Summary of Safety and Effectiveness

Original PMA P010012

CONTAK CD^^ CRT-D System

and

EASYTRAK^ ^ Coronary Venous Steroid-Eluting Single-Electrode Pace/Sense
Lead, Models 4510, 4511, 4512, 4513

Summary of Safety and Effectiveness

# General Information

+-------------------+--------------------------------------------------+
| Device Generic    | Cardiac Resynchonization Therapy Defibrillator   |
| Name:             | (CRT-D) System                                   |
+-------------------+--------------------------------------------------+
| Device Trade      | Guidant CONTAK CD^^ CRT-D system including the: |
| Name:             |                                                  |
|                   | -   CONTAK CD^ ^CRT-D pulse generator Model 1823 |
|                   |                                                  |
|                   | -   Software Application Model 2848 (Version     |
|                   |     3.1)                                         |
|                   |                                                  |
|                   |     EASYTRAK^^ Coronary Venous Steroid-Eluting  |
|                   |     Single Electrode Pace/Sense Lead, Models     |
|                   |     4510, 4511, 4512, 4513                       |
|                   |                                                  |
|                   |     System accessories:                          |
|                   |                                                  |
|                   | -   Finishing Wire, Models 6730, 6731, 6732,     |
|                   |     6733                                         |
|                   |                                                  |
|                   | -   Suture Sleeve, Model 6741                    |
|                   |                                                  |
|                   | -   LV^^-1 Lead Cap, Model 6742                 |
|                   |                                                  |
|                   | -   LV^^-1 Lead Port Plug, Model 6743           |
|                   |                                                  |
|                   | -   Lead Adapter, Model 6744                     |
+-------------------+--------------------------------------------------+
| Applicant's Name  | GUIDANT Corporation, Cardiac Rhythm Management\  |
| and Address:      | 4100 Hamline Avenue North\                       |
|                   | St. Paul, Minnesota 55112-5798                   |
+-------------------+--------------------------------------------------+
| PMA Number:       | P010012                                          |
+-------------------+--------------------------------------------------+
| Preapproval       | April 29, 2002                                   |
| Inspection        |                                                  |
+-------------------+--------------------------------------------------+
| Date of Panel     | July 10, 2001                                    |
| Recommendations   |                                                  |
+-------------------+--------------------------------------------------+
| Date of Notice of | May 02, 2002                                     |
| Approval to       |                                                  |
| Applicant         |                                                  |
+-------------------+--------------------------------------------------+

# Indications For Use

## CONTAK CD CRT-D System

The CONTAK CD CRT-D System is indicated for use in the following:

Patients who are at high risk of sudden cardiac death due to ventricular
arrhythmias and who have moderate to severe heart failure \[New York
Heart Association (NYHA) Class III/IV\] including left ventricular
dysfunction (ejection fraction (EF) ≤ 35%) and QRS duration ≥120 ms and
remain symptomatic despite stable, optimal heart failure drug therapy.

Patient populations at high risk of sudden cardiac death due to
ventricular arrhythmias include, but are not limited to, those with:

-   Survival of at least one episode of cardiac arrest (manifested by
    the loss of con­sciousness) due to a ventricular tachyarrhythmia.

-   Recurrent, poorly tolerated sustained ventricular tachycardia (VT).

> NOTE: The clinical outcome of hemodynamically stable, sustained-VT
> patients is not fully known. Safety and effectiveness studies have not
> been conducted.

-   Prior myocardial infarction, left ventricular ejection fraction of
    ≤35%, and a documented episode of nonsustained VT, with an inducible
    ventricular tach­y-arrhythmia. Patients suppressible with IV
    procainamide or an equivalent antiar­rhythmic (drug) have not been
    studied.

## EASYTRAK Lead

The Guidant EASYTRAK coronary venous, steroid-eluting, single-electrode
pace/sense leads, Models 4510/4511/4512/ 4513, are transvenous leads
intended for chronic left ventricular pacing and sensing via the
coronary veins when used in conjunction with a compatible Guidant
cardiac resynchronization therapy (CRT) device that accepts the\
LV-1 connector.

# System Description

## CONTAK CD CRT-D Pulse Generator

The Guidant CONTAK CD CRT-D pulse generator, Model 1823, provides
ventricular tachyarrhythmia and cardiac resynchronization therapies.
Ventricular tachyarrhythmia therapy is for the treatment of VT and
ventricular fibrillation (VF), rhythms that are associated with sudden
cardiac death (SCD). Cardiac resynchronization therapy uses simultaneous
biventricular electrical stimulation to synchronize ventricular
contractions. The device uses accelerometer-based adaptive-rate
bradycardia therapy similar to Guidant's commercially available
VENTAK^®^ family of implantable cardioverter defibrillators (ICDs). The
pulse generator, an atrial lead, and two ventricular leads connected in
parallel configuration constitute the implantable portion of the CRT-D
system. The pulse generator accepts one atrial lead (IS-1 connector
type), one coronary venous lead (LV-1 connector type) (EASYTRAK^^), and
one cardioversion/ defibrillation lead (DF-1/IS-1 connector type).

Cardioversion/defibrillation therapies include a range of low- and
high-energy shocks using either a biphasic or monophasic waveform. The
CONTAK CD CRT-D pulse generator uses the Guidant TRIAD^®^ electrode
system for defibrillation energy delivery. By using the metal­lic housing
of the pulse generator as an active electrode, combined with the Guidant
ENDOTAK (approved in P910073) two-electrode defibrillation lead, energy
is sent via a dual-current pathway from the distal shocking electrode to
the proximal electrode and to the pulse generator case. The CONTAK CD
CRT-D system also offers a variety of antitachycardia pacing (ATP)
schemes to terminate slower, more stable ventricular tachyarrhythmias.
Bradycardia pac­ing with resynchronization therapy, including
adaptive-rate features, is available to detect and treat
bradyarrhythmias and to support the cardiac rhythm after defibrillation
therapy.

The ZOOM^®^ Programming System, which includes the Model 2920
Programmer/ Recorder/ Monitor (PRM) (approved in P840068/S039,
P910077/S031, P940031/S023, and P960040/S013), the Model 2848 Software
Application (Version 3.1), and an accessory telemetry wand, constitutes
the external portion of the CONTAK CD CRT-D system. The external
components allow interrogation and program­ming of the pulse generator as
well as access to the device\'s diagnostic features. The CONTAK CD CRT-D
system can be programmed to provide a variety of therapy options. It
also can provide noninvasive diagnostic testing and therapy history
data.

## EASYTRAK Lead 

The EASYTRAK coronary venous, steroid-eluting single-electrode
pace/sense leads, Models 4510/4511/4512/4513, provide chronic pacing and
sensing of the left ventricle. The lead is placed by inserting it
through the coronary sinus and into a branch of the car­diac veins. The
over-the-wire design has an open inner lumen which allows passage over a
guide wire.

The lead features a single pacing electrode. Distal to the electrode is
a drug collar with an anti-inflammatory glucocorticosteroid. The distal
end of the lead has passive fixation tines, and the tip is constructed
of soft silicone rubber.

The electrode is connected by a multifilar conductor coil to the
terminal pin on the proximal end of the lead. The LV-1 terminal pin is
hollow to allow for insertion of the guide wire and is streamlined to
facilitate guide catheter removal. The LV-1 lead port in the header of a
compatible heart failure device has sealing rings that electrically
insulate the terminal pin. The EASYTRAK lead is constructed of silicone
rubber tubing, which electri­cally insulates the coil. Additionally, an
abrasion-resistant polyurethane sleeve over the sil­icone insulation
covers all but the terminal and distal-most portion of the lead body.

The EASYTRAK lead is used in conjunction with the CONTAK CD CRT-D Model
1823 pulse generator, or a compatible Guidant CRT device, that accepts
the LV-1 connector.

Implant accessory devices are available for use with the EASYTRAK lead.
Implant accessory devices include guiding catheters, guide wires,
finishing wires, and balloon catheters that are labeled for use with the
EASYTRAK lead.

# Contraindications

The CONTAK CD CRT-D system is contraindicated for use in the following:

-   Patients whose ventricular tachyarrhythmias may have a reversible
    cause such as\
    1) digitalis intoxication, 2) electrolyte imbalance, 3) hypoxia, 4)
    sepsis, or

-   Patients whose ventricular tachyarrhythmias may have a transient
    cause, such as 1) acute myocardial infarction, 2) electrocution,
    or 3) drowning.

# Warnings and Precautions

See device labeling.

# Adverse Events

## Observed Adverse Events

The VENTAK^®^ CHF/CONTAK^®^ CD/EASYTRAK^®^ Biventricular Pacing Study
(hereafter referred to as the CONTAK CD Study) was a prospective,
randomized, controlled, multicenter, double-blind study conducted at 47
sites in the United States and enrolled a total of 581 patients. Of
these, 57 patients initially underwent a thoracotomy procedure to
receive the Guidant Model 1822 VENTAK CHF AICD; 7 patients underwent a
repeat procedure to receive an EASYTRAK lead. An additional 510 patients
initially underwent an implant procedure to receive the Model 1823
CONTAK CD CRT-D pulse generator along with the EASYTRAK  (Models
4510/4511/4512/4513) coronary venous, single-electrode pace/sense lead
for a total of 517 patients who underwent an EASYTRAK lead implant
procedure. In 69 patients the EASYTRAK lead implant attempt was
unsuccessful.

Table 1 provides information on all adverse events reported from implant
through the randomization period in patients attempted or implanted with
the EASYTRAK lead. During this period, a total of 765 events were
reported in 310 patients. Of these, 155 were classified as
complications, and 610 were classified as observations.

Table 1: Adverse Events Through the Randomization Period

(765 Events in 517 patients implanted or attempted with the EASYTRAK
lead, 2559 total device months)

  -------------------------------------------------------------------------------------------------------
                         \#           % Complic-ations\   Complications   % \             Observatrions
                         Of Events\   (Patients)          per\            Observations\   per\
                         (# of                            100 Device\     (Patients)      100  Device\
                         pts)^a^                          Months\                         Months (Events)
                                                          (Events)                        
  ---------------------- ------------ ------------------- --------------- --------------- ---------------
                                                                                          

  **Total Adverse        765 (310)    23.4 (121)          6.0 (155)       51.8 (268)      23.5 (610)
  Events**                                                                                

  **PG-Related Events**                                                                   

  Migration of device    1 (1)        0.0 (0)             0.0 (0)         0.2 (1)         0.0 (1)

  Pacemaker mediated     3 (3)        0.0 (0)             0.0 (0)         0.6 (3)         0.1 (3)
  tachycardia (PMT)                                                                       

  Telemetry difficulty   1 (1)        0.2 (1)             0.0 (1)         0.0 (0)         0.0 (0)

  **LV Lead-Related                                                                       
  Events**                                                                                

  Loss of capture        43 (41)      5.6 (29)            1.1 (29)        2.5 (13)        0.5 (14)

  Inappropriate shock    1 (1)        0.0 (0)             0.0 (0)         0.2 (1)         0.0 (1)
  due to oversensing                                                                      

  Insulation breach      1 (1)        0.2 (1)             0.0 (1)         0.0 (0)         0.0 (0)
  observed                                                                                

  Multiple counting^b^   31 (22)      1.0 (5)             0.2 (5)         3.9 (20)        1.0 (26)

  Phrenic                15 (15)      0.4 (2)             0.1 (2)         2.5 (13)        0.5 (13)
  nerve/diaphragm                                                                         
  stimulation                                                                             

  **RA Lead-Related                                                                       
  Events**                                                                                

  Loss of capture        6 (6)        1.0 (5)             0.2 (5)         0.2 (1)         0.0 (1)

  Oversensing            3 (3)        0.0 (0)             0.0 (0)         0.6 (3)         0.1 (3)

  Undersensing           1 (1)        0.2 (1)             0.0 (1)         0.0 (0)         0.0 (0)

  **RV Lead-Related                                                                       
  Events**                                                                                

  Loss of capture        10 (9)       0.6 (3)             0.1 (3)         1.2 (6)         0.3 (7)

  Elevated DFTs          6 (6)        0.4 (2)             0.1 (2)         0.8 (4)         0.2 (4)

  Inappropriate shock    49 (38)      0.4 (2)             0.1 (2)         7.2 (37)        1.8 (47)
  above rate cutoff                                                                       

  Inappropriate shock    5 (4)        0.0 (0)             0.0 (0)         0.8 (4)         0.2 (5)
  due to oversensing                                                                      

  Non-conversion of VF   1 (1)        0.2 (1)             0.0 (1)         0.0 (0)         0.0 (0)

  Oversensing            2 (2)        0.0 (0)             0.0 (0)         0.4 (2)         0.1 (2)

  Phantom shock          2 (2)        0.0 (0)             0.0 (0)         0.4 (2)         0.1 (2)

  Phrenic                5 (5)        0.4 (2)             0.1 (2)         0.6 (3)         0.1 (3)
  nerve/diaphragm                                                                         
  stimulation                                                                             

  **Subtotal             **186        **9.5 (49)**        **2.1 (54)**    **19.0 (98)**   **5.1 (132)**
  Device-Related         (135)**                                                          
  Events**                                                                                

  **Procedure-Related                                                                     
  Events**                                                                                

  AV Block               7 (7)        0.0 (0)             0.0 (0)         1.4 (7)         0.3 (7)

  Coronary sinus         5 (5)        0.0 (0)             0.0 (0)         1.0 (5)         0.2 (5)
  dissection                                                                              

  Coronary venous        5 (5)        0.2 (1)             0.0 (1)         0.8 (4)         0.2 (4)
  perforation                                                                             

  Hematoma               11 (10)      0.8 (4)             0.2 (4)         1.2 (6)         0.3 (7)

  Hypotension            7 (7)        0.0 (0)             0.0 (0)         1.4 (7)         0.3 (7)

  Infection,             7 (7)        0.6 (3)             0.1 (3)         0.8 (4)         0.2 (4)
  post-operative wound                                                                    

  Pneumothorax           7 (7)        0.8 (4)             0.2 (4)         0.6 (3)         0.1 (3)

  Post surgical wound    10 (9)       0.2 (1)             0.0 (1)         1.5 (8)         0.3 (9)
  discomfort                                                                              

  Renal failure          5 (5)        0.2 (1)             0.0 (1)         0.8 (4)         0.2 (4)

  Other^c^               18 (18)      1.2 (6)             0.2 (6)         2.3 (12)        0.5 (12)

  **Subtotal Procedure   **79 (71)**  **3.9 (20)**        **0.7 (17)**    **10.0 (51)**   **2.2 (56)**
  Related Events**                                                                        

  **Cardiovascular                                                                        
  Related Events**                                                                        

  AV Block               3 (3)        0.0 (0)             0.0 (0)         0.6 (3)         0.1 (3)

  Arrhythmia - SVT       49 (42)      0.2 (1)             0.0 (1)         7.9 (41)        1.8 (48)

  Arrhythmia - VT        20 (17)      1.0 (5)             0.2 (5)         2.7 (14)        0.6 (15)

  Arrhythmia - brady     16 (14)      0.2 (1)             0.0 (1)         2.5 (13)        0.6 (15)

  Cardiac arrest         2 (2)        0.4 (2)             0.1 (2)         0.0 (0)         0.0 (0)

  Chest pain             30 (20)      1.0 (5)             0.2 (5)         3.1 (16)        1.0 (25)

  Coagulopathy           3 (3)        0.2 (1)             0.0 (1)         0.4 (2)         0.1 (2)

  Congestive heart       140 (91)     3.5 (18)            0.7 (18)        16.1 (83)       4.7 (122)
  failure                                                                                 

  Distal thromboemboli   3 (2)        0.0 (0)             0.0 (0)         0.4 (2)         0.1 (3)

  Dizziness              17 (17)      0.0 (0)             0.0 (0)         3.3 (17)        0.7 (17)

  Dyspnea (shortness of  16 (13)      0.0 (0)             0.0 (0)         2.5 (13)        0.6 (16)
  breath)                                                                                 

  Fatigue                10 (10)      0.0 (0)             0.0 (0)         1.9 (10)        0.4 (10)

  Hypertension           1 (1)        0.0 (0)             0.0 (0)         0.2 (1)         0.0 (1)

  Hypotension            11 (9)       0.2 (1)             0.0 (1)         1.7 (9)         0.4 (10)

  Myocardial infarction  2 (2)        0.0 (0)             0.0 (0)         0.4 (2)         0.1 (2)

  Pacemaker syndrome     1 (1)        0.0 (0)             0.0 (0)         0.2 (1)         0.0 (1)

  Palpitations           2 (2)        0.0 (0)             0.0 (0)         0.4 (2)         0.1 (2)

  Pulmonary edema        6 (6)        0.4 (2)             0.1 (2)         0.8 (4)         0.2 (4)

  Shock                  4 (4)        0.2 (1)             0.0 (1)         0.6 (3)         0.1 (3)

  Stroke syndrome or CVA 4 (4)        0.0 (0)             0.0 (0)         0.8 (4)         0.2 (4)

  Syncope                9 (9)        0.0 (0)             0.0 (0)         1.7 (9)         0.3 (9)

  Thrombosis             3 (3)        0.0 (0)             0.0 (0)         0.6 (3)         0.1 (3)

  Vascular related       6 (6)        1.0 (5)             0.2 (5)         0.2 (1)         0.0 (1)

  **Subtotal             **358        **7.7 (40)**        **1.6 (42)**    **35.6 (184)**  **12.2 (316)**
  Cardiovascular Related (200)**                                                          
  Events**                                                                                

  **Total                **142 (92)** **6.2 (32)**        **1.5 (39)**    **13.5 (70)**   **4.0 (103)**
  Non-cardiovascular                                                                      
  Related Events**                                                                        
  -------------------------------------------------------------------------------------------------------

a\. The total number of patients for a given event represents the unique
number of patients who experienced that event. The total may not be
equal to the sum of patients with complications or observations because
some patients experienced more than one event that fell into both
categories.**A total of 109 deaths occurred during the study. These
deaths occurred during the study periods as shown in Table 2 along with
the cause of death as adjudicated by an independent events committee.**

Table 2: Deaths that Occurred During the Study

> All patients enrolled, N=581\* Day 31 to 120 for Phase I patients, day
> 31 to 210 for Phase II patients
>
> \*\* Day 121 and beyond for Phase I patients, day 211 and beyond for
> Phase II patients

## Possible Adverse Events

Based on the literature and ICD implant experience, the following
alphabetical list includes possible adverse events associated with
implantation of an ICD system:

+---------------------------------+------------------------------------+
| -   Acceleration of arrhythmias | -   Infection                      |
+---------------------------------+------------------------------------+
| -   Air embolism                | -   Lead displacement/dislodgment  |
+---------------------------------+------------------------------------+
| -   Allergic reaction           | -   Lead insulation breakage or    |
|                                 |     abrasion                       |
+---------------------------------+------------------------------------+
| -   Bleeding                    | -   Lead tip deformation and/or    |
|                                 |     breakage                       |
+---------------------------------+------------------------------------+
| -   Cardiac tamponade           | -   Local tissue reaction          |
+---------------------------------+------------------------------------+
| -   Chronic nerve damage        | -   Muscle and nerve stimulation   |
+---------------------------------+------------------------------------+
| -   Conductor coil fracture     | -   Myocardial trauma (e.g.,       |
|                                 |     cardiac perforation,           |
| -   Death                       |     irritability, injury)          |
+---------------------------------+------------------------------------+
| -   Elevated thresholds         | -   Myopotential sensing           |
+---------------------------------+------------------------------------+
| -   Erosion/extrusion           | -   Oversensing/undersensing       |
+---------------------------------+------------------------------------+
| -   Extracardiac stimulation    | -   Pacemaker mediated tachcardia  |
|     (e.g., phrenic, diaphragm,  |                                    |
|     chest wall)                 |                                    |
+---------------------------------+------------------------------------+
|                                 | -   Pericardial rub, effusion      |
+---------------------------------+------------------------------------+
| -   Fibrotic tissue formation   | -   Pneumothorax                   |
|     (e.g., keloid formation)    |                                    |
|                                 | -   Random component failures      |
| -   Fluid accumulation          |                                    |
+---------------------------------+------------------------------------+
| -   Formation of hematomas or   | -   Shunting current or insulating |
|     cysts                       |     myocardium during              |
|                                 |     defibrillation with internal   |
|                                 |     or external paddles            |
+---------------------------------+------------------------------------+
| -   Heart block                 |                                    |
+---------------------------------+------------------------------------+
| -   Inability to defibrillate   | -   Thrombosis/thromboemboli       |
|     or pace                     |                                    |
+---------------------------------+------------------------------------+
| -   Inappropriate therapy       | -   Valve damage                   |
|     (e.g., shocks, ATP, pacing) |                                    |
+---------------------------------+------------------------------------+
| -   Incomplete lead connection  | -   Venous occlusion               |
|     with pulse generator        |                                    |
+---------------------------------+------------------------------------+
|                                 | -   Venous trauma (e.g.,           |
|                                 |     perforation, dissection,       |
|                                 |     erosion)                       |
+---------------------------------+------------------------------------+

Patients susceptible to frequent shocks despite antiarrhythmic medical
management may develop psychological intolerance to an implantable
system that may include the following:

+-----------------------------------+----------------------------------+
| -   Dependency                    | -   Fear of shocking while       |
|                                   |     conscious                    |
+-----------------------------------+----------------------------------+
| -   Depression                    | -   Fear that shocking           |
|                                   |     capability may be lost       |
+-----------------------------------+----------------------------------+
| -   Fear of premature battery     | -   Imagined shocking            |
|     depletion                     |                                  |
+-----------------------------------+----------------------------------+

In addition to the implantation of an ICD system, possible adverse
events associated with implantation of a coronary venous lead system are
listed below in alphabetical order:

+------------------------+---------------------------------------------+
| -   Allergic reaction  | -   Coronary venous trauma (e.g.,           |
|     to contrast media  |     perforation, dissection, erosion)       |
+------------------------+---------------------------------------------+
| -   Breakage/failure   | -   Prolonged exposure to fluoroscopic      |
|     of implant tools   |     radiation                               |
+------------------------+---------------------------------------------+
| -   Coronary venous    | -   Renal failure from contrast media used  |
|     occlusion          |     to visualize coronary veins             |
+------------------------+---------------------------------------------+

# Alternate Practices and Procedures

Patients who require an ICD and also have heart failure are routinely
treated with a commercially available ICD and medications. Medications
include both those to treat arrhythmias and medications to treat heart
failure. Additional medical treatments for heart failure include, but
are not limited to, exercise and nutrition programs. Alternative
therapies for the treatment of ventricular arrhythmias, as deemed
appropriate by the physician based upon electrophysiological (EP)
testing and other diagnostic evaluation, include antiarrhythmic
medication, electrical ablation, cardiac surgery, and electronic devices
including pacemaker and other commercially available ICD systems, or a
combination thereof.

# Marketing History

The CONTAK CD CRT-D System and the EASYTRAK lead (Models 4510/4511/
4512/4513) are distributed commercially outside the United States. These
devices are approved for sale in the European Economic Community,
Australia, New Zealand, Canada, Hong Kong, Singapore, Indonesia,
Lebanon, Malaysia, Malta, Mexico, Israel, Egypt, Saudi Arabia, Turkey,
Czech Republic, Slovakia, Slovenia, India, South Africa, and Latin
America (Argentina, Bolivia, Chile, Columbia, Dominican Republic,
Ecuador, Panama, Venezuela, Uruguay).

Neither the CONTAK CD CRT-D System nor the EASYTRAK leads have been
withdrawn from market in any country for any reason related to the
safety and effectiveness.

# Summary of Pre-Clinical Studies

Prior to initiation of clinical studies, Guidant conducted the following
bench testing (i.e., components, assemblies, device system and software
tests), biocompatibility evaluation, sterilization validation, and
animal studies on the CONTAK CD CRT-D System. These studies were
performed in accordance with established national and international
industry standards such as ANSI/AAMI PC69:2000; ISO 5841-3: 1992(E); ISO
11318:1993(E); prEN45502 Active Implantable Medical Devices, Part 2-1
(Requirements for active implantable medical devices intended to treat
bradyarrythmia), (draft) November 1996; and the Association for the
Advancement of Medical Instrumentation (AAMI) Pacemaker Standard, August
1975; or Guidant\'s product specification. The test results demonstrated
that the CONTAK CD CRT-D pulse generator, EASYTRAK lead and the entire
CONTAK CD CRT-D system met the requirements set by these standards
(sections that apply, as outlined in the following tables), and
Guidant\'s specifications. The following tables provide brief
descriptions of the verification and validation tests conducted on the
CONTAK CD CRT-D system and EASYTRAK^^ lead.

## Pulse Generator: Design Verification Testing (DVT)

The design verification testing of the CONTAK CD CRT-D Model 1823 pulse
generator included component, electronic and mechanical tests (including
packaging and shipping), electromagnetic compatibility evaluation,
battery capacity test, pulse generator software design verification and
programmer software application tests as described below:

***Component Testing:*** Except for the lead connector assembly, the
major components for the CONTAK CD CRT-D pulse generator are identical
to the legally marketed VENTAK AV III DR (PMA P960040). The lead
connector assembly was modified to include three new components, the
header, the outer lead seals, and the IS-1/LV-1 Connector Block. These
new components were tested and passed (Table 3).

Table 3: Component Testing

+----------------------------------------------------+------+----------+
| Summary of Component Testing\*                     | Sa   | Test     |
|                                                    | mple | Results  |
|                                                    | Size |          |
|                                                    |      | (Pa      |
|                                                    |      | ss/Fail) |
+====================================================+======+==========+
| **Header:** Visual inspection, dimensional         | 1 to | Pass     |
| analysis, thermal shock, high temp/high humidity   | 35   |          |
| storage, cytotoxicity, pyrogenicity, material      |      |          |
| analysis.                                          |      |          |
+----------------------------------------------------+------+----------+
| **Outer Lead Seals**: Visual inspection,           | 1 to | Pass     |
| dimensional inspection; cytotoxicity,              | 105  |          |
| pyrogenicity, material analysis.                   |      |          |
+----------------------------------------------------+------+----------+
| **IS-1/LV-1 Connector Block:** Visual inspection,  | 1 to | Pass     |
| dimensional inspection, material analysis.         | 32   |          |
+----------------------------------------------------+------+----------+
| \*Materials used in these components were tested   |      |          |
| and met the requirements of ISO-10993,             |      |          |
| \"Biological Evaluation of Medical Devices Part 1: |      |          |
| Evaluation and Testing (1997)                      |      |          |
+----------------------------------------------------+------+----------+

***Electronic and Mechanical Design Verification Tests:*** Because of
the similarity (same electronics and firmware) between the legally
marketed VENTAK AV III DR and the CONTAK CD CRT-D pulse generator,
electrical design verification testing for the VENTAK AV III DR applies
to the CONTAK CD CRT-D pulse generator and was not repeated. Mechanical
design verification test was performed on CONTAK CD CRT-D devices that
were exposed to a representative manufacturing process, including
sterilization cycles and vibration tests (Table 4).

Table 4: Pulse Generator Design Verification Testing

+----------------------------------------------------+------+----------+
| Summary of Pulse Generator DVT                     | Sa   | Test     |
|                                                    | mple | Results  |
|                                                    | Size |          |
|                                                    |      | (Pa      |
|                                                    |      | ss/Fail) |
+====================================================+======+==========+
| **Electronic Design Verification Testing**         |      |          |
+----------------------------------------------------+------+----------+
| Tests were conducted on the VENTAK AV III DR at    | 5    | Pass     |
| three different stages of the pulse generator:     |      |          |
| welded PG assembly, PG assembly with external      |      |          |
| battery connections, and hybrid system board.      |      |          |
| Tests were conducted in the following functional   |      |          |
| areas: Telemetry operation, sensing, pacing,       |      |          |
| shocking, magnet, beeper, electrograms, device     |      |          |
| clock, battery status, and faults/error handling.  |      |          |
+----------------------------------------------------+------+----------+
| **Mechanical Design Verification Testing**         |      |          |
+----------------------------------------------------+------+----------+
| Tests were conducted on the CONTAK CD CRT-D in the | 1 to | Pass     |
| main functional areas: mechanical requirements,    | 10   |          |
| environmental tests, and package and shipping      |      |          |
| tests. Such tests included internal atmosphere and |      |          |
| hermeticity, connector assembly lead and adapter   |      |          |
| compatibility, thermal shock and cycling,          |      |          |
| vibration, and dimensional analysis. The           |      |          |
| IS-1/DF-1/LV-1 connector assembly met requirements |      |          |
| of ISO 5841-3: 1992(E) and ISO 11318: 1993(E).     |      |          |
+----------------------------------------------------+------+----------+
| Packaging and Shipping tests were done to ensure   | 4    | Pass     |
| that the device remains damage free and that the   |      |          |
| package remains functional while in transit and    |      |          |
| storage mode prior to implant. Labeling must       |      |          |
| remain legible.                                    |      |          |
+----------------------------------------------------+------+----------+

***Electromagnetic Compatibility (EMC) Evaluation:*** The CONTAK CD
CRT-D Model 1823 pulse generator was evaluated to ensure that the device
will operate safely in the presence of commonly encountered
electromagnetic interference (EMI) such as cellular phones, cordless
phones, electronic article surveillance systems (EASS), and radios
designed for the home (provided labeled guidances are adhered to).
Testing was based on prEN45502 Active Implantable Medical Devices, Part
2-1: Requirements for active implantable medical devices intended to
treat bradyarrythmia (cardiac pacemakers) Version 9.0, draft Nov. 1996
and the AAMI Pacemaker Standard, August 1975. Since the CONTAK CD CRT-D
pulse generator uses the same electronics and device firmware as the
legally marketed VENTAK AV III DR, test results from the VENTAK AV III
DR apply to the CONTAK CD CRT-D. A subset of tests was repeated on the
CONTAK CD CRT-D to evaluate the effects of adding the left ventricular
lead (Table 5).

Table 5: Electromagnetic Compatibility (EMC) Testing

+-----------------------------------------------------+------+---------+
| Summary of Electromagnetic Compatibility (EMC)      | Sa   | Test    |
| Testing                                             | mple | Results |
|                                                     | Size |         |
|                                                     |      | (Pas    |
|                                                     |      | s/Fail) |
+=====================================================+======+=========+
| VENTAK AV III DR pulse generator performance was    | 3    | Pass\*  |
| evaluated when subjected to the following:          |      |         |
+-----------------------------------------------------+------+---------+
| -   Radiated radio frequency; pulsed and continuous |      |         |
|     wave up to 200 V/m field strength, (27, 72,     |      |         |
|     450, 900, 1800, 2450, and 3100 MHz) based on    |      |         |
|     the AAMI pacemaker standard, Aug 1975.          |      |         |
|                                                     |      |         |
| -   Testing at 27 & 72 MHz was repeated for the     |      |         |
|     CONTAK CD CRT-D.\*                              |      |         |
+-----------------------------------------------------+------+---------+
| -   Conducted frequency from 16.6 Hz to 50 MHz as   |      |         |
|     defined in prEN45502 Active Implantable Medical |      |         |
|     Devices. Part 2-1Requirements for active        |      |         |
|     implantable medical devices intended to treat   |      |         |
|     bradyarrythmia (cardiac pacemakers). Version    |      |         |
|     9.0.                                            |      |         |
+-----------------------------------------------------+------+---------+
| -   High voltage external defibrillation shocks.    |      |         |
+-----------------------------------------------------+------+---------+
| -   Exposure to electrostatic discharge pulses.     |      |         |
+-----------------------------------------------------+------+---------+
| -   Exposure to Electronic Article Surveillance     |      |         |
|     Systems (EASS) per Georgia Technical Institute  |      |         |
|     EASS test protocol for Implantable Medical      |      |         |
|     Devices, Version 2.0.                           |      |         |
+-----------------------------------------------------+------+---------+
| -   Exposure to electrocautery                      |      |         |
+-----------------------------------------------------+------+---------+
| -   Exposure to static magnetic fields up to 10mT   |      |         |
|     (the reed switch is activated/ deactivated when |      |         |
|     the field is maintained at \>1.0mT.)            |      |         |
+-----------------------------------------------------+------+---------+
| Summary of Cellular Telephone Testing for VENTAK AV |      |         |
| III DR                                              |      |         |
+-----------------------------------------------------+------+---------+
| Resistance to Interference from Cellular Telephones | 1    | Pass    |
| (450 MHZ to 1100 MHz)                               |      |         |
+-----------------------------------------------------+------+---------+
| Resistance to Interference from Cellular Telephones | 1    | Pass    |
| (850 MHZ to 2500 MHz)                               |      |         |
+-----------------------------------------------------+------+---------+
| Resistance to Interference from Cellular Telephones | 1    | Pass    |
| U. S. Cellular telephones. (NADC = TDMA-50) (MIRS = |      |         |
| TDMA-11)                                            |      |         |
+-----------------------------------------------------+------+---------+
| The CONTAK CD CRT-D was also tested for EMI         | 3    | Pass    |
| simulating cellular phone emissions per the         |      |         |
| ANSI/AAMI PC69:2000 (Active Implantable Medical     |      |         |
| Devices - Electromagnetic Compatibility (EMC) test  |      |         |
| protocols for Implantable Cardiac Pacemakers and    |      |         |
| Implantable Cardioverter Defibrillators.)           |      |         |
+-----------------------------------------------------+------+---------+

\*Guidant reported that there were no instances of memory errors,
parameter changes, reset conditions or damage from any test. Three
devices showed the expected reversion to noise mode in the presence of
conducted signals of sufficient amplitude and frequency. Three devices
showed susceptibility to pulsed RF at 27 MHz and slight susceptibility
to pulsed RF at 72 MHZ; these levels are comparable to other legally
marketed implantable defibrillator devices.

***Battery Capacity Test***: The CONTAK CD CRT-D battery is identical to
the VENTAK AV III DR battery; therefore, the VENTAK AV III DR battery
testing applies to the CONTAK CD CRT-D and was not repeated. However, a
Battery Capacity Test was performed for the CONTAK CD CRT-D pulse
generator to establish the usable capacity of the cell (battery) and the
reserve capacity between ERI (Elective Replacement Indicator) and EOL
(End Of Life) when used with the pulse generator's electronics (Table
6).

Table 6: Battery CapacityTesting

+-------------------------------------------------+---------+----------+
| Summary of Battery CapacityTesting              | Sample  | Test     |
|                                                 | Size    | Results  |
|                                                 |         |          |
|                                                 |         | (Pa      |
|                                                 |         | ss/Fail) |
+=================================================+=========+==========+
| The Battery Capacity Test used a set of         | 6 flex  | Pass     |
| calculations, with data provided by the battery | ass     |          |
| manufacturer and data measured in Guidant's     | emblies |          |
| laboratory, to calculate usable battery         | and 6   |          |
| capacity. The battery met Guidant               | sets of |          |
| specification.                                  | ba      |          |
|                                                 | tteries |          |
+-------------------------------------------------+---------+----------+

***Pulse Generator Software Design Verification Test:*** The CONTAK CD
CRT-D pulse generator software (also known as firmware) is identical to
the VENTAK AV III DR pulse generator software. Design verification
testing of the software incorporated in the CONTAK CD CRT-D pulse
generators encompassed two different areas: the Flash EPROM and the
Read-Only Memory on the chip (microcontrol) (Table 7).

Table 7: Pulse Generator Software Design Verification Test

+----------------------------------------------------+------+----------+
| Summary of Pulse Generator Software Design         | Sa   | Test     |
| Verification Test:                                 | mple | Results  |
|                                                    | Size |          |
| (from VENTAK AV III DR)                            |      | (Pa      |
|                                                    |      | ss/Fail) |
+====================================================+======+==========+
| Using an automated test system, the testing        | PG   | Pass     |
| verified the proper operation and interaction of   | Soft |          |
| the various tasks to be executed by the software   | ware |          |
| (according to the test requirements specification) |      |          |
| to ensure proper function, timing, and data        |      |          |
| exchange. The firmware version number is 1.0.02.   |      |          |
+----------------------------------------------------+------+----------+

***Model 2848 Software Application Design Verification Test:*** Design
verification testing of the Model 2848 Programmer Software Application
(the PRM Software, Version 3.1) was performed to ensure that the
software meets the functional software requirements specifications.
Testing was conducted with either a CONTAK CD CRT-D system including a
CONTAK CD CRT-D Model 1823 pulse generator and a Model 2920 PRM
(Programmer, Recorder, Monitor) with the Model 2909 Multiple Application
Utility (MAU) and Model 2848 Software Application installed on it, or
the same system with a pulse generator simulator replacing the CONTAK CD
CRT-D pulse generator (Table 8).

Table 8: Model 2848 Software (Version 3.1) Application DVT

+------------------------------------------------------+------+--------+
| Summary of Model 2848 Software Application DVT       | Sa   | Test   |
|                                                      | mple | R      |
|                                                      | Size | esults |
|                                                      |      |        |
|                                                      |      | (Pass  |
|                                                      |      | /Fail) |
+======================================================+======+========+
| Testing includes the functional software             | PG   | Pass   |
| requirements associated with each window/feature.    | Soft | with 2 |
| The software version number is Version 3.1 for use   | ware | anoma  |
| with the Model 2920 PRM.                             |      | lies\* |
+------------------------------------------------------+------+--------+

\*1) Under certain circurmstances at the end of a pacing threshold test,
after pulling the telemetry wand out of range, a text box indicating
"Out of Range/Telemetry Noise" remains and threshold values will not
display on the dialog window until the wand is replaced; this is not
expected to occur under actual use. 2) Under certain circumstances when
the PRM is in disk mode, the Last Interrogation Date field is blank on
the Battery Status screen and in the printed report. These anomalies
have no effect on therapy or patient safety.

## EASYTRAK Lead: Design Verification Testing 

Electrical and mechanical integrity of the EASYTRAK lead were performed
to demonstrate conformance to a battery of lead tests and are summarized
below (Table 9). All leads were preconditioned with shelf life,
temperature cycling, and shipping test conditions prior to functional
testing.

Table 9: EASYTRAK Lead DVT

+-----------------------------------------------------+------+---------+
| Summary of EASYTRAK Lead DVT                        | Sa   | Test    |
|                                                     | mple | Results |
|                                                     | Size |         |
|                                                     |      | (Pas    |
|                                                     |      | s/Fail) |
+=====================================================+======+=========+
| **Full Lead Testing:**                              |      |         |
+-----------------------------------------------------+------+---------+
| [Packaging visual]{.underline} verified that the    | 12   | Pass    |
| packaging met the requirements of the sterile pack  |      |         |
| and final pack engineering documents.               |      |         |
+-----------------------------------------------------+------+---------+
| [Guide Catheter Compatibility]{.underline} testing  | 48   | Pass    |
| verified that the EASYTRAK Lead passed through the  |      |         |
| EASYTRAK guide catheters with no damage to the lead |      |         |
| or guide catheter.                                  |      |         |
+-----------------------------------------------------+------+---------+
| [Guide Wire Compatibility]{.underline} testing      | 48   | Pass    |
| verified that all 0.014\" guide wires indicated for |      |         |
| use with the EASYTRAK Lead passed through the lead  |      |         |
| and guide catheter and could be withdrawn from the  |      |         |
| lead with no damage to the lead or guide wire.      |      |         |
+-----------------------------------------------------+------+---------+
| [Finishing Wire Compatibility]{.underline} testing  | 48   | Pass    |
| verified that the finishing wire could track to the |      |         |
| transition of the lead and was able to be withdrawn |      |         |
| from the lead with no damage to the lead or         |      |         |
| finishing wire.                                     |      |         |
+-----------------------------------------------------+------+---------+
| [Axial Load]{.underline} testing verified that the  | 48   | Pass    |
| lead can withstand implant forces and demonstrated  |      |         |
| compliance to the requirements defined by prEN      |      |         |
| 45502-2-1, section 23.3. (draft Nov. 96).           |      |         |
+-----------------------------------------------------+------+---------+
| [Electrical Resistance:]{.underline} DC Resistance  | 12   | Pass    |
| was required to be between 10 and 22 ohms.          |      |         |
+-----------------------------------------------------+------+---------+
| [Insulation Integrity Pressure]{.underline} testing | 12   | Pass    |
| verified the integrity of the insulation. Leads     |      |         |
| were pressurized to 14 ± 2 PSI with dry nitrogen;   |      |         |
| leads must not exhibit evidence of nitrogen         |      |         |
| leakage.                                            |      |         |
+-----------------------------------------------------+------+---------+
| [Pacing Impedance]{.underline}: was tested per the  | 12   | Pass    |
| prEN 45502-Part 2-1, (draft Nov. 96).               |      |         |
+-----------------------------------------------------+------+---------+
| **LV-1 Terminal Testing:** The LV-1 connector is a  |      |         |
| proprietary connector designed for compatibility    |      |         |
| with Guidant pulse generators with an LV-1 port.    |      |         |
+-----------------------------------------------------+------+---------+
| [LV-1 Insertion/Withdrawal:]{.underline} this test  | 12   | Pass    |
| verified that the LV-1 terminal meets maximum       |      |         |
| insertion/withdrawal requirements per ISO           |      |         |
| 11318:1993(E).                                      |      |         |
+-----------------------------------------------------+------+---------+
| [LV-1 Pin Setscrew Deformation:]{.underline} this   | 12   | Pass    |
| test verified that set screw forces can not deform  |      |         |
| the lead connector to the extent that insertion and |      |         |
| withdrawal forces become excessive.                 |      |         |
+-----------------------------------------------------+------+---------+
| [LV-1 Low Voltage Seal Integrity:]{.underline} this | 12   | Pass    |
| test verified that the LV-1 connector seal rings    |      |         |
| could electrically isolate the pin and the external |      |         |
| environment.                                        |      |         |
+-----------------------------------------------------+------+---------+
| [LV-1 High Voltage Seal Integrity]{.underline}:     | 12   | Pass    |
| this test verified that the LV-1 connector seal     |      |         |
| rings could electrically isolate the pin and the    |      |         |
| external environment under high voltage conditions. |      |         |
+-----------------------------------------------------+------+---------+
| **Flex Fatigue Testing:**                           |      |         |
+-----------------------------------------------------+------+---------+
| [LV-1 Connector Flex Fatigue]{.underline} testing   | 12   | Pass    |
| assessed the fatigue resistance of the LV-1         |      |         |
| terminals and demonstrated conformance to the prEN  |      |         |
| 45502 Part 2-1 Connector Flex Test, Section 23.5    |      |         |
| Test 2 (draft Nov. 1996).                           |      |         |
+-----------------------------------------------------+------+---------+
| [Bell Mouth Flex Fatigue Test of Lead               | 12   | Pass    |
| Conductor]{.underline} verified compliance of the   |      |         |
| lead conductor with the requirements of prEN 45502  |      |         |
| Section 23.5 Test 1 (draft Nov. 1996).              |      |         |
+-----------------------------------------------------+------+---------+
| [Buckle Flex Fatigue Test of Lead Body              | 12   | Pass    |
| Conductor]{.underline} verified the ability of the  |      |         |
| lead body conductor to withstand ten years (420     |      |         |
| million cycles) of flexing.                         |      |         |
+-----------------------------------------------------+------+---------+
| **Manufacturing Process Validation for              |      |         |
| Bond/Weld/Strength Testing:**                       |      |         |
+-----------------------------------------------------+------+---------+
| All welded electro-mechanical connections must      | 12   | Pass    |
| withstand a minimum assembly joint pull force. All  |      |         |
| load-bearing molded and bonded connections must     |      |         |
| have a minimum dry pull strength. The dry retention |      |         |
| force between the steroid collar and electrode      |      |         |
| molding must also meet the minimum force per        |      |         |
| specifications.                                     |      |         |
+-----------------------------------------------------+------+---------+

##  System: Design Validation Testing

Design validation testing that was conducted on the CONTAK CD CRT-D
system included system features tests and a simulated use test (field
study). In addition, an animal study carried out under Good Laboratory
Practices was also conducted pre-clinically (Table 10).

Table 10: System Design Validation Testing

+--------------------------------------------------+--------+----------+
| System Design Validation Testing                 | Sample | Test     |
|                                                  | Size   | Results  |
|                                                  |        |          |
|                                                  |        | (Pa      |
|                                                  |        | ss/Fail) |
+==================================================+========+==========+
| **System Features Tests:** Tests were conducted  | 2      | Pass     |
| to exercise major features of the CONTAK CD      | s      |          |
| CRT-D system. Each test demonstrated the         | ystems |          |
| functionality of a given feature and verified    | cons   |          |
| that the programmer had properly loaded          | isting |          |
| parameters into the pulse generator. Feature     | of     |          |
| groups tested included device family, programmer | CONTAK |          |
| support, lead support, tachy modes,              | CD     |          |
| tachyarrhythmia detection, tachyarrhythmia       | CRT-D  |          |
| therapy, bradycardia modes, bradycardia therapy, | PG and |          |
| diagnostics, and faults/error handling. The      | prog   |          |
| system performed as expected based on the        | rammer |          |
| specifications.                                  | sof    |          |
|                                                  | tware. |          |
+--------------------------------------------------+--------+----------+
| **Simulated Use Test:** From a field user        | 2      | Pass     |
| perspective, Guidant field clinical engineers    | users  |          |
| evaluated the performance of the CONTAK CD CRT-D | per    |          |
| system and EASYTRAK lead and verified that the   | formed |          |
| labeling/manuals were easily understood and the  | tests. |          |
| entire CONTAK CD CRT-D system and EASYTRAK lead  |        |          |
| performed as expected during clinical use.       |        |          |
| Clinical scenarios were simulated using the      |        |          |
| pulse generator, programmer (PRM), PRM software, |        |          |
| a cardiac signal simulater, and the EASYTRAK     |        |          |
| lead and accessories (guide catheter, guidewire, |        |          |
| and finishing wire).                             |        |          |
+--------------------------------------------------+--------+----------+
| **Animal Study:** Study verified that the CONTAK | 3      | Pass     |
| CD CRT-D system and EASYTRAK leads including     | a      |          |
| CONTAK CD CRT-D Model 1823 pulse generator,      | nimals |          |
| EASYTRAK lead, guide catheter, occluding guiding |        |          |
| catheter, guidewire, finishing wire, lead        |        |          |
| stabilizer, LV-1 Port Plug, LV-1 Adapter, and    |        |          |
| Model 2848 software, along with a commercially   |        |          |
| available atrial pace/sense lead and a           |        |          |
| ventricular pace/sense/shocking lead, were       |        |          |
| compatible and performed safely in an *in-vivo*  |        |          |
| canine model. Testing demonstrated that the      |        |          |
| system performed safely in an *in-vivo* animal   |        |          |
| model.                                           |        |          |
+--------------------------------------------------+--------+----------+

## CONTAK CD CRT-D System & EASYTRAK Lead: Safety and Risk Analysis 

The safety and risk analysis of the CONTAK CD CRT-D system was conducted
to identify potential hazards and their causes, and to take appropriate
actions to minimize patient and user risk. Analysis included the
following:

**Hazard Analysis:** Hazard Analysis identified potential hazards with
using the system devices and documented the response taken to control
the probability of occurence or to minimize the risk. Potential hazards
were peer reviewed for adequacy of the mitigation; residual risk was
deemed acceptable.

**Failure Modes and Effects Criticality Analysis (FMECA):** FMECA
identified potential design, test, or process inadequacies that could
adversly affect the safety and performance of the device and recommended
corrective actions to eliminate or minimize these inadequacies. Three
recommendations were identified and were incorporated into device
testing scheme.

**Reliability Prediction Analysis:** The Reliability Prediction Analysis
was performed using field performance failure rates of similar pulse
generators along with the "Parts Stress Analysis Prediction" procedure
in MIL-HDBK-217F in the absence of field performance data. The analysis
resulted in an expected field performance of 0.1461% failures/month.

## Biocompatibility Evaluation

The biocompatibility of the tissue contacting materials used in the
CONTAK CD CRT-D pulse generator, and the EASYTRAK lead and lead
accessories was established in previous PMA applications (P890061,
P910077, P960040 and P910073, P950001, P960060 respectively). Pulse
generator materials include: polyurethane, titanium, and silicone rubber
that are all currently used in Guidant\'s commercially available ICD
devices.

Materials used in the EASYTRAK lead that have direct long-term tissue or
blood contact include: titanium, platinum, silicone rubber (including
silicone rubber with titanium oxide pigment), polyurethane, and
polytetrafluroethylene (PTFE). In addition, the drug collar contains
Dexamethasone Acetate in liquid silicone rubber. The biocompatibility of
titanium, platinum, silicone rubber, and Dexamethasone Acetate has been
established in previous PMA applications (P910073, P950001, P960060).
Materials that have a new use in the EASYTRAK lead include silicone
rubber with titanium oxide pigment, polyurethane, and PTFE. Guidant
performed biocompatibility testing on these materials and all were
determined to be biocompatible. Biocompatibility testing included
cytotoxicity, hemolysis, Ames Mutagenicity, and acute and chronic system
toxicity.

Materials used in the CONTAK CD CRT-D pulse generator, and the EASYTRAK
lead and lead accessories were tested and met the requirements of
ISO-10993, \"Biological Evaluation of Medical Devices Part 1: Evaluation
and Testing (1997).

## Sterilization Validation

Sterilization assessments were performed and validated that the CONTAK
CD CRT-D Model 1823 pulse generator, EASYTRAK leads, and system
accessories can be effectively sterilized with the Getinge Oxyfume
2000^®^ or the 100% ethylene oxide (EtO) sterilization process. These
processes are identical to those used for Guidant's commercially
available ICD pulse generators and leads.

For the CONTAK CD CRT-D Model 1823 pulse generator, the sterility
assurance factor (SAL) was estimated to be 10^-24^. For the EASYTRAK
lead, suture sleeve, LV-1 Lead Cap, LV-1 Lead Port Plug, and Model 6744
Lead Adapter the SAL was estimated to be 10^-16^. For the Finishing
Wire, the SAL was estimated to be 10^-37^.

## Animal Studies

Guidant conducted an animal study in compliance with Good Laboratory
Practice (GLP) regulations (21 CFR, Part 58) with the CONTAK CD CRT-D
system in an *in-vivo* canine model to demonstrate that the system meets
user needs and intended uses. The ani­mal study also addressed the
compatibility of the system components and verified that the components
of the CONTAK CD CRT-D system were compatible, and the system performed
safely for its intended use.

In addition to the system study described above, Guidant conducted a
series of animal studies to verify that the EASYTRAK lead is safe for
chronic implantation. These studies demonstrated that the EASYTRAK lead
is biocompatible and biostable after chronic (six months) implantation
in canines and that the lead remains in position once implanted.

## Shelf Life for PMA Devices

Table 11: Device Shelf Life

+---------------------------------------+------------------------------+
| Device                                | Shelf Life                   |
+=======================================+==============================+
| CONTAK CD CRT-D pulse generator,      | Expiration dating for this   |
| Model 1823                            | device has been established  |
|                                       | and approved at 1 year from  |
|                                       | the battery-attach date.     |
+---------------------------------------+------------------------------+
| EASYTRAK Lead, 4510, 4511, 4512, 4513 | Expiration dating for this   |
|                                       | device has been established  |
|                                       | and approved at 2 years from |
|                                       | the date of sterilization.   |
+---------------------------------------+------------------------------+
| Accessory:                            | Expiration dating for this   |
|                                       | device has been established  |
| -   Finishing Wire, Models 6730,      | and approved at 2 years from |
|     6731, 6732, 6733                  | the date of sterilization.   |
+---------------------------------------+------------------------------+
| Accessories:                          | Expiration dating for these  |
|                                       | devices has been established |
| -   Suture Sleeve, Model 6741         | and approved at 4 years from |
|                                       | the date of sterilization.   |
| -   LV-1 Lead Cap, Model 6742         |                              |
|                                       |                              |
| -   LV-1 Lead Port Plug, Model 6742   |                              |
|                                       |                              |
| -   Lead Adapter, Model 6744          |                              |
+---------------------------------------+------------------------------+

# Summary of Clinical Studies

Guidant conducted the CONTAK CD Study to demonstrate the safety and
effectiveness of the CONTAK CD CRT-D system and to demonstrate a
reasonable assurance of the safety and effectiveness of biventricular
stimulation, or cardiac resynchronization therapy (CRT), using the
Guidant Model 1822 VENTAK CHF AICD and Model 1823 CONTAK CD CRT-D pulse
generator along with the EASYTRAK (Models 4510/4511/4512/4513) coronary
venous steroid-eluting single-electrode pace/sense lead.

The CONTAK CD Study failed to prospectively demonstrate effectiveness of
the CRT function of the device. The CONTAK CD Study met the Lead and
System Effectiveness endpoints as well as the Lead and System Safety
endpoints (as defined on page 22). Subgroup analysis revealed a
population of patients that had Class III/IV heart failure at the time
of randomization that appeared to have improvements on certain
functional endpoints, including the peak VO2 and the six minute hall
walk. A second study was performed (Focused Confirmatory Study) using
this subgroup of patients to confirm the effectiveness of CRT.

##  CONTAK CD Study

### Study Design

The CONTAK CD Study was a prospective randomized, controlled,
multicenter, double-blind study conducted at 47 sites in the United
States and enrolled a total of 581 patients. All patients enrolled were
intended to be implanted with a device capable of delivering both CRT
and treating ventricular tachyarrhythmias. Patients were randomized to
CRT Off (VVI lower rate 40) or CRT On (VDD). The study began as a
crossover design (called "Phase I") and enrolled 248 patients with a
primary endpoint of functional status with three months of follow-up.
The study was later modified to a parallel design (called "Phase II")
and enrolled 333 patients with a longer, six-month follow-up. The data
from the first three months of the crossover phase were pooled with data
from the six-month parallel phase. The visit schedule and testing
requirements remained the same. Additionally, while the study originally
used the VENTAK CHF AICD in conjunction with epicardial leads placed via
thoracotomy, the CONTAK CD CRT-D and EASYTRAK lead (placed
transvenously) were added to the protocol later in the study.

### Inclusion/Exclusion Criteria

Patients enrolled in the study were required to meet the following
inclusion criteria:

-   Meet the general indication for ICD implant

-   Symptomatic heart failure despite optimal drug therapy (ACE
    inhibitors with diuretic and/or digoxin, as determined to be
    indicated and tolerated by the patient's physician-investigator)

-   Left ventricular ejection fraction ≤ 35%

-   QRS duration ≥ 120 ms

-   Age ≥ 18 years

-   Normal sinus node function

Patients were excluded from the investigation if they met any of the
following criteria:

-   Meet the general indications for permanent antibradycardia pacing,
    including pacemaker dependence

-   Have chronic, medically refractory atrial tachyarrhythmias

-   Require concomitant cardiac surgery

-   Are unable to undergo device implant, including general anesthesia
    if required

-   Are unable to comply with the protocol and follow-up requirements,
    including exercise testing

-   Have a life expectancy of less than six months due to other medical
    conditions

-   Have amyloid disease (amyloidosis)

-   Have hypertrophic obstructive cardiomyopathy

-   Require in-hospital continuous intravenous inotropes

-   Have pre-existing cardioversion/defibrillation leads other than
    those specified in the investigational plan (unless the investigator
    intends to replace them with permitted cardioversion/defibrillation
    leads)

-   Women who are pregnant or not using medically accepted birth control

-   Have a mechanical tricuspid prosthesis

-   Involved in other cardiovascular clinical investigations of active
    therapy or treatment

### Follow-up schedule

  ---------------- ------------------------------------------------------
  Pre-implant      Initial assessment of patient eligibility; taking of
  visit            patient history.

  Implant          Implant of investigational devices and acute device
                   testing. Randomization status (CRT or No CRT) was
                   assigned for implementation after a 30-day Recovery
                   Period.

  Recovery Period  Minimum 30-day period over which the patient recovered
                   from the implant procedure and had his/her heart
                   failure medications adjusted, but with no CRT
                   regardless of the randomization assignment.

  Post-Recovery    First visit after the Recovery Period in which
  Visit            patients underwent Special Testing^\*^ to establish
                   their baseline condition, after which the
                   randomization assignment was implemented (CRT or No
                   CRT).

  Three- and       Evaluation of randomized therapy with Special
  six-month Visits Testing^\*^ and device function at three- and
                   six-months after the Post-Recovery Visit.

  Quarterly Visits After the six-month visit, patients were seen for
                   routine evaluation of device function and patient
                   condition.
  ---------------- ------------------------------------------------------

\* Special Testing included a Symptom-Limited Treadmill Test with
measurement of oxygen uptake (Peak VO~2~), a Six-Minute Walk,
Echocardiography, Holter monitoring, blood chemistry testing, and a
Quality of Life (QOL) questionnaire.

### Patient Groups

The CONTAK CD Study included patients with symptomatic heart failure
despite optimal drug therapy as defined in the inclusion criteria. This
population included patients who were NYHA Class II, III, or IV at the
time of implant.

Based upon the clinical results from the covariate analyses in this
study, and the internal consistency of these clinical findings with
those from other completed CRT studies, the patient subgroup with NYHA
Class III/IV heart failure in this study was examined further.

***All Patients:*** All patients (NYHA Class II/III/IV at the time of
implant) implanted with an investigational system (N=501). Ten patients
died and one withdrew before the Post-Recovery Visit. Therefore, therapy
effectiveness analyses used N=490.

***NYHA Class III/IV (Advanced Heart Failure)**:* This subgroup was
defined as those patients with moderate to severe heart failure at the
time of the Post-Recovery Visit (N=227). A percentage of patients either
had an improvement or worsening of their NYHA Class during the
post-implant recovery period. The patients in the Advanced Heart Failure
subgroup were only those who remained in NYHA Class III/IV at the end of
the post recovery period. This subgroup was determined from interaction
analysis of pre-selected covariates with the functional status
endpoints.

### Endpoints

The CONTAK CD Study had three investigational elements consisting of:

**CRT Effectiveness:**

*Primary:* Composite endpoint consisting of all-cause mortality,
hospitalization for heart failure, and ventricular tachyarrhythmia
requiring device intervention.

*Secondary:* Peak VO~2~ derived from a symptom-limited exercise test and
Quality of Life as measured by the Minnesota Living with Heart Failure
Questionnaire^©^.

*Additional:* Six-Minute Walk, NYHA Class, Echocardiographic Analysis,
Change in Norepinephrine, and Change in Heart Rate.

Lead and System Effectiveness:

*Lead:* Left ventricular pacing thresholds, biventricular sensing,
biventricular lead impedance, and lead placement success rate.

*System:* VF detection time, biventricular antitachycardia pacing (ATP)
efficacy.

Lead and System Safety:

*Lead*: Incidence of lead-related adverse events.

*System:* Incidence of severe, device-related adverse events and
operative mortality.

### Study Results

####  Patient Accountability

Figure 1: Enrollment and Follow-Up of Randomized Patients

![](media/image1.png){width="4.497222222222222in"
height="6.517361111111111in"}

#### Baseline Characteristics

Table 12: Pre-Implant Assessment

All patients implanted, N=501**\* P-values for comparing means were
calculated with Student's t-test; p-values for comparing proportions
were calculated with Pearson's chi-squared test.**

\*\* PR interval and QRS duration were not obtained for thoracotomy
patients

Table 13: Pre-Implant History

> All patients implanted, N=501\* P-values were calculated with
> Pearson's chi-squared test

#### CRT Effectiveness

##### Heart Failure Progression (Composite Index)

The Composite Index (primary endpoint) was a combination of three
events: all-cause mortality, hospitalization for heart failure, and
VT/VF event requiring therapy. A committee consisting of three heart
failure specialists and an electrophysiologist reviewed and adjudicated
all patient deaths and all hospitalizations, defined as an admission
greater than 23 hours. Outpatient care, emergency room care, and clinic
visits less than 23 hours were collected but not considered to be
hospitalizations for the purposes of analysis.

Table 14: Composite Index

All patients implanted and active 31 days post-implant

+-------------+------------------+---+-----+---+-----+--------------+
| Group       | Heart Failure    | C |     | N |     | Relative     |
|             | Mortality or     | R |     | o |     | Reduction    |
|             | Morbidity Event  | T |     | C |     | with CRT     |
|             |                  |   |     | R |     |              |
|             |                  |   |     | T |     |              |
+-------------+------------------+---+-----+---+-----+--------------+
|             |                  | N | \%  | N | \%  |              |
+-------------+------------------+---+-----+---+-----+--------------+
| All         | Death from any   | 1 | 4.5 | 1 | 6.5 | 15%          |
| Patients    | cause            | 1 |     | 6 |     |              |
|             |                  |   |     |   |     | p=0.35       |
| (NYHA       |                  |   |     |   |     |              |
| II/III/IV)  |                  |   |     |   |     |              |
|             |                  |   |     |   |     |              |
| (n=490)     |                  |   |     |   |     |              |
+-------------+------------------+---+-----+---+-----+--------------+
|             | HF               | 3 | 1   | 3 | 1   |              |
|             | hospitalization  | 2 | 3.1 | 9 | 5.9 |              |
+-------------+------------------+---+-----+---+-----+--------------+
|             | VT/VF            | 3 | 1   | 3 | 1   |              |
|             |                  | 6 | 4.7 | 9 | 5.9 |              |
+-------------+------------------+---+-----+---+-----+--------------+
| NYHA Class  | Death from any   | 1 | 9.4 | 1 | 1   | 22%          |
| III/IV      | cause            | 1 |     | 1 | 0.0 |              |
|             |                  |   |     |   |     | p=0.23       |
| (n=227)     |                  |   |     |   |     |              |
+-------------+------------------+---+-----+---+-----+--------------+
|             | HF               | 2 | 1   | 2 | 2   |              |
|             | hospitalization  | 3 | 9.7 | 7 | 4.5 |              |
+-------------+------------------+---+-----+---+-----+--------------+
|             | VT/VF            | 2 | 1   | 2 | 2   |              |
|             |                  | 1 | 7.9 | 2 | 0.0 |              |
+-------------+------------------+---+-----+---+-----+--------------+

Twenty-seven patients died during the therapy phase. Mortality
stratified by treatment group and cause, as adjudicated by the Events
Committee, is shown in Table 15. The Kaplan-Meier (Figure 2) shows total
survival by treatment group.

Table 15: Mortality Stratified by Treatment Group and Cause

All patients implanted and active at 31 days post-implant, N=490

  --------------------------------------- --------------- ---------------
  Deaths                                  CRT\            No CRT\
                                          (N=245)         (N=245)

  Cardiac, pump failure                   4 (1.6%)        9 (3.7%)

  Cardiac, arrhythmic                     1 (0.4%)        0 (0.0%)

  Cardiac, other                          2 (0.8%)        1 (0.4%)

  Non-cardiac                             2 (0.8%)        3 (1.2%)

  Unknown                                 2 (0.8%)        3 (1.2%)

  Total                                   11 (4.5%)       16 (6.5%)
  --------------------------------------- --------------- ---------------

Figure 2: Kaplan Meier Curve

> ![](media/image2.png){width="4.000694444444444in"
> height="3.479861111111111in"}

Table 16 presents the reasons for hospitalization within the treatment
period as determined by the Events Committee.

Table 16: Patients Hospitalized during Treatment Period\*

All patients implanted and active at 31 days post-implant, N=490

+---------------+--------+--------+--------+--------+--------+--------+
|               | All Pa |        |        | NYHA   |        |        |
|               | tients |        |        | Class  |        |        |
|               |        |        |        | III/IV |        |        |
+---------------+--------+--------+--------+--------+--------+--------+
| Reason for \  | *      | **No   | **T    | *      | **No   | **T    |
| Ho            | *CRT** |  CRT** | otal** | *CRT** |  CRT** | otal** |
| spitalization |        |        |        |        |        |        |
|               | **(N=  | **(N=  | **(N=  | **(N=  | **(N=  | **(N=  |
|               | 245)** | 245)** | 490)** | 117)** | 110)** | 227)** |
+---------------+--------+--------+--------+--------+--------+--------+
| Heart Failure | 32     | 39     | 71     | 23     | 27     | 50     |
+---------------+--------+--------+--------+--------+--------+--------+
| Cardiac -     | 20     | 25     | 45     | 14     | 14     | 28     |
| other         |        |        |        |        |        |        |
+---------------+--------+--------+--------+--------+--------+--------+
| Noncardiac    | 26     | 19     | 45     | 14     | 14     | 28     |
+---------------+--------+--------+--------+--------+--------+--------+
| **Total       | **66** | **70** | *      | **40** | **46** | **86** |
| Hospi         |        |        | *136** |        |        |        |
| talizations** |        |        |        |        |        |        |
+---------------+--------+--------+--------+--------+--------+--------+

\* Represents number of patients with each category of hospitalization.
Patients may have multiple hospitalizations that fall into different
categories

##### Peak VO2

Peak VO~2~ was determined from a standardized protocol for exercise
testing as a means of measuring a patient's capacity for performing
physical activity.

Figure 3: Change in Peak VO~2~

![](media/image3.png){width="3.9993055555555554in" height="3.78125in"}

  --------------- -------------- --------- --------- --------- --------- ---------
                  All Patients                       NYHA                
                                                     Class               
                                                     III/IV              

  Peak VO~2~\     CRT\           No CRT\   P-val     CRT\      No CRT\   P-val\*
  (ml/kg/min)     (N=216)        (N=201)             (N= 96)   (N= 80)   

  Post-recovery   13.5 +/- 0.2   13.5 +/-  \-        12.0 +/-  12.0 +/-  \-
  Visit                          0.2                 0.3       0.3       

  3 Months        14.3 +/- 0.2   13.9 +/-  0.206     12.8 +/-  12.1 +/-  0.084
                                 0.2                 0.4       0.4       

  6 Months        14.4 +/- 0.3   13.6 +/-  0.030     13.8 +/-  12.0 +/-  0.003
                                 0.3                 0.5       0.5       
  --------------- -------------- --------- --------- --------- --------- ---------

\*P-values reflect the between-group differences with respect to
baseline.

##### Six-Minute Walk

The Six-Minute Walk test is a measure of a patient's ability to sustain
exercise during an activity similar to that which a patient may
typically perform on a daily basis. For this test, patients are
instructed to walk as far as possible in 6 minutes in a level corridor.
**Figure 4** provides the change in Six-Minute Walk.

Figure 4: Change in Six Minute Walk

![](media/image4.png){width="3.9993055555555554in" height="3.78125in"}

  --------------- -------------- --------- --------- --------- --------- ---------
                  All Patients                       NYHA                
                                                     Class               
                                                     III/IV              

  Six Minute Walk CRT\           No CRT\   P-val\*   CRT\      No CRT\   P-val\*
  Distance        (N=224)        (N=220)             (N= 99)   (N= 90)   
  (meters)                                                               

  Post-recovery   317 +/- 5      317 +/- 5 \-        268 +/- 9 268 +/- 9 \-
  Visit                                                                  

  3 Months        348 +/- 7      331 +/- 8 0.058     312 +/-   280 +/-   0.028
                                                     12        12        

  6 Months        353 +/- 8      332 +/- 8 0.043     327 +/-   288 +/-   0.029
                                                     14        15        
  --------------- -------------- --------- --------- --------- --------- ---------

\*P-values reflect the between-group differences with respect to
baseline.

##### Quality of Life

Quality of Life (QOL) (Figure 5) was assessed using the 21 question
Minnesota Living with Heart Failure questionnaire. Each question is
answered by the patient, ranking each item on a scale ranging from 0 to
5. A lower total score indicates an improved quality of life.

Figure 5: Change in Quality of Life

![](media/image5.png){width="3.9993055555555554in" height="3.78125in"}

  ----------------- -------------- ----------- ------------- ----------- ----------- -------------
                    All Patients                             NYHA Class              
                                                             III/IV                  

  **QOL (points)**  **CRT\         **No CRT\   **P-val\***   **CRT\      **No CRT\   **P-val\***
                    (N=234)**      (N=225)**                 (N=107)**   (N= 96)**   

  **Post-recovery   41.8 +/- 1.1   41.8 +/-    \-            52.7 +/-    52.7 +/-    \-
  Visit**                          1.1                       1.5         1.5         

  **3 Months**      36.6 +/- 1.5   37.3 +/-    0.711         41.9 +/-    47.5 +/-    0.078
                                   1.6                       2.4         2.6         

  **6 Months**      34.8 +/- 1.8   36.9 +/-    0.395         37.2 +/-    47.3 +/-    0.017
                                   1.8                       3.1         3.2         
  ----------------- -------------- ----------- ------------- ----------- ----------- -------------

\*P-values reflect the between-group differences with respect to
baseline.

##### NYHA Class

The determination for New York Heart Association (NYHA) Class is based
on mutual assessment by the patient and the patient\'s physician of the
patient's heart failure symptoms both at rest and while performing
ordinary physical activity. NYHA Class was determined at each follow-up
visit by a physician who was blinded to the patient's randomized
therapy.

Figure 6: Changes in NYHA Class

![](media/image6.png){width="5.99375in" height="2.3666666666666667in"}

  --------------- -------------- ------ ----------- ------ ------------- ----------- ------ ----------- ------ -------------
                  All Patients                                           NYHA Class                            
                                                                         III/IV                                

                  **CRT                 **No CRT           **P-val\***   **CRT\             **No CRT\          **P-val\***
                  (N=109)**             (N=116)**                        (N= 45)**          (N= 48)**          

  Change in \     N              \%     N           \%                   N           \%     N           \%     
  NYHA Class                                                                                                   

  Improve 2 or    12             11.0   2           1.7    0.10          12          26.7   2           4.2    0.006
  More Classes                                                                                                 

  Improve 1 Class 27             24.8   35          30.2                 21          46.7   24          50.0   

  No Change       56             51.4   59          50.9                 10          22.2   18          37.5   

  Worsen 1 Class  13             11.9   19          16.4                 2           4.4    4           8.3    

  Worsen 2 or     1              0.9    1           0.9                  0           0.0    0           0.0    
  More Classes                                                                                                 
  --------------- -------------- ------ ----------- ------ ------------- ----------- ------ ----------- ------ -------------

\*P-value was calculated from Mantel-Haenszel test and reflects the
between-group differences with respect to baseline.

##### Echocardiography

Several echocardiography (echo) variables were identified to assist in
measuring the possible hemodynamic impact of CRT as shown in Table 17.
The limitation of this data is that patients are measured while at rest,
and therefore, the data may not reflect any hemodynamic benefit that may
be observed when patients are exercising and performing their daily
activities.

##### Table 17: Echocardiography ResultsMeasures of Sympathetic Tone

Mean Norepinephrine levels (Table 18) and Mean Heart Rate (Table 19)
were examined as markers of how CRT may influence the excessive
sympathetic drive associated with chronic heart failure.

Table 18: Mean Norepinephrine Results

  ------------------- -------------- --------- --------- --------- --------- ---------
                      All Patients                       NYHA                
                                                         Class               
                                                         III/IV              

  **Norepinephrine\   CRT\           No CRT\   P-val     CRT\      No CRT\   P-val
  (pg/mL)**           (N=228)        (N=217)             (N=104)   (N= 90)   

  **Post-recovery     663 +/- 19     663 +/-   \-        720 +/-   720 +/-   \-
  Visit**                            19                  31        31        

  **3 Months**        651 +/- 31     681 +/-   0.479     685 +/-   743 +/-   0.463
                                     32                  55        60        

  **6 Months**        658 +/- 40     738 +/-   0.143     681 +/-   827 +/-   0.163
                                     41                  75        79        
  ------------------- -------------- --------- --------- --------- --------- ---------

Table 19: Mean Heart Rate Results

  ----------------- -------------- --------- --------- --------- --------- ---------
                    All Patients                       NYHA                
                                                       Class               
                                                       III/IV              

  **Heart Rate      CRT\           No CRT\   P-val     CRT\      No CRT\   P-val
  (bpm)**           (N=240)        (N=233)             (N=113)   (N=101)   

  **Post-recovery   72.3 +/- 0.6   72.3 +/-  \-        74.5 +/-  74.5 +/-  \-
  Visit**                          0.6                 1.0       1.0       

  **3 Months**      70.8 +/- 0.8   72.1 +/-  0.20      74.1 +/-  73.9 +/-  0.94
                                   0.8                 1.2       1.3       

  **6 Months**      69.4 +/- 1.0   70.2 +/-  0.58      70.6 +/-  72.5 +/-  0.40
                                   1.0                 1.6       1.6       
  ----------------- -------------- --------- --------- --------- --------- ---------

#### EASYTRAK Lead and System Effectiveness

##### Lead Measurements

Figure 7: EASYTRAK Lead Threshold Measurements

All patients implanted with an EASYTRAK lead at first implant, N=443

![](media/image7.png){width="3.1465277777777776in"
height="2.2680555555555557in"}

  ---------------------------------------------------------------------------
  Statistic            Implant   3 Months 6 Months 12       18       24
                                                   Months   Months   Months
  -------------------- --------- -------- -------- -------- -------- --------
  N                    435       347      330      233      103      25

  Mean +/- SD          1.8 +/-   1.7 +/-  1.9 +/-  1.8 +/-  1.8 +/-  2.0 +/-
                       1.2       1.3      1.5      1.2      1.1      1.2

  Range                0.2 - 7.5 0.2 -    0.2 -    0.4 -    0.6 -    0.6 -
                                 7.5      7.5      7.5      7.5      5.0

  Upper Tolerance      3.8       3.8      4.3      3.8      3.7      3.9
  Limit                                                              
  ---------------------------------------------------------------------------

\* EASYTRAK lead models: 4511, 4512, and 4513

It was hypothesized that the upper tolerance limit of the chronic left
ventricular pacing threshold of the EASYTRAK lead be less than 5.5 V to
ensure that an adequate safety margin exists. Chronic left ventricular
pacing thresholds shown in Figure 7 are within this limit.

Figure 8: EASYTRAK Biventricular Sensed R-wave Amplitude

All patients implanted with an EASYTRAK lead at first implant, N=443

![](media/image8.png){width="3.5680555555555555in"
height="2.5083333333333333in"}

  ---------------------------------------------------------------------------
  Statistic            Implant   3 Months 6 Months 12       18       24
                                                   Months   Months   Months
  -------------------- --------- -------- -------- -------- -------- --------
  N                    433       346      326      220      99       23

  Mean +/- SD          10.0 +/-  9.9 +/-  9.9 +/-  9.8 +/-  8.9 +/-  8.5 +/-
                       5.2       4.4      4.5      4.4      3.5      3.3

  Range                1.9 -     1.4 -    1.7 -    1.2 -    2.6 -    2.2 -
                       25.0      25.0     25.0     25.0     20.4     13.6
  ---------------------------------------------------------------------------

Mean chronic biventricular R-wave amplitudes are measured as a
combination of the R-waves from both the right ventricle (commercially
available ENDOTAK lead) and the left ventricle (EASYTRAK lead). It was
hypothesized that the mean biventricular R-wave amplitude be greater
than 5 mV to ensure proper sensing (Figure 8). The performance of the
EASYTRAK lead system was significantly above this value (p\<0.01).

Figure 9: EASYTRAK Biventricular Pacing Impedance

All patients implanted with an EASYTRAK lead at first implant, N=443

![](media/image9.png){width="3.9965277777777777in"
height="2.7916666666666665in"}

  --------------------------------------------------------------------------------
  Statistic    Implant   3 Months   6 Months   12 Months   18 Months   24 Months
  ------------ --------- ---------- ---------- ----------- ----------- -----------
  N            436       355        336        237         107         26

  Mean +/- SD  340 +/-   352 +/- 47 349 +/- 50 351 +/- 51  347 +/- 46  356 +/- 67
               46                                                      

  Range        243 - 550 248 - 519  186 - 534  237 - 513   254 - 507   267 - 520

  95% CI       (336,     (347, 357) (344, 355) (345, 358)  (338, 356)  (329, 383)
               344)                                                    
  --------------------------------------------------------------------------------

The impedance measured by the CONTAK CD CRT-D device is the parallel
combination of the left ventricular (EASYTRAK) and right ventricular
(ENDOTAK) leads simultaneously. Therefore, the biventricular lead
impedance will be substantially less than that of either lead alone. It
was hypothesized that the lower limit of the 95% confidence interval of
the mean chronic biventricular lead impedance would be greater than 200
Ω to ensure proper pulse generator function. The lower limit of the 95%
confidence interval of the chronic biventricular lead impedance exceeds
this value (Figure 9).

##### EASYTRAK Lead Placement Success Rate

The EASYTRAK lead was implanted in 448/517 (87%) of patients who
underwent the implant procedure. Table 20 shows the reasons for
inability to place the EASYTRAK lead. Table 21 provides the EASYTRAK
lead implant success rate.

Table 20: Reasons for unsuccessful EASYTRAK Lead implant

Patients with unsuccessful attempt to implant EASYTRAK lead (N=69)

  --------------------------------------------------- --------- ----------
  Reason                                              \# of pts \%

  Inability to locate or cannulate the coronary sinus 29        42.0

  Dislodgment of EASYTRAK lead while removing guide   13        18.8
  catheter                                                      

  Inability to advance the lead to a stable position  11        15.9

  Inability to obtain adequate pacing thresholds      6         8.7

  Procedure stopped due to coronary sinus dissection  5         7.2
  or perforation                                                

  Procedure stopped due to transient AV block         1         1.4

  Procedure stopped due to venous perforation during  1         1.4
  subclavian stick                                              

  Reason not stated                                   1         1.4

  Extracardiac stimulation                            1         1.4

  Inability to place an atrial pace/sense lead        1         1.4

  Total                                               69        100%
  --------------------------------------------------- --------- ----------

Table 21: EASYTRAK Lead Placement Success Rate

All patients implanted or attempted with EASYTRAK lead (N=517)\* Defined
as an EASYTRAK implant procedure that is concluded with the implant of
the investigational cardiac resynchronization system.

Although some situations such as patient anatomy and poor thresholds
cannot be avoided, increased investigator experience with the EASYTRAK
lead and accessories was associated with improved success, decreased
total procedure time (measured skin-to-skin), and decreased fluoroscopy
exposure time (Figure 10).

Figure 10: EASYTRAK Success Rate, Procedure Time, Fluoroscopy Exposure
Time

![](media/image10.png){width="5.989583333333333in"
height="2.7159722222222222in"}

##### Biventricular Antitachycardia Pacing (ATP) Conversion Efficacy Performance

The conversion rate of induced monomorphic ventricular tachycardia (MVT)
was 64% and that of spontaneous MVT was 88%.

##### Ventricular Tachyarrhythmia Detection Time

The VENTAK CHF AICD and CONTAK CD CRT-D devices sense events from both
ventricles simultaneously. Ventricular tachyarrhythmia detection time
was analyzed to determine if the additional lead had an adverse effect
on sensing VT/VF. Guidant\'s ICDs typically have a detection time of two
seconds. The VF detection time of 2.1 ± 0.6 seconds was statistically
significantly lower than 6 seconds[^1] (p\<0.01), demonstrating that
there was no statistically significant prolongation of induced VF
detection times with the additional left ventricular lead. There were
also no adverse events reported in which a VENTAK CHF AICD or CONTAK CD
CRT-D device failed to detect a spontaneous ventricular tachyarrhythmia.

#### EASYTRAK Lead and System Safety

##### EASYTRAK Lead Safety

Safety was established using the rate of adverse events that are either
related to the EASYTRAK lead or to the implant procedure necessary to
place the EASYTRAK lead.

An EASYTRAK lead implant procedure was performed in 517 patients with
448 patients (86.7%) being successfully implanted with the EASYTRAK
lead.[^2] The upper boundary of the 95% confidence interval was
hypothesized to be less than 23% at six months (Table 22).

Table 22: Lead Related Adverse Events at Six Months

  -------------------------- --------- ------------- ---------------------
  Patient Population         N         Event Rate    95% Confidence
                                       (%)           Interval

  All Patients               517       12.2          \[9.4, 15.0\]

  NYHA Class III/IV          201       17.4          \[12.7, 22.7\]
  -------------------------- --------- ------------- ---------------------

Fifty-three lead-related adverse events were reported during the
clinical investigation of the EASYTRAK lead among the 448 patients who
were implanted with an EASYTRAK lead. Twenty-seven procedure-related
adverse events were reported among the 517 patients who underwent the
implant procedure for an EASYTRAK lead. The overall lead-related adverse
event rate was 14.5% \[95% CI (11.5--17.5%)\]. Table 23 reports
lead-related adverse events observed during the CONTAK CD Study.

Table 23: EASYTRAK Lead-Related Adverse Events throughout the Study

All patients implanted (N=448) All patients attempted (N=517)

  -------------------------------------------------------------------------
  Adverse Events                          Total          \% of pts (95% Cl)
  --------------------------------------- -------------- ------------------
  **Lead-Related, N = 448**                              

  Loss of capture/lead dislodgment        31^a^          6.9 (4.6--9.3)

  Ventricular oversensing                 11             2.5 (1.0--3.9)

  Extracardiac stimulation                9              2.0 (0.7--3.3)

  Insulation breach                       2              0.4 (0.0--1.1)

  **Procedure-Related, N = 517**                         

  Transient AV block                      6              1.2 (0.2--2.1)

  Coronary venous dissection              5              1.0 (0.1--1.8)

  Coronary venous perforation             5              1.0 (0.1--1.8)

  Transient renal failure                 5              1.0 (0.1--1.8)

  Pericardial effusion                    2              0.4 (0.0--0.9)

  Finishing wire left in lead             1              0.2 (0.0--0.6)

  Right ventricular lead dislodgment      1              0.2 (0.0--0.6)

  Guide wire fracture                     1              0.2 (0.0--0.6)

  Hypotension due to blood loss           1              0.2 (0.0--0.6)

  **Total (unique patients)**             75             14.5(11.5--17.5)
  -------------------------------------------------------------------------

a\. Twenty-six events were successfully corrected in a repeat procedure

The most common of the 53 lead-related adverse events (\>1% incidence)
included loss of left ventricular capture (31 patients, 6.9%),
ventricular oversensing (11 patients, 2.5%), and extracardiac
stimulation (9 patients, 2.0%). These events were typically resolved
with surgical intervention.

The most common of the 27 procedure-related adverse events (\>1%
incidence) included coronary venous trauma (10 patients, 2.0%),
transient atrioventricular block (6 patients, 1.2%), and transient renal
failure (5 patients, 1.0%). These events were typically resolved without
intervention and no permanent long-term sequelae were reported.

##### Severe, Device-Related Adverse Events and Operative Mortality

Table 24: Adverse Events and Operative Mortality

> All patients attempted or implanted (N=567)\*Percent is of patients
> with at least one event

The incidence of severe, device-related events was reported in 7 of 567
patients (1.2%); this was significantly less than the hypothesized rate
of 20% (p\<0.01) (Table 24).\
Table 25 reports system, device-related, severe adverse events observed
during the CONTAK CD Study.

Table 25: System, device-related, severe adverse events

**All patients attempted or implanted (N=567)**

  ----------------------------------------------- -------- ---------------
  Adverse Event                                   \# of    \% of pts (95%
                                                  pts      CI)

  Telemetry difficulty; device explanted          2        0.4 (0.0--0.9)

  Ventricular tachycardia during CPX testing      1        0.2 (0.0--0.5)

  Coronary sinus perforation                      1        0.2 (0.0--0.5)

  Inappropriate shock due to oversensing          1        0.2 (0.0--0.5)

  Lead dislodgment                                1        0.2 (0.0--0.5)

  Anaphylaxis in association with use of a        1        0.2 (0.0--0.5)
  pulmonary artery catheter                                
  ----------------------------------------------- -------- ---------------

Operative mortality, defined as death from any cause within 30 days of
implant, was reported in 12 of 567 patients (2.1%) undergoing the
implant procedure. The outcome is significantly less than the
hypothesized rate of 9% (p\<0.01). Table 26 reports the cause of death
for operative mortality.

Table 26: Cause of Death for Operative Mortality

All patients attempted or implanted, N=567

+------------------------------------+----------+----------+----------+
| Cause of Death                     | Implants | Attempts | Total    |
|                                    |          |          |          |
|                                    | N=501    | N=66     | N=567    |
+------------------------------------+----------+----------+----------+
| Cardiac: Pump Failure              | 5        | 1        | 6        |
+------------------------------------+----------+----------+----------+
| Cardiac: Arrhythmic                | 2        | 1        | 3        |
+------------------------------------+----------+----------+----------+
| Non-Cardiac                        | 2        | 0        | 2        |
+------------------------------------+----------+----------+----------+
| Unknown                            | 1        | 0        | 1        |
+------------------------------------+----------+----------+----------+
| **Total**                          | **10**   | **2**    | **12**   |
+------------------------------------+----------+----------+----------+

##### System Safety Profile

Analysis of system safety was performed on the complication-free rate of
device-related adverse events, regardless of whether or not they were
related to the investigational device (Figure 11). Table 27 outlines the
device related complications. This study used an acceptance criterion
such that the lower boundary of the 95% confidence interval could not be
less than 70%.

Table 27: Device-related Complications\*

All patients implanted (N=448) All patients attempted (N=517)

  ----------------------------------------------- -------- ---------------
  Complication                                    \# of    \% of pts
                                                  pts      

  **All patients implanted (N=448)**                       

  Loss of LV capture                              31       6.9

  Loss of right atrial capture                    7        1.6

  Ventricular oversensing                         6        1.3

  Extracardiac stimulation                        5        1.1

  **All patients attempted or implanted (N=517)**          

  Infections                                      7        1.4
  ----------------------------------------------- -------- ---------------

\*This table represents patients attempted or implanted with the
EASYTRAK lead, most common (\> 1%) device-related complications
reported.

Figure 11: System Safety

![](media/image11.png){width="4.042361111111111in"
height="2.229861111111111in"}

System safety for the All Patients group and the NYHA Class III/IV
subgroup as determined by the device-related complication-free rate was
within the 70% acceptance boundary for safety.

#### Verification of CRT Delivery

The delivery of biventricular pacing throughout the CONTAK CD Study was
confirmed by comparing the programmed device output to the biventricular
pacing threshold and demonstrating that capture was maintained in daily
activities and during exercise.

The investigational plan recommended programming the device output to at
least twice the biventricular pacing voltage threshold.
Electrocardiograms (ECGs) from Holter Monitors during daily activities
were received and analyzed to verify that total capture was maintained
at the 3-month and 6-month visits and to ensure that the safety margin
was adequate. Cardiopulmonary exercise tests (CPX) were performed on
patients who were randomized to receive CRT therapy at 3- and 6- month
visits.

-   In 623 evaluations of safety margin at baseline, three-, and
    six-months, the device output was programmed to deliver a voltage
    approximately three times that necessary to stimulate both
    ventricles.

-   A total of 1139 Holter monitors were placed throughout the study at
    baseline, three- and six-months. The tests indicated only 4
    instances (0.4%) of inappropriate pacing or sensing that were all
    corrected with device programming.

-   A total of 316 CPX tests at the three- and six-month follow-up
    visits were performed in patients with CRT who also had
    interpretable ECG results. Of these, 277 (88%) had continuous CRT
    delivery throughout exercise. The remaining 39 patients (12%) had
    continuous CRT delivery until the sinus rate exceeded the maximum
    tracking rate (MTR).

## Focused Confirmatory Study

### Study Design 

The Focused Confirmatory Study (FCS) was a prospective multicenter study
conducted in the United States in 127 patients who participated in an
exercise performance study. The purpose of the FCS was:

-   To confirm effectiveness results related to functional capacity
    measures, specifically the Peak VO~2~ and 6 minute hall walk,
    previously reported in the NYHA Class III/IV Subgroup of the CONTAK
    CD Study.

CRT was provided in the same manner for the FCS as for the CONTAK CD
Study. The EASYTRAK lead, along with market approved right atrial and
right ventricular leads were used to provide biventricular stimulation.

### Study Patients

The patients in the FCS had the same heart failure indications as the
patients in the NYHA Class III/IV subgroup of the CONTAK CD Study; i.e.,
patient inclusion criteria included NYHA Class III or IV while on drug
therapy, QRS duration ≥ 120 ms, and Left Ventricular Ejection Fraction
(LVEF) ≤ 35%.

A baseline physical assessment and functional measures were performed
prior to CRT system implant. Patients were eligible for participation in
the study if they were capable of walking between 150 and 425m. In
addition to a Six-Minute Walk test, other special tests were performed
prior to implant consisting of a symptom-limited treadmill test and
completion of the Minnesota Living with Heart Failure Questionnaire to
assess Quality of Life. CRT therapy was enabled immediately upon device
implant. Patients were followed at one week, one month, three months,
six months and every three months thereafter for a routine physical
assessment and device evaluation. Special testing as defined above was
repeated at three months and six months post-implant.

Prior to study entry, patients were stable on optimal heart failure
medications (ACE inhibitors or substitute \> 1 month and beta blockers
\> 3 months). Patients were excluded if they were indicated for either a
pacemaker or ICD or if they were hospitalized for heart failure in the
month prior to enrollment.

### Baseline Demographics

The patient characteristics at study entry are summarized in Table 28.

Table 28: Pre-implant Characteristics of Study Patients (N=127)

+-----------------+--------------+-----------------------+------------+
| Characteristic  | All Patients | Characteristic        | All        |
|                 | Receiving    |                       | Patients   |
|                 | CRT          |                       | Receiving  |
|                 |              |                       | CRT        |
+-----------------+--------------+-----------------------+------------+
| Age (years)     | 61 ± 12      | QRS width (ms)        | 159 ± 27   |
+-----------------+--------------+-----------------------+------------+
| Male Gender (%) | 69%          | LBBB/NSIVCD (%)       | 91%        |
+-----------------+--------------+-----------------------+------------+
| NYHA Class III  | 94%          | Heart failure         | 91%        |
| (%)             |              | medications (%)       |            |
|                 |              |                       | 77%        |
|                 |              | -   ACE inhibitor or  |            |
|                 |              |     ARB               | 76%        |
|                 |              |                       |            |
|                 |              | -   Beta blockers     | 98%        |
|                 |              |                       |            |
|                 |              | -   Digoxin           |            |
|                 |              |                       |            |
|                 |              | -   Diuretics         |            |
+-----------------+--------------+-----------------------+------------+
| Ischemic        | 49%          |                       |            |
| Etiology (%)    |              |                       |            |
+-----------------+--------------+-----------------------+------------+
| LVEF (%)        | 23 ± 7       |                       |            |
+-----------------+--------------+-----------------------+------------+
| Resting heart   | 73 ± 12      |                       |            |
| rate (bpm)      |              |                       |            |
+-----------------+--------------+-----------------------+------------+

### Inclusion Criteria

Inclusion criteria included:

-   Moderate or severe heart failure, defined as symptomatic heart
    failure for at least six months with NYHA Class III or IV symptoms
    at the time of enrollment, AND at least one of the following events
    in the previous 12 months:

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-   Hospitalization for heart failure management

-   Outpatient visit in which intravenous (IV) inotropes or vasoactive
    infusion were administered continuously for at least 4 hours

-   Emergency room visit of at least twelve hours duration in which IV
    heart failure medications were administered (including diuretics)

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```
-   QRS ≥ 120 ms and PR interval \> 150 ms from any two leads of a
    12-lead ECG

-   Left ventricular ejection fraction ≤ 35%

-   Left ventricular end diastolic dimension ≥ 60 mm (required only if
    LVEF measured by echo)

-   Age ≥ 18 years

-   Optimal pharmacologic therapy for heart failure

-   Able to walk between 150 and 425m in a six minute walk test

### Major Differences between CONTAK CD CRT-D and Focused Confirmatory Study Patients

Some of the major differences between the study populations included:

-   Patients were excluded from the FCS if they were indicated for
    either a pacemaker or implantable cardioverter defibrillator (ICD).
    Patients in the CONTAK CD Study were excluded if they met the
    indications for a pacemaker; however, they were required to meet the
    general indications for an ICD.

-   Patients were excluded from the FCS if they were hospitalized for
    heart failure in the month prior to enrollment, whereas, there was
    no exclusion for hospitalization for heart failure in the month
    prior to enrollment for the CONTAK CD CRT-D patients.

-   Patients in the FCS must have been on stable, optimal heart failure
    medications, including beta blocker therapy for three months, prior
    to study entry. Patients in the CONTAK CD Study could be optimized
    on drug therapy between the time from device implant until the
    treatment phase (either CRT or no-CRT) began.

-   Patients in the FCS had baseline measurements performed prior to
    implant. Patients in the CONTAK CD Study had baseline measurements
    performed post-implant, but before programming of the randomized
    therapy.

-   77% (N=127) of patients in the FCS were on beta blockers compared to
    42% (N=227) in the CONTAK CD Study.

-   49% (N=127) of the patients in the FCS had ischemic etiology
    compared to 68% (N=227) in the CONTAK CD Study.

### Endpoints

The primary endpoints of the study were peak VO~2~ and six minute walk
distance. The study was designed to show a mean change in peak VO~2~ of
at least 1 ml/kg/min and a 95% lower confidence bound (LCB) at least 0.5
ml/kg/min. The study was also designed to detect a statistically
significant improvement in the Six Minute Walk Distance at a one-sided
significance level of 0.10. Additionally, two ancillary analyses of
Quality of Life Score and NYHA Class had to demonstrate a change that
was directionally favorable towards CRT using descriptive statistics.

### Study Results

Peak VO~2~

A statistically significant improvement from baseline of 0.94 ± 0.30
ml/kg/min with a 95% LCB of 0.45 was observed in peak VO~2~ after six
months of CRT.

Six-Minute walk Distance

Statistically significant improvements versus baseline were observed in
Six-Minute Walk Distance after six months of CRT with an observed mean
improvement of 50.9 ± 10.4 m. with a 95% LCB of 37.6 m.

Quality of Life

Consistent with the other analyses, a statistically significant
improvement of 23.9 ± 2.6 points was observed in the Quality of Life
score after six months of CRT with a 95% LCB of 19.7points.

New York Heart Association Class

After six months of CRT, a statistically significant improvement in NYHA
class was observed with 60.4% of patients improving one or more NYHA
class.

## Conclusions Drawn from the Studies

### Safety

The CONTAK CD CRT-D System and the EASYTRAK lead met the primary and
secondary safety endpoints. Results were within protocol specified
performance criteria for the rate of severe device related adverse
events, antitachycardia pacing (ATP) conversion efficacy, ventricular
tachyarrhythmia detection time, rate of lead related adverse events, and
operative mortality. The lead placement success rate also met specified
performance criteria.

In addition, analysis of the CONTAK CD CRT-D System and EASYTRAK lead
safety was performed on the complication-free rate of device-related
adverse events. The system was found to be within the acceptance
boundary for safety.

There was no difference in the mortality or the number of
hospitalizations between the treatment and control group.

### Effectiveness

The initial CONTAK CD Study did not fully establish effectiveness of
cardiac resynchronization therapy for the treatment of heart failure. A
subgroup of patients with Class III/IV heart failure were observed to
perform better on functional tests including Peak VO2 and Six-Minute
Hall Walk. The results of the Focused Confirmatory Study were used to
establish a reasonable assurance of effectiveness for cardiac
resynchronization therapy in that group of patients using specific
functional endpoints. Additionally, supporting evidence, such as
echocardiographic measurements, which showed reductions in left
ventricular intracavitary dimensions and an improvement in left
ventricular ejection fraction for patients randomized to CRT for six
months were used to demonstrate effectiveness.

The EASYTRAK lead met both the primary and secondary effectiveness
objectives. Results were within protocol specified performance criteria
for the following: chronic left ventricular pacing thresholds, chronic
biventricular lead impedances, and chronic biventricular R-wave
amplitudes.

# Panel Recommendation

The Circulatory Systems Devices Panel met on July 10, 2001 and voted not
approvable (5-2), based mainly on the lack of sufficient evidence of
effectiveness in the patient population studied in the CONTAK CD Study.
The Panel concluded that there were no notable safety concerns with the
device but that additional CRT effectiveness data was the single
outstanding item needed to bring the CONTAK CD CRT-D System & EASYTRAK
lead PMA to an approvable status.

# CDRH Decision

FDA agreed with the panel that additional information was needed to
determine the effectiveness of the device. The Focused Confirmatory
Study was submitted by Guidant to meet this requirement. In that study,
the sponsor was able to adequately replicate the functional
effectiveness results seen in the Class III/IV subgroup from the
original study. Combining the results of both studies together, the
sponsor has established a reasonable level of effectiveness for the CRT
portion of this device in the treatment of heart failure in the defined
population. The results from the original CONTAK CD study were
sufficient to support the safety of the system as a whole and the
effectiveness of the ICD portion of the device.

In addition, the conditions of approval include a 3-year evaluation of
mortality and chronic lead performance and adverse clinical events on
1,000 patients to assess the long-term safety of the device. Physicians
will also be required to undergo training by the sponsor prior to
implanting the system.

On April 29, 2002 the sponsor's manufacturing facility was inspected and
found to be in compliance with the Quality System Regulations (21 CFR
820).

FDA issued an approval order for P010012 on May 02, 2002. This decision
was based on the entire results of the original CONTAK CD Study and the
Focused Confirmatory Study.

# Approval Specifications

  --------------------------------------- -------------------------------
  Directions for Use:                     **See labeling**

  Hazards to Health from Use of the       **See Indications,
  Device:                                 Contraindications, Warnings,
                                          Precautions, and Adverse Events
                                          in the Labeling**

  Post-approval Requirements,             **See approval order.**
  Restrictions:                           
  --------------------------------------- -------------------------------

  -----------------------------------------------------------------------
  Measurement                                 N      \%     95% CI
  ------------------------------------------- ------ ------ -------------
  Severe, Device-Related Adverse Events (Type 7      1.2    (0.3%, 2.1%)
  I)\*                                                      

  All-Cause Operative Mortality (\<=30 Days   12     2.1    (0.9%, 3.3%)
  Post Implant)                                             
  -----------------------------------------------------------------------

  ------------------------------------------------------------------------
  Measurement                                             All Procedures
  ------------------------------------------------------- ----------------
  Number of patients implanted or attempted               517

  Number of placements\* of the EASYTRAK Lead             448

  Rate                                                    87%

  95% CI                                                  (84%, 90%)
  ------------------------------------------------------------------------

  -------------------------------------------------------------------------------------------------
                              CRT                 No CRT                 Between Groups   
  ----------- --------------- ----- ------------- -------- ------------- ---------------- ---------
  Parameter   Timepoint       N     Mean +/- SE   N        Mean +/- SE   Mean +/- SE      P-val

  All                                                                                     
  Patients                                                                                

  LVIDd (mm)  Post-recovery   228   70.4 +/- 0.5  219      70.4 +/- 0.5  0                \-
              Visit                                                                       

              Change at 6     228   -3.4 +/- 0.6  219      -0.3 +/- 0.6  -3.1 +/- 0.9     \<0.001
              Months                                                                      

  LVIDs (mm)  Post-recovery   228   58.3 +/- 0.5  219      58.3 +/- 0.5  0                **-**
              Visit                                                                       

              Change at 6     228   -4.0 +/- 0.7  219      -0.7 +/- 0.7  -3.3 +/- 0.9     \<0.001
              Months                                                                      

  LVEF (%)    Post-recovery   222   27.8 +/- 0.3  216      27.8 +/- 0.3  0                **-**
              Visit                                                                       

              Change at 6     222   5.1 +/- 0.7   216      2.8 +/- 0.7   2.4 +/- 1.0      0.020
              Month                                                                       

  NYHA Class                                                                              
  III/IV                                                                                  

  LVIDd (mm)  Post-recovery   104   71.2 +/- 0.7  92       71.2 +/- 0.7  0                \-
              Visit                                                                       

              Change at 6     104   -4.9 +/- 1.0  92       -0.2 +/- 1.1  -4.7 +/- 1.5     0.001
              Months                                                                      

  LVIDs (mm)  Post-recovery   104   59.2 +/- 0.7  92       59.2 +/- 0.7  0                **-**
              Visit                                                                       

              Change at 6     104   -5.4 +/- 1.1  92       -0.6 +/- 1.1  -4.8 +/- 1.5     0.002
              Months                                                                      

  LVEF (%)    Post-recovery   99    26.9 +/- 0.5  91       26.9 +/- 0.5  0                **-**
              Visit                                                                       

              Change at 6     99    6.0 +/- 1.1   91       2.3 +/- 1.2   3.7 +/- 1.7      0.029
              Months                                                                      
  -------------------------------------------------------------------------------------------------

##### 

+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             |                | A |     |     |     | N   |     |     |
|             |                | l |     |     |     | YHA |     |     |
|             |                | l |     |     |     | Cl  |     |     |
|             |                |   |     |     |     | ass |     |     |
|             |                | P |     |     |     | III |     |     |
|             |                | a |     |     |     | /IV |     |     |
|             |                | t |     |     |     |     |     |     |
|             |                | i |     |     |     |     |     |     |
|             |                | e |     |     |     |     |     |     |
|             |                | n |     |     |     |     |     |     |
|             |                | t |     |     |     |     |     |     |
|             |                | s |     |     |     |     |     |     |
+=============+================+===+=====+=====+=====+=====+=====+=====+
| **Chara     |                |   | **C | **N | **  | **C | **N | **  |
| cteristic** |                |   | RT\ | o C | P-v | RT\ | o C | P-v |
|             |                |   | (N= | RT\ | al\ | (N= | RT\ | al\ |
|             |                |   | 248 | (N= | *** | 117 | (N= | *** |
|             |                |   | )** | 253 |     | )** | 110 |     |
|             |                |   |     | )** |     |     | )** |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
| Primary     | Monomorphic VT |   | 148 | 136 | 0   | 72  | 48  | 0   |
| Tachy       | (MVT)          |   | (59 | (53 | .44 | (61 | (43 | .03 |
| Arrhythmia  |                |   | .7) | .8) |     | .5) | .6) |     |
| \[N (%)\]   |                |   |     |     |     |     |     |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Polymorphic VT |   | 16  | 20  |     | 7 ( | 7 ( |     |
|             | (PVT)          |   | (   | (   |     | 6   | 6   |     |
|             |                |   | 6   | 7   |     | .0) | .4) |     |
|             |                |   | .5) | .9) |     |     |     |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Nonsustained   |   | 58  | 63  |     | 30  | 35  |     |
|             | VT             |   | (23 | (24 |     | (25 | (31 |     |
|             |                |   | .4) | .9) |     | .6) | .8) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Ventricular    |   | 26  | 32  |     | 8 ( | 18  |     |
|             | Fibrillation   |   | (10 | (12 |     | 6   | (16 |     |
|             | (VF)           |   | .5) | .6) |     | .8) | .4) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Other          |   | 0 ( | 2 ( |     | 0 ( | 2 ( |     |
|             |                |   | 0   | 0   |     | 0   | 1   |     |
|             |                |   | .0) | .8) |     | .0) | .8) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
| Other       | Paroxysmal     |   | 43  | 62  | 0   | 21  | 29  | 0   |
| Arrhythmias | Atrial Fib.    |   | (17 | (24 | .05 | (17 | (26 | .13 |
| \[N (%)\]   |                |   | .3) | .5) |     | .9) | .4) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Atrial Flutter |   | 10  | 13  | 0   | 3 ( | 7 ( | 0   |
|             |                |   | (   | (   | .55 | 2   | 6   | .16 |
|             |                |   | 4   | 5   |     | .6) | .4) |     |
|             |                |   | .0) | .1) |     |     |     |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
| Arrhythmia/ | LBBB           |   | 133 | 138 | 0   | 59  | 59  | 0   |
| Conduction  |                |   | (53 | (54 | .83 | (50 | (53 | .55 |
| Disorder    |                |   | .6) | .5) |     | .4) | .6) |     |
|             |                |   |     |     |     |     |     |     |
| \[N (%)\]   |                |   |     |     |     |     |     |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | RBBB           |   | 35  | 31  |     | 21  | 14  |     |
|             |                |   | (14 | (12 |     | (17 | (12 |     |
|             |                |   | .1) | .3) |     | .9) | .7) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Non-Specific   |   | 80  | 84  |     | 37  | 37  |     |
|             |                |   | (32 | (33 |     | (31 | (33 |     |
|             |                |   | .3) | .2) |     | .6) | .6) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
| Etiology    | Ischemic       |   | 167 | 178 | 0   | 76  | 78  | 0   |
| \[N (%)\]   |                |   | (67 | (70 | .47 | (65 | (70 | .34 |
|             |                |   | .3) | .4) |     | .0) | .9) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+
|             | Non-Ischemic   |   | 81  | 75  |     | 41  | 32  |     |
|             |                |   | (32 | (29 |     | (35 | (29 |     |
|             |                |   | .7) | .6) |     | .0) | .1) |     |
+-------------+----------------+---+-----+-----+-----+-----+-----+-----+

  --------------------------------------------------------------------------------------------------------------
                                  All Patients                             NYHA Class              
                                                                           III/IV                  
  -------------------- ---------- -------------- ----------- ------------- ----------- ----------- -------------
  **Characteristic**              **CRT\         **No CRT\   **P-val\***   **CRT\      **No CRT\   **P-val\***
                                  (N=248)**      (N=253)**                 (N=117)**   (N=110)**   

  Age at Implant       N          248            253                       117         110         
  (years)                                                                                          

                       Mean +/-   66.0 +/- 10.5  66.3 +/-    0.73          66.1 +/-    65.8 +/-    0.80
                       SD                        10.5                      10.5        10.5        

                       Range      26.1 - 82.6    29.5 - 86.3               26.1 - 82.5 38.3 - 85.3 

  Gender \[N (%)\]     Male       210 (84.7)     211 (83.4)  0.70          90 (76.9)   86 (78.2)   0.82

                       Female     38 (15.3)      42 (16.6)                 27 (23.1)   24 (21.8)   

  NYHA Class \[N (%)\] II         80 (32.3)      83 (32.8)   0.66          20 (17.1)   11 (10.0)   0.08

                       III        148 (59.7)     144 (56.9)                85 (72.6)   78 (70.9)   

                       IV         20 ( 8.1)      26 (10.3)                 12 (10.3)   21 (19.1)   

  Concomitant          ACE or ARB 212 (85.5)     224 (88.5)  0.31          95 (81.2)   98 (89.1)   0.10
  Medications \[N                                                                                  
  (%)\]                                                                                            

                       Beta       119 (48.0)     117 (46.2)  0.70          53 (45.3)   44 (40.0)   0.42
                       Blocker                                                                     

                       Digoxin    172 (69.4)     171 (67.6)  0.67          84 (71.8)   75 (68.2)   0.55

                       Diuretic   217 (87.5)     210 (83.0)  0.16          108 (92.3)  95 (86.4)   0.15

  Qualifying LVEF (%)  N          248            253                       117         110         

                       Mean +/-   21.4 +/- 6.6   21.5 +/-    0.74          20.6 +/-    21.1 +/-    0.61
                       SD                        6.7                       6.4         6.2         

                       Range      5.0 - 35.0     10.0 - 35.0               8.0 - 35.0  10.0 - 35.0 

  PR Interval\*\* (ms) N          224            222                       107         91          

                       Mean +/-   205 +/- 42     202 +/- 49  0.44          204 +/- 41  200 +/- 54  0.60
                       SD                                                                          

                       Range      88 - 336       104 - 400                 136 - 336   110 - 400   

  Qualifying QRS       N          226            224                       109         93          
  Duration\*\* (ms)                                                                                

                       Mean +/-   160 +/- 27     156 +/- 26  0.06          164 +/- 27  152 +/- 24  \<0.01
                       SD                                                                          

                       Range      120 - 240      120 - 264                 120 - 240   120 - 222   

  Resting Heart Rate   N          248            253                       117         110         
  (bpm)                                                                                            

                       Mean +/-   73 +/- 12      75 +/- 14   0.37          75 +/- 13   74 +/- 15   0.61
                       SD                                                                          

                       Range      43 - 108       48 - 120                  43 - 108    50 - 120    

  Systolic Blood       N          247            253                       116         110         
  Pressure (mmHg)                                                                                  

                       Mean +/-   118 +/- 21     118 +/- 21  0.95          116 +/- 20  117 +/- 23  0.72
                       SD                                                                          

                       Range      79 - 197       70 - 190                  79 - 191    74 - 190    

  Diastolic Blood      N          247            253                       116         110         
  Pressure (mmHg)                                                                                  

                       Mean +/-   67 +/- 12      69 +/- 12   0.27          68 +/- 12   67 +/- 14   0.85
                       SD                                                                          

                       Range      31 - 100       40 - 109                  31 - 100    40 - 109    
  --------------------------------------------------------------------------------------------------------------

  --------------------------------------------------------------------------------------------
                                 Cause of Death                                      
  -------------------- --------- ---------------- ------------ ----------- --------- ---------
  Study Period         \# of pt\ Cardiac:\        Cardiac:\    Cardiac:\   Non-\     Unknown
                       deaths    Pump\            Arrhythmic   Other       Cardiac   
                                 Failure                                             

  After unsuccessful   2         1                1            0           0         0
  implant procedure                                                                  

  Peri-operative (\<=  10        5                2            0           2         1
  30 days)                                                                           

  Randomized therapy   16        9                0            1           3         3
  phase\*: No CRT                                                                    

  Randomized therapy   11        4                1            2           2         2
  phase\*: CRT                                                                       

  Post-randomized      70        28               5            1           16        20
  therapy phase\*\*                                                                  

  **Total**            **109**   **47**           **9**        **4**       **23**    **26**
  --------------------------------------------------------------------------------------------

b\. Sensing of two ventricular intrinsic events when only one intrinsic
event is present due to intraventricular conduction delay.

c\. Other procedure related events occurred in three patients or fewer:
Guide wire fracture (1), Hemorrhage (3), Finishing wire left in lead
(1), Non-conversion of VF (1), Perforation, arterial (1), Perforation,
cardiac (1), Perforation, venous (2), Pericardial effusion (3),
Pericarditis (1), Physiological reaction (1).

[^1]: Detection time at implant with legally marketed Guidant ICD
    devices is typically two seconds and investigators have stated that
    an additional delay of 3 to 5 seconds would be a clinically
    significant event. The expected detection time is 2 seconds \[95%
    CI: (0, 6 sec)\].

[^2]: For purposes of defining event rates, a denominator of 448 will be
    used for those adverse events that pertain to chronically implanted
    EASYTRAK leads and a denominator of 517 will be used for those
    adverse events that pertain to the implant procedure of the EASYTRAK
    lead.