**FDA Questions for Circulatory System Devices Panel**

**Acorn CorCap Cardiac Support Device**

**P040049**

**June 22, 2005**

**Evaluation of Device Safety**

The patient operative reports indicate that performing a subsequent
operation on CorCap patients was complicated by the presence of dense
adhesions.

1.  Please comment on whether placement of the CorCap device, and the
    resulting increased difficulty for follow-on surgery, especially
    coronary bypass operations, will compromise patient safety during a
    subsequent operation.

Forty two patients had evidence of constrictive physiology on at least
one echocardiogram after CorCap implantation.

2.  Please comment on whether there is adequate information to assess
    whether placement of the CorCap CSD causes clinically significant
    pericardial constriction.

The regulations under which a Pre Market Application is assessed for
marketing approval require demonstration of a reasonable assurance of
safety.

3.  Please comment on whether the information provided in the Panel
    Pack, and resented at this meeting, is sufficient to demonstrate a
    reasonable assurance of safety for the CorCap devic system.

**Evaluation of Device Effectiveness**

As the protocol evolved during the course of the trial FDA requested
that NYHA class be assessed by a blinded observer rather than by the
site investigator. Blinded assessment of NYHA class at entry was not
available for more than half of the patients; their NYHA class (for the
purpose of the statistical analysis of the composite primary
effectiveness endpoint) was imputed using a statistical model.

4.  Please comment on whether the imputation of NYHA class compromises
    the analysis of the composite primary effectiveness endpoint, which
    includes NYHA class as one element.

The primary determination of device effectiveness was assessed by a
composite of mortality, NYHA score and the necessity of re-operation for
worsening heart failure. As individual measures neither mortality nor
NYHA class were statistically significantly improved in device as
compared to control patients. However, CorCap patients experienced
significantly fewer re-operations (to treat worsening heart failure)
than did patients in the control group.

5.  Please comment on the extent to which possible physician treatment
    bias (reluctance to refer for or to perform re-operation on CorCap
    patients) might have affected the disparity in the number of device
    vs. control patients who received a re-operation (major cardiac
    procedure) for worsening heart failure.

6.  If it is your opinion that physician treatment bias did affect the
    number of re-operations in device patients please indicate whether
    you think such bias affected the outcome of the primary
    effectiveness endpoint; if so, to what degree?

7.  FDA notes that the incremental effectiveness of the CorCap when used
    together with MVR appears to be less than that of the CorCap alone.
    Please comment on this apparent difference in effectiveness between
    the two groups.

8.  Please comment on whether the results of this clinical trial are
    sufficient to demonstrate a reasonable assurance of effectiveness
    for the CorCap CSD.

Secondary measures of device effectiveness included measures of
ventricular geometry (e.g., left ventricular dimensions) and patient
quality of life (MLHF and SF-36) and functional status (6 minute walk
and MVO~2~).

9.  Please comment on whether some or all of the secondary measures of
    device effectiveness can be used to assess the effectiveness of the
    CorCap CSD. If your answer is "yes", please explain which measures
    are useful, and how you interpret them.

10. Please comment on whether the benefits of CorCap CSD therapy
    outweigh its risks.

**Labeling**

One aspect of the pre-market evaluation of a new product is the review
of its labeling. The labeling must objectively describe which patients
are appropriate for treatment, indicate potential adverse events
associated with the use of the device, and explain how the product
should be used to maximize clinical benefit and minimize adverse events.
If you recommend approval of the device, please address the following
questions regarding product labeling.

11. With reference to the proposed labeling:

    a.  The majority of patients studied had dilated cardiomyopathy and
        yet the number one cause of heart failure in the U.S. is
        ischemic cardiomyopathy. Please comment on whether the results
        of this study can be extrapolated to an ischemic cardiomyopathic
        population.

    b.  Do the proposed Indications for Use adequately define the
        patient population studied and for which the device will be
        marketed?

    c.  Are there any additional warning, precautions, or
        contraindications that you think should be included in the
        labeling to assist practitioners?

**Training**

Selection of patients to receive heart failure therapy with, and
surgical placement of, the CorCap CSD requires the referring
cardiologist and the surgeon to assess multiple factors, some of which
are unique to the device. The sponsor has not included a physician
training program as part of the proposed labeling.

12. Please comment on whether a physician training program is necessary
    for this device system. If your answer is "yes" please comment
    regarding the specific elements that should be included in the
    training program.

**Post Approval Study**

The sponsor has proposed a post-approval study to include up to 348
patients who will be followed for 5 years, the intent being to follow
the long-term performance of the CorCap CSD in the general patient
population.

13. Given the concerns expressed above, please comment as to the
    suitability of the proposed post approval study. If additional
    elements should be included, what are they?

14. Please comment on an appropriate comparison group to evaluate the
    safety and effectiveness of the CorCap CSD against, based on the
    results of surveillance during a 5-year period.

Traditionally, the most common etiology of heart failure is ischemic
disease, however, a majority of patients in the clinical trial had heart
failure that was idiopathic (61%), and the trial included a much smaller
number of patients with heart failure due to ischemic disease (10%).

15. Should the post approval study accurately reflect the distribution
    of prevalent heart disease etiology in the general population? If
    so, how should this be achieved?

16. Are there any other elements that the sponsor should include in
    their proposed post-approval study?