PB0017 - High prevalence and wide variety of clonal haematopoiesis-driver mutations in patients with severe aortic valve stenosis undergoing transcatheter aortic valve replacement

Sunday, July 10, 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
ND

Nicolas Duployez

PharmD, PhD
Department of Hematology, CHU Lille, F-59000 Lille
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
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
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
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
CP

Claude Preudhomme

PharmD, PhD
Department of Hematology, CHU Lille, F-59000 Lille
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
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

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 (AVS), the most common acquired heart valve disease, is now considered as an active process of valve calcification mediating by chronic inflammation and similar to atherosclerosis. Clonal hematopoiesis of indeterminate potential (CHIP), defined by the presence of somatic mutations in hematopoietic stem cells without other hematologic abnormalities, was detected in 10 to 20% of general population aged>70 years and has been associated with atherosclerosis and inflammation. One recent study has reported the presence of mutations in CHIP-genes, DNMT3A and TET2 in a third of patients with severe AVS and an association with mortality following transcatheter aortic valve replacement (TAVR), a procedure that elicits a thromboinflammatory state.

Aims: To assess the full profile of CHIP-driver genes in AVS patients undergoing TAVR and determine whether CHIP is associated with thromboinflammatory state biological features (blood cell count, systemic inflammation/thrombosis markers).

Methods: High-throughput sequencing of a 67-genes panel was performed on blood-DNA from 270 AVS patients, free of hematological malignancy and undergoing TAVR (age: 82±7 years, 42% male).

Results: A total of 444 mutations (with a variant allele frequency > 1%) in 35 genes were detected in 202 of 270 patients (CHIP prevalence: 50%, 71% and 78% of patients aged < 70 years, 70-80 years and >80 years). Despite a high prevalence of mutations in the most frequently mutated genes DNMT3A (129 patients, 48%) and TET2 (117 patients, 43%), mutations in PPM1D, ASXL1, SF3B1, TP53, CBL and SRSF2 were also identified in at least 5% of patients. However, the presence of CHIP was not associated with thromboinflammatory state biological features.

Conclusion(s): This study shows that CHIP prevalence is very high in AVS patients undergoing TAVR. These new data support the inflammatory and atherosclerotic background of AVS. Future studies clarifying the relationships between CHIP, AVS development and TAVR complications are needed.