P930Inflammatory leukocyte phenotypes are associated with increased mortality after transfemoral transcatheter aortic valve implantation
Authors: Hoffmann J , Mas-Peiro S , Boeckling F , Rasper T , Berkowitsch A , Fichtlscherer S , Dimmeler S , Zeiher A M , Vasa-Nicotera M 
Published: October 2019

Abstract

Background
Systemic inflammatory response syndrome (SIRS) was shown to be a strong predictor of mortality in patients undergoing transcatheter aortic valve implantation (TAVI). However, given the rather non-specific nature of the SIRS criteria and their limited applicability in the modern era of TAVI, including lower periprocedural complication rates and shorter hospitalization periods in experienced competence centers, there is a need for defining novel prognostic inflammatory signatures for improved patient risk stratification. Thus, the objective of the present study was to characterize and assess the prognostic relevance of circulating leukocyte subsets, including phenotypical heterogeneity of monocytes and effector T cells, before and at various times after transfemoral TAVI.

Methods and results
129 consecutive patients (59% male, mean age 82.3±5.6 years) with severe symptomatic aortic stenosis (Pmean 44.2±17mmHg), and high or prohibitive operative risk (mean EuroSCORE II 5.9; STS score 4.1) admitted to our clinic for TAVI were included into the study. Peripheral blood samples were obtained pre-procedurally (baseline, BL), directly after the intervention, and at 24h and 3 days after TAVI, and analyzed for inflammatory and cardiac biomarkers, including hs-CRP, IL-6, hs-TropT, and NT-proBNP. Differential myeloid and T-cell subset (Th1, Th2, Th17, Th1/Th17, Th22, Tregs) distribution and kinetics were analyzed using multiparameter flow cytometry. Neutrophil (P<0.001 vs. BL) as well as classical and intermediate monocyte counts were significantly elevated at 24h (both p<0.0001 vs. BL), whereas non-classical monocytosis developed 3 days after TAVI (P<0.0001 vs. BL). Among CD4+ T-cell subsets, the percentage of Tregs and Th17 significantly increased (both P<0.0001 at 24h vs. BL) after valve implantation. Remarkably, these changes were independent on the valve type (balloon- vs. self-expandable) and no significant effects of predilatation were observed (p>0.05 for all cell subsets). Univariate analysis showed that elevated levels of NT-proBNP (HR: 3.4, 95% CI: 1.7–6.8; P=0.0005), hsCRP (HR: 1.4, 95% CI: 1.2–1.7; P=0.0003), and IL-6 (HR: 1.0, 95% CI: 1.0–1.03; P=0.0007), lower counts of Th2 cells (HR: 0.94, 95% CI: 0.90–0.94; P=0.0045), as well as increased percentages of Th17 cells (HR: 1.2, 95% CI: 1.0–1.4; P=0.023), and of non-classical monocytes (HR=1.019, 95% CI: 1.001–1.039; P=0.049) were independently associated with 12-month all-cause mortality. When included in the regression model with STS score, these inflammatory biomarkers provided higher area under ROC curve and category-free net reclassification improvementof 59% at 1 year (P=0.0001).
ROC curves inflammation markers add STS

Conclusions
Our findings demonstrate for the first time an association of inflammatory leukocyte phenotypes with increased mortality after TAVI. Specific monocytic and T-cell signatures might therefore provide novel additive biomarkers to improve individual risk stratification in patients with severe aortic stenosis.