Inflammatory signatures are associated with increased mortality after transfemoral transcatheter aortic valve implantation

Abstract

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 cutoff 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 ...

Differential systemic inflammatory responses after TAVI: The role of self versus balloon expandable devices

“…Previous studies have reported that developing a systemic inflammatory response syndrome (SIRS) after transcatheter valve implantation (TAVI) is associated with poor prognosis [ 1 – 7 ]. In recent years, much effort has gone into improving existing prognostic models for risk stratification of patients undergoing TAVI.…”

Prognostic value of systemic inflammatory response syndrome after transcatheter aortic valve implantation

“…SIRS was more frequent in patients with adverse short-term outcome and was independently associated with long-term mortality. Previous studies reported a variable prevalence of SIRS after TAVI ranging from 10 to 73% 4,5,12–15 . Several possible mechanisms can concur to cause SIRS.…”

Impact of Systemic Inflammatory Response Syndrome on Clinical, Echocardiographic, and Computed Tomographic Outcomes Among Patients Undergoing Transcatheter Aortic Valve Implantation

“…A recent subgroup analysis of the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) trial showed that IL-1β-targeting therapy may decrease heart failure-related hospitalization and mortality ( 38 ). Lately, a proof-of-concept study, showed, for the first time, an association of specific inflammatory phenotypes (immune signatures) with increased mortality after TAVI ( 39 ). Thus, suggesting that distinct monocyte and T-cell signatures might stand as novel biomarkers to be considered in risk stratifying patients with severe aortic stenosis undergoing TAVI, and possibly guiding potential anti-inflammatory treatment.…”