Effect of TTR stabilisers on strain values derived by echocardiography in patients with wild type ATTR Amyloidosis

Introduction
Transthyretin stabilisers are the only established therapy for patients with TTR amyloidosis and cardiac involvement and have demonstrated to slow disease progression. However, evaluation of therapy response and estimation of prognosis remains a field of further research.

Methods
We retrospectively analysed a cohort of consecutive patients presented at out institution from 2021 to 2024 with confirmed cardiac wtATTR-cardiomyopathy (wtATTR-CM) regarding their echocardiographic response after initiation of TTR-stabilizer (Tafamidis 61mg once daily) therapy. All patients received transthoracic echocardiography before and 6 months after therapy initiation. LA, RA, LV and RV strain values were retrospectively measured using TOMTEC arena auto strain feature (TOMTEC build 559920) by an experienced investigator in a blinded fashion. The R-gated method was used for all parameters. Background therapy was stable for all patients. Between group differences were calculated using Mann-Whitney-U test or Wilcoxon rank sum test if applicable.

Results
We identified 45 patients (80% male, mean age 78,1 years) who fulfilled the inclusion criteria and had adequate image quality to perform a full evaluation (6 patients were excluded due to image quality). The second investigation was performed after a median of 194 days of TTR-stabilizer therapy. All patients had decreased strain values for all cardiac chambers compared to healthy adults and referencs values. There were stable measurements at follow-up for LV global longitudinal strain (GLS) (-10.35% vs. -10.13%, p > 0.05). Strain parameters of right ventricular function increased slightly for right ventricular free wall strain (RVFWS: -12.3% vs. – 13.6, p< 0.05) and remained stable for right ventricular longitudinal strain (RVLS: -9,8% vs. -9,7%, p >0.05). Left atrial reservoir strain (LASr: 8.4% vs. 9.6%, p< 0.05) improved significantly . Right atrial reservoir strain improved numerically but did not achieve clinical significance (RASr: 9.1% vs. 9.8%, p>0.05). There was a positive correlation between decrease in NT-proBNP and improvement of presumably load-dependent strain values (LASr and RASr) whereas this could not be demonstrated for GLS, suggesting a biomarker equivalent of therapy response. Presence of atrial fibrillation showed numerically more often deterioration in strain values than patients with sinus rhythm.

Conclusion
As previously reported there was no improvement in left ventricular global longitudinal strain und TTR-stabilizer therapy. However, more load depended strain parameters for the left and right atrium as well as the right ventricle showed short-term improvements suggesting therapy response. Further research to investigate whether this short-term response can be correlated to improved long-term clinical outcomes is warranted.