A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome

Sherene Shalhub, Peter H. Byers, Kelli L. Hicks, Kristofer Charlton-Ouw, Devin Zarkowsky, Dawn M. Coleman, Frank M. Davis, Ellen S. Regalado, Giovanni De Caridi, K. Nicole Weaver, Erin M. Miller, Marc L. Schermerhorn, Katie Shean, Gustavo Oderich, Mauricio Ribeiro, Cole Nishikawa, Christian Alexander Behrendt, E. Sebastian Debus, Yskert von Kodolitsch, Richard J. PowellMelanie Pepin, Dianna M. Milewicz, Peter F. Lawrence, Karen Woo

Research output: Contribution to journalArticle

Abstract

Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. Methods: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared. Results: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years). Conclusions: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.

Original languageEnglish (US)
JournalJournal of vascular surgery
DOIs
StatePublished - Jan 1 2019

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Ehlers-Danlos Syndrome
Blood Vessels
Pathology
Abdominal Aortic Aneurysm
Aneurysm
Rupture
Arteries
Tunica Media
Mesenteric Arteries
Collagen Type III
Iliac Artery
False Aneurysm
Renal Artery
Missense Mutation
Connective Tissue
Glycine
Fistula
Dissection
Emergencies
Retrospective Studies

Keywords

  • Arterial aneurysm
  • Arterial dissection
  • Arterial rupture
  • COL3A1 mutation
  • Vascular Ehlers-Danlos syndrome

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

Cite this

A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome. / Shalhub, Sherene; Byers, Peter H.; Hicks, Kelli L.; Charlton-Ouw, Kristofer; Zarkowsky, Devin; Coleman, Dawn M.; Davis, Frank M.; Regalado, Ellen S.; De Caridi, Giovanni; Weaver, K. Nicole; Miller, Erin M.; Schermerhorn, Marc L.; Shean, Katie; Oderich, Gustavo; Ribeiro, Mauricio; Nishikawa, Cole; Behrendt, Christian Alexander; Debus, E. Sebastian; von Kodolitsch, Yskert; Powell, Richard J.; Pepin, Melanie; Milewicz, Dianna M.; Lawrence, Peter F.; Woo, Karen.

In: Journal of vascular surgery, 01.01.2019.

Research output: Contribution to journalArticle

Shalhub, S, Byers, PH, Hicks, KL, Charlton-Ouw, K, Zarkowsky, D, Coleman, DM, Davis, FM, Regalado, ES, De Caridi, G, Weaver, KN, Miller, EM, Schermerhorn, ML, Shean, K, Oderich, G, Ribeiro, M, Nishikawa, C, Behrendt, CA, Debus, ES, von Kodolitsch, Y, Powell, RJ, Pepin, M, Milewicz, DM, Lawrence, PF & Woo, K 2019, 'A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome', Journal of vascular surgery. https://doi.org/10.1016/j.jvs.2019.01.069
Shalhub, Sherene ; Byers, Peter H. ; Hicks, Kelli L. ; Charlton-Ouw, Kristofer ; Zarkowsky, Devin ; Coleman, Dawn M. ; Davis, Frank M. ; Regalado, Ellen S. ; De Caridi, Giovanni ; Weaver, K. Nicole ; Miller, Erin M. ; Schermerhorn, Marc L. ; Shean, Katie ; Oderich, Gustavo ; Ribeiro, Mauricio ; Nishikawa, Cole ; Behrendt, Christian Alexander ; Debus, E. Sebastian ; von Kodolitsch, Yskert ; Powell, Richard J. ; Pepin, Melanie ; Milewicz, Dianna M. ; Lawrence, Peter F. ; Woo, Karen. / A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome. In: Journal of vascular surgery. 2019.
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title = "A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome",
abstract = "Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. Methods: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared. Results: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7{\%} male, 86{\%} Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1{\%} missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6{\%}; 50.9{\%} male; 88.5{\%} Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4{\%}). The most commonly affected arteries were the mesenteric arteries (31.7{\%}), followed by cerebrovascular (16.5{\%}), iliac (16.5{\%}), and renal arteries (12.2{\%}). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4{\%}), followed by stenting (2.5{\%}). Aortic pathology was noted in 17 individuals (32{\%}; 58.8{\%} male; 94.1{\%} Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6{\%}) at a median age of 36 years (IQR, 28-51 years). Conclusions: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.",
keywords = "Arterial aneurysm, Arterial dissection, Arterial rupture, COL3A1 mutation, Vascular Ehlers-Danlos syndrome",
author = "Sherene Shalhub and Byers, {Peter H.} and Hicks, {Kelli L.} and Kristofer Charlton-Ouw and Devin Zarkowsky and Coleman, {Dawn M.} and Davis, {Frank M.} and Regalado, {Ellen S.} and {De Caridi}, Giovanni and Weaver, {K. Nicole} and Miller, {Erin M.} and Schermerhorn, {Marc L.} and Katie Shean and Gustavo Oderich and Mauricio Ribeiro and Cole Nishikawa and Behrendt, {Christian Alexander} and Debus, {E. Sebastian} and {von Kodolitsch}, Yskert and Powell, {Richard J.} and Melanie Pepin and Milewicz, {Dianna M.} and Lawrence, {Peter F.} and Karen Woo",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jvs.2019.01.069",
language = "English (US)",
journal = "Journal of Vascular Surgery",
issn = "0741-5214",
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TY - JOUR

T1 - A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome

AU - Shalhub, Sherene

AU - Byers, Peter H.

AU - Hicks, Kelli L.

AU - Charlton-Ouw, Kristofer

AU - Zarkowsky, Devin

AU - Coleman, Dawn M.

AU - Davis, Frank M.

AU - Regalado, Ellen S.

AU - De Caridi, Giovanni

AU - Weaver, K. Nicole

AU - Miller, Erin M.

AU - Schermerhorn, Marc L.

AU - Shean, Katie

AU - Oderich, Gustavo

AU - Ribeiro, Mauricio

AU - Nishikawa, Cole

AU - Behrendt, Christian Alexander

AU - Debus, E. Sebastian

AU - von Kodolitsch, Yskert

AU - Powell, Richard J.

AU - Pepin, Melanie

AU - Milewicz, Dianna M.

AU - Lawrence, Peter F.

AU - Woo, Karen

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. Methods: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared. Results: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years). Conclusions: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.

AB - Objective: Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder owing to pathogenic variants in COL3A1 that lead to impaired type III collagen production. We aim to describe the contemporary multi-institutional experience of aortic and arterial pathology in individuals with vEDS, to evaluate disease patterns and refine management recommendations. Methods: This cross-sectional, retrospective study of individuals with genetically confirmed vEDS was conducted between 2000 and 2015 at multiple institutions participating in the Vascular Low Frequency Disease Consortium. Aortic and arterial events including aneurysms, pseudoaneurysms, dissections, fistulae, or ruptures were studied. Demographics, COL3A1 variants, management, and outcomes data were collected and analyzed. Individuals with and without arterial events were compared. Results: Eleven institutions identified 86 individuals with pathogenic variants in COL3A1 (47.7% male, 86% Caucasian; median age, 41 years; interquartile range [IQR], 31.0-49.5 years; 65.1% missense COL3A1 variants). The median follow-up from the time of vEDS diagnosis was 7.5 years (IQR, 3.5-12.0 years). A total of 139 aortic/arterial pathologies were diagnosed in 53 individuals (61.6%; 50.9% male; 88.5% Caucasian; median age, 33 years; IQR, 25.0-42.3 years). The aortic/arterial events presented as an emergency in 52 cases (37.4%). The most commonly affected arteries were the mesenteric arteries (31.7%), followed by cerebrovascular (16.5%), iliac (16.5%), and renal arteries (12.2%). The most common management was medical management. When undertaken, the predominant endovascular interventions were arterial embolization of medium sized arteries (13.4%), followed by stenting (2.5%). Aortic pathology was noted in 17 individuals (32%; 58.8% male; 94.1% Caucasian; median age, 38.5 years; IQR, 30.8-44.7 years). Most notably, four individuals underwent successful abdominal aortic aneurysm repair with excellent results on follow-up. Individuals with missense mutations, in which glycine was substituted with a large amino acid, had an earlier onset of aortic/arterial pathology (median age, 30 years; IQR, 23.5-37 years) compared with the other pathogenic COL3A1 variants (median age, 36 years; IQR, 29.5-44.8 years; P = .065). There were 12 deaths (22.6%) at a median age of 36 years (IQR, 28-51 years). Conclusions: Most of the vEDS arterial manifestations were managed medically in this cohort. When intervention is required for an enlarging aneurysm or rupture, embolization, and less frequently stenting, seem to be well-tolerated. Open repair of abdominal aortic aneurysm seems to be as well-tolerated as in those without vEDS; vEDS should not be a deterrent to offering an operation. Future work to elucidate the role of surgical interventions and refine management recommendations in the context of patient centered outcomes is warranted.

KW - Arterial aneurysm

KW - Arterial dissection

KW - Arterial rupture

KW - COL3A1 mutation

KW - Vascular Ehlers-Danlos syndrome

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