The Association Between Inflammatory Indices and Mortality in Patients with Moderate-to-Severe Tricuspid Regurgitation

BackgroundTricuspid regurgitation (TR) is a common valvular lesion associated with high mortality, yet readily accessible prognostic biomarkers remain scarce. We aimed to evaluate the associations of the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) with long-term mortality in patients with moderate-to-severe TR. MethodsIn this retrospective cohort (TRAIL study, NCT06926959), 1,349 patients with moderate-to-severe TR were followed for a median of 4.9 years. Multivariable Cox regression and restricted cubic spline analyses assessed the associations between log-transformed SII/NLR and all-cause mortality. Missing covariates were handled by multiple imputation. ResultsDuring follow-up, 523 deaths (39%) occurred. Each one-unit increase in log-transformed SII (LnSII) and NLR (LnNLR) was associated with a 26% (Hazard Ratio (HR)=1.26, 95% Confidence Interval (CI)=1.14-1.41) and 57% (HR=1.57, 95% CI: 1.39-1.77) increased risk of all-cause mortality, respectively. Compared to the lowest quartile, the highest quartile conferred a 45% increased risk for SII (HR=1.45, 95% CI: 1.13-1.85) and a 126% increased risk for NLR (HR=2.26, 95% CI: 1.72-2.97). Restricted cubic splines revealed non-linear relationships (P-nonlinearity=0.009 for SII; P=0.016 for NLR) with inflection points at LnSII=5.553 and LnNLR=0.466. The association of NLR was stronger in non-hypertensive patients (P-interaction=0.006), while SII remained consistent across subgroups. ConclusionsElevated SII and NLR are independently associated with increased all-cause mortality in moderate-to-severe TR, with NLR exhibiting enhanced predictive value in non-hypertensive individuals. These inexpensive indices may improve risk stratification and guide management. Clinical PerspectiveWhat Is New? O_LIThis study is the first to explore the association between the systemic immune-inflammation index (SII) and neutrophil-to-lymphocyte ratio (NLR) and mortality in patients with moderate-to-severe tricuspid regurgitation (TR). C_LIO_LIWe identified a non-linear relationship with clear risk thresholds and found that the prognostic power of NLR was significantly stronger in non-hypertensive patients. C_LI What Are the Clinical Implications? O_LISII and NLR provide a simple, low-cost tool for improved risk stratification in clinical practice. C_LIO_LIThese findings highlight systemic inflammation as a potential therapeutic target in TR management. C_LIO_LIAssessment of hypertension status could help personalize the application of these biomarkers, particularly for NLR. C_LI