Transcatheter Valve Replacement in Severe Tricuspid Regurgitation (TRISCEND II)

Authors, Journal, Affiliations, Type, DOI

• Authors: Hahn RT, Makkar R, Thourani VH, Makar M, Sharma RP, Haeffele C, Davidson CJ, Narang A, O'Neill B, Lee J, Yadav P, Zahr F, Chadderdon S, Eleid M, Pislaru S, Smith R, Szerlip M, Whisenant B, Sekaran NK, Garcia S, Stewart-Dehner T, Thiele H, Kipperman R, Koulogiannis K, Lim DS, Fowler D, Kapadia S, Harb SC, Grayburn PA, Sannino A, Mack MJ, Leon MB, Lurz P, Kodali SK; for the TRISCEND II Trial Investigators
• Journal: N Engl J Med 2025;392:115–26
• Published: January 9, 2025 (online October 30, 2024)
• Affiliations: 45 centres — Columbia University, Cedars-Sinai, Piedmont Heart Institute, Northwestern, Henry Ford, Mayo Clinic, Baylor Scott and White, Intermountain, Cleveland Clinic, Heart Center Leipzig, and others in USA and Germany
• Type: Multinational, prospective, randomized, controlled trial (pivotal; FDA Breakthrough Device Program)
• Funding: Edwards Lifesciences
• DOI: https://doi.org/10.1056/NEJMoa2401918
• ClinicalTrials.gov: NCT04482062

Overview

TRISCEND II is a pivotal international RCT (N=400, 2:1 randomization) comparing the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy versus medical therapy alone in patients with severe symptomatic tricuspid regurgitation. At 1 year, TTVR was superior on a hierarchical composite primary outcome (win ratio 2.02, 95% CI 1.56–2.62, P<0.001), driven primarily by quality-of-life improvements. TR was reduced to mild or less in 95.2% of TTVR patients. Key periprocedural risks included severe bleeding (15.4% vs 5.3%) and new permanent pacemaker implantation (17.4% vs 2.3%); no significant mortality benefit was demonstrated at 1 year, as the trial was not powered for individual endpoints.

Keywords

Tricuspid regurgitation, transcatheter tricuspid valve replacement, EVOQUE system, TRISCEND II, win ratio, KCCQ-OS, NYHA functional class, 6-minute walk distance, pacemaker implantation, severe bleeding, right ventricular reverse remodeling, hierarchical composite outcome

Key Takeaways

Background

• Severe TR is associated with disabling symptoms and increased mortality; isolated TV surgery is performed infrequently and patients often present late with high operative mortality
• Tricuspid TEER (T-TEER) vs medical therapy (TRILUMINATE Pivotal) demonstrated QoL benefit; however T-TEER often leaves residual TR and greater residual TR correlates with worse outcomes
• TTVR reduces TR to mild or less in >95% of patients and may offer greater TR elimination than TEER
• TRISCEND II was designed to compare EVOQUE TTVR + medical therapy vs medical therapy alone

Methods

• Design: International, multicenter, prospective RCT; 2:1 randomization (TTVR + medical therapy vs medical therapy alone); 45 centres in USA and Germany; May 2021–April 2023
• Sample size: 400 patients randomized (267 TTVR, 133 control); procedure attempted in 259 TTVR patients
• Phased analysis: Initial 150 patients = FDA Breakthrough Device Pathway cohort (safety at 30 days; TR + QoL at 6 months); full 400-patient cohort analyzed here at 1 year
• Eligibility: Age ≥18, severe TR (scale 0–5: none/trace/mild/moderate/severe/massive/torrential), symptoms or HF hospitalization despite medical therapy, anatomically suitable for EVOQUE
• Key exclusions: Severely depressed RV systolic function; eGFR ≤25 ml/min/1.73m²; long-term renal replacement therapy; prior heart transplant; life expectancy <12 months; anatomy precluding device delivery
• Baseline characteristics: Mean age 79.2 years; 75.5% women; 94.9% atrial fibrillation; mean STS mortality score 9.7%; >50% had massive or torrential TR at baseline
• Post-procedure anticoagulation: Warfarin or anticoagulant + aspirin recommended for ≥6 months
• Follow-up: 30 days, 6 months, 1 year (annual follow-up through 5 years planned)
• Primary outcome (hierarchical composite, win ratio method):
  1. Death from any cause
  2. Durable RVAD implantation or heart transplantation
  3. Post-index TV surgery or percutaneous TV intervention
  4. Annualized rate of HF hospitalization
  5. KCCQ-OS improvement ≥10 points
  6. NYHA functional class improvement ≥1 class
  7. 6-minute walk distance improvement ≥30 m
• Statistical analysis: Finkelstein–Schoenfeld method for significance (α=0.05); win ratio for effect size; 80.9% power for 400 patients; modified intention-to-treat population

Results — Primary Composite (1 Year)

• Win ratio: 2.02 (95% CI 1.56–2.62; P<0.001) favouring TTVR
• Win breakdown (TTVR wins vs control wins):
  • Death from any cause: 14.8% vs 12.5%
  • Post-index TV intervention: 3.2% vs 0.6%
  • KCCQ-OS ≥10-point improvement: 23.1% vs 6.0%
  • NYHA ≥1 class improvement: 10.2% vs 0.8%
  • 6MWD ≥30 m improvement: 1.1% vs 0.9%
  • HF hospitalization rate: 9.7% vs 10.0% (control had more wins here — TTVR did NOT win on HF hospitalization)
  • No patients in either group received RVAD or heart transplantation

Results — Kaplan–Meier Clinical Outcomes (1 Year)

• All-cause mortality: 12.6±2.1% (TTVR) vs 15.2±3.3% (control) — directionally favourable, not powered for significance
• Landmark analysis (from 30 days): Death at 1 year 9.4±1.9% (TTVR) vs 15.2±3.3% (control) — periprocedural 30-day mortality accounts for early divergence
• HF hospitalization: 20.9±2.6% vs 26.1±4.1%
• Death or first HF hospitalization: 28.4±2.8% vs 33.3±4.3%
• Death or post-index TV intervention: 13.7±2.2% vs 20.8±3.7%

Results — Functional and Quality-of-Life Outcomes (1 Year)

• KCCQ-OS ≥10-point improvement: 66.4% (TTVR) vs 36.5% (control); mean increase 18.4 points (95% CI 15.4–21.4)
• NYHA ≥1 class improvement: 78.9% vs 24.0%
• 6MWD ≥30 m improvement: 47.6% vs 31.8%; mean increase 23.2 m (95% CI 9.4–37.1)

Results — Echocardiographic Outcomes (1 Year)

• TTVR group TR severity at 1 year: No TR 72.6%; mild 22.6%; moderate 3.8%; severe 0.9% → TR ≤mild in 95.2%
• Control group TR severity at 1 year: Mild 2.3%; moderate 13.8%; severe 41.4%; massive 19.5%; torrential 23.0%
• RV reverse remodeling (TTVR vs control):
  • RV end-diastolic dimension: −5.8 mm (95% CI −7.3 to −4.3) vs 0.0 mm (95% CI −1.8 to 1.8)
  • IVC expiration diameter: −4.8 mm (95% CI −5.8 to −3.9) vs −0.3 mm (95% CI −1.5 to 1.0)
  • TAPSE: −4.2 mm (95% CI −5.0 to −3.4) vs −0.2 mm (95% CI −1.4 to 1.0) — decrease expected as afterload increases with TR elimination
  • RV fractional area change: −9.3% (95% CI −11.0 to −7.5) vs −3.9% (95% CI −6.2 to −1.6)
• Reduction in markers of liver congestion also noted at 1 year

Results — Safety Outcomes

• Death causes (TTVR): HF in 10 (6 biventricular, 4 RV dysfunction), infection/sepsis 4, stroke 2, thromboembolism 2, major bleeding 1, cancer 1, other
• Pacemaker types (TTVR, no prior pacemaker, n=45 new PPMs): Single-chamber leadless 18, single-chamber 11, dual-chamber 8, dual-chamber leadless 1, triple-chamber (CRT) 6
• Between 31 and 365 days, severe bleeding rates were similar: 5.3% (TTVR) vs 4.7% (control) — suggesting excess bleeding is predominantly periprocedural (anticoagulation + antiplatelet protocol)
• Gastrointestinal bleeding rates exceed 15/100 patient-years in medically treated TR patients (>80% on long-term anticoagulation, >20% cirrhosis)

Discussion

• The win ratio of 2.02 was driven primarily by QoL (KCCQ-OS) and functional (NYHA) improvements, exceeding the magnitude of improvement reported after T-TEER
• TR reduction was achieved even though >50% of patients had massive or torrential TR at baseline; patients with the highest baseline TR severity had the largest win ratio increases
• Favorable RV reverse remodeling (RV EDD −5.8 mm, IVC −4.8 mm) was observed, potentially influencing long-term outcomes; remaining RV contractile function was associated with increases in forward stroke volume
• Pacemaker rate (17.8% at 30 days, 27.8% in those without prior pacemaker) is similar to rates after surgical TV repair (6–14%) and replacement (15–34%); prior studies show PPM after surgical TV replacement does not worsen long-term survival
• Periprocedural anticoagulation: Excess 30-day bleeding (10.4%) likely attributable to protocol recommending anticoagulant + antiplatelet; after protocol modification at one site, 30-day bleeding decreased without increased valve thrombosis
• The trial was not powered to detect mortality or HF hospitalization differences; the numerical trends were favourable but non-significant

Limitations

• 2:1 randomization → small control group (n=133), further reduced by disproportionate withdrawals and crossovers after 1 year
• Crossovers allowed after 1-year visit — may introduce survival bias in longer-term follow-up
• Not powered for individual endpoints (mortality, HF hospitalization)
• High prevalence of hypertension, AF, and LVEF >50% suggests many patients had atrial secondary TR (lower mortality subtype vs ventricular) — may confound mortality comparisons
• Protocol-defined mITT excluded 8 post-randomization patients (no attempted procedure)
• Early operator inexperience may have exaggerated procedural complication rates
• May not be generalizable to patients with more varied anatomies and coexisting conditions

Key Concepts Mentioned

• concepts/Tricuspid-Regurgitation — primary subject; EVOQUE TTVR vs medical therapy; win ratio 2.02; TR reduction; RV reverse remodeling
• concepts/Valvular-Heart-Disease — broader context; guideline framework
• concepts/RV-PA-Coupling — RV function assessment before and after TTVR (afterload mismatch risk)

Key Entities Mentioned

• entities/Atrial-Fibrillation — 94.9% prevalence in cohort; atrial secondary TR subtype
• entities/Heart-Failure — primary symptom driver; HF hospitalization endpoint
• entities/TAVI — Edwards Lifesciences funding; structural heart disease programme context

Wiki Pages Updated

• wiki/sources/ttvr-triscendii-nejm-2025.md — created
• wiki/sourceindex.md — new entry added
• wiki/wikiindex.md — Tricuspid-Regurgitation entry updated (date 2026-05-19; TRISCEND II data added)
• wiki/concepts/Tricuspid-Regurgitation.md — TRISCEND II 1-year RCT data added; contradictions updated; source_count 4→5