Transcatheter Repair for Patients with Tricuspid Regurgitation (TRILUMINATE Pivotal)

Authors, Journal, Affiliations, Type, DOI

• Authors: Sorajja P, Whisenant B, Hamid N, Naik H, Makkar R, Tadros P, Price MJ, Singh G, Fam N, Kar S, Schwartz JG, Mehta S, Bae R, Sekaran N, Warner T, Makar M, Zorn G, Spinner EM, Trusty PM, Benza R, Jorde U, McCarthy P, Thourani V, Tang GHL, Hahn RT, Adams DH; for the TRILUMINATE Pivotal Investigators
• Journal: N Engl J Med 2023;388:1833–42
• Published: March 4, 2023 (updated May 18, 2023)
• Affiliations: 65 centres — Minneapolis Heart Institute, Intermountain Medical Center, Cedars-Sinai, Scripps, UC Davis, McMaster, Northwestern, Columbia, Mount Sinai, Piedmont/Marcus Valve Center, and others in USA, Canada, and Europe
• Type: International, prospective, randomized, controlled trial (pivotal)
• Funding: Abbott Structural Heart
• DOI: https://doi.org/10.1056/NEJMoa2300525
• ClinicalTrials.gov: NCT03904147

Overview

TRILUMINATE Pivotal is the foundational pivotal RCT (N=350, 1:1 randomization) establishing the TriClip transcatheter tricuspid edge-to-edge repair (TEER) system as superior to medical therapy alone for symptomatic severe TR. Win ratio was 1.48 (95% CI 1.06–2.13, P=0.02), driven entirely by QoL improvements (KCCQ ≥15-point improvement 49.7% vs 26.4%; mean KCCQ change +12.3 vs +0.6 points). TR was reduced to ≤moderate in 87.0% at 30 days with excellent safety: 98.3% MAE-free, no increase in pacemaker implantation (2.9% both groups), no device embolization or thrombosis. Importantly, no significant difference was seen in mortality (9.4% vs 10.6%) or HF hospitalization rate — the control group had a marginally lower rate (0.21 vs 0.17 events/patient-year).

Keywords

Tricuspid regurgitation, transcatheter edge-to-edge repair, TEER, TriClip, TRILUMINATE Pivotal, win ratio, KCCQ, quality of life, tricuspid valve surgery, heart failure hospitalization

Key Takeaways

Background

• Severe TR associated with substantial morbidity, impaired cardiac output, congestive right heart failure, fatigue, peripheral edema, and poor long-term survival
• Medical therapy largely limited to diuretics; surgery carries 8–10% operative mortality (national registry data) and patients often present late with RV/hepatorenal dysfunction
• Prior non-randomized registry studies showed TEER reduced TR and improved symptoms, but RCT data vs medical therapy were lacking
• ACC/AHA 2020 at time of trial: Class I surgical recommendation only for TR at time of left-heart surgery; no transcatheter class recommendation

Methods — Trial Design

• Design: International, prospective, randomized, controlled, open-label trial; 1:1 randomization; 65 centres in USA, Canada, and Europe; August 2019 – September 2021
• Sample size: N=350 (175 TEER vs 175 control); 84% power; prespecified reestimation confirmed adequacy
• Device: TriClip Transcatheter Tricuspid Valve Repair system (Abbott); 25-French femoral venous delivery catheter; one or more clips apposes leaflets permanently; performed under general anesthesia with echo + fluoroscopic guidance
• Procedural details: TEER performed within 14 days of randomization; mean 2.2±0.7 clips/patient; mean device time 90±66 minutes; median hospital stay 1.0 day (IQR 1.0–2.0)
• Follow-up: 1, 6, 12 months; 5-year follow-up planned; symptom assessment + 6MWT + KCCQ at each visit
• Analysis population: Intention-to-treat (all randomized); per-protocol, as-treated, and attempted-procedure sensitivity analyses also performed

Methods — Patients

• Eligibility: Symptomatic (NYHA II/III/IVa) severe TR confirmed by independent echo lab; PA systolic pressure <70 mm Hg; ≥30 days stable GDMT; no other CV condition requiring intervention; intermediate or greater surgical risk (local heart team assessment); mandatory right heart catheterization
• Baseline characteristics: Mean age 78±7 years (range 51–96); 54.9% women; 90.0% AF; 80.9% hypertension; 93.9% functional TR
• Echocardiographic baseline: Mean LVEF 59.0±9.9%; CO 4.2±1.2 L/min; RV end-diastolic diameter 5.1±0.8 cm; TV annular diameter 4.4±0.7 cm; RA volume 148.1±84.3 ml; 70.7% had massive or torrential TR (grade 4–5)
• Clinical history: 36.9% prior mitral or aortic valve interventions; 25.1% HF hospitalization in prior year; 14.9% prior CIED

Methods — Primary and Secondary Endpoints

• Primary (hierarchical composite, win ratio method):
  1. Death from any cause or TV surgery
  2. HF hospitalization
  3. KCCQ improvement ≥15 points at 1 year
• Powered secondary endpoints (tested hierarchically after primary significance):
  1. Freedom from MAE at 30 days (performance goal ≥90%)
  2. Change from baseline KCCQ score at 1 year
  3. TR reduction to ≤moderate at 30 days
  4. Change from baseline 6MWD at 1 year
• MAE definition: CV death, new-onset kidney failure, endocarditis treated with surgery, non-elective CV surgery for TriClip-related adverse event

Results — Primary Endpoint (1 Year)

• Win ratio: 1.48 (95% CI 1.06–2.13; P=0.02) favouring TEER
• Raw wins: 11,348 (TEER) vs 7,643 (control) with 11,634 ties
• Death/TV surgery: 9.4% TEER vs 10.6% control (KM) — no significant difference
• HF hospitalization rate: 0.21/pt-yr TEER vs 0.17/pt-yr control — no significant difference (control marginally lower)
• KCCQ ≥15-point improvement: 49.7% (73/147) TEER vs 26.4% (39/148) control — primary driver of win ratio
• Results consistent across sensitivity analyses (as-treated, per-protocol, COVID-19 sensitivity)

Results — Secondary and Additional Endpoints

• Freedom from MAE at 30 days: 98.3% (169/172) in attempted-procedure population — exceeded 90% performance goal (P<0.001); 3 MAE: 2 new-onset renal failure, 1 CV death
• Mean KCCQ change at 1 year: +12.3±1.8 (TEER) vs +0.6±1.8 (control); P<0.001
  • Without imputation: +15.2±22.3 vs +4.8±18.3
• TR ≤moderate at 30 days: 87.0% (140/161) TEER vs 4.8% (7/146) control (P<0.001)
• TR ≤moderate at 1 year: 88.1% (126/143) TEER vs 5.7% (8/141) control
• NYHA class I/II at 1 year: 83.9% (125/149) TEER vs 59.5% (88/148) control
• 6MWD change at 1 year: −8.1±10.5 m TEER vs −25.2±10.3 m control (P=0.25, NS)
  • Without imputation: +11.5±111.4 m TEER vs −8.7±109.7 m control

Results — QoL Correlated with Degree of TR Reduction (Key Insight)

• TR ≤moderate at 1 year: mean KCCQ +15.6±22.0 pts
• TR severe/massive/torrential at 1 year: mean KCCQ +3.8±18.4 pts
• ≥2 grade TR reduction: mean KCCQ +18 pts
• 1 grade reduction: mean KCCQ +6 pts
• No change in TR: mean KCCQ +2 pts
• TR worsened: mean KCCQ ~0 pts
• Implication: The magnitude of TR reduction directly determines QoL benefit; residual TR limits clinical gain

Results — Procedural Outcomes

• Device implantation success: 98.8% (170/172 attempted-procedure patients)
• 3 patients withdrew consent before procedure
• 97.7% discharged home; 4 to nursing home; 0 procedural deaths
• Single-leaflet device attachment: 7.0% (12/172) within 30 days — no subsequent events; no associated MAEs at 12 months
• Tricuspid mean gradient ≥5 mm Hg: 8 patients at 30 days — no clinical symptoms, no intervention required
• No device embolization or thrombosis in any patient

Results — Safety Profile (1 Year)

• Pacemaker rate identical in both groups (2.9%) — TEER does not increase conduction risk
• Echo core laboratory was aware of group assignments (potential grading bias for TR severity)

Discussion

• The win ratio of 1.48 was driven by QoL improvement; neither mortality nor HF hospitalization differed between groups
• HF hospitalization lower than predicted in both groups — possibly Hawthorne effect or rigorous patient selection (RHC-mandated eligibility, clear attribution of symptoms to TR)
• TR reduction durability was maintained at 1 year in the majority (88.1% ≤moderate)
• The QoL–TR correlation is clinically important: greater TR reduction produces proportionally better QoL gains, motivating complete TR elimination strategies
• The open-label design is a limitation, though follow-up assessors were blinded; echo core lab was aware of group assignments, a potential source of TR grading bias

Limitations

• Open-label trial — potential for ascertainment bias in QoL reporting despite blinded follow-up assessment
• Echo core laboratory not blinded to group assignments — potential TR severity grading bias
• Conducted during COVID-19 pandemic; COVID-19 sensitivity analysis performed (results similar)
• Enrolled patients anatomically and hemodynamically selected — may not generalize to all TR anatomies (large coaptation gaps, complex anatomy, CIED leads)
• Not powered for mortality or HF hospitalization individually
• HF hospitalization lower than predicted in both groups — may reflect patient selection, Hawthorne effect, or inadequate statistical power for this endpoint
• 5-year follow-up needed to determine whether QoL benefit translates into survival benefit

Key Concepts Mentioned

• concepts/Tricuspid-Regurgitation — primary subject; TriClip TEER vs medical therapy; win ratio; QoL-TR correlation; safety
• concepts/Valvular-Heart-Disease — broader guideline context
• concepts/RV-PA-Coupling — RV function selection criterion (PA systolic pressure <70 mm Hg required)

Key Entities Mentioned

• entities/Atrial-Fibrillation — 90.0% prevalence; functional TR dominant aetiology
• entities/Heart-Failure — HF hospitalization endpoint; GDMT requirement at enrollment

Wiki Pages Updated

• wiki/sources/tvteer-triluminate-nejm-2023.md — created
• wiki/sourceindex.md — new entry added
• wiki/wikiindex.md — Tricuspid-Regurgitation entry updated
• wiki/concepts/Tricuspid-Regurgitation.md — TRILUMINATE section expanded with primary citation, QoL-TR correlation data, and safety detail; source_count 5→6