International Journal of Cardiovascular Sciences. 29/Apr/2025;38:e20240223.

Cardiac Amyloidosis TTR: The Hidden Culprit Behind Aortic Stenosis in the Elderly

Sandrigo Mangini , Lígia Lopes Balsalobre Trevizan

DOI: 10.36660/ijcs.20240223

This Editorial is referred by the Research article "Prevalence of Cardiac Amyloidosis in Elderly Patients With Aortic Stenosis".

Calcific aortic stenosis (AS), a condition marked by leaflet fibrosis and calcification, is driven by mechanical stress and biological stimuli that activate pro-inflammatory pathways. It results from a complex, progressive process that occurs over many years, and becomes increasingly prevalent with age. Aging itself is associated with a “low-grade inflammatory state”, which promotes and sustains various pathological conditions, including cardiac amyloidosis (CA)^, that is mostly related to wild-type transthyretin (TTR) and less commonly to variant TTR and light chain amyloidosis (AL). CA is phenotypically associated with heart failure with preserved ejection fraction (HFPEF), and wild type TTR is estimated to be prevalent in approximately 13% of elderly over 60. However, different from calcific AS that has a similar gender distribution, the wild-type TTR is more prevalent in men.

In a study with elderly patients, Conte et al. reported amyloid deposition in 37% of stenotic aortic valves, 10% of sclerotic valves, and no findings of amyloid in controls. Amyloid deposition was linked to greater fibrosis and calcification. Imunohistochemistry suggested involvement of serum amyloid A1 (SAA1) and TTR. These findings indicate that amyloid deposition in aortic valves may be more common and is related to aging and degenerative changes.

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