{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:59:12Z","timestamp":1781614752542,"version":"3.54.5"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In wild-type transthyretin amyloidosis (ATTRwt), the deposition of transthyretin in the myocardium leads to progressive heart failure. However, little is known about the short-term natural progression of this disease and potential predictors of outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives &amp; methods<\/jats:title>\n                    <jats:p>Therefore, this study longitudinally analyzed the clinical findings (ECG, echocardiography, and laboratory tests) of 65 patients suffering from ATTRwt at baseline and at follow-up visits after 12\u2009months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 44 patients (67.7%) presented with abnormal ECGs, prolonged PR and QRS durations and low-voltage patterns. Pacemaker placement was performed in eleven patients (16.9%). At the one-year follow-up visit, we detected significant increases in the QRS duration (from 119.7\u2009\u00b1\u20094.0 to 125.9\u2009\u00b1\u20094.3\u2009ms;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05), intraventricular septum thickness (from 18.9\u2009\u00b1\u20090.5\u2009mm to 19.9\u2009\u00b1\u20090.5\u2009mm;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) and ejection fraction (EF) (from 45.4\u2009\u00b1\u20092.1% to 38.9\u2009\u00b1\u20092.6%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05) compared with those at the baseline visit. During follow-up, 16 patients (24.6%) died. Predictors of worse outcomes were progression in QRS duration, low EF, reduced renal function, impaired right ventricular function and the need for pacemaker implantation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In ATTRwt, precise evaluation via routine cardiac diagnosis helps to identify patients with an elevated risk of mortality. Patients with prolonged QRS duration, progressive myocardial hypertrophy, right ventricular failure, reduced renal function and the need for cardiac pacemakers are at increased risk for one-year mortality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04078-4","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T12:18:37Z","timestamp":1760962717000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Progression of QRS duration \u2013 a potential surrogate marker of survival in ATTRwt amyloidosis patients"],"prefix":"10.1186","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0139-4200","authenticated-orcid":false,"given":"Selina","family":"Hein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabian","family":"aus dem Siepen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja M.","family":"Zierleyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Knoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo A.","family":"Katus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Frey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnt V.","family":"Kristen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"4078_CR1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.20517\/2574-1209.2022.05","volume":"6","author":"M De Gaspari","year":"2022","unstructured":"De Gaspari M, Finato N, Basso C. Cardiac amyloidosis: The pathologist\u2019s point of view. Vessel Plus. 2022;657.","journal-title":"Vessel Plus"},{"issue":"5","key":"4078_CR2","first-page":"343","volume":"91","author":"A Eriksson","year":"1983","unstructured":"Eriksson A, Eriksson P, Olofsson BO, et al. The cardiac atrioventricular conduction system in familial amyloidosis with polyneuropathy. A clinico-pathologic study of six cases from Northern Sweden. Acta Pathol Microbiol Immunol Scand A. 1983;91(5):343\u201349.","journal-title":"Acta Pathol Microbiol Immunol Scand A"},{"issue":"5","key":"4078_CR3","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1016\/0002-9343(77)90870-1","volume":"62","author":"RL Ridolfi","year":"1977","unstructured":"Ridolfi RL, Bulkley BH, Hutchins GM. The conduction system in cardiac amyloidosis. Clinical and pathologic features of 23 patients. Am J Med. 1977;62(5):677\u201386.","journal-title":"Am J Med"},{"issue":"22","key":"4078_CR4","doi-asserted-by":"publisher","first-page":"2872","DOI":"10.1016\/j.jacc.2019.04.003","volume":"73","author":"FL Ruberg","year":"2019","unstructured":"Ruberg FL, Grogan M, Hanna M, et al. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol. 2019;73(22):2872\u201391.","journal-title":"J Am Coll Cardiol"},{"issue":"3","key":"4078_CR5","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1161\/CIRCULATIONAHA.115.018852","volume":"133","author":"LH Connors","year":"2016","unstructured":"Connors LH, Sam F, Skinner M, et al. Heart failure resulting from age-related cardiac amyloid disease associated with Wild-Type Transthyretin: A prospective, observational cohort study. Circulation. 2016;133(3):282\u201390.","journal-title":"Circulation"},{"issue":"30","key":"4078_CR6","doi-asserted-by":"publisher","first-page":"2799","DOI":"10.1093\/eurheartj\/ehx589","volume":"39","author":"JD Gillmore","year":"2018","unstructured":"Gillmore JD, Damy T, Fontana M, et al. A new staging system for cardiac transthyretin amyloidosis. Eur Heart J. 2018;39(30):2799\u2013806.","journal-title":"Eur Heart J"},{"issue":"10","key":"4078_CR7","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1016\/j.jacc.2016.06.033","volume":"68","author":"M Grogan","year":"2016","unstructured":"Grogan M, Scott CG, Kyle RA, et al. Natural history of wild-type transthyretin cardiac amyloidosis and risk stratification using a novel staging system. J Am Coll Cardiol. 2016;68(10):1014\u201320.","journal-title":"J Am Coll Cardiol"},{"issue":"2","key":"4078_CR8","doi-asserted-by":"publisher","first-page":"e000098","DOI":"10.1161\/JAHA.113.000098","volume":"2","author":"JH Pinney","year":"2013","unstructured":"Pinney JH, Whelan CJ, Petrie A, et al. Senile systemic amyloidosis: Clinical features at presentation and outcome. J Am Heart Assoc. 2013;2(2):e000098.","journal-title":"J Am Heart Assoc"},{"issue":"45","key":"4078_CR9","doi-asserted-by":"publisher","first-page":"4722","DOI":"10.1093\/eurheartj\/ehac363","volume":"43","author":"A Martinez-Naharro","year":"2022","unstructured":"Martinez-Naharro A, Patel R, Kotecha T, et al. Cardiovascular magnetic resonance in light-chain amyloidosis to guide treatment. Eur Heart J. 2022;43(45):4722\u201335.","journal-title":"Eur Heart J"},{"key":"4078_CR10","first-page":"353","volume":"7","author":"H Bazett","year":"1920","unstructured":"Bazett H. An analysis of the time-relations of electrocardiograms. Heart. 1920;7:353\u201370.","journal-title":"Heart"},{"issue":"3","key":"4078_CR11","doi-asserted-by":"publisher","first-page":"e006619","DOI":"10.1161\/CIRCHEARTFAILURE.119.006619","volume":"13","author":"F Cappelli","year":"2020","unstructured":"Cappelli F, Vignini E, Martone R, et al. Baseline ECG features and arrhythmic profile in transthyretin versus light chain cardiac amyloidosis. Circ Heart Fail. 2020;13(3):e006619.","journal-title":"Circ Heart Fail"},{"issue":"6","key":"4078_CR12","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1016\/j.jelectrocard.2008.06.021","volume":"41","author":"JE Madias","year":"2008","unstructured":"Madias JE. Low QRS voltage and its causes. J Electrocardiol. 2008;41(6):498\u2013500.","journal-title":"J Electrocardiol"},{"key":"4078_CR13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1136\/hrt.82.2.192","volume":"82","author":"BW Lb","year":"1999","unstructured":"Lb BW, Tolagen K, Wranne B. Echocardiographic assessment of ejection fraction in left ventricular hypertrophy. Heart. 1999;82:192\u201398.","journal-title":"Heart"},{"key":"4078_CR14","unstructured":"Therneau Terry M TL, Elizabeth A, Cynthia C. Survival Analysis 2024. Available from: https:\/\/cran.r-project.org\/web\/packages\/survival\/survival.pdf; https:\/\/github.com\/therneau\/survival."},{"key":"4078_CR15","unstructured":"Knoll M. dataAnalysisMisc: Collection of functions for daily tasks. R package version 0.99.11. 2020. Available from: http:\/\/github.com\/mknoll\/dataAnalysisMisc."},{"key":"4078_CR16","unstructured":"R Core Team. R: A language and environment for statistical computing. Vienna (Austria): R Foundataion for Statistical Computing; 2018. Available from: https:\/\/www.R-project.org\/."},{"issue":"16","key":"4078_CR17","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1093\/eurheartj\/ehab072","volume":"42","author":"P Garcia-Pavia","year":"2021","unstructured":"Garcia-Pavia P, Rapezzi C, Adler Y, et al. Diagnosis and treatment of cardiac amyloidosis: A position statement of the ESC working group on myocardial and pericardial diseases. Eur Heart J. 2021;42(16):1554\u201368.","journal-title":"Eur Heart J"},{"issue":"3","key":"4078_CR18","doi-asserted-by":"publisher","first-page":"101604","DOI":"10.1016\/j.jacadv.2025.101604","volume":"4","author":"C Guenancia","year":"2025","unstructured":"Guenancia C, Lequeux B, Amara W, et al. Management of rhythm and conduction disorders in cardiac amyloidosis: A French nationwide Delphi study. JACC Adv. 2025;4(3):101604.","journal-title":"JACC Adv"},{"issue":"1","key":"4078_CR19","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1185\/03007995.2012.754348","volume":"29","author":"T Coelho","year":"2013","unstructured":"Coelho T, Maurer MS, Suhr OB. THAOS - The transthyretin amyloidosis outcomes survey: Initial report on clinical manifestations in patients with hereditary and wild-type transthyretin amyloidosis. Curr Med Res Opin. 2013;29(1):63\u201376.","journal-title":"Curr Med Res Opin"},{"issue":"6\u20137","key":"4078_CR20","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1016\/j.ejheart.2007.01.012","volume":"9","author":"AV Kristen","year":"2007","unstructured":"Kristen AV, Perz JB, Schonland SO, et al. Non-invasive predictors of survival in cardiac amyloidosis. Eur J Heart Fail. 2007;9(6\u20137):617\u201324.","journal-title":"Eur J Heart Fail"},{"issue":"6","key":"4078_CR21","first-page":"537","volume":"81","author":"K Kruczak","year":"2013","unstructured":"Kruczak K, Duplaga M, Sanak M, et al. Transthyretin amyloidosis with pulmonary involvement in a patient with monoclonal gammapathy. Pneumonol Alergol Pol. 2013;81(6):537\u201341.","journal-title":"Pneumonol Alergol Pol"},{"issue":"5","key":"4078_CR22","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/ehf2.12308","volume":"5","author":"YY Mints","year":"2018","unstructured":"Mints YY, Doros G, Berk JL, et al. Features of atrial fibrillation in wild-type transthyretin cardiac amyloidosis: A systematic review and clinical experience. ESC Heart Fail. 2018;5(5):772\u201379.","journal-title":"ESC Heart Fail"},{"issue":"1","key":"4078_CR23","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3109\/13506129.2015.1135792","volume":"23","author":"M Nakagawa","year":"2016","unstructured":"Nakagawa M, Sekijima Y, Yazaki M, et al. Carpal tunnel syndrome: A common initial symptom of systemic wild-type ATTR (ATTRwt) amyloidosis. Amyloid. 2016;23(1):58\u201363.","journal-title":"Amyloid"},{"issue":"13","key":"4078_CR24","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.1161\/CIRCULATIONAHA.108.843334","volume":"120","author":"C Rapezzi","year":"2009","unstructured":"Rapezzi C, Merlini G, Quarta CC, et al. Systemic cardiac amyloidoses: Disease profiles and clinical courses of the 3 main types. Circulation. 2009;120(13):1203\u201312.","journal-title":"Circulation"},{"issue":"2","key":"4078_CR25","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1007\/s00392-017-1167-1","volume":"107","author":"FAD Siepen","year":"2018","unstructured":"Siepen FAD, Bauer R, Voss A, et al. Predictors of survival stratification in patients with wild-type cardiac amyloidosis. Clin Res Cardiol. 2018;107(2):158\u201369.","journal-title":"Clin Res Cardiol"},{"issue":"38","key":"4078_CR26","doi-asserted-by":"publisher","first-page":"2585","DOI":"10.1093\/eurheartj\/ehv338","volume":"36","author":"E Gonzalez-Lopez","year":"2015","unstructured":"Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello G, et al. Wild-type transthyretin amyloidosis as a cause of heart failure with preserved ejection fraction. Eur Heart J. 2015;36(38):2585\u201394.","journal-title":"Eur Heart J"},{"issue":"1","key":"4078_CR27","doi-asserted-by":"publisher","first-page":"e000289","DOI":"10.1136\/openhrt-2015-000289","volume":"3","author":"T Damy","year":"2016","unstructured":"Damy T, Maurer MS, Rapezzi C, et al. Clinical, ECG and echocardiographic clues to the diagnosis of TTR-related cardiomyopathy. Open Heart. 2016;3(1):e000289.","journal-title":"Open Heart"},{"issue":"2","key":"4078_CR28","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1007\/s11517-013-1115-9","volume":"52","author":"M Kania","year":"2014","unstructured":"Kania M, Rix H, Fereniec M, et al. The effect of precordial lead displacement on ECG morphology. Med Biol Eng Comput. 2014;52(2):109\u201319.","journal-title":"Med Biol Eng Comput"},{"key":"4078_CR29","doi-asserted-by":"crossref","unstructured":"Sorodoc V, Indrei L, Dobroghii C, et al. Amiodarone therapy: Updated practical insights. J Clin Med. 2024;13(20).","DOI":"10.3390\/jcm13206094"},{"issue":"3","key":"4078_CR30","first-page":"112","volume":"12","author":"N Teymouri","year":"2022","unstructured":"Teymouri N, Mesbah S, Navabian SMH, et al. ECG frequency changes in potassium disorders: A narrative review. Am J Cardiovasc Dis. 2022;12(3):112\u201324.","journal-title":"Am J Cardiovasc Dis"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04078-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-04078-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04078-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T12:29:34Z","timestamp":1781612974000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13023-025-04078-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":30,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4078"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-04078-4","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]},"assertion":[{"value":"15 May 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 October 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ethics Committee Heidelberg with the number S186-2013.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"523"}}