Key Points:
- The TRISCEND II trial is the first randomized controlled trial to evaluate transcatheter tricuspid valve replacement (TTVR) for severe tricuspid regurgitation (TR).
- TRISCEND II randomized 400 patients with symptomatic severe TR in a 2:1 ratio to TTVR with the EVOQUE system plus optimal medical therapy (OMT) or OMT alone. The 1-year primary endpoint previously demonstrated superiority of TTVR. Control patients were eligible for crossover to TTVR after 1 year.
- At 2 years, TTVR was associated with durable near-elimination of TR (94.9% with mild or less) and sustained improvement in quality of life (KCCQ-OS increase of 17.8 points). There was no significant difference in all-cause mortality between TTVR and control in the modified intent-to-treat analysis, but high rates of crossover limited 2-year comparisons.
- A post-hoc Bayesian sensitivity analysis accounting for crossover and withdrawal suggested a significant mortality benefit with TTVR but new pacemaker or ICD implantation was significantly higher in the TTVR group.
Severe tricuspid regurgitation is common and is associated with reduced quality of life, recurrent heart failure hospitalizations, and increased mortality. Isolated surgical tricuspid valve intervention carries high operative risk, particularly in the elderly population. Transcatheter approaches to tricuspid valve disease have emerged as potential alternatives, but randomized evidence for transcatheter tricuspid valve replacement (TTVR) has been limited. The TRISCEND II trial compared the EVOQUE TTVR system, a transfemoral self-expanding bioprosthetic valve, to optimal medical therapy (OMT) alone. The 1-year primary endpoint of TRISCEND II demonstrated superiority of TTVR, but longer-term data is needed to assess the durability of these benefits.
On March 30th 2026, the results of “Two-Year Outcomes of Transcatheter Tricuspid Valve Replacement for Severe Tricuspid Regurgitation: The TRISCEND II Randomized Trial” were presented at ACC Scientific Sessions 2026 in New Orleans, LA. This study reported the 2-year clinical, echocardiographic, and quality-of-life outcomes following randomization, as well as 1-year outcomes for control patients who crossed over to TTVR.
The TRISCEND II trial randomized 400 patients with symptomatic ≥severe TR in a 2:1 ratio to TTVR with the EVOQUE system plus OMT (n=267) or OMT alone (control, n=133). The EVOQUE system is a self-expanding nitinol-framed bioprosthetic valve delivered transfemorally via a 28 Fr delivery system, available in four sizes (44mm, 48mm, 52mm, 56mm). Patients in the control group were eligible to cross over to TTVR after completing their 1-year follow-up visits. Safety outcomes were analyzed in the modified intent-to-treat (mITT) population: the TTVR mITT group included the 259 patients who had the procedure attempted, while the control mITT group included all 133 patients per their randomization assignment, including those who later crossed over. Effectiveness outcomes, including TR grade and KCCQ overall summary (KCCQ-OS) score, were analyzed by treatment received (as-treated).
Of the 267 patients randomized to TTVR, 200 patients remained in the TTVR mITT group at two years (94% visit completion rate). Of the 133 randomized to the control arm, after dropout, deaths, and 58 crossovers to TTR, there were 28 patients on OMT alone at 2 years (68% visit completion rate). Baseline characteristics were similar between the TTVR and control groups: mean age was approximately 79 years, over three-quarters were female, the majority had NYHA class III-IV symptoms, over 90% had atrial fibrillation, and more than one-third had a pre-existing pacemaker or CIED. TR etiology was predominantly secondary. The mean STS score for mitral valve replacement was nearly 10%, indicating a high surgical risk population.
In the mITT analysis at 2 years, there was no significant difference between TTVR and control in all-cause mortality (19.1% vs 25.3%; p=0.192), heart failure hospitalization (26.8% vs 32.2%; p=0.312), or the composite of all-cause mortality or heart failure hospitalization (36.0% vs 43.7%; p=0.161). The investigators noted that interpretation of these 2-year comparisons is limited by the high crossover rate. When control patients were stratified by crossover status, TTVR patients had significantly lower all-cause mortality compared to control non-crossover patients (19.1% vs 44.9%; p<0.001), while control crossover patients had a 2-year mortality of 29.4% (TTVR vs crossover p=0.497). Cumulative severe bleeding at 2 years was 19.7% in the TTVR group versus 15.8% in the control group (p=0.409), though severe bleeding was significantly higher in TTVR at 1 year (15.4% vs 5.3%; p=0.003). New pacemaker or ICD implantation among pacemaker-naive patients was significantly higher in the TTVR group at 2 years (31.5% vs 15.0%; p=0.008).
In the as-treated analysis, TTVR resulted in near-elimination of TR at 2 years: 94.9% of TTVR patients had mild or less TR, compared with 95.0% of crossover patients (1 year post-implant) and only 15.4% of OMT-only patients. The KCCQ-OS score improved from baseline by 17.8 points in the TTVR group and 19.6 points in the crossover group at their respective 2-year post-implant timepoints, compared with 14.1 points in the OMT-only group. Post-hoc Bayesian sensitivity analyses with multiple imputation modeling, designed to estimate outcomes had the control group been preserved without crossover or withdrawal, suggested a significant reduction in all-cause mortality with TTVR (19.1% vs 29.4%; p=0.03) and a significant improvement in KCCQ-OS (change from baseline of 17.6 vs 1.9 points; p<0.01). Crossover patients had similar outcomes 1 year post-implant as those originally randomized to TTVR. These results support the durability and effectiveness of TTVR with the EVOQUE system for patients with symptomatic severe TR, though the higher need for pacemakers and the large amount of crossover must be considered.
Sample size is a major limitation: the study was not powered for individual components such as all-cause mortality or heart failure hospitalization. Due to 2:1 randomization, the high crossover rate (43.6%), deaths, and withdrawals, there was high attrition and low sample at 2 years in the control group, limiting the ability to detect between-group differences. Since the post-hoc Bayesian analyses were not prespecified, these findings are hypothesis-generating.
Vinod Thourani, MD, FACS, FACC, of the Piedmont Heart Institute in Atlanta, GA, concluded: “Treatment with transcatheter tricuspid valve replacement resulted in significant and sustained near-elimination of tricuspid regurgitation at two years with associated improvements in quality of life. All-cause mortality was not significantly different between TTVR and control based on assignment at randomization, but crossover analysis demonstrated significantly lower mortality in TTVR compared to control patients who did not cross over. Crossover patients had similar outcomes one year post-implant as those originally randomized to TTVR.”