Outcome of Patients With Severe Functional TR According to Medical, Transcatheter or Surgical Treatment (TRIGISTRY)

Outcome of Patients With Severe Functional Tricuspid Regurgitation

Tricuspid regurgitation (TR) is a public health problem: moderate / severe TR are common, especially in ageing populations, and affect 4% of the population >75 years old, totaling approximately 1.6 million in the US and 3 million in Europe. TR is associated with an increased risk of mortality and morbidity. Contrasting with TR prevalence and the magnitude of the problem, the vast majority of patients are medically treated with diuretics to relieve their symptoms and a curative surgical treatment for isolated severe TR is seldom performed. Reluctance to perform an ITVS can be explained in the one hand by the limited evidence that TR correction improves outcomes and on the other hand, ITVS is associated to high observed in-hospital mortality rates (≈ 10% remarkably consistent in most series across the literature). Severity of the clinical presentation is the main predictor of outcome after surgery. The TRI-SCORE, is a dedicated, simple and accurate risk score model to predict in-hospital mortality after ITVS that could guide the clinical decision-making process at the individual level. Excellent outcomes can be achieved when patients present with low TRI-SCORE. These results suggest adopting a more pro-active approach for TV interventions, and to intervene earlier in the course of the disease in patients with severe isolated TR, irrespective of TR mechanism / etiology, before the occurrence of advanced / irreversible consequences such as severe RV dilatation / dysfunction, renal and liver failure, and intractable heart failure. Recently transcatheter tricuspid valve interventions (TTVI) have emerged recently as a less invasive option to surgery to cure patients with TR.

What is the best treatment between medical, surgical or transcatheter therapy to consider and the best timing for each patient are not clearly defined. The aim of the study is to compare outcome of patients with significant functional TR according to medical, transcatheter or surgical treatment after matching per TRISCORE.

Study Overview

• Status: Enrolling by invitation
• Conditions: Tricuspid Regurgitation
• Intervention / Treatment: Procedure: Surgery or Transcatheter tricuspid valve intervention

Detailed Description

Tricuspid regurgitation (TR) is a public health problem: moderate / severe TR are common, especially in ageing populations, and affect 4% of the population >75 years old, totaling approximately 1.6 million in the US and 3 million in Europe. The literature is consistent showing that TR is a serious condition, associated with morbidity (reduction in exercise capacity, heart failure) and mortality that increase with TR severity.

Current American College of Cardiology (ACC) / American Heart Association (AHA) and European Society of Cardiology (ESC) / European Association of Cardio-Thoracic Surgery guidelines (EACTS) guidelines recommend performing an isolated tricuspid valve surgery (ITVS) in patients with severe secondary (and primary) TR (with or without previous left-sided surgery), who are symptomatic or have right ventricle (RV) dilatation, in the absence of severe RV or left ventricular (LV) dysfunction and severe pulmonary vascular hypertension.

Contrasting with TR prevalence and the magnitude of the problem, the vast majority of patients are medically treated with diuretics to relieve their symptoms and a curative surgical treatment for isolated severe TR is seldom performed ITVS represents only 8% of all tricuspid valve (TV) surgeries and a tricuspid valve intervention is mostly performed at the same time that left-sided heart valve surgery. Thus, only 10% of patients admitted in France with a diagnosis of significant TR are referred for an intervention.

Reluctance to perform an ITVS can be explained in the one hand by the limited evidence that TR correction improves outcomes. Indeed, there is no large randomized multicentric study in the literature to compare medical vs surgical treatment of TR. A recent study did not show difference in long-term survival for patients who undergo surgical intervention compared to medical management alone but this was a non-randomized retrospective single-center study with a small propensity matched sample (62 patients in each group) and matching was performed according to parameters that are not specific to the RV. On the other hand, ITVS is associated to high observed in-hospital mortality rates (≈ 10% remarkably consistent in most series across the literature). In a large French multicentric registry of 466 patients gathering all consecutive patients who underwent a non-congenital ITVS on native valve for severe TR at 12 tertiary centers during a 11-year period (2007-2017), in-hospital mortality was 10% as in other series, but this average rate was hiding important disparities. Mortality rate was indeed markedly variable and was predicted by the severity of the pre-operative clinical, biological and echocardiographic presentation while TR mechanism / etiology had limited impact. As there is no dedicated STS risk score model for ITVS, and the logistic EuroSCORE and the EuroSCORE II were not designed for ITVS, the investigators have developed TRI-SCORE, a dedicated, simple and accurate risk score model to predict in-hospital mortality after ITVS that could guide the clinical decision-making process at the individual level. TRI-SCORE was based on eight clinical (age ≥70 years, NYHA functional class III-IV, right-sided heart failure signs, daily dose of furosemide ≥125 mg), laboratory (glomerular filtration rate <30 ml/min, elevated total bilirubin) and echocardiographic (LV ejection fraction <60%, moderate/severe RV dysfunction) parameters easy to ascertain and capturing the impact of TR on the RV, the liver and the kidneys. This risk score model, on a 0-12 points scale, provided both an excellent discrimination (C-index >0.75) and calibration with a predicted mortality rate ranging from 1% for 0 point to 65% for ≥9 points irrespective of TR mechanism / etiology. Half of patients were referred for an intervention late in the course of the disease with moderately (4-6) or severely elevated (>6) scores, and therefore high mortality rates. In contrast, low in-hospital and 1-year mortality rates (0% to 4%) were achieved in patients with low score (≤3). Our results suggest adopting a more pro-active approach for TV interventions, and to intervene earlier in the course of the disease in patients with severe isolated TR, irrespective of TR mechanism / etiology, before the occurrence of advanced / irreversible consequences such as severe RV dilatation / dysfunction, renal and liver failure, and intractable heart failure.

Transcatheter tricuspid valve interventions (TTVI) are still at an early stage with a large number of percutaneous TV devices currently under development. TTVI are mostly a repair, especially edge-to-edge repair, with promising initial results in the first real world registries with patients at high surgical risk. Therefore, TTVI, as a less-invasive alternative to surgery, may push for an extension of the number of patients treated.

What is the best treatment between medical, surgical or transcatheter therapy to consider and the best timing for each patient are not clearly defined. The aim of the study is to compare outcome of patients with significant functional TR according to medical, transcatheter or surgical treatment after matching per TRISCORE.

• Study Type: Observational
• Enrollment (Estimated): 3500

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
    • Vienna Medical University
• Canada
  • Québec, Canada
    • IUCPQ
  • Toronto, Canada
    • St Michael's Hospital
  • Vancouver, Canada
    • St Paul Hospital
  • Ontario
    • Ottawa, Ontario, Canada, K1Y 4W7
      • University of Ottawa Heart Institute
• France
  • Amiens, France
    • Amiens University Hospital
  • Créteil, France
    • Henri Mondor Hospital
  • Lille, France
    • Chu Lille
  • Lyon, France
    • Department of Cardiovascular Surgery and Transplantation, Louis Pradel Cardiovascular Hospital
  • Marseille, France
    • APHM, La Timone Hospital, Cardiology Department
  • Nancy, France
    • Department of Cardiology, University Hospital of Nancy-Brabois
  • Nantes, France
    • CHU de Nantes
  • Paris, France
    • Department of Cardiology, Bichat Claude Bernard Hospital
  • Rennes, France
    • CHU de Rennes
  • Rouen, France
    • CHU Charles Nicolle
  • Saint-Denis, France
    • Cardiology Department, Centre Cardiologique du Nord
  • Toulouse, France
    • Rangueil University Hospital
• Germany
  • Bad Oeynhausen, Germany
    • Herz- und Diabeteszentrum
  • Berlin, Germany
    • Charité Universitätsmedizin Berlin
  • Bonn, Germany
    • Bonn University Hospital
  • Cologne, Germany
    • University of Cologne
  • Frankfurt, Germany
    • Cardiovascular center Frankfurt
  • Hamburg, Germany
    • Albertinen Heart and Vascular Center
  • Hamburg, Germany
    • Asklepios clinic Sankt Georg
  • Hamburg, Germany
    • University Heart and Vascular Center
  • Leipzig, Germany
    • Leipzig University Hospital
  • Mainz, Germany
    • University Medical Center of Mainz
  • Munich, Germany
    • Munich Großhadern
• Israel
  • Tel Aviv, Israel
    • Tel Aviv Medical Center
• Italy
  • Milan, Italy
    • Instituto Auxologico Italiano, IRCCS
  • Milan, Italy
    • San Raffaele University Hospital
• Netherlands
  • Leiden, Netherlands
    • Leiden University Medical Center
• Spain
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • Hospital 12 de Octubre
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Hospital Clinico San Carlos
  • Madrid, Spain
    • Puerta de Hierro
• Switzerland
  • Bern, Switzerland
    • Hopital Universitaire de Bern
  • Lugano, Switzerland
    • Istituto Cardiocentro Ticino
  • Zurich, Switzerland
    • Zurich Heart Center
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10029
      • Mount Sinai
    • New York, New York, United States, 10467
      • Montefiore Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The investigators will enroll 3 populations of patients with isolated functional TR

• Patients who remained under conservative management
• Patients who underwent an isolated valve surgery
• Patients who underwent a transcatheter valve intervention

Description

Inclusion Criteria:

• Age ≥ 18 years
• Isolated (no left-valvular heart disease (mitral regurgitation) >2)
• AND Functional
• AND Moderate to severe or severe Tricuspid regurgitation

Exclusion Criteria:

• Congenital valvular disease,
• Previous tricuspid valve intervention,
• Organic tricuspid valvular disease
• Associated valvular heart disease

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Conservative management; Patients with TR who did not undergo a tricuspid valve intervention	Procedure: Surgery or Transcatheter tricuspid valve intervention; Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention
Isolated tricuspid valve surgery; Patients with TR who underwent a Isolated tricuspid valve surgery.	Procedure: Surgery or Transcatheter tricuspid valve intervention; Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention
Transcatheter tricuspid valve intervention; Patients with TR who underwent a transcatheter tricuspid valve intervention.	Procedure: Surgery or Transcatheter tricuspid valve intervention; Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival at 2 years	Mortality	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival free of heart failure admission at 2 years	Patients alive and never admitted for heart failure	2 years
Survival and heart failure readmissions	Patients alive or never admitted for heart failure	up to 10 years

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: David Messika-Zeitoun, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: April 11, 2023
• First Submitted That Met QC Criteria: April 11, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Valve Diseases; Tricuspid Valve Insufficiency; Surgical Procedures, Operative
• Other Study ID Numbers: TRIGISTRY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: A steering committee will organize the publication plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No