Podocan and Wnt Pathway in the Development of Aortopathy in Bicuspid Valve Disease
Podocan and Wnt Pathway in the Development of Aortopathy in Bicuspid Valve Disease
Bicuspid Aortic Valve (BAV) disease is a common cardiac anomaly that is associated with
 valvular abnormalities, both stenosis and regurgitation, and aortopathy. It is also shown to
 play role in abnormal aortic distensibility and stiffness with impairment of aortic
 elasticity and Left ventricular dysfunction. Mechanism of aortopathy is complex and is not
 understood completely. In a recent study podocan is found in extracellular matrix (ECM) of
 human aorta and is found to be accumulated in human abdominal aortic aneurysms. There is no
 current effective therapy that can alter the progression of aortic dilatation in bicuspid
 valve disease. Aortic surgery and aortoplasty is the only treatment in severely dilated aorta
 and aortic dissection. In this study the aim is to investigate the association between
 podocan and Wnt pathway in development and pathogenesis of aortopathy. This could provide
 more effective and physiological understanding of disease process and potential target in
 prevention and treatment for aortopathy.
Patients with known BAV will be enrolled in two inclusion criteria categories:

 - Group A: Patients who are scheduled to have a cardiac MRI

 Procedures for Group A: MRI will be used as a standard procedure to confirm the morphology of
 bicuspid valve especially in uncertain cases and to do accurate aortic measurements. Patients
 who agree to participate will provide informed consent prior to their cardiac MRI/CT. A 6
 minute walk test to measure baseline functional status will be performed after consent. All
 patients having a cardiac MRI/CT have an IV line placed as normal procedure. When then line
 has been placed, prior to contrast infusion a blood sample will be collected to test for
 circulatory Podocan and Wnt pathway molecules. At 24 months post procedure the following
 information will be collected from the participants' charts for endpoint analysis:

 -  All cause mortality

 -  Hospital admissions for Aortic dissection, Congestive heart failure, endocarditis or
 cardiac death

 -  Valve replacement or aortic graft surgery

 -  Group B: Patients who have already had an MRI within the past year

 Procedures for Group B: MRI will be used as a standard procedure to confirm the morphology of
 bicuspid valve especially in uncertain cases and to do accurate aortic measurements. Patients
 who agree to participate will report to the Clinical Research Division (CRD ) for a research
 visit to enroll in the study. At this visit, the patient will provide informed consent,
 complete a 6 minute walk test to measure baseline functional status , and will have blood
 drawn by venipuncture to obtain a blood sample to test for circulatory Podocan and Wnt
 pathway molecules. At 24 months post procedure the following information will be collected
 from the participants' charts for endpoint analysis:

 -  All cause mortality

 -  Hospital admissions for Aortic dissection, Congestive heart failure, endocarditis or
 cardiac death

 -  Valve replacement or aortic graft surgery

 All patients who do undergo valve replacement or aortic graft surgery within the 24 month
 follow up period, will have their valve tissue samples analyzed for podocan levels. These
 tissues are removed as a routine part of the surgery and sent to the clinical laboratory at
 Bassett. The number of tissue samples collected during this procedure can range from one to
 four based on the exact nature and location of the aortic pathology. The Bassett Clinical Lab
 will prepare additional paraffin blocks and slides of the tissue for the research study.

 A blood sample will also be taken at the time of the patient's post-op MRI to test for
 circulatory Podocan and Wnt pathway molecules. This usually occurs about 6-9 months after
 surgery.

 It is expected that 100 participants will be enrolled in the study over 18 months. This is a
 sample size of convenience for this pilot study based the current volume of patients
 undergoing cardiac MRI/CT for evaluation of valvular disease. Of these 100 patients, it is
 estimated that 25 will undergo surgery as described above within the study period.

 Baseline analysis will be performed to study the association between circulatory Podocan and
 Wnt regulatory molecules (Wnt-1, Wnt-3, Dkk-1, WIF-1, sFRP-1, sFRP-3) measured by ELISA in
 peripheral blood and tissue samples of aortic root/ascending aorta.

 Each participant's chart will be reviewed at the time of enrollment and the following
 variables will be abstracted from the medical record:

 -  age,

 -  gender,

 -  ethnicity,

 -  Most recent Ht, Wt, BP, HR

 -  BMI

 -  Tobacco use/history

 -  Alcohol use/ history

 -  Comorbidities

 -  HTN

 -  Hyperlipidemia

 -  Diabetes

 -  CKD

 -  Cancer

 -  CAD

 -  Info from previous echocardiogram:

 -  Ejection fraction

 -  Valve area

 -  Gradient

 -  Info from previous cardiac cath (if done):

 -  Presence/absence of coronary stenosis

 -  Location and degree of stenosis

 -  Aortic valve area

 -  Calculation of valve area

 -  Info from previous ECG:

 -  Rhythm

 -  LVH

 -  Medications

 -  Laboratory data:

 -  Lipids

 -  Chemistries

 -  CBC

 -  HgA1C

 -  Troponin

 -  BNP
Inclusion Criteria:

 -  Age 18 or greater

 -  Patients with known BAV diagnosed by echocardiography, previous MRI, or cardiac CT

 -  Scheduled for cardiac MRI or have had a cardiac MRI within the past year

 -  Able to provide informed consent

 -  Ambulatory and expected to be able to complete 6 minute walk test

 Exclusion Criteria:

 -  Patients without BAV

 -  Patients who have already had surgery for aortic valve problems and/or aortopathy

 -  Unable to complete 6 minute walk test (ex. Wheelchair bound)