary veins, while the
    assistant injects saline mixed with a small amount of blood into the
    left atrium. Observe for leaks. A dental tool is used to break the
    seal between the tester and connector. If there are any leaks,
    sutures are placed at this time. On the right side, fluid is simply
    injected into the right atrium under pressure, since the inferior
    and superior vena cava are already obstructed by the caval tapes.
    Again, closure of leaks with a 3-0 MH polypropylene suture is done
    at this time.

**7.4 Outflow Connectors**

-   Great vessel connections are made. The pulmonary artery anastomosis
    is made first. The lengths of the outflow connectors are determined
    by placing the artificial ventricles in position within the
    pericardial cavity. Place the outflow connector between the aortic
    or pulmonic valve and its respective great vessel and measure the
    distance. Cut outflow connectors to the appropriate lengths, usually
    3 to 5 cm.

-   The pulmonary artery anastomosis is made with a running 4-0
    polypropylene suture in an end-to-end fashion, beginning with
    lateral wall and running the back wall of the anastomosis from the
    inside (Figure 6).

![](media/image8.jpeg){width="2.0243055555555554in"
height="3.4895833333333335in"}

**Figure 6: Outflow Connector Suturing**

-   A similar anastomosis is made with the aortic suture line. Then, the
    outflow connector leak tester is used, which is inserted into the
    aortic outflow connector. Saline is injected under pressure,
    observed for leaks, and then any leaks are closed with a 4-0
    polypropylene suture. The pulmonary artery needs to be cross-clamped
    in order to test the integrity of the pulmonary artery to connector
    anastomosis. The pulmonary artery and aortic tester is the same, but
    smaller, than the one utilized for the atrial inflow connector.

**7.5** **Connect Artificial Ventricles**

-   Once adequate hemostasis of all suture lines is established,
    placement of the artificial ventricles begins. First, the left
    artificial ventricle is connected (Figure 7).

![](media/image9.jpeg){width="3.7430555555555554in" height="4.53125in"}

**Figure 7: Connect Ventricles**

-   Grasp the left inflow connector with two large Mayo clamps placed
    side by side, with a good hold of the connector. The opposite side
    of the plastic fitting for the connector of the artificial left
    ventricle is placed within the connector, and the operator pulls
    with the Mayo clamps and pushes the artificial left ventricle into
    the inflow connector. The position in which the heart sits for the
    duration of the support of the patient is determined by the
    orientation of the artificial left ventricle as it is placed into
    the left atrial inflow connector. Therefore, a careful assessment of
    exactly where the aortic outflow connector will connect to the
    artificial left ventricle, and the anticipated position of the
    artificial left ventricle should be made before the connection of
    the atrial inflow connector is completed. It is then an easy matter
    to snap on the aortic outflow connector, taking care not to twist
    the connector or aorta. While this is being done, the artificial
    left ventricle should be filled with saline through the aortic valve
    as well as the outflow connector. Once the connection is made, the
    patient is placed in a steep Trendelenburg position and large vent
    sites are placed in the highest point of the aortic outflow
    connector and the aorta for removal of air.

-   The artificial right ventricle is then connected. The atrial
    connection is made first, again taking care with the orientation of
    the artificial right ventricle so that the direction of flow from
    the outlet valve is appropriate for the anatomy of the patient.
    After the atrial connection is made, the pulmonary outflow
    connection is made, again, taking care not to twist. Before
    connecting the pulmonary outflow connector graft, the chokers on the
    superior and inferior vena cava should be removed. This allows a
    flow of blood into the right atrium and the right artificial
    ventricle, and flushes air out as the connection to the pulmonary
    artery is made (Figure 8).

![](media/image10.jpeg){width="3.3493055555555555in"
height="3.7472222222222222in"}

**Figure 8: CardioWest TAH Final Position**

-   With the patient in extremely steep Trendelenburg position and lungs
    being slowly ventilated, begin pumping at a very slow rate (40 BPM,
    40%SYS, 180mmHg-LDP, 60mmHg-RDP, 0mmHg-VAC). Agitation of the
    artificial ventricles, as well as atria, is done at this time. If
    available, monitor for air bubbles in the atria and aorta with
    transesophageal echo to help decide when the device has been
    completely de-aired. As air is slowly removed from the device,
    increase pumping rate and pressure. Generally, this process takes
    about 10 minutes and should be done with patience and attention to
    remove air before the CardioWest TAH takes over from the heart-lung
    machine. Decrease flow on the heart-lung machine temporarily to help
    move air through the lungs and into the device. Once satisfied that
    all air is out of the device, close vent sites and begin full
    pumping as the heart-lung machine is weaned off. The patient should
    be kept in steep Trendelenburg for an additional 15-20 minutes.

-   As the table is flattened out, try to position the artificial
    ventricles within the mediastinum. The pleura on both sides should
    not be opened and the pericardium should be left intact for closure.
    In smaller patients, there may be a need to force the right
    ventricle under the left edge of the sternum. Care should be taken
    to examine the left pulmonary veins and the inferior vena cava for
    evidence of compression. This is facilitated with trans-esophageal
    echo.

-   Check for hemostasis. After protamine has been administered and
    hemostasis obtained, a trial closure of the sternum is done using
    towel clips. If the fit of the device is judged adequate by
    hemodynamic stability and by transesophageal echo examination of the
    caval and pulmonary venous flows, reopen the chest and bring
    together the edges of the Gortex sheets to form a tent or
    neo-pericardium. Take care to make a loose fit, without impingement
    upon the cavae and tension on the device. Prior to closure of the
    cephalic part of the neo-pericardium, pass a rectangular piece of
    Gortex membrane around the proximal ascending aorta and anchor with
    non-absorbable suture. This is to provide a surgical plane at
    explant between the aorta and pulmonary artery to facilitate
    encircling and cross clamping the aorta.

-   One chest tube is placed in the neo-pericardium and a second in the
    native pericardial space. Irrigate with antibiotic solution before
    closure. Close the sternum and remaining incision in a routine
    fashion. Check device output, central venous pressure, and device
    filling when the chest is closed, because chest closure may alter
    the anatomy, causing pressure on the left-sided pulmonary veins,
    inferior vena cava, and occasionally the right-sided pulmonary
    veins. If decreased flow is noted, the chest must be reopened and
    changes made in the position of the device. One change has been to
    mobilize the diaphragmatic attachment of the pericardium, allowing
    the device to sit more leftward in the chest. This requires opening
    the left pleura, allowing the CardioWest TAH to slightly migrate
    into the left pleural space. If decreased flow is still observed,
    the right artificial ventricle may need to be anchored to a rib
    using umbilical tape (Figure 9).

> ![](media/image11.jpeg){width="4.677777777777778in"
> height="3.1180555555555554in"}

**Figure 9: Solution to a Fit Problem**

**8.0 Operator's Manual for Console**

The operator's manual, Part \# 960001, contains detailed information on
the setup, operation and troubleshooting of the CardioWest TAH system. A
brief description of the contents is given as a reference.

-   **Introduction to the External Console:** Describes the system
    overview, indications for use, and warnings.

-   **Features and Operations:** Describes the operation of the
    controller, power supply, air supply, vacuum pump, UPS, alarms and
    computer.

-   **Unpacking and Initial Setup:** Covers unpacking instructions and
    initial setup.

-   **Performance Verification:** Describes the console test procedure
    and the preparation for standing by for an implant.

-   **Clinical Use:** Describes console operation, readying system for
    clinical use, CardioWest TAH startup, patient transport, transfer to
    backup controller, and console replacement.

-   **Specifications:** Describes the CardioWest TAH physical and
    performance specifications.

-   **Routine Maintenance and System Checkout:** Describes console
    checkout, batteries, cleaning, and checkout procedure.

-   **Field Service Guide:** Describes air tank replacement, scheduled
    servicing, air tank connector O-ring replacement, controller pilot
    pressure calibration, controller replacement, fuse replacement,
    inactive storage, and crating instructions.

    **8.1 Warnings for Console Operation**

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-   **DO NOT** operate or adjust system without proper training.

-   **DO NOT** operate console on an air supply of substandard or
    unknown quality, either from tanks or in-house compressors.

-   **DO NOT** use a controller outside of its planned maintenance
    cycle.

-   **DO NOT** intentionally operate a system having only one functional
    controller for any longer than is necessary to switch systems.

-   **DO NOT** defeat the alarm system by turning it off, tampering with
    the alarm mute button, by muffling the audible alarms, or by any
    other means.

-   **DO NOT** expose the system to any unusual environment, i.e.
    electric or magnetic fields, dampness or temperature extremes.

-   **DO NOT** leave key in primary controller key switch during an
    implant. The key may be kept on Velcro near top right side of the
    backup air supply compartment.

-   **DO** have a backup system in a state of ready standby.

-   **DO** set backup controller parameters to the same values as the
    primary controller.

-   **DO** have a controller switch key attached to the console.

-   **DO** keep system casters locked except for transport.

-   **DO** have a number of spare charged air tanks on hand.

    **8.2 Readying Console for Clinical Use**

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-   Two consoles should be in ready standby mode. Ensure that backup
    batteries are fully charged.

-   Verify that each system has been connected to AC power with the
    SYSTEM POWER switch in the ON (1) position

-   Confirm that each controller AC POWER/BATT CHRG lamp is on.

-   Before moving system to Operating Room, moisten a clean cloth with
    an antibacterial agent and wipe down all exterior surfaces of the
    console.

-   Do not spray any cleaning agent directly on system.

    **8.3 CardioWest TAH Startup Procedures**

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-   Turn SYSTEM POWER switch OFF (0); disconnect system mains power cord
    and move system to patient site.

-   Position the rear side of the console within driveline length of the
    patient's chest.

-   Lock front casters (wheels).

-   Connect system power cord and turn SYSTEM POWER switch ON (1).

-   Verify console AC POWER and CHARGE LEDs are green, indicating system
    has AC power.

-   Verify that both controller AC POWER/BATT CHRG indicator lights are
    on.

-   Connect main air supply and verify pressure is 50--110 psi (340-575
    kPa) at system power interface panel gauge.

-   Open primary and reserve air tank valves and verify they are fully
    charged.

-   Set primary and backup controllers to values listed below:

> Left Drive Pressure = 0 mmHg; Right Drive Pressure = 0 mmHg
>
> Vacuum = 0 mmHg
>
> Heart Rate = 40 bpm
>
> Systolic Duration = 33%
>
> Be sure vacuum remains off until the patient's mediastinum is closed.

-   Turn computer on. Wait for WCOMDU to load. Select Patient Monitoring
    Mode. Enter patient identification requested. Inhibit WCOMDU alarms
    during startup.

-   Be sure that LDP, RDP and VACUUM are zero. Turn primary CONTROLLER
    key switch On and press controller ALARM RESET button.

-   Turn ALARM SYSTEM key switch to ON. Mute console hardware alarms
    until LDP \> 90 mmHg and RDP \> 20 mmHg.

-   Verify controller is operating normally; connect left ventricle
    driveline to controller upon order by surgeon. After left ventricle
    is connected and de-aired, await instructions from surgeon to start.
    To start left ventricle, raise LDP to about 100 mmHg. You should see
    a slight overload of the cardiopulmonary bypass waveform and WCOMDU
    may show a small output.

-   Connect right ventricle driveline to controller. After right
    ventricle is connected and de-aired, await surgeon's instructions to
    start the right ventricle. To start right ventricle, raise RDP to 40
    mmHg.

-   As perfusionist begins to slow venous return, CardioWest TAH filling
    should increase. As filling increases, adjust drive pressures, heart
    rate and systolic duration to prevent full fill and to provide full
    ejection. Normal range is LDP= 170-210 mmHg, RDP= 60-100 mmHg, %
    Systole=50-60. Be vigilant during the weaning process, you may need
    to make rapid adjustments. Observe WCOMDU waveforms for signs of
    flow obstruction and other cardiac output information.

-   After chest is closed, vacuum may be started (normal range is
    approximately 10 mmHg). Do not exceed 30 mmHg vacuum.

-   Remove key from the primary controller key switch before moving
    patient.

-   Pneumatic drive ejection pressures should be set to achieve full
    ejection. Pressure tracings on the monitoring computer can be viewed
    to assure the right drive pressure is set to overcome the pulmonary
    systolic pressure, and the left drive pressure is set to overcome
    the aortic systolic pressure.

-   The CardioWest TAH rate should be set to achieve a stroke volume
    between 50 and 65 milliliters on the monitoring computer. CardioWest
    TAH beat rates should be between 100 and 130 beats per minute.

**9.0 Explantation Procedures**

> Explantation of the device should be handled like any other redo
> cardiac procedure. Great care should be taken in the separation of the
> sternum from the device, the great vessel connector, and the
> drivelines. Explantation may be easier if the device is covered with a
> Gortex membrane.
>
> Cardiopulmonary bypass is initiated with dual caval cannulation with
> tourniquets, the aorta is cross-clamped, and the CardioWest TAH is
> turned off. The artificial ventricles are separated from the atrial
> inflow cannula. The great vessels outflow connectors are amputated at
> the level of the connector/great vessel anastomosis. The artificial
> ventricles are transected at the base to the driveline conduit
> connection, and the CardioWest TAH is removed from the operating
> field. The driveline conduits are pulled through the skin. The
> remaining atria inflow connectors are still in the remaining portion
> of ventricular muscle where they were initially sutured. They are
> removed by transecting the AV groove throughout. The remaining atria
> and great vessels can now be trimmed to accept the donor heart.

**10.0 System Components**

> The CardioWest TAH system is comprised of the following:

-   Implant Kit - Part \# 500101 (Sterile)

> Contains left artificial ventricle, right artificial ventricle, 2
> inflow connectors, 2 outflow connectors, and an ancillary pack with
> drivelines, inflow pressure test plug, outflow pressure test plug,
> locking ties, and 2 de-airing needles (all sterile). All sterile
> components are packaged in double aseptic transfer packages.

-   Surgical Spares Kit - Part \# 500177 (Sterile)

> Contains inflow connector, outflow connector, drivelines, inflow
> pressure test plug, outflow pressure test plug, and locking ties.

-   Circulatory Support System (External Console) -- Part \# 500207
    (Non-sterile)

-   Air Tank - Part \# 390004 (Non-sterile)

> There should be two complete implant kits, one surgical spares kit,
> two circulatory support systems and eight air tanks.

**Appendix A**

**Patient Selection and Management**

Management and coordination of successful CardioWest TAH support
requires a multidisciplinary team that has experience with circulatory
support systems. Teams can include surgeons, cardiologists, heart
transplant coordinators, perfusionists, engineers, nurses, cardiac
rehabilitation therapists and coagulation specialists. The following
reports the experience of the largest enrolling clinical site,
University Medical Center, Tucson, Arizona:

**Patient Selection**

Successful bridge to transplant with the CardioWest TAH involved
selecting patients who were transplant eligible and who additionally
were assessed in two main areas: 1) evaluation of fit of the CardioWest
TAH in the patient's chest, and 2) evaluation of the potential for
reversal of any end organ dysfunction.

Once the CardioWest TAH is implanted, and there were no fit issues, flow
was maximized through the CardioWest TAH. The controller average
settings during the trial were: left drive pressure of 180-220 mmHg,
right drive pressure of 50-70mmHg, device rate of 110-130 BPM, percent
systole of 50-55%, and diastolic vacuum of 8-12 mmHg. With these
settings an average device output was 6.5-7.5 LPM, with a CVP of 8-12
mmHg.

The CardioWest TAH is specified for patients with body surface areas of
at least 1.7 m². At a cardiac index of 2.5 l/min/m², the calculated flow
would be 4.25 liters/min. This is the flow used to simulate hypotensive
conditions tested during product reliability testing. The TAH console is
pre-set with an alarm to indicate flows \<3.5 l/min.

With normalized hemodynamics, device outputs remained relatively
constant, changing as the CVP fluctuated. This "Starling like response",
(where an increase in CVP fills the CardioWest TAH with more volume,
which is ejected on the next beat, increasing device output), required
no controller adjustments. Constant device output and high flow under
normal CVP provided good washing of the artificial ventricles.

**Anticoagulation therapy**

The level of anticoagulation will vary depending on the patient's
coagulation status. In general, the patient required systemic
anticoagulation, similar to that used for patients with mechanical
valves. The following guidelines were used by the largest enrolling
clinical site:

*Pre-operative baseline*

Results of PT, PTT, bleeding time, TEG, platelet count, platelet
aggregation studies and fibrinogen were obtained.

*Intra-operative period*

Heparinized for CBP per usual routine. Protamine was used for reversal
per usual routine.

*Post-operative period (immediate)*

Dipyridamole was started at 100 mg -250 mg PO or NG every 6 hours. The
dose was adjusted to balance platelet aggregation factors: collagen
factor kept positive; ADP, epinephrine, arachnadonic acid factors were
kept negative. If all factors were positive, the dose of dipyridamole
was maximized. If only one factor other than collagen is positive,
dipyridamole or ASA were increased until only collagen was positive.
Platelet aggregation studies were checked twice per week.

ASA was started when platelet aggregation showed any factor other than
collagen was positive, usually within 24 hours post-operative. The ASA
dose was started between 81-650 mg PO per day. If all platelet
aggregation factors were positive and the dipyridamole was already
started, 325 mg of ASA was used per day to start. If only one factor,
other than collagen, was positive, ASA was started at 81 mg per day. The
dipyridamole was adjusted according to the results of Platelet Factor 4
and Beta Thromboglobulin. If these tests were elevated, the platelets
are very active and the dipyridamole needed to be increased. ASA is
adjusted with the platelet aggregation and bleeding time studies. The
bleeding time was kept between 10 - 20 min if possible.

If the collagen was negative, too much dipyridamole or ASA was being
given; daily dosages of one or both were decreased to prevent bleeding.

Pentoxifylline 400 mg was started PO every 8 hours in the early
post-operative period (2-3 days). Pentoxifylline could be increased if
fibrinogen increased above normal.

*Post-operative (chest tubes pulled)*

IV Heparin was started at 25,000 units in 250 cc of D5W at 500-1000
units per hour, when chest tubes were discontinued. IV Heparin was
continued to maintain PTT at 50-55 sec for 2 weeks, then converted to
Coumadin to keep INR 2.5-3.5 or PT 18-22 sec then IV Heparin was
stopped.

Exit Site Management

Take care to keep driveline exit sites clean and dry. Infections should
be treated according to hospital protocol.

**Appendix B**

**Outline of Training Program**

Operation of this device should only be undertaken by personnel trained
in accordance with the SynCardia Training Program. The training will
include the following topics:

1)  Indications and Contraindications

2)  System Overview

3)  Implant Procedures

4)  Operation of the console

5)  Explant Procedures

6)  Patient Management

7)  Summary of Clinical Studies

8)  Animal Procedure -- a minimum of one implant needs to be performed.

9)  Cadaver Study -- a minimum of one study to practice surgical
    technique and to become familiar with fitting the device.

10) Surgical Proctors -- surgeons may view an implantation of the device
    at a center of excellence or have oversight during the initial case.

**Appendix C**

**Materials Matrix**

The CardioWest TAH ventricle components are manufactured from the raw
materials as defined in the matrix below. The artificial ventricles have
met the test requirements of ISO 10993, *Biological Evaluation of
Medical Devices.*

CardioWest TAH Patient Contacting Materials Matrix

+--------------------------------+-------------------------------------+
| ***Component***                | ***Material***                      |
+--------------------------------+-------------------------------------+
| > Ventricle and diaphragm      | Segmented polyurethane              |
+--------------------------------+-------------------------------------+
|                                | Nylon                               |
+--------------------------------+-------------------------------------+
| > Inflow connector             | > Segmented polyurethane            |
+--------------------------------+-------------------------------------+
|                                | > Polyester fabric                  |
+--------------------------------+-------------------------------------+
| > Outflow connector            | > Segmented polyurethane            |
+--------------------------------+-------------------------------------+
|                                | > Polyethylene material             |
+--------------------------------+-------------------------------------+
| > Valves                       | > Titanium and pyrolitic carbon     |
|                                | > (Medtronic Hall Heart Valves)     |
+--------------------------------+-------------------------------------+
| > Drivelines                   | > Polyvinyl chloride tubing         |
+--------------------------------+-------------------------------------+