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The CRONOS-ATTR study aimed to improve early detection of ATTR-CM by integrating multimodal data (clinical, electrocardiographic, and echocardiographic) within a model-guided medicine framework.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using artificial intelligence (AI) algorithms from CardiolyseECGSoftware and Ligence Heart, along with human intelligence (multidimensional interpretable models), we standardized and harmonized heterogeneous data sources into a unified patient-specific model (PSM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A machine learning model based on XGBoost was trained on a cohort of 124 patients and achieved strong diagnostic performance (AUC 0.84), with high sensitivity and precision. The model provided interpretable outputs using SHAP values, facilitating clinical understanding and trust. This approach not only enabled accurate early detection of ATTR-CM but also demonstrated feasibility for integration into real-world clinical workflows.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings support the use of explainable AI to enhance screening strategies for cardiac amyloidosis and establish a foundation for scalable, automated tools that can be embedded within healthcare systems.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11548-026-03640-0","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T13:05:27Z","timestamp":1782306327000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Model-guided medicine for early diagnosis of transthyretin-associated cardiac amyloidosis using multimodal data integration and standardized interoperable models (the CRONOS-ATTR study)"],"prefix":"10.1007","author":[{"given":"Ra\u00fal","family":"Ramos-Polo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergi","family":"Yun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorena","family":"Herrador","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"de Frutos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00edlvia","family":"Jovells-Vaqu\u00e9","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreea Eunice","family":"Cosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Ricarte Marin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Herrero Ant\u00f3n de Vez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oriol","family":"Guardia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Casasnovas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Enjuanes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Revent\u00f3s Puigjaner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Gonz\u00e1lez-Costello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-720X","authenticated-orcid":false,"given":"Josep","family":"Com\u00edn-Colet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"3640_CR1","doi-asserted-by":"publisher","DOI":"10.1007\/S40119-021-00219-5","volume":"10","author":"MH Rozenbaum","year":"2021","unstructured":"Rozenbaum MH, Large S, Bhambri R, Stewart M, Whelan J, van Doornewaard A, Dasgupta N, Masri A, Nativi-Nicolau J (2021) Impact of delayed diagnosis and misdiagnosis for patients with transthyretin amyloid cardiomyopathy (ATTR-CM): a targeted literature review. 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This collaboration is formalized under the \u201cACUERDO DE COLABORACI\u00d3N EN ACTIVIDADES DE INVESTIGACI\u00d3N Y DESARROLLO Y COTITULARIDAD DE LOS DERECHOS DE PROPIEDAD INDUSTRIAL E INTELECTUAL QUE SE DERIVEN DE LOS RESULTADOS DE DICHAS ACTIVIDADES ENTRE, L\u2019HOSPITAL UNIVERSITARI DE BELLVITGE, EL INSTITUT D\u2019INVESTIGACI\u00d3 BIOM\u00c8DICA DE BELLVITGE Y ALMA IT SYSTEMS S.L.\u201d, signed by the parties on January 25, 2023. Two of the researchers involved in the development of this study, Hugo Herrero Ant\u00f3n de Vez and Oriol Guardia, are affiliated with Alma IT Systems. Hugo Herrero Ant\u00f3n de Vez serves on the administration board of Alma, is the director of Research and Development, and is an expert in model-guided medicine (MGM). Oriol Guardia was employed as an engineer at Alma at the time this research was conducted. Both researchers declare a conflict of interest as a result of their positions within Alma. This disclosure is made in compliance with the requirements for transparency and to ensure that any potential conflicts of interest are fully acknowledged in relation to the results of this study. Silvia Jovells-Vaqu\u00e9 is hired with a PERIS grant. Please note that the present research did not receive any funding from a PERIS grant.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Informed consent was obtained from all subjects involved in this study. All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments. Approval was granted by the Ethics Committee of Bellvitge University Hospital.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed Consent Statement and Ethics approval"}}]}}