{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:46:13Z","timestamp":1791992773656,"version":"4.4.0"},"reference-count":32,"publisher":"American Medical Association (AMA)","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Cardiol"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"\n Importance<\/jats:title>\n Left atrial (LA) dysfunction may play an important role in the pathophysiology of transthyretin amyloidosis with cardiomyopathy (ATTR-CM) and is driven by LA remodeling and amyloid infiltration.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To evaluate the prognostic significance of LA structure and function among patients with ATTR-CM and to assess the effects of vutrisiran on these parameters.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n Post hoc analyses were conducted of the HELIOS-B phase 3 randomized clinical trial, which enrolled patients with ATTR-CM between December 2019 and August 2021 at 87 sites in 26 countries. Median (IQR) follow-up was 36 (33-36) months. Data were analyzed from July through November 2025.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Vutrisiran (25 mg subcutaneously every 3 months) vs placebo.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The primary outcome was all-cause mortality (ACM) and recurrent cardiovascular events. LA structure (LA volume index [LAVi]) and function (LA reservoir [LASr], conduit [LAScd], and contractile strain [LASct]) were assessed, including the effect of vutrisiran on these measures at 30 months.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total of 655 patients were enrolled. Among 644 patients with measurable LA strain (median [IQR] age, 77 [72-80] years; 48 female patients [7.5%]; 569 (88.4%) with wild-type ATTR), mean (SD) LA strain measures were substantially below normal (LASr: 9.5% [6.0%]; LAScd: 6.9% [3.9%]; LASct: 4.2% [4.0%]). Patients with worse LASr had more advanced disease, more atrial fibrillation, and more left ventricular systolic and diastolic dysfunction. LASr and LASct were independently associated with ACM and recurrent cardiovascular events (LASr: hazard ratio [HR] per 5% worsening, 1.37; 95% CI, 1.13-1.68;\n P<\/jats:italic>\n \u2009=\u2009.002; LASct: HR per 5% worsening, 1.53; 95% CI, 1.08-2.17;\n P<\/jats:italic>\n \u2009=\u2009.02), recurrent heart failure hospitalizations (LASr: HR, 1.66; 95% CI, 1.22-2.25;\n P<\/jats:italic>\n \u2009=\u2009.001; LASct: HR, 2.23; 95% CI. 1.46-3.71;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001), and incident atrial fibrillation (LASr: HR, 1.30; 95% CI, 1.03-1.63;\n P<\/jats:italic>\n \u2009=\u2009.03; LASct: HR, 2.02; 95% CI, 1.38-2.96;\n P<\/jats:italic>\n \u2009&amp;lt;\u2009.001). In contrast, LAVi was not associated with these outcomes. LA strain measures at baseline did not modify the treatment effect of vutrisiran on ACM and recurrent cardiovascular events (LASr:\n P<\/jats:italic>\n value for interaction\u2009=\u2009.60; LAScd:\n P<\/jats:italic>\n value for interaction\u2009=\u2009.58; LASct:\n P<\/jats:italic>\n value for interaction\u2009=\u2009.47). Vutrisiran attenuated worsening in LA strain vs placebo at month 30 (LASr: +1.2%; 95% CI, +0.4% to +1.9%; LAScd: +0.8%; 95% CI, +0.3% to +1.4%; LASct: +0.8%; 95% CI, 0% to +1.6%).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Per the results of this secondary analysis of the HELIOS-B randomized clinical trial, LA dysfunction is common among patients with ATTR-CM and portends a worse prognosis. Consistent with its beneficial effects on other measures of cardiac structure and function, vutrisiran attenuated worsening in LA strain at 30 months, supporting the importance of LA function in the pathophysiology of ATTR-CM and the ability of silencer therapy with vutrisiran to attenuate worsening atrial myopathy in amyloid heart disease.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT04153149<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamacardio.2026.2992","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T15:30:54Z","timestamp":1787153454000},"page":"971","source":"Crossref","is-referenced-by-count":0,"title":["Left Atrial Structure and Function, Clinical Outcomes, and Efficacy of Vutrisiran in Transthyretin Amyloidosis With Cardiomyopathy"],"prefix":"10.1001","volume":"11","author":[{"given":"Karola S.","family":"Jering","sequence":"first","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Manafi","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"},{"name":"Department of Internal Medicine, University of Pittsburgh Medical Center Harrisburg, Harrisburg, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole K.","family":"Bart","sequence":"additional","affiliation":[{"name":"Department of Cardiology, St Vincent\u2019s Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narayana","family":"Prasad","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah M.","family":"Birkhoelzer","sequence":"additional","affiliation":[{"name":"University Hospitals Dorset, Bournemouth, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Hamatani","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lairez","sequence":"additional","affiliation":[{"name":"HealthAge Institute, Department of Cardiology, Toulouse University Hospital, University of Toulouse, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Tsujita","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian D.","family":"Gillmore","sequence":"additional","affiliation":[{"name":"National Amyloidosis Centre, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathew S.","family":"Maurer","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Columbia University Irving Medical Center, New York Presbyterian Hospital, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick Y.","family":"Jay","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals, Cambridge, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hicham","family":"Skali","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Fontana","sequence":"additional","affiliation":[{"name":"National Amyloidosis Centre, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Solomon","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"1","key":"hoi260041r1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jcmg.2021.06.022","article-title":"Clinical importance of left atrial infiltration in cardiac transthyretin amyloidosis.","volume":"15","author":"Bandera","year":"2022","journal-title":"JACC Cardiovasc Imaging"},{"issue":"11","key":"hoi260041r2","doi-asserted-by":"publisher","first-page":"2019","DOI":"10.1002\/ejhf.2650","article-title":"Atrial amyloidosis: mechanisms and clinical manifestations.","volume":"24","author":"Vergaro","year":"2022","journal-title":"Eur J Heart Fail"},{"issue":"9","key":"hoi260041r3","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1001\/jama.2024.0442","article-title":"Cardiac amyloidosis due to transthyretin protein: a review.","volume":"331","author":"Ruberg","year":"2024","journal-title":"JAMA"},{"issue":"8","key":"hoi260041r4","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1016\/j.jcmg.2025.04.007","article-title":"Primary left atrial cardiopathy in transthyretin amyloidosis cardiomyopathy by multimodality imaging: implications for thrombotic events.","volume":"18","author":"Ozbay","year":"2025","journal-title":"JACC Cardiovasc Imaging"},{"issue":"16","key":"hoi260041r5","doi-asserted-by":"publisher","first-page":"1549","DOI":"10.1016\/j.jacc.2022.01.053","article-title":"Association of left atrial structure and function with heart failure in older adults.","volume":"79","author":"Inciardi","year":"2022","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"hoi260041r6","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1093\/ehjci\/jeab202","article-title":"Left atrial strain predicts incident atrial fibrillation in the general population: the Copenhagen City Heart Study.","volume":"23","author":"Hauser","year":"2021","journal-title":"Eur Heart J Cardiovasc Imaging"},{"issue":"3","key":"hoi260041r7","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1002\/ejhf.1643","article-title":"Left atrial function in heart failure with preserved ejection fraction: a systematic review and meta-analysis.","volume":"22","author":"Khan","year":"2020","journal-title":"Eur J Heart Fail"},{"issue":"1","key":"hoi260041r8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/13506129.2022.2091985","article-title":"Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial.","volume":"30","author":"Adams","year":"2023","journal-title":"Amyloid"},{"issue":"1","key":"hoi260041r9","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1056\/NEJMoa2409134","article-title":"Vutrisiran in patients with transthyretin amyloidosis with cardiomyopathy.","volume":"392","author":"Fontana","year":"2025","journal-title":"N Engl J Med"},{"issue":"10","key":"hoi260041r10","doi-asserted-by":"publisher","first-page":"3560","DOI":"10.1038\/s41591-025-03851-z","article-title":"Effects of vutrisiran on cardiac structure and function in patients with transthyretin amyloidosis with cardiomyopathy: secondary outcomes of the HELIOS-B trial.","volume":"31","author":"Jering","year":"2025","journal-title":"Nat Med"},{"issue":"22","key":"hoi260041r11","doi-asserted-by":"publisher","first-page":"1998","DOI":"10.1001\/jama.2025.4347","article-title":"CONSORT 2025 statement: updated guideline for reporting randomized trials.","volume":"333","author":"Hopewell","year":"2025","journal-title":"JAMA"},{"issue":"30","key":"hoi260041r12","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1093\/eurheartj\/ehx589","article-title":"A new staging system for cardiac transthyretin amyloidosis.","volume":"39","author":"Gillmore","year":"2018","journal-title":"Eur Heart J"},{"issue":"6","key":"hoi260041r13","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1093\/ehjci\/jey042","article-title":"Standardization of left atrial, right ventricular, and right atrial deformation imaging using two-dimensional speckle tracking echocardiography: a consensus document of the EACVI\/ASE\/Industry Task Force to standardize deformation imaging.","volume":"19","author":"Badano","year":"2018","journal-title":"Eur Heart J Cardiovasc Imaging"},{"issue":"3","key":"hoi260041r14","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1093\/ehjci\/jev014","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.","volume":"16","author":"Lang","year":"2015","journal-title":"Eur Heart J Cardiovasc Imaging"},{"issue":"4","key":"hoi260041r15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","article-title":"Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging.","volume":"29","author":"Nagueh","year":"2016","journal-title":"J Am Soc Echocardiogr"},{"issue":"1","key":"hoi260041r16","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.echo.2016.09.007","article-title":"Normal ranges of left atrial strain by speckle-tracking echocardiography: a systematic review and meta-analysis.","volume":"30","author":"Pathan","year":"2017","journal-title":"J Am Soc Echocardiogr"},{"issue":"10","key":"hoi260041r17","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1093\/ehjci\/jex097","article-title":"Left atrial structure and function in cardiac amyloidosis.","volume":"18","author":"Nochioka","year":"2017","journal-title":"Eur Heart J Cardiovasc Imaging"},{"key":"hoi260041r18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2025.12.033","article-title":"Atrial Mechanical contraction predicts cerebrovascular risk in patients with transthyretin amyloid cardiomyopathy and sinus rhythm.","author":"Porcari","year":"2026","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"hoi260041r19","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/j.echo.2021.08.008","article-title":"Normal values of left atrial size and function and the impact of age: results of the World Alliance Societies of Echocardiography Study.","volume":"35","author":"Singh","year":"2022","journal-title":"J Am Soc Echocardiogr"},{"issue":"7","key":"hoi260041r20","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1002\/ejhf.1464","article-title":"Left atrial strain and compliance in the diagnostic evaluation of heart failure with preserved ejection fraction.","volume":"21","author":"Reddy","year":"2019","journal-title":"Eur J Heart Fail"},{"issue":"3","key":"hoi260041r21","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/j.jcmg.2024.08.005","article-title":"Mavacamten-associated temporal changes in left atrial function in obstructive HCM: insights from the VALOR-HCM trial.","volume":"18","author":"Desai","year":"2025","journal-title":"JACC Cardiovasc Imaging"},{"issue":"11","key":"hoi260041r22","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/j.jcmg.2023.01.015","article-title":"Prognostic utility of left atrial strain to predict thrombotic events and mortality in amyloid cardiomyopathy.","volume":"16","author":"Akintoye","year":"2023","journal-title":"JACC Cardiovasc Imaging"},{"issue":"21","key":"hoi260041r23","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.122.026875","article-title":"Left atrial strain and the risk of atrial arrhythmias from extended ambulatory cardiac monitoring: MESA.","volume":"11","author":"Huber","year":"2022","journal-title":"J Am Heart Assoc"},{"issue":"3","key":"hoi260041r24","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCIMAGING.123.016197","article-title":"Left atrial strain predicts subclinical atrial fibrillation detected by long-term continuous monitoring in elderly high-risk individuals.","volume":"17","author":"Olsen","year":"2024","journal-title":"Circ Cardiovasc Imaging"},{"issue":"3","key":"hoi260041r25","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/j.jcmg.2022.11.004","article-title":"Atrial longitudinal strain predicts new-onset atrial fibrillation: a systematic review and meta-analysis.","volume":"16","author":"Serenelli","year":"2023","journal-title":"JACC Cardiovasc Imaging"},{"issue":"4","key":"hoi260041r26","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1161\/01.CIR.92.4.835","article-title":"Left atrial size and the risk of stroke and death. the Framingham Heart Study.","volume":"92","author":"Benjamin","year":"1995","journal-title":"Circulation"},{"issue":"5","key":"hoi260041r27","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1161\/CIRCULATIONAHA.116.024825","article-title":"Contemporary assessment of left ventricular diastolic function in older adults: the Atherosclerosis Risk in Communities Study.","volume":"135","author":"Shah","year":"2017","journal-title":"Circulation"},{"issue":"6","key":"hoi260041r28","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.jacc.2025.06.022","article-title":"Effects of vutrisiran on cardiac function and outcomes in patients with transthyretin amyloidosis with cardiomyopathy.","volume":"86","author":"Jering","year":"2025","journal-title":"J Am Coll Cardiol"},{"issue":"14","key":"hoi260041r29","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.1093\/eurheartj\/ehz905","article-title":"Echocardiographic phenotype and prognosis in transthyretin cardiac amyloidosis.","volume":"41","author":"Chacko","year":"2020","journal-title":"Eur Heart J"},{"issue":"7","key":"hoi260041r30","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1253\/circrep.CR-25-0066","article-title":"Comparing effects of tafamidis in controlling left ventricular and left atrial strains in patients with wild-type transthyretin amyloid cardiomyopathy.","volume":"7","author":"Eguchi","year":"2025","journal-title":"Circ Rep"},{"issue":"5","key":"hoi260041r31","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.3390\/jcm14051538","article-title":"One-year echocardiographic follow-up in transthyretin cardiac amyloidosis: impact of tafamidis treatment.","volume":"14","author":"Restelli","year":"2025","journal-title":"J Clin Med"},{"issue":"1","key":"hoi260041r32","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1080\/13506129.2022.2131385","article-title":"Impact of tafamidis on myocardial strain in transthyretin amyloid cardiomyopathy.","volume":"30","author":"Rettl","year":"2023","journal-title":"Amyloid"}],"container-title":["JAMA Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/articlepdf\/2852974\/jamacardiology_jering_2026_oi_260041_1790870211.79466.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:00:58Z","timestamp":1791990058000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamacardiology\/fullarticle\/2852974"}},"subtitle":["A Secondary Analysis of the HELIOS-B Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":32,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jamacardio.2026.2992","relation":{},"ISSN":["2380-6583"],"issn-type":[{"value":"2380-6583","type":"print"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}