AI-echocardiography: an eagle eye for the prognostic staging of ATTR cardiomyopathy

This Editorial Comment refers to ‘AI-based echocardiographic assessment for monitoring disease progression in transthyretin cardiac amyloidosis’ by L. Venneri et al., https://doi.org/10.1002/ejhf.70073, published in volume 27, issue 12, 2025 of European Journal of Heart Failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) arises from the deposition of misfolded transthyretin in the extracellular space of the myocardium. This leads to a progressive restrictive cardiomyopathy with an overall poor prognosis. Up to recently, there were no therapeutic options to slow or halt the progression of the disease. However, with the approval of tafamidis by the FDA in 2019 based on its morbidity- and mortality-reducing effect in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT),1 ATTR-CM has become a treatable, though not yet curable, disease. Whereas such so-called TTR stabilizers (e.g. tafamidis, acoramidis) act by stabilizing TTR tetramers to prevent the formation of misfolded protein monomers, antisense oligonucleotides (e.g. inotersen, eplontersen) and siRNA-based therapeutics (e.g. patisiran, vutrisiran) directly inhibit TTR synthesis. More recent drug developments, which act at a later stage of the disease and include antibodies that are able to clear deposited amyloid through immune-related processes, are currently under investigation. Given the increasing availability of different therapeutic options, risk stratification tools are gaining importance, as they may facilitate personalized treatment and support the monitoring of disease progression and treatment response in ATTR-CM.