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Review ariticle | DOI: https://doi.org/10.31579/2690-4861/630
1Department of Cardiac Surgery, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
2DZHK (German Centre for Cardiovascular Research), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany.
3Department of Cardiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
4 Centre for Cardiovascular Innovation, St Paul’s and Vancouver General Hospital, Vancouver, Canada.
5Cardiovascular Translational Laboratory, Providence Research & Centre for Heart Lung Innovation, Vancouver, Canada.
6Centre for Heart Valve Innovation, St. Paul’s Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
7Department of Cardiology and Angiology, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
8Department of Vascular Surgery, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany (R.B.).
*Corresponding Author: Georg Lutter, Department of Cardiac Surgery, University Hospital Schleswig-Holstein (UKSH), Kiel, Germany.
Citation: Zhang Xiling, Nina Sophie Pommert, David Meier, Stephanie L. Sellers, Hatim Seoudy, et al, (2025), Transcatheter Tricuspid Valve Replacement: will it take over? Review Article, International Journal of Clinical Case Reports and Reviews, 22(4); DOI:10.31579/2690-4861/630
Copyright: © 2025, Georg Lutter. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Received: 26 November 2024 | Accepted: 17 December 2024 | Published: 22 January 2025
Keywords: tricuspid regurgitation; heart valve replacement; transcatheter; stents; clini-cal outcomes
Severe tricuspid regurgitation (TR) is a prevalent and challenging condition associated with poor survival outcomes and significant morbidtiy. Medical therapy alone often fails to provide adequate symptom relief, and standalone surgical intervention is liked to high mortality rates, making it a less favorable option unless combined with left-sided valve surgery.
The advent of transcatheter tricuspid interventions has provided new therapeutic possi-bilities, particularly for high-risk patients who are ineligible for conventional surgery. However, many patients remain unsuitable for transcatheter tricuspid repair, or achieve only limited benefits from such procedures. In this context, Transcatheter tricuspid valve replacement (TTVR) has rapidly emerged as a promising alternative, offering the po-tential for more effective treatment outcomes. This review explores the latest advance-ments in TTVR devices, highlights key clinical experiences, and discusses the chal-lenges and limitations of this evolving strategy. Additionally, we address patient selec-tion criteria, procedural outcomes, and future directions in the field, emphasizing the potential of TTVR to transform the management of severe TR.
Tricuspid regurgitation (TR) is a prevalent form of valvular heart disease with extensive research establishing its severity as an independent predictor of mortality[1]. The European Society of Cardiology / European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines recommend tricuspid valve repair or replacement for patients with moderate to severe primary or secondary TR, especially when performed in conjunction with left-sided heart surgery, as a Class I indication[2]. However, managing isolated TR, particularly when accompanied by right ventricular dysfunction, remains challenging, with perioperative mortality rates reaching up to 10%[2].
Transcatheter tricuspid valve intervention (TTVI) offers an innovative therapeutic approach aimed at mitigating the risks associated with conventional surgical procedures. Moreover, compared to treatment with oral medications alone, TTVI may be associated with higher survival rates and lower rates of heart failure rehospitalization[3]. Recent advancements have introduced various TTVI techniques, providing minimally invasive alternatives that have shown promising initial results. The spectrum of TTVI includes both transcatheter tricuspid valve repair (TTVr) and replacement (TTVR), each tailored to specific patient needs. While TTVr has demonstrated commendable safety and efficacy, anatomical considerations such as unfavorable tricuspid valve morphology, or excessive annular dilatation with large coaptation gap may preclude the use of edge-to-edge repair. For these individuals, TTVR sometimes represents the only potential alternative[4].
This review will comprehensively examine the different types of valves currently available and their respective statuses in clinical trials. Furthermore, it will analyze the ongoing challenges and developmental trends in the field of TTVR, emphasizing its potential to significantly advance the therapeutic landscape for TR.
Transcatheter Tricuspid Valve Replacement-Current Landscape
Since the first-in-human implantation, TTVR has advanced rapidly[5]. Early devices were temporarily set aside due to technical limitations and the complex anatomy of the tricuspid valve, which posed challenges in initial design and clinical application. However, with advancements in imaging navigation, catheter technology, and materials science, TTVR techniques have gradually improved, now encompassing two primary approaches: orthotopic and heterotopic replacement. Orthotopic replacement involves directly implanting a new valve at the tricuspid valve site, while heterotopic replacement positions the valve stent within the vena cava[6]. Multiple new devices are currently entering clinical trials, with some demonstrating significant efficacy in high-risk patients, thereby promoting the standardization and diversification of TTVR techniques. Table 1 shows the orthotopic and heterotopic tricuspid valve replacement devices currently under development and tested.
| Device | Manufacturer | Access | Anchoring | Trials |
| Orthotopic | ||||
| VDyne | VDyne | Transfemoral | Septal anchor | NCT05797519 |
| Cardiovalve | Venus MedTech | Transfemoral | TV leaflets | NCT04100720 |
LuX-Valve Lux-Valve Plus | Jenscare Biotechnology | Transatrial Transjugular | Septal anchor and anterior leaflet grasp | NCT05436028 NCT05436028 |
| EVOQUE* | Edwards Lifescience | Transfemoral | TV leaflets/ annulus | NCT04221490 NCT04482062 |
| Intrepid | Medtronic | Transfemoral | Perimeter oversizing | NCT04433065 |
| Trisol | Trisol Medical | Transjugular | Tricuspid annulus | NCT04905017 |
| TRiCares | TRiCares | Transfemoral | Tricuspid annulus | NCT05126030 |
| NaviGate | NaviGate Cardiac Structures | Transatrial | TV leaflets/ annulus | N/A |
| Heterotopic | ||||
| Sapien XT | Edwards Lifescience | Transfemoral | Preceding stent implantation | NCT02339974 |
| TricValve | P+F Products + Features | Transfemoral | N/A | NCT04141137 |
| Tricento | MEDIRA | Transfemoral | N/A | N/A |
Table 1: Orthotopic and heterotopic tricuspid valve replacement devices currently under development and tested. The Evoque valved stent received CE mark*. The scaffolds of these valved stents are made of nitinol. TV: tricuspid valve
Orthotopic Transcatheter Tricuspid Valve Replacement
VDyne
The VDyne valve (VDyne, Inc., Maple Grove, MN, USA, Fig. 1A) consists of a dual-frame nitinol prosthesis, housing a 30 mm porcine tri-leaflet valve. The outer frame is asymmetrically designed (like an oyster, pear-like) with five different fixation mechanisms: a tab at the right ventricular outflow tract, small tabs at the lateral or free wall of the right ventricle (RV), a small tab at the postero-septal wall, and a large tab beyond the posterior annulus. This design aims to anatomically conform to the native annulus while allowing for minor oversizing (larger atrial and ventricular hub). The valve is available in five sizes, suitable for any tricuspid annulus with a circumference of up to 180 mm. Additional sizes under development. The valve is deployed using a single 28Fr catheter and features a unique side-loading delivery system in which the prosthesis is crimped vertically rather than radially. Even after full expansion and positioning it can be fully recaptured[7].
The initial thirteen patients receiving the 3rd generation of human implants were all successfully treated[7]. Early feasibility trials are currently underway in multiple regions globally (VISTA, NCT05797519), and the device has been designated as a breakthrough device by the U.S. Food and Drug Administration (FDA).
Cardiovalve
The Cardiovalve (Venus MedTech, Hangzhou, China, Fig. 1B) device comprises a self-expanding nitinol stent and bovine pericardial leaflets. It
features an atrial flange to assist with anchoring and incorporates leaflet capture technology to prevent valve migration. The valve is delivered via a low-profile 28F delivery system through the femoral vein. The Cardiovalve is suitable for patients with an annulus diameter ranging from 36 to 55 mm and a right ventricular length exceeding 45 mm[8].
Currently, an early feasibility study of Cardio valve is being conducted in the United States (NCT04100720), enrolling 15 patients. The primary endpoints include the absence of device- or procedure-related adverse events within 30 days post-procedure. However, this study has been intermittently interrupted due to technical issues. The new TARGET trial has commenced (NCT05486832), aiming to enroll 100 patients to evaluate the safety and performance of the Cardio valve system.
LuX-Valve
The LuX-Valve (Jenscare Biotechnology, Ningbo, China, Fig. 1C) is a self-expanding bovine pericardial valve also mounted on a nitinol stent. It stands out from traditional stent devices with its unique anchoring mechanism, which secures placement through anterior leaflet clamps and a ventricular anchor, significantly reducing stress on the cardiac walls and minimizing the risk of complications.
This innovative bioprosthesis is available in four sizes, ranging from 30 to 55 mm, and includes eight skirted atrial disc options, making it suitable for native tricuspid annulus diameters from 25 to 50 mm. Implantation is facilitated by a flexible 32Fr delivery system via a transatrial approach, enhancing procedural adaptability and patient recovery[9].
In clinical evaluations, Lu et al.[9] documented the first deployment of the LuX-Valve for transcatheter tricuspid valve replacement in patients at high risk for tricuspid regurgitation. The procedure was successful in all 12 patients, with 90.9% exhibiting no residual tricuspid regurgitation at the 30-day postoperative follow-up.
Additionally, Sun et al.[10] observed a significant reduction in tricuspid regurgitation severity over a 12-month period in a similar patient cohort, although one patient succumbed to right heart failure within three months post-operation.
The second-generation LuX-Valve is transitioning to a transjugular approach. The first-in-human study of the LuX-Valve Plus demonstrated significant results, with all patients successfully receiving the implant and achieving none/trace TR within 30 days[11]. Results from 76 patients under early compassionate use showed that at 1 month, 95.0% of patients had TR of ≤2+, and 86.8% had TR of ≤1+[12].
Currently, multiple studies (NCT06568003, NCT05436028) are evaluating the safety and efficacy of transjugular tricuspid valve replacement using the LuX-Valve Plus system.
Evoque
The EVOQUE tricuspid valve replacement system (Edwards Lifescience, Irvine, CA, USA, Fig. 1D) features a self-expanding nitinol stent, bovine pericardial leaflets, an intra-annular sealing skirt, and anchoring devices. This system is available in three sizes: In 44 mm, 48 mm, and in 52 mm. It utilizes a low-profile, multi-plane 28Fr delivery system designed for femoral artery implantation, making it adaptable to a wide range of anatomical structures.
The TRISCEND trial (NCT04221490) evaluated the safety and performance of the EVOQUE system in patients with symptomatic TR of at least moderate severity, despite receiving medical therapy. At 1 year, 97.6% of implanted patients had TR of mild or less, with 69.0% exhibiting none or only trace TR[13].
The TRISCEND II trial (NCT04482062) aims to assess the safety and efficacy of the EVOQUE system compared to optimal medical therapy (OMT) for patients with at least severe TR. Initial six-month follow-up results from the first 150 patients demonstrated that the EVOQUE system effectively eliminated TR in approximately 78% of participants, with nearly 99
Timing of Intervention
For intervention in TR, currently only the ESC/ EACTS guidelines provide a Class I indication, which is for severe symptomatic TR. Wang et al[31]. compared the characteristics and outcomes of patients with Class I indications for severe symptomatic TR to those without such indications who underwent early surgery. The results showed significantly better short- and long-term outcomes in the early surgery group. Although the patients in Class I were older, with more pronounced symptoms and higher NYHA classifications, resulting in notable differences in baseline characteristics, the small sample size may also have influenced these findings. Nevertheless, this raises a new consideration: should we wait until Class I indications are met before intervening? In fact, the longer the wait for Class I indications, the greater the likelihood of developing risk factors such as right ventricular dysfunction, atrial fibrillation, and renal impairment, which in turn increase both surgical and long-term risks. With the emergence and advancement of new TTVI devices, a lower-risk surgical alternative is now available, potentially offering a new therapeutic strategy for early intervention in TR.
Patient selection
Clinically, secondary TR accounts for 90% of all TR cases[32]. In the early stages of the disease[33], where right ventricular dilation is not yet severe and tricuspid annular dilation occurs without significant leaflet tethering, transcatheter annuloplasty systems like the Cardioband. Tricuspid Valve Repair System are effective in repairing TR[34]. As the disease progresses to the second stage, further dilation of the RV and tricuspid annulus compromises leaflet coaptation, resulting in progressive leaflet tethering. At this juncture, the likelihood of achieving successful repair with an annuloplasty ring alone diminishes, necessitating a combination of edge-to-edge repair and annuloplasty[35, 36]. Notably, performing TTVR at this stage may completely resolve TR. Compared to transcatheter edge-to-edge repair, TTVR can attain a mild or lesser degree of residual TR in almost all patients within 30 days and 1-year (Figure 3)[9, 10, 37-41]. This resolution of TR can be maintained for up to one year, showcasing favorable functional outcomes that may positively influence long-term survival and functional status. In the third stage, as leaflet tethering further deteriorates, TR escalates to massive or torrential levels, rendering repair efforts potentially futile[42].
For patients with preserved or mildly to moderately impaired right ventricular function, TTVR should be considered the treatment of choice. In patients with end-stage heart failure who are on pharmacological treatment, employing TTVR or CAVI as a compassionate therapy is viable, but requires meticulous assessment of the patient’s condition[43].
Apart from survival rates, improvements in quality of life are also an important consideration. In both the TRILUMINATE pivotal trial[44] and the TRISCEND II pivotal trial[45], significant quality of life benefits were observed compared to OMT alone, and these benefits were associated with the degree of TR reduction. In the TRILUMINATE trial, improvements in Kansas City Cardiomyopathy Questionnaire Overall Summary Score scores were similar across groups, regardless of baseline TR severity. In contrast, in the TRISCEND II trial, the extent of quality of life improvement was directly related to baseline TR severity, with patients with more severe baseline TR experiencing greater health status benefits[45]. In addition, there were differences in the timeline of health status improvement between the two trials. In the TRILUMINATE Pivotal trial, the majority of patients showed significant improvement by 30 days post–transcatheter edge-to-edge repair. In contrast, in the TRISCEND II Pivotal trial, only moderate improvement was observed at 30 days, with continued improvement over the following six months[45]. This may be due to a transient increase in right ventricular afterload associated with TTVR.
Based on experience with mitral valve surgery, valve repair is generally prioritized over valve replacement, as conventional valve replacement surgery requires resection of subvalvular structures. This disruption to the subvalvular apparatus can damage the normal ventricular architecture, gradually leading to ventricular ‘sphericalization’ and impairing ventricular function[46, 47]. TTVR does not directly affect the papillary muscles and chordae tendineae; however, the implanted prosthetic valve stent may exert a mild mechanical effect on adjacent tissues. In certain cases, the position of the implant may slightly alter the geometry of the right ventricle, indirectly impacting the position and tension of the papillary muscles. Nevertheless, this effect is typically minimal and, in the vast majority of cases, does not lead to functional abnormalities.
CAVI is specifically engineered to alleviate congestion in patients with severe torrential TR who are either ineligible for surgery or present a high surgical risk. The fundamental mechanism of CAVI involves deploying a valved stent at the junction between the inferior vena cava and the right atrium to mitigate regurgitation. This intervention significantly reduces hepatic congestion, which subsequently improves hepatic and renal function, leading to decreased symptoms only of ascites and peripheral edema[48]. Moreover, CAVI has the potential to enhance right ventricular output, thereby augmenting cardiac output. Nonetheless, it is important to note that this approach is unlikely to ameliorate right ventricular function or influence the process of right ventricular reshape remodeling, thus categorizing it as a palliative procedure.
From the perspectives of safety and efficacy, the technology underpinning CAVI continues to necessitate rigorous validation through ongoing clinical trials. Furthermore, its effectiveness must be evaluated against optimal medical therapy within the framework of randomized controlled trials to establish a robust base of evidence.
Figure 3: Thirty-day and one-year outcomes of transcatheter tricuspid valve intervention[9, 10, 37-41]
Valve durability and anticoagulation
Similar to transcatheter aortic or mitral valves, an inevitable issue with transcatheter tricuspid valves is their durability. Based on past experiences, the durability of bioprosthetic valves typically ranges from 10 to 15 years[49, 50]. However, the durability of right-sided cardiac transcatheter bioprosthetic valved stents remains unclear. The location of the tricuspid valve makes it more susceptible to the complex hemodynamic effects within the heart, particularly in the low-pressure regions. Although the pressure in this area is relatively low, factors such as regurgitation and turbulent flow contribute to increased risks of calcification and wear. Consequently, the durability of the tricuspid valve is generally lower compared to other heart valves. Tissue-engineered bioabsorbable heart valves may offer a strategic approach. Currently, tissue-engineered heart valves have achieved encouraging results in the pulmonary valve domain[51]. Nevertheless, further research is required in the tricuspid valve area.
Currently, there is a lack of evidence-based guidelines for antithrombotic therapy in patients undergoing transcatheter tricuspid valve interventions[52]. Drawing from the experience with surgical bioprosthetic valves, in the absence of an indication for long-term oral anticoagulation (OAC), it is considered reasonable to administer vitamin K antagonists for 6 months following TTVR[53]. Notably, due to the relatively lower blood flow in the right heart chambers, the risk of thrombosis in right-sided prosthetic valves is higher than in left-sided valves[54]. Therefore, an extended duration of OAC may be recommended. After TTVr, single antiplatelet therapy may be considered. However, since most patients already require anticoagulation due to pre-existing atrial fibrillation, they are typically maintained on long-term OAC[55]. Major bleeding is the most common serious complication following TTVI, highlighting the need for further research to determine the optimal duration of anticoagulation after transcatheter tricuspid valve intervention.
Right ventricular dysfunction
Although transcatheter TTVR can effectively eliminate TR, a subsequent complication is the decline in RV function. Right ventricular systolic dysfunction persists 30 days post-operation, which may indicate that the mechanical function of the RV had already been impaired under chronic severe TR but was masked by the reduced afterload[56]. Following TTVR, the significant reduction in TR leads to a sharp increase in afterload, thereby negatively affecting RV function.
Sugimoto et al[57]. proposed a novel load-independent method for measuring RV contractility and found that RV dysfunction in patients with severe TR at baseline did not change after tricuspid valve surgery. While postoperative RV function can predict the outcomes of tricuspid valve surgery, the results of transcatheter devices warrant further investigation. For instance, the single-leaflet design of the Trisol valve, with its high closing volume, can mitigate the sharp increase in afterload that follows the reduction of TR.
In conclusion, while TTVR shows promise in addressing TR, careful consideration of RV function and ongoing research into device-specific impacts on afterload are essential to optimize patient outcomes.
Transvenous leads and transcatheter tricuspid valve devices
The incidence of TR increases exponentially in patients with implanted cardiac electronic devices[58]. This increase is significantly attributed to the leads passing through the tricuspid valve, which can directly interfere with the normal movement of the leaflets, preventing them from closing completely[59]. Prolonged lead friction may also cause structural degeneration or damage to the tricuspid valve[60]. Additionally, long-term interactions can lead to an inflammatory response, resulting in local fibrosis or scar formation, which further impairs leaflet function[61].
Endocardial leads can become trapped between the valve stent and the endocardium, resulting in transvenous lead entrapment.
In the TRISCEND trial, all nine patients with pre-existing pacemakers had their right ventricular leads trapped by the Evoque valve[37]. If a trans-tricuspid lead becomes trapped, it cannot be fully removed in the event of device infection, necessitating alternative surgical extraction and prolonged antibiotic therapy, both of which carry significant mortality risks. In cases of device infection, prolonged suppressive antibiotic therapy has been associated with a 25% mortality rate at one month post-hospitalization and a 90% mortality rate at five years, with an estimated median survival of 1.43 years. Additionally, 18% of patients experience recurrence within one year[62]. The need for surgical extraction also poses serious morbidity risks, particularly in the population undergoing TTVR due to high surgical risk.
In appropriate patients, percutaneous transvenous lead extraction (TLE) may be considered prior to the TTVR procedure[63]. It is important to consider that in patients with TR, the lead may have been embedded or formed scar tissue due to prolonged presence. Removing the lead may further damage the tricuspid valve, leading to more severe regurgitation or acute valve dysfunction. In the ELECTRa registry, out of 3,555 patients who underwent TLE, 0.02-0.59% experienced worsening of tricuspid valve function post-TLE[64]. Polewczyk A et al. reported that in a study of 2,631 patients, 2.5
TR is no longer overlooked, as it significantly contributes to cardiac morbidity and mortality. With the rapid advancement of TTVR therapies, tricuspid regurgitation can now be effectively corrected, avoiding the adverse risks associated with traditional surgery.
TTVR devices offer clear advantages over surgical tricuspid valve replacement and transcatheter repair, reducing mortality and complication rates while effectively treating TR. Additionally, TTVR devices are less dependent on anatomical factors and the underlying TR etiology. Although some devices have received clinical approval, research on TTVR remains limited. Further studies with larger populations, longer follow-ups, and standardized management strategies are needed to advance this field.
Early feasibility studies show promising results and ongoing research continues to explore TTVR’s potential. For patients with severe TR who lack other treatment options, TTVR offers significant hope for the future.
Abbreviations
CAVI :Caval valve implantation
CE :Conformité Européene
ESC :European Society of Cardiology
EACTS :European Association for Cardio-Thoracic Surgery
FDA :Food and Drug Administration
MR :Mitral regurgitation
OAC :Oral anticoagulation
RA :Right atrium
RV :Right ventricle
TLE :Transvenous lead extraction
TR :Tricuspid regurgitation
TTVI :Transcatheter tricuspid valve intervention
TTVr :Transcatheter tricuspid valve repair
TTVR :Transcatheter tricuspid valve replacement
TV :Tricuspid valve
Conceptualization, X.Z. and G.L.; methodology, G.L.; data curation, D.M., S.L.S.; writing—original draft preparation, Z.X., G.L. and N.S.P; writing—review and editing, T.P., D.M., S.L.S., D.F., G.W., O.J.M., H.S., T.A. and R.B.; visualization, D.F. and H.S.; supervision, G.L.; project administration, G.L.; funding acquisition, G.L. All authors have read and agreed to the published version of the manuscript.
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