Associations between blood cell-based inflammatory indices and their changes and mortality in patients undergoing transcatheter aortic valve replacement: a retrospective investigation with prospective multicenter cohort validation study

BACKGROUND: Chronic inflammation is a driver of cardiovascular diseases, including valvular calcification. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil percentage-to-albumin ratio (NPAR) are promising markers of systemic inflammation. However, research on the predictive value of dynamic changes in these indices for clinical outcomes in patients undergoing transcatheter aortic valve replacement (TAVR) remains limited. MATERIALS AND METHODS: This study employed a retrospective single-center cohort (2012-2023, n = 1629) with validation in a prospective multicenter cohort (2023-2024, n = 443). The primary endpoint was all-cause mortality. All participants were stratified into tertiles based on pre- and post-TAVR values of NLR, PLR, and NPAR. Multivariate Cox proportional hazards regression models and restricted cubic spline (RCS) models were used to assess associations of pre-TAVR, post-TAVR, and dynamic changes in these three composite inflammatory markers with mortality. Receiver operating characteristic (ROC) curves and time-dependent Harrell's C-index were applied to evaluate the time-varying predictive value of these markers for mortality. RESULTS: Multivariable-adjusted Cox regression models showed that the highest tertile of inflammatory markers (both pre- and post-TAVR) was associated with a higher risk of all-cause mortality than the lowest tertile (pre-TAVR: NLR, aHR = 1.61, P = 0.032; PLR, aHR = 1.88, P = 0.003; NPAR, aHR = 1.69, P = 0.027). Multivariable-adjusted Cox regression and ROC analysis showed that post-TAVR inflammatory markers demonstrated a greater predictive value for mortality than pre-TAVR values. Time-dependent Harrell's C-index analysis showed high and time-constant predictive values of the pre- and post-TAVR NLR, PLR, and NPAR for mortality. An increase in post-TAVR inflammatory markers from baseline was associated with a sharp rise in mortality risk. Replicate analyses in the multicenter prospective cohort validated the robustness of the findings from our single-center analysis. CONCLUSIONS: Post-TAVR NLR, PLR, and NPAR exhibit superior predictive value for mortality compared to pre-TAVR values, with NPAR being the most powerful predictor. Measurement of these three blood cell-based composite inflammatory markers enables precise risk stratification of TAVR patients. Further interventional studies targeting these markers, especially NPAR, are warranted.