In-depth Characterization of Atriogenic Secondary Tricuspid Regurgitation Due to Atrial Fibrillation

NCT05749107 | Recruiting

• 1 other identifier: 09M202
• Study Type: observational
• Target: 1,050
• Locations: 1 country
• Sites: 2

Brief Summary

1050 patients with persistent/permanent atrial fibrillation (AF) will be studied using conventional and advanced (three-dimensional and deformation imaging) echocardiography. Patients with moderate/severe isolated secondary tricuspid regurgitation (STR) will undergo blood tests to assess their proteomic profile and cardiac CT to measure the tricuspid annulus geometry. The project will aim to 1. assess the prevalence of moderate/severe isolated STR in patients with AF; 2. identify the mechanisms associated with the development of moderate-severe STR in patients with AF; 3. identify the proteomic profile associated with significant growth of tricuspid valve leaflets as a mechanism to protect patients with AF from the development of moderate/severe STR; 4. evaluate the effects of the restoration of sinus rhythm on the severity of STR and the remodeling of the right heart cardiac structures (i.e. right ventricle, right atrium, and tricuspid valve apparatus).

Conditions

Heart Valve Incompetence; Atrial Fibrillation, Persistent

Keywords

Functional tricuspid regurgitation; Three-dimensional echocardiography; Doppler echocardiography; Right ventricular function; Atrial fibrillation

Outcome Measures

Primary Outcomes (3)

• Incidence of either moderate or severe functional tricuspid regurgitation

  To assess the prevalence of moderate or severe atriogenic secondary tricuspid regurgitation (STR) in patients with persistent/permanent atrial fibrillation (AF), and to develop valve-specific metrics and parameters to assess STR severity by echocardiography.

  1 year

• To identify the mechanisms leading to moderate/severe STR during AF.

  STR severity varies among patients with persistent/permanent AF and comparable RV and RA remodeling. The role of RV and RA size, shape, and function on the extent of tricuspid annulus dilation and dysfunction remains to be clarified. Moreover, it is unknown whether the leaflets of the tricuspid valve can adapt to the stretch exerted on them by the progressive dilation of the tricuspid annulus. The contribution of leaflet adaptation to the pathophysiology of STR and its molecular determinants remains to be clarified

  3 years

• To evaluate the extent of the right heart structure remodeling occurring after the recovery of the sinus rhythm and its effects on STR severity.

  Patients undergoing sustained cardioversion to sinus rhythm (both electrical and pharmacological) and/or ablation of AF, will be followed at 1, 3, and 12 months after the procedure by recording electrocardiogram and complete 2D Doppler and 3DE to assess the extent of the remodeling of the RV, the RA, and the tricuspid valve apparatus. Patients with atriogenic moderate/severe STR without clinical indication to either cardioversion or ablation of the AF, and patients with none/mild atriogenic STR will be followed with clinical assessment, and complete 2D, Doppler and 3DE at 6 months and 1 year. The severity of STR will be quantified by measuring EROA, regurgitant volume, and regurgitant fraction.

  3 years

Secondary Outcomes (1)

• Development of an interpretable predictive model by using and integrating a variety of statistical and artificial intelligence (AI) techniques.

  3 years

Study Arms (1)

Atrial secondary tricuspid regurgitation

Patients with persistent/permanent atrial fibrillation and any degree of isolated tricuspid regurgitation

Diagnostic Test: Echocardiography; Combination Product: Proteomic analyses

Interventions

Echocardiography DIAGNOSTIC_TEST

Identify AF patients at risk of developing moderate/severe STR and those who will benefit from restoring the normal sinus rhythm

Atrial secondary tricuspid regurgitation

Proteomic analyses COMBINATION_PRODUCT

To identify the mechanisms leading to moderate/severe STR during AF.

Atrial secondary tricuspid regurgitation

Eligibility Criteria

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

Study Population

Patients undergoing echocardiography stud because of persistent/permanent atrial fibrillation

You may qualify if:

• age\> 18 years
• persistent/permanent atrial fibrillation
• good acoustic apical window
• left ventricular ejection fraction \> 50%
• pulmonary artery systolic pressure\< 50 mm Hg
• no more than mild mitral or aortic valve disease
• ability to attend clinical and echocardiographic follow-ups
• signature of the study informed consent

You may not qualify if:

• pregnancy
• implanted pace-maker or ICD
• previous heart valve surgery or transcatheter treatment
• previous heart transplant
• organic tricuspid regurgitation

Sponsors & Collaborators

• Istituto Auxologico Italiano: lead
• Ministry of Health, Italy: collaborator

Study Sites (2)

Istituto Auxologico Italiano, IRCCS

Milan, Select A State, 20149, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

NOT YET RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum and plasma specimen for proteomic and miRNA analyses

MeSH Terms

Conditions

Atrial Fibrillation

Interventions

Echocardiography

Condition Hierarchy (Ancestors)

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cardiac Imaging Techniques; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Ultrasonography; Heart Function Tests; Diagnostic Techniques, Cardiovascular

Central Study Contacts

Luigi Badano, MD, Ph.D.

CONTACT

+390261911; l.badano@auxologico.it

Denisa Muraru, MD, Ph.D.

CONTACT

+390261911; luigi.badano@unimib.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 18, 2023
• First Posted: March 1, 2023
• Study Start: December 2, 2022
• Primary Completion: December 2, 2024
• Study Completion: November 2, 2025
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF
• Time Frame: Available now, till the end of the study
• Access Criteria: Data will be made available upon reasonable request

Locations

IT (2)