Platelet Adhesion in the Pathobiology of Aortic Stenosis

NCT05550896 | Active Not Recruiting

• 1 other identifier: HSR220332
• Study Type: observational
• Target: 65
• Locations: 1 country
• Sites: 1

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.

Conditions

Aortic Valve Stenosis

Outcome Measures

Primary Outcomes (1)

• Evidence for High Shear Patterns on Echocardiography

  Low-amplitude high velocity signals on spectral Doppler

  4 years

Secondary Outcomes (1)

• Plasma markers of VWF

  4 years

Study Arms (2)

Mild to moderate AS

Patients with mild to moderate AS by echocardiography

Diagnostic Test: Echocardiogaphy

Controls

Age and sex match controls with no AS by echocardiography

Diagnostic Test: Echocardiogaphy

Interventions

Echocardiogaphy DIAGNOSTIC_TEST

Assessment of high velocity low amplitude signals on Doppler echocardiography

Controls; Mild to moderate AS

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

* Age-matched to the Aortic Valve Disease group * Referred for echocardiography for a clinical indication * Absence of valve disease

You may qualify if:

• 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.

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

Location

Related Publications (1)

• Ozawa K, Muller MA, Varlamov O, Hagen MW, Packwood W, Morgan TK, Xie A, Lopez CS, Chung D, Chen J, Lopez JA, Lindner JR. Reduced Proteolytic Cleavage of von Willebrand Factor Leads to Aortic Valve Stenosis and Load-Dependent Ventricular Remodeling. JACC Basic Transl Sci. 2022 Jun 29;7(7):642-655. doi: 10.1016/j.jacbts.2022.02.021. eCollection 2022 Jul.

  PMID: 35958695 BACKGROUND

MeSH Terms

Conditions

Aortic Valve Stenosis

Condition Hierarchy (Ancestors)

Aortic Valve Disease; Heart Valve Diseases; Heart Diseases; Cardiovascular Diseases; Ventricular Outflow Obstruction

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Vice Chief for Research, Cardiovascular Division

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 22, 2022
• Study Start: January 3, 2023
• Primary Completion (Estimated): August 30, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)