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Science Matters
In our monthly series, editorial team member Dr. Michael Katsnelson MD, PhD, FACC provides a summary of recently published clinical research article.
Research Summary of the TRILUMINATE Pivotal Randomized Trial
About the Author: Michael Katsnelson MD, PhD, FACC is currently a research fellow at Washington University in St. Louis School of Medicine. He specializes in advanced heart failure/transplant cardiology and his main research interest lies in studying the role of the innate immune system in the progression of ischemic cardiomyopathy.
Background: There is currently a dearth of evidence regarding the optimal therapy for tricuspid regurgitation (TR) in patients with heart failure. Currently the only class I guideline dealing with the management of TR recommends the surgical repair/replacement of the tricuspid valve in the setting of severe TR or dilation of the tricuspid annulus and concomitant left sided valve surgery. Isolated tricuspid valve surgery is associated with a high degree of morbidity/mortality due to a variety of medical comorbidities and frailty present in patients with severe TR. The systemic veins have a large capacity for absorbing excess volume and patients with severe TR typically live for years without experiencing symptoms. They tend to present with fatigue, dyspnea or lower extremity edema when the disease process has progressed to the advanced stages. Furthermore, the chronic venous congestion present in patients with severe TR results in renal and hepatic dysfunction which further increases the surgical risk. Consequently, there has been a great deal of interest in the development of minimally invasive transcatheter interventions including tricuspid transcatheter edge-to-edge repair (T-TEER). This technique utilizes a device to grasp and approximate the valve leaflets, thus decreasing the coaptation gap and reducing the degree of TR.
Study Design: The TRILUMINATE Pivotal Trial was an international multi-center randomized clinical trial performed in patients with symptomatic severe TR. The trial utilized the TriClip transcatheter system for TEER. The patients were randomized in a 1:1 ratio to medical therapy plus TriClip device or medical therapy alone. The degree of TR pre and post procedure was graded into one of five categories: mild, moderate, severe, massive or torrential. Major adverse events were assessed including cardiovascular mortality, new-onset renal failure, endocarditis requiring surgery or a TriClip related complication including device embolization or thrombosis. Prespecified secondary endpoints included recurrent heart failure hospitalization, freedom from all-cause mortality, freedom from tricuspid valve surgery and freedom from tricuspid valve intervention at 2 years of follow-up.
Results: A majority of patients enrolled in the trial had multiple medical comorbidities, diminished quality of life as evidenced by the KCCQ score, and symptomatic heart failure NYHA class III/IV. Most of the patients had evidence of massive or torrential TR noted on echocardiography. The study demonstrated a significant reduction in the risk of heart failure hospitalization in the device treated group compared to those patients treated with medical therapy alone. Freedom from all cause mortality, tricuspid valve surgery and tricuspid valve interventions was significantly higher in the device treated group compared to the optimal medical therapy group and this was primarily driven by a reduction in the need for tricuspid valve intervention. In the device treated group, 84% of patients were able to achieve a sustained reduction in the degree of TR to the mild or moderate range. Patients in the device treated group achieved a significantly higher improvement in the KCCQ score compared to patients treated with medical therapy alone. This improvement in quality of life was evident within 30 days following the procedure and sustained throughout the two-year follow up period. Adverse events including stroke, TIA, need for tricuspid valve surgery, cardiogenic shock and new conduction abnormality requiring permanent pacemaker implantation were similar in the device treated and control groups.
Significance of Findings: The study demonstrated that TEER is a safe and effective therapy to decrease recurrent heart failure hospitalization and improve symptoms in patients with right sided heart failure and severe TR. Interestingly, the divergence in rates of heart failure hospitalization between the device treated and medical therapy group did not occur until after one year of follow-up, suggesting that he beneficial effects of TEER on right ventricular remodeling may not be observed until years following the procedure. Overall mortality was not affected by TEER as patients in both the device treated and medical therapy groups experienced similar mortality rates compared to the age-matched general population. The authors of the study allowed patients in the optimal medical therapy group to cross over to the device group after one year of follow-up. Indeed, close to 60% of the patients who started the trial in the medical therapy arm crossed over to the device treatment group during the second year of follow-up. Therefore the effect of TEER on heart failure hospitalization may have been attenuated as patients with greater degrees of TR and more heart failure symptoms crossed over into the device treatment group following one year of medical therapy. Nonetheless, the study demonstrated that treatment of patients with severe TR using the TriClip system resulted in symptomatic improvement and a reduction in the rate of heart failure hospitalization. Continued monitoring of this patient cohort over the next several years may demonstrate beneficial effects on overall mortality and end-organ function.
Link to Article - https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.125.074536
