Have TRILUMINATE, TRISCEND II, and TRI.FR changed the way you think about tricuspid regurgitation?
Price: The randomized trials have shaped my thinking in several important ways. First, they have demonstrated that tricuspid regurgitation primarily affects patients’ quality of life and functional status, while an impact on mortality has not yet been convincingly shown. Second, they have confirmed that transcatheter therapies can effectively treat tricuspid regurgitation (TR) in a large proportion of patients. Third, they have highlighted the central importance — and complexity — of right ventricular function when selecting patients for intervention. At the same time, these studies illustrate the tension between trial designs intended for regulatory approval and the level of evidence required for broad guideline recommendations.
Geisler: Yes, certainly. First of all, it has changed our mind that tricuspid regurgitation is a treatable valve disease and we need to do more than medical therapy alone. No matter, if we aim for repair or replacement, we can at least substantially improve quality of life and probably more. QOL is an important endpoint in this comorbid and elderly population (remember average age in these trials was nearly 80 of age). These trials have also substantially raised our awareness of the disease in the setting of heart failure and left-sided valvular heart disease. Residual TR after optimal medical therapy and left-sided interventions is a viable therapeutic target that should be a solid component of a comprehensive heart failure treatment. These trials have also opened the discussion how should we treat TR with a perspective of an individualized and stage-based therapy. In my point of view, we should not ask anymore whether to treat TR at all but rather who are the best patients to benefit from a specific device therapy.
Are we moving toward significantly earlier intervention in patients with severe TR?
Price: Although robust evidence defining the optimal timing of intervention is still lacking, the available data strongly suggest that earlier treatment is likely to be beneficial. Once advanced hepatic or renal dysfunction and right ventricular remodeling have developed, correcting TR may come too late to influence long-term prognosis. In addition, both transcatheter repair and replacement appear technically more favorable before severe leaflet tethering, large coaptation gaps, and advanced RV dysfunction occur. While proving the benefit of earlier intervention in randomized trials will be challenging, it is probably the right direction for the field. Earlier treatment may ultimately also be necessary to demonstrate reductions in mortality, rather than symptom improvement alone.
Geisler: We definitely need to move in this direction. I am sure that we will see more signals on mortality and heart failure hospitalization in the long run if we treat patients earlier and effectively. In order to treat TR earlier we need to improve awareness and screening methods. In the past, we have focused on a symptom-based approach leading to delayed referral of patients with advanced right heart failure. In contrast, a rather disease-based approach should be pursued. This could be achieved by standardized assessment of TR and annular dilatation during routine screening echocardiograms. Follow-up of patients with moderate TR, annular, atrial and/or ventricular dilatation should take place more closely. In addition, we need to build heart valve networks similarly to heart failure networks to discuss treatment options and achieve earlier transferal from GPs and practice cardiologist to heart valve centers. We have gained positive experience at our center by involvement of heart valve coordinators to serve as central interface between patients, referring doctors, heart failure specialists and structural heart interventionalists to ameliorate timely referral to therapy.
Which patients are currently best suited for repair, and which for replacement?
Price: Transcatheter edge-to-edge repair (TEER) is currently best suited for patients with predominantly antero-septal regurgitant jets, smaller coaptation gaps, less advanced TR, favorable leaflet anatomy, and for those who are poor candidates for long-term oral anticoagulation. In contrast, transcatheter valve replacement (TTVR) may be preferable in patients with torrential TR, large coaptation gaps, extensive leaflet involvement, CIED-associated TR not amenable to lead extraction, preserved right ventricular function, and the ability to tolerate lifelong anticoagulation. Looking ahead, repair and replacement are unlikely to compete with one another; instead, they will coexist as complementary treatment strategies, with the relative use of each approach evolving alongside technological advances, new device approvals, and increasing clinical experience.
Geisler: This is a good question, and we do not have the definite answer in the absence of randomized head-to-head comparisons. The two options complement each other very well. From my experience of individual patient courses in clinical practice, I think that TEER is more beneficial at earlier stages in the absence of advanced right ventricular dilatation and torrential TR. There are also anatomical factors (e.g. coaptation gap <8 mm, anterior-septal TR pathology, absence of multiple scallops, low GLIDE Score), that make a substantial TR reduction by transcatheter repair more likely. Primary candidates for TTVR are more likely those with massive or torrential TR, large coaptation gaps, relevant leaflet tethering, leaflet anatomy unfavorable for grasping and failed previous repair. Still, we need more data from comparative trials. Finally, both approaches have been used in a staged fashion, e.g. TEER first strategy and in case of TEER failure over time, TTVR. Also, with novel leaflet modification techniques like ELASTA-T, we will be able to treat more patients in a staged approach which becomes relevant for life-time management if TR deteriorates over time after TEER.
How important are RV function, systemic congestion, and frailty in treatment timing and patient selection?
Price: A comprehensive assessment of right ventricular function is essential for both patient selection and peri-procedural management. RV performance may also influence the choice between repair and replacement in anatomically suitable patients. Optimizing volume status before intervention is equally important, while frailty should always be considered when balancing the potential benefits of complete TR elimination against procedural risk, particularly in elderly patients.
Geisler: These aspects are very important. RV dysfunction, and this is still a matter of debate how to define it best, is not an absolute contraindication. Very severe RV dysfunction was an exclusion criterion in the above trials. In my clinical practice, I do not generally avoid treatment of patients with severe RV-dysfunction, but it is important to be aware for the pre- and post-procedural management (e.g. inotrope/fluid management before and after T-TEER/TTVR, hemodynamic monitoring on ICU/IMC). It is still not clear how to treat patients with severely impaired RV-function. T-TEER might be a better option to avoid RV afterload mismatch. Understanding and risk prediction of RV failure after tricuspid is a very relevant topic and we will need better risk stratification tools (e.g. for prediction of pressure volume curves) and device iterations to mitigate the risk (e.g. by device fenestration or heterotopic devices to allow for atrial reservoir function). Systemic congestion should be avoided as this is usually a sign of advanced disease. We should improve our screening methods to a more disease-based approach to treat the disease before it comes to systemic congestion. Systemic congestion is of course important to assess before any planned tricuspid therapy, as this will require pre-hab measurements to improve procedural outcome. Frailty is an underestimated and one of the most poorly defined parameters. Current scores for evaluation of periprocedural/surgical risk (e.g. EuroScore II, STS, TRI-Score, EuroTR Score) do not take frailty into account, although it is a potent risk modifier, stronger than age. We do not know the true effects of TR treatment in frail patients and whether the positive effect on safety, quality of life und functional capacity improvement observed in the above trials can be translated into these patients who generally have a reduced physiological reserve. Registry data suggest that frail patients, although at higher risk for mortality and hospitalizations, still benefit from TR-treatment. We have some insight from the TAVR field that frail patients particularly benefit from prehab measurements like nutritional optimization and exercise therapy and this may likely also apply to the setting of transcatheter tricuspid therapies.
Do you believe tricuspid interventions will eventually improve prognosis beyond symptom relief and quality of life?
Price: The available evidence already suggests that transcatheter repair reduces heart failure hospitalizations during longer-term follow-up. Although similar benefits have not yet been consistently demonstrated for transcatheter replacement, improvements in procedural technique, patient selection, and device technology are likely to translate into better clinical outcomes over time. Demonstrating a mortality benefit will remain difficult because many patients are treated at an advanced stage of disease when irreversible organ damage and frailty are already present. Earlier intervention, preventing progression to end-stage disease, may ultimately improve survival, although this will require large trials with prolonged follow-up.
Geisler: Yes, I believe we continuously learn from the trials and registries to improve patient selection and to identify those patients who will have the biggest prognostic benefit. We already see some signals depending on the procedural success to achieve residual TR <=1+. In registries, this result is associated with the lowest mortality after T-TEER and depending on the change from baseline TR we also see signals on mortality and heart failure hospitalization after T-TTVR. We probably won't see effects beyond quality of life and symptom relief if at all in patients at the very late stage of the disease in particular when RV-dysfunction is advanced. In addition, we need longer follow-up of the patients. Of note, we start to see a significant reduction of heart failure hospitalization in the TRILUMINATE and TRI.FR trial and mortality in the TRISCEND trial compared to patients who remained on medical therapy only at 2 years. I am sure that these differences will become even more evident in the longer term.
What do you currently consider the biggest unresolved challenge in the field: timing, patient selection, imaging, or evidence?
Price: All of these aspects remain important, but the greatest current limitation is the lack of robust evidence. Existing randomized trials are affected by crossover, unequal randomization, and relatively low event rates, making it difficult to establish definitive recommendations. From a practical standpoint, however, the major daily challenge remains selecting the optimal therapy for each individual patient — repair or replacement. Multimodality imaging is fundamental to this process and will become increasingly important. Echocardiography and cardiac CT already form the backbone of patient assessment, while cardiac MRI is likely to play a greater role in evaluating TR severity and RV function. Intracardiac echocardiography will probably become more widely adopted as technology advances, and artificial intelligence may further improve procedural planning by identifying optimal leaflet grasping zones, facilitating device alignment, and predicting procedural outcomes.
Geisler: It is difficult to grade these challenges as they interact somehow. All aspects are crucial and need further refinement. I think we are on a good way to creating evidence. If you just look at the myriads of data which have been created in recent times and are currently underway for a disease where a few years ago there was very sparse evidence. I would also add some points. Patient lifetime management will become more important once we treat the disease earlier. How can we optimize patient pathways? How should we follow these patients up and how do we assess long-term durability? Can we personalize tricuspid therapy to achieve improvement of mortality and heart failure hospitalization? Additionally, we will have to face the question if therapies are cost-effective in times of financial restrictions across health care systems. In addition, TR treatment requires multidisciplinary management by involvement of structural heart interventionalists, surgeons, heart failure specialists and electrophysiologists in case of atrial functional TR and pacemakers. This involvement needs to be coordinated early, for example to address questions whether patients should undergo rhythm control first, which pacemaker strategy should be pursued in patients with pre-existing TR and how should lead management be pursued in patients with lead associated TR. These are all relevant questions that will also challenge us in daily clinical practice in future.
How do you expect the results of these trials to influence future guidelines and everyday clinical practice in the US and Europe?
Price: Current guideline recommendations will likely continue to focus primarily on improvements in symptoms and quality of life, although the emerging reduction in heart failure hospitalizations observed with longer follow-up will increasingly influence future recommendations. Because regulatory trials were primarily designed to achieve device approval rather than generate the highest level of guideline evidence, widespread clinical adoption may continue to outpace formal guideline updates. Ultimately, successful implementation of transcatheter tricuspid therapies will depend on selecting the right treatment for the right patient. Every patient should therefore be evaluated for both repair and replacement, allowing therapy to become increasingly individualized as experience and evidence continue to grow.
Geisler: The results of TRILUMINATE and EVOQUE already have had a great impact on both sides of the Atlantic. In the US they led to approval of the TriClip™ and the EVOQUE™ device by the FDA. The TRI.FR trial was reassuring and confirmed the positive effects of edge-to-edge therapy in a European patient population. The results of the trials already substantially impacted the recommendation for transcatheter tricuspid therapies in the latest ESC 2025 guidelines. Thus, a more widespread use of these therapies can be expected in US and Europe. These and ongoing trials will likely lead to increased awareness of the disease and help to facilitate referrals, support Heart Team decisions and further impact guideline recommendations in both US and Europe. Access to these therapies and reimbursement situation differ across European countries and US though. Although in Europe we have gained experience with these therapies for longer time due to the earlier CE-marking, access is still highly variable because reimbursement varies at the national and also regional and hospital level. This may be different in the US where broader reimbursement after FDA approval may allow the treatment of a wider patient population. There is an ongoing discussion about the prerequires and minimum performance figure for offering TR treatment and thus these therapies may be more centralized in heart valve centers in Germany. Whether future trial evidence and guidelines recommendations can influence this process will be of interest.
