Abstract Background There are currently no disease-modifying therapies for aortic valve stenosis (AS). AS is associated with transthyretin cardiac amyloidosis (TTR-CA). TTR-CA, in turn, can be treated with tafamidis, which stabilises the transthyretin protein, preventing dissociation and subsequent formation of amyloid fibrils. While tafamidis has been shown to improve mortality rates and quality of life for patients with TTR-CA, its effects on AS progression are unknown. Purpose In this study, by evaluating whether or not tafamidis use is associated with AS progression, we sought to determine whether tafamidis could have potential as a treatment for the progression of AS. There are currently no disease-modifying medical treatments for AS. Methods We retrospectively identified TTR-CA patients who met two criteria: at least mild AS, and 12 months or more of tafamidis treatment. A total of 20 patients were found. For each patient, two echocardiograms prior to and post-treatment initiation were measured (for post-treatment echocardiograms, one echo was performed during the initial 12 months, and one echo after the initial 12 months). We measured four parameters in each echo: AV Maximum Velocity (Vmax) AV Mean Gradient (MG) Dimensionless Index (DVI) AV Area (AVA) The correlation between tafamidis treatment and each measurement was tested via a mixed-effects model (time-by-drug interaction), and the rate of change in each measure of AS was estimated by a linear regression model. Results A total of 20 patients met inclusion criteria. The rate of change of Vmax pre-tafamidis was 6.02 cm/sec/year, and on tafamidis it was 2.66 cm/sec/year, p = 0.71 (Figure 1A). The rate of change of MG pre-tafamidis was 0.74 mmHg/year, and on tafamidis it was 0.01 mmHg/year, p = 0.54 (Figure 1B). The rate of change of DVI pre-tafamidis was -0.02/year, and on tafamidis it was -0.04/year, p = 0.32 (Figure 1C). The rate of change of AVA pre-tafamidis was -0.06 cm²/year, and on tafamidis it was -0.12 cm²/year, p = 0.36 (Figure 1D). Conclusion There was a non-significant trend of reduced progression in Vmax and MG while on tafamidis, but no trend or significant association for the rate of change in DVI and AVA. These results do not establish an association between tafamidis and AS progression, but the trend toward less progression in Vmax and MG might suggest merit in further study. Larger, prospective studies with longer follow-up periods may further explore these potential trends and better assess any effects of tafamidis on AS progression.
Patel et al. (Sat,) studied this question.