Novel Insights on Transthyretin Presence in Stenotic Aortic Valves

A recent study by researchers at Uppsala University uncovered surprising findings regarding the presence and nature of transthyretin (TTR) in stenotic aortic valves. Presented at the International Symposium on Amyloidosis, Ulrika and colleagues’ findings explore the prevalence and characteristics of amyloid deposits in resected stenotic aortic valves, shedding light on potential implications for understanding the implications of amyloidogenic TTR deposition in the pathogenesis of aortic stenosis (AS).

Amyloid deposits in resected AS valves have been documented previously, with studies indicating that 4% to 16% of patients with AS have transthyretin cardiac amyloidosis (ATTR-CA). However, researchers at Uppsala University revealed amyloid deposits in over 75% of AS valves, suggesting a more widespread deposition of TTR in stenotic aortic valves. The precise nature of these amyloid deposits in AS valves remains unclear, prompting further investigation.

Study investigators aimed to better understand the nature of amyloid aggregates in AS valves, specifically focusing on the involvement of TTR.

The research involved 110 nonselected, deidentified AS valves resected due to AS. Amyloid presence was assessed through scrapings from all valves, graded on a scale of 0 to 4+. Each valve extract underwent analysis via Western blot using a rabbit antiserum against TTR 50-127. Additionally, AS valve sections were stained with Congo Red and a TTR monoclonal antibody to identify amyloid deposits.

The study found amyloid deposits in 89% (98/110) of the stenotic aortic valves, with TTR present in 104 of the extracts. Valves containing fragmented TTR exhibited moderate to large amounts of amyloid on Congo Red slides (2+ and 3+). Immunohistochemistry revealed more than one type of amyloid present. Notably, full-length TTR was the predominant form in AS valves, though its precise nature remains undetermined. Fragmented TTR, typically seen in systemic wild-type ATTR amyloidosis, was rare in AS valves.

This study underscores the high prevalence of amyloid deposits in AS valves and highlights the complex nature of TTR involvement. These insights pave the way for further research into the nature of amyloid deposits in AS valves, their potential implications for delineating AS pathogenesis, and avenues for novel treatment.