The Destination Therapy Evaluation for Failing Fontan Study

Study Design:

This is a single center nonrandomized observational study led by the PI. However, patients
will be recruited from other centers to participate in this trial. The recruited patients
will be ineligible for cardiac transplantation at the referring institution. The study
institution will also evaluate the patient for cardiac transplantation. If the patient is
determined to be ineligible for transplantation at the study institution, the patient will
have met the study inclusion criteria pertaining to two institutional turn downs for
transplant. The protocol has been designed this way to attract the proposed 20 study
patients, and to allow for a second opinion as to whether the patient is a transplant
candidate. The patient may pursue cardiac transplantation at an institution that deems
him/her transplant eligible, if applicable.

Those patients who are not candidates for transplantation could then be considered for the
proposed research study. Patients will need to sign an informed consent to be screened for
the study.

Patients who meet the inclusion and exclusion criteria will be implanted with the HeartMate
II VAD and data will be collected as described below in the section "data collection".
Patients who fail to meet the study inclusion and exclusion criteria will be asked to
participate in a sub-study. The sub-study will collect screening and baseline data, as
clinically indicated.

Primary Endpoint:

The primary endpoint is to examine survival without a disabling stroke at two years (defined
as a score of four or greater on the Modified Rankin Scale). Patients that reach the primary
endpoint of survival without a disabling stroke at two years will be considered a success in
this study. The percent of patients that have a successful outcome should be targeted at 80%
of patients that survive to 2 years without a disabling stroke in the general Destination
Therapy patient population at Providence Sacred Heart Medical Center. The current survival
rate is 53% survival at 2 years. Therefore, a primary endpoint of 40% survival (8 out of 20
patients) to 2 years without a disabling stroke is purposed. Data related to freedom from a
disabling stroke is roughly based on the work published by Tsukui et al. that showed 33-75%
freedom from cerebrovascular accidents at 6 months in differing device groups of patients
waiting as bridge-to-transplant candidates.

Secondary Endpoints:

Safety, functional status, total-days-alive following hospital discharge, and quality of
life assessments will be evaluated as secondary endpoints. Secondary endpoints will be
evaluated throughout the study and at one- and two- year follow-up time points after the
last patient has been enrolled into the study. The study is designed to improve quality of
life, in addition to length of life.

- Safety will be evaluated for all cause mortality, incidence of serious adverse events,
as per the Interagency Registry for Mechanically Assisted Circulatory Support
(INTERMACS) definitions (except for modified bleeding and neurocognitive event
definitions), and Incidence of device replacement or device repair due to failure.

- Functional status and hospitalizations will be evaluated by the cardio-pulmonary stress
test (V.O2 peak), New York Heart Association class, 6-minute walk test, and total
number of days alive out-of-hospital.

- Quality of life will be assessed through the Minnesota Living with Heart Failure and
Euro-QOL questionnaires.

Inclusion Criteria:

- Able to sign Informed Consent and Release of Medical Information forms

- Age greater than or equal to 18 years

- Appropriate surgical candidate for the HeartMate II LVAD

- Willing to consider treatment with the HeartMate II LVAD

- BSA greater than or equal to 1.2

- Female patients must be using adequate contraceptive methods or be unable to become
pregnant (2 years post-menopausal or surgically sterilized)

- Patient has Stage D heart failure for, at least, 60 days despite optimal medical
management for at least the last 60 days

- Functional limitation due to heart failure as defined by at least ONE of the
following:

1. A history of a progressive downhill course manifested by a restricted quality of
life, or increasing hospital admissions, or increasing medication requirements

2. Presence of protein losing enteropathy

- Ineligible for cardiac transplantation at Sacred Heart Medical Center and at least
one other UNOS approved heart transplant center, in the judgment of that center's
multidisciplinary transplant team

- Ability to read, understand and implement the instructions for use for the HeartMate
II LVAD

Exclusion Criteria:

- Technical obstacles that pose an inordinately high surgical risk, in the judgment of
the investigator

- Uncorrectable acquired coagulopathy

- Primary coagulopathy or platelet disorder, including thrombocytopenia with absolute
platelet count < 80k or active state of disseminated intravascular coagulation

- Contraindication to the administration of heparin, warfarin or anti-platelet agents

- Severe intrinsic pulmonary disease in the judgment of the investigator

- On mechanical ventilatory support and unable to be weaned

- Patient is under consideration for reparative cardiac surgery (likely to result in
clinical resolution of the heart failure in the judgment of the investigator)

- Prior implantation of an assist device

- Mechanical prosthetic aortic or mitral valve that will not be converted to a
bio-prosthesis at time of VAD implantation

- Moderate or severe (>1+) aortic insufficiency as determined by echocardiogram that is
not amenable to surgical repair or replacement

- Evidence of severe intrinsic hepatic disease as defined as biopsy proven liver
cirrhosis with a likelihood of less than two years survival; or liver enzyme values
(AST, ALT or total bilirubin) that are > 3 times the upper limit of normal within 30
days prior to surgery, except if the result of acute heart failure decompensation as
determined by the investigator

- Creatinine of > 3.5mg/dl or any form of dialysis within 24 hours prior to surgery

- Stroke within 90 days prior to surgery, or history of cerebral vascular disease with
significant (> 80%) extra cranial or intra cranial stenosis documented by carotid
doppler study or angiography, without evidence of collateral flow documented by
transcranial doppler study

- Alzheimer's disease and/or impaired cognitive function, or any other form of
irreversible dementia (or both) that is confirmed by a neurological exam

- Patient has evidence of an untreated abdominal aortic aneurysm ≥ 5 cm as measured by
abdominal ultrasound

- Suspected or active systemic infection within 48 hours prior to surgery

- Significant peripheral vascular disease as defined by rest pain or ulceration

- Patient in whom abdominal surgery is planned

- Positive serum pregnancy test, for women of childbearing potential

- Recent history of psychiatric disease or psycho-social maladaptive behaviors
(including drug or alcohol abuse) that are likely to impair compliance with the study
protocol, in the judgment of the investigator

- Therapy with an investigational intervention at the time of screening, or plan to
enroll patient in additional investigational intervention study during participation
in this trial

- Patient has a condition, other than heart failure, which would limit survival to less
than 2 years

- Patient is eligible for cardiac transplantation