TY  - JOUR
A1  - Hoffmann, Jedrzej
A1  - Mas-Peiro, Silvia
A1  - Berkowitsch, Alexander
A1  - Böckling, Felicitas Juana
A1  - Rasper, Tina
A1  - Pieszko, Konrad
A1  - De Rosa, Roberta
A1  - Hiczkiewicz, Jarosław
A1  - Burchardt, Paweł
A1  - Fichtlscherer, Stephan
A1  - Zeiher, Andreas M.
A1  - Dimmeler, Stefanie
A1  - Vasa-Nicotera, Mariuca
T1  - Inflammatory signatures are associated with increased mortality after transfemoral transcatheter aortic valve implantation
T2  - ESC heart failure
N2  - Aims: Systemic inflammatory response, identified by increased total leucocyte counts, was shown to be a strong predictor of mortality after transcatheter aortic valve implantation (TAVI). Yet the mechanisms of inflammation-associated poor outcome after TAVI are unclear. Therefore, the present study aimed at investigating individual inflammatory signatures and functional heterogeneity of circulating myeloid and T-lymphocyte subsets and their impact on 1 year survival in a single-centre cohort of patients with severe aortic stenosis undergoing TAVI. Methods and results: One hundred twenty-nine consecutive patients with severe symptomatic aortic stenosis admitted for transfemoral TAVI were included. Blood samples were obtained at baseline, immediately after, and 24 h and 3 days after TAVI, and these were analysed for inflammatory and cardiac biomarkers. Myeloid and T-lymphocyte subsets were measured using flow cytometry. The inflammatory parameters were first analysed as continuous variables; and in case of association with outcome and area under receiver operating characteristic (ROC) curve (AUC) ≥ 0.6, the values were dichotomized using optimal cut-off points. Several baseline inflammatory parameters, including high-sensitivity C-reactive protein (hsCRP; HR = 1.37, 95% CI: 1.15–1.63; P < 0.0001) and IL-6 (HR = 1.02, 95% CI: 1.01–1.03; P = 0.003), lower counts of Th2 (HR = 0.95, 95% CI: 0.91–0.99; P = 0.009), and increased percentages of Th17 cells (HR = 1.19, 95% CI: 1.02–1.38; P = 0.024) were associated with 12 month all-cause mortality. Among postprocedural parameters, only increased post-TAVI counts of non-classical monocytes immediately after TAVI were predictive of outcome (HR = 1.03, 95% CI: 1.01–1.05; P = 0.003). The occurrence of SIRS criteria within 48 h post-TAVI showed no significant association with 12 month mortality (HR = 0.57, 95% CI: 0.13–2.43, P = 0.45). In multivariate analysis of discrete or dichotomized clinical and inflammatory variables, the presence of diabetes mellitus (HR = 3.50; 95% CI: 1.42–8.62; P = 0.006), low left ventricular (LV) ejection fraction (HR = 3.16; 95% CI: 1.35–7.39; P = 0.008), increased baseline hsCRP (HR = 5.22; 95% CI: 2.09–13.01; P < 0.0001), and low baseline Th2 cell counts (HR = 8.83; 95% CI: 3.02–25.80) were significant predictors of death. The prognostic value of the linear prediction score calculated of these parameters was superior to the Society of Thoracic Surgeons score (AUC: 0.88; 95% CI: 0.78–0.99 vs. 0.75; 95% CI: 0.64–0.86, respectively; P = 0.036). Finally, when analysing LV remodelling outcomes, ROC curve analysis revealed that low numbers of Tregs (P = 0.017; AUC: 0.69) and increased Th17/Treg ratio (P = 0.012; AUC: 0.70) were predictive of adverse remodelling after TAVI. Conclusions: Our findings demonstrate an association of specific pre-existing inflammatory phenotypes with increased mortality and adverse LV remodelling after TAVI. Distinct monocyte and T-cell signatures might provide additive biomarkers to improve pre-procedural risk stratification in patients referred to TAVI for severe aortic stenosis.
KW  - Inflammation
KW  - T cells
KW  - Monocytes
KW  - Aortic stenosis
KW  - TAVI
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/63947
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-639472
SN  - 2055-5822
N1  - SFB834 funding to Stefanie Dimmeler and Mariuca Vasa-Nicotera and Cardiopulmonary Systems (CPI, Exc2026) by the German Research Foundation (Deutsche Forschungsgemeinschaft). This study was also supported by a postdoctoral grant by the DZHK (Bundesministerium für Bildung und Forschung).
VL  - 7
IS  - 5
SP  - 2597
EP  - 2610
PB  - Wiley
CY  - Chichester
ER  -