When Does Treating Tricuspid Regurgitation Change the Course of Heart Failure?

For decades, most cases of severe tricuspid regurgitation (TR) were accepted as a bystander consequence of right heart disease rather than as a therapeutic target. Diuretics are provided to relieve congestion but do not correct the regurgitant lesion, with isolated tricuspid surgery typically considered only as a last option after advanced right-sided heart failure (HF), right ventricular (RV) dysfunction, or end-organ injury develops, at which time surgical morbidity and mortality are high. Transcatheter tricuspid valve intervention (TTVI) has disrupted this paradigm. The question facing cardiologists is no longer whether TR can be reduced safely with TTVI, but when and in whom reducing TR becomes clinically meaningful.

Several completed randomized TTVI trials with either replacement or repair technologies have addressed these issues. In the TRISCEND II trial, 400 patients with symptomatic severe TR were randomized in a 2:1 ratio to transcatheter tricuspid valve replacement (TTVR) with the EVOQUE system (Edwards Lifesciences, Irvine, CA) plus medical therapy or medical therapy alone. At 30 days, TR was reduced to moderate or less in 98.1% of treated patients compared with 15.4% on medical therapy alone. At 1 year, TTVR improved the hierarchical primary outcome of all-cause death, heart transplantation or RV assist device implantation, post-index tricuspid-valve intervention, HF hospitalization (HFH), ≥10 point improvement in Kansas City Cardiomyopathy Score (KCCQ) overall summary score, New York Heart Association (NYHA) functional class, and ≥30 meter improvement in 6-minute walk distance (win ratio (WR), 2.02; 95% confidence interval (CI), 1.56–2.62; P<0.001). The treatment effect was driven by improvements in symptoms and QOL rather than reductions in death or HFH. TTVR was associated with higher rates of severe bleeding (15.4% vs. 5.3%) and new permanent pacemaker implantation (17.4% vs. 2.3%).[1]

In the 350-patient TRILUMINATE randomized trial, tricuspid transcatheter edge-to-edge repair (T-TEER) with the TriClip system (Abbott, Santa Clara, CA) improved the hierarchical primary outcome of death or tricuspid-valve surgery, HFH, and improvement in KCCQ by ≥15 points at 1 year (WR, 1.48; 95% CI, 1.06-2.13). At 30 days, TR was reduced to moderate or less in 87.0% of treated patients compared with 4.8% receiving medical therapy. Health status as measured by KCCQ improved substantially, but mortality and HFH were not reduced at 1 year.[2] The quality-of-life (QOL) benefit of T-TEER has been challenged because in open-label trials (a limitation that applies to all completed TTVI studies), the magnitude of the true symptomatic benefit of TR correction is uncertain given substantial improvements that derive from placebo and Hawthorne effects.

With longer-term follow-up in this trial, however, a possible prognostic benefit to T-TEER emerged. In the expanded 572-patient TRILUMINATE population, recurrent HFH rates through 2 years were lower with T-TEER than with medical therapy, 0.19 versus 0.26 per patient-year (HR, 0.72; 95% CI, 0.53–0.98), with similar rates of all-cause mortality.[3] However, the interpretation of the 2-year outcomes is complicated by substantial crossover from the control group to TTVI at 1 year.

In the Tri.Fr trial, among 300 patients with symptomatic severe TR, the primary ordered composite 1-year clinical outcome of freedom from death or HFH and symptomatic improvement assessed by change in NYHA class and the patient global assessment (PGA) score was improved from 40.6% in patients receiving medical therapy alone to 74.1% after T-TEER with the TriClip (p<0.001). Massive or torrential TR persisted in only 6.8% of T-TEER-treated patients versus 53.5% of control group patients. KCCQ scores increased by 15.9 points with T-TEER vs. 0.4 points with medical therapy. Similar to TRILUMINATE, the beneficial treatment effects through 1-year follow-up were anatomic and symptom-related rather than reductions in death or HFH.[4]

The recent TRIC-I-HF outcomes suggest that T-TEER may provide a prognostic improvement. This trial randomized 360 patients with symptomatic severe TR and an increased risk of future HF events to TTVI (98.3% T-TEER with either the TriClip or the Pascal (Edwards) system) plus medical therapy or medical therapy alone. TTVI improved the hierarchical 1-year primary outcome of death, HFH, and improvement in KCCQ by ≥15 points (WR, 2.42; 95% CI, 1.76-3.33). Importantly, freedom from all-cause death or time-to first HFH through 3 years was 52.4% with intervention and 21.0% with medical therapy (HR, 0.40; 95% CI, 0.29-0.55), with significant reductions noted in both death and HFH alone.[5] The cumulative 3-year crossover rate in the control arm was 43.7%, but TTVI was only permitted after a qualifying HFH. While confirmation is required from long-term follow-up in other trials, these data suggest that T-TEER may provide a prognostic benefit in a high-risk heart failure patient population.

TRIC-I-HF further suggests that baseline risk, disease stage, and follow-up duration may determine whether anatomic correction of severe TR can improve prognosis. TRISCEND II, TRILUMINATE and Tri.Fr enrolled lower-risk patients; symptomatic and health-status benefits were demonstrated despite relatively low 1-year death and HFH rates. TRIC-I-HF deliberately enriched enrollment for patients in whom severe TR had been associated with a higher probability of subsequent HF events and demonstrated reduced death and HFH.

While these data need to be replicated in additional trials, these findings collectively suggest that considering the therapeutic window for tricuspid interventions may be particularly important to identify the patient in whom the right-heart disease is sufficiently advanced to benefit from TR correction but not so advanced that recovery is unlikely (Central Illustration). For practicing cardiologists, this concept changes the referral question from not only, “Is the TR severe enough for intervention?” to “Has the TR become clinically consequential and is there enough right-heart reserve for its safe correction?” Recurrent/refractory congestive symptoms or HFHs despite appropriate diuretic therapy, progressive renal or hepatic disease due to venous hypertension, declining functional capacity, and progressive right-sided remodeling should prompt multidisciplinary evaluation. Conversely, severe RV dysfunction, advanced pulmonary vascular disease, or irreversible cardiorenal and hepatic injury may identify a stage at which eliminating TR may not be tolerated or cannot fully reverse the underlying syndrome.

Contemporary guidelines already point toward this approach, but the evidence is advancing quickly. The 2025 ESC/EACTS guidelines state that TTVI should be considered in high-risk patients with symptomatic severe TR despite optimal medical therapy, in the absence of severe RV dysfunction or precapillary pulmonary hypertension.[6] Importantly, these recommendations were formulated when randomized evidence primarily supported improvements in quality-of-life, TR severity, and RV remodeling. TRIC-I-HF was subsequently reported and adds randomized evidence for reduced death and HFH in an enriched high-risk population.

Important uncertainties remain. The completed trials to date have all been open-label, their hierarchical outcomes included patient-reported measures (i.e., they were underpowered for clinical events), and their populations and event rates differed. TRIC-I-HF (the most positive trial) was modest-sized, and its outcomes warrant future studies for confirmation. More precise characterization of RV reserve, pulmonary vascular disease, venous congestion, and reversibility of renal and hepatic dysfunction will be necessary to define the subgroups of patients who are most likely to benefit. Further defining differences in the safety and efficacy of tricuspid repair vs. replacement (including the importance of residual TR after intervention) is essential and will require head-to-head comparative trials for certainty.

Interventional tricuspid therapeutics has moved beyond proving that TR can be reduced to the critical issue of identifying patient subgroups in which TR reduction alters the clinical trajectory of right-sided heart failure. The sweet spot of not intervening too early while not waiting until irreversible RV and end-organ dysfunction have developed has not yet been established. The next advance will depend less on proving that a new device “works” and more on identifying the predictors (clinical characteristics and parameters of cardiac structure/function) of improved patient prognosis after TR treatment.

 References

1.     Hahn RT, Makkar R, Thourani VH, et al. Transcatheter valve replacement in severe tricuspid regurgitation. N Engl J Med. 2025;392(2):115-126. doi:10.1056/NEJMoa2401918.

2.     Sorajja P, Whisenant B, Hamid N, et al. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med. 2023;388(20):1833-1842. doi:10.1056/NEJMoa2300525.

3.     Kar S, Makkar RR, Whisenant BK, et al. Two-year outcomes of transcatheter edge-to-edge repair for severe tricuspid regurgitation: the TRILUMINATE Pivotal randomized controlled trial. Circulation. 2025;151(23):1630-1638. doi:10.1161/CIRCULATIONAHA.125.074536.

4.     Donal E, Dreyfus J, Leurent G, et al. Transcatheter edge-to-edge repair for severe isolated tricuspid regurgitation: the Tri.Fr randomized clinical trial. JAMA. 2025;333(2):124-132. doi:10.1001/jama.2024.21189.

5.     Hausleiter J, Stocker TJ, Geisler T, et al. Tricuspid-valve intervention in heart failure. N Engl J Med. Published online August 30, 2026. doi:10.1056/NEJMoa2606934.

6.     Praz F, Borger MA, Lanz J, et al. 2025 ESC/EACTS Guidelines for the management of valvular heart disease. Eur Heart J. 2025;46(44):4635-4736. doi:10.1093/eurheartj/ehaf194.