Abstract Body (Do not enter title and authors here): Introduction
Transthyretin cardiac amyloidosis (ATTR-CA) is an important cause of heart failure for which tafamidis is the only FDA-approved therapy. Diflunisal is an NSAID that is also effective in improving cardiovascular outcomes in ATTR-CA and is utilized in regions where tafamidis is unavailable or cost-prohibitive. Data comparing the efficacy of these agents are lacking.

Research Question
To compare longitudinal changes in cardiac structure by echocardiography and cardiac biomarkers among patients with ATTR-CA treated with tafamidis or diflunisal over 36 months.

Methods
Among 425 sequential ATTR-CA patients seen at the Boston University Amyloidosis Center between 2016 and 2022, following exclusion for single visits (194) and for receiving TTR-silencer or multiple therapies (67), the final cohort was 164 patients: 109 were treated with tafamidis (ATTR-CA-T, 86% wild-type) and 55 with diflunisal (ATTR-CA-D, 54% wild-type). Echocardiographic wall thickness was re-measured by a single observer, while LVEF, global longitudinal strain (GLS, expressed in absolute value), NT-proBNP, troponin I, prealbumin, and creatinine were collected from the electronic health record at baseline and 36 months with differences between the measures calculated for each patient and compared using paired t-tests.

Results
At baseline, while the ATTR-CA-D cohort was older and had a higher proportion of variant ATTR-CA (p<0.001), the ATTR-CA-T cohort had more advanced disease as demonstrated by increased wall thickness, lower LVEF, worse GLS, higher creatine, and worse cardiac biomarkers (Table 1). After 36 months of treatment compared to baseline (n=23 for ATTR-CA-D and n=36 for ATTR-CA-T), the ATTR-CA-D group showed increase in septal thickness (0.5mm, p=0.04) and posterior wall thickness (0.6mm, p=0.006), while GLS (-5.6%, p<0.001) and LVEF (-5.9%, p=0.02) were decreased. There were no significant echocardiographic changes after 36 months in the ATTR-CA-T group and cardiac biomarker change was similar.

Conclusion
These data suggest that tafamidis may be more effective than diflunisal in arresting echocardiographic progression in ATTR-CA. Further studies are necessary to assess the association of these changes with cardiovascular outcomes.