Negative Impact of TET2 Mutations on Long-Term Survival After Transcatheter Aortic Valve Replacement

Fanny Lassalle; Nicolas Duployez; Flavien Vincent; Antoine Rauch; Tom Denimal; Mickael Rosa; Julien Labreuche; David Dombrowicz; Bart Staels; Claude Preudhomme; Sophie Susen; Eric Van Belle; Annabelle Dupont

doi:10.1016/j.jacbts.2023.04.010

Negative Impact of TET2 Mutations on Long-Term Survival After Transcatheter Aortic Valve Replacement

JACC Basic Transl Sci. 2023 Jul 19;8(11):1424-1435. doi: 10.1016/j.jacbts.2023.04.010. eCollection 2023 Nov.

Affiliations

¹ University of Lille, Inserm, Centre Hospitalier Universitaire Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
² Unite Mixte de Recherche (UMR) 9020-UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Institut de Recherche contre le Cancer de Lille, University of Lille, CNRS, Inserm, Centre Hospitalier Universitaire Lille, Lille, France.
³ Department of Biostatistics, Centre Hospitalier Universitaire Lille, Lille, France.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is considered as being a novel age-related risk factor for cardiovascular diseases. By capture-sequencing of a 67-gene panel, we established a large spectrum of CHIP in 258 patients with aortic valve stenosis undergoing transcatheter aortic valve replacement (TAVR) and assessed their association with long-term survival after TAVR. One or several CHIP variants in 35 genes were identified in 68% of the cohort, DNMT3A and TET2 being the 2 most frequently mutated genes. Patients carrying a TET2-CHIP-driver variant with low variant allele frequency (2%-10%) had a significant decrease in overall survival 5 years after TAVR.

Keywords: aortic valve stenosis; clonal hematopoiesis; survival; transcatheter aortic valve replacement.