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

Recruiting

• Conditions: Atrial Fibrillation, Persistent; Heart Valve Incompetence
• Interventions: Diagnostic Test: Echocardiography; Combination Product: Proteomic analyses

• Registration Number: NCT05749107
• Lead Sponsor: Istituto Auxologico Italiano

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).

Detailed Description

Not available

Study Timeline

• Study Start: 2022-12-02
• Study First Submitted: 2023-02-18
• Study First Submitted QC: 2023-02-28
• Study First Posted: 2023-03-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-13
• Last Update Posted: 2024-03-15
• Primary Completion: 2024-12-02
• Study Completion: 2025-11-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1050

Inclusion Criteria

• 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

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Atrial secondary tricuspid regurgitation	Proteomic analyses	Patients with persistent/permanent atrial fibrillation and any degree of isolated tricuspid regurgitation
Atrial secondary tricuspid regurgitation	Echocardiography	Patients with persistent/permanent atrial fibrillation and any degree of isolated tricuspid regurgitation

Primary Outcome Measures

Name	Time	Method
Incidence of either moderate or severe functional tricuspid regurgitation	1 year	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.
To evaluate the extent of the right heart structure remodeling occurring after the recovery of the sinus rhythm and its effects on STR severity.	3 years	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.
To identify the mechanisms leading to moderate/severe STR during AF.	3 years	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

Secondary Outcome Measures

Name	Time	Method
Development of an interpretable predictive model by using and integrating a variety of statistical and artificial intelligence (AI) techniques.	3 years	Clinical, echocardiographic, and biomarker parameters that might predict either the development of moderate/severe STR in patients with AF or the likelihood of reduction of STR severity after cardioversion in sinus rhythm will be identified and integrated in an expert system based on fuzzy reasoning.

Trial Locations

Locations (2)

Istituto Auxologico Italiano, IRCCS; 🇮🇹 Milan, Select A State, Italy

IRCCS Ospedale San Raffaele; 🇮🇹 MIlan, Italy