CorMatrix ECM Study: To Identify Inflammatory Markers Following CABG With/Without ECM

The pericardium's main function is to secrete proteins that ensure proper functioning within
the pericardial space and to maintain pericardial pressure. Once dissected the pericardium
is usually left open at the end of surgery due to the difficulty in realigning the edges and
to avoid adverse effects cause by an inflammatory response. The body's inflammatory response
is one of protection and healing of an injury. However many of the inflammatory biomarkers
released can cause adverse outcomes after cardiac surgery, including: renal failure,
myocardial infarction, atrial fibrillation, stroke and death.

CorMatrix extra cellular matrix (ECM) Technology is a Food and Drug Administration (FDA)
approved unique extra cellular implant material used for pericardial closure and
reconstruction. Pericardial reconstruction using porcine intestinal ECM is a novel
application. ECM combines the innate attributes of nature with the precision of science to
help the heart heal itself. It is an acellular biomaterial that does not encapsulate when
surgically implanted, but is gradually remodeled, leaving behind organized and healthy
tissue. The body's tissue begins remodeling at the surgical site while the ECM maintains the
needed tissue support. When implanted, the ECM acts as a scaffold into which the patient's
cells migrate and integrate, stimulating the patient's natural wound-healing mechanisms. As
the patient's cells become active, they lay down their own collagen, which matures over time
to form strong and permanent tissue repair without leaving behind permanent foreign
material. Because the ECM contains primarily collagen, the device is gradually replaced as
the patient's tissue gradually turns over in a natural state of self-renewal.

A retrospective study compared the incidence of post operative atrial fibrillation (POAF) in
patients treated with the CorMatrix ECM for pericardial closure following isolated coronary
artery bypass graft (CABG) versus patients not treated with the patch. The retrospective
study comprised of 222 patients. 111 were treated with the CorMatrix ECM and the other 111
were not. Results showed POAF in 34 of 111 control patients but only 20 in 111 CorMatrix ECM
treated patients, indicating a 54% decrease in the risk of POAF in the CorMatrix ECM treated
patients. This study shows a statistically significant reduction in the risk of POAF in
patients undergoing an isolated CABG with pericardial closure using the CorMatrix ECM.

This is an unblinded, randomized study to identify proteomic inflammatory biomarkers to
determine if there are differences in the biomarkers in patients who are treated using the
CorMatrix ECM implant to close the pericardium and the patients whose pericardium is left
open (the current standard of care). The study will be located at the Inova Heart and
Vascular Institute (IHVI). The CorMatrix ECM will be implanted during the CABG surgical
procedure in the IHVI cardiovascular operating rooms (CVOR).

Sixty (60) patients who are routinely scheduled for a CABG will be recruited and randomly
assigned to one of the two groups. There will be thirty (30) patients in each group. The
control "No Intervention" group will not receive the CorMatrix ECM during surgery, leaving
the pericardium open according to current standard of care. The treatment "Cormatrix" group
will receive the CorMatrix EMC during surgery for the closure of the pericardium according
to the specific recommended surgical technique.

Pericardial fluid and blood samples will be collected from all patients. Pericardial fluid
and blood samples will undergo novel nanoparticle based biomarker discovery technology to
harvest proteomic biomarkers at the George mason University. In addition, patients will have
their cardiac rhythm continually assessed during their hospital stay and then at their
follow up appointments with their surgeon and cardiologist to determine whether they
developed POAF post discharge.

Both genders, greater than eighteen (18) years of age, will be included in the research.
There are no enrollment restrictions based upon race or ethnic origin and it is expected
their inclusion will be representative of the population undergoing CABG at IHVI. Pregnant
women are excluded from the study.

Inclusion Criteria:

- Subject is ≥18 years of age

- Subject must be selected as a candidate for isolated Coronary Artery Bypass Graft
(CABG) procedure

- Subject has a Left Ventricular Ejection Fraction (LVEF) of ≥30%

- Subject is able and willing to provide written informed consent and HIPAA
authorization

- Subject has a life expectancy of at least one year

Exclusion Criteria:

- Subject is scheduled for other concomitant surgical procedures (carotid surgery
included)

- Subject has a known hypersensitivity to porcine material

- Subject has a religious or cultural objection to the use of blood or porcine products

- Subject is scheduled for Off Pump Coronary Artery Bypass procedures (OPCAB)

- Subject has a history of diagnosed treated or un-treated pre-operative atrial
fibrillation or any other type of cardiac arrhythmia

- Subject has a history of anti-arrhythmic drug treatment in the past six (6) months

- Subject has an implantable cardiac device (e.g., pacemakers, implantable cardioverter
defibrillators)

- Subject has a history of an accessory pathway disorder (e.g., Wolff-Parkinson-White
syndrome)

- Subject has a documented myocardial infarction (MI) within six (6) weeks prior to
study enrollment

- Subject needs emergent cardiac surgery (i.e., cardiogenic shock)

- Subject requires intra-aortic balloon pump or intravenous inotropes

- Subject has had an infection within six (6) weeks preceding surgery requiring
antibiotic therapy

- Subject is on pre-surgical immunosuppressive therapy (corticosteroids included)

- Subject has chronic inflammatory disease (leukemia, lymphoma, arthritis, rheumatoid,
lupus, Crohn's disease, ulcerative colitis, hepatitis C, HIV)

- Subject has had therapeutic radiation to the pericardium, either prior to surgery or
expected during the three (3) week period following surgery

- There is an inability to approximate the graft and pericardium edge along the entire
extent of the defect

- Subject is incarcerated

- Subject is participating in concomitant research studies of investigational products
(e.g., Appendage closure devices, septal defect patches)

- Subject is unable to provide informed consent