Background
Tricuspid regurgitation (TR) is a condition in which the tricuspid valve does not close properly, allowing blood to leak backward from the right ventricle into the right atrium. When TR becomes severe, it can lead to fatigue, shortness of breath, swelling in the legs and abdomen, reduced exercise capacity, repeated heart failure hospitalizations, and a marked decline in quality of life. Patients with advanced TR often have limited treatment options, because medical therapy can relieve symptoms but does not correct the valve leak itself.
The TRISCEND II trial was designed to test whether transcatheter tricuspid valve replacement (TTVR) with the EVOQUE system could improve outcomes in symptomatic patients with at least severe TR when added to standard medical therapy. The main trial showed clinical benefit overall. This report focuses on whether the degree of TR at baseline changed the response to treatment over time.
Why baseline TR severity matters
TR severity is commonly described as severe, massive, or torrential. These categories reflect progressively larger amounts of backward blood flow and more advanced valve failure. In practice, patients with massive or torrential TR tend to have more congestion, more symptoms, and more advanced right-sided heart disease than those with severe TR alone.
Understanding whether TTVR works equally well across these severity groups is important for clinicians. If benefit is similar regardless of baseline severity, the procedure may be appropriate for a wide range of patients. If benefit is greater in more advanced disease, that may suggest earlier recognition and timely referral are still essential, but that patients with the most advanced disease should not be excluded from treatment.
Study design
TRISCEND II was a multicenter, prospective randomized trial that enrolled 400 symptomatic patients with at least severe TR. Participants were assigned in a 2:1 ratio to either:
1. TTVR with the EVOQUE transcatheter valve plus medical therapy, or
2. Medical therapy alone.
For this post hoc analysis, patients were grouped by baseline TR severity into two cohorts:
– Severe TR: 172 patients
– Massive or torrential TR: 220 patients
The study included independent oversight through an echocardiographic core laboratory, a clinical events committee, and a data safety monitoring board, which strengthens the reliability of the imaging assessments and event adjudication.
The investigators examined clinical outcomes and quality of life at 1 year. They also assessed all-cause mortality and hospitalization for heart failure at 18 months using Kaplan-Meier estimates.
Key findings at 1 year
The most striking result was the ability of TTVR to nearly eliminate significant TR in both severity groups. One year after the procedure, TR was reduced to mild or less in:
– 95.2% of patients with baseline severe TR
– 95.3% of patients with baseline massive or torrential TR
This indicates that the EVOQUE system provided durable and powerful valve competence across the full range of advanced TR severity studied.
The primary safety and effectiveness endpoint was analyzed using a win ratio, a method that compares multiple outcomes in a prioritized way. A win ratio greater than 1 favors the intervention. In this study, TTVR outperformed control regardless of baseline TR severity:
– Severe TR cohort: win ratio 1.64, 95% confidence interval 1.11 to 2.43
– Massive/torrential TR cohort: win ratio 2.20, 95% confidence interval 1.55 to 3.14
These results show that the procedure was beneficial in both groups and that the magnitude of benefit appeared numerically larger in patients with more advanced TR.
Clinical interpretation of the 1-year results
The reduction in regurgitation is important not only as an echocardiographic measure, but also because it can translate into less venous congestion, improved functional capacity, and better daily functioning. For patients with TR, symptom relief often means being able to walk farther, climb stairs more easily, and experience fewer limitations from fluid retention and fatigue.
The trial’s results suggest that correcting the valve leak with TTVR may address the underlying hemodynamic problem more effectively than medical therapy alone. Diuretics and other medications can reduce congestion, but they do not repair the valve. TTVR, by contrast, aims to restore valve function directly.
Findings at 18 months
At 18 months, mortality was similar between the TTVR and control groups in both TR severity strata:
– Severe TR: rate difference 0.2%, with confidence interval from -11.6 to 11.9
– Massive/torrential TR: rate difference -5.8%, with confidence interval from -17.6 to 6.0
These results indicate no clear mortality separation at 18 months, although the follow-up period may still be too short, and the sample size may be too small, to detect a survival advantage in this complex population.
Heart failure hospitalization told a more nuanced story. In the massive/torrential cohort, TTVR showed a favorable reduction in hospitalization for heart failure compared with control:
– Severe TR: rate difference 9.8%, confidence interval from -3.0 to 22.7
– Massive/torrential TR: rate difference -15.2%, confidence interval from -28.9 to -1.5
This suggests that patients with the most advanced valve leakage may derive a stronger clinical benefit in terms of reducing decompensated heart failure episodes and the need for hospitalization.
What the results mean for patients and clinicians
These findings support several practical conclusions.
First, TTVR is effective at reducing TR to mild or less in most patients with at least severe TR, including those with massive or torrential regurgitation.
Second, the treatment benefit is not limited to one baseline severity subgroup. Patients with severe TR and those with more advanced disease both improved, which is reassuring for real-world decision-making.
Third, the signal for fewer heart failure hospitalizations in the massive/torrential group suggests that patients with more advanced disease may gain particular clinical benefit from valve replacement beyond symptom relief alone.
Fourth, because mortality was similar at 18 months, the main near-term advantages appear to be better valve function, improved functional status, improved quality of life, and fewer heart failure admissions rather than a proven early survival benefit.
How the win ratio should be understood
The win ratio is not as intuitive as a simple comparison of event rates, but it is useful in complex trials where several outcomes matter. Instead of focusing on only one endpoint, such as death or hospitalization, the win ratio prioritizes clinically important outcomes and compares paired patients between groups. A win ratio above 1 means the treatment group had more favorable outcomes overall.
In TRISCEND II, the favorable win ratios in both severity groups reinforce that TTVR produced a broad clinical advantage over medical therapy alone.
Strengths of the trial
Several features make TRISCEND II an important study:
– Randomized design, which reduces bias
– Multicenter enrollment, improving generalizability
– Independent echocardiographic core laboratory, improving imaging consistency
– Clinical events committee and data safety monitoring board oversight, strengthening event assessment and patient safety monitoring
– Assessment of both hard clinical outcomes and quality-of-life measures
These elements support the credibility of the findings and help place them in the context of modern structural heart intervention research.
Important limitations
As with any clinical trial analysis, there are limitations to consider.
This was a post hoc subgroup analysis, meaning the severity-based comparisons were not the primary randomized comparison planned at the outset. Such analyses are valuable for hypothesis generation and clinical interpretation, but they are less definitive than primary endpoint analyses.
In addition, the follow-up period for mortality and heart failure hospitalization was 18 months. Structural heart interventions may show larger differences over longer periods, especially if sustained relief from volume overload improves right ventricular function and reduces recurrent congestion over time.
Another important issue is that patients enrolled in a specialized trial may not represent all individuals with TR seen in routine practice. Real-world patients often have more comorbidities, more frailty, or more advanced right-sided heart failure, which can affect procedural risk and outcomes.
Broader clinical context
For many years, treatment for significant TR has focused primarily on diuretics and management of underlying causes such as atrial fibrillation, pulmonary hypertension, left-sided valve disease, or cardiomyopathy. Surgical tricuspid valve repair or replacement has traditionally been reserved for selected patients because operative risk is often high, especially when patients present late in the disease course.
Transcatheter therapies are changing this landscape. TTVR offers a minimally invasive alternative for patients who may be poor surgical candidates. The TRISCEND II findings are especially relevant because they show robust valve reduction even in patients with the most advanced TR severity, a group that has historically had few effective options.
Practical takeaways
The main message from this analysis is straightforward: patients with symptomatic at least severe TR benefit from TTVR, and that benefit is seen whether baseline disease is severe or massive/torrential. The procedure reliably reduces the valve leak, improves symptoms and quality of life, and may reduce heart failure hospitalizations, especially in patients with more advanced TR.
For clinicians, this supports early referral to a heart team experienced in structural interventions when a patient with TR becomes symptomatic despite medical therapy. For patients, it reinforces that advanced tricuspid valve disease is no longer a purely medical problem without procedural options.
Conclusion
In the TRISCEND II trial, transcatheter tricuspid valve replacement with the EVOQUE system plus medical therapy produced substantial and durable reduction in TR across baseline severity groups. At 1 year, nearly all treated patients had TR reduced to mild or less. At 18 months, mortality was similar between groups, but heart failure hospitalization was lower in patients with massive or torrential TR. Overall, the data suggest that TTVR provides meaningful benefit for patients with at least severe TR, with a signal that those with more advanced disease may gain the greatest clinical advantage.
