Clinical trial NCT05825898: Outcome of Patients with Severe Functional TR According to Medical, Transcatheter or Surgical Treatment
Official title: Outcome of Patients with Severe Functional Tricuspid Regurgitation
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Tricuspid Regurgitation
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2023-04-24
Enrollment: 3500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: We will enrolled 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

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.

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

Primary outcomes:
measure: Survival at 2 years
timeFrame: 2 years
Secondary outcomes:
measure: Survival free of heart failure admission at 2 years
timeFrame: 2 years
measure: Survival and heart failure readmissions
timeFrame: up to 10 years
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Rochester
state: Minnesota
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Montefiore Health System
state: New York
city: New-York
country: United States
facility: Mount Sinai
state: New York
city: Vienna
country: Austria
facility: Vienna Medical University
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
city: Québec
country: Canada
facility: IUCPQ
city: Toronto
country: Canada
facility: St Michael's Hospital
city: Vancouver
country: Canada
facility: St Paul Hospital
city: Amiens
country: France
facility: Amiens University Hospital
city: Créteil
country: France
facility: Henri Mondor Hospital
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: Department of Cardiovascular Surgery and Transplantation, Louis Pradel Cardiovascular Hospital
city: Marseille
country: France
facility: APHM, La Timone Hospital, Cardiology Department
city: Nancy
country: France
facility: Department of Cardiology, University Hospital of Nancy-Brabois
city: Nantes
country: France
facility: CHU de Nantes
city: Paris
country: France
facility: Department of Cardiology, Bichat Claude Bernard Hospital
city: Rennes
country: France
facility: CHU de RENNES
city: Rouen
country: France
facility: CHU Charles Nicolle
city: Saint-Denis
country: France
facility: Cardiology Department, Centre Cardiologique du Nord
city: Toulouse
country: France
facility: Rangueil University Hospital
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum
city: Berlin
country: Germany
facility: Charité Universitätsmedizin Berlin
city: Bonn
country: Germany
facility: Bonn University Hospital
city: Frankfurt
country: Germany
facility: Cardiovascular center Frankfurt
city: Hamburg
country: Germany
facility: Albertinen Heart and Vascular Center
city: Hamburg
country: Germany
facility: Asklepios clinic Sankt Georg
city: Hamburg
country: Germany
facility: University Heart and Vascular Center
city: Köln
country: Germany
facility: University of Cologne
city: Leipzig
country: Germany
facility: Leipzig University Hospital
city: Mainz
country: Germany
facility: University Medical Center of Mainz
city: Munich
country: Germany
facility: Munich Großhadern
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical center
city: Milan
country: Italy
facility: Instituto Auxologico Italiano, IRCCS
city: Milan
country: Italy
facility: San Raffaele University Hospital
city: Leiden
country: Netherlands
facility: Leiden University Medical center
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Gregorio Marañón
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
city: Madrid
country: Spain
facility: Puerta de Hierro
city: Bern
country: Switzerland
facility: Hopital Universitaire de Bern
city: Lugano
country: Switzerland
facility: Istituto Cardiocentro Ticino
city: Zürich
country: Switzerland
facility: Zurich Heart Center
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: David Messika-Zeitoun
role: PRINCIPAL_INVESTIGATOR
References: