Platelet Adhesion in the Pathobiology of Aortic Stenosis

Sponsor
University of Virginia (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05550896
Collaborator
(none)
65
1
67
1

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
  • Diagnostic Test: Echocardiogaphy

Study Design

Study Type:
Observational
Anticipated Enrollment :
65 participants
Observational Model:
Case-Control
Time Perspective:
Prospective
Official Title:
Platelet Adhesion in the Pathobiology of Aortic Stenosis
Anticipated Study Start Date :
Oct 31, 2022
Anticipated Primary Completion Date :
Aug 30, 2027
Anticipated Study Completion Date :
Jun 1, 2028

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

  1. Evidence for High Shear Patterns on Echocardiography [4 years]

    Low-amplitude high velocity signals on spectral Doppler

Secondary Outcome Measures

  1. Plasma markers of VWF [4 years]

    Plasma markers including VWF antigen, oxidation, cleavage; and ADAMTS13 activity

Eligibility Criteria

Criteria

Ages Eligible for Study:
25 Years and Older
Sexes Eligible for Study:
All

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:

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

Responsible Party:
Jonathan Lindner, MD, Professor of Medicine, Vice Chief for Research, Cardiovascular Division, University of Virginia
ClinicalTrials.gov Identifier:
NCT05550896
Other Study ID Numbers:
  • HSR220332
First Posted:
Sep 22, 2022
Last Update Posted:
Sep 22, 2022
Last Verified:
Sep 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Sep 22, 2022