{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:41:04Z","timestamp":1791319264520,"version":"4.3.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"vor","delay-in-days":440,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18k08078"],"award-info":[{"award-number":["18k08078"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18k08078"],"award-info":[{"award-number":["18k08078"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>A fourth heart sound (S4) was reported to be almost never present in patients with amyloid light-chain cardiomyopathy. There have been no reports on S4 in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). This study aimed to clarify the clinical implications of S4 in patients with ATTRwt-CM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Seventy-six patients with ATTRwt-CM (mean age: 80.4 \u00b1 5.4 years, 68 males) who had undergone phonocardiography (PCG) were retrospectively assessed. We measured S4 amplitude on digitally recorded PCG. S4 was considered to be present when its amplitude was 1.0 mm or greater on the PCG. Distinct S4 was defined as S4 with an amplitude of 2.0 mm or greater, which is usually recognizable by auscultation. According to the rhythm and presence or absence of S4, the patients were divided into three groups, namely, sinus rhythm (SR) with S4, SR without S4, and non-SR. Non-SR consisted of atrial fibrillation, atrial flutter, and atrial tachycardia. Thirty-six patients were in SR and the remaining 40 patients were in non-SR. In the 36 patients in SR, S4 was shown by PCG to be present in 17 patients (47%), and distinct S4 was recognized in 7 patients (19%) by auscultation. In patients who were in SR, those with S4 had higher systolic blood pressure (124 \u00b1 15 vs. 99 \u00b1 8 mmHg, P &amp;lt; 0.001), lower level of plasma B-type natriuretic peptide (308 [interquartile range (IQR): 165, 354] vs. 508 [389, 765] pg\/mL, P = 0.034) and lower level of high-sensitivity cardiac troponin T (0.068 [0.046, 0.089] vs. 0.109 [0.063, 0.148] ng\/mL, P = 0.042) than those without S4. There was no significant difference in left atrium (LA) volume index or LA reservoir strain between patients with S4 and without S4. Patients with S4 had more preserved LA systolic function than those without S4 (peak atrial filling velocity: 53 \u00b1 25 vs. 34 \u00b1 9 cm\/s, P = 0.033; LA contractile strain: 4.1 \u00b1 2.1 vs. 1.6 \u00b1 2.0%, P = 0.012). Patients in SR without S4 had worse short-term prognosis compared with the other two groups (generalized Wilcoxon test, P = 0.033).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>S4 was present in 47% of the patients in SR with ATTRwt-CM. Patients in SR without S4 had more impaired LA systolic function than those in SR with S4. The absence of S4 portends a poor short-term prognosis in patients with ATTRwt-CM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.14937","type":"journal-article","created":{"date-parts":[[2024,8,2]],"date-time":"2024-08-02T00:39:44Z","timestamp":1722559184000},"page":"4000-4008","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Importance of Fourth Heart Sound and Preserved Left Atrial Function in Wild-Type Transthyretin Amyloidosis"],"prefix":"10.1093","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3307-8555","authenticated-orcid":false,"given":"Yuri","family":"Ochi","sequence":"first","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naohito","family":"Yamasaki","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Kubo","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichi","family":"Baba","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayoshi","family":"Hirota","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoyuki","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Kitaoka","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University , Kochi ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,8,1]]},"reference":[{"key":"2026012113114916300_ehf214937-bib-0001","volume-title":"Clinical methods: The history, physical, and laboratory examinations","author":"Williams","year":"1990","edition":"3rd edition"},{"key":"2026012113114916300_ehf214937-bib-0002","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1136\/hrt.48.1.1","article-title":"The frontiers of cardiomyopathy","volume":"48","author":"Goodwin","year":"1982","journal-title":"Br Heart J"},{"key":"2026012113114916300_ehf214937-bib-0003","doi-asserted-by":"crossref","first-page":"2790","DOI":"10.1001\/jama.1978.03280530054029","article-title":"Current concepts of the genesis of heart sounds II. Third and fourth sounds","volume":"239","author":"Abrams","year":"1978","journal-title":"JAMA"},{"key":"2026012113114916300_ehf214937-bib-0004","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1161\/CIRCULATIONAHA.108.843334","article-title":"Systemic cardiac amyloidoses: Disease profiles and clinical courses of the 3 main types","volume":"120","author":"Rapezzi","year":"2009","journal-title":"Circulation"},{"key":"2026012113114916300_ehf214937-bib-0005","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1161\/CIRCULATIONAHA.115.018852","article-title":"Heart failure resulting from age-related cardiac amyloid disease associated with wild-type transthyretin: A prospective, observational cohort study","volume":"133","author":"Connors","year":"2016","journal-title":"Circulation"},{"key":"2026012113114916300_ehf214937-bib-0006","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000098","article-title":"Senile systemic amyloidosis: clinical features at presentation and outcome","volume":"2","author":"Pinney","year":"2013","journal-title":"Am Heart Assoc"},{"key":"2026012113114916300_ehf214937-bib-0007","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1093\/eurheartj\/ehx043","article-title":"Clinical characteristics of wild-type transthyretin cardiac amyloidosis: Disproving myths","volume":"38","author":"Gonz\u00e1lez-L\u00f3pez","year":"2017","journal-title":"Eur Heart J"},{"key":"2026012113114916300_ehf214937-bib-0008","doi-asserted-by":"publisher","first-page":"2047","DOI":"10.1161\/CIRCULATIONAHA.104.489187","article-title":"Diagnosis and management of the cardiac amyloidosis","volume":"112","author":"Falk","year":"2005","journal-title":"Circulation"},{"key":"2026012113114916300_ehf214937-bib-0009","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.jaccao.2021.08.009","article-title":"THAOS investigators. Temporal trends of wild-type transthyretin amyloid cardiomyopathy in the transthyretin amyloidosis outcomes survey","volume":"3","author":"Nativi-Nicolau","year":"2021","journal-title":"JACC CardioOncol"},{"key":"2026012113114916300_ehf214937-bib-0010","doi-asserted-by":"publisher","first-page":"1610","DOI":"10.1253\/circj.CJ-20-0110","article-title":"JCS 2020 guideline on diagnosis and treatment of cardiac amyloidosis","volume":"84","author":"Kitaoka","year":"2020","journal-title":"Circ J"},{"key":"2026012113114916300_ehf214937-bib-0011","doi-asserted-by":"publisher","first-page":"880","DOI":"10.1001\/jamacardio.2016.2839","article-title":"Multicenter study of planar technetium 99 m pyrophosphate cardiac imaging: Predicting survival for patients with ATTR cardiac amyloidosis","volume":"1","author":"Casta\u00f1o","year":"2016","journal-title":"JAMA Cardiol"},{"key":"2026012113114916300_ehf214937-bib-0012","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.jacc.2005.05.073","article-title":"Noninvasive etiologic diagnosis of cardiac amyloidosis using 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid scintigraphy","volume":"46","author":"Perugini","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2026012113114916300_ehf214937-bib-0013","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1093\/eurheartj\/ehab072","article-title":"Diagnosis and treatment of cardiac amyloidosis: A position statement of the ESC working group on myocardial and pericardial diseases","volume":"42","author":"Garcia-Pavia","year":"2021","journal-title":"Eur Heart J"},{"key":"2026012113114916300_ehf214937-bib-0014","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1253\/circj.CJ-17-0650","article-title":"Third and fourth heart sounds and myocardial fibrosis in hypertrophic cardiomyopathy","volume":"82","author":"Sato","year":"2018","journal-title":"Circ J"},{"key":"2026012113114916300_ehf214937-bib-0015","doi-asserted-by":"publisher","DOI":"10.1111\/anec.12932","article-title":"Absent fourth heart sound as a marker of adverse events in hypertrophic cardiomyopathy with sinus rhythm","volume":"27","author":"Sakai","year":"2022","journal-title":"Ann Noninvasive Electrocardiol"},{"key":"2026012113114916300_ehf214937-bib-0016","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2018.06.004","article-title":"Guidelines for performing a comprehensive transthoracic echocardiographic examination in adults: recommendations from the American Society of Echocardiography","volume":"32","author":"Mitchell","year":"2019","journal-title":"J Am Soc Echocardiogr"},{"key":"2026012113114916300_ehf214937-bib-0017","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1136\/heartjnl-2012-301961","article-title":"Echo-Doppler assessment of diastole: Flow, function and haemodynamics","volume":"99","author":"Gillebert","year":"2013","journal-title":"Heart"},{"key":"2026012113114916300_ehf214937-bib-0018","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"},{"key":"2026012113114916300_ehf214937-bib-0019","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"},{"key":"2026012113114916300_ehf214937-bib-0020","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/s0002-9149(00)00870-5","article-title":"Left atrial kinetic energy in AL amyloidosis: Can it detect early dysfunction?","volume":"86","author":"Murphy","year":"2000","journal-title":"Am J Cardiol"},{"key":"2026012113114916300_ehf214937-bib-0021","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1056\/NEJM199211263272205","article-title":"Brief report: Atrial systolic failure in primary amyloidosis","volume":"327","author":"Plehn","year":"1992","journal-title":"N Engl J Med"},{"key":"2026012113114916300_ehf214937-bib-0022","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.carpath.2006.01.005","article-title":"Patterns of isolated atrial amyloid: A study of 100 hearts on autopsy","volume":"15","author":"Steiner","year":"2006","journal-title":"Cardiovasc Pathol"},{"key":"2026012113114916300_ehf214937-bib-0023","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.jjcc.2016.07.012","article-title":"High recurrence of atrial fibrillation in patients with high tissue atrial natriuretic peptide and amyloid levels after concomitant maze and mitral valve surgery","volume":"69","author":"Park","year":"2017","journal-title":"J Cardiol"},{"key":"2026012113114916300_ehf214937-bib-0024","doi-asserted-by":"publisher","first-page":"3198","DOI":"10.1002\/ehf2.13442","article-title":"Restricted left atrial dilatation can visually differentiate cardiac amyloidosis from hypertrophic cardiomyopathy","volume":"8","author":"Higashi","year":"2021","journal-title":"ESC Heart Fail"},{"key":"2026012113114916300_ehf214937-bib-0025","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"},{"key":"2026012113114916300_ehf214937-bib-0026","doi-asserted-by":"publisher","first-page":"100633","DOI":"10.1016\/j.ijcha.2020.100633","article-title":"Electromechanical dissociation of left atrium in patients with cardiac amyloidosis by magnetic resonance: Prognostic and clinical correlates","volume":"31","author":"Aquaro","year":"2020","journal-title":"Int J Cardiol Heart Vasc"},{"key":"2026012113114916300_ehf214937-bib-0027","doi-asserted-by":"publisher","first-page":"1508","DOI":"10.1016\/j.jcmg.2021.01.016","article-title":"Prognostic utility of echocardiographic atrial and ventricular strain imaging in patients with cardiac amyloidosis","volume":"14","author":"Huntjens","year":"2021","journal-title":"JACC Cardiovasc Imaging"},{"key":"2026012113114916300_ehf214937-bib-0028","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.jcmg.2021.08.005","article-title":"Too stiff but still got rhythm: Left atrial myopathy and transthyretin cardiac amyloidosis","volume":"15","author":"Poterucha","year":"2022","journal-title":"JACC Cardiovasc Imaging"}],"container-title":["ESC Heart Failure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/11\/6\/4000\/64516858\/eschf_11_6_4000.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eschf\/article-pdf\/11\/6\/4000\/64516858\/eschf_11_6_4000.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T18:13:48Z","timestamp":1769019228000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eschf\/article\/11\/6\/4000\/8269335"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,1]]},"references-count":28,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,8,1]]},"published-print":{"date-parts":[[2024,12,1]]}},"URL":"https:\/\/doi.org\/10.1002\/ehf2.14937","relation":{},"ISSN":["2055-5822"],"issn-type":[{"value":"2055-5822","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,8,1]]},"assertion":[{"value":"2023-08-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-18","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}