# Tricuspid Regurgitation correction, because our patient's worth it

Erwan Donal, Prayuth Rasmeehirun, Marina Petersen Saadi, Emma Bajeux

► To cite this version:

Erwan Donal, Prayuth Rasmeehirun, Marina Petersen Saadi, Emma Bajeux. Tricuspid Regurgitation correction, because our patient's worth it. European Heart Journal Supplements, 2025, 10.1093/eur-heartjsupp/suaf094. hal-05449121

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1 Tricuspid Regurgitation correction, because our patient's worth

2 it.

3 Running title: value of correcting tricuspid regurgitation

4 Erwan Donal¹, MD, PhD, Prayuth Rasmeehirun¹, MD, Marina PETERSEN SAADI¹, MD, Emma

5 Bajeux, MD

6 ¹University of Rennes, CHU Rennes, Inserm, LTSI - UMR 1099, F-35000 Rennes, France

7 Word Count:

8 Conflicts of Interest: ED received a grant and fees from GE healthcare and Abbott

9 Correspondance :

10 Erwan Donal MD PhD

11 CHU Rennes Pontchaillou Hospital

12 2 rue Henri le Guilloux

13 35033 Rennes, France

14 erwan.donal@chu-rennes.fr

15 +33617708567

16

17 Abstract

18 Tricuspid regurgitation (TR), once considered a passive marker of advanced cardiac
19 disease, is increasingly recognized as an independent contributor to morbidity, mortality,
20 and healthcare burden. Recent evidence, including the pivotal TRILUMINATE trial or Tri-Fr
21 and supporting cost-effectiveness models, suggest that the correction of TR—particularly
22 with transcatheter edge-to-edge repair (TEER) systems —can significantly improve patient
23 outcomes and offer good value for money in European healthcare settings. This article
24 explores the clinical rationale and economic imperative for considering TR as a modifiable
25 and actionable target in modern cardiology.

26 **Key words:** tricuspid regurgitation, transcatheter edge-to-edge repair, medico-economical
27 value

28
## 1 Introduction: Rethinking the Forgotten Valve

Tricuspid regurgitation has long been underdiagnosed, undertreated, and underappreciated in clinical cardiology (1)(2). Historically, its presence was viewed as a secondary phenomenon—an indicator of left-sided heart disease or pulmonary hypertension rather than an independent clinical issue. However, registry studies (3, 4, 5) and newer prospective trials have challenged this narrative, revealing that moderate-to-severe TR is independently associated with increased mortality and hospitalization—even when adjusted for left heart disease and pulmonary pressures.

## 9 The Burden of Disease

TR affects an estimated 1.6 million people in Europe with moderate-to-severe forms, many of whom are elderly and symptomatic. Most patients experience fatigue, peripheral oedema, hepatic congestion, and decreased functional status. In real-world registries, TR severity correlates with poorer outcomes and reduced quality of life—yet less than 10% of patients receive any form of procedural intervention. Even among patients undergoing mitral or aortic surgery, TR is often ignored or worsens post-operatively(6, 7).

Moreover, beyond clinical outcomes, TR is associated with significant economic costs: frequent heart failure hospitalizations, high use of diuretics, and progressive multi-organ dysfunction drive resource use. Given Europe's aging population and rising prevalence of heart failure, TR presents a growing public health challenge. (6)

## 20 Why Medical Therapy Falls Short

Guideline-directed medical therapy for TR focuses on symptom relief—typically with loop diuretics and aldosterone antagonists—but does not modify disease progression or valvular pathology. Unlike left-sided valvular disease, there is no pharmacological treatment that reverses TR. As a result, most patients spiral into recurrent decompensations, requiring repeated hospitalizations with declining organ function.

A critical insight from recent trials is that despite adequate medical therapy, patients remain highly symptomatic, and TR progression continues. This therapeutic gap underscores the need for procedural options that directly address the valve mechanism (8, 9, 10, 11, 12, 13).

## 30 A Paradigm Shift: The Emergence of Transcatheter Therapies

Surgical options for isolated TR are limited by high operative risk, with perioperative mortality exceeding 8–10% in many series. The high-risk profile of the typical TR patient—elderly, frail, often with right heart dysfunction and renal or hepatic impairment—renews surgery unattractive(14, 15).
1 This gap has spurred the development of transcatheter approaches, particularly TEER,
2 specifically engineered for the tricuspid valve. CE-marked in Europe in 2020, one T-TEER
3 offers a catheter-based approach that avoids open-heart surgery, aligning with the risk
4 profile of most TR patients (figure 1).

5 Clinical Evidence:

6 The TRILUMINATE Pivotal Trial

7 The TRILUMINATE Pivotal trial, a multicentre randomized controlled study, included 572
8 patients with severe symptomatic TR. Patients were randomized to either T-TEER + optimal
9 medical therapy or medical therapy alone. At 2-year follow-up, key findings included:

10 A 28% relative reduction in annualized heart failure hospitalizations with T-TEER
11 (0.19 vs 0.26 events/patient-year, p=0.02).

12 • 84% of T-TEER patients had TR reduced to moderate or less at 2 years vs 8% in
13 controls.

14 • Significant and sustained improvements in KCCQ scores (mean +15 points).

15 • A favourable safety profile, with low rates of procedural complications, stroke, or
16 need for pacemaker implantation.

17 • In the crossover cohort (control patients switched to T-TEER after 1 year), delayed
18 intervention was still effective, but at the cost of worsening symptoms and higher
19 HF hospitalization rates prior to crossover(8, 10, 16).

20 Importantly, although mortality was not significantly different at 2 years, the divergence in
21 HF hospitalization rates and sustained quality-of-life gains support a therapeutic benefit
22 that may become more evident with longer follow-up.

23 The TRI-FR Trial – A European RCT Demonstrating Clinical Benefit of T-TEER

24 The TRI-FR trial was a landmark investigator-initiated, multicentre, randomized controlled
25 trial conducted in 24 French-belgium centers. It evaluated the efficacy and safety of T-
26 TEER, in addition to optimal medical therapy, compared with optimal medical therapy
27 alone, in patients with severe symptomatic secondary tricuspid regurgitation (TR) who were
28 deemed at high or prohibitive surgical risk(13, 17).

29 A total of 300 patients were randomized (151 to T-TEER, 149 to control). Key findings at 12
30 months included:

31 • A statistically significant improvement in the primary endpoint, a hierarchical
32 composite of all-cause death, heart failure hospitalization, and change in health
33 status (patient global assessment and NYHA-class).
1. The end-point from Triluminate was also highly in favour of the T-TEER group.

2. Reduction in TR severity:

3. At 12 months, 76.7% of patients in the T-TEER group had TR ≤ moderate, compared with only 6.8% in the control group (P < 0.001).

5. Improvement in health status:

6. The median improvement in KCCQ-OS score at 12 months was +17.9 points in the T-TEER group vs +3.0 points in the control group (P < 0.001) (18).

8. Lower heart failure hospitalization burden:

9. Although the individual components of the primary endpoint did not reach significance, the trend toward fewer HF hospitalizations and better quality of life favoured the intervention group.

12. Safety:

13. T-TEER was associated with a low rate of serious device-related adverse events (2.3% at 30 days), and no significant excess in mortality or stroke compared to controls.

16. Mechanistic insights:

17. Echocardiographic assessment showed the relevance for getting the best possible reduction in TR. There has been clearly demonstrated the relationship between the quality of the TR correction and the change in the quality of life. It could be extrapolated to a beneficial effect on the late occurrence of hospitalization and death.

22. The TRI-FR trial is the first positive randomized controlled trial conducted in Europe to demonstrate that treating severe TR with transcatheter therapy improves clinical outcomes, functional status, and echocardiographic parameters compared with medical therapy alone. Its success reinforces the role of T-TEER as a viable and effective treatment strategy in selected high-risk patients, particularly those with atrial functional TR, preserved right ventricular function, and suitable valve anatomy.

28

29. Medico-economic assessment Cost-effectiveness of T-TEER in France1. Modeling based on data from the TRILUMINATE study. Using a Markov model from the French public payer perspective, a cost-effectiveness study modelled T-TEER over a 10-year horizon in patients mirroring those in the TRILUMINATE trial(10). Key outcomes included:

33. +1.18 life-years gained and +1.38 QALYs versus medical therapy.
1. Incremental cost-effectiveness ratio (ICER): €22,005/QALY—well below commonly accepted thresholds.

3. Robust sensitivity analyses confirmed the model's stability under various assumptions, including real-world mortality inputs (bRIGHT registry(19)). The bRIGHT registry is highly reassuring about the robustness of the therapy with stable results recently demonstrated at 2-years follow-up.

7. Costs were driven primarily by device acquisition and procedure but offset by reduced hospitalization and improved utilities.

9. These findings demonstrate that T-TEER is not only clinically beneficial but economically viable in the French system—and potentially across similar European health systems with shared reimbursement structures.

## 2. Cost-utility analysis alongside TRI-FR trial

13. A cost-effectiveness evaluation alongside the Tri-FR trial is currently underway in order to compare the two strategies (Clip for the tricuspid valve + best medical treatment versus best medical treatment alone) on the dual dimension of QALYs and costs from the French National Healthcare Insurance perspective with a 12-month time horizon for the entire population and a 24-month horizon for the first 150 patients enrolled in the trial (17). The data required for the calculation of the incremental cost-utility ratio will be derived from the study's eCRF matched with data from the French Health Insurance database (called SNDS i.e. Système National des Données de santé) that ensuring a comprehensive measurement of healthcare consumption over the considered time horizon (hospitalizations, consultations, procedures, rehabilitation, imaging and laboratory tests, both in-hospital and outpatient).

24. These results, expected in early 2026, will allow estimation of the cost-effectiveness of TEERs versus medication using utility data collected prospectively via the EQ-5D-5L (vs mapping from the KCCQ scores) and a comprehensive description of patients' care pathways up to 24 months.

## Beyond France: Implications for European Health Policy

29. Other studies including health economic evaluations are currently underway, notably in the Netherlands (NCT05628779). The economic value demonstrated by one French cost-effectiveness model for T-TEER could be broadly applicable across Europe for several reasons, Tri-FR will provide in the upcoming months a validation of the model(17):

33. Comparable healthcare structures and payer expectations:
34. France's public payer model shares key characteristics with many EU systems (e.g.,
1 Italy, Germany, Spain), where interventions are evaluated on QALY-based thresholds
2 and hospital cost offsets from reduced rehospitalizations. The T-TEER ICER in
3 France—€22,005/QALY—falls well below conventional willingness-to-pay
4 thresholds of €30,000–€50,000 in most EU settings.

5 • Cross-national modelling confirms value:

6 Similar Markov modelling of T-TEER has been conducted in:

7 o Poland and Turkey, with ICERs between €10,000–€24,000/QALY, indicating consistency in cost-effectiveness under differing unit costs and healthcare resource utilizations.
8
9

10 o UK, where NICE considers interventions cost-effective below £30,000/QALY.
11 While no formal NICE appraisal exists yet for T-TEER, a probabilistic
12 sensitivity analysis using UK-specific costs and utilities confirmed that the
13 intervention would likely meet NICE cost-effectiveness criteria (20)

14 • European Society for Cardiology and EUnetHTA alignment
15 (https://www.eunethta.eu/hta-core-model):
16 The EUnetHTA Core Model, adopted for multi-country evaluations, promotes
17 transferability of economic models when patient populations, disease progression,
18 and care pathways are similar—which is the case for TR patients in Europe. The ESC
19 Heart Failure guidelines also emphasize reducing hospitalization burden in
20 guideline-directed management, underscoring the clinical-economic alignment of
21 interventions like T-TEER(21).

22 The expected cost-effectiveness of T-TEER modelled in the French model might not be
23 unique to France. Given shared patient profiles, disease burden, and healthcare goals
24 across EU nations, the economic rationale for adopting T-TEER is sound and transferable.
25 National HTA bodies should consider this evidence when evaluating reimbursement
26 pathways.

27 Unmet Needs and Future Directions

28 Despite encouraging data, several barriers remain (figure 2):

29 • Lack of awareness or reluctance to refer patients for TR evaluation and treatment.

30 • Limited access to specialized structural heart teams and centres with TEER capability.

32 • Reimbursement and regulatory hurdles in some EU countries.

33 • A need for longer-term data (>5 years).

34 Future priorities include:
1. Developing risk scores to identify patients who benefit most.

2. Integrating TR screening into heart failure pathways.

3. Expanding TEER training and program capacity.

4. Evaluating combinations with other transcatheter therapies. Results have been presented for transcatheter tricuspid valve replacement -TTVR) and the relative value of this new therapy as compare to T-TEER remains completely unknown.

7 **Conclusion: A Call for Action**

8 Europe stands at a turning point in the management of tricuspid regurgitation. With high-quality evidence from both randomized trials and real-world registries, and with robust cost-effectiveness data soon to be enriched by the TRI-FR economic analysis, the case for early and active intervention in severe TR is compelling. Healthcare systems must now pivot from passive observation to proactive treatment—leveraging TEER not as an exception for the few, but as a new standard for the many.

14 If health systems embrace this opportunity, they can alleviate the burden of heart failure hospitalizations, improve patient quality of life, and invest resources in interventions that deliver long-term value. The forgotten valve no longer needs to be forgotten.

17 **Data Availability:** The data underlying this article will be shared on reasonable request to the corresponding author.

19

20

21 references

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27 2. Guerin A, Dreyfus J, Le Tourneau T, Sportouch C, Lairez O, Eicher JC, et al. Secondary tricuspid regurgitation: Do we understand what we would like to treat? Arch Cardiovasc Dis. 2019;112(10):642-51.

29 3. Topilsky Y, Maltais S, Medina Inojosa J, Oguz D, Michelena H, Maalouf J, et al. Burden of Tricuspid Regurgitation in Patients Diagnosed in the Community Setting. JACC Cardiovasc Imaging. 2019;12(3):433-42.

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39 2021;42(36):3599-726.

40

41

42 Legends figures

43 Figure 1: schematic representation of the unmet need and the value to considere tricuspid

44 transcatheter edge-to-edge repair (T-TEER)
1. Figure 2: summary representation of the main value of transcatheter correction of tricuspid regurgitations

2.

<figure><img src="image_2.png" /><figcaption>Figure 1
254x190 mm (x DPI)</figcaption></figure>

3
4
5
<figure><img src="image_3.png" /><figcaption>Figure 2</figcaption></figure>

1

2
**What is already known**

Patients with isolated
symptomatic severe
tricuspid regurgitation
have few treatment options

<figure><img src="image_4.png" /></figure>

**What this study adds**

The T-TEER provides a
minimally invasive option
for severe tricuspid
regurgitation

<figure><img src="image_5.png" /></figure>

* Optimal medical management

• Safe & effective

• Cost-effective