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This cohort study aimed to evaluate the mutational landscape of CHIP and its\u2019 influence on clinical outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>194 patients with AVS undergoing transcatheter aortic valve replacement (TAVR) were sequenced using a capture panel for multiple CH driver mutations and follow up conducted for three years.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>We found high prevalences (77.8%) of a broad spectrum of CH-driver mutations across 38 genes, with 34% of patients fulfilling the diagnostic criteria for CHIP. Evaluating the impact of CHIP driver mutations on outcomes, the presence of CHIP was associated with mortality only when adjusting for confounding factors (HR: 2.143, 95% CI: 1.029\u20134.461, p\u2009=\u20090.042), while the presence of CH driver mutations at low VAF showed no association with mortality (p\u2009=\u20090.377). However, when excluding <jats:italic>DNMT3A-<\/jats:italic>CHIP, we found a significant association of CHIP with mortality in univariate (p\u2009=\u20090.022) and multivariable (HR: 2.976, 95% CI: 1.381\u20136.411, p\u2009=\u20090.005) analyses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>As the first study to evaluate a broad spectrum of CH driver mutations at all variant allele frequencies in the context of aortic valve stenosis, we found CHIP to be a frequent phenomenon and CH-driver mutations to be highly prevalent in patients with severe AVS. CHIP, other than <jats:italic>DNMT3A<\/jats:italic>-CHIP, was associated with increased mortality even after successful TAVR. The presence of CH driver mutations at low allele frequencies was not associated with mortality.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1007\/s00392-025-02658-9","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T14:54:20Z","timestamp":1746456860000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Mutational landscape and impact of clonal hematopoiesis of indeterminate potential in severe aortic valve stenosis"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-2084-8463","authenticated-orcid":false,"given":"Ra\u00fal Nicolas","family":"Jamin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baravan","family":"Al-Kassou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Kleuker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Shamekhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedikt","family":"Bartsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar","family":"Ackerschott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muntadher","family":"Al Zaidi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Billig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus Moritz","family":"Graef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malte","family":"Kelm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Baldus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Nickenig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eicke","family":"Latz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Zimmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"2658_CR1","doi-asserted-by":"publisher","first-page":"1002","DOI":"10.1016\/j.jacc.2013.05.015","volume":"62","author":"RLJ Osnabrugge","year":"2013","unstructured":"Osnabrugge RLJ, Mylotte D, Head SJ et al (2013) Aortic stenosis in the elderly. 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