Platelet Adhesion in the Pathobiology of Aortic Stenosis

University of Virginia

Status

Enrolling

Conditions

Aortic Valve Stenosis

Treatments

Diagnostic Test: Echocardiogaphy

Study type

Observational

Funder types

Other

Identifiers

NCT05550896

HSR220332

Details and patient eligibility

About

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.

Enrollment

65 estimated patients

Sex

All

Ages

25+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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: