Platelet Adhesion in the Pathobiology of Aortic Stenosis

Study Overview
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Brief Summary
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Aortic stenosis (AS) is a serious and common condition that affects 2-3% of the population >65 years of age in Western countries. It is also responsible for extraordinarily high healthcare expenditures, estimated to be over $6 billion annually,2 in part because the primary treatment for severe AS is aortic valve replacement (AVR) which is resource-intensive. Valve abnormalities are frequently recognized before AS becomes severe, or before there is need for guideline-directed procedural intervention, thereby providing an opportunity for pharmacologic intervention to slow disease progression. Yet, all attempts to prevent AS progression in those with degenerative non-congenital forms of disease have failed. The only non-procedural intervention that benefits patients with moderate or greater AS is the aggressive treatment of hypertension, which reduces net left ventricular (LV) afterload (valvulo-arterial impedance [Zva]) and can slow secondary LV remodeling. The overall goal of this proposal is to integrate advanced imaging and vascular biology to study how von Willebrand factor (VWF) and platelet adhesion promote AS progression through many parallel pathways, thereby representing a potential therapeutic target. We are hypothesizing that blood markers of abnormal VWF proteolysis and platelet-derived factors, and abnormal valve shear patterns which can be detected by advanced analysis of spectral Doppler on echocardiography are predictors for progressive AS.

Official Title
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Platelet Adhesion in the Pathobiology of Aortic Stenosis

Conditions
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Aortic Valve Stenosis

Intervention / Treatment
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* Diagnostic Test: Echocardiogaphy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria For AS group Age >25 years of age Mild or moderate calcific, non-congenital aortic stenosis by echocardiography within the prior 3 months defined as: aortic valve area 1.0 cm2 - 1.9 cm2 and either peak velocity of >2.5 m/s and <4.0 m/s with normal or mildly reduced stroke volume index (>25 ml/m2), or VTI ratio (LVOT:AoV) of <0.5 and >0.25 with abnormal stroke volume (<35 ml/m2 or >60 ml/m2). Age and sex-matched control subjects undergoing echocardiography with no aortic stenosis, and no more than mild severity disease of other valves. Inclusion criteria for Control Group Exclusion Criteria: -

Ages Eligible for Study
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Minimum Age: 25 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Mild to moderate AS<br>Patients with mild to moderate AS by echocardiography | Diagnostic Test: Echocardiogaphy<br>* Assessment of high velocity low amplitude signals on Doppler echocardiography<br>|
| Controls<br>Age and sex match controls with no AS by echocardiography | Diagnostic Test: Echocardiogaphy<br>* Assessment of high velocity low amplitude signals on Doppler echocardiography<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evidence for High Shear Patterns on Echocardiography | Low-amplitude high velocity signals on spectral Doppler | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma markers of VWF | Plasma markers including VWF antigen, oxidation, cleavage; and ADAMTS13 activity | 4 years |