PMID- 31126764
OWN - NLM
STAT- MEDLINE
DCOM- 20200527
LR  - 20210701
IS  - 1097-6809 (Electronic)
IS  - 0741-5214 (Print)
IS  - 0741-5214 (Linking)
VI  - 70
IP  - 5
DP  - 2019 Nov
TI  - A multi-institutional experience in the aortic and arterial pathology in 
      individuals with genetically confirmed vascular Ehlers-Danlos syndrome.
PG  - 1543-1554
LID - S0741-5214(19)30337-4 [pii]
LID - 10.1016/j.jvs.2019.01.069 [doi]
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.
CI  - Copyright (c) 2019 Society for Vascular Surgery. Published by Elsevier Inc. All 
      rights reserved.
FAU - Shalhub, Sherene
AU  - Shalhub S
AD  - Division of Vascular Surgery, Department of Surgery, University of Washington 
      School of Medicine, Seattle, Wash. Electronic address: shalhub@uw.edu.
FAU - Byers, Peter H
AU  - Byers PH
AD  - Departments of Pathology and Medicine (Medical Genetics), University of 
      Washington School of Medicine, Seattle, Wash.
FAU - Hicks, Kelli L
AU  - Hicks KL
AD  - Division of Vascular Surgery, Department of Surgery, University of Washington 
      School of Medicine, Seattle, Wash.
FAU - Charlton-Ouw, Kristofer
AU  - Charlton-Ouw K
AD  - Department of Cardiothoracic and Vascular Surgery, University of Texas Health 
      Science Center at Houston, Houston, Tex.
FAU - Zarkowsky, Devin
AU  - Zarkowsky D
AD  - Division of Vascular and Endovascular Surgery, Department of Surgery, University 
      of California San Francisco, San Francisco, Calif.
FAU - Coleman, Dawn M
AU  - Coleman DM
AD  - Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann 
      Arbor, Mich.
FAU - Davis, Frank M
AU  - Davis FM
AD  - Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann 
      Arbor, Mich.
FAU - Regalado, Ellen S
AU  - Regalado ES
AD  - Division of Medical Genetics, Department of Internal Medicine, University of 
      Texas Health Science Center at Houston, Houston, Tex.
FAU - De Caridi, Giovanni
AU  - De Caridi G
AD  - Department of Cardiovascular and Thoracic Sciences, University of Messina, 
      Messina, Italy.
FAU - Weaver, K Nicole
AU  - Weaver KN
AD  - Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 
      Cincinnati, Ohio.
FAU - Miller, Erin M
AU  - Miller EM
AD  - Divisions of Cardiology and Human Genetics, University of Cincinnati School of 
      Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
FAU - Schermerhorn, Marc L
AU  - Schermerhorn ML
AD  - Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical 
      Center, Boston, Mass.
FAU - Shean, Katie
AU  - Shean K
AD  - Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical 
      Center, Boston, Mass.
FAU - Oderich, Gustavo
AU  - Oderich G
AD  - Division of Vascular Surgery, Mayo Clinic, Rochester, Minn.
FAU - Ribeiro, Mauricio
AU  - Ribeiro M
AD  - Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, 
      Medical School of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
FAU - Nishikawa, Cole
AU  - Nishikawa C
AD  - Department of Surgery, University of California, Davis Medical Center, 
      Sacramento, Calif.
FAU - Behrendt, Christian-Alexander
AU  - Behrendt CA
AD  - Department of Vascular Medicine, University Heart Center Hamburg, University 
      Medical Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Debus, E Sebastian
AU  - Debus ES
AD  - Department of Cardiology, University Heart Center Hamburg, University Medical 
      Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - von Kodolitsch, Yskert
AU  - von Kodolitsch Y
AD  - Department of Cardiology, University Heart Center Hamburg, University Medical 
      Center Hamburg-Eppendorf, Hamburg, Germany.
FAU - Powell, Richard J
AU  - Powell RJ
AD  - Division of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
FAU - Pepin, Melanie
AU  - Pepin M
AD  - Departments of Pathology and Medicine (Medical Genetics), University of 
      Washington School of Medicine, Seattle, Wash.
FAU - Milewicz, Dianna M
AU  - Milewicz DM
AD  - Division of Medical Genetics, Department of Internal Medicine, University of 
      Texas Health Science Center at Houston, Houston, Tex.
FAU - Lawrence, Peter F
AU  - Lawrence PF
AD  - Division of Vascular Surgery, University of California Los Angeles, Los Angeles, 
      Calif.
FAU - Woo, Karen
AU  - Woo K
AD  - Division of Vascular Surgery, University of California Los Angeles, Los Angeles, 
      Calif.
LA  - eng
GR  - K08 DK107934/DK/NIDDK NIH HHS/United States
GR  - UL1 TR000423/TR/NCATS NIH HHS/United States
GR  - UL1 TR002319/TR/NCATS NIH HHS/United States
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190521
PL  - United States
TA  - J Vasc Surg
JT  - Journal of vascular surgery
JID - 8407742
RN  - 0 (COL3A1 protein, human)
RN  - 0 (Collagen Type III)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Aneurysm/*epidemiology/genetics/pathology/therapy
MH  - Aorta/*pathology/surgery
MH  - Arteries/*pathology/surgery
MH  - Child
MH  - Child, Preschool
MH  - Collagen Type III/*genetics/metabolism
MH  - Cross-Sectional Studies
MH  - Ehlers-Danlos Syndrome/*complications/diagnosis/genetics/pathology
MH  - Embolization, Therapeutic/statistics & numerical data
MH  - Endovascular Procedures/methods/statistics & numerical data
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Testing/statistics & numerical data
MH  - Humans
MH  - Infant
MH  - Male
MH  - Middle Aged
MH  - Mutation, Missense
MH  - Retrospective Studies
MH  - Young Adult
PMC - PMC8240141
MID - NIHMS1530041
OTO - NOTNLM
OT  - Arterial aneurysm
OT  - Arterial dissection
OT  - Arterial rupture
OT  - COL3A1 mutation
OT  - Vascular Ehlers-Danlos syndrome
COIS- Conflicts of Interest: None
EDAT- 2019/05/28 06:00
MHDA- 2020/05/28 06:00
PMCR- 2021/06/29
CRDT- 2019/05/26 06:00
PHST- 2018/09/07 00:00 [received]
PHST- 2019/01/23 00:00 [accepted]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2020/05/28 06:00 [medline]
PHST- 2019/05/26 06:00 [entrez]
PHST- 2021/06/29 00:00 [pmc-release]
AID - S0741-5214(19)30337-4 [pii]
AID - 10.1016/j.jvs.2019.01.069 [doi]
PST - ppublish
SO  - J Vasc Surg. 2019 Nov;70(5):1543-1554. doi: 10.1016/j.jvs.2019.01.069. Epub 2019 
      May 21.