{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:45:33Z","timestamp":1782992733572,"version":"3.54.5"},"reference-count":16,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Thrombotic events, including acute ischemic stroke, are more common in individuals with congenital heart disease (CHD). Whether common thrombophilia variants contribute to thrombotic risk in this population remains unclear. We evaluated whether prothrombin G20210A (\n                      <jats:italic toggle=\"no\">F2<\/jats:italic>\n                      c.97G&gt;A) and factor V Leiden (\n                      <jats:italic toggle=\"no\">F5<\/jats:italic>\n                      c.1601G&gt;A; p.Arg534Gln) are associated with thrombotic events in CHD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Participants in the Pediatric Cardiac Genomics Consortium with exome sequencing and electronic medical record data were identified. Individuals were stratified by prothrombin G20210A and factor V Leiden genotypes, ventricular physiology, and antithrombotic therapy. The primary outcome was the presence of\n                      <jats:italic toggle=\"no\">International Classification of Diseases<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">ICD<\/jats:italic>\n                      ) or Phecodes (phenotype codes) for thrombotic events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Among 4008 participants (median age, 11.4 [interquartile range, 5.1\u201317.9] years; 44.4% boys), thrombotic events occurred in 737 (18%), including 93 (13%) with acute ischemic stroke. Compared with the Genome Aggregation Database, the CHD cohort had a lower prevalence of heterozygous prothrombin G20210A and factor V Leiden variants. Variant prevalence did not differ between participants with and without thrombotic events. Single\u2010ventricle CHD was associated with higher thrombosis frequency than biventricular CHD (35% versus 16%,\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      \u22640.0001), without differences in variant prevalence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">In this multicenter CHD cohort, prothrombin G20210A and factor V Leiden were not significantly associated with thrombotic outcomes, supporting recommendations against routine screening. Given low variant prevalence, the study was powered to exclude only large associations. Reduced variant frequency suggests survivorship bias beginning in fetal life. Larger integrated clinical\u2013genomic studies are needed to refine thrombotic risk stratification in CHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique Identifier: NCT03347214.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.046959","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:43:37Z","timestamp":1772628217000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Prothrombin G20210A and Factor V Leiden Variants Are Not Associated With Thrombotic Events in Congenital Heart Disease: An Observational Trial"],"prefix":"10.1161","volume":"15","author":[{"given":"Feria A.","family":"Ladha","sequence":"first","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"VanderPluym","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5592-1728","authenticated-orcid":false,"given":"Enrique","family":"Mondragon\u2010Estrada","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Boston Children\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0235-7543","authenticated-orcid":false,"given":"Paul","family":"Avillach","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Harvard Medical School","place":["Boston"]},{"name":"Harvard T. H. Chan School of Public Health","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Brueckner","sequence":"additional","affiliation":[{"name":"Yale University School of Medicine","place":["New Haven"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3438-5685","authenticated-orcid":false,"given":"Wendy K.","family":"Chung","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Harvard Medical School","place":["Boston"]},{"name":"Columbia University Medical Center","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6732-8949","authenticated-orcid":false,"given":"James F.","family":"Cnota","sequence":"additional","affiliation":[{"name":"Heart Institute, Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]},{"name":"Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8527-5027","authenticated-orcid":false,"given":"Bruce D.","family":"Gelb","sequence":"additional","affiliation":[{"name":"Mindich Child Health and Development Institute and Department of Pediatrics, Icahn School of Medicine at Mount Sinai","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8991-0638","authenticated-orcid":false,"given":"Matthew","family":"Lewis","sequence":"additional","affiliation":[{"name":"Columbia University","place":["New York"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6024-3037","authenticated-orcid":false,"given":"Cong","family":"Liu","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-8521","authenticated-orcid":false,"given":"Amy E.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Boston Children\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6380-1209","authenticated-orcid":false,"given":"Christine E.","family":"Seidman","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Brigham and Women\u2019s Hospital","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5916-442X","authenticated-orcid":false,"given":"Martin","family":"Tristani\u2010Firouzi","sequence":"additional","affiliation":[{"name":"University of Utah School of Medicine","place":["Salt Lake City"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3421-4763","authenticated-orcid":false,"given":"Michael","family":"Wagner","sequence":"additional","affiliation":[{"name":"Cincinnati Children\u2019s Hospital Medical Center","place":["Cincinnati"]},{"name":"University of Cincinnati College of Medicine","place":["Cincinnati"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7816-2646","authenticated-orcid":false,"given":"Sarah U.","family":"Morton","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Harvard Medical School","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7794-9017","authenticated-orcid":false,"given":"Jane W.","family":"Newburger","sequence":"additional","affiliation":[{"name":"Boston Children\u2019s Hospital","place":["Boston"]},{"name":"Harvard Medical School","place":["Boston"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Pediatric Cardiac Genomics Consortium Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(19)30402-X"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtha.2023.03.005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000436140.77832.7a"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2022.803408"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.029375"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/STR.0000000000000183"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-023-03315-6"},{"key":"e_1_3_2_9_2","first-page":"44","article-title":"Hereditary thrombophilia","volume":"90","author":"Dautaj A","year":"2019","unstructured":"Dautaj A, Krasi G, Bushati V, Precone V, Gheza M, Fioretti F, Sartori M, Costantini A, Benedetti S, Bertelli M, et\u00a0al. Hereditary thrombophilia. Acta Biomed. 2019;90:44\u201346.","journal-title":"Acta Biomed"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1592333"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.300297"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06045-0"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03012459"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1017\/S1047951105000053"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-130-9-199905040-00013"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2014.12.001"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002302"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.125.046959","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:12:47Z","timestamp":1782990767000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.125.046959"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2026,3,17]]}},"alternative-id":["10.1161\/JAHA.125.046959"],"URL":"https:\/\/doi.org\/10.1161\/jaha.125.046959","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"assertion":[{"value":"2025-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e046959"}}