Platelet Adhesion in the Pathobiology of Aortic Stenosis

NCT ID: NCT05550896

Last Updated: 2023-04-21

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 65 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-01-03
• Study Completion Date: 2028-06-01

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

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Mild to moderate AS

Patients with mild to moderate AS by echocardiography

Echocardiogaphy

Intervention Type: DIAGNOSTIC_TEST

Assessment of high velocity low amplitude signals on Doppler echocardiography

Controls

Age and sex match controls with no AS by echocardiography

Echocardiogaphy

Intervention Type: DIAGNOSTIC_TEST

Assessment of high velocity low amplitude signals on Doppler echocardiography

Interventions

Echocardiogaphy

Assessment of high velocity low amplitude signals on Doppler echocardiography

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

-

• Minimum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Virginia

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Lindner, MD

Professor of Medicine, Vice Chief for Research, Cardiovascular Division

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Virginia

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Jonathan Lindner, MD

Role: CONTACT

jlindner@virginia.edu

434 297-9442

Facility Contacts

Jonathan Lindner, MD

Role: primary

jlindner@virginia.edu

434-297-9442

References

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.

Reference Type: BACKGROUND

PMID: 35958695 (View on PubMed)

Other Identifiers

HSR220332

Identifier Type: -

Identifier Source: org_study_id