{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T20:38:38Z","timestamp":1773866318050,"version":"3.50.1"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">The cause of chronic thromboembolic pulmonary hypertension (CTEPH) remains largely unknown. Recently, clonal hematopoiesis (CH) has been reported to be associated with cardiovascular and thromboembolic diseases. Here, we investigated the prevalence and clinical impact of CH in patients with CTEPH.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Whole\u2010exome sequencing and deep\u2010panel sequencing were performed in 214 patients with CTEPH. Clinical data before and after treatment were compared between patients with and without CH. RNA sequencing and serum analysis were performed to explore the pathogenesis that CH contributes to CTEPH. Among the enrolled patients, 20.1%, notably 44.4% who were 80 to 89\u2009years old, had variants in CH\u2010associated genes. In regard to clinical impact, B\u2010type natriuretic peptide levels and home oxygen therapy rate were significantly higher, and 6\u2010minute walk distance was significantly shorter after treatment in patients with CH than in those without CH. Moreover, novel clot reformation in the pulmonary artery despite the use of anticoagulants and additional angioplasty events after treatment completion were more frequent in patients with CH. RNA sequencing analysis revealed that blood coagulation and neutrophil extracellular trap formation pathways were enriched in patients with CH. Additionally, serum citrullinated histone H3 levels were higher in patients with CH than those without CH. These results were consistent in the subgroup of patients who did not have the history of hematological disorders.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The findings in this study raise the possibility that CH will induce a more prothrombotic state through neutrophil activation and neutrophil extracellular trap formation, contributing to pathogenesis and poor treatment response in patients with CTEPH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.035498","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T03:35:24Z","timestamp":1732764924000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Clonal Hematopoiesis in Chronic Thromboembolic Pulmonary Hypertension"],"prefix":"10.1161","author":[{"given":"Mizuki","family":"Momoi","sequence":"first","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5576-5789","authenticated-orcid":false,"given":"Yoshinori","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"},{"name":"Institute for Integrated Sports Medicine Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyoshi","family":"Kunimoto","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Immune Regulation Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1376-2760","authenticated-orcid":false,"given":"Takumi","family":"Inami","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Kyorin University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6758-2015","authenticated-orcid":false,"given":"Fuyuki","family":"Miya","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Anzai","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0450-0331","authenticated-orcid":false,"given":"Shinichi","family":"Goto","sequence":"additional","affiliation":[{"name":"Institute for Integrated Sports Medicine Keio University School of Medicine Tokyo Japan"},{"name":"Division of Cardiovascular Medicine Brigham and Women\u2019s Hospital Boston MA USA"},{"name":"Harvard Medical School Boston MA USA"},{"name":"Division of General Internal Medicine &amp; Family Medicine, Department of General and Acute Medicine Tokai University School of Medicine Isehara Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayaka","family":"Miura","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Immune Regulation Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Shinya","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takahiro","family":"Hiraide","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kohsuke","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7770-2519","authenticated-orcid":false,"given":"Jin","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1413-0482","authenticated-orcid":false,"given":"Keiichi","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4724-3299","authenticated-orcid":false,"given":"Masaki","family":"Ieda","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenjiro","family":"Kosaki","sequence":"additional","affiliation":[{"name":"Center for Medical Genetics Keio University School of Medicine Tokyo Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Immune Regulation Yokohama City University Graduate School of Medicine Yokohama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8034-1005","authenticated-orcid":false,"given":"Masaharu","family":"Kataoka","sequence":"additional","affiliation":[{"name":"Department of Cardiology Keio University School of Medicine Tokyo Japan"},{"name":"The Second Department of Internal Medicine University of Occupational and Environmental Health Kitakyushu Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac237"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00087608"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2013.02.005"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1209657"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01694-2021"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2022.02.002"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/pul2.12110"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehac419"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-07-746453"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1701719"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135204"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-26435-0"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2017.12.037"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2019.05.013"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408617"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0041-1733856"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.144.suppl_1.12959"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-66-0158"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2019.08.022"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2819-2"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.14797\/mdcj-12-4-213"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23230"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-018-2486-6"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2022.08.013"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04544.x"},{"key":"e_1_3_1_29_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112322"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.116.307634"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005861"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aan8292"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00626-2020"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21093339"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/evidoa2200310"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0896-8"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-020-00710-0"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2021.1678"},{"key":"e_1_3_1_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2021.03.002"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2019.11.008"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.124.035498","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T03:35:29Z","timestamp":1732764929000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.124.035498"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":40,"alternative-id":["10.1161\/JAHA.124.035498"],"URL":"https:\/\/doi.org\/10.1161\/jaha.124.035498","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,27]]},"assertion":[{"value":"2024-07-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e035498"}}