[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"detail-sidebar-cat-0-en-105":3,"doc-seo-433303-105":59,"doc-detail-433303-en":130},{"code":4,"msg":5,"data":6},0,"success",[7,13,18,23,28,33,38,43,48,51,55],{"id":8,"doc_module":4,"doc_module_name":9,"category_name":10,"show_sort_weight":11,"slug":12},1,"Document","Story & Novel",90,"story-novel",{"id":14,"doc_module":4,"doc_module_name":9,"category_name":15,"show_sort_weight":16,"slug":17},2,"Literature",80,"literature",{"id":19,"doc_module":4,"doc_module_name":9,"category_name":20,"show_sort_weight":21,"slug":22},4,"Exam",70,"exam",{"id":24,"doc_module":4,"doc_module_name":9,"category_name":25,"show_sort_weight":26,"slug":27},5,"Comic",60,"comic",{"id":29,"doc_module":4,"doc_module_name":9,"category_name":30,"show_sort_weight":31,"slug":32},6,"Technology",50,"technology",{"id":34,"doc_module":4,"doc_module_name":9,"category_name":35,"show_sort_weight":36,"slug":37},7,"Healthcare",40,"healthcare",{"id":39,"doc_module":4,"doc_module_name":9,"category_name":40,"show_sort_weight":41,"slug":42},8,"Research & Report",30,"research-report",{"id":44,"doc_module":4,"doc_module_name":9,"category_name":45,"show_sort_weight":46,"slug":47},9,"Religion & Spirituality",20,"religion-spirituality",{"id":46,"doc_module":4,"doc_module_name":9,"category_name":49,"show_sort_weight":46,"slug":50},"World Cup","world-cup",{"id":52,"doc_module":4,"doc_module_name":9,"category_name":53,"show_sort_weight":52,"slug":54},10,"Lifestyle","lifestyle",{"id":56,"doc_module":4,"doc_module_name":9,"category_name":57,"show_sort_weight":24,"slug":58},19,"General","general",{"code":4,"msg":60,"data":61},"ok",{"site_id":62,"language":63,"slug":64,"title":65,"keywords":66,"description":67,"schema_data":68,"social_meta":123,"head_meta":125,"extra_data":127,"updated_unix":129},105,"en","transthyretin-amyloid-cardiomyopathy-from-cause-to-novel-treatments","Transthyretin amyloid cardiomyopathy: from cause to novel treatments","","Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive heart disorder characterized by amyloid deposition that eventually impairs cardiac performance. Recent therapeutic progress tracks a growing understanding of ATTR-CM pathophysiology, including a hypothesis that disease progression is driven by an imbalance between amyloid production and natural clearance. TTR stabilizers slow functional decline by preserving the TTR tetramer, while gene-silencing and gene-editing reduce hepatic TTR synthesis, yet neither fully restores amyloid clearance capacity. Monoclonal antibodies targeting TTR amyloid are under development, with early trials suggesting potential reversal of progression and improved heart function.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/transthyretin-amyloid-cardiomyopathy-from-cause-to-novel-treatments/433303/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/transthyretin-amyloid-cardiomyopathy-from-cause-to-novel-treatments/433303.png","ImageObject",300,407,{"name":92,"@type":93},"dhado","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-31","2026-09-29",true,{"@type":102,"interactionType":103,"userInteractionCount":39},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"What defines transthyretin amyloid cardiomyopathy (ATTR-CM)?","Question",{"text":112,"@type":113},"ATTR-CM is defined by progressive amyloid deposition in the heart that impairs cardiac function over time.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"How might imbalance between amyloid production and clearance drive progression?",{"text":117,"@type":113},"The document describes an emerging hypothesis that an in vivo imbalance between amyloid production and natural clearance may drive disease progression, though it still needs validation.",{"name":119,"@type":110,"acceptedAnswer":120},"Why are new agents still needed beyond TTR stabilizers and gene-silencing therapies?",{"text":121,"@type":113},"TTR stabilizers and gene-silencers reduce amyloid formation or production, but they do not enhance the body’s limited capacity to clear existing amyloid deposits.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},433303,1790741633,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":39,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144,"preview_page_count":4},5909893218464,"https://ap-avatar.wpscdn.com/davatar_085a072bc5b1113ac321206ff7593b45","European Heart Journal (2026) 47, 54–63 [https://doi.org/10.1093/eurheartj/ehaf667](https://doi.org/10.1093/eurheartj/ehaf667)  \nSTATE OF THE ART REVIEW  \nHeart failure and cardiomyopathies  \nTransthyretin amyloid cardiomyopathy: from cause to novel treatments  \nMarianna Fontana  1,*, Alberto Aimo2,3, Michele Emdin  2,3, Aldostefano Porcari  1,4,5, Scott D. Solomon6, Philip N. Hawkins  1, and Julian D. Gillmore1  \n1National Amyloidosis Centre, University College London, Royal Free Campus, Rowland Hill Street, London NW3 2PF, UK; 2Health Science Interdisciplinary Center, Scuola Superiore Sant’Anna, Pisa, Italy; 3Cardiology Department, Fondazione Toscana Gabriele Monasterio, Pisa, Italy; 4Cardiovascular Department, Center for Diagnosis and Treatment of Cardiomyopathies, Azienda Sanitaria Universitaria Giuliano-Isontina (ASUGI), University of Trieste, Trieste, Italy; 5European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Trieste, Italy; and 6Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA  \nReceived 1 March 2025; revised 1 April 2025; accepted 16 August 2025; online publish-ahead-of-print 1 October 2025  \nGraphical Abstract  \nBlockade of further amyloid deposition Amyloid clearance  \nLiver  \nTTR tetramer  \nMonomer  \nMisfolded monomer  \nAmyloid 􀀅brils  \nATTR  \ncardiomyopathy  \nNatural mechanisms: macrophages, complement?  \nMonoclonal Abs: NNC019–0001 (PRX004) ALXN2220 (NI006)  \nATTR cardiomyopathy: from mechanisms to treatments  \nBalance between amyloid deposition and clearance: theoretical models  \nLow rate of natural clearance + reduction of new amyloid deposition  \nHigh rate of natural clearance + reduction of new amyloid deposition  \nLow rate of natural clearance + reduction of new amyloid deposition + treatment promoting amyloid clearance  \n Patisiran, Vutrisiran, Inotersen, Eplontersen, nex-z  Tafamidis, Acoramidis  \nLow natural clearance,  \nuntreated  \nAmyloid  \nTime  \n Rate of amyloid production  Amyloid burden  \n Rate of amyloid clearance  \nStart of treatment  \nthat  new amyloid production  \nStart of treatment  \nthat  new amyloid production  \nStart of treatment  \nthat  new amyloid production  \nStart of treatment  \nthat  deposits  \nImbalance between amyloid deposition and clearance as the driver of transthyretin amyloidosis onset and progression: perspectives for treatment. Abs, antibodies; nex-z, nexiguran ziclumeran; TTR, transthyretin.  \n* Corresponding author. Tel: +44 20 7433 2764, Fax: +44 20 7433 2803, [Email:](Email: m.fontana@ucl.ac.uk)[ m.fontana@ucl.ac.uk](Email: m.fontana@ucl.ac.uk)  \n© The Author(s) 2025. Published by Oxford University Press on behalf of the European Society of Cardiology.  \nThis is an Open Access article distributed under the terms of the Creative Commons Attribution License ([https://creativecommons.org/licenses/by/4.0/](https://creativecommons.org/licenses/by/4.0/)), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.  \nAbstract  \nTransthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive disorder marked by amyloid deposition in the heart, ultimately impairing cardiac function. Recent treatment advances have paralleled an evolving understanding of ATTR-CM pathophysiology. One emerging hypothesis suggests that an imbalance between in vivo amyloid production and natural clearance may drive disease progression, a conceptual framework that still requires validation. Transthyretin (TTR) stabilizers, such as tafamidis and acoramidis, mitigate amyloid formation by promoting the native tetrameric conformation of circulating TTR, thereby slowing functional decline and prolonging survival. Similarly, TTR gene silencers inhibit hepatic TTR synthesis, and gene-editing therapy with nexiguran ziclumeran offers an additional strategy to reduce amyloid production. However, these approaches do not enhance the body’s limited capacity ","cbCaimIJsRuaiMCS","https://ap.wps.com/l/cbCaimIJsRuaiMCS","pdf",954449,"English","# Heart failure and cardiomyopathies\n## Transthyretin amyloid cardiomyopathy: from cause to novel treatments\n## Abstract\n## Keywords\n## Systemic amyloidosis and ATTR overview","[{\"question\":\"What defines transthyretin amyloid cardiomyopathy (ATTR-CM)?\",\"answer\":\"ATTR-CM is defined by progressive amyloid deposition in the heart that impairs cardiac function over time.\"},{\"question\":\"How might imbalance between amyloid production and clearance drive progression?\",\"answer\":\"The document describes an emerging hypothesis that an in vivo imbalance between amyloid production and natural clearance may drive disease progression, though it still needs validation.\"},{\"question\":\"Why are new agents still needed beyond TTR stabilizers and gene-silencing therapies?\",\"answer\":\"TTR stabilizers and gene-silencers reduce amyloid formation or production, but they do not enhance the body’s limited capacity to clear existing amyloid deposits.\"}]","Transthyretin amyloid cardiomyopathy: from cause to novel treatments | PDF",1790663508,25]