Platelet Adhesion in the Pathobiology of Aortic Stenosis
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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|
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Mild to moderate AS Patients with mild to moderate AS by echocardiography |
Diagnostic Test: Echocardiogaphy
Assessment of high velocity low amplitude signals on Doppler echocardiography
|
Controls Age and sex match controls with no AS by echocardiography |
Diagnostic Test: Echocardiogaphy
Assessment of high velocity low amplitude signals on Doppler echocardiography
|
Outcome Measures
Primary Outcome Measures
- Evidence for High Shear Patterns on Echocardiography [4 years]
Low-amplitude high velocity signals on spectral Doppler
Secondary Outcome Measures
- Plasma markers of VWF [4 years]
Plasma markers including VWF antigen, oxidation, cleavage; and ADAMTS13 activity
Eligibility Criteria
Criteria
Inclusion Criteria For AS group
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Age >25 years of age
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Mild or moderate calcific, non-congenital aortic stenosis by echocardiography within the prior 3 months defined as:
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aortic valve area 1.0 cm2 - 1.9 cm2 and either
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peak velocity of >2.5 m/s and <4.0 m/s with normal or mildly reduced stroke volume index (>25 ml/m2), or
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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:
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | University of Virginia | Charlottesville | Virginia | United States | 22908 |
Sponsors and Collaborators
- University of Virginia
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
- HSR220332