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Tafamidis, a transthyretin stabilizer, has been the first and for years the only available disease-modifying therapy, with proven survival benefit. However, a significant proportion of patients continue to experience clinical deterioration, underscoring the need for effective monitoring strategies to guide individual patient management and to serve as surrogate endpoints in clinical trials and in real-world clinical follow up. Current approaches to disease monitoring are largely adapted from heart failure management and include periodic assessment of clinical status, biomarkers, imaging, and functional capacity. Nevertheless, real-world data highlight important limitations, particularly in detecting early disease progression among treated patients. As novel therapies become increasingly available, early identification of suboptimal treatment response is critical to inform timely therapeutic decisions. Developing and validating a reproducible, easy framework for disease monitoring thus remain an urgent research priority. This narrative review summarizes current evidence on monitoring patients with ATTR and heart involvement, including both treated and untreated individuals. It also outlines future directions in this evolving field, emphasizing key knowledge gaps and opportunities for improvement.<\/jats:p>","DOI":"10.1007\/s10741-025-10588-x","type":"journal-article","created":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T06:37:10Z","timestamp":1766385430000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Monitoring heart involvement in treated and untreated transthyretin amyloidosis"],"prefix":"10.1007","volume":"31","author":[{"given":"Giulio","family":"Sinigiani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Milani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"De Michieli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe Damiano","family":"Sanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Perlini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Cipriani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Palladini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"issue":"6","key":"10588_CR1","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1056\/NEJMra023144","volume":"349","author":"G Merlini","year":"2003","unstructured":"Merlini G, Bellotti V (2003) Molecular mechanisms of amyloidosis. 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Prof Cipriani has received consulting income from AstraZeneca, and has advisory role for Pfizer, AstraZeneca, Alnylam and Bayer. Prof Palladini has advisory role for Alexion, Abbvie, Bayer, GSK, Life Molecular Science, Neuroimmune, Protego, Pfizer, Prothena, Regeneron, and has received honoraria from Janssen. Prof Milani has received honoraria from Jansen, Prothena, Pfizer, Bayer, Sebia and has advisory role for Siemens. Dr Sanna has received Cardiac ATTR Amyloidosis Fellowship grant funded by International Society of Amyloidosis (2023\u20132024); honoraria for lectures\/teaching courses and travel support to attend scientific meetings: (Alnylam 2023\u20132024), AstraZeneca (2024), Pfizer (2024). L. De Michieli has received honoraria or travel grants from Pfizer Inc, Alnylam Pharmaceuticals, AstraZeneca Spa, Takeda Pharmaceutical, Chiesi, Sanofi and Euro Medica. Prof. Stefano Perlini has advisory role for Pfizer, AstraZeneca, Alnylam, Bayer and Prothena, and has received honoraria from Prothena, Pfizer, and AstraZeneca. The remaining authors have nothing to disclose.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"15"}}