Abstract 11860: Poly-2-Methyl-2-Oxazoline as a Novel Mitigation Strategy in Bioprosthetic Heart Valves Affected by Calcification and Structural Degeneration in Patients With Metabolic Syndrome

Abstract

I: Bioprosthetic heart valves (BHV) engineered from glutaraldehyde-fixed bovine pericardium (GBP) are widely used for surgical and transcatheter interventions and affected by structural valve degeneration (SVD), often associated with calcification. Risk factors for accelerated SVD are under study. Susceptibility to oxidation, glycation and protein infiltration are key mechanisms. Here we characterize mechanisms of accelerated SVD in patients with metabolic syndrome (MetS) and propose a novel mitigation strategy with poly-2-methyl-2-oxazoline (POZ) coating. M: Retrospective chart review assessed risk factors for accelerated SVD. BHVs affected by SVD were selected (N=24) with/without MetS and next-generation proteomics with enrichment analysis (STRING-Db) performed. Unmodified (U) GBP and POZ GBP were incubated in serum from patients (N=128) with/without MetS to mimic protein absorption. U-GBP and POZ-GBP were subcutaneously implanted in Zucker Diabetic Fatty rats and controls. GBPs were analyzed with immunohistochemistry (IHC), differential scanning calorimetry (DSC), second-harmonic generation (SHG) and scanning electron microscopy (SEM). R: Kaplan Meier log-rank test (N = 251 patients) revealed patients with MetS were at increased risk of accelerated SVD (p = 0.004). Proteomics revealed (N=452) permanently incorporated proteins were differentially expressed (log2FC >0.58, qvalue<0.05) between MetS and nonMetS. Proteins involved in ECM remodeling and immune activation pathways were overrepresented (Fig 1). IHC, DSC, SHG and SEM results from revealed that POZ-GBP reduced protein infiltration, reduced calcification, and preserved structural integrity when compared to U-GBP. C: Accelerated SVD associated with MetS with calcification and serum protein accumulation is risk factor dependent and can be mitigated with POZ. This opens a possibility to chemically modify biomaterials for patients with this highly prevalent comorbidity.