Aneurysm Growth Rate Research Articles

Aortic Wall Inflammation in the Pathogenesis, Diagnosis and Treatment of Aortic Aneurysms

The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications-which may be lethal-serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms.

Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition

Abdominal aortic aneurysm (AAA) formation and expansion is highly complex and multifactorial, and the improvement of animal models is an important step to enhance our understanding of AAA pathophysiology. In this study, we explore our ability to influence aneurysm growth in a topical elastase plus β-Aminopropionitrile (BAPN) mouse model by varying elastase concentration and by altering the cross-linking capability of the tissue. To do so, we assess both chronic and acute effects of elastase concentration using volumetric ultrasound. Our results suggest that the applied elastase concentration affects initial elastin degradation, as well as long-term vessel expansion. Additionally, we assessed the effects of BAPN by (1) removing it to restore the cross-linking capability of tissue after aneurysm formation and (2) adding it to animals with stable aneurysms to interrupt cross-linking. These results demonstrate that, even after aneurysm formation, lysyl oxidase inhibition remains necessary for continued expansion. Removing BAPN reduces the aneurysm growth rate to near zero, resulting in a stable aneurysm. In contrast, adding BAPN causes a stable aneurysm to expand. Altogether, these results demonstrate the ability of elastase concentration and BAPN to modulate aneurysm growth rate and severity. The findings open several new areas of investigation in a murine model that mimics many aspects of human AAA.

Meta-analysis suggests statins reduce mortality after abdominal aortic aneurysm repair.

The necessity and efficacy of statin treatment for abdominal aortic aneurysm (AAA) remains controversial. This systematic review and meta-analysis was conducted to investigate the effects of statin therapy on the outcomes of patients with AAA. The Cochrane library, Embase, and MedLine were searched comprehensively to identify relevant cohort studies and randomized controlled trials. The primary outcomes included short- and long-term mortality after AAA repair, and secondary outcomes included the incidence of perioperative cardiovascular complications, sac shrinkage after endovascular aneurysm repair, and the growth rate of the aneurysms. Short-term mortality was defined as all-cause 30-day or in-hospital postoperative mortality. Long-term mortality was defined as the all-cause mortality at the end of follow-up period (≥1year). A random effects model was used to combine the results of included studies. Forest plots were created to show the pooled results of each outcome. One post hoc analysis of a randomized trial and 36 cohort studies (n= 134,290 patients) were included in this systematic review. The average score of included studies by Newcastle-Ottawa Scale was 7.76. Patients taking or not taking statin therapy were all diagnosed with unruptured AAA, and 59.9% of these patients were given statin therapy. Compared with statin nonusers, patients in statin therapy had significantly lower long-term mortality (odds ratio, 0.67; 95% confidence interval, 0.59-0.75; P< .001; I2= 71.7%), and short-term mortality after aneurysmal repair (odds ratio, 0.51; 95% confidence interval, 0.36-0.73; P< .001; I2= 81.4%). No significant difference was found between patients taking or not taking statin treatment on perioperative cardiovascular complications or sac shrinkage after endovascular aneurysm repair or growth rate of AAA under surveillance. These findings suggest that statin use is associated with a significant decrease in long- and short-term mortality in patients after AAA repair. Based on these results, statin therapy is worth being used in clinical practice for the management of AAA.

Ascending thoracic aortic aneurysm growth is minimal at sizes that do not meet criteria for surgical repair.

Historic studies of nonsyndromic ascending thoracic aortic aneurysms (aTAAs) reported that the typical aTAA growth rate was approximately 0.6 mm/year, but data were limited due to relatively few studies using computed tomography (CT) imaging. Our purpose was to reevaluate the annual growth rate of nonsyndromic aTAAs that do not meet criteria for surgical repair in veterans in the contemporary era, using modern CT imaging suitable for highly accurate and reproducible aneurysm measurement. Nonsurgical patients (diameter <5.5 cm) undergoing aneurysm surveillance at a Veterans Affairs Medical Center with repeat CT imaging performed 3 to 5 years apart were identified. Maximum diameter was determined by a single radiologist using multiplanar reformat-based measurements. Average rate of aneurysm growth was evaluated based on longest available follow-up. Sixty-seven patients were included. Average follow-up time was 4.06±0.83 years. Patients were exclusively male, with average age of 68.1±6.0 years, and the majority had a history of smoking (n=52, 78%), hypertension (n=52, 78%), and dyslipidemia (n=48, 72%). Average baseline aneurysm diameter was 44.0±3.2 mm and average growth rate was 0.11±0.31 mm/year, with no difference in growth rate between patients with initial diameter ≤45 vs. >45 mm. Only 3 patients experienced clinically significant changes in diameter with magnitude greater than 5% of baseline. In this veteran population, most patients did not experience significant annual aneurysm growth over up to 5 years of follow-up, regardless of initial diameter. Thus, in the modern era, aTAAs may not grow as quickly as previously described, which will be important in determining appropriate intervals for aneurysm surveillance based upon risk-benefit ratio.

Prevalence and risk of progressive aortic aneurysm and dissection in adults with conotruncal anomalies.

Conotruncal anomalies share common embryogenic defects of the outflow tracts and great arteries, which result in a predisposition to aortic aneurysms. The purpose of this study was to describe the prevalence and risk of progressive aortic aneurysms in adults with conotruncal anomalies. Retrospective study of adults with conotruncal anomalies that underwent cross-sectional imaging 2003-20. Aneurysm was defined as aortic root/mid-ascending aorta >2.1 mm/m2/>1.9 mm/m2, progressive aneurysm as increase by >2 mm, and severe aneurysm as dimension >50 mm. Of 2261 patients (38 ± 12 years; male 58%), 1167 (52%) had an aortic aneurysm, and 205 (14%) had a severe aortic aneurysm. Mean annual increase in aortic root/mid-ascending aorta was 0.3 ± 0.1 mm/0.2 ± 0.1 mm. The 3-, 5-, and 7-year cumulative incidence of the progressive aortic aneurysm was 4%, 7%, and 9%, respectively. The rate of aneurysm growth decreased with age, with no significant growth after age 40 years. There was an excellent correlation between aortic indices from cross-sectional imaging and echocardiography. Of 950 females, 184 had ≥1 pregnancy, and 81 (44%) of the 184 patients had aortic aneurysm prior to pregnancy. There was no aortic dissection or progression of the aortic aneurysm during pregnancy. Overall, there was no aortic dissection during 7984 patient-years of follow-up. Aortic aneurysm was common in patients with conotruncal anomalies. However, the risk of progressive aneurysm or dissection was low. Collectively, these data suggest a benign natural history and perhaps a less frequent need for cross-sectional imaging. Further studies are required to determine the optimal timing for surgical intervention in this population.

Associations of Genes for Killer Cell Immunoglobulin-like Receptors and Their Human Leukocyte Antigen-A/B/C Ligands with Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) is an immune-mediated disease with a genetic component. The multifactorial pathophysiology is not clear and there is still no pharmacotherapy to slow the growth of aneurysms. The signal integration of cell-surface KIRs (killer cell immunoglobulin-like receptors) with HLA (ligands, human leukocyte class I antigen molecules) modulates the activity of natural killer immune cells. The genetic diversity of the KIR/HLA system is associated with the risk of immune disorders. This study was a multivariate analysis of the association between genetic variants of KIRs, HLA ligands, clinical data and AAA formation. Genotyping was performed by single polymerase chain reaction with sequence-specific primers using commercial assays. Patients with HLA-A-Bw4 have a larger aneurysm by an average of 4 mm (p = 0.008). We observed a relationship between aneurysm diameter and BMI in patients with AAA and co-existing CAD; its shape was determined by the presence of HLA-A-Bw4. There was also a nearly 10% difference in KIR3DL1 allele frequency between the study and control groups. High expression of the cell surface receptor KIR3DL1 may protect, to some extent, against AAA. The presence of HLA-A-Bw4 may affect the rate of aneurysm growth and represents a potential regional pathogenetic risk of autoimmune injury to the aneurysmal aorta.

The Hyperattenuating Crescent Sign Is Not Necessarily a Sign of Impending Aortic Aneurysm Rupture

The "crescent sign" is a hyperattenuating crescent-shaped region on CT within the mural thrombus or wall of an aortic aneurysm. Although it has previously been associated with aneurysm instability or impending rupture, the literature is largely based on retrospective analyses of urgently repaired aneurysms. We strove to more rigorously assess the association between an isolated "crescent sign" and risk of impending aortic rupture. Patients were identified by querying a single health system PACS database for radiology reports noting a crescent sign. Adult patients with a CT demonstrating a descending thoracic, thoracoabdominal, or abdominal aortic aneurysm and "crescent sign" between 2004 and 2019 were included, with exclusion of those showing definitive signs of aortic rupture on imaging. A total of 82 patients were identified. Aneurysm size was 7.1 ± 2.0 cm. Thirty patients had emergent or urgent repairs during their index admission (37%), 19 had elective repairs at a later date (23%), and 33 patients had no intervention due to either patient choice or prohibitive medical comorbidities (40%). Patients without intervention had a median follow up of 275 days before death or loss to follow up. In patients undergoing elective intervention, 6,968 patient-days elapsed between presentation and repair, with zero episodes of acute rupture (median 105 days). Patients undergoing elective repair had smaller aneurysms compared to those who underwent emergent/urgent repair (6.2 ± 1.3 vs. 7.7 ± 2.1 cm, P=0.008). No surgical candidate with an aneurysm smaller than 8 cm ruptured. There were 31 patients with previous axial imaging within 2 years prior to presentation with a "crescent sign," with mean aneurysm growth rate of 0.85 ± 0.62 cm per 6 months [median 0.65, range 0-2.6]. Those with aneurysms sized below 5.5 cm displayed decreased aneurysm growth compared to patients with aneurysm's sized 5.5-6.5 cm or patients with aneurysms greater than 6.5 cm (0.12 vs. 0.64 vs. 1.16 cm per 6 months, P= 0.002). The finding of an isolated radiographic "crescent sign" without other signs of definitive aortic rupture (i.e., hemothorax, aortic wall disruption, retroperitoneal bleeding) is not necessarily an indicator of impending aortic rupture, but may be found in the setting of rapid aneurysm growth. Many factors, including other associated radiographic findings, aneurysm size and growth rate, and patient symptomatology, should guide aneurysm management in these patients. We found that patients with minimal symptoms, aneurysm sizes below 6.5 cm, and no further imaging findings of aneurysm instability, such as periaortic fat stranding, can be successfully managed with elective intervention after optimization of comorbid factors with no evidence of adverse outcomes.

Metformin therapy is not associated with the lower prevalence of ascending aortic aneurysm in diabetic patients.

Metformin therapy has previously been associated with reduced abdominal aortic aneurysm growth rate in diabetic patients and shown to suppress the formation and progression of abdominal aortic aneurysm in normoglycemic mice. Here, we investigated the association between Metformin treatment and prevalence of aneurysm in the ascending aorta (AscAA). A total of 734 patients undergoing open-heart surgery for AscAA and/or aortic valve disease were studied. Diabetes status and medication use were self-reported by the patients in a systematic questionnaire. Aortic dilatation was defined as an aortic root or ascending aortic diameter ≥4.0 cm. High-sensitivity C-reactive protein levels were assessed as a measure of systemic inflammation. We could confirm the inverse association between diabetes and AscAA prevalence (16% vs 43.9%, for diabetic and non-diabetic patients, respectively; Odds ratio 0.243; 95% CI, 0.129-0.460, P < 0.001). Furthermore, in diabetic patients, Metformin treatment was associated with lower high-sensitivity C-reactive protein levels. There was, however, no difference in the prevalence of AscAA among diabetic patients with and without Metformin treatment (16% vs 16% for treated and non-treated patients, respectively; OR 1.039; 95% CI 0.26-4.19, P = 0.957). Our data do not support a protective effect of Metformin therapy in AscAA formation. 161, 173.

A Novel Hypothesis: A Role for Follicle Stimulating Hormone in Abdominal Aortic Aneurysm Development in Postmenopausal Women.

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which can potentially be fatal due to exsanguination following rupture. Although AAA is less prevalent in women, women with AAA have a more severe AAA progression compared to men as reflected by enhanced aneurysm growth rates and a higher rupture risk. Women are diagnosed with AAA at an older age than men, and in line with increased osteoporosis and cardiovascular events, the delayed AAA onset has been attributed to the reduction of the protective effect of oestrogens during the menopausal transition. However, new insights have shown that a high follicle stimulating hormone (FSH) level during menopause may also play a key role in those diseases. In this report we hypothesize that FSH may aggravate AAA development and progression in postmenopausal women via a direct and/or indirect role, promoting aorta pathology. Since FSH receptors (FSHR) are reported on many other cell types than granulosa cells in the ovaries, it is feasible that FSH stimulation of FSHR-bearing cells such as aortic endothelial cells or inflammatory cells, could promote AAA formation directly. Indirectly, AAA progression may be influenced by an FSH-mediated increase in osteoporosis, which is associated with aortic calcification. Also, an FSH-mediated decrease in cholesterol uptake by the liver and an increase in cholesterol biosynthesis will increase the cholesterol level in the circulation, and subsequently promote aortic atherosclerosis and inflammation. Lastly, FSH-induced adipogenesis may lead to obesity-mediated dysfunction of the microvasculature of the aorta and/or modulation of the periaortic adipose tissue. Thus the long term increased plasma FSH levels during the menopausal transition may contribute to enhanced AAA disease in menopausal women and could be a potential novel target for treatment to lower AAA-related events in women.

Growth of unruptured aneurysms: A meta-analysis of natural history and endovascular studies

The growth of unruptured intracranial aneurysms (UIAs) is a strong predictor of rupture. Clinical observations suggest that some UIAs might grow faster after endovascular treatment than untreated UIAs. There are no head-to-head comparisons of incidence rates of UIAs thus far. MethodsWe searched PubMed, Embase and Google Scholar for relevant articles from the inception of the databases to March 2020. We pooled and compared the incidence rates for the growth of aneurysms from natural history studies and endovascular treatment studies. Generalized linear models were used for confounder adjustment for the prespecified confounders age, size and location. ResultsTwenty-five studies (10 describing growth in natural history and 15 reporting growth after endovascular therapy) considering 6325 aneurysms were included in the meta-analysis. The median size of aneurysms was 3.7 mm in the natural history studies and 6.4 mm in endovascular treatment studies (p = 0.001). The pooled incidence rate (IR) of growth was significantly higher in endovascular treatment studies (IR 52 per 1000 person-years, with a 95% confidence interval (CI) 36–79) compared to natural history studies (IR 28 per 1000 person-years, 95% CI 17 – 46, p-value < 0.01) after adjustment for confounders. ConclusionOur results suggest that the incidence rate of cerebral aneurysm growth might be higher after endovascular therapy than the incidence rates reported in natural history studies. These results should be viewed in light of the risk of bias of the individual studies and the risk of ecological bias.

A Volumetric Metric for Monitoring Intracranial Aneurysms: Repeatability and Growth Criteria in a Longitudinal MR Imaging Study.

The reliability of contrast-enhanced MRA in monitoring serial volumetric changes of unruptured intracranial aneurysms has not been established. We aimed to determine the coefficient of variance of contrast-enhanced MRA in measuring aneurysm volumes, thus establishing criteria for aneurysm growth and permitting identification of variables predictive of growth. Aneurysm volumes were measured from serial contrast-enhanced MRA studies of patients with untreated intracranial aneurysms who underwent >2 sequential MR imaging evaluations. After coregistering all sequential studies in 3D space for each aneurysm and signal intensity normalization, aneurysm volume was determined across all time points. A linear mixed effects model was built to estimate the coefficient of variance of the measurement as well as to determine predictive variables. Growth was defined as relative growth exceeding 2 times the measurement coefficient of variance (sudden growth, as 4 times the coefficient of variance). A total of 95 patients with 112 aneurysms were included (5.9 scans during 4.0 years on average, 616 scan measurements in total). The coefficient of variance was 5.5% of the aneurysm volume, and the relative growth rate was dependent on the location: anterior cerebral artery, 4.52% per year; vertebral artery, 2.46% per year; middle cerebral artery, 2.74% per year; basilar artery, 2.36% per year; internal carotid artery, 1.14% per year. Thirty-six of 112 (32%) aneurysms were characterized as growing, and 11/36 of them had an episode of sudden growth. Volume measurement of unruptured intracranial aneurysms by contrast-enhanced MRA seems a reliable metric for tracking the growth trajectory of aneurysms. Furthermore, the aneurysm growth rate differs among different locations.

Outcomes after EVAR in females are similar to males

IntroductionWomen are less likely to develop infrarenal abdominal aortic aneurysm; however, when they do, it is almost always associated with challenging anatomy, more rapid aneurysmal growth rate and earlier rupture. Women generally have poorer outcomes following open aneurysm repair; and in this respect, the present study aims to evaluate if it is so after endovascular repair.MethodsA retrospective analysis of our database was performed for patients underwent endovascular aneurysm repair (EVAR) between January 2013–March 2020. 249 elective EVAR patients were evaluated. Patients were categorized according to gender and 26 patients (10.4%) were female. Demographics and pre-peri-postoperative findings were compared. Propensity score matching (ratio 1:1) was performed to reduce selection bias.ResultsIn the overall unmatched cohort, female population had more diabetes mellitus (p = 0.016) and hypertension (p = 0.005). However, coronary artery disease (p = 0.005) and coronary artery bypass grafting (p = 0.006) were more in male gender. Non-IFU implantation was higher in female group (38.5% vs. 11.5%, p = 0.025). After propensity matching, even though it was not statistically significant, early mortality for female gender was higher when compared to male gender (7.7% and 0%, respectively, p = 0.490). In the follow-up period, no difference in all-cause mortality, secondary interventions or complications have been observed between the genders.ConclusionChallenging anatomy and subsequently treated patients outside IFU may be the reasons for higher morbidity and mortality in women. However, despite these factors female and male patients revealed equivalent early and late results.

Implementation of collagen fiber dispersion in a growth and remodeling model of arterial walls

Imaging studies have shown, and more recently quantified, the collagen fiber dispersions within the aortic wall. Simultaneously, experimental and numerical studies highlight a significant influence of the dispersion on the aortic mechanical response. On the other hand, none of the numerical studies describing the adaptation of healthy and diseased aortas in response to different stimuli take fiber dispersion into account. In this study, we present the first implementation of a fiber dispersion model based on the generalized structure tensor approach into a constrained mixture growth and remodeling model of the aortic wall. Additionally, a new definition of the fiber pre-stretch tensor compatible with fiber dispersion is proposed. The new extended model was implemented into a finite element analysis program, and the influence of collagen fiber dispersions and mean fiber angles on aneurysm growth and the distribution of stresses inside the aortic wall were studied on a three-layered axisymmetric model of a fusiform abdominal aortic aneurysm as well as on non-symmetric aneurysm. In the analyses, the dispersion parameters and the mean fiber angles were varied in the range of measured values for healthy abdominal aortas and aneurysms. Results show a reasonable behavior during an extension-inflation test and the expected evolution of residual stresses during adaptation due to hypertension. Moreover, they show that changes in fiber dispersions and mean fiber angles have a significant influence on the aneurysm evolution and the stress distribution. For example, simulations with increased fiber dispersion in the intima or the media showed a slower aneurysm growth, while the opposite was true for the adventitia. Mean fiber direction closer to the circumferential direction resulted in a stiffer response in the aortic inflation analysis, and it also decreased the aneurysm growth rate.

Circulating Biomarkers for the Prediction of Abdominal Aortic Aneurysm Growth.

Background: Abdominal aortic aneurysm represents a distinct group of vascular lesions, in terms of surveillance and treatment. Screening and follow-up of patients via duplex ultrasound has been well established and proposed by current guidelines. However, serum circulating biomarkers could earn a position in individualized patient surveillance, especially in cases of aggressive AAA growth rates. A systematic review was conducted to assess the correlation of AAA expansion rates with serum circulating biomarkers. Methods: A data search of English medical literature was conducted, using PubMed, EMBASE, and CENTRAL, until 7 March 2021, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines. Studies reporting on humans, on abdominal aortic aneurysm growth rates and on serum circulating biomarkers were included. No statistical analysis was conducted. Results: A total of 25 studies with 4753 patients were included. Studies were divided in two broad categories: Those reporting on clinically applicable (8 studies) and those reporting on experimental (17 studies) biomarkers. Twenty-three out of 25 studies used duplex ultrasound (DUS) for following patients. Amongst clinically applicable biomarkers, D-dimers, LDL-C, HDL-C, TC, ApoB, and HbA1c were found to bear the most significant association with AAA growth rates. In terms of the experimental biomarkers, PIIINP, osteopontin, tPA, osteopontin, haptoglobin polymorphisms, insulin-like growth factor I, thioredoxin, neutrophil extracellular traps (NETs), and genetic factors, as polymorphisms and microRNAs were positively correlated with increased AAA expansion rates. Conclusion: In the presence of future robust data, specific serum biomarkers could potentially form the basis of an individualized surveillance strategy of patients presenting with increased AAA growth rates.

Determining the optimal interval for imaging surveillance of ascending aortic aneurysms.

BackgroundCardiovascular guidelines recommend (bi-)annual computed tomography (CT) or magnetic resonance imaging (MRI) for surveillance of the diameter of thoracic aortic aneurysms (TAAs). However, no previous study has demonstrated the necessity for this approach. The current study aims to provide patient-specific intervals for imaging follow-up of non-syndromic TAAs.MethodsA total of 332 patients with non-syndromic ascending aortic aneurysms were followed over a median period of 6.7 years. Diameters were assessed using all available imaging techniques (echocardiography, CT and MRI). Growth rates were calculated from the differences between the first and last examinations. The diagnostic accuracy of follow-up protocols was calculated as the percentage of subjects requiring pre-emptive surgery in whom timely identification would have occurred.ResultsThe mean growth rate in our population was 0.2 ± 0.4 mm/year. The highest recorded growth rate was 2.0 mm/year, while 40.6% of patients showed no diameter expansion during follow-up. Females exhibited significantly higher growth rates than men (0.3 ± 0.5 vs 0.2 ± 0.4 mm/year, p = 0.007). Conversely, a bicuspid aortic valve was not associated with more rapid aortic growth. The optimal imaging protocol comprises triennial imaging of aneurysms 40–49 mm in diameter and yearly imaging of those measuring 50–54 mm. This strategy is as accurate as annual follow-up, but reduces the number of imaging examinations by 29.9%.ConclusionsIn our population of patients with non-syndromic TAAs, we found aneurysm growth rates to be lower than those previously reported. Yearly imaging does not lead to changes in the management of small aneurysms. Thus, lower imaging frequencies might be a good alternative approach.

Culture-Negative Mycotic Aortic Aneurysms Probably Have a Less Severe Clinical Nature Than Culture-Positive Counterparts

Mycotic aortic aneurysm constitutes a potentially devastating disease that necessitates prompt suspicion and diagnosis. There is no exact consensus for treatment, but removal of infected tissues and prolonged use of antimicrobials based on the identified causative microorganisms seem widely acceptable and have been similarly practiced worldwide. However, some patients still show no identified microorganisms. In this study, we sought to determine whether there are any clinical significance or differences of note in culture-negative mycotic aortic aneurysms. Between October 2003 and August 2018, 71 patients were identified as treated for mycotic aortic aneurysms at a single tertiary institution. Review of medical records and imaging studies were completed to collect the following information: demographics, previous medical/surgical history regarding potential infection sources, laboratory and radiologic findings, clinical presentations, treatment method, and morbidity and mortality rates. For analysis, patients were categorized into two groups: the blood and/or tissue culture-positive (CP) group and the blood and/or tissue culture-negative (CN) group. The latter was further divided as CN with identified microorganism by molecular biologic methods [CN(+)] and CN with no identified microorganism [CN(-)]. More patients in the CP group were symptomatic than were in the CN(+) group (100% vs. 80%; P = 0.034). However, identification of causative microorganisms did not result in a difference in symptom status upon comparing the [CP + CN(+)] and [CN(-)] groups. Inflammatory markers were the most elevated in the CP group and least elevated in the CN(-) group. The aneurysm growth rate seemed slower in the CN(-) group than in the CN(+) and CP groups (1.3 vs. 3.4 vs. 9 mm/month respectively). Aneurysm rupture at initial presentation was more prevalent in the CP group (33.3%). 18F-Fluorodeoxyglucose-positron emission tomography showed increased uptake regardless of whether or not the microorganisms were identified. Early mortality and disease-specific mortality rates during the follow-up period were higher in the CP group but without statistical significance. Compared with the CP group, the CN groups appeared clinically less severe, and also exhibited a relatively less devastating course as exhibited by the slower aneurysm expansion rate and smaller number of ruptured aneurysms at the initial presentation.

Central Hypertension in Patients With Thoracic Aortic Aneurysms: Prevalence and Association With Aneurysm Size and Growth.

Hypertension (HTN) has the greatest population-attributable risk for aortic dissection and is highly prevalent among patients with thoracic aortic aneurysms (TAAs). Although HTN is diagnosed based on brachial blood pressure (bBP), central HTN (central systolic blood pressure [cSBP] ≥130 mm Hg) is of interest as it better reflects blood pressure (BP) in the aorta. We aimed to (i) evaluate the prevalence of central HTN among TAA patients without a diagnosis of HTN, and (ii) assess associations of bBP vs. central blood pressure (cBP) with aneurysm size and growth. One hundred and five unoperated subjects with TAAs were recruited. With validated methodology, cBP was assessed with applanation tonometry. Aneurysm size was assessed at baseline and follow-up using imaging modalities. Aneurysm growth rate was calculated in mm/year. Multivariable linear regression adjusted for potential confounders assessed associations of bBP and cBP with aneurysm size and growth. Seventy-seven percent of participants were men and 49% carried a diagnosis of HTN. Among participants without diagnosis of HTN, 15% had central HTN despite normal bBP ("occult central HTN"). In these patients, higher central systolic BP (cSBP) and central pulse pressure (cPP) were independently associated with larger aneurysm size (β ± SE = 0.28 ± 0.11, P = 0.014 and cPP = 0.30 ± 0.11, P = 0.010, respectively) and future aneurysm growth (β ± SE = 0.022 ± 0.008, P = 0.013 and 0.024 ± 0.009, P = 0.008, respectively) while bBP was not (P > 0.05). In patients with TAAs without a diagnosis of HTN, central HTN is prevalent, and higher cBP is associated with larger aneurysms and faster aneurysm growth.

30143 Asymptomatic Thoracic Aortic Aneurysm Growth Rates and Predicting Factors: A Systematic Review and Meta-Analysis

ABSTRACT IMPACT: Through conducting this systematic review and meta-analysis, we will elucidate which factors influence thoracic aortic aneurysm growth, which will further help clinicians to properly stratify and manage their patients with TAAs. OBJECTIVES/GOALS: Thoracic aortic aneurysms (TAA) are an indolent but fatal disease, and the patient characteristics that predict both overall growth and growth rate are still not well characterized. Our goal is to conduct a systematic review and meta-analysis in other to better describe different patient characteristics that predict TAA growth. METHODS/STUDY POPULATION: M.M. conducted a search of Ovid MEDLINE, Embase, and Scopus to identify articles. Inclusion criteria were any longitudinal study reporting asymptomatic TAA growth, growth rates, or clinical proxies for growth such as dissection, rupture, emergency surgery, and death. M.H and P.B. independently applied the criteria to the results of the search. Conflicts were resolved by N.B. Data was extracted and risk of bias assessed independently by M.H. and P.B. Summary estimates of the outcome variables are combined across studies using standard meta-analysis methods. Heterogeneity is assessed via forest plots, chi2 test (Q test), and I2 statistic. Sensitivity analysis is conducted to assess robustness of the findings. RESULTS/ANTICIPATED RESULTS: The literature search resulted in 3,419 abstracts, of which 176 were included and thus require a full text review. Cohen’s Kappa coefficient was 0.64, indicating substantial agreement and high inter-rater reliability. We describe four categories of patient characteristics influencing the growth of asymptomatic TAAs: demographics, genetic or inheritable conditions, hemodynamic or biomechanical factors, and serum biomarkers. We describe the measure of effect for all variables. We anticipate there is a significant level of heterogeneity between studies, and potentially moderate risk of bias for many of the included studies as they are retrospective and observational in nature. Furthermore, we anticipate publication bias and evaluate it with funnel plots. DISCUSSION/SIGNIFICANCE OF FINDINGS: Understanding the factors that influence the growth of asymptomatic thoracic aortic aneurysms (TAA) is paramount, as the size and growth rate of TAAs dictates the clinical course. Little is understood about the degree to which different characteristics influence growth. This meta-analysis will help elucidate factors that promote TAA growth.

Increased Virulence of Descending Thoracic and Thoracoabdominal Aortic Aneurysms in Women

A retrospective review was performed of the Aortic Institute at Yale-New Haven Hospital between 1990 and 2018. Of 907 patients with descending thoracic/thoracoabdominal aortic sizes, excluding those with connective tissue disease, the mean aortic diameter was 4.1 cm in men (68%) and 4.8 cm in women (32%). The median radiologic follow-up was ∼3 years in each subgroup. The mean growth rate was significantly greater in women (0.25 cm/year) than in men (0.17 cm/year). Dissection, rupture, aortic death, or a combination of the three occurred twice as frequently for women (5.8%) than for men (2.3%). A thoracic aortic diameter >5.0 cm was associated with significantly higher composite endpoints of rupture, dissection, and death in women (33%) than in men (26%). Women diagnosed with descending thoracic/thoracoabdominal aneurysms have faster aneurysm growth and higher rates of dissection, rupture, and aortic death than men. Women should be considered for intervention for thoracoabdominal aneurysms possibly at smaller diameters than 5.5 to 6.0 cm.

Aortic Stiffness, Central Blood Pressure, and Pulsatile Arterial Load Predict Future Thoracic Aortic Aneurysm Expansion.

Thoracic aortic aneurysm is a disease associated with high morbidity and mortality. Clinically useful strategies for medical management of thoracic aortic aneurysm are critically needed. To address this need, we sought to determine the role of aortic stiffness and pulsatile arterial load on future aneurysm expansion. One hundred five consecutive, unoperated subjects with thoracic aortic aneurysm were recruited and prospectively followed. By combining arterial tonometry with echocardiography, we estimated measures of aortic stiffness, central blood pressure, steady, and pulsatile arterial load at baseline. Aneurysm size was measured at baseline and follow-up with imaging; growth was calculated in mm/y. Stepwise multivariable linear regression assessed associations of arterial stiffness and load measures with aneurysm growth after adjusting for potential confounders. Mean±SD age, baseline aneurysm size, and follow-up time were 62.6±11.4 years, 46.24±3.84 mm, and 2.92±1.01 years, respectively. Aneurysm growth rate was 0.43±0.37 mm/y. After correcting for multiple comparisons, higher central systolic (β±SE: 0.026±0.009, P=0.007), and pulse pressures (β±SE: 0.032±0.009, P=0.0002), carotid-femoral pulse wave velocity (β±SE: 0.032±0.011, P=0.005), amplitudes of the forward (β±SE: 0.044±0.012, P=0.0003) and reflected (β±SE: 0.060±0.020, P=0.003) pressure waves, and lower total arterial compliance (β±SE: -0.086±0.032, P=0.009) were independently associated with future aneurysm growth. Measures of aortic stiffness and pulsatile hemodynamics are independently associated with future thoracic aortic aneurysm growth and provide novel insights into disease activity. Our findings highlight the role of central hemodynamic assessment to tailor novel risk assessment and therapeutic strategies to patients with thoracic aortic aneurysm.