Glycation and Serum Albumin Infiltration Contribute to the Structural Degeneration of Bioprosthetic Heart Valves

• Published in: JACC. Basic to translational science Vol. 5; no. 8; pp. 755 - 766
• Main Authors: Frasca, Antonio, Xue, Yingfei, Kossar, Alexander P., Keeney, Samuel, Rock, Christopher, Zakharchenko, Andrey, Streeter, Matthew, Gorman, Robert C., Grau, Juan B., George, Isaac, Bavaria, Joseph E., Krieger, Abba, Spiegel, David A., Levy, Robert J., Ferrari, Giovanni
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.08.2020; Elsevier
• Subjects: advanced glycation end products; aortic valve disease; biomaterial; bioprosthetic heart valve; Cardiovascular; CLINICAL RESEARCH; PBS; SVD; CML; biomaterial; IHC; SAVR; advanced glycation end products; aortic valve disease; BP; TAVR; BHV; SHG; bioprosthetic heart valve; EOA; HSA; AGE; N-carboxymethyl-lysine; phosphate-buffered saline; effective orifice area; bovine pericardium; second harmonic generation; immunohistochemistry; advanced glycation end product; structural valve degeneration; transcatheter aortic valve replacement; surgical aortic valve replacement; human serum albumin
• ISSN: 2452-302X; 2452-302X
• DOI: 10.1016/j.jacbts.2020.06.008

[Display omitted] •Two novel and interacting mechanisms contributing to BHV SVD are reported: glycation and serum albumin infiltration.•Glycation product formation and serum albumin deposition were observed in 45 clinical BHV explanted due to SVD as well as BHV tissue subcutaneously implanted in rats.•In vitro exposure to glycation and serum albumin elicited collagen network misalignment similar to that seen in clinical and rat explant BHV tissue.•Glycation was sufficient to impair BHV hydrodynamic function in ISO-5840-compliant pulse duplication testing and concomitant serum albumin infiltration exacerbated these effects. Valvular heart diseases are associated with significant cardiovascular morbidity and mortality, and often require surgical and/or percutaneous repair or replacement. Valve replacement is limited to mechanical and biological prostheses, the latter of which circumvent the need for lifelong anticoagulation but are subject to structural valve degeneration (SVD) and failure. Although calcification is heavily studied, noncalcific SVD, which represent roughly 30% of BHV failures, is relatively underinvestigated. This original work establishes 2 novel and interacting mechanisms—glycation and serum albumin incorporation—that occur in clinical valves and are sufficient to induce hallmarks of structural degeneration as well as functional deterioration.