Platelet Adhesion in the Pathobiology of Aortic Stenosis

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.

Eligibility

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:

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Conditions2

Locations1 site

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