The FUnctional TricUspid REgurgitation by 3D EChocardiography Cooperative Study (FUTURE 3D)

Prospective, multicenter, observational study to enroll consecutive patients with functional tricuspid regurgitation (FTR) with the primary aim to:

• Use patients' outcomes as a reference to try to define the threshold values for the different grades of FTR severity; and secondary aims to:
• Use 3D echocardiography to assess the relationships among the geometry (size and shape) of the right ventricle, right atrium, tricuspid annulus, and tricuspid leaflets according to the underlying cardiac condition (i.e., atrial fibrillation, pulmonary hypertension, right ventricular cardiomyopathy, congenital heart diseases, etc.)
• Assess the accuracy, and incremental diagnostic and prognostic value of a new software package to measure tricuspid annulus and valve geometry
• Develop new parameters of FTR severity that take into account the lower momentum of the tricuspid regurgitant jet (compared with the mitral regurgitation jet), the complex anatomy of the regurgitant orifice, and both the intra-beat and respiratory variation of the regurgitant volume
• Test the hypothesis that there is no actual grading but a continuum of increased risk of adverse outcome with the increase of FTR severity, and we need robust quantitative metrics (for example, the regurgitant fraction - currently not included in guidelines - which takes into account the right ventricular volume and function) more than grading schemes to assess the severity of the diseases and the effect of treatments
• Test the hypothesis that the relationship between FTR severity and the outcome may be different according to the underlying cardiac condition (i.e., atrial fibrillation, pulmonary hypertension, right ventricular cardiomyopathy, congenital heart diseases, post-cardiac surgery, etc.) as this will affect the timing for interventions

Study Overview

• Status: Recruiting
• Conditions: Echocardiography, Transthoracic; Heart Valve Incompetence
• Intervention / Treatment: Diagnostic test: Echocardiography

• Study Type: Observational
• Enrollment (Estimated): 1500

Contacts and Locations

• Study Contact: Name: Luigi Badano, MD, Ph.D.; Phone Number: +3902619112319; Email: l.badano@auxologico.it
• Study Contact Backup: Name: Denisa Muraru, MD, Ph.D.; Phone Number: +3902619112319; Email: d.muraru@auxologico.it

Study Locations

• Italy
  • Milan, 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
    • Sub-Investigator: Michele Tomaselli, MD
    • Sub-Investigator: Mara Gavazzoni, MD
    • Sub-Investigator: Francesco Perelli, MD
    • Sub-Investigator: Andrea Cascella, MD
    • Sub-Investigator: Samantha Fisicaro, RS
  • Padova, Italy, 35128
    • Terminated
    • University of Padova
• Romania
  • Bucharest, Romania
    • Recruiting
    • University of Medicine and Pharmacy Carol Davila
    • Contact: Noela Radu, MD; Email: noela.radu91@gmail.com
  • Craiova, Romania, 200349
    • Recruiting
    • University of Medicine and Pharmacy of Craiova
    • Contact: Diana Florescu, MD; Email: dianarflorescu@yahoo.com

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 with at least mild functional tricuspid regurgitation and good apical acoustic window

Description

Inclusion Criteria:

• older than 18 years,
• signed informed consent to be part of this study,
• no pregnancy,
• the presence of at least one of the following cardiac conditions: a. Permanent atrial fibrillation b. Pulmonary arterial hypertension c. Left heart diseases with increased postcapillary pressure d. Right ventricular cardiomyopathy e. Right ventricular infarction f. Chronic thromboembolic pulmonary embolism g. Congenital diseases with right ventricular volume overload (atrial septal defect, interventricular septal defect, pulmonary regurgitation) h. Previous left heart valve surgery I. Good enough acoustic window and patient cooperation to obtain 3D echo data sets of the right ventricle, right atrium and tricuspid valve with a minimum temporal resolution of 20 vps l. Availability for clinical and echocardiography follow-up

Exclusion Criteria:

• Unwillingness to be part of the study
• Primary tricuspid valve disease
• Patient already scheduled for tricuspid valve repair/replacement
• Cardiac pacemaker, ICD or CRT leads
• Poor acoustic window
• Impossibility of left lateral decubitus position
• Extreme heart rates (<50 or >100 bpm)
• Previous LVAD implantation

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Functional tricuspid regurgitation; Patients with functional tricuspid regurgitation	Diagnostic test: Echocardiography; - Develop new parameters of FTR severity that take into account the lower momentum of the tricuspid regurgitant jet (compared with the mitral regurgitation jet), the complex anatomy of the regurgitant orifice, and both the intra-beat and respiratory variation of the regurgitant volume
Control subjects; Healthy volunteers

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite endpoint	death from any cause and hospitalization for heart failure	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Right heart remodeling in various cardiac conditions affecting the right heart	Use 3D echocardiography to assess the relationships among the geometry (size and shape) of the right ventricle, right atrium, tricuspid annulus and tricuspid leaflets according to the underlying cardiac condition (i.e. atrial fibrillation, pulmonary hypertension, right ventricular cardiomyopathy, congenital heart diseases etc.)	5 years
3D echo software validation	Assess the accuracy, and incremental diagnostic and prognostic value of a new software package to measure tricuspid annulus and valve geometry	1 year
Improve grading of FTR	Develop new parameters of FTR severity that take into account the lower momentum of the tricuspid regurgitant jet (compared with the mitral regurgitation jet), the complex anatomy of the regurgitant orifice, and bot the intra-beat and respiratory variation of the regurgitant volume	2 years
Clinical significance of categorical grading	Test the hypothesis that there is no actual grading, but a continuum of increased risk of adverse outcome with the increase of FTR severity and we need robust quantitative metrics (for example the regurgitant fraction - currently not included in guidelines - which takes into account the right ventricular volume and function) more than grading schemes to assess the severity of the diseases and the effect of treatments	5 years
Define different phenotypes of FTR	Test the hypothesis that the relationship between FTR severity and outcome may be different according to the underlying cardiac condition (i.e. atrial fibrillation, pulmonary hypertension, right ventricular cardiomyopathy, congenital heart diseases, post-cardiac surgery etc.) as this will affect the timing for interventions	5 years

Collaborators and Investigators

• Sponsor: Istituto Auxologico Italiano
• Collaborators: Denisa Muraru; Michele Tomaselli; Mara Gavazzoni
• Investigators: Study Director: Luigi Badano, MD, Ph.D., Istituto Auxologico Italiano, IRCCS

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2020
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): April 21, 2027

Study Registration Dates

• First Submitted: February 17, 2023
• First Submitted That Met QC Criteria: February 17, 2023
• First Posted (Actual): February 28, 2023

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 15, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Doppler echocardiography; Right ventricular function; Functional tricuspid regurgitation; Three-dimensional echocardiography; Right atrial function
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Valve Diseases; Tricuspid Valve Insufficiency
• Other Study ID Numbers: 09C040

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data will be made available upon reasonable request

Drug and device information, study documents

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