Outcome of Patients with Severe Functional TR According to Medical, Transcatheter or Surgical Treatment

NCT ID: NCT05825898

Last Updated: 2025-03-28

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 3500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2026-12-31

Brief Summary

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.

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.

Conditions

Tricuspid Regurgitation

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: RETROSPECTIVE

Study Groups

Conservative management

Patients with TR who did not undergo a tricuspid valve intervention

Surgery or Transcatheter tricuspid valve intervention

Intervention Type: PROCEDURE

Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention

Isolated tricuspid valve surgery

Patients with TR who underwent a Isolated tricuspid valve surgery.

Surgery or Transcatheter tricuspid valve intervention

Intervention Type: PROCEDURE

Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention

Transcatheter tricuspid valve intervention

Patients with TR who underwent a transcatheter tricuspid valve intervention.

Surgery or Transcatheter tricuspid valve intervention

Intervention Type: PROCEDURE

Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention

Interventions

Surgery or Transcatheter tricuspid valve intervention

Isolated tricuspid valve surgery or Transcatheter tricuspid valve intervention

Intervention Type: PROCEDURE

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ottawa Heart Institute Research Corporation

OTHER

Sponsor Role: lead

Responsible Party

David Messika-Zeitoun

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Messika-Zeitoun

Role: PRINCIPAL_INVESTIGATOR

Ottawa Heart Institute Research Corporation

Locations

Mayo Clinic Rochester

Rochester, Minnesota, United States

Mount Sinai

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Montefiore Health System

New York, New York, United States

Vienna Medical University

Vienna, , Austria

University of Ottawa Heart Institute

Ottawa, Ontario, Canada

IUCPQ

Québec, , Canada

St Michael's Hospital

Toronto, , Canada

St Paul Hospital

Vancouver, , Canada

Amiens University Hospital

Amiens, , France

Henri Mondor Hospital

Créteil, , France

CHU Lille

Lille, , France

Department of Cardiovascular Surgery and Transplantation, Louis Pradel Cardiovascular Hospital

Lyon, , France

APHM, La Timone Hospital, Cardiology Department

Marseille, , France

Department of Cardiology, University Hospital of Nancy-Brabois

Nancy, , France

CHU de Nantes

Nantes, , France

Department of Cardiology, Bichat Claude Bernard Hospital

Paris, , France

CHU de RENNES

Rennes, , France

CHU Charles Nicolle

Rouen, , France

Cardiology Department, Centre Cardiologique du Nord

Saint-Denis, , France

Rangueil University Hospital

Toulouse, , France

Herz- und Diabeteszentrum

Bad Oeynhausen, , Germany

Charité Universitätsmedizin Berlin

Berlin, , Germany

Bonn University Hospital

Bonn, , Germany

University of Cologne

Cologne, , Germany

Cardiovascular center Frankfurt

Frankfurt, , Germany

Albertinen Heart and Vascular Center

Hamburg, , Germany

Asklepios clinic Sankt Georg

Hamburg, , Germany

University Heart and Vascular Center

Hamburg, , Germany

Leipzig University Hospital

Leipzig, , Germany

University Medical Center of Mainz

Mainz, , Germany

Munich Großhadern

Munich, , Germany

Tel Aviv Medical center

Tel Aviv, , Israel

Instituto Auxologico Italiano, IRCCS

Milan, , Italy

San Raffaele University Hospital

Milan, , Italy

Leiden University Medical center

Leiden, , Netherlands

Hospital 12 de Octubre

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Gregorio Marañón

Madrid, , Spain

Hospital Ramón y Cajal

Madrid, , Spain

Puerta de Hierro

Madrid, , Spain

Hopital Universitaire de Bern

Bern, , Switzerland

Istituto Cardiocentro Ticino

Lugano, , Switzerland

Zurich Heart Center

Zurich, , Switzerland

Countries

United States; Austria; Canada; France; Germany; Israel; Italy; Netherlands; Spain; Switzerland

Other Identifiers

TRIGISTRY

Identifier Type: -

Identifier Source: org_study_id