Abstract 17056: Hierarchical Clustering of ‘Inflammaging’ Markers Reveals Pro-Inflammatory Cytokines to Associate With Outcome Independent of Chronologic Age After TAVR

Abstract

Background: Aortic valve stenosis (AVS) is an age-related disease lacking effective causal therapies. Aging is linked to cellular senescence, which leads to the secretion of the “senescence-associated secretory phenotype” (SASP). Recent evidence suggests a connection between AVS and SASP expression. Aim: The study aimed to assess expression patterns and the prognostic impact of SASP components in patients undergoing transcatheter valve replacement (TAVR) for severe AVS. Methods: We analyzed 12 SASP components in plasma from 320 patients undergoing TAVR between February 2017 and September 2021, using the Luminex® Assay (Bio-Techne, Germany). Follow-Up was conducted up to 3 years after TAVR with all-cause mortality as the primary endpoint. Hierarchical clustering was performed to identify patterns of SASP expression, and clusters were analyzed for their impact on survival, associations with age and frailty of patients. Significant covariates (p<0.1), as identified by univariate regression, were included in the AFT model for survival analyses. Results: The patients’ median age was 83.2 years (95%CI 82.4 - 83.9), with 39.7% being female. Hierarchical clustering revealed 3 main clusters, characterized by circulating concentrations of pro-inflammatory cytokines (Fig. A). Clusters with higher levels of pro-inflammatory SASP components showed worse survival after adjusting for covariates (COPD, previous stroke, NYHA class, eGFR, anemia) (Fig. B). Patients’ age did not differ between clusters, but those in clusters with higher levels of pro-inflammatory markers were more likely to be frail (Fig. C). Conclusion: In elderly patients undergoing TAVR for severe AVS, pro-inflammatory SASP components are associated with worse survival, independent of chronologic age. These findings suggest a role of cellular senescence and markers of ‘inflammaging’ in outcomes of patients with AVS and might also enhance risk stratification in patients with AVS undergoing TAVR.