Interleukin-6, soluble interleukin-6 receptor, and outcomes after transcatheter aortic valve implantation: an exploratory biomarker substudy of a prospective multicenter cohort

Severe aortic stenosis can be treated with transcatheter aortic valve implantation (TAVI). Identifying clinical and laboratory factors that predict clinical outcomes after TAVI may facilitate more informed decision-making. We aimed to assess the incidence of major adverse cardiac and cerebrovascular events (MACCE) within 12 months after TAVI and long-term survival according to baseline interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels. In this biomarker substudy of a prospective multicenter cohort, we evaluated clinical outcomes after TAVI according to baseline IL-6 signal and sIL-6R concentration. We included only patients with an available baseline stored plasma sample. Patients were stratified into high and low IL-6 and sIL-6R groups. Two primary end points were analyzed: (i) 12-month MACCE, and (ii) long-term overall survival. Secondary end points included the individual components of MACCE. Stored baseline plasma was available for measurements in 62 patients who underwent TAVI between December 2018 and September 2021 across three clinical sites. Patients with high IL-6 had a higher 12-month MACCE risk in age- and sex-adjusted Firth penalized Cox regression analysis (HR 3.31; 95%CI 1.02–11.04, P = 0.0458) but not in unadjusted analysis (log-rank P = 0.07). The association was not robust to alternative cutoffs and the age- and sex-adjusted continuous analysis of IL-6 also did not show a statistically significant association (hazard ratio per 1-SD increase, 1.52, 95% CI, 0.86 to 2.46, P = 0.13). No significant associations were observed in the primary models between IL-6 and long-term overall survival or between sIL-6R and either primary end point. High IL-6 signal at baseline may be associated with increased 12-month MACCE risk after TAVI, although this finding was sensitive to IL-6 categorization and was not statistically significant in continuous analysis. Baseline sIL-6R concentration was not significantly associated with the analyzed clinical outcomes. These findings should be considered exploratory and hypothesis-generating.