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Acute Stanford type B aortic dissection-who benefits from genetic testing?

ABSTRACT: Background: Stanford type B aortic dissection is a rare, life-threatening complex phenotype associated with several modifiable and genetic risk factors. In the current study of a hospital-based, consecutive series of aortic dissection patients we propose a selection based on age and family history of aortic disease for genetic testing and detection of causative gene variants.

Methods: In this single center cohort study from 2013 to 2018 patients with acute Stanford type B aortic dissections were consecutively treated and analyzed by next generation sequencing based on selection criteria (age of disease onset ?45 years and/or positive familial history for aortic disease) to detect genome-wide pathogenic variants in protein-coding sequences and to identify large copy number variants (CNV). Variants in a predefined panel of 30 genes associated with the familial thoracic aortic aneurysm and dissection (TAAD) syndrome were evaluated.

Results: From 105 patients nine matched selection criteria for genetic testing. Next-generation sequencing analysis revealed causal variants in FBN1 (fibrillin-1) in three patients: a pathogenic missense variant [c.6661T>C, p.(Cys2221Arg)] and two truncating variants [c.4786C>T, p.(Arg1596Ter)] and [c.6366C>CA, p.(Asp2123GlufsTer5)]. A fourth patient carried a large (>1,000,000 bp) CNV in the long arm of chromosome 10, deleting eleven genes, including the whole ACTA2 (actin alpha 2) gene. The latter two genetic findings have not been reported before.

Conclusions: Selection of patients on the basis of young age and familial inheritance of aortic disease favors the identification of disease-causing genetic variants in a clinical cohort of patients with Stanford type B aortic dissection.

SUBMITTER: Erhart P

PROVIDER: S-EPMC7711383 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Acute Stanford type B aortic dissection-who benefits from genetic testing?

Erhart Philipp P Gieldon Laura L Ante Marius M Körfer Daniel D Strom Tim T Grond-Ginsbach Caspar C Böckler Dittmar D

Journal of thoracic disease 20201101 11

<h4>Background</h4>Stanford type B aortic dissection is a rare, life-threatening complex phenotype associated with several modifiable and genetic risk factors. In the current study of a hospital-based, consecutive series of aortic dissection patients we propose a selection based on age and family history of aortic disease for genetic testing and detection of causative gene variants.<h4>Methods</h4>In this single center cohort study from 2013 to 2018 patients with acute Stanford type B aortic dis ...[more]

PMID: 33282382

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Project description:BACKGROUND:Acute Stanford type A aortic dissection is often fatal, with a high mortality rate and requiring emergency intervention. Salvage surgery aims to keep the patient alive by addressing severe aortic regurgitation, tamponade, primary tear, and organ malperfusion and, if possible, prevent the late dissection-related complications in the proximal and downstream aorta. Unfortunately, no optimal standard treatment or technique to treat this disease exists. Total arch replacement with frozen elephant trunk technique plays an important role in treating acute type A aortic dissection. We aim to describe a modified elephant trunk technique and report its short-term outcomes. METHODS:From February 2018 to August 2019, 16 patients diagnosed with acute Stanford type A aortic dissection underwent surgery with the modified frozen elephant trunk technique at Xiamen Heart Center (male/female: 9/7; average age: 56.1?±?7.6?years). All perioperative variables were recorded and analyzed. We measured the diameters of the ascending aorta, aortic arch, and descending aorta on the bifurcation of the pulmonary and abdominal aortas and compared the diameters at admission, before discharge, and 3?months after discharge. RESULTS:Fifteen patients (93.8%) had hypertension. The primary tears were located in the lesser curvature of the aortic arch and ascending aorta in 5 (31.3%) and 9 patients (56.3%), respectively, and no entry was found in 2 patients (12.5%). The dissection extended to the iliac artery and distal descending aorta in 14 (87.6%) and 2 patients (12.5%), respectively. The duration of cardiopulmonary bypass (CPB), cross-clamping, and antegrade cerebral perfusion were 215.8?±?40.5, 140.8?±?32.3, and 55.1?± 15.2?min, respectively. Aortic valve repair was performed in 15 patients (93.8%). Bentall procedure was performed in one patient (6.3%). Another patient received coronary artery repair (6.3%). The diameters at all levels were greater on discharge than those on admission, except the aortic arch. After 3?months, the true lumen diameter distal to the frozen elephant trunk increased, indicating false lumen thrombosis and/or aortic remodeling. CONCLUSIONS:The modified frozen elephant trunk technique for acute Stanford type A aortic dissection is safe and feasible and could be used for organ malperfusion. Short-term outcomes are encouraging, but long-term outcomes require further investigation.

Project description:Background: Stanford type A aortic dissection (ATAAD) is a common life-threatening event in the aorta. Recently, immune disorder has been linked to the risk factors that cause ATAAD at the molecular level. However, the specific immune-related gene signature during the progression is unclear. Methods: The GSE52093 and GSE98770 datasets related to ATAAD from the Gene Expression Omnibus (GEO) database were acquired. The immune gene expression levels were analyzed by single sample gene set enrichment analysis (ssGSEA). The correlations between gene networks and immune scores were determined by weighted gene correlation network analysis (WGCNA). The different immune subgroups were finally divided by consensus clustering. The differentially expressed genes (DEGs) were identified and subsequent functional enrichment analyses were conducted. The hub genes were identified by protein-protein interaction (PPI) network and functional similarities analyses. The immune cell infiltration proportion was determined by the CIBERSORT algorithm. Results: According to the ssGSEA results, the 13 ATAAD samples from the GEO database were divided into high- and low-immune subgroups according to the ssGSEA, WGCNA, and consensus clustering analysis results. Sixty-eight immune-related DEGs (IRDEGs) between the two subgroups were enriched in inflammatory-immune response biological processes, including leukocyte cell-cell adhesion, mononuclear cell migration, and myeloid leukocyte migration. Among these IRDEGs, 8 genes (CXCR4, LYN, CCL19, CCL3L3, SELL, F11R, DPP4, and VAV3) were identified as hub genes that represented immune-related signatures in ATAAD after the PPI and functional similarities analyses. The proportions of infiltrating CD8 T cells and M1 macrophages were significantly higher in ATAAD patients in the immune-high group than the immune-low group. Conclusion: Eight immune-related genes were identified as hub genes representing potential biomarkers and therapeutic targets linked to the immune response in ATAAD patients.

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Acute Stanford type B aortic dissection-who benefits from genetic testing?

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Acute Stanford type B aortic dissection-who benefits from genetic testing?

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