{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:30:46Z","timestamp":1791545446889,"version":"4.3.4"},"reference-count":46,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T00:00:00Z","timestamp":1574985600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Pathogenic variants in TGFBR1, TGFBR2 and SMAD3 genes cause Loeys-Dietz syndrome, and pathogenic variants in FBN1 cause Marfan syndrome. Despite their similar phenotypes, both syndromes may have different cardiovascular outcomes. Methods: Three expert centers performed a case-matched comparison of cardiovascular outcomes. The Loeys-Dietz group comprised 43 men and 40 women with a mean age of 34 \u00b1 18 years. Twenty-six individuals had pathogenic variants in TGFBR1, 40 in TGFBR2, and 17 in SMAD3. For case-matched comparison we used 83 age and sex-frequency matched individuals with Marfan syndrome. Results: In Loeys-Dietz compared to Marfan syndrome, a patent ductus arteriosus (p = 0.014) was more prevalent, the craniofacial score was higher (p &lt; 0.001), the systemic score lower (p &lt; 0.001), and mitral valve prolapse less frequent (p = 0.003). Mean survival for Loeys-Dietz and Marfan syndrome was similar (75 \u00b1 3 versus 73 \u00b1 2 years; p = 0.811). Cardiovascular outcome was comparable between Loeys-Dietz and Marfan syndrome, including mean freedom from proximal aortic surgery (53 \u00b1 4 versus 48 \u00b1 3 years; p = 0.589), distal aortic repair (72 \u00b1 3 versus 67 \u00b1 2 years; p = 0.777), mitral valve surgery (75 \u00b1 4 versus 65 \u00b1 3 years; p = 0.108), and reintervention (20 \u00b1 3 versus 14 \u00b1 2 years; p = 0.112). In Loeys-Dietz syndrome, lower age at initial presentation predicted proximal aortic surgery (HR = 0.748; p &lt; 0.001), where receiver operating characteristic analysis identified \u226433.5 years with increased risk. In addition, increased aortic sinus diameters (HR = 6.502; p = 0.001), and higher systemic score points at least marginally (HR = 1.175; p = 0.065) related to proximal aortic surgery in Loeys-Dietz syndrome. Conclusions: Cardiovascular outcome of Loeys-Dietz syndrome was comparable to Marfan syndrome, but the severity of systemic manifestations was a predictor of proximal aortic surgery.<\/jats:p>","DOI":"10.3390\/jcm8122079","type":"journal-article","created":{"date-parts":[[2019,11,29]],"date-time":"2019-11-29T10:58:21Z","timestamp":1575025101000},"page":"2079","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Case-matched Comparison of Cardiovascular Outcome in Loeys-Dietz Syndrome versus Marfan Syndrome"],"prefix":"10.3390","volume":"8","author":[{"given":"Kristina","family":"M\u00fchlst\u00e4dt","sequence":"first","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8878-1507","authenticated-orcid":false,"given":"Julie","family":"De Backer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"},{"name":"Department of Cardiology, University Hospital Ghent, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yskert","family":"von Kodolitsch","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Kutsche","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3094-7807","authenticated-orcid":false,"given":"Laura","family":"Mui\u00f1o Mosquera","sequence":"additional","affiliation":[{"name":"Department of Pediatric Cardiology and Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Brickwedel","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evaldas","family":"Girdauskas","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Mir","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Mahlmann","sequence":"additional","affiliation":[{"name":"University Center for Vascular Medicine and Division of Angiology, Department of Internal Medicine III, University Hospital Carl Gustav Carus, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Tsilimparis","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Staebler","sequence":"additional","affiliation":[{"name":"Radiologische Praxis M\u00fcnchen Grosshadern, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauritz","family":"Schoof","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heide","family":"Seidel","sequence":"additional","affiliation":[{"name":"Institute for Human Genetics at Klinikum rechts der Isar, Technical University Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Berger","sequence":"additional","affiliation":[{"name":"Department of Medical Biometry and Epidemiology, all at the University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Bernhardt","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blankenberg","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilo","family":"K\u00f6lbel","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Detter","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5992-4633","authenticated-orcid":false,"given":"Katalin","family":"Sz\u00f6cs","sequence":"additional","affiliation":[{"name":"German Aorta Center Hamburg at Centre of Cardiology and Cardiovascular Surgery, University Medical Center Hamburg-Hospital Eppendorf, 20246 Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Kaemmerer","sequence":"additional","affiliation":[{"name":"Department of Congenital Heart Disease and Pediatric Cardiology, Deutsches Herzzentrum M\u00fcnchen, Technical University M\u00fcnchen, 80636 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1097\/HCO.0000000000000023","article-title":"Heritable thoracic aortic disorders","volume":"29","author":"Pyeritz","year":"2014","journal-title":"Curr. 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