Prevalence and Significance of ATTR Aortic Valve Amyloidosis in Degenerative Aortic Stenosis (RACAMYL)

Cardiac amyloidosis is a restrictive cardiomyopathy with a potentially severe prognosis that can be life-threatening. It is linked in the vast majority of cases to a light chain deposition of immunoglobulin or transthyretin. Although myocardial involvement is predominant, other locations are possible: the atrioventricular conduction system, coronary arteries and valve leaflets. In systematic histological analyzes, deposits of amyloidosis infiltrating the aortic valve have been reported with a frequency of up to 74% for degenerative RA. The nature of these deposits has never been established because the immunostaining carried out all remained negative, probably due to decalcification prior to cutting. Currently, these deposits are considered to be local degenerative phenomena without clinical repercussions. However, the use of bone scintigraphy has shown a high prevalence, between 14 and 16%, of ATTR cardiac amyloidosis in patients with severe RA. The diagnosis of ATTR amyloidosis has been proven histologically in a few patients. Sequencing of the TTR gene has shown that they are mainly wild forms. In fact, the prevalence of transthyretin mutations in our local cohort is 20%.

The objective of this study is to determine by proteomic analysis based on mass spectrometry, the prevalence of ATTR aortic valve amyloidosis in patients undergoing surgical valve replacement for degenerative aortic stenosis.

Study Overview

• Status: Recruiting
• Conditions: Amyloidosis
• Intervention / Treatment: Diagnostic test: Proteomic analysis

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Olivier LAIREZ, MD; Phone Number: +33 5 61 32 28 73; Email: lairez.o@chu-toulouse.fr
• Study Contact Backup: Name: Magali COLOMBAT, MD; Phone Number: +33 5 31 15 61 40; Email: colombat.m@chu-toulouse.fr

Study Locations

• France
  • Toulouse, France
    • Recruiting
    • university hospital center Toulouse
    • Contact: Audrey TOMASIK; Phone Number: +33 5 61 77 85 97; Email: tomasik.a@chu-toulouse.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patient over 18 years old
• Degenerative aortic stenosis
• Aortic valve replacement surgery
• Signature of the informed consent form

Exclusion Criteria:

• Non-degenerative aortic stenosis: bicuspid, rheumatic disease, aortic regurgitation
• Persons under a system of legal protection for adults (guardianship, curatorship, etc.)
• Pregnant women

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: patients undergoing surgical valve replacement for degenerative aortic stenosis	Diagnostic test: Proteomic analysis; Proteomic analysis based on mass spectrometry on the sample of valve tissues.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prevalence rate of valvular ATTR amyloidosis	calculation of the prevalence rate of valvular ATTR amyloidosis with its 95% confidence interval.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of ATTR myocardial amyloidosis revealed by bone scintigraphy	The prevalence of ATTR myocardial amyloidosis revealed by bone scintigraphy (HMDP scan) will be calculated	1 year
percentage of wild ATTR myocardial amyloidosis	The percentage of wild ATTR forms will be calculated	1 year
percentage of mutated ATTR myocardial amyloidosis	The percentage of mutated ATTR forms will be calculated	1 year
Prevalence of types of amyloidosis other than ATTR	The prevalence of types of amyloidosis other than ATTR will be calculated	1 year

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Magali COLOMBAT, MD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: November 13, 2020
• First Submitted That Met QC Criteria: November 13, 2020
• First Posted (Actual): November 19, 2020

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 21, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: ATTR aortic valve amyloidosis
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Proteostasis Deficiencies; Aortic Valve Stenosis; Amyloidosis
• Other Study ID Numbers: RC31/19/0446

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No