{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T05:31:36Z","timestamp":1791869496112,"version":"4.3.4"},"reference-count":33,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T00:00:00Z","timestamp":1698019200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Marfan syndrome (MFS) is an autosomal-dominant multisystem connective tissue disorder that is based on mutations in the FBN1 gene and variably affects different organs, including the heart. In this study, we investigated cardiac function with a focus on the left atrium (LA) in a relatively large cohort of patients with MFS. After screening of 1165 patients that had been examined in our center between 2016 and 2020, 231 adult MFS patients with and without aortic operation were included in our study and compared to a healthy control group (n = 106). Cardiac function was assessed by transthoracic echocardiography and NT-proBNP was used as a secretory marker. Most (94.8%) of the patients received genetic testing. Left ventricular function was within normal ranges and not impaired. Interestingly, we found that LA size and secretory activity were increased in MFS patients, despite normal left ventricular filling pressures. This finding was even more pronounced in MFS patients with prior aortic surgery. A correlation between LA size or NT-proBNP levels and the type of pathogenic FBN1 variant could not be identified. Right ventricular function and right atrial size were increased only in MFS patients that had undergone aortic surgery. In conclusion, these findings suggest that MFS leads to structural changes in the LA that are not solely resulting from left ventricular dysfunction, but probably can be considered a primary pathology of MFS.<\/jats:p>","DOI":"10.3390\/diagnostics13203278","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T05:54:35Z","timestamp":1698040475000},"page":"3278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Is Marfan Syndrome Associated with Primary Structural Changes in the Left Atrium?"],"prefix":"10.3390","volume":"13","author":[{"given":"Kun","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7605-6946","authenticated-orcid":false,"given":"Lucas","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3659-0914","authenticated-orcid":false,"given":"Isabel","family":"Schobert","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karla","family":"Philipp","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8819-6209","authenticated-orcid":false,"given":"Georg","family":"B\u00f6ning","sequence":"additional","affiliation":[{"name":"Department of Radiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank R.","family":"Heinzel","sequence":"additional","affiliation":[{"name":"2. Medical Clinic, Municipal Clinic Dresden, 01324 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leif-Hendrik","family":"Boldt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petra","family":"Gehle","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Cardiology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin, Humboldt Universit\u00e4t zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany"},{"name":"German Centre for Cardiovascular Research (DZHK), 10785 Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/S0140-6736(05)67789-6","article-title":"Marfan\u2019s syndrome","volume":"366","author":"Judge","year":"2005","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/sj.ejhg.5201851","article-title":"Marfan syndrome: Clinical diagnosis and management","volume":"15","author":"Dean","year":"2007","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1080\/14779072.2019.1704625","article-title":"Features of Marfan syndrome not listed in the Ghent nosology\u2014The dark side of the disease","volume":"17","author":"Demolder","year":"2019","journal-title":"Expert. Rev. Cardiovasc. Ther."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1136\/jmg.2009.072785","article-title":"The revised Ghent nosology for the Marfan syndrome","volume":"47","author":"Loeys","year":"2010","journal-title":"J. Med. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e150","DOI":"10.1161\/01.CIR.0000155243.70456.F4","article-title":"Treatment of aortic disease in patients with Marfan syndrome","volume":"111","author":"Milewicz","year":"2005","journal-title":"Circulation"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/352337a0","article-title":"Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene","volume":"352","author":"Dietz","year":"1991","journal-title":"Nature"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1056\/NEJM199010043231402","article-title":"Location on chromosome 15 of the gene defect causing Marfan syndrome","volume":"323","author":"Kainulainen","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1083\/jcb.103.6.2499","article-title":"Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils","volume":"103","author":"Sakai","year":"1986","journal-title":"J. Cell Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.matbio.2017.07.004","article-title":"Marfan syndrome; A connective tissue disease at the crossroads of mechanotransduction, TGFbeta signaling and cell stemness","volume":"71\u201372","author":"Ramirez","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Takeda, N., Hara, H., Fujiwara, T., Kanaya, T., Maemura, S., and Komuro, I. (2018). TGF-beta Signaling-Related Genes and Thoracic Aortic Aneurysms and Dissections. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19072125"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1136\/heartjnl-2020-317706","article-title":"Mortality and morbidity in patients with congenital heart disease hospitalised for viral pneumonia","volume":"107","author":"Diller","year":"2021","journal-title":"Heart"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S0735-1097(02)02699-2","article-title":"Long-term outcome in patients with Marfan syndrome: Is aortic dissection the only cause of sudden death?","volume":"41","author":"Yetman","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Demolder, A., von Kodolitsch, Y., Muino-Mosquera, L., and De Backer, J. (2020). Myocardial Function, Heart Failure and Arrhythmia in Marfan Syndrome: A Systematic Literature Review. Diagnostics, 10.","DOI":"10.3390\/diagnostics10100751"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1186\/s13023-020-01581-8","article-title":"Myocardial disease and ventricular arrhythmia in Marfan syndrome: A prospective study","volume":"15","author":"Devos","year":"2020","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.ijcard.2005.10.010","article-title":"Primary impairment of left ventricular function in Marfan syndrome","volume":"112","author":"Devos","year":"2006","journal-title":"Int. J. Cardiol."},{"key":"ref_16","first-page":"15","article-title":"NT-proBNP and diastolic left ventricular function in patients with Marfan syndrome","volume":"12","author":"Gehle","year":"2016","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1093\/ejechocard\/jep110","article-title":"Biventricular and atrial diastolic function assessment using conventional echocardiography and tissue-Doppler imaging in adults with Marfan syndrome","volume":"10","author":"Kiotsekoglou","year":"2009","journal-title":"Eur. J. Echocardiogr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1007\/s00418-018-1686-5","article-title":"A heart for fibrillin: Spatial arrangement in adult wild-type murine myocardial tissue","volume":"150","author":"Steijns","year":"2018","journal-title":"Histochem. Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1161\/01.RES.86.5.571","article-title":"Atrial but not ventricular fibrosis in mice expressing a mutant transforming growth factor-beta(1) transgene in the heart","volume":"86","author":"Nakajima","year":"2000","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1093\/eurjhf\/hfq127","article-title":"Evidence for Marfan cardiomyopathy","volume":"12","author":"Alpendurada","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1136\/heartjnl-2011-300169","article-title":"Intrinsic biventricular dysfunction in Marfan syndrome","volume":"97","author":"Aalberts","year":"2011","journal-title":"Heart"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1111\/j.1540-8175.2010.01359.x","article-title":"Impaired biventricular deformation in Marfan syndrome: A strain and strain rate study in adult unoperated patients","volume":"28","author":"Kiotsekoglou","year":"2011","journal-title":"Echocardiography"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1392","DOI":"10.1016\/j.echo.2011.09.004","article-title":"Biventricular performance in patients with marfan syndrome without significant valvular disease: Comparison to normal subjects and longitudinal follow-up","volume":"24","author":"Scherptong","year":"2011","journal-title":"J. Am. Soc. Echocardiogr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s10741-019-09785-2","article-title":"Right ventricular function after cardiac surgery: The diagnostic and prognostic role of echocardiography","volume":"24","author":"Mandoli","year":"2019","journal-title":"Heart Fail. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/eurjhf\/hfp112","article-title":"Independent relationship of left atrial size and mortality in patients with heart failure: An individual patient meta-analysis of longitudinal data (MeRGE Heart Failure)","volume":"11","author":"Rossi","year":"2009","journal-title":"Eur. J. Heart Fail."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.jcmg.2016.11.003","article-title":"Left Atrial Reverse Remodeling: Mechanisms, Evaluation, and Clinical Significance","volume":"10","author":"Thomas","year":"2017","journal-title":"JACC Cardiovasc. Imaging"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Abd El Rahman, M., Haase, D., Rentzsch, A., Olchvary, J., Schafers, H.J., Henn, W., Wagenpfeil, S., and Abdul-Khaliq, H. (2015). Left ventricular systolic dysfunction in asymptomatic Marfan syndrome patients is related to the severity of gene mutation: Insights from the novel three dimensional speckle tracking echocardiography. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0124112"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1161\/01.CIR.102.15.1788","article-title":"Clinical utility of Doppler echocardiography and tissue Doppler imaging in the estimation of left ventricular filling pressures: A comparative simultaneous Doppler-catheterization study","volume":"102","author":"Ommen","year":"2000","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/ng1116","article-title":"Dysregulation of TGF-beta activation contributes to pathogenesis in Marfan syndrome","volume":"33","author":"Neptune","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_30","first-page":"1071","article-title":"Clinical utility gene card for: Marfan syndrome type 1 and related phenotypes [FBN1]","volume":"18","author":"Arbustini","year":"2010","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3291","DOI":"10.1093\/eurheartj\/ehw154","article-title":"The search for genotype\/phenotype correlation in Marfan syndrome: To be or not to be?","volume":"37","author":"Loeys","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/s41569-020-0381-0","article-title":"Cardiac natriuretic peptides","volume":"17","author":"Goetze","year":"2020","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.hfc.2006.08.005","article-title":"Gene expression, processing, and secretion of natriuretic peptides: Physiologic and diagnostic implications","volume":"2","author":"Ramos","year":"2006","journal-title":"Heart Fail. Clin."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/20\/3278\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:10:05Z","timestamp":1760130605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/20\/3278"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,23]]},"references-count":33,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["diagnostics13203278"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13203278","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,23]]}}}