Case-matched Comparison of Cardiovascular Outcome in Loeys-Dietz Syndrome versus Marfan Syndrome.

Mühlstädt, Kristina; De Backer, Julie; von Kodolitsch, Yskert; Kutsche, Kerstin; Muiño Mosquera, Laura; Brickwedel, Jens; Girdauskas, Evaldas; Mir, Thomas S; Mahlmann, Adrian; Tsilimparis, Nikolaos; Staebler, Axel; Schoof, Lauritz; Seidel, Heide; Berger, Jürgen; Bernhardt, Alexander M; Blankenberg, Stefan; Kölbel, Tilo; Detter, Christian; Szöcs, Katalin; Kaemmerer, Harald

doi:10.3390/jcm8122079

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Title:: Case-matched Comparison of Cardiovascular Outcome in Loeys-Dietz Syndrome versus Marfan Syndrome.
Document type:: Article; Journal Article
Author(s):: Mühlstädt, Kristina; De Backer, Julie; von Kodolitsch, Yskert; Kutsche, Kerstin; Muiño Mosquera, Laura; Brickwedel, Jens; Girdauskas, Evaldas; Mir, Thomas S; Mahlmann, Adrian; Tsilimparis, Nikolaos; Staebler, Axel; Schoof, Lauritz; Seidel, Heide; Berger, Jürgen; Bernhardt, Alexander M; Blankenberg, Stefan; Kölbel, Tilo; Detter, Christian; Szöcs, Katalin; Kaemmerer, Harald
Abstract:: 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 ± 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 < 0.001), the systemic score lower (p < 0.001), and mitral valve prolapse less frequent (p = 0.003). Mean survival for Loeys-Dietz and Marfan syndrome was similar (75 ± 3 versus 73 ± 2 years; p = 0.811). Cardiovascular outcome was comparable between Loeys-Dietz and Marfan syndrome, including mean freedom from proximal aortic surgery (53 ± 4 versus 48 ± 3 years; p = 0.589), distal aortic repair (72 ± 3 versus 67 ± 2 years; p = 0.777), mitral valve surgery (75 ± 4 versus 65 ± 3 years; p = 0.108), and reintervention (20 ± 3 versus 14 ± 2 years; p = 0.112). In Loeys-Dietz syndrome, lower age at initial presentation predicted proximal aortic surgery (HR = 0.748; p < 0.001), where receiver operating characteristic analysis identified ≤33.5 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.
Journal title abbreviation:: J Clin Med
Year:: 2019
Journal volume:: 8
Journal issue:: 12
Fulltext / DOI:: doi:10.3390/jcm8122079
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/31795342
TUM Institution:: Institut für Humangenetik; Klinik für Kinderkardiologie und angeborene Herzfehler (Prof. Hess)
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