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

In-depth Characterization of Atriogenic Secondary Tricuspid Regurgitation Due to Atrial Fibrillation. Prevalence, Mechanisms, Advanced Quantification of Regurgitation Severity, and Relative Impact of Sinus Rhythm Restoration on the 3D Remodeling of Right Heart Chambers and Tricuspid Valve Apparatus

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).

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation, Persistent; Heart Valve Incompetence
• Intervention / Treatment: Diagnostic test: Echocardiography; Combination product: Proteomic analyses

• Study Type: Observational
• Enrollment (Estimated): 1050

Contacts and Locations

• Study Contact: Name: Luigi Badano, MD, Ph.D.; Phone Number: 2319 +390261911; Email: l.badano@auxologico.it
• Study Contact Backup: Name: Denisa Muraru, MD, Ph.D.; Phone Number: 2319 +390261911; Email: luigi.badano@unimib.it

Study Locations

• Italy
  • MIlan, Italy, 20132
    • Not yet recruiting
    • IRCCS Ospedale San Raffaele
    • Contact: Pasquale Vergara, MD, Ph.D.; Email: vergara.pasquale@hsr.it
  • Select A State
    • Milan, Select A State, Italy, 20149
      • Recruiting
      • Istituto Auxologico Italiano, IRCCS
      • Contact: Luigi Badano, MD, Ph.D.; Phone Number: 2319 +3902619111; Email: l.badano@auxologico.it
      • Contact: Denisa Muraru, MD, Ph.D.; Phone Number: 2319 +3902619111; Email: d.muraru@auxologico.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients undergoing echocardiography stud because of persistent/permanent atrial fibrillation

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Atrial secondary tricuspid regurgitation; Patients with persistent/permanent atrial fibrillation and any degree of isolated tricuspid regurgitation	Diagnostic test: Echocardiography; Identify AF patients at risk of developing moderate/severe STR and those who will benefit from restoring the normal sinus rhythm; Combination product: Proteomic analyses; To identify the mechanisms leading to moderate/severe STR during AF.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of an interpretable predictive model by using and integrating a variety of statistical and artificial intelligence (AI) techniques.	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.	3 years

Collaborators and Investigators

• Sponsor: Istituto Auxologico Italiano
• Collaborators: Ministry of Health, Italy

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2022
• Primary Completion (Estimated): December 2, 2024
• Study Completion (Estimated): November 2, 2025

Study Registration Dates

• First Submitted: February 18, 2023
• First Submitted That Met QC Criteria: February 28, 2023
• First Posted (Actual): March 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Atrial fibrillation; Doppler echocardiography; Right ventricular function; Functional tricuspid regurgitation; Three-dimensional echocardiography
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Valve Diseases; Atrial Fibrillation; Tricuspid Valve Insufficiency
• Other Study ID Numbers: 09M202

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data will be made available upon reasonable request
• IPD Sharing Time Frame: Available now, till the end of the study
• IPD Sharing Access Criteria: Data will be made available upon reasonable request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

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