{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T02:46:02Z","timestamp":1794192362954,"version":"4.8.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,9,3]],"date-time":"2019-09-03T00:00:00Z","timestamp":1567468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Excellence Cluster of Cardiopulmonary Systems"},{"DOI":"10.13039\/100010447","name":"German Centre for Cardiovascular Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Clonal haematopoiesis of indeterminate potential (CHIP), defined as the presence of an expanded somatic blood cell clone without other haematological abnormalities, was recently shown to increase with age and is associated with coronary artery disease and calcification. The most commonly mutated CHIP genes, DNMT3A and TET2, were shown to regulate inflammatory potential of circulating leucocytes. The incidence of degenerative calcified aortic valve (AV) stenosis increases with age and correlates with chronic inflammation. We assessed the incidence of CHIP and its association with inflammatory blood cell phenotypes in patients with AV stenosis undergoing transfemoral aortic valve implantation (TAVI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Targeted amplicon sequencing for DNMT3A and TET2 was performed in 279 patients with severe AV stenosis undergoing TAVI. Somatic DNMT3A- or TET2-CHIP-driver mutations with a VAF \u2265 2% were detected in 93 out of 279 patients (33.3%), with an age-dependent increase in the incidence from 25% (55\u201369\u2009years) to 52.9% (90\u2013100\u2009years). Patients with DNMT3A- or TET2-CHIP-driver mutations did not differ from patients without such mutations in clinical parameters, concomitant atherosclerotic disease, blood cell counts, inflammatory markers, or procedural characteristics. However, patients with DNMT3A- or TET2-CHIP-driver mutations had a profoundly increased medium-term all-cause mortality following successful TAVI. Differential myeloid and T-cell distributions revealed pro-inflammatory T-cell polarization in DNMT3A-mutation carriers and increased pro-inflammatory non-classical monocytes in TET2-mutation carriers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This is the first study to show that acquired somatic mutations in the most commonly mutated CHIP-driver genes occur frequently in patients with severe degenerative AV stenosis, are associated with increased pro-inflammatory leucocyte subsets, and confer a profound increase in mortality following successful TAVI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz591","type":"journal-article","created":{"date-parts":[[2019,8,8]],"date-time":"2019-08-08T07:35:19Z","timestamp":1565249719000},"page":"933-939","source":"Crossref","is-referenced-by-count":228,"title":["Clonal haematopoiesis in patients with degenerative aortic valve stenosis undergoing transcatheter aortic valve implantation"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3828-8180","authenticated-orcid":false,"given":"Silvia","family":"Mas-Peiro","sequence":"first","affiliation":[{"name":"Department of Medicine, Cardiology, Goethe University Hospital , Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"},{"name":"German Centre for Cardiovascular Research, Berlin, Partner Site Frankfurt Rhine-Main , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedrzej","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Goethe University Hospital , Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"},{"name":"German Centre for Cardiovascular Research, Berlin, Partner Site Frankfurt Rhine-Main , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Fichtlscherer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Goethe University Hospital , Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"},{"name":"German Centre for Cardiovascular Research, Berlin, Partner Site Frankfurt Rhine-Main , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Dorsheimer","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haematology\/Oncology, Goethe University Hospital , Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael A","family":"Rieger","sequence":"additional","affiliation":[{"name":"Department of Medicine, Haematology\/Oncology, Goethe University Hospital , Frankfurt, Germany"},{"name":"Frankfurt Cancer Institute, Frankfurt , Germany"},{"name":"German Cancer Consortium and German Cancer Research Centre , Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Dimmeler","sequence":"additional","affiliation":[{"name":"German Centre for Cardiovascular Research, Berlin, Partner Site Frankfurt Rhine-Main , Germany"},{"name":"Institute for Cardiovascular Regeneration, Goethe University , Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariuca","family":"Vasa-Nicotera","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Goethe University Hospital , Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"},{"name":"German Centre for Cardiovascular Research, Berlin, Partner Site Frankfurt Rhine-Main , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas M","family":"Zeiher","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Goethe University Hospital , Theodor-Stern-Kai 7, 60590 Frankfurt, Germany"},{"name":"German Centre for Cardiovascular Research, Berlin, Partner Site Frankfurt Rhine-Main , Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,3]]},"reference":[{"key":"2022102610534692700_ehz591-B1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1182\/blood-2015-03-631747","article-title":"Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes","volume":"126","author":"Steensma","year":"2015","journal-title":"Blood"},{"key":"2022102610534692700_ehz591-B2","doi-asserted-by":"crossref","first-page":"2488","DOI":"10.1056\/NEJMoa1408617","article-title":"Age-related clonal hematopoiesis associated with adverse outcomes","volume":"371","author":"Jaiswal","year":"2014","journal-title":"N Engl J Med"},{"key":"2022102610534692700_ehz591-B3","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMoa1701719","article-title":"Clonal hematopoiesis and risk of atherosclerotic cardiovascular 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