• Suengwon Lee, Robert J Levy, Abigail J Christian, Stanley L Hazen, Nathan E Frick, Eric K Lai, Juan B Grau, Joseph E Bavaria, and Giovanni Ferrari.
• The Children's Hospital of Philadelphia, PA.
• J Am Heart Assoc. 2017 May 8; 6 (5).

BackgroundBioprosthetic heart valves (BHVs), fabricated from glutaraldehyde-pretreated 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 BHV dysfunction.Methods And ResultsForty-seven explanted BHV aortic valve replacements were retrieved at reoperation for clinically severe BHV dysfunction over the period 2010-2016. Clinical explant analyses of BHV leaflets for calcium (atomic absorption spectroscopy) and oxidized amino acids, per mass spectroscopy, were primary end points. Comorbidities for earlier BHV explant included diabetes mellitus and coronary artery bypass grafting. Mean calcium levels in BHV leaflets were significantly increased compared with unimplanted BHV (P<0.001); however, time to reoperation did not differ comparing calcified and noncalcified BHV. BHV dityrosine, an oxidized amino acid cross-link, was significantly increased in the explants (227.55±33.27 μmol/mol [dityrosine/tyrosine]) but was undetectable in unimplanted leaflets (P<0.001). BHV regional analyses revealed that dityrosine, ranging from 57.5 to 227.8 μmol/mol (dityrosine/tyrosine), was detectable only in the midleaflet samples, indicating the site-specific nature of dityrosine formation. 3-Chlorotyrosine, an oxidized amino acid formed by myeloperoxidase-catalyzed chlorinating oxidants, correlated with BHV calcium content in leaflet explant analyses from coronary artery bypass graft patients (r=0.62, P=0.01) but was not significantly correlated with calcification in non-coronary artery bypass graft explanted BHV.ConclusionsBoth increased BHV leaflet calcium levels and elevated oxidized amino acids were associated with bioprosthesis dysfunction necessitating reoperation; however, BHV calcium levels were not a determinant of implant duration, indicating a potentially important role for oxidized amino acid formation in BHV dysfunction.© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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