Evaluating TTR Gene-silencing Drugs in Transthyretin Cardiac Amyloidosis Using Advanced Imaging: A Systematic Review

Objectives

This systematic review aims to synthesize current evidence on the effect of transthyretin (TTR) gene-silencing therapies in transthyretin cardiac amyloidosis (ATTR-CM) patients using advanced cardiac imaging modalities.

Materials and Methods

A systematic search was conducted in PubMed, ScienceDirect, Scopus, and Cochrane Library according to PRISMA 2020 guidelines to identify observational studies. The primary endpoint was extracellular volume (ECV). Secondary outcomes included other imaging-derived parameters. Data were extracted and summarized as mean differences (MD) with 95% confidence intervals (CI).

Results

A total of four studies were included. Most studies evaluated patisiran, with additional data on inotersen  and eplontersen. Two studies demonstrated significant reductions in ECV. One study reported a decrease in septal ECV at 1 year (MD 3.845; 95% CI 2.708–4.98; p < 0.001) and 2 years (MD 6.892; 95% CI 5.103–8.680; p < 0.001). Another study showed a reduction in global ECV (MD −6.2; 95% CI −9.5 to −3.0; p = 0.001). For secondary outcomes, a significant reduction in volumetric heart-to-lung ratio assessed by single-photon emission computed tomography was observed (p = 0.028), while planar measurements were not statistically significant. Additionally, progressive reductions in left ventricular mass were reported over time. Due to heterogeneity in measurement sites and differences in reported data, quantitative pooling was not performed.

Conclusion

TTR gene-silencing therapies are associated with favorable improvements in myocardial tissue characteristics and cardiac structure in ATTR-CM based on advanced imaging. However, evidence remains limited and requires validation in larger and robust studies.

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