Blog

TRILUMINATE Trial

CardioNerds Journal Club is a monthly forum for CardioNerds to discuss and breakdown recent publications on twitter and are produced with a corresponding infographic and detailed blog post. For more information, check out the CardioNerds Journal Club Page. This Journal Club focuses on the TRILUMINATE Trial

Table of contents for the The TRILUMINATE Trial summary:

TRILUMINATE TRIAL - CardsJC

Transcatheter Repair for Patients with Tricuspid Regurgitation: The TRILUMINATE Pivotal Randomized clinical trial

March 4, 2023

Authors: Paul Sorajja, Brian Whisenant, Nadira Hamid, Hursh Naik, Raj Makkar, Peter Tadros, Matthew J. Price, Gagan Singh, Neil Fam, Saibal Kar, Jonathan G. Schwartz, Shamir Mehta, Richard Bae, Nishant Sekaran, Travis Warner, Moody Makar,George Zorn, Erin M. Spinner, Phillip M. Trusty, Raymond Benza, Ulrich Jorde, Patrick McCarthy, Vinod Thourani, Gilbert H.L. Tang, Rebecca T. Hahn, and David H.Adams

Link to Manuscript: https://www.nejm.org/doi/full/10.1056/NEJMoa2300525

  • Untreated severe tricuspid regurgitation (TR) has been associated with poor quality of life and long-term survival. 1
  • Severe TR can  cause right sided heart failure  leading to fatigue and peripheral edema.
  • Per the 2021 European Society of Cardiology and European Association for Cardiothoracic Surgery guidelines, for patients who are symptomatic with isolated, severe TR without severe right ventricular dysfunction, surgery is a class I recommendation. 2
  • However, many patients present more clinically decompensated despite the use of intravenous diuretics that increase the risk of surgery including right ventricular dysfunction and hepatorenal dysfunction
  • Mortality rates for isolated tricuspid valve surgery have ranged from 8-10% in certain studies.3, 4
  • Treatment of TR with transcatheter edge-to-edge repair (TEER)  uses a transvenous approach and approximates the tricuspid valve leaflets by using a clip to hold the leaflets together, to reduce the amount of actual regurgitation
  • Initial single-arm studies of TEER have shown significant reduction in amount of TR, hospitalization rates, NYHA class, 6-minute walk test, and symptoms. 5, 6

Current Guidelines for surgical treatment of TR

Study Rationale

  • The clinical benefit of TEER compared to conservative therapy (ie, diuretics) in severe, isolated TR is unknown.

Objective

The TRILUMINATE study aims to evaluate the safety and effectiveness of TEER in symptomatic patients with severe TR compared to medical therapy alone.

Trial:

  • International, multi-center randomized controlled trial

Intervention

  • Tricuspid TEER was done with the TriClip Tricuspid Valve Repair system, with a 25-French delivery catheter to place one or more TriClip devices on the tricuspid-valve leaflets. The goal was to permanently appose the tricuspid valve leaflets with the use of echocardiographic and fluoroscopic guidance.
  • The procedure was done via the femoral vein and patients were placed under general anesthesia.

Enrollment Criteria

  • Patients with TR that was confirmed by an independent echocardiography lab as severe, were symptomatic (NYHA class II-IV), had a pulmonary artery systolic pressure < 70 mmHg, received stable (≥ 30 days) guideline-directed medical therapy for heart failure, had no other cardiovascular conditions in need of surgical correction (i.e., severe aortic stenosis or mitral regurgitation), and were at intermediate or greater surgical risk.
  • Surgical risk was determined by the local heart team, which consisted of board-certified specialists in cardiac surgery, interventional cardiology, echocardiography, and heart failure.
  • Clinical follow up was done at 1, 6, and 12 months with each appointment aimed at the assessment of symptoms, 6-minute walk test, and quality-of-life measurement with the Kansas City Cardiomyopathy Questionnaire (KCCQ).

Statistical Analysis

  • A sample of 350 patients would provide 84% power to show superiority of TEER to the control, with a two-sided alpha level of 0.05. 
  • Primary endpoint analysis was done with  the Finkelstein-Schoenfeld method and a win ratio, along with the use of the intention-to-treat population based on their assigned treatment.
  • Analyses were also done in a per-protocol population, as-treated population, and an attempted-procedure population.

Participant Characteristics:

  • Mean age – 78±7 years (51- 96 years)
  • Women – 54.9%
  • Functional tricuspid regurgitation – 323/344 (93.9%)
  • Hypertension – 283 patients (80.9%)
  • Atrial fibrillation – 315 patients (90%)
  • Previous mitral or aortic valve interventions – 129 patients (36.9%)
  • Hospitalization for heart failure <1 year of enrollment – 88 patients (25.1%)
  • History of cardiac implantable electronic rhythm device – 52 patients (14.9%)

Outcomes

Conclusions

  • Tricuspid TEER is safe in patients with severe TR, reduced the severity of TR to moderate or less and was associated with a significant improvement in quality of life.
  • TEER with TriClip may be a promising minimally invasive therapy for patients with severe TR who are not eligible for tricuspid valve surgery.

Limitations & Considerations

  • Potential bias in patient’s perception of their health status in open-label design.
  • Hawthorne effect may have contributed to improved management of the disease in the intervention arm.
  • Results may not apply to patients with anatomical or hemodynamic findings that differ from those utilized in selection criteria during enrollment into trial.
  • Long-term follow up is required to assess survival and hospitalizations for heart failure beyond 1 year.
  • There is a need for future studies to help identify which patients and specifically anatomies are most suited to treatment.
  1. Topilsky Y, Maltais S, Medina Inojosa J, et al. Burden of tricuspid regurgitation in patients diagnosed in the community setting. JACC Cardiovasc Imaging 2019;12:433-442.
  2. Vahanian A, Beyersdorf F, Praz F, et al. 2021 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J 2022;43:561-632.
  3. Zack CJ, Fender EA, Chandrashekar P, et al. National trends and outcomes in isolated tricuspid valve surgery. J Am Coll Cardiol 2017;70:2953-2960.
  4. Kilic A, Saha-Chaudhuri P, Rankin JS, Conte JV. Trends and outcomes of tricuspid valve surgery in North America: an analysis of more than 50,000 patients from the Society of Thoracic Surgeons database. Ann Thorac Surg 2013;96:1546-1552.
  5. Nickenig G, Weber M, Lurz P, et al. Transcatheter edge-to-edge repair for reduction of tricuspid regurgitation: 6-month outcomes of the TRILUMINATE single-arm study. Lancet 2019;394:2002-2011.
  6. Lurz P, Stephan von Bardeleben R, Weber M, et al. Transcatheter edge-to-edge repair for treatment of tricuspid regurgitation. J Am Coll Cardiol 2021;77:229-239.
You are currently viewing TRILUMINATE Trial