Summary of Safety and Effectiveness Data

The Eclipse PMR Holmium Laser System

Table of Contents

1\. General Information [2](#general-information)

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

3\. Contraindications [2](#contraindications)

4\. Warnings and Precautions [3](#warnings-and-precautions)

5\. Device Description [3](#device-description)

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

7\. Marketing History [4](#marketing-history)

8\. Adverse Events 4

8.1 Observed adverse events 4

8.2 potential adverse events 5

9\. Summary of Pre-Clinical Studies
[6](#summary-of-pre-clinical-studies)

9.1 Biocompatibility Testing 6

9.2 Sterility Testing 6

9.3 Catheter Functionality Testing [7](#catheter-functionality-testing)

9.4 Laser functionality testing [8](#electrical-safety-testing)

9.5 ecg monitor functionality testing 8

9.6 Shipping Validation 9

10\. Summary of Clinical Studies 10

10.1 Study Design [10](#study-design)

10.2 Patient Description and accountability
[10](#patient-description-and-accountability)

10.3 Results [11](#results)

10.4 BELIEF Study Results 15

11\. Conclusions Drawn from the Studies
[16](#conclusions-drawn-from-the-studies)

12\. Panel Recommendation [16](#panel-recommendation)

13\. FDA Decision [16](#fda-decision)

14\. Approval Specifications [16](#approval-specifications)

Summary of Safety and Effectiveness Data

**Eclipse PMR Holmium Laser System**

Eclipse Surgical Technologies, Inc.

# General Information

> Device Generic Name: Percutaneous Myocardial Revascularization (PMR)
> device
>
> Device Trade Name: Eclipse PMR Holmium Laser System
>
> Includes:
>
> New Star Holmium Laser\
> Axcis Laser Catheter\
> Axcis Aligning Catheter\
> Ivy ECG Monitor
>
> Applicant's Name and Address: Eclipse Surgical Technologies, Inc.
>
> 1049 Kiel Court
>
> Sunnyvale, CA 94089
>
> PMA Application Number: P970029/S004
>
> Date of Panel Recommendation:
>
> Date of Notice of Approval to the Applicant:

# Indications and Usage

The Eclipse PMR System is indicated for use in percutaneous myocardial
revascularization (PMR) procedures to decrease angina and increase
exercise tolerance in patients with chronic angina (Canadian
Cardiovascular Society Angina Scale Class III or IV) which is refractory
to medical treatment and secondary to objectively demonstrated coronary
artery disease and with a region of the myocardium with reversible
ischemia not amenable to direct coronary revascularization.

# Contraindications

No contraindications known.

# Warnings and Precautions

> See [warnings and precautions]{.smallcaps} in the final draft labeling
> (Instructions for Use) for a complete list. Precautions to be followed
> during the PMR procedure include, but are not limited to:

-   The Eclipse PMR System should only be used by properly trained
    cardiologists.

-   The wall thickness in the targeted region should be assessed prior
    to the PMR procedure using echocardiography. PMR should not be
    performed in areas of the myocardium that are:

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-   Less than 8 mm in wall thickness

-   Infarcted

-   In the region of the mitral valve, mitral valve apparatus, or
    papillary muscle

-   In the region of a left ventricular mural thrombus

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-   PMR should only be performed under fluoroscopic observation and care
    must be taken not to duplicate channel locations since firing into a
    previously formed channel may cause perforation.

-   If the patient experiences ventricular fibrillation during the
    procedure, the procedure should be discontinued and the arrhythmia
    treated as appropriate. A defibrillator should be readily available
    at all times.

# Device Description

> The Eclipse PMR Holmium Laser System is composed of the New Star
> Holmium: YAG laser, laser energy delivery system and ECG monitor. The
> laser radiation emitted from this system has a wavelength of
> approximately 2.1 microns, which is in the mid-infrared (invisible)
> range of the electromagnetic spectrum. Water is the target absorber
> for this laser wavelength. This laser emits 350 microsecond laser
> radiation pulses at a 35 millisecond pulse repetition interval. The
> energy output from the laser aperture is 2.7 Joules while the clinical
> level is 2 Joules per pulse. The pulses are synchronized with the
> cardiac cycle through the ECG monitor which provides a trigger signal
> to allow synchronization of the heartbeat with the delivery of laser
> energy. There is a visible laser beam used for calibration.
>
> The laser energy is delivered to the target tissue via an optical
> fiber. The Axcis PMR Delivery System has been designed for this
> purpose and consists of the Axcis Laser Catheter and the Axcis
> Aligning Catheter. The Axcis Laser Catheter contains a single solid
> core optical fiber of approximately 365 micron diameter terminated
> with a quartz lens surrounded by 4 penetration-depth limiting nitinol
> petals at the distal end and contained within a catheter shaft of
> braided PEBAX. A gold marker band is present at the distal end to
> facilitate fluoroscopic visualization of the catheter. A stainless
> steel Introducer Tool is used to fold the petals forward prior to
> insertion of the Laser Catheter into the Aligning Catheter. Rotation,
> advancement and retraction of the catheter is controlled with the
> proximal controller portion of the device. The Axcis Aligning Catheter
> is an approximately 9 French braid-reinforced catheter with a soft
> distal tip. The distal portion comes in 5 configurations to access
> various shaped ventricles.

# Alternative Practices or Procedures

> PMR is intended to treat a group of patients who are not candidates
> for alternative interventions. PMR is a non-surgical, percutaneous
> approach to the heart. The only alternative practices for preventing,
> curing, or mitigating the symptoms which PMR is intended to treat in
> this subset of angina patients are maximal anti-anginal medication and
> TMR, a surgical approach to revascularize the heart.

# Marketing History

These devices have not been marketed in the United States. The following
devices have received the CE mark:

> New Star Holmium Laser
>
> Axcis Laser Catheter
>
> Axcis Aligning Catheter
>
> Ivy ECG Monitor
>
> The Eclipse PMR System has been marketed in the following countries:
> Germany, The Netherlands, Italy, Spain, Austria, the United Kingdom,
> Switzerland, Norway, India, China, and Canada. Axcis Aligning
> Catheters from lots manufactured after February 1999 were voluntarily
> recalled by Eclipse in February 2001 for delamination of the inner
> lining which was not associated with any adverse events. Two lots of
> Axcis Laser Catheters were voluntarily recalled by Eclipse in April
> 1999 due to three instances of lens separation during procedures.
> There were no clinical sequellae as a result of these events.

# Adverse Events

## Observed Adverse Events

> The randomized trial of PMR, the PACIFIC Study, compared PMR plus
> medication (PMR+MEDs) with medication alone (MEDs) and enrolled 200
> subjects who were studied for an average of 11.1 months.

There were no intra-procedural deaths in the study. Within 30 days of
treatment, one PMR+MEDs patient died of cardiac causes. During 12 months
follow-up an additional six PMR+MEDs patients died (5 from cardiac
causes and 1 respiratory arrest) and 2 subjects in the MEDs group died
(both due to cardiac causes).

> Serious adverse events which occurred in the study are summarized in
> **Table 1**.

Table 1: Serious Adverse Events\* in the PACIFIC PMR Randomized Trial

Includes all adverse events, both related and unrelated to PMR, sorted
by system affected.

+-------------------------+---------+----------+-----------+---------+
|                         | **P     |          | **MEDs    |         |
|                         | MR+MEDs |          | (n=100)** |         |
|                         | (n      |          |           |         |
|                         | =100)** |          |           |         |
+-------------------------+---------+----------+-----------+---------+
| **Event^1\ ^**          | **P     | **Number | *         | *       |
|                         | atients | of       | *Patients | *Number |
|                         | with    | Events** | with      | of      |
|                         | Event** |          | Event**   | E       |
|                         |         |          |           | vents** |
+-------------------------+---------+----------+-----------+---------+
| ## All CV events        | 50      | 108      | 48        | 103     |
| combined {#all-cv-event |         |          |           |         |
| s-combined .unnumbered} |         |          |           |         |
+-------------------------+---------+----------+-----------+---------+
| Angina                  | 25      | 49       | 39        | 74      |
+-------------------------+---------+----------+-----------+---------+
| Arrhythmias^2^          | 11      | 12       | 4         | 6       |
+-------------------------+---------+----------+-----------+---------+
| Death (all causes)      | 7       | 7        | 2         | 2       |
+-------------------------+---------+----------+-----------+---------+
| Heart Failure           | 8       | 8        | 2         | 2       |
+-------------------------+---------+----------+-----------+---------+
| Injury to heart         | 3       | 3        | 0         | 0       |
| structure (perforation) |         |          |           |         |
+-------------------------+---------+----------+-----------+---------+
| Myocardial infarction   | 11      | 12       | 5         | 8       |
+-------------------------+---------+----------+-----------+---------+
| Other cardiovascular^3^ | 16      | 18       | 7         | 9       |
+-------------------------+---------+----------+-----------+---------+
| Thromboembolic disorder | 4       | 4        | 2         | 3       |
+-------------------------+---------+----------+-----------+---------+
| ## All DER Events C     | 1       | 1        | 2         | 3       |
| ombined {#all-der-event |         |          |           |         |
| s-combined .unnumbered} |         |          |           |         |
+-------------------------+---------+----------+-----------+---------+
| ## All GU Events        | 2       | 2        | 2         | 2       |
| Combined {#all-gu-event |         |          |           |         |
| s-combined .unnumbered} |         |          |           |         |
+-------------------------+---------+----------+-----------+---------+
| ## All GEN Events C     | 10      | 11       | 7         | 7       |
| ombined {#all-gen-event |         |          |           |         |
| s-combined .unnumbered} |         |          |           |         |
+-------------------------+---------+----------+-----------+---------+
| All GI Events Combined  | 8       | 12       | 3         | 4       |
+-------------------------+---------+----------+-----------+---------+
| All NEU Events Combined | 3       | 4        | 1         | 1       |
+-------------------------+---------+----------+-----------+---------+
| All PSY Events Combined | 2       | 2        | 1         | 2       |
+-------------------------+---------+----------+-----------+---------+
| All RES Events Combined | 7       | 10       | 3         | 4       |
+-------------------------+---------+----------+-----------+---------+
| All AE Combined         | 56      | 159      | 52        | 130     |
+-------------------------+---------+----------+-----------+---------+

^1^Abbreviations: CV = cardiovascular, DER = dermatologic, GEN =
general, GI = gastrointestinal, GU = genitourinary, HEM = hematologic,
LAB = laboratory, MET = metabolic, MUS = musculoskeletal, NEU =
neurologic, PSY = psychiatric, RES = respiratory, AE = adverse events.

^2^Arrhythmias (number of patients with each in treatment/control
groups) were: arrhythmia (0/2), ventricular arrhythmia (1/0), AV block
complete (1/0), bradycardia (4/1), atrial fibrillation (2/0), atrial
flutter (2/0), heart block (1/0), tachycardia (0/1).

^3^Other cardiovascular events (number of patients with each in
treatment/control groups) were: heart arrest (4/0), syncope (2/2),
vascular disease peripheral (3/2), amblyopia (0/1), vascular anomaly
(1/0), cellulitis (1/0), creatine PK increase (1/0), pericardial
effusion (1/0), embolism (1/0), hypotension (1/0), artery occlusion
(0/1), carotid occlusion (0/1), coronary stenosis (1/0), ulcer (1/0).

## Potential Adverse Events

Adverse events potentially associated with the use of PMR but not
observed in the study include (in alphabetical order):

> Allergic reaction to contrast reagent Fragmented catheters and lens
> tip
>
> Arterial dissection Left ventricular dysfunction
>
> Bleeding Renal insufficiency
>
> Cardiogenic shock Vascular damage

# Summary of Pre-Clinical Studies

## Biocompatibility Testing

All patient contacting components of the fiberoptic delivery system
underwent biocompatibility testing in accordance with FDA General
Program Memorandum #G95-1, which provides an FDA-modified matrix of
International Standard ISO-10993, "Biological Evaluation of Medical
Devices Part 1: Evaluation and Testing." The Introducer Tool is composed
of stainless steel, which is a known biocompatible material. **Table 2**
summarizes the biocompatibility tests conducted and the results. Test
results demonstrate that all devices are biocompatible for their
intended use.

Table 2: Summary of Axcis PMR Delivery System Biocompatibility Testing

  -------------------- --------------------------------------------------
  **Test**             **Results**

  Cytotoxicity         System was non-cytotoxic.

  Sensitization        System did not cause delayed dermal contact
                       sensitization.

  Intracutaneous       System did not cause significant irritation or
  Reactivity           toxicity.

  Systemic Toxicity    System was not toxic systemically and did not
                       cause mortality.

  Hemolysis            System was non-hemolytic.

  Complement           System activated 14% of the normalized positive
  Activation           control result.\*

  Thrombogenicity      System exhibited minimal thrombogenicity.

  Pyrogenicity         System was non-pyrogenic.
  -------------------- --------------------------------------------------

> \* Test report notes that all biomaterials activate complement to some
> extent and that an acceptable level has not yet been established.

## Sterility Testing

The Axcis Laser Catheter and Axcis Aligning Catheter are single-use
devices which are provided pre-sterilized to the user. These devices are
sterilized using an ethylene oxide (EtO) cycle. The Introducer Tool is a
reusable device which is sterilized by the hospital, using a recommended
steam autoclave cycle. The sterilization cycles were validated to ensure
successful sterilization to a Sterility Assurance Level (SAL) of 10^-6^.
**Table 3** summarizes the sterilization validations performed.

Table 3: Summary of Sterility Testing

+-------------+----------------------------+--------------------------+
| **Device**  | **Validation Test Method** | **Test Results**         |
+-------------+----------------------------+--------------------------+
| **Axcis     | Testing was performed      | Devices met the SAL      |
| Laser       | using the biological       | acceptance criteria. All |
| Catheter    | indicator overkill method. | residual levels met the  |
| &**         | The following residual     | FDA acceptance criteria. |
|             | levels were measured:      | Testing demonstrated     |
| **Axcis     | ethylene oxide (EtO),      | that the devices can be  |
| Aligning    | ethylene chlorohydrin      | successfully sterilized  |
| Catheter**  | (ECH) and ethylene glycol  | using the specified EtO  |
|             | (EG).                      | cycle.                   |
+-------------+----------------------------+--------------------------+
| *           | Testing was performed      | Devices met the SAL      |
| *Introducer | using the biological       | acceptance criteria.     |
| Tool**      | indicator overkill method. | Testing demonstrated     |
|             |                            | that the devices can be  |
|             |                            | successfully sterilized  |
|             |                            | using the specified      |
|             |                            | gravity or prevacuum     |
|             |                            | steam sterilization      |
|             |                            | methods.                 |
+-------------+----------------------------+--------------------------+

> In addition, cleaning evaluation studies were performed with the
> Introducer Tool to validate procedures for cleaning the device prior
> to sterilization and re-use.
>
> ***Shelf Life Studies***

Twenty-four month accelerated aging studies were performed on the Axcis
Laser Catheter and Axcis Aligning Catheter devices. These studies
demonstrated that sterility, package integrity, and product
functionality is maintained for a minimum of 24 months. Based upon these
results, a shelf life of two years has been established for these
devices.

## Catheter Functionality Testing

*In vitro* testing was performed with the Axcis Laser Catheter and Axcis
Aligning Catheter devices to demonstrate that they function as intended
and meet the requirement of FDA "Guidance for the Submission of Research
and Marketing Application for Interventional Cardiology Devices (May
1993)".

The Axcis Laser Catheter was tested to assess the mechanical integrity,
optical integrity and functionality of the device. The sequence of tests
was designed to provide a baseline quality assessment followed by
clinical simulation challenge tests and post challenge assessment.
Challenge tests included Repeated Introduction, Repeated Laser Firing in
Saline, Channel Creation in Porcine Heart, Repeated Flexion of the
Distal Lens Assembly and Torque and Rotational Control. The effects of
the challenge tests on the device were monitored by Visual Inspection,
Optical Energy Transmission, Tip Temperature, and Spatial Output
Measurement tests. Devices were also subjected to final destructive
tests. The results of the *in vitro* tests demonstrated that the Laser
Catheters performed according to the specified acceptance criteria for
the tests.

The Axcis Aligning Catheters were tested to ensure functionality of
torque and rotational control functions and ability to maintain flow
rates. Tests included Dimensional and Visual Inspections, Repeated
Introduction, Torque and Rotational Control, Tip Shape Retention, and
Sustained Pressurization. Aligning Catheters were also tested by Peak
Pressure at Failure and destructive Torque and Tensile testing. The
results of the *in vitro* tests demonstrated that the Aligning Catheters
performed according to the specified acceptance criteria for the tests.

> The Axcis PMR Delivery System was tested *in vivo* in the porcine
> model to characterize acute and chronic physiologic responses to the
> creation of endocardial channels. Results demonstrated that
> endocardial channels were histologically similar to the transmural
> channels created using a surgical approach to the heart. The safety of
> the device in the porcine model was demonstrated by the lack of
> arrhythmic events and lack of long term effect on myocardial function.

## Laser Functionality Testing

### Electrical Safety Testing

An independent laboratory evaluated the electrical safety of the New
Star laser. The New Star laser was tested and was found to be in
compliance with IEC 601-1/EN60601, the European standard for general
safety requirements for medical electrical equipment, and IEC
601-2-22/EN 60601-2-22, the European standard for particular
requirements for laser equipment. As part of meeting the IEC 601-2-22
standard, the New Star laser was also found to be in compliance with IEC
601-1-2, the European electromagnetic compatibility immunity standard.
In addition, the New Star laser was tested for, and was found to be in
compliance with, EN 55011 for Group I, Class A, 1991 the European
electromagnetic interference standard for conducted emissions and
radiated emissions.

### Software Validation

> The New Star laser software was validated by testing the error codes
> according to safety, functional performance and software architectural
> specification. Where appropriate, tests were performed with the Axcis
> PMR Delivery System devices. All portions of the test were completed
> successfully.

### Laser Reliability

Reliability and life testing was performed for the New Star laser. There
were no failures of the laser during the life test and the reliability
testing significantly exceeded the requirement.

### Environmental Validation

Environmental testing was performed and demonstrated compliance of the
New Star laser with the environmental requirements. The devices were
tested and found to maintain sterile barrier properties after testing.

## ECG Monitor Functionality Testing

### Electrical Safety Testing

The ECG monitor was tested by the manufacturer, Ivy Biomedical, Branford
CT and found to meet the requirements of EN55011 for Group I, Class A,
1991 for conducted emissions and radiated emissions. The monitor
complies with EN 61000-4-2, 1995-01, electrostatic discharge immunity;
EN 61000-4-3 1995-02, radiated electromagnetic immunity; EN 61000-4-4
1995-01 electrical fast transient/burst immunity and EN 50141 1994
conducted disturbance induced by RF fields.

### Software Validation

The software for the ECG monitor was validated and found to perform
within specifications.

### Reliability Testing

The ECG delayed trigger function used to synchronize the heartbeat with
the delivery of laser energy was tested and the results demonstrated
that the trigger position displayed on the monitor corresponded to the
actual trigger output. In addition, testing demonstrated that the ECG
monitor reliably produced a trigger pulse and that the laser was
reliably triggered by the signal produced by the monitor.

## Shipping Validation

The shipping validation for the New Star Laser was performed according
to ASTM D4169 Distribution Cycle 12, Assurance Level 1. All test results
passed the required ASTM standards with no exceptions. Shipping and
handling tests of the Laser Catheter and Aligning Catheters were
conducted per the requirements of ASTM D4169, Distribution Cycle 13,
Assurance Level 1. The results validated the integrity of the packaging
and the functionality of the devices after testing. More than 20,000 ECG
units have been shipped with no history of problems with the packaging.

# Summary of Clinical Studies

> The Eclipse PMR Holmium Laser System was evaluated in a prospective,
> randomized, controlled trial, the PACIFIC Study, which compared PMR
> plus medication (PMR+MEDs) with medication alone (MEDs). A total of
> 200 patients were enrolled in the study between November 1997 and
> August 1998. The study ended in August 1999 when the final 12 month
> follow-up visits were completed.

## Study Design

> The PACIFIC multi-center, prospective, randomized controlled trial was
> conducted at 11 U.S. sites. The study was conducted in patients with
> Canadian Cardiovascular Society class III or IV angina, ejection
> fraction [\>]{.underline}30%, and an area of reversible ischemia, who
> were not candidates for other interventions. Patients were excluded
> from the study if they had had a Q wave MI within the previous 3
> months or a non-Q wave MI within the previous 6 weeks, if they had
> heart failure requiring a dose of diuretic equivalent to \>80 mg Lasix
> per day, had clinically significant ventricular arrhythmias, left
> ventricular thrombus, aortic valve stenosis with valve area \<1.5cm^2^
> , myocardial wall thickness less than 8 mm in the area intended for
> treatment, a significant change in oral anti-anginal medication within
> the 14 days prior to treatment or hospitalization for unstable angina.
> Other exclusions from the study were persons with significant
> alterations in angina pattern or clinical status since the last
> coronary angiogram, cardiac transplant, inability to perform exercise
> tolerance testing without significant risk, failure to experience
> angina during testing, baseline renal insufficiency, severe peripheral
> vascular disease, impaired fluoroscopic visualization for any reason,
> and those who were poor candidates for interventional cardiac
> procedures.
>
> The objectives of the study were to evaluate whether the Eclipse PMR
> System, when used to create small channels into the myocardium, could
> provide improvement at 12 months in Canadian Cardiovascular Society
> Angina Scale (CCSAS) classification and Exercise Tolerance Test (ETT)
> results. The secondary endpoint was improvement in quality of life as
> measured by the Seattle Angina Questionnaire.

## Patient Description and Accountability

Patients were randomized into the study between November 1997 and August
1998 at 11 United States centers. Patients were randomly assigned to the
two treatment groups: 100 to percutaneous myocardial revascularization
plus medical management (PMR+MEDs) and 100 to medical management (MEDs).
There were 200 patients randomized into the study and there were 17
withdrawals and 9 deaths. All of the remaining 174 patients reached the
one year follow-up time point. The patient baseline characteristics and
cardiac risk factors are described in **Table 4**.

Table 4: Patient Baseline Characteristics and Cardiac Risk Factors

+----------------------------+------------+------------+-------------+
|                            | **         | **MEDs**   | **P Value** |
|                            | PMR+MEDs** |            |             |
+----------------------------+------------+------------+-------------+
| n patients =               | 100        | 100        |             |
+----------------------------+------------+------------+-------------+
| Male                       | 84% (84)   | 86% (86)   | 0.843       |
|                            |            |            |             |
| Female                     | 16% (16)   | 14% (14)   |             |
+----------------------------+------------+------------+-------------+
| Age (Years)                |            |            | 0.554       |
+----------------------------+------------+------------+-------------+
| > Mean ± SD                | 63 ± 9.4   | 62 ± 10.1  |             |
+----------------------------+------------+------------+-------------+
| > Range {Min, Max}         | \[39, 83\] | \[38, 90\] |             |
+----------------------------+------------+------------+-------------+
| Pre Ejection Fraction (%)  |            |            | 0.933       |
+----------------------------+------------+------------+-------------+
| > Mean ± SD                | 51 ± 9.9   | 51 ± 8.6   |             |
+----------------------------+------------+------------+-------------+
| History of Diabetes        | 49% (49)   | 43% (43)   | 0.478       |
+----------------------------+------------+------------+-------------+
| History of Smoking         | 28% (28)   | 23% (23)   | 0.754       |
|                            |            |            |             |
| Never                      | 11% (11)   | 11% (11)   |             |
|                            |            |            |             |
| Current                    | 61% (61)   | 66% (66)   |             |
|                            |            |            |             |
| Former                     |            |            |             |
+----------------------------+------------+------------+-------------+
| History of Hypertension    | 69% (69)   | 79% (79)   | 0.146       |
+----------------------------+------------+------------+-------------+
| History of Hyperlipidemia  | 70% (70)   | 88% (88)   | 0.003       |
+----------------------------+------------+------------+-------------+
| Family History of CAD      | 65% (65)   | 76% (76)   | 0.038       |
+----------------------------+------------+------------+-------------+
| History of MI              | 64% (64)   | 68% (68)   | 0.654       |
+----------------------------+------------+------------+-------------+
| Previous PTCA              | 9% (9)     | 7% (7)     | 0.076       |
+----------------------------+------------+------------+-------------+
| Previous CABG              | 35% (35)   | 38% (38)   |             |
+----------------------------+------------+------------+-------------+
| History of both PTCA and   | 42% (42)   | 51% (51)   |             |
| CABG                       |            |            |             |
+----------------------------+------------+------------+-------------+

## Results

### Procedure Description and Data

> PMR was performed using a percutaneous access route typical of other
> interventional cardiac procedures. The Laser Catheter containing the
> fiber optic was introduced through the Aligning Catheter and used to
> apply laser energy to the endocardial surface of the left ventricle.
> As the fiber was advanced, pulsed laser energy was delivered to the
> myocardium to a create channels with a depth of 6-8 mm. PMR channels
> were placed approximately 1 cm apart using fluoroscopic visualization
> for catheter placement. The laser was synchronized to fire at the
> electrocardiographic R-wave, when the left ventricle was at maximum
> contractile width.
>
> The number of PMR channels created during the procedure ranged from 8
> to 35 (mean 16.1), using an energy of 2 Joules per pulse.
>
> There were no intra-procedural deaths. Within 30 days of PMR, 1
> patient died of cardiac causes. There were no deaths in the control
> group within 30 days of enrollment.

### Primary Outcome Measures

> **Angina Improvement:** Angina improvement was defined as improvement
> in angina symptoms from baseline by at least 2 angina classes, based
> on the Canadian Cardiovascular Society definition of angina. All
> patients had Class III or IV angina at baseline. **Figure 1** shows
> the percent of patients who had angina improvement at 3, 6 and 12
> months follow-up. At each follow-up time point, a significantly larger
> percent of PMR+MEDs patients experienced angina improvement than MEDs
> patients.

Figure 1: Angina Improvement at 3, 6 and 12 months\*

> ![](media/image1.wmf){width="3.7in" height="2.834722222222222in"}

+-----------------+----------------------+-----------------+----------+
|                 | **PMR+MEDS**         | **MEDs**        | **P      |
|                 |                      |                 | -value** |
+-----------------+----------------------+-----------------+----------+
| **Baseline      | 62.0% (n = 62)       | 62.0% (n = 62)  | 1.000    |
| Class III**     |                      |                 |          |
|                 | 38.0% (n = 38)       | 38.0% (n = 38)  |          |
| **Class IV**    |                      |                 |          |
+-----------------+----------------------+-----------------+----------+
| **3 Months**    | 47.0% (n = 47)       | 6.0% (n = 6)    | \<0.001  |
|                 |                      |                 |          |
| **Success**     |                      |                 |          |
+-----------------+----------------------+-----------------+----------+
| **6 Months**    | 45.0% (n = 45)       | 6.0% (n = 6)    | \<0.001  |
|                 |                      |                 |          |
| **Success**     |                      |                 |          |
+-----------------+----------------------+-----------------+----------+
| **12 Months**   | 42.0% (n = 42)       | 8.0% (n = 8)    | \<0.001  |
|                 |                      |                 |          |
| **Success**     |                      |                 |          |
+-----------------+----------------------+-----------------+----------+

> \* Last observation carried forward analysis (LOCF). In this analysis
> values for patients who were withdrawn or had re-interventions were
> the values obtained at the visit prior to withdrawal or
> re-intevention. For patients who died the value was set at '5' (normal
> CCSAS specifies values of 1-4). Angina improvement is an improvement
> of 2 or more classes from baseline to 3, 6, or 12 months. Otherwise
> failure is indicated.

Angina was also assessed using a standard questionnaire administered in
a blinded fashion by a clinical research organization. Responses were
evaluated by an independent cardiologist. This independent assessment
was introduced late in the study; consequently, the numbers of paired
baseline-12 months assessments was small. The results of the independent
angina assessment also showed significantly more patients in the treated
group, 51.5% (17/33 ), showed at least 2 CCSAS class improvement
compared with the control group, 19.4% (7/36).

**Exercise Tolerance Improvement:** Maximal exercise tolerance times
were assessed at baseline and at 3, 6 and 12 month follow-up using a
standardized Modified Bruce Protocol at all sites. The results were
interpreted by an independent core laboratory. **Figure 2** shows the
percent of patients with improvement in total exercise duration at all
follow-up time points. At each time point PMR+MEDs patients were able to
exercise for a significantly greater time than MEDs patients.

Figure 2: Improvement in Total Exercise Duration at 3, 6, and 12
months\*

![](media/image2.wmf){width="3.7in" height="2.9131944444444446in"}

+----------------------------+--------------+---------------+---------+
|                            | #####        | **MEDs**      | **P-    |
|                            | #### PMR+MED |               | value** |
|                            | s {#pmrmeds  |               |         |
|                            | .unnumbered} |               |         |
+----------------------------+--------------+---------------+---------+
| **Baseline**               | 451.7 (n=99) | 419.6 (n=97)  | 0.244   |
+----------------------------+--------------+---------------+---------+
| **3-Month Improvement**    | 64.1 (n=99)  | -7.4 (n=95)   | \<0.001 |
+----------------------------+--------------+---------------+---------+
| **6-Month Improvement**    | 74.0 (n=99)  | 1.5 (n=96)    | 0.001   |
+----------------------------+--------------+---------------+---------+
| **12-Month Improvement**   | 50.8 (n=99)  | -6.4 (n=97)   | 0.014   |
+----------------------------+--------------+---------------+---------+

> \* Last observation carried forward analysis (LOCF). In this analysis
> values for patients who were withdrawn or had re-interventions were
> the values obtained at the visit prior to withdrawal or
> re-intervention. Patients who died were scored at zero minutes.
> Although standard exercise test protocols were created and distributed
> to all sites, not all subjects were tested using these protocols. Only
> patients using the same protocol at baseline and during follow-up
> evaluations were included in the final cohort for the effectiveness
> evaluation. Failure to use the same protocol accounts for missing data
> (n = \<100% even with LOCF).

### Secondary Outcome Measure

**Quality of Life:** Subjects were required to complete the
self-administered quality of life questionnaire at baseline, 3, 6 and 12
months using the Seattle Angina Questionnaire (SAQ). The SAQ consists of
11 questions about activities that represent major aspects of physical
function, including personal care, ambulation, household tasks, and
recreational activities. Each answer has a weight associated with it and
the weighted answers were used to derive five quality of life indices
based on physical limitation, anginal stability, anginal frequency,
treatment satisfaction and disease perception. The 12 month improvement
in quality of life scores is illustrated in **Figure 3**. For each of
the five indices, PMR+MEDs patients reported a significantly greater
improvement in quality of life than the MEDs patients.

Figure 3: Improvement in Quality of Life at 12 months\*

![](media/image5.wmf)

Abbreviations: Physical = Physical Limitation, Stability = Anginal
Stability, Frequency = Anginal Frequency, Satisfaction = Treatment
Satisfaction, Perception = Disease Perception.

  --------------------------------- -------------- ------------ -------------
  **Improvement**                   **PMR+MEDs**   **MEDs**     **P-value**

  Physical Limitation Scale         12.3 (n=95)    0.4 (n=95)   \<0.001

  Anginal Stability Scale           26.0 (n=96)    4.2 (n=96)   \<0.001

  Anginal Frequency Scale           19.3 (n=95)    7.1 (n=97)   \<0.003

  Treatment Satisfaction Score      9.4 (n=96)     1.7 (n=97)   \<0.001

  Disease Perception/QOL Score      28.5 (n=96)    9.1 (n=97)   \<0.001
  --------------------------------- -------------- ------------ -------------

> \* Last observation carried forward analysis (LOCF). In this analysis
> values for patients who were withdrawn or had re-interventions were
> the values obtained at the visit prior to withdrawal or
> re-intervention. Patients who died were scored at zero (higher scores
> indicate better quality of life). Missing baseline data accounts for n
> = \<100% even with LOCF.

### Medication Use

At 12 months follow-up, more PMR+MEDs patients decreased or remained the
same in the use of anti-anginal medications compared with the MEDs
patients. A higher proportion of patients in the PMR+MEDs group
increased the use of diuretics compared with the MEDs group. However,
changes in the use of other agents which, like diuretics, are used to
treat congestive heart failure did not differ proportionally between the
groups. Although the use of lipid/cholesterol regulating drugs was
significantly higher in the MEDs group at baseline, changes in the use
of these drugs was exactly equivalent between the two groups. Therefore,
the incidence of hyperlipidemia and use of lipid/cholesterol regulators
does not account for the significant improvement in angina and ETT
observed in the PMR+MEDs group.

### Morbidity and Mortality

> There were no intra-procedure deaths. Within 30 days of PMR, 1 patient
> died of cardiac causes. During 12 months follow-up, an additional 6
> patients in the PMR group died (5 due to cardiac causes and 1 due to
> respiratory arrest). Two patients in the MEDs group died. Kaplan-Meier
> analysis of the proportion of patients who died in each of the study
> groups did not demonstrate a difference in the risk of death
> associated with PMR treatment (p = 0.17, 2-Tail Fisher's Exact Test).

## BELIEF Study Results

> The **B**linded **E**valuation of **L**aser **I**ntervention
> **E**lectively **F**or Angina Pectoris (BELIEF Study) was a double
> blinded randomized study of the effects of treatment with percutaneous
> myocardial revascularization (PMR) plus medication compared with Sham
> treatment plus medication. Sham treatment was carried out in a manner
> in which neither the patient nor the Investigator knew which
> randomized treatment, PMR+MEDs or Sham+MEDs, was being implemented.
> The study was carried out at two investigational sites in Norway.
> Eclipse sponsored the study only to the extent of providing study
> planning and protocol design consultation and partial financial
> support.
>
> The system used in the BELIEF Study, the Axcis PMR Delivery System
> with the New Star laser, is the same as that used in the PACIFIC
> trial. Moreover, the study design of the BELIEF Study was quite
> similar to that of the PACIFIC Study. Both were randomized studies
> comparing the safety and effectiveness of the Eclipse PMR System
> against a control; both has angina improvement as the primary
> endpoint; and both studies had nearly identical eligibility criteria.
>
> At the 6 month follow-up, 64% of patients in the PMR+MEDs group
> improved one or more CCSAS functional classes compared with 38% n the
> Sham+Meds group (p=0.02). Additionally, significantly more patients in
> the PMR+MEDs group improved two or more CCSAS functional classes
> compared to the Sham+MEDS group (41% vs. 13% respectively; p=0.005).
> There were no significant differences between the two groups in ETT
> duration. Patients in the PMR group also showed significantly better
> Seattle Angina Questionnaire anginal stability subscores at 6 months
> compared to Sham patients.
>
> These data demonstrate that patients treated with PMR experience a
> significant improvement in angina symptoms compared to a Sham
> procedure. This double blinded randomized study demonstrates that the
> benefit derived from PMR is not principally due to a placebo effect.
> Consequently, these data demonstrate that PMR results in a dramatic
> improvement in angina classification in subjects with medically
> refractory angina who have no other treatment options.

# Conclusions Drawn from the Studies

> The preclinical studies indicate that the Eclipse PMR System has the
> appropriate physical and performance characteristics for its intended
> use as stated in the labeling.
>
> Data from the multi-center PACIFIC Study showed that in patients with
> Class III or IV angina, ejection fraction [\>]{.underline}30%, and an
> area of reversible ischemia, who were not candidates for other
> interventions, percutaneous myocardial revascularization performed
> with the Eclipse PMR System provides significant reduction in the
> severity of angina and significant increase in exercise duration in
> patients treated with PMR compared with controls. Mortality was
> similar between the groups through one year.

# Panel Recommendation

> *To be determined*

# FDA Decision

> To be determined.

# Approval Specifications

> **Directions for Use:** See Final Draft Labeling (Information for Use)
>
> **Hazards to Health from Use of the Device**: See [Indications,
> Contraindications, Warnings and Precautions,]{.smallcaps} and [Adverse
> Events]{.smallcaps} in the labeling.
>
> **Post-approval Requirements and Restrictions**

Revision History

> Printed - Monday, November 13, 2023
>
> \- Eclipse internal revisions, versions 1-4
>
> \- Initial draft received from sponsor, version 4.0 May 17, 2001