{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T00:29:56Z","timestamp":1789259396027,"version":"build-2803163510"},"posted":{"date-parts":[[2025,11,30]]},"group-title":"Cardiovascular Medicine","reference-count":37,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,11,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Bicuspid aortic valve (BAV) is the most common congenital heart malformation and predisposes to thoracic aortic aneurysms. The Montalcino Aortic Consortium (MAC) registry collects genetic and phenotypic data on individuals with heritable thoracic aortic disease genes (HTAD PVs) that primarily regulate smooth muscle cell contraction or TGF-\u03b2 signaling (TGF-\u03b2 PVs, termed Loeys-Dietz Syndrome (LDS)). We evaluated associations between BAV, HTAD PVs and aortic outcomes in the MAC cohort.<\/jats:p>\n                <jats:p>\n                  BAV was present in 48 (6%) of 816 MAC participants (age 38 [IQR 20-52] years, 51% female) and was not significantly increased in males or in the entire TGF-\u03b2 PV group (417 with TGF-\u03b2 PVs, p=0.14) but was enriched in participants with\n                  <jats:italic>TGFBR1<\/jats:italic>\n                  or\n                  <jats:italic>TGFBR2<\/jats:italic>\n                  PVs (16\/168, 10% vs. 32\/648, 5%, PR 1.93 [1.08, 3.43], p&lt;0.05). BAV was associated with aortic regurgitation (AR, 17\/46, 37% vs. 84\/752, 11%, PR 3.3 [2.2-5.1],\n                  <jats:italic>P&lt;<\/jats:italic>\n                  0.001), younger age at first aortic event (24 vs. 40 years, p&lt;0.001), primarily reflecting increased proximal aortic repair (27\/48, 56% vs. 227\/768, 30%, PR 1.90 [1.45, 2.50],\n                  <jats:italic>P&lt;<\/jats:italic>\n                  0.0001), but not aortic dissection (6\/48, 13% vs. 134\/768, 18%, P&gt;0.5). Sinus of Valsalva dilation (Z&gt;3, 25\/48, 52% vs. 128\/768, 17%,\n                  <jats:italic>P&lt;<\/jats:italic>\n                  0.0001) and ascending aorta dilation (Z&gt;3, 12\/48, 25% vs. 26\/768, 3%,\n                  <jats:italic>P&lt;<\/jats:italic>\n                  0.0001) were more common in participants with BAV. Participants with both TGF-\u03b2 PV and BAV more frequently had aortic valve surgery (17\/30, 57% vs. 110\/387, 28%, PR 1.99 [1.40-2.83], p&lt;0.01) and sinus of Valsalva dilation (20\/29, 69% vs. 91\/258, 35% PR 1.96 [1.40-2.63], p&lt;0.001), but not ascending dilation, than participants with TGF-\u03b2 PV who did not have BAV.\n                <\/jats:p>\n                <jats:p>\n                  BAV is enriched in individuals with HTAD PV, most prominently in the subgroup with\n                  <jats:italic>LDS TGFBR1<\/jats:italic>\n                  and\n                  <jats:italic>TGFBR2<\/jats:italic>\n                  , and is associated with accelerated aortic valve and aortic diseasebut does not confer an increased risk for aortic dissection. These observations highlight the potential benefits of genetic testing for BAV patients who have a family history of HTAD, a sinus of Valsalva aneurysm, or clinical features suggestive of LDS.\n                <\/jats:p>","DOI":"10.1101\/2025.11.26.25341124","type":"posted-content","created":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T20:40:16Z","timestamp":1764535216000},"source":"Crossref","is-referenced-by-count":2,"title":["Bicuspid Aortic Valve in Heritable Thoracic Aortic Disease: Insights from the Montalcino Aortic Consortium"],"prefix":"10.64898","author":[{"given":"Kishan L.","family":"Asokan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neha","family":"Muraly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongchuan","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deep 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