By Michael H. Crawford, MD, Editor
SYNOPSIS: A further analysis of the quality-of-life parameters in a trial of tricuspid transcatheter edge-to-edge repair (T-TEER) in patients with severe symptomatic tricuspid regurgitation vs. medical therapy alone has shown that T-TEER is associated with significant benefits in physical functioning and quality of life that are sustained for one year and were proportional to the magnitude of regurgitation reduction.
SOURCE: Arnold SV, Goates S, Sorajja P, et al. Health status after transcatheter tricuspid-valve repair in patients with severe tricuspid regurgitation. J Am Coll Cardiol 2024;83:1-13.
The Trial to Evaluate Cardiovascular Outcomes in Patients Treated with the Tricuspid Valve Repair System Pivotal (TRILUMINATE Pivotal) trial of tricuspid edge-to-edge transcatheter valve repair (T-TEER) with the TriClip device (manufactured by Abbott) showed that tricuspid regurgitation (TR) was reduced and functional status, as well as health status, was improved compared to medical therapy alone, but there was no difference in heart failure hospitalizations or mortality at one year. Since severe TR patients tend to be older with a higher comorbidity burden, perhaps improving mortality and reducing heart failure admissions are unrealistic goals as opposed to improving symptoms. Thus, this analysis of TRILUMINATE Pivotal focused on the functional and health status outcomes in more detail.
TRILUMINATE Pivotal was a prospective, multicenter, randomized, open-label trial of T-TEER vs. medical therapy alone in patients with severe symptomatic TR. In addition to severe TR, the patients had to have class II-IV symptoms, a pulmonary artery systolic pressure < 70 mmHg, be on guideline-directed medical therapy, and have no other conditions, such as mitral regurgitation, that needed correction. Disease-specific health status was assessed via the Kansas City Cardiomyopathy Questionnaire (KCCQ), which has a range of 0-100, with higher scores corresponding to better health status. Changes in KCCQ of 5 or more are considered clinically significant, with a KCCQ ≥ 60 and no decline from baseline of > 10 points being considered alive and well.
Generic health status was evaluated by the Medical Outcomes Study Short Form 36 (SF-36) Health Survey, which includes eight elements of health status, including physical and mental aspects. The SF-36 population mean is 50 and changes of > 2.5 points are considered clinically significant. The two metrics were assessed before T-TEER, at one month post-procedure, and after one year of follow-up. Heterogeneity in health status was assessed by performing subgroup analyses of a variety of clinical parameters. The primary endpoint was changes in these scores at one year.
Between 2019 and 2021, 332 patients were enrolled from 80 centers in the United States, Europe, and Canada (mean age 78 years, 55% women). Compared to medical therapy alone, T-TEER demonstrated a significant improvement in the KCCQ score (9.4 points; 95% confidence interval [CI], 5.3-13.4 points) at one month that was maintained at one year (10.4 points; 95% CI, 6.3-14.6 points).
Also, T-TEER patients were more likely to be alive and well at one year (75% vs. 46%, P < 0.001) with a number needed to treat of 3.5. An interaction analysis showed that the benefit of T-TEER decreased as baseline KCCQ score increased (P < 0.001) but was effective for scores up to 80. The SF-36 also showed modest improvements in the physical component vs. medical therapy (5.2 points; 95% CI, 2.3-7.1 points) but not the mental component. Improved health status after T-TEER was associated with reduced one-year mortality and heart failure hospitalizations. Further analyses exhibited that the health status benefits of T-TEER largely could be explained by the magnitude of TR reduction. The authors concluded that, compared to medical therapy alone, T-TEER was associated with significant and sustained improvements in health status in patients with severe TR.
COMMENTARY
The initial report from the TRILUMINATE Pivotal trial was disappointing in that the combined endpoint showed a benefit from T-TEER but only because of quality-of-life (QOL) parameters, not the hard endpoints of mortality and heart failure hospitalizations.1 However, making patients feel better also is a worthy goal of any treatment. Accordingly, this deeper dive into the health status measures in TRILUMINATE Pivotal is of interest.
The results support the use of T-TEER in symptomatic patients with severe TR to reduce symptoms, increase physical functional status, and improve QOL. Also, the T-TEER patients were more likely to be alive and well at one year, with a number needed to treat of < 4. In addition, they showed that those with a cardiac output ≥ 2 L/min/m2 were more likely to benefit from T-TEER. Since the patients enrolled mostly had normal left ventricular function and systolic pulmonary artery pressures < 70 mmHg, this suggests that right ventricular function is an important determinant of the success of T-TEER. Finally, one must consider the alternative to T-TEER, surgical valve replacement, which rarely is performed because of reported perioperative mortality rates of 10%.
TRILUMINATE Pivotal has weaknesses to consider. It was not blinded, so softer endpoints may be subject to bias, especially since mortality and heart failure hospitalizations were not significantly different. However, the magnitude of benefit in QOL measures was more than expected with a placebo effect and it persisted for one year, which would be unlikely for a placebo effect. Also, the association of the improved QOL outcomes with the degree of TR reduction and the observation that the magnitude of benefit was greatest among those with a low KCCQ at baseline supports the results.
In addition, no exploration of right ventricular function or other hemodynamic factors was done. One hopes that the upcoming imaging substudy will elucidate these issues. Finally, there is no detailed description of medical therapy in the comparator group. Almost all were on diuretics, which is the mainstay of medical therapy, but the intensity of follow-up management is not described.
In my experience, managing these patients medically takes frequent follow-up visits and careful regulation of diuretics and their off-target effects (e.g., low potassium). Surprisingly, two-thirds of the patients were on beta-blockers for unclear reasons since they are unlikely to reduce TR and could impair right ventricular function. Clearly, we need more information before T-TEER becomes the standard of care for severe symptomatic TR.
REFERENCE
- Sorajja P, Whisenant B, Hamid N, et al. Transcatheter repair for patients with tricuspid regurgitation. N Engl J Med 2023;388:1833-1842.
