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Published in: Clinical Research in Cardiology 5/2023

Open Access 21-01-2023 | Aortic Valve Stenosis | Original Paper

Long-term risk associated with clonal hematopoiesis in patients with severe aortic valve stenosis undergoing TAVR

Authors: Silvia Mas-Peiro, Graziella Pergola, Alexander Berkowitsch, Manja Meggendorfer, Michael A. Rieger, Mariuca Vasa-Nicotera, Stefanie Dimmeler, Andreas M. Zeiher

Published in: Clinical Research in Cardiology | Issue 5/2023

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Abstract

Background

Mutations in the clonal hematopoiesis of indeterminate potential (CHIP)-driver genes DNMT3A and TET2 have been previously shown to be associated with short-term prognosis in patients undergoing TAVR for aortic valve stenosis. We aimed to extend and characterize these findings on long-term outcome in a large cohort.

Methods

A total of 453 consecutive patients undergoing TAVR were included in an up to 4-year follow-up study. Next-generation sequencing was used to identify DNMT3A- and/or TET2-CHIP-driver mutations. Primary endpoint was all-cause mortality. Since CHIP-driver mutations appear to be closely related to DNA methylation, results were also assessed in patients who never smoked, a factor known to interfere with DNA methylation.

Results

DNMT3A-/TET2-CHIP-driver mutations were present in 32.4% of patients (DNMT3A n = 92, TET2 n = 71), and were more frequent in women (52.4% vs. 38.9%, p = 0.007) and older participants (83.3 vs. 82.2 years, p = 0.011), while clinical characteristics or blood-derived parameters did not differ. CHIP-driver mutations were associated with a significantly higher mortality up to 4 years after TAVR in both univariate (p = 0.031) and multivariate analyses (HR 1.429, 95%CI 1.014–2.013, p = 0.041). The difference was even more pronounced (p = 0.011) in never smokers. Compared to TET2 mutation carriers, patients with DNMT3A mutations had significantly less frequently concomitant coronary and peripheral artery disease.

Conclusion

DNMT3A- and TET2-CHIP-driver mutations are associated with long-term mortality in patients with aortic valve stenosis even after a successful TAVR. The association is also present in never smokers, in whom no biasing effect from smoking on DNA methylation is to be expected.

Graphical Abstract

Appendix
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Literature
27.
go back to reference Raddatz MA, Silver AJ, Farbereger E et al (2021) Clonal hematopoiesis is associated with incident severe aortic stenosis. Circulation 144:A9334 Raddatz MA, Silver AJ, Farbereger E et al (2021) Clonal hematopoiesis is associated with incident severe aortic stenosis. Circulation 144:A9334
Metadata
Title
Long-term risk associated with clonal hematopoiesis in patients with severe aortic valve stenosis undergoing TAVR
Authors
Silvia Mas-Peiro
Graziella Pergola
Alexander Berkowitsch
Manja Meggendorfer
Michael A. Rieger
Mariuca Vasa-Nicotera
Stefanie Dimmeler
Andreas M. Zeiher
Publication date
21-01-2023
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 5/2023
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-022-02135-7

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