Liver extracellular volume improves after transcatheter tricuspid valve intervention: seminal insights from TRILUMINATE Pivotal imaging substudy

Background

Severe tricuspid regurgitation (TR) causes systemic venous and liver congestion promoting extracellular matrix expansion. Liver extracellular volume (L-ECV) quantified by cardiac magnetic resonance (CMR) is a non-invasive assessment of hepatic extracellular matrix remodeling and a prognostic marker of congestion which was recently shown to be associated with adverse outcomes in TR patients. The clinical impact of tricuspid intervention and the subsequent changes in TR severity following treatment with tricuspid transcatheter edge-to-edge repair (T-TEER) on L-ECV has not been previously described.

Methods

TRILUMINATE Pivotal is the first randomized (1:1) trial evaluating T-TEER (TriClip) vs guideline-directed medical therapy (GDMT) alone in symptomatic, severe TR patients. A concurrent single-arm cohort enrolled patients with complex anatomy for T-TEER. A pre-specified, prospective multicentric imaging substudy was conducted at 10 sites, which included CMR and 4D-CT evaluation of cardiac anatomy and function at baseline and 30 days post-treatment, and a final 4D-CT at 1 year. L-ECV was assessed by identifying liver parenchyma on short-axis cardiac T1 mapping pre- and post-contrast carefully excluding artifacts and blood pool/vessels. Imaging was randomly analyzed by an independent core lab without knowledge of TR reduction.

Results

Forty-five patients with evaluable baseline L-ECV (mean age 78 years; 69% female; hypertension 78%; renal disease 31%; MELD-XI score 12 pts) were included (T-TEER=28, GDMT alone=17). Right-sided adverse cardiac remodeling was observed, with a right ventricular (RV) end-diastolic volume of 210 ± 81 mL, a right atrial (RA) end-diastolic volume of 176 ± 98 mL, and a mean tricuspid valve anatomic regurgitant orifice area of 83 ± 60 mm². Median (Q1, Q3) baseline L-ECV was 34% (31, 39). L-ECV was positively correlated with TR volume (r=0.50, p=0.0005), RV and RA end-diastolic volumes (r=0.54, p=0.0001 and r=0.35, p=0.02, respectively), and MELD-XI score (r=0.51, p=0.0004) at baseline.

At 30 days, L-ECV decreased significantly in T-TEER treated patients (-2% on average, p=0.046), whereas in GDMT patients a significant increase was observed (+3% on average, p=0.007). Between-group difference favored T-TEER after adjusting for baseline L-ECV (p=0.0005). A greater proportion of T-TEER patients experienced L-ECV reduction (61% vs 25%), while most GDMT patients experienced an increase (63% vs 30%). Of note, traditional liver biomarkers including ALT, AST and bilirubin showed no significant changes over time in either treatment group.

Conclusions

In the TRILUMINATE Pivotal imaging substudy, most patients with severe TR who received T-TEER with TriClip had demonstrable improvement of L-ECV within 30-days. L-ECV improvement associated with TR reduction and RV reverse remodeling provides additional objective evidence supporting the clinical benefit of T-TEER in these patients.