{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,13]],"date-time":"2026-04-13T13:53:12Z","timestamp":1776088392930,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Pfizer SLU"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Hereditary transthyretin amyloidosis (ATTRv) is an autosomal-dominant systemic disease, where amyloid fibrils accumulate especially in the peripheral and autonomic nervous systems and in the heart. The aim of the present work was to outline the follow-up and type of management received by asymptomatic carriers (ACs) and Coutinho stage 1 ATTRv patients in Spain. Methods: A cross-sectional, non-interventional study was conducted throughout seven experienced hospitals in Spain. A total of 86 ACs without neurological symptoms and 19 Coutinho stage 1 ATTRv patients diagnosed 12 months before their enrollment were included. Clinical and demographic data, red flags, and neurological and cardiological evaluations were gathered. In addition, site variables were collected from four centers to describe the clinical management of ATTRv. Results: ATTRv clinical management varied depending on the center setting but was primarily overseen by neurology and internal medicine, which were responsible for the holistic follow-up of ACs and patients. Routinely, neurologists, neurophysiologists, cardiologists, and internal medicine conducted the follow-up. Specialties involved in initial AC assessment were neurophysiologists and cardiologists in 100% of cases, neurologists (75%), internists and geneticists (50%), and ophthalmologists (25%). A review of the medical tests performed proved an exhaustive management of the study population. Stable patients were followed up every 6 months, while those under evolution were monitored every 3\u20136 months. The frequency of monitoring of ACs was annual, and carriers classified with doubtful disease onset were visited every 3\u20136 months. Conclusions: The EMPATIa study provides valuable insights into the management of ATTRv in a real-world clinical setting in highly experienced hospitals in Spain. It demonstrates that multidisciplinary practice and enhanced disease awareness may lead to a reduction in diagnostic delay.<\/jats:p>","DOI":"10.3390\/jcm13247587","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T05:55:45Z","timestamp":1734069345000},"page":"7587","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Management of Hereditary Transthyretin Amyloidosis (ATTRv) Patients and Asymptomatic Carriers in Spain: The EMPATIa Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-0843","authenticated-orcid":false,"given":"In\u00e9s","family":"Losada L\u00f3pez","sequence":"first","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Son Ll\u00e0tzer, Palma de Mallorca, 07198 Palma, Spain"},{"name":"Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis, Instituto de Investigaci\u00f3n Sanitaria de las Islas Baleares (IdISBa), 07198 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Gonzalez-Moreno","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Son Ll\u00e0tzer, Palma de Mallorca, 07198 Palma, Spain"},{"name":"Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis, Instituto de Investigaci\u00f3n Sanitaria de las Islas Baleares (IdISBa), 07198 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Buades Rein\u00e9s","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Son Ll\u00e0tzer, Palma de Mallorca, 07198 Palma, Spain"},{"name":"Balearic Research Group in Genetic Cardiopathies, Sudden Death and TTR Amyloidosis, Instituto de Investigaci\u00f3n Sanitaria de las Islas Baleares (IdISBa), 07198 Palma, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teresa","family":"Sevilla","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Universitari i Polit\u00e8cnic La Fe & IIS La Fe Universitat de Val\u00e8ncia, 46010 Valencia, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernando","family":"Martinez Valle","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Vall d\u2019Hebron, 08035 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luc\u00eda","family":"Gal\u00e1n D\u00e1vila","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Cl\u00ednico San Carlos, IdISSC, 28040 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francisco","family":"Mu\u00f1oz Beamud","sequence":"additional","affiliation":[{"name":"Internal Medicine Department, Hospital Universitario Juan Ram\u00f3n Jim\u00e9nez, 21005 Huelva, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jos\u00e9 Eulalio","family":"B\u00e1rcena Llona","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Universitario Cruces, 48903 Barakaldo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Romero Acebal","sequence":"additional","affiliation":[{"name":"Neurology Department, Hospital Universitario Virgen de la Victoria, 29010 M\u00e1laga, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Tarilonte","sequence":"additional","affiliation":[{"name":"Pfizer S.L.U., 28108 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5081-6469","authenticated-orcid":false,"given":"Francesca","family":"Setaro","sequence":"additional","affiliation":[{"name":"Pfizer S.L.U., 28108 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105313","DOI":"10.1016\/j.neuint.2022.105313","article-title":"Transthyretin: Its function and amyloid formation","volume":"155","author":"Ueda","year":"2022","journal-title":"Neurochem. Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s10741-021-10080-2","article-title":"Screening for ATTR amyloidosis in the clinic: Overlapping disorders, misdiagnosis, and multiorgan awareness","volume":"27","author":"Karam","year":"2022","journal-title":"Heart Fail. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"w30053","DOI":"10.4414\/SMW.2021.w30053","article-title":"Management of transthyretin amyloidosis","volume":"151","author":"Condoluci","year":"2021","journal-title":"Swiss Med. Wkly."},{"key":"ref_4","first-page":"126","article-title":"Transthyretin amyloid cardiomyopathy","volume":"156","author":"Dominguez","year":"2021","journal-title":"Med. Clin."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1038\/s41467-019-08609-z","article-title":"A molecular mechanism for transthyretin amyloidogenesis","volume":"10","author":"Yee","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s13023-022-02359-w","article-title":"Clinical and genetic profile of patients enrolled in the Transthyretin Amyloidosis Outcomes Survey (THAOS): 14-year update","volume":"17","author":"Dispenzieri","year":"2022","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1080\/13506129.2018.1556156","article-title":"Early diagnosis of ATTR amyloidosis through targeted follow-up of identified carriers of TTR gene mutations","volume":"26","author":"Damy","year":"2019","journal-title":"Amyloid"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ibrahim, R.B., Liu, Y.T., Yeh, S.Y., and Tsai, J.W. (2019). Contributions of Animal Models to the Mechanisms and Therapies of Transthyretin Amyloidosis. Front. Physiol., 10.","DOI":"10.3389\/fphys.2019.00338"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/s13023-024-03304-9","article-title":"A description of variant transthyretin amyloidosis (ATTRv) stage 1 patients and asymptomatic carriers in Spain: The EMPATIa study","volume":"19","author":"Sevilla","year":"2024","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1007\/s00415-019-09688-0","article-title":"Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy","volume":"268","author":"Adams","year":"2021","journal-title":"J. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41582-019-0210-4","article-title":"Hereditary transthyretin amyloidosis: A model of medical progress for a fatal disease","volume":"15","author":"Adams","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/jns.12153","article-title":"\u201cRed-flag\u201d symptom clusters in transthyretin familial amyloid polyneuropathy","volume":"21","author":"Obici","year":"2016","journal-title":"J. Peripher. Nerv. Syst."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e13296","DOI":"10.1111\/eci.13296","article-title":"Multidisciplinary approach in the management of hATTR","volume":"50","author":"Losada","year":"2020","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e006075","DOI":"10.1161\/CIRCHEARTFAILURE.119.006075","article-title":"Expert Consensus Recommendations for the Suspicion and Diagnosis of Transthyretin Cardiac Amyloidosis","volume":"12","author":"Maurer","year":"2019","journal-title":"Circ. Heart Fail."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1161\/CIRCULATIONAHA.118.038169","article-title":"Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis","volume":"140","author":"Lane","year":"2019","journal-title":"Circulation"},{"key":"ref_16","first-page":"149","article-title":"Clinical profile and outcome of cardiac amyloidosis in a Spanish referral center","volume":"74","author":"Oteo","year":"2021","journal-title":"Rev. Esp. Cardiol. (Engl. Ed.)"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1097\/WCO.0000000000000289","article-title":"First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy","volume":"29","author":"Adams","year":"2016","journal-title":"Curr. Opin. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/13506129.2019.1627312","article-title":"Assessment of patients with hereditary transthyretin amyloidosis\u2014Understanding the impact of management and disease progression","volume":"26","author":"Coelho","year":"2019","journal-title":"Amyloid"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1080\/13506129.2022.2052838","article-title":"Guidelines and new directions in the therapy and monitoring of ATTRv amyloidosis","volume":"29","author":"Ando","year":"2022","journal-title":"Amyloid"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1002\/ejhf.2198","article-title":"Expert consensus on the monitoring of transthyretin amyloid cardiomyopathy","volume":"23","author":"Bengel","year":"2021","journal-title":"Eur. J. Heart Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1080\/14737167.2021.1933948","article-title":"Health and economic impact of the correct diagnosis of transthyretin cardiac amyloidosis in Spain","volume":"21","author":"Formiga","year":"2021","journal-title":"Expert Rev. 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