PB1258 - Modulation of monocytes inflammatory and hemostatic phenotype after transcatheter aortic valve replacement and consequences on post-procedural complications

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

FL

Fanny Lassalle

PharmD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
FV

Flavien Vincent

MD, PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
MR

Mickael Rosa

PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
AR

Antoine Rauch

MD, PhD
Univ.Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
FD

Florent Dumezy

PharD
Department of Hematology, CHU Lille
Lille, Nord-Pas-de-Calais, France
CR

Christophe Roumier

PharmD
Department of Hematology, CHU Lille
Lille, Nord-Pas-de-Calais, France
DD

David Dombrowicz

PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
CG

Celine Gheeraert

PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
PL

Philippe Lefebvre

PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
BS

Bart Staels

PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
AV

André Vincentelli

MD, PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
EV

Eric Van Belle

MD, PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011- EGID, F-59000 Lille, France
Lille, Nord-Pas-de-Calais, France
Sophie Susen, MD, PhD

Professor, MD, PhD
CRC-MHC, Lille University Hospital, Lille, France
Lille, Nord-Pas-de-Calais, France

Presenting Author(s)

AD

Annabelle Dupont, Pharm D PhD

PharmD, PhD
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, F5900 Lille, France
59000 Lille, Nord-Pas-de-Calais, France

Background: Aortic valve stenosis, the most common valvular disorder in the elderly, leads to a very disturbed blood flow (low arterial pulsatility, high shear stress). Its treatment consists in a transcatheter aortic valve replacement (TAVR) allowing an immediate reopening of the valve with sudden pulsatility and shear stress correction. However, TAVR remains an inflammatory procedure, whose main post-procedural complications are bleeding and thrombosis involving mechanisms poorly understood. Recently, a close link between blood coagulation and innate immune system has been described, termed immunothrombosis, including monocytes as major actor.

Aims: To study the modulation of circulating monocytes phenotype due to acute changes of blood flow conditions in order to better understand the mechanisms involved in post-procedural complications of TAVR.

Methods: Patients who underwent TAVR were included in the study (NCT02628509). We studied the circulating monocytes subpopulations repartition by flow cytometry before (T0) and one day after TAVR (D1) for 36 patients and performed transcriptomic analysis of classical monocytes at T0 and D1 for 12 patients after cell sorting.

Results: We observed an increase of monocytes levels at D1 versus T0 (p < 0.0001), linked to an increase of classical (CD14++CD16-) and intermediate (CD14++CD16+) monocytes (p < 0.0001 for both). High preprocedural rates of intermediate monocytes were associated with one-year mortality whereas high postprocedural levels of non-classical monocytes (CD14+CD16++) were associated with bleeding or thrombotic complications at one month. Transcriptomic analysis revealed 267 up- and 28 down-regulated genes at D1 versus T0. The most upregulated genes encoded for leukocyte activation and inflammatory response and among genes implicated in coagulation, THBD (thrombomodulin) and F5 (factor V) were the 2 most upregulated genes.

Conclusion(s): TAVR modulates monocytes inflammatory and hemostatic phenotype in link with TAVR post-procedural complications suggesting that immunothrombosis processes play a role in the occurrence of TAVR post-procedural complications.