Matrix Metalloproteinase and Aortic Aneurysm: A Two-sample Mendelian Randomization Study.

BACKGROUND: Studies have linked matrix metalloproteinases (MMPs) to both thoracic aortic aneurysm and abdominal aortic aneurysm (TAA and AAA). The precise MMPs entailed in this procedure, however, were still unknown. This study used a two-sample Mendelian randomization (MR) analysis to look into the causal relationship between MMPs and the risk of TAA and AAA. METHODS: Eight MMPs, including MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-12, and MMP-13, were found among people of European ancestry with accessible Genome-Wide Association Studies (GWAS). We employed the findings from Genome-Wide Association Studies (GWAS) for 8 MMPs, and TAA and AAA from the FinnGen consortiums (3,201 cases and 317,899 controls, respectively) were used in a two-sample MR analysis. The primary method of analysis for MR was the inverse variance weighted (IVW) method, along with analyses of heterogeneity and horizontal pleiotropy. 31 single-nucleotide polymorphisms connected to MMP were retrieved. RESULTS: IVW demonstrated a negative causal association between TAA and AAA and serum MMP-12 levels. The incidence of TAA decreased by 1.031% for every 1 ng/mL increase in serum MMP-12 [odds ratio (OR) = 0.897, 95% confidence interval (CI): 0.831-0.968, P = 0.005]. The incidence of AAA fell by 1.653% (OR = 0.835, 95% CI: 0.752-0.926, P = 0.001) for every 1 ng/mL increase in serum MMP-12. There was no horizontal pleiotropy or heterogeneity in the MR data (P > 0.05). CONCLUSIONS: The levels of TAA and AAA and serum MMP-12 are causally related. MMP-12 is a factor that reduces the risk of AAA and TTA. Our study suggested that MMP-12 level is causally associated with a decreased risk of TAA and AAA.

Fate of the unoperated ascending thoracic aortic aneurysm: three-decade experience from the Aortic Institute at Yale University.

AIMS: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention. METHODS AND RESULTS: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression. CONCLUSION: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention.

INFLAMMATORY FACTORS IN DISSECTION OF THORACIC AORTIC ANEURYSM.

In recent years, the prevalence of thoracic aortic aneurysm has increased, and in most cases this pathological condition is diagnosed accidentally. The aim of the current study was to determine the relationship of clinical, laboratory and morphological data with the presence of aorta wall dissection in patients with thoracic aortic aneurysm to reveal factors associated with aorta dissection. MATERIALS AND METHODS: The following data of 109 patients mean aged of 53 years with thoracic aortic aneurysm (43 patients with aortic dissection) were analyzed: presence/absence of arterial hypertension, indicators of general blood analysis and blood biochemistry, immunomorphological characteristics of the expression of Von Willebrand factor. RESULTS: Statistically significant differences were found between the incidence of arterial hypertension with respect to the presence or absence of aortic dissection (p=0.002), the relationship between the content of lymphocytes (p=0.021), segmented neutrophils (p=0.001) and the presence of Von Willebrand factor in the medial layer of the aorta, i.e., the prevalence of vasa vasorum (p=0.018), with aortic dissection. The average expression area of Willebrand factor in the medial layer of the aorta during dissection was 3.6 (1.5)%, and in patients without aortic dissection - 0.8 (0.3)%. CONCLUSION: The results of the study indicate that aortic dissection in patients with thoracic aortic aneurysm is associated with high blood pressure and is accompanied by the development of an inflammatory reaction.

Incidence and risk factors for interval aortic events during staged fenestrated-branched endovascular aortic repair.

OBJECTIVE: Staged endovascular repair of complex aortic aneurysms with first-stage thoracic endovascular aortic repair may decrease the risk of spinal cord ischemia (SCI) associated with fenestrated-branched endovascular aortic repair (FB-EVAR) of thoracoabdominal aortic aneurysms or optimize the proximal landing zone in the cases requiring total aortic arch repair. However, a limitation of multistaged procedures is the risk of interval aortic events (IAEs) including mortality from a ruptured aneurysm. We aim to identify the incidence of and risk factors associated with IAEs during staged FB-EVAR. METHODS: This was a single-center, retrospective review of patients who underwent planned staged FB-EVAR from 2013 to 2021. Clinical and procedural details were reviewed. End points were the incidence of and risk factors associated with IAEs (defined as rupture, symptoms, and unexplained death) and outcomes in patients with or without IAEs. RESULTS: Of 591 planned FB-EVAR patients, 142 underwent first-stage repairs. Twenty-two did not have a planned second stage because of frailty, preference, severe comorbidities, or complications after the first stage and were excluded. The remaining 120 patients (mean age: 73 ± 6 years, 51% female) were planned for second-stage completion FB-EVAR and comprised our cohort. The incidence of IAEs was 13% (16 of 120). This included confirmed rupture in 6 patients, possible rupture in 4, symptomatic presentation in 4, and early unexplained interval death with possible rupture in 2. The median time to IAEs was 17 days (range: 2-101 days), and the median time to uncomplicated completion repairs was 82 days (interquartile range: 30-147 days). Age, sex, and comorbidities were similar between the groups. There were no differences in familial aortic disease, genetically triggered aneurysms, aneurysm extent, or presence of chronic dissection. Patients with IAEs had significantly larger aneurysm diameters than those without IAEs (76.6 vs 66.5 mm, P ≤ .001). This difference persisted with indexing for body surface area (aortic size index: 3.9 vs 3.5 cm/m2, P = .04) and height (aortic height index: 4.5 vs 3.9 cm/m, P ≤ .001). IAE mortality was 69% (11 of 16) compared with no perioperative deaths for those with uncomplicated completion repairs. CONCLUSIONS: The incidence of IAEs was 13% in patients planned for staged FB-EVAR. This represented a notable morbidity, including rupture, which must be balanced with SCI and landing zone optimization when planning repair. Larger aneurysms, especially when adjusted for body surface area, are associated with IAEs. Minimizing time between stages vs single-stage repairs for larger (>7 cm) complex aortic aneurysms in patients with reasonable SCI risk should be considered when planning repair.

The epidemiology of pathologically confirmed clinically isolated aortitis: a North American population-based study.

OBJECTIVES: Clinically isolated aortitis (CIA) refers to inflammation of the aorta without signs of systemic vasculitis or infection. Population-based data on the epidemiology of CIA in North America is lacking. We aimed to investigate the epidemiology of pathologically confirmed CIA. METHODS: Residents of Olmsted County, Minnesota were screened for thoracic aortic aneurysm procedures with current procedural terminology codes between January 1, 2000, and December 31, 2021, using the resources of the Rochester Epidemiology Project. The medical records of all patients were manually reviewed. CIA was defined as histopathologically confirmed active aortitis diagnosed by evaluation of aortic tissue obtained during thoracic aortic aneurysm surgery in the absence of any infection, rheumatic disease, or systemic vasculitis. Incidence rates were age and sex adjusted to the 2020 United States total population. RESULTS: Eight incident cases of CIA were diagnosed during the study period; 6 (75%) of them were female. Median (IQR) age at diagnosis of CIA was 78.3 (70.2-78.9) years; all were diagnosed following ascending aortic aneurysm repair. The overall age and sex adjusted annual incidence rate of CIA was 8.9 (95% CI, 2.7-15.1) per 1,000,000 individuals over age 50 years. The median (IQR) duration of follow-up was 8.7 (1.2-12.0) years. The overall mortality compared to the age and sex matched general population did not differ (standardised mortality ratio: 1.58; 95% CI, 0.51-3.68). CONCLUSIONS: This is the first population-based epidemiologic study of pathologically confirmed CIA in North America. CIA predominantly affects women in their eighth decade and is quite rare.

No Sex Differences in the Prevalence of Intracranial Aneurysms in Patients with Ascending Thoracic Aortic Aneurysms: A Multi-Center Experience.

BACKGROUND: Previous studies suggest a coprevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in the detection/treatment of IAs in patients with ascending thoracic aortic aneurysms (ATAA) relative to patients without ATAA. METHODS: Surgical cases of ATAA repaired at 3 sites from January 1998 to December 2018 were retrospectively reviewed. Out of these patients, those with intracranial vascular imaging were selected for our study, and these individuals were concurrently randomly matched with a control group of patients who underwent intracranial vascular imaging without an ATAA in a 1:1 ratio by age, sex, smoking history, and year of intracranial vascular imaging. Conditional logistic regression was used to calculate odds ratios (OR). RESULTS: We reviewed 2176 ATAA repairs. 74% (n = 1,615) were men. Intracranial vascular imaging was available in 298 (13.7%) patients. Ninteen patients were found to have 22 IAs for a prevalence of 6.4%. Mean size of IA was 4.6 ± 3.3 mm; mean age at IA detection, 63.4 ± 12.1 years. IA was present on head imaging in 4.7% of male and 12.5% of female patients. Eleven (58%) patients were men. The OR of having IA in female versus male patients is 2.90, 95% confidence interval [CI] [1.08-7.50], P = 0.029. Time from IA diagnosis to ATAA repair was 1.7 ± 116.2 months. Two patients underwent treatment for IA, one ruptured and one unruptured. All were diagnosed before ATAA repair. Treatment included 1 clipping and 1 coiling with subsequent reintervention of the coiling using a flow diversion device. In the matched group of patients who had intracranial vascular imaging without ATAA, the rate of IA is 5.0%. IA was detected in 3.8% of males and 9.4% of female patients for an OR of 2.59, 95% CI [0.84-7.47], P = 0.083. Association within our study and matched groups, the OR of developing an IA with and without ATAA was not statistically significant 1.29, 95% CI [0.642.59], P = 0.48. There was also no evidence of sex differences in the association of ATAA with IA (interaction P = 0.88). The OR for the association of ATAA with IA was 1.33, 95% CI [0.46-3.84], P = 0.59 in females and 1.25, 95% CI [0.49-3.17], P = 0.64 in males. CONCLUSIONS: Our study found that IA was present in 6.4% of patients with ATAA who had intracranial vascular imaging available. The odds of IA were 1.29 times higher than a matched cohort of patients who had intracranial vascular imaging without ATAA but this failed to achieve statistical significance. We found that the odds of IA were more than 2 times higher in females than males for both those with ATAA (OR = 2.90) and those without ATAA (OR = 2.59); however, it only reached statistical significance in those with ATAA.

Expanding the genetic and phenotypic spectrum of ACTA2-related vasculopathies in a Dutch cohort.

PURPOSE: Heterozygous pathogenic/likely pathogenic (P/LP) variants in the ACTA2 gene confer a high risk for thoracic aortic aneurysms and aortic dissections. This retrospective multicenter study elucidates the clinical outcome of ACTA2-related vasculopathies. METHODS: Index patients and relatives with a P/LP variant in ACTA2 were included. Data were collected through retrospective review of medical records using a standardized questionnaire. RESULTS: A total of 49 individuals from 28 families participated in our study. In total, 20 different ACTA2 variants were detected. Aortic events occurred in 65% of the cases (78.6% index patients and 47.6% relatives). Male sex and hypertension emerged as significantly associated with aortic events. Of 20 individuals, 5 had an aortic diameter of <45 mm (1.77 inches) at the time of the type A dissection. Mean age at first aortic event was 49.0 ± 12.4 years. Severe surgical complications for type A and type B dissection occurred in 25% and 16.7% of the cases and in-hospital mortality rates were 9.5% and 0%, respectively. CONCLUSION: P/LP ACTA2 variants are associated with an increased risk for an aortic event and age-related penetrance, which emphasizes the importance of early recognition of the disease. Caregivers should be aware of the risk for aortic dissections, even in individuals with aortic diameters within the normal range.

Increased risk of thoracic aortic complications among patients with giant cell arteritis: a nationwide, population-based cohort study.

OBJECTIVE: To assess the risk of aortic aneurysms (AA), aortic dissections (AD) and peripheral arterial disease (PAD) among patients with GCA. METHODS: In this nationwide, population-based cohort study using Danish national health registries, we identified all incident GCA patients ≥50 years between 1996 and 2018 who redeemed three or more prescriptions for prednisolone. Index date was the date of redeeming the third prednisolone prescription. Case definition robustness was checked through sensitivity analysis. We included general population referents matched 1:10 by age, sex and calendar time. Using a pseudo-observation approach, we calculated 5-, 10- and 15-year cumulative incidence proportions (CIP) and relative risks (RR) of AA, AD and PAD with death as a competing risk. RESULTS: We included 9908 GCA patients and 98 204 referents. The 15-year CIP of thoracic AA, abdominal AA, AD and PAD in the GCA cohort were 1.9% (95% CI 1.5, 2.2), 1.8% (1.4-2.2), 1.0% (0.7-1.2) and 4.8% (4.2-5.3). Compared with the referents, the 15-year RR were 11.2 (7.41-16.9) for thoracic AA, 6.86 (4.13-11.4) for AD, 1.04 (0.83-1.32) for abdominal AA and 1.53 (1.35-1.74) for PAD. Among GCA patients, female sex, age below 70 years and positive temporal artery findings were risk factors for developing thoracic AA. The median time to thoracic AA was 7.5 years (interquartile range 4.4-11.2) with a number needed to be screened of 250 (167-333), 91 (71-111) and 53 (45-67) after 5, 10 and 15 years. CONCLUSION: Patients with GCA have a markedly increased risk of developing thoracic AA and AD, but no increased risk of abdominal AA.

Women with thoracoabdominal aortic aneurysms have increased frailty and more complex aortic anatomy compared with men.

OBJECTIVE: Operative repair of thoracoabdominal aortic aneurysms (TAAAs) is high risk, and many patients will be unfit for intervention. Prior studies have noted lower rates of repair for women than for men. The reasons for this disparity have remained unknown but could include a greater burden of co-morbid illness or anatomic barriers. Frailty could also contribute to the lower intervention rates but has rarely been reported in preoperative risk assessments. The aim of the present study was to assess the sex-related differences in clinical comorbidities, anatomic suitability, and frailty among an unselected cohort of patients who had presented with TAAAs. METHODS: All patients with extent I to V TAAAs confirmed by computed tomography imaging between 2009 and 2019 at a single institution were reviewed. Patients were included regardless of whether they had undergone repair. Clinical comorbidities, anatomic details, and metrics of frailty were collected and used to determine operative risk. RESULTS: Of the 578 identified patients, 233 (40%) were women. The women were older than the men at diagnosis (71 years vs 68 years; P = .006) but had had similar comorbidities, with the exception of lower rates of coronary artery disease (37% vs 47%; P = .04) and higher rates of chronic obstructive pulmonary disease (45% vs 36%; P = .008). The Society for Vascular Surgery clinical comorbidity score was similar between the sexes. Women were less likely to have undergone prior aortic surgery (32% vs 53%; P < .0001) but had had more extensive aneurysms (P = .007) with greater rates of prohibitive anatomic risk factors (open repair, 31% vs 17% [P = .01]; endovascular repair, 33% vs 28% [P = .32]). The metrics of frailty were higher for the women, including recent unintentional weight loss (11% vs 5%; P = .002), limited physical activity tolerance (46% vs 31%; P < .0001), and the need for ambulatory assistance (13% vs 6%; P < .0001). Of the 578 patients, 55% of the women and 30% of the men had had at least one frailty metric that was prohibitive for open repair (P = .0006). The women had also scored higher on the modified frailty index (P = .009). For open repair, 74% of women and 61% of men had at least one prohibitive risk factor. The women were also more likely to have multiple types of prohibitive risk factors. Compared with the men, the women were less likely to be offered repair (60% vs 74%; P = .0009) and less likely to undergo repair (44% vs 62%; P = .0001). CONCLUSIONS: Women with TAAAs had increased metrics of frailty and anatomic risk that were not captured by comorbidity-based risk assessments. This suggests that frailty, together with complex anatomy, could explain the lower intervention rates for women with TAAAs.

Age-related differences in acute aortic dissection.

OBJECTIVE: The present study investigated the differences in clinical characteristics, treatments, and outcomes of patients with acute aortic dissection (AAD) in different age groups. METHODS: The present single-center retrospective study was conducted from August 2014 to August 2020. The patients were divided into three groups: age <45 years (young group), age 45 to 59 years (middle-age group), and age >59 years (elderly group). Type A (TAAD) and type B (TBAD) aortic dissection were evaluated separately using the latest definitions. RESULTS: The mean age at onset was 52.4 years in our cohort of 602 patients. The young group included a large proportion of male patients (86%). The body mass index and body surface area were higher in the young group. The proportion of non-true lumen blood supply of branches on the abdominal aorta in the young group (27%-55%) was greater than that in the others. In the young group, the distal extent of dissection in 84% of TAAD and 89% of TBAD exceeded the abdominal aortic branch cluster (AABC) compared with 36% of TAAD and 58% of TBAD in the elderly group. The multivariate analysis revealed that age <45 years (odds ratio, 5.15; P < .001) and D-dimer level (odds ratio, 1.05; P = .001) were risk factors for intimal flap tear exceeding the AABC. The proportion of visceral and lower limb malperfusion increased from 4.8% to 36.9% as the intimal flap tear exceeded the AABC. CONCLUSIONS: Compared with middle-age and elderly patients, young patients with AAD had two characteristics (ie, obesity and an intimal flap that had frequently exceeded the branches of the aorta). These two factors resulted in a greater proportion of non-true lumen blood supply, increased visceral and lower limb malperfusion, and an increase in potential associated risks.

Extrathoracic Aneurysms in Marfan Syndrome: A Systematic Review of the Literature.

BACKGROUND: Marfan syndrome (MS) most often shows as thoracic aortic aneurysm (TAA) or aortic dissection, but it may also involve other vascular territories. This study aimed to identify those extrathoracic vascular manifestations most frequently associated with MS. METHODS: A systematic review of the literature with Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was carried out. The following databases were included: MEDLINE, Embase, Web of Science, Cumulative Index of Nursing and Health Sciences Literature (CINHAL); Spanish database MEDESY Cochrane Central Register of Controlled Trials (CENTRAL). RESULTS: A total of 10,008 articles were identified, leaving 155 for the first stage of data analysis (total incidence of aneurysms) and 83 for the second (descriptive data analysis). Overall, 518 aneurysms were identified: 149 in the head and neck, 94 in the extremities, and 275 in the aortic, iliac, and visceral sectors. Mostly, they were simultaneously discovered during studies of the TAA. In the abdominal aorta, the presentation with rupture in 11 of 32 patients stands out. Resection and bypass were the most frequently used methods for repair in the treated cases. CONCLUSIONS: Although its frequency in the general population is unknown, this systematic review suggests that extrathoracic aneurysmal arterial involvement in the MS may be more frequent than expected. We believe screening for aneurysms in other vascular sectors may be advisable, especially in patients with MS and TAA.

Socioeconomic disparities in surveillance and follow-up of patients with thoracic aortic aneurysm.

BACKGROUND: Thoracic aortic aneurysm (TAA) is a significant risk factor for aortic dissection and rupture. Guidelines recommend referral of patients to a cardiovascular specialist for periodic surveillance imaging with surgical intervention determined primarily by aneurysm size. We investigated the association between socioeconomic status (SES) and surveillance practices in patients with ascending aortic aneurysms. METHODS: We retrospectively reviewed records of 465 consecutive patients diagnosed between 2013 and 2016 with ascending aortic aneurysm ≥4 cm on computed tomography scans. Primary outcomes were clinical follow-up with a cardiovascular specialist and aortic surveillance imaging within 2 years following index scan. We stratified patients into quartiles using the area deprivation index (ADI), a validated percentile measure of 17 variables characterizing SES at the census block group level. Competing risks analysis was used to determine interquartile differences in risk of death before follow up with a cardiovascular specialist. RESULTS: Lower SES was associated with significantly lower rates of surveillance imaging and referral to a cardiovascular specialist. On competing risks regression, the ADI quartile with lowest SES had lower hazard of follow-up with a cardiologist or cardiac surgeon before death (hazard ratio: 0.46 [0.34, 0.62], p < .001). Though there were no differences in aneurysm size at time of surgical repair, patients in the lowest socioeconomic quartile were more frequently symptomatic at surgery than other quartiles (92% vs. 23%-38%, p < .001). CONCLUSION: Patients with lower SES receive less timely follow-up imaging and specialist referral for TAAs, resulting in surgical intervention only when alarming symptoms are already present.

National trends in thoracic aortic aneurysms and dissections in patients with Marfans and Ehlers Danlos syndrome.

INTRODUCTION: Connective tissue disorders predispose patients to earlier aortic dissections and aneurysms. However, there is limited large cohort data given its low incidence. METHODS: The National Inpatient Sample was searched for all adults with Marfans (MFS) and Ehlers Danlos (EDS) disease between 2010 and 2017. ICD codes were used to select those with a type A aortic dissection or aneurysm. RESULTS: There was a total of 19,567 cases, giving the estimated incidence of MFS and EDS of 18 and 22.4 per 100k people, respectively. After inclusion criteria, there were 2553 MF and 180 EDS patients. There was no statistical difference in mortality between the MFS and EDS cohorts (4.6% vs. 2.8%, p = .26). EDS patients were more likely to undergo a TEVAR procedure (2.8% vs. 1.0%, p = .03). MF patients were more likely to have a complication of acute kidney injury (p = .02). EDS patients were more likely older (50 vs. 42, p < .001) and female (47% vs. 33%, p < .001). MFS patients were more likely to have a type A aortic dissection (44% vs. 31%, p < .001). The majority (89%) of patients were treated at urban teaching hospitals. On univariable logistic regression, aortic dissection was a predictor for mortality (odds ratio 7.31, p < .001). The type of connective tissue disease was not a significant predictor. CONCLUSIONS: National level estimates show low mortality for patients with MF or ED presenting to the hospital with aortic dissection or aneurysm. The differences in age and gender can guide surveillance for these patient populations, leading to more elective admissions and reduced hospital mortality.

Familial Clustering of Aortic Size, Aneurysms, and Dissections in the Community.

BACKGROUND: Ruptured aortic aneurysm and aortic dissections are potentially preventable disorders associated with high mortality. Screening of individuals at risk may translate into elective surgical interventions and lowered mortality. It is uncertain if the risk of aortic dilation of varying degrees aggregates within families. METHODS: We investigated the risk of having thoracic and abdominal aortic sizes in the highest quartile (measured by computed tomography scans and indexed for body size) if at least 1 parent did so in the Framingham Heart Study cohorts, and estimated the incidence rates and hazard ratios of developing aortic aneurysm or dissection among first-degree relatives of those with aortic aneurysm or dissection, in comparison with age- and sex-matched controls (1:10 for aortic aneurysm and 1:100 for aortic dissection) using the Danish nationwide administrative registries. RESULTS: In the Framingham Heart Study, offspring (n=235) whose parent(s) had a sex- and age-standardized aortic size in the upper quartile had a multivariable-adjusted ≈3-fold increased odds ratio of belonging to the upper quartile themselves. In Denmark, a total of 68 939 individuals (mean age, 42 years) had a first-degree relative with aortic aneurysm and 7209 persons (mean age, 39 years) had a first-degree relative with aortic dissection. During an average follow-up of 7 years, first-degree relatives of patients with aortic aneurysm and dissection had a hazard ratio of 6.70 (95% CI, 5.96-7.52) for developing aortic aneurysm and a hazard ratio of 9.24 (95% CI, 5.53-15.44) for dissection in comparison with matched controls. These estimates remained unchanged on adjusting for several comorbidities, including prevalent hypertension, bicuspid aortic valve, and the Marfan syndrome. For both aortic aneurysm and dissections, the absolute event rates approached 1 per 1000 person-years for first-degree relatives versus 11 to 13 (aortic aneurysm) and 2 to 3 (aortic dissections) per 100 000 person-years among controls. CONCLUSIONS: Increased aortic size, a precursor of aortic aneurysm and a risk factor for dissection, clusters in families. The incidence rates of aortic aneurysm and dissections approach the incidence rates of other common cardiovascular conditions in first-degree relatives, supporting the use of systematic screening for these conditions.

Characterization of syndromic, nonsyndromic familial, and sporadic type B aortic dissection.

OBJECTIVE: Type B aortic dissection (TBAD) is commonly thought of as a sporadic event. However, an increasing body of data has suggested that genetic factors can influence TBAD. Our aim was to determine the prevalence of heritable TBAD, defined as either syndromic TBAD or nonsyndromic familial TBAD and to detail the natural history and long-term clinical outcomes compared with patients with "sporadic" TBAD without an identified syndrome or family history. METHODS: The clinical records of 389 patients with TBAD who had presented to a single health care system from 1995 to 2017 were reviewed. A family history was obtained by interview and/or medical record review. Syndromic TBAD was defined as TBAD in patients with Marfan, Loeys-Dietz, or vascular Ehlers-Danlos syndrome. Nonsyndromic familial TBAD was defined as a family history of aortic or arterial aneurysm or dissection and/or sudden death in a first- or second-degree relative in the absence of a known syndrome. Patients with syndromic and nonsyndromic familial TBAD were compared with patients with sporadic TBAD in terms of the comorbid conditions, aortic repair, and mortality. RESULTS: Of 389 patients (71.2% male) with TBAD, the etiology of TBAD was heritable in 27.9% (9.6% syndromic; 18.3% nonsyndromic familial TBAD) and 72.1% sporadic of the cases. Patients with syndromic and nonsyndromic familial TBAD had been more frequently referred in the chronic phase than were the patients with sporadic TBAD (35.5% vs 44.1% vs 25.8%; P = .014) and had presented at a younger age (40.6 ± 10.9 years vs 55.2 ± 11.3 years vs 62 ± 12.9 years; P < .001) and with lower blood pressure at acute TBAD (systolic, 159.2 ± 21 mm Hg vs 178.9 ± 39.3 mm Hg vs 186.1 ± 38.4, P = .01; diastolic, 84.3 ± 17.3 mm Hg vs 91.4 ± 24.1 mm Hg vs 101.6 ± 22.3 mm Hg, P = .001). Among patients with acute TBAD surviving to discharge from the initial hospitalization, thoracic endovascular aortic repair (TEVAR) had been performed in 115 patients, with no significant differences in TEVAR usage in the three groups. However, those with syndromic and nonsyndromic familial TBAD had had a greater incidence of retrograde aortic dissection after TEVAR (33.3% vs 15% vs 3%; P = .006). They had also required a greater number of arch repairs (30% vs 10.5% vs 3.6%; P < .001) and had died at a younger age (47.7 ± 13.1 years vs 65.7 ± 13.7 years vs 72.8 ± 12.7 years; P < .001). Aortic-related mortality was more common among patients with syndromic TBAD (36.7% vs 12.3% vs 17.6%; P = .016). CONCLUSIONS: In our single-institutional experience, heritable TBAD accounted for one in four patients with TBAD. Nonsyndromic familial TBAD was twice as common as syndromic TBAD and appeared to share many clinical features. Identifying these patients early in their disease course and personalizing their care might improve their survival.

Splanchnic occlusive disease predicts for spinal cord injury after open descending thoracic and thoracoabdominal aneurysm repair.

OBJECTIVE: In the present study, we sought to discern the effects of splanchnic occlusive disease (SOD; renal, superior mesenteric, and/or celiac axis arteries) on spinal cord injury (SCI; paraparesis or paraplegia) and major adverse events (MAE) after descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysm (TAAA) open repair. METHODS: Patients who had undergone DTA/TAAA repair at our institution were dichotomized according to the presence of SOD, which was investigated as a predictive factor of our primary (SCI) and secondary (operative mortality, myocardial infarction, stroke, tracheostomy, de novo dialysis, MAE, survival) endpoints. Risk adjustment used both propensity score matching and multivariable logistic regression. RESULTS: From July 1997 to October 2019, 888 patients had undergone DTA/TAAA repair, of whom 19 were excluded from our analysis for missing data. SOD was absent in 712 patients and present in 157 patients. The patients with SOD had presented with a greater incidence of preoperative renal impairment (61 [38.9%] vs 175 [24.6%]; P < .01) and peripheral arterial disease (60 [38.2%] vs 162 [22.8%]; P < .01] and decreased left ventricular ejection fraction (45%; interquartile range, 10%; vs 50%; interquartile range, 4%; P < .01). The etiology of aortic disease was more frequently dissection in the SOD group (56.1% vs 43.7%) and more frequently nondissecting aneurysm in the non-SOD group (56.3% vs 43.9%; P < .01). Patients without SOD had presented with aneurysms more cranially located (DTA, 34.0% vs 7.6%; extent I TAAA, 44.0% vs 7.6%). In contrast, patients with SOD had presented with aneurysms more caudally located (extent II TAAA, 36.9% vs 8.6%; extent III TAAA, 30.6% vs 11.0%; extent IV TAAA, 17.2% vs 2.5%; P < .01). Propensity score matching led to 144 pairs, with SOD significantly associated with SCI (10 [6.9%] vs 2 [1.4%]; P = .03) and MAE (47 [32.6%] vs 26 [15%]; P < .01). Ten-year survival was reduced in those with SOD (31.5% vs 45.2%; P < .01). Conditional multivariable regression confirmed SOD to be a predictor of SCI in the matched sample (odds ratio, 6.60; P = .02). CONCLUSIONS: Our results have shown that SOD is a significant predictor of SCI in patients undergoing open DTA/TAAA repair. The investigation of measures to prolong neuronal ischemia tolerance (eg, hypothermia) is warranted for such patients.

Impact of thoracic aortic aneurysm on outcomes of transcatheter aortic valve replacement: A nationwide cohort analysis.

BACKGROUND: The use of transcatheter aortic valve replacement (TAVR) has expanded to patient populations of varying surgical risk in light of recent clinical trials, yet its role in patients with aortic stenosis and coexisting thoracic aortic aneurysm (TAA) is not well-delineated. We aimed to evaluate whether risk factors and in-hospital outcomes vary between TAVR patients with and without an unruptured TAA. METHODS: The Nationwide Readmissions Database was queried for patients hospitalized between January 2012 and December 2017 who underwent TAVR with and without an unruptured TAA. In-hospital outcomes were compared between cohorts after adjusting for sex, comorbidities, and TAVR approach, and in a subgroup analysis that excluded those with bicuspid aortic valves. RESULTS: Among 171,011 TAVR patients, 1,677 (1%) presented with TAA. Patients with TAA were younger (median age 80 vs. 82 years, p < .001) and more likely to have bicuspid aortic valves (9.3% vs. 0.9%, p < .001). Among patients with aneurysm, 2.6% died, 2.2% developed stroke, 1% developed aortic dissection, and 1.4% experienced cardiac tamponade while hospitalized. After adjusting for age, sex, bicuspid aortic valve, and all comorbidities, TAA was associated with significantly higher risk of post-TAVR aortic dissection (OR = 2.117, 95% CI [1.304-3.435], p = .002) and cardiac tamponade (OR = 1.682, 95% CI [1.1-2.572], p = .02). CONCLUSIONS: While the overall incidence of post-TAVR complications is low, patients with an unruptured TAA should be carefully considered by the Heart Team in weighing the additional risks of aortic dissection and cardiac tamponade after TAVR with those associated with surgery.

Numerical knockouts-In silico assessment of factors predisposing to thoracic aortic aneurysms.

Myriad risk factors-including uncontrolled hypertension, aging, and diverse genetic mutations-contribute to the development and enlargement of thoracic aortic aneurysms. Detailed analyses of clinical data and longitudinal studies of murine models continue to provide insight into the natural history of these potentially lethal conditions. Yet, because of the co-existence of multiple risk factors in most cases, it has been difficult to isolate individual effects of the many different factors or to understand how they act in combination. In this paper, we use a data-informed computational model of the initiation and progression of thoracic aortic aneurysms to contrast key predisposing risk factors both in isolation and in combination; these factors include localized losses of elastic fiber integrity, aberrant collagen remodeling, reduced smooth muscle contractility, and dysfunctional mechanosensing or mechanoregulation of extracellular matrix along with superimposed hypertension and aortic aging. In most cases, mild-to-severe localized losses in cellular function or matrix integrity give rise to varying degrees of local dilatations of the thoracic aorta, with enlargement typically exacerbated in cases wherein predisposing risk factors co-exist. The simulations suggest, for the first time, that effects of compromised smooth muscle contractility are more important in terms of dysfunctional mechanosensing and mechanoregulation of matrix than in vessel-level control of diameter and, furthermore, that dysfunctional mechanobiological control can yield lesions comparable to those in cases of compromised elastic fiber integrity. Particularly concerning, therefore, is that loss of constituents such as fibrillin-1, as in Marfan syndrome, can compromise both elastic fiber integrity and mechanosensing.

Incidence and predictors of thoracic aortic damage in biopsy-proven giant cell arteritis.

Objective: To describe the frequency and predisposing factors of aortic structural disease among patients with biopsy-proven giant cell arteritis (GCA).Method: A retrospective review identified all patients with biopsy-proven GCA from 1998 to 2013 with aortic imaging. Kaplan-Meier methods were used to estimate cumulative incidence and Cox models were used to examine potential predictors of development of aneurysm/dilatation of the thoracic aorta.Results: The cohort included 114 patients with aortic imaging performed within a median time of 1.8 months from GCA diagnosis. Fifty-seven patients (50%) had at least one additional follow-up imaging study. At the first imaging study, 8% had evidence of aneurysm/dilatation and 25% thickening of the thoracic aorta. Excluding prevalent cases, the cumulative incidence for aneurysm/dilatation of the thoracic aorta during follow-up was 0% at both 1 year and 2 years but increased to 10% at 5 years. The sole predictor for development of thoracic aortic aneurysm/dilatation was current smoking (hazard ratio 28.8, 95% confidence interval 1.62, 511.4; p = 0.02).Conclusion: Thoracic aortic aneurysm/dilatation was seen in 8% of patients at baseline. Among patients without aortic disease, the cumulative incidence of aortic disease was 10% at 5 years after diagnosis. Current smokers were at an increased risk for developing thoracic aortic damage. Surveillance for aortic damage should be pursued in patients with GCA, particularly those with a smoking history.

Prevalence of Thoracic Aortic Aneurysms in Patients with Degenerative Abdominal Aortic Aneurysms: Results from the Prospective ACTA Study.

OBJECTIVE: There are no recommendations for screening for thoracic aortic aneurysms (TAAs), even in patients with infrarenal abdominal aortic aneurysms (AAAs). The aims of this study were to determine the prevalence of TAAs in patients with AAAs and to analyse the risk factors for this association. METHODS: This was a multicentre prospective study. The Aortic Concomitant Thoracic and Abdominal Aneurysm (ACTA) study included 331 patients with infrarenal AAAs > 40 mm between September 2012 and May 2016. These patients were prospectively enrolled in three French academic hospitals. RESULTS: Patients were classified as having a normal, aneurysmal, or ectatic (non-normal, non-aneurysmal) thoracic aorta according to their maximum aortic diameter indexed by sex, age, and body surface area. Thoracic aortic ectasia (TAE) was defined as above or equal to the 90th percentile of normal aortic diameters according to gender and body surface area. Descending TAA was defined as ≥ 150% of the mean normal value, and ascending TAA as > 47 mm in men and 42 mm in women; 7.6% (n = 25) had either an ascending (seven cases; 2.2%) or descending aortic TAA (18 cases; 5.4%), and 54.6% (n = 181) had a TAE. Among the 25 patients with TAAs, five required surgery; two patients had TAAs related to penetrating aortic ulcers < 60 mm in diameter, and three had a TAA > 60 mm. In the multinomial regression analysis, atrial fibrillation (AF) (odds ratio [OR] 11.36, 95% confidence interval [CI] 2.18 - 59.13; p = .004) and mild aortic valvulopathy (OR 2.89, 1.04-8.05; p = .042) were independent factors associated with TAAs. Age (OR 1.06, CI 1.02 - 1.09; p = .003) and AF (OR 4.36, 1.21 - 15.61; p = .024) were independently associated with ectasia. CONCLUSION: This study confirmed that TAAs coexisting with AAAs are not rare, and one fifth of these TAAs are treated surgically. Systematic screening by imaging the whole aorta in patients with AAAs is clinically relevant and should lead to an effective prevention policy.