Podocan and Wnt Pathway in Left Ventricular Remodeling of Aortic Stenosis
Podocan and Wnt Pathway in Left Ventricular Remodeling of Aortic Stenosis
Aortic stenosis is a major cause of morbidity around the world. Progressive aortic stenosis
 leads to cardiac hypertrophy as a compensatory response. A maladaptive response may lead to
 heart failure at varying degrees of severity of aortic stenosis in individual patients. The
 predicting factors for the occurrence of a maladaptive response are not well defined.
 Therefore current medical therapy for aortic stenosis is considered insufficient and may
 actually cause harm. The only effective therapy for severe, symptomatic aortic stenosis is
 aortic valve replacement. It has been found in an experimental study that Podocan determines
 the degree of cardiac hypertrophy in response to pressure overload via the Wnt-pathway. The
 possible prognostic role of secreted circulating Wnt modulators in aortic stenosis has also
 recently gained attention. This project will attempt to establish the prognostic role of
 circulatory Podocan and Wnt modulators for maladaptive left ventricular response to aortic
 stenosis. This may help identify patients at particular risk to develop left ventricular
 dysfunction with aortic stenosis and improve understanding of the mechanisms of left
 ventricular remodeling in aortic stenosis. Hence, this may also later act as an important
 background in finding more effective therapies to prevent or delay maladaptive left
 ventricular response in aortic stenosis.
Valvular heart disease is a common clinical indication to assess patients with cardiac MRI.
 Cardiac MRI is comprehensive study that uses multiple imaging sequences.Cardiac MRI is
 indicated to image native and prosthetic aortic valves. Planimetry of the aortic valve is
 valuable for determination of the severity of aortic stenosis. Cardiac MRI is the most
 accurate and reproducible imaging modality to assess left ventricular function and mass. Left
 ventricular (LV) function is a primary determinant of outcomes following aortic valve
 replacement. LV mass is increased in severe aortic stenosis. Variations in the morphology of
 hypertrophy in response to aortic stenosis have been detected by cardiac MRI. Cardiac MRI is
 commonly used to assess aortic stenosis in the context of discordant information from
 alternative imaging modalities and low gradient aortic stenosis.

 It is expected that 100 participants will be enrolled in the study over 24 months. This is
 sample size was agreed upon after discussion with the statistics team.

 Patients who agree to participate will provide informed consent prior to their cardiac MRI. A
 6 minute walk test to measure baseline functional status will be done after consent,
 preferably just prior to reporting to the MRI suite for their scheduled test. Standard
 cardiac MRI will be obtained. All patients having a cardiac MRI have an IV line placed as
 normal procedure. When the line has been placed, prior to contrast infusion (if applicable)or
 other medication administration, blood samples will be collected to test for circulatory
 Podocan and Wnt pathway molecules. Approximately 20 cc will be drawn in total. All specimens
 will be sent to the experimental lab of Dr. Paul Klotman at Baylor Medical Center. All of the
 Podocan & Wnt pathway effectory molecules assays will be completed by Dr. Klotman's lab.

 The following measurements will be collected from the cardiac MRI:

 LV end diastolic (ED) volume: ml LV ED index: ml/m2 LV end systolic (ES) volume: ml LV ES
 index: ml/m2 LV ejection fraction (EF): % LV Stroke Volume: ml LV Stroke Index: ml/m2 LV
 Cardiac Output: L/min LV Cardiac Index: L/min/M2 LV Mass: g LV Mass index: g/m2

 At 12 months post procedure the following information will be collected from the
 participants' charts for endpoint analysis:

 All cause mortality Cardiac mortality Hospital admissions for valvular disease related
 clinical events such as congestive heart failure, angina, syncope Valve replacement surgery

 Patients who do undergo valve replacement surgery during the 12 month follow up period and
 are scheduled to undergo a post-op follow up cardiac MRI (expected to be at 9-12 months
 post-op) will be asked to provide additional blood samples to test for circulatory Podocan
 and Wnt pathway molecules at the time of the MRI.

 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, Heart Rate BMI Tobacco use/history Alcohol
 use/ history Comorbidities

 -  Hypertension

 -  Hyperlipidemia

 -  Diabetes

 -  Chronic Kidney Disease

 -  Cancer

 -  CAD

 Info from previous echocardiogram:

 -  Ejection fraction

 -  Valve area

 -  Gradient

 Info from previous cardiac cath (if done):

 -  Presence/absence of coronary stenosis

 -  Location & degree of stenosis

 -  Aortic valve area

 -  Calculation of valve area

 Info from previous ECG:

 -  Rhythm

 -  Left Ventricular Hypertrophy Medications

 Laboratory data:

 -  Lipids

 -  Chemistries

 -  Complete Blood Count

 -  Hemoglobin A1C

 -  Troponin

 -  B-type Natriuretic Peptide
Inclusion Criteria:

 -  Age 18 or greater

 -  Scheduled for Cardiac MRI

 -  Patients with known aortic valve area of less than 1 cm² on echocardiogram

 -  Able to provide informed consent

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

 Exclusion Criteria:

 -  Other significant (moderate or severe) valvular heart disease

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