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Daniela Pedicino, Rocco Vergallo, Transcatheter repair for severe tricuspid regurgitation: are we going in the right direction?, European Heart Journal, Volume 44, Issue 23, 14 June 2023, Pages 2064–2065, https://doi.org/10.1093/eurheartj/ehad219
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Comment on the article ‘Transcatheter repair for patients with tricuspid regurgitation’, which was published in the New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2300525.
The Trial to Evaluate Cardiovascular Outcomes in Patients Treated with the Tricuspid Valve Repair System Pivotal (TRILUMINATE Pivotal) is a company-funded, open-label, randomized, controlled trial (RCT) aiming to compare percutaneous tricuspid transcatheter edge-to-edge repair (T-TEER) vs. medical therapy in symptomatic patients with severe tricuspid regurgitation (TR).1
Patients with symptomatic severe TR were enrolled at 65 centres in the USA, Canada, and Europe and were randomized in a 1:1 ratio to receive either T-TEER with the TriClip Transcatheter Tricuspid Valve Repair system (Abbott Vascular) or medical therapy. Inclusion criteria were: echocardiographic evidence of severe TR at an independent laboratory, a New York Heart Association (NYHA) functional class II to IVa, a pulmonary artery systolic pressure <70 mmHg, stable treatment with guideline-directed medical therapy for heart failure (HF) for at least 30 days, no other cardiovascular disease requiring interventional or surgical correction (e.g. severe aortic stenosis or mitral regurgitation), intermediate or greater risk for surgery as defined by the local Heart Team.
The primary endpoint was a hierarchical composite including all-cause death or tricuspid-valve surgery, hospitalization for HF, and an improvement in quality of life (QoL, defined as an increase of at least 15 points in the Kansas City Cardiomyopathy Questionnaire, KCCQ) at 1-year follow-up. Secondary endpoints included: freedom from major adverse events (defined as cardiovascular death, renal failure, endocarditis requiring surgery, and device-related adverse event requiring surgery) within 30 days (T-TEER group only), the change from baseline in the KCCQ score at 1-year follow-up, and a reduction in TR severity to moderate or less within 30 days.
A total of 350 patients (mean age, 78 years; 55% female) were enrolled between August 2019 and September 2021 (175 T-TEER, and 175 medical therapy). The vast majority (94%) of patients had functional TR, and 25% had been hospitalized for HF in the previous year. The severity of TR was categorized as grade 4 or 5 (massive or torrential) in 71% of patients. The device was successfully implanted in 99% of cases, with a mean of 2.2 clips per patient. The median length of stay in the hospital was 1 day. The primary endpoint favoured the T-TEER group as compared with the control group [win ratio, 1.48; 95% confidence interval (CI), 1.06 to 2.13; P = 0.02]. The incidence of all-cause death or tricuspid valve surgery at 1 year was not different between the T-TEER group and medical therapy group (9.4% vs. 10.6%; P = 0.75). The rate of HF hospitalization was 0.21 events per patient-year in the T-TEER group and 0.17 events per patient-year in the control group.
An increase in KCCQ ≥15 points was recorded in 50% of patients in the T-TEER group and in 26% of those in the medical therapy group (P < 0.001). Change in KCCQ score from baseline to 1 year was significantly greater in the T-TEER group than in the control group (12.3 vs. 0.6 points; P < 0.001), with consistent findings across subgroups based on demographic and clinical variables, haemodynamic characteristics, and right heart size and function. The improvement in QoL was directly related to the degree of TR reduction. At 30 days, the percentage of patients with TR of no greater than moderate severity was 87% in the T-TEER group and 5% in the medical therapy group (P < 0.001). At 30 days, 98% of patients treated with T-TEER were free from major adverse events, with no device embolization or thrombosis. Three major adverse events occurred within 30 days: new-onset kidney failure in two patients and one death from cardiovascular cause.
Comment
The negative effects of TR have been neglected for a long time. However, recent evidence showed that its prevalence (0.6%) is very close to that of severe aortic stenosis and, if left untreated, is associated with poor QoL and high mortality.2 These premises, in combination with the high perioperative mortality of surgery (4%–17%), shifted the attention towards percutaneous therapy.3 Of note, current European guidelines suggest considering transcatheter tricuspid valve interventions as a possible therapy for secondary TR in inoperable patients, to be performed at experienced Heart Valve Centres (Class IIb).4
T-TEER, first with MitraClip (Abbott Vascular) device and, more recently, with dedicated TriClip (Abbott Vascular) devices, represents the most used technology so far, with good safety profile.5 The TRILUMINATE Pivotal is the first RCT in symptomatic patients with at least severe TR; it shows that T-TEER is safe and effective in reducing TR and improving QoL at 1 year.1 In this regard, an important limitation is represented by the open-label design of the study with a high probability of a biased perception of symptom relief amongst the patients receiving the percutaneous intervention as compared to those in the medical therapy group. Moreover, despite a significant TR reduction, only a modest decrease in diuretic dosage was recorded over 1 year. Alongside, the feasibility and safety data with up to 98% of patients remaining free from major adverse events at 30 days should be interpreted considering that the study had been conducted in highly experienced centres.
There were no apparent between-group differences in mortality or in the rate of HF hospitalization at 1 year, and both outcomes occurred less frequently than predicted when the trial was designed. Thus, larger and adequately powered studies with longer follow-up will be needed to understand the real impact of this procedure on mortality and HF hospitalization.
It should also be considered that there were improvements in device design during the study, with about half of the patients in the T-TEER arm treated with the first-generation TriClip system and half with the newer TriClip G4. Moreover, most (∼70%) of the enrolled patients had either massive or torrential TR with right ventricular dilatation (mean right ventricular end-diastolic diameter 50 mm) and dysfunction (∼50% patients with tricuspid annular plane systolic excursion <17 mm). This might suggest that, in more advanced disease, percutaneous treatment no longer impacts prognosis. However, the results of this trial do not allow drawing any indication on which kind of patients might benefit most from T-TEER and in which stage of the disease the procedure is expected to produce optimal results.6 Indeed, these findings raise a key point in the treatment of valvular heart diseases: the right time of intervention. The history of trials of the percutaneous treatment of mitral regurgitation has shown us the significant improvements in outcomes that follow longer experience, with better devices and better imaging. Moreover, the evidence from both mitral and tricuspid valves taught us how patient selection and time of intervention are important to achieve successful results.3,7,8 Currently, no univocal indications exist on treatment for TR, and only a few algorithms have been proposed.9,10 The poor knowledge of the disease, combined with scarce experience with the tricuspid valve and the absence of symptoms until a very advanced stage of TR, is probably responsible for patients being referred to the Heart Valve Center too late for tricuspid intervention.
In this perspective, the results of the TRILUMINATE Pivotal trial should be considered encouraging although longer term follow-up will be essential to draw more solid conclusions, possibly based on hard endpoints and/or objective measures of functional status.
References
Author notes
Conflicts of interest D.P. received speaker’s fees from Daiichi-Sankyo, outside the submitted work. R.V. received consulting or lecturing fees from Abbott Vascular, Amgen, and Terumo, outside the submitted work.
