A multi-institutional experience in the aortic and arterial pathology in individuals with genetically confirmed vascular Ehlers-Danlos syndrome
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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: J VASC SURG, Vol. 70, No. 5, 11.2019, p. 1543-1554.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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
N1 - Copyright © 2019 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.
PY - 2019/11
Y1 - 2019/11
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 - Adolescent
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Aneurysm/epidemiology
KW - Aorta/pathology
KW - Arteries/pathology
KW - Child
KW - Child, Preschool
KW - Collagen Type III/genetics
KW - Cross-Sectional Studies
KW - Ehlers-Danlos Syndrome/complications
KW - Embolization, Therapeutic/statistics & numerical data
KW - Endovascular Procedures/methods
KW - Female
KW - Follow-Up Studies
KW - Genetic Testing/statistics & numerical data
KW - Humans
KW - Infant
KW - Male
KW - Middle Aged
KW - Mutation, Missense
KW - Retrospective Studies
KW - Young Adult
U2 - 10.1016/j.jvs.2019.01.069
DO - 10.1016/j.jvs.2019.01.069
M3 - SCORING: Journal article
C2 - 31126764
VL - 70
SP - 1543
EP - 1554
JO - J VASC SURG
JF - J VASC SURG
SN - 0741-5214
IS - 5
ER -