{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T04:39:10Z","timestamp":1790829550100,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Background<\/jats:title>\n \n Bioprosthetic heart valves (\n BHVs<\/jats:styled-content>\n ), fabricated from glutaraldehyde\u2010pretreated bovine pericardium or porcine aortic valves, are widely used for the surgical or interventional treatment of heart valve disease. Reoperation becomes increasingly necessary over time because of\n BHV<\/jats:styled-content>\n dysfunction.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Forty\u2010seven explanted\n BHV<\/jats:styled-content>\n aortic valve replacements were retrieved at reoperation for clinically severe\n BHV<\/jats:styled-content>\n dysfunction over the period 2010\u20132016. Clinical explant analyses of\n BHV<\/jats:styled-content>\n leaflets for calcium (atomic absorption spectroscopy) and oxidized amino acids, per mass spectroscopy, were primary end points. Comorbidities for earlier\n BHV<\/jats:styled-content>\n explant included diabetes mellitus and coronary artery bypass grafting. Mean calcium levels in\n BHV<\/jats:styled-content>\n leaflets were significantly increased compared with unimplanted\n BHV<\/jats:styled-content>\n (\n P<\/jats:italic>\n <0.001); however, time to reoperation did not differ comparing calcified and noncalcified\n BHV<\/jats:styled-content>\n .\n BHV<\/jats:styled-content>\n dityrosine, an oxidized amino acid cross\u2010link, was significantly increased in the explants (227.55\u00b133.27\u00a0\u03bcmol\/mol [dityrosine\/tyrosine]) but was undetectable in unimplanted leaflets (\n P<\/jats:italic>\n <0.001).\n BHV<\/jats:styled-content>\n regional analyses revealed that dityrosine, ranging from 57.5 to 227.8\u00a0\u03bcmol\/mol (dityrosine\/tyrosine), was detectable only in the midleaflet samples, indicating the site\u2010specific nature of dityrosine formation. 3\u2010Chlorotyrosine, an oxidized amino acid formed by myeloperoxidase\u2010catalyzed chlorinating oxidants, correlated with\n BHV<\/jats:styled-content>\n calcium content in leaflet explant analyses from coronary artery bypass graft patients (\n r<\/jats:italic>\n =0.62,\n P<\/jats:italic>\n =0.01) but was not significantly correlated with calcification in non\u2013coronary artery bypass graft explanted\n BHV<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Both increased\n BHV<\/jats:styled-content>\n leaflet calcium levels and elevated oxidized amino acids were associated with bioprosthesis dysfunction necessitating reoperation; however,\n BHV<\/jats:styled-content>\n calcium levels were not a determinant of implant duration, indicating a potentially important role for oxidized amino acid formation in\n BHV<\/jats:styled-content>\n dysfunction.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.117.005648","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T20:40:22Z","timestamp":1494276022000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":61,"title":["Calcification and Oxidative Modifications Are Associated With Progressive Bioprosthetic Heart Valve Dysfunction"],"prefix":"10.1161","volume":"6","author":[{"given":"Suengwon","family":"Lee","sequence":"first","affiliation":[{"name":"The Children's Hospital of Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Levy","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail J.","family":"Christian","sequence":"additional","affiliation":[{"name":"The Children's Hospital of Philadelphia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley L.","family":"Hazen","sequence":"additional","affiliation":[{"name":"The Cleveland Clinic","place":["Cleveland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan E.","family":"Frick","sequence":"additional","affiliation":[{"name":"University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric K.","family":"Lai","sequence":"additional","affiliation":[{"name":"University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan B.","family":"Grau","sequence":"additional","affiliation":[{"name":"Ottawa Heart Institute","place":["Ottawa, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph E.","family":"Bavaria","sequence":"additional","affiliation":[{"name":"University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Ferrari","sequence":"additional","affiliation":[{"name":"University of Pennsylvania","place":["Philadelphia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1016\/S0003-4975(02)03840-7","article-title":"Results of bioprosthetic versus mechanical aortic valve replacement performed with concomitant coronary artery bypass grafting","volume":"74","author":"Akins CW","year":"2002","unstructured":"Akins CW, Hilgenberg AD, Vlahakes GJ, MacGillivray TE, Torchiana DF, Madsen JC. 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