Format

Send to

Choose Destination
J Vasc Surg. 2019 Nov;70(5):1543-1554. doi: 10.1016/j.jvs.2019.01.069. Epub 2019 May 21.

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

Author information

1
Division of Vascular Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash. Electronic address: shalhub@uw.edu.
2
Departments of Pathology and Medicine (Medical Genetics), University of Washington School of Medicine, Seattle, Wash.
3
Division of Vascular Surgery, Department of Surgery, University of Washington School of Medicine, Seattle, Wash.
4
Department of Cardiothoracic and Vascular Surgery, University of Texas Health Science Center at Houston, Houston, Tex.
5
Division of Vascular and Endovascular Surgery, Department of Surgery, University of California San Francisco, San Francisco, Calif.
6
Section of Vascular Surgery, Department of Surgery, University of Michigan, Ann Arbor, Mich.
7
Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Tex.
8
Department of Cardiovascular and Thoracic Sciences, University of Messina, Messina, Italy.
9
Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
10
Divisions of Cardiology and Human Genetics, University of Cincinnati School of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
11
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center, Boston, Mass.
12
Division of Vascular Surgery, Mayo Clinic, Rochester, Minn.
13
Division of Vascular and Endovascular Surgery, Department of Surgery and Anatomy, Medical School of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.
14
Department of Surgery, University of California, Davis Medical Center, Sacramento, Calif.
15
Department of Vascular Medicine, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
16
Department of Cardiology, University Heart Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
17
Division of Vascular Surgery, Dartmouth-Hitchcock Medical Center, Lebanon, NH.
18
Division of Vascular Surgery, University of California Los Angeles, Los Angeles, Calif.

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

PMID:
31126764
DOI:
10.1016/j.jvs.2019.01.069

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center