Transthyretin levels increase in patients with severe AS following TAVI

Background/Introduction The coexistence of transthyretin cardiac amyloidosis and severe aortic stenosis (AS) is increasingly recognised, yet the underlying pathophysiology remains debated. Emerging evidence suggests that high shear stress across the stenotic valve may induce conformational changes in the transthyretin (TTR) tetramer, promoting its dissociation and subsequent myocardial infiltration. Purpose To investigate whether the relief of mechanical obstruction after an aortic valve replacement modulates circulating TTR levels. Methods In this prospective observational study (Sept 2025–Jan 2026), we enrolled patients with severe AS undergoing transcatheter aortic valve implantation (TAVI). Serum TTR was quantified via Luminex xMAP technology at baseline (within one month pre-intervention) and at three months post-procedure. A non-AS control group was used for baseline comparison. Statistical analysis was performed using R-Studio (version 4.5.2), employing paired t-tests for longitudinal changes and independent t-tests for group comparisons, with p < 0.05 considered significant. Multivariable analysis was employed to adjust for confounders, including nutritional status, albumin, and renal function. Results Thirteen AS patients treated with TAVI and 30 control subjects were enrolled. There was no difference between AS and control subjects in age (80.6 ± 6.9 vs. 79.6 ± 8 years), male gender, CRP, and creatinine levels. Baseline TTR levels in patients with AS were lower than those in the control group (96.8 ± 50.3 mg/L vs 152.0 ± 93.0 mg/L, p value 0.05) but did not reach statistical significance (Figure 1). In Patients with AS treated with TAVI, serum TTR concentration increased significantly from 96.8 ± 50.3 mg/L at baseline to 141 ± 61.5 mg/L at follow-up (p = 0.04) (Figure 2). Individual data inspection demonstrated that all patients with low baseline TTR levels (< 50 mg/L) exhibited a marked post-procedural increase in concentration. Conclusions Patients with severe aortic stenosis present lower levels of circulating TTR. The relief of mechanical obstruction in patients with severe AS following TAVI is associated with an increase in circulating TTR levels. Elimination of valvular shear stress may promote TTR tetramer stabilisation and restoration of protein homeostasis.