Key Points
• In the extended 2 year follow up of the randomized TRI-FR trial, transcatheter edge to edge repair plus optimal medical therapy reduced the composite of first heart failure hospitalization, tricuspid valve surgery, or cardiovascular death compared with medical therapy alone.
• The primary composite endpoint was reduced with T-TEER, with a hazard ratio of 0.56 and a 44% relative risk reduction.
• T-TEER was also associated with a marked reduction in recurrent heart failure hospitalizations, with 37 events versus 64 in the medical therapy alone group, corresponding to a rate ratio of 0.52.
Severe isolated tricuspid regurgitation remains a difficult clinical problem, marked by chronic systemic venous congestion, recurrent heart failure hospitalizations, substantial symptom burden, and poor quality of life. Prior randomized trials have consistently shown improvements in tricuspid regurgitation severity and symptoms after transcatheter intervention, but an early benefit in hard clinical outcomes has been less clear. According to the TRI-FR investigators, an important limitation of prior studies has been relatively short follow up and, in some cases, early crossover, potentially obscuring the longer-term clinical impact of tricuspid repair.
The extended follow up of TRI-FR builds on a trial registered at ClinicalTrials.gov under NCT04646811, where it is listed as a study of transcatheter edge to edge repair for severe secondary tricuspid insufficiency. In patients with severe isolated tricuspid regurgitation, TRI-FR explored whether adding T TEER to optimal medical therapy could improve longer term heart failure related outcomes compared with medical therapy alone. The investigators also published an editorial comment regarding TRI-FR in JACC last year in November.
Unlike prior randomized trials of T-TEER, the design of the TRI-FR trial did not allow patients assigned to the control group to cross over to receive T-TEER during follow-up due to the French national health insurance system not reimbursing for the TriClip T-TEER device used in the trial. As a result, patients in both randomized groups continued to be followed prospectively, as prespecified in the study protocol, allowing the investigators to report long-term clinical outcomes beyond two years without treatment crossover.
The enrolled population reflected an advanced right heart failure phenotype. Mean age was 78 years, 64% were women, 95% had atrial fibrillation, 42% were in NYHA class III or IV, and 91% had massive or torrential tricuspid regurgitation. Baseline symptom burden and biomarker profiles were substantial in both groups, underscoring the advanced nature of disease at enrollment.
The primary extension outcome was the composite of time to first heart failure hospitalization, tricuspid valve surgery, or cardiovascular death. Over a median follow-up of approximately 35 months, this endpoint was significantly reduced in the T TEER group. The investigators reported a hazard ratio of 0.56 with a 95% confidence interval of 0.36 to 0.88 and p = 0.0109, corresponding to a 44% relative risk reduction. The longer term follow up also highlighted a meaningful reduction in recurrent heart failure burden. Total heart failure hospitalizations were 64 in the optimal medical therapy alone group and 37 in the T TEER plus medical therapy group, yielding a rate ratio of 0.52 with p = 0.0073. The average rate of heart failure hospitalization per 100 person years was 16.5 with medical therapy alone versus 9.28 with T TEER plus medical therapy. In addition, 42 patients in the medical therapy arm experienced at least one heart failure hospitalization compared with 27 patients in the T TEER arm.
Notably, the temporal pattern of benefit appeared to evolve over time. Only 39% of all heart failure hospitalizations occurred during the first year of follow-up, suggesting that shorter studies may underestimate the full therapeutic effect of intervention in this disease state. The investigators emphasized that because severe secondary tricuspid regurgitation is closely tied to chronic congestion and progressive right sided heart failure, analyses based only on time to first event may miss an important portion of the disease burden.
Mortality alone was not clearly different between groups during follow-up. Total deaths were 30 in the medical therapy group and 32 in the T TEER group, while cardiovascular deaths were 12 and 10, respectively. However, tricuspid valve surgery was far less frequent after T TEER, occurring in 1 patient versus 10 patients in the medical therapy alone group.
Taken together, the extended follow up of TRI-FR suggests that transcatheter tricuspid repair may do more than improve symptoms. By reducing regurgitant volume, lowering venous pressure, and interrupting the cycle of congestion, decompensation, and readmission, T TEER appeared to modify the downstream trajectory of right sided heart failure. These findings strengthen the case that severe tricuspid regurgitation is not merely a marker of advanced disease, but a treatable driver of clinically meaningful outcomes.