Identification of Genetic Causes of Calcific Aortic Valve Disease

This study aims to identify the molecular genetic causes of the variability in development of calcific aortic valve disease in bicuspid and tricuspid aortic valves and their associated aortic dilation.

Study Overview

• Status: Active, not recruiting
• Conditions: Aortic Valve Disease; Aortic Valve Insufficiency; Aortic Aneurysm; Aortic Diseases; Aortic Valve Calcification; Calcific Aortic Stenosis; Calcific Aortic Stenosis - Bicuspid Valve; Aortic Valve Cusp Abnormality; Aortic Valve Disease Mixed
• Intervention / Treatment: Procedure: Patients scheduled to undergo aortic valve replacement or aortic surgery at BIDMC will be approached for participation in this study.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The investigators wish to identify the molecular genetic causes of the variability in development of calcific aortic valve disease and aortic dilation in patients with a plan to undergo elective aortic valve replacement and/or ascending aortic surgery at BIDMC.

Description

Inclusion Criteria:

• Patients with a plan to undergo elective aortic valve replacement and/or ascending aortic surgery

Exclusion Criteria:

• Age < 20 years
• Unable/unwilling to consent
• History of aortic valve replacement or transcatheter aortic valve replacement (TAVR)
• History of endocarditis
• History of rheumatic fever
• History of chest radiotherapy
• History of organ transplant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bicuspid aortic valve; We wish to investigate the etiology of calcific aortic valve disease, and aortic dilation or aneurysm in patients with a bicuspid aortic valve undergoing aortic valve replacement or aortic surgery.	Procedure: Patients scheduled to undergo aortic valve replacement or aortic surgery at BIDMC will be approached for participation in this study.; Adult patients undergoing aortic valve replacement (AVR) and/or aortic resection will be enrolled.
Tricuspid aortic valve; Data and samples will be compared using a control group comprised of patients with a tricuspid aortic valve undergoing aortic surgery.	Procedure: Patients scheduled to undergo aortic valve replacement or aortic surgery at BIDMC will be approached for participation in this study.; Adult patients undergoing aortic valve replacement (AVR) and/or aortic resection will be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of expression signatures of aortic valve development and calcification in the macroscopically normal and abnormal portions of aortic valves excised during aortic valve replacement.	We will take a portion of the aortic valve and/or aortic tissue that is routinely excised for aortic valve or aortic replacement for expression analyses and generation of fibroblast cell lines. In collaboration with the Department of Pathology, we have established methods to take sufficient "normal" and abnormal tissue while allowing formal routine pathological evaluation. All tissue samples for expression analysis will be transported in iced RNALater and later frozen in a -80°C research freezer, prior to next generation sequencing. We may use tissue samples to develop cell lines for indefinite use.	8 years

Collaborators and Investigators

• Sponsor: Beth Israel Deaconess Medical Center
• Collaborators: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2018
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 31, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 4, 2019

Study Record Updates

• Last Update Posted (Actual): May 30, 2025
• Last Update Submitted That Met QC Criteria: May 25, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Metabolic Diseases; Ventricular Outflow Obstruction; Congenital Abnormalities; Cardiovascular Abnormalities; Aneurysm; Calcium Metabolism Disorders; Aortic Valve Disease; Aortic Valve Stenosis; Constriction, Pathologic; Heart Defects, Congenital; Aortic Aneurysm; Aortic Valve Insufficiency; Heart Valve Diseases; Calcinosis; Aortic Diseases
• Other Study ID Numbers: 2018P000380

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No