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Objective/Introduction Increased vascular tortuosity may be an independent marker of generalized aortic pathology. This study investigates the association between descending thoracic aortic tortuosity, aneurysm pathophysiology, and outcomes following EVAR in AAA patients. Methods Patients who underwent elective EVAR between 2004 and 2018 were reviewed. Thoracic tortuosity index (TTI) was measured using 3D reconstruction software. Patients were dichotomized across the median TTI into high tortuosity [HT] (TTI >1.27, Figure1(a) ) and low tortuosity [LT] (TTI ≤1.27, Figure 1(b) ) groups. Perioperative complications, postoperative outcomes, and CT-based features of thoracic aortic wall degeneration ( Figure 1(c)-(e) ) were collected and analyzed. Results 136 patients underwent treatment: 70 HT patients, including 54 males and 16 females (mean age: 77 years), and 66 LT patients, including 62 males and 4 females (mean age: 70 years) (age; P < .001). LT patients exhibited greater prevalence of hypercholesterolemia and diabetes (P = .045, P = .01). Presence of degenerative aortic wall markers was greater in HT patients (P = .045). HT patients had higher incidence of multiple aneurysms concurrently present in their aorta compared to LT (32.8% vs 11.3%; P = .002). Frequency of AAA rupture/dissection was 4.3% for HT and 1.5% for LT (P = .339). A trend was observed in all cause 30-day mortality in the HT group (P = .061). Other perioperative complications and postoperative outcomes were similar between groups. Conclusion High TTI was associated with older age at time of EVAR, greater prevalence of degenerative markers in the descending thoracic aortic wall, and widespread aorto-iliac dilation. While not predictive of EVAR outcomes, TTI can provide valuable information regarding aneurysm pathophysiology.

Aneurysm sac regression following endovascular repair (EVAR) of an abdominal aortic aneurysm (AAA) is an established indicator of surgical success. However, even with a completely excluded aneurysm, the degree of aortic sac regression may vary. This study evaluates the relationship between aneurysm sac regression after EVAR and the presence of morphological features in the thoracic aorta that can be associated with a subclinical aortic dissection, termed dissection morphology in this study.Patients who underwent EVAR to repair an infrarenal aortic aneurysm at Mount Sinai Hospital between 1996 and 2017 with a postoperative CT scan and a 3-year follow-up scan available for analysis were included in the study. Patients with a type I or type III endoleak were not included. The thoracic aorta was evaluated for dissection morphology on CT scan, which included the presence of aortic dissection, penetrating aortic ulcers, and intramural hematomas. AAA sac regression after EVAR was compared between patients with dissection morphology (n = 157) and patients without those characteristics (n = 141). An independent investigator performed the CT analysis and was blinded to the degree of sac regression.Demographics and comorbid clinical conditions were compared between patients with and without dissection morphology. There were no significant differences in age, gender, smoking habits, or cardiovascular conditions. The median AAA diameter after EVAR, over the course of the study, in patients with dissection morphology decreased by 11.30 mm (-17.20, -3.60) compared to a median change of 0.30 mm (-8.60, 8.60) in patients without dissection morphology features (p 0.001). Patients with dissection morphology also had fewer type II endoleaks in postoperative follow-up scans (22.9% vs. 53.9%, p 0.001). Additionally, patients with dissection morphology had longer EVAR operative times (192.00 min [167.25, 230.00] vs.174.00 min [150.00, 215.00], p = 0.004). AAA-related mortality after 3 years was not significantly different between the 2 groups (p = 1.0).The presence of imaging features consistent with dissection morphology in the thoracic aorta correlated with greater AAA sac regression and fewer type II endoleaks after EVAR. Assessing these imaging features in patients undergoing EVAR may be useful in understanding aneurysm behavior in terms of aneurysm growth, risk of rupture, and outcomes following endovascular surgery. Identifying differential rates of aneurysm sac regression may have implications regarding the role of subclinical dissections in the etiology of AAA development.

Objective The objective of this study was to better understand the pathophysiology and underlying genetic mechanisms behind two abdominal aortic aneurysm (AAA) subtypes using computed tomographic imaging in combination with whole genome sequencing. Methods Patients with a known AAA and European ancestry were included in this investigation and underwent genetic and image analysis. Patients with AAAs and indications of descending thoracic aortic pathology (aortic dissection, penetrating aortic ulcers, intramural hematoma, atheromas, ulcerative plaque, and intramural ulceration, and intimal flaps/tears) were classified as having thoracic aortic disease, grouped together, and compared with patients with an AAA and a normal descending thoracic aorta. Whole genome sequencing was then performed on the 93 patients who had imaging features consistent with thoracic aortic disease and the 126 patients with a normal descending thoracic aorta. Results The results of this study suggest one variant-level, four gene-level, and one gene set-level associations in patients with thoracic aortic disease who also had an AAA. The variant rs79508780 located in TSEN54 achieved study-wide significance (P = 1.71E-06). BATF3 and SMLR1 were significantly associated and EFCAB3 and TAF4 were reached suggestive assocation with a diseased descending thoracic aorta (P = 5.23E-26, P = 1.86E-25, P = 1.54E-05, and P = 8.31E-05, respectively). Gene sets were also compiled using MSigDB and trait-based index single nucleotide variation from major genome-wide association studies. GO_DNA_DOUBLE_STRAND_BREAK_PROCESSING, a gene set related to double-stranded DNA break repair, was significantly associated with thoracic aortic disease in AAA patients (P = 1.80E-06). Conclusions This pilot study provides further evidence that an AAA may be the end result of multiple degenerative pathways. Genetic variations in vitamin D signaling, cholesterol metabolism, extracellular matrix breakdown, and double-stranded DNA break repair pathways were associated with European patients who had an AAA and thoracic aortic disease. Additionally, this study provides support for the application of a radiogenomic approach for the investigation of other potential pathologies that could lead to the development of an AAA or influence future management decisions. (JVS–Vascular Science.) Clinical Relevance In this study, we provide evidence that abdominal aortic aneurysms (AAAs) may be a result of multiple pathophysiologies rather than a single disease. We have identified genetic variants involved in vitamin D signaling, cholesterol metabolism, extracellular matrix breakdown, and double-stranded DNA break repair associated with structural defects in the aortic wall in patients with AAAs who are of European descent. Patients with AAAs and structural defects in the thoracic aorta have been previously linked to differential behavior after endovascular aneurysm repair. These patients with wall defects exhibited greater sac regression, a marker of surgical success, after endovascular aneurysm repair. Our study demonstrates the usefulness of a radiogenomic approach for elucidating mechanisms behind the formation and future behavior of AAAs that could aid surgeons in making future procedural and management decisions.

Abdominal aortic aneurysm (AAA) disease is multifactorial with both environmental and genetic risk factors. The current research in AAA revolves around genetic profiles and expression studies in both human and animal models. Variants in genes involved in extracellular matrix degradation, inflammation, the renin-angiotensin system, cell growth and proliferation and lipid metabolism have been associated with AAA using a variety of study designs. However, the results have been inconsistent and without a standard animal model for validation. Thus, despite the growing body of knowledge, the specific variants responsible for AAA development, progression and rupture have yet to be determined. This review explores some of the more significant genetic studies to provide an overview of past studies that have influenced the current understanding of AAA etiology. Expanding our understanding of disease pathogenesis will inform research into novel diagnostics and therapeutics and ultimately to improve outcomes for patients with AAA.

Aneurysms of the abdominal aorta (AAA) are relatively common - affecting as many as 8% of men and 1% of women over the age of 65. AAAs are characterized by a 50% increase in the diameter of the aneurysmal aorta compared with the normal vessel. Degeneration of structural components of the aortic wall is believed to be central in the pathogenesis of AAAs. The exact mechanism of degeneration is not well characterized, although degradation of elastin and collagen has been clearly shown. At least six genetic variants have been associated with AAA in genome-wide association studies: CDKN2BAS1, DAB2IP, LDLR, LRP1, SORT1, and IL6R. These variants reach genome-wide significance; however, they have not been replicated in multiple cohorts, nor have they been clearly shown to be disease causative. AAA is a challenging disease for investigation because it is most often asymptomatic and generally has a late disease onset, making it difficult to diagnose. Determination of the genetic mechanism behind aneurysm formation, progression, and rupture crosses disciplines requiring input from multiple fields of study, larger patient cohorts, and the evolving modalities of genetic testing.