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

https://doi.org/10.1016/j.jacbts.2020.06.008Get rights and content
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Highlights

  • 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.

Summary

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.

Key Words

advanced glycation end products
aortic valve disease
biomaterial
bioprosthetic heart valve

Abbreviations and Acronyms

AGE
advanced glycation end product
BHV
bioprosthetic heart valve
BP
bovine pericardium
CML
N-carboxymethyl-lysine
EOA
effective orifice area
HSA
human serum albumin
IHC
immunohistochemistry
PBS
phosphate-buffered saline
SAVR
surgical aortic valve replacement
SHG
second harmonic generation
SVD
structural valve degeneration
TAVR
transcatheter aortic valve replacement

Cited by (0)

This work was supported by National Institutes of Health grants R01s HL122805 (to Dr. Ferrari) and HL143008 (to Drs. Levy and Ferrari), T32s HL007915 (to Drs. Levy and Rock), HL007854 (to Dr. Kossar) and HL007343 (to Dr. Frasca), The Kibel Fund for Aortic Valve Research (to Drs. Ferrari and Levy), The Valley Hospital Foundation ’Marjorie C Bunnel’ charitable fund (to Drs. Ferrari and Grau), the American Diabetes Association Pathway to Stop Diabetes Grant 1-17-VSN-04 and the SENS Research Foundation (to Dr. Spiegel), and both Erin’s Fund and the William J Rashkind Endowment of the Children’s Hospital of Philadelphia (to Dr. Levy). Dr. Spiegel is cofounder and chief scientific adviser at REVEL Pharmaceuticals. Dr. Levy is a consultant for WL Gore. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.