Molecular Pathogenesis and the Possible Role of Mitochondrial Heteroplasmy in Thoracic Aortic Aneurysm

Thoracic aortic aneurysm (TAA) is a life-threatening condition associated with high mortality, in which the aortic wall is deformed due to congenital or age-associated pathological changes. The mechanisms of TAA development remain to be studied in detail, and are the subject of active research. In this review, we describe the morphological changes of the aortic wall in TAA. We outline the genetic disorders associated with aortic enlargement and discuss the potential role of mitochondrial pathology, in particular mitochondrial DNA heteroplasmy, in the disease pathogenesis.

Assessment of Computational Histopathology in Thoracic Aortic Aneurysm

Background and Hypothesis: Thoracic aortic aneurysm (TAA) histopathology includes elastic fiber (EF) abnormalities, mucoid extracellular matrix (MECM) accumulation, and smooth muscle derangement in the aortic medial layer. While semi-quantitative grading of these characteristics is a standard practice, computational characterization of medial layer components may facilitate novel quantitative analyses at higher throughput. We hypothesized that computational results would correlate with results of semi-quantitative grading of aortic histopathology. Experimental Design: Formalin-fixed, paraffin-embedded human aortic tissue sections were stained with Movat’s pentachrome to characterize aortic microstructure. Sections were also immunostained for nitrotyrosine residues to assess oxidative stress. Samples were initially graded semi-quantitatively by two independent blinded readers. Next, computational histopathology software was used a) to quantify the proportions of EF, MECM, and cellular area in the medial layer of pentachrome-stained sections and b) to quantify the distribution and intensity of positive nitrotyrosine staining in immunostained sections. Association between semi-quantitative grading and computed values was tested with ANOVA. Results: The cohort included 74 participants who underwent prophylactic aortic replacement for TAA and 23 healthy controls. The mean age was 54±17 years. On average, EFs accounted for 49% (range 6-90%) of medial tissue area, whereas MECM accounted for 25% (1-73%). The overall semi-quantitative grade of medial degeneration severity was associated with decrease in EF fraction (p=0.02). The grade of EF thinning also strongly correlated with decrease in EF fraction (p=1x10-6). Meanwhile, grade for accumulation of MECM was associated with increase in MECM (p=0.004). Increased semi-quantitative grading for nitrotyrosine levels was associated with increased nuclear signal optical density (p=9x10-10) and greater percentage of cells labeled as strongly positive (p=8x10-10). Conclusion and Potential Impact: We observed significant correlations between computed quantitative values and semi-quantitative grading. This suggests that computational histopathology is a valid method for investigation of human TAA tissues.

Double Barreled Graft (Chimney) as a Strategy to Preserve Supraortic Branches in Contained Ruptured Thoracic Aneurysm Thoraco Endovascular Aortic Aneurysmal Repair- A Case Report

Out of many strategies that are used to treat aortic arch disease, including open surgery, branched techniques, and hybrid repair with Thoracic Endovascular Aortic Aneurysmal Repair (TEVAR) and supra-aortic branch reconstruction and fenestration, Thoracic Endovascular Aortic Aneurysmal Repair (TEVAR) incorporating chimney is frequently used in unstable and morbid patients not suitable for other procedures. We describe here a case of contained rupture of a thoracic aortic aneurysm, which was treated with TEVAR incorporating a double chimney to the left common carotid and left subclavian arteries. There was an uncomplicated course of the procedure with complete coverage of aneurysm with stent-graft and open aortic arch vessels when followed up to 6 months. There were no complications noted as well. In this case we took the precaution to upsize the stent-graft by 20% to 30% also for adequate coverage of aneurysm we had to adopt to the chimney technique. To prevent complications like gutter and endoleaks, the kissing technique was used during deployment. In addition, there was adequate coverage of chimney-grafts with adequate proximal projection.