Thoracic Aortic Aneurysm Group Research Articles

Long-term results of etiology-based thoracic endovascular aortic repair: a single-center experience

The use of thoracic endovascular aortic repair (TEVAR) for thoracic aortic aneurysm (TAA) and Stanford type B aortic dissection (TBAD) has been increasing; however, in terms of etiology, the differences of long term after TEVAR outcomes remain unexplored. Thus, we investigated etiology-specific long-term results of TEVAR for TAA and TBAD. A total of 421 TEVAR procedures were performed at our institution from July 2007 to December 2021; 249 TAA cases and 172 TBAD cases were included. Traumatic aortic dissection and aortic injury cases were excluded. The mean observation duration was 5.7 years. The overall 30-day mortality rate was 1.4% (n = 6), with 1.2% (n = 3) in the TAA group and 1.7% (n = 3) in the TBAD group. The overall incidence of postoperative stroke was 0.9% (n = 4), with 1.2% (n = 3) and 0.6% (n = 1) in the TAA and TBAD groups, respectively (p = 0.90). Paraplegia developed in 1.7% (n = 7) of patients, with 2.4% (n = 6) in the TAA group and 0.6% (n = 1) in the TBAD group. Freedom from aortic-related death was not significantly different between the two etiologies; however, thoracic reintervention was more common in the TBAD group (p = 0.003), with endoleak being the most common indication for reintervention. Additionally, retrograde type A aortic dissection occurred in four TBAD cases, while migration occurred in three TAA cases. The perioperative results of TEVAR for TAA and TBAD were satisfactory. The long-term results were unfavorable owing to the occurrence of etiology-specific and common complications. In terms of the high frequency of reintervention, the long-term complications associated with TEVAR are etiology specific.

The correlation study between the length and angle of ascending aortic and the incidence risk of acute type A aortic dissection.

This study utilized computed tomography angiography (CTA) to assess the risk of acute type A aortic dissection (ATAAD) by analyzing the imaging morphology indicators of the ascending aorta, along with the relevant risk factors associated with aortic dissection. The study utilized a retrospective observational research design. The population consisted of 172 patients who received treatment in the Department of Cardiothoracic Surgery at Qilu Hospital, Shandong University, from January 2018 to December 2022. The patients were divided into two groups: the ATAAD group (n = 97) and the thoracic aortic aneurysm group (TAA, n = 75). Demographic data and ascending aorta CTA measurements were collected from all patients. Single factor and multivariate logistic regression were employed to analyze the statistical differences in clinical data and ascending aorta CTA imaging morphology indicators between the two groups. The variables were included in logistic multivariate analysis for further screening, indicating that the length of the ascending aorta (LAA) before ATAAD (OR = 3.365; 95% CI :1.742-6.500, P<0.001), ascending arch angle (asc-arch angle, OR = 0.902; 95% CI: 0.816-0.996, P = 0.042) and the maximum aortic diameter (MAD) before ATAAD, (OR = 0.614; 95% CI: 0.507-0.743, P<0.001) showed statistically significant differences. This study suggests that increased LAA and MAD, as well as a smaller asc-arch angle may be high-risk factors for the onset of ATAAD.

Augmentation Index in Patients with Thoracic Aortic Aneurysm: A Matched Case-Control Study.

Thoracic aortic aneurysms (TAA) may be associated with complications such as rupture and dissection, which can lead to a fatal outcome. Increased central arterial stiffness has been proposed to be present in patients with TAA compared to unmatched controls. We aimed to assess whether wall properties in patients with TAA are also altered when compared to a matched control group. Applanation tonometry was performed in 74 adults with TAA and 74 sex, age, weight, height, and left ventricular ejection fraction matched controls. Subsequently analysis of the pulse wave was done using the SphygmoCor System. For comparing the two groups, AIx was adjusted to a heart rate of 75/min (AIx@75). 148 1-to-1 matched participants were included in the final model. There was no significant difference in the Alx@75 between the TAA group and the matched control group [mean (SD) of 24.7 (11.2) % and 22.8 (11.2) %, p = 0.240]. Adjusted for known cardiovascular risk factors, there was no association between TAA and AIx@75. Patients with TAA showed comparable arterial wall properties to cardiovascular risk factor matched controls. Since higher arterial stiffness is associated with TAA progression, it remains to be investigated if increased central arterial stiffness is a relevant factor of TAA emergence.

Low copper levels measured in the aortic wall of New Zealand patients with non-syndromic ascending thoracic aortic aneurysm.

OBJECTIVESStudies in animals have shown causal relationships between copper (Cu) deficiency and the development of thoracic aortic aneurysms (TAAs) [1, 2]. Cu deficiency is widespread in New Zealand (NZ) soils; the high soil pH from the use of lime fertilizers reduces the bioavailability of Cu for grazing animals and growing plants; this, in turn, reduces Cu availability in the NZ human food chain. Our study is a pilot study to explore associations between Cu and TAA. We measured Cu levels in aneurysmal aortic tissues in patients undergoing Bentall procedures and non-aneurysmal aortic tissue from coronary artery bypass graft patients.METHODSAortic samples were collected from 2 groups of patients during elective open-heart surgery over 4 months between November 2017 and February 2018. The groups were a TAA group, patients with non-syndromic aortic aneurysm and without the bicuspid aortic valve or known infectious or inflammatory condition (ANEURYSM; n = 13), and a control coronary artery bypass graft group (CONTROL; n = 44). Standardized digested dry tissue weighed samples were analysed from both groups. Tissue extraction of trace elements was carried out using HCl-H2O2 digestion and a highly sensitive analytical technique, inductively coupled plasma mass spectrometry—used to measure elemental concentrations.RESULTSCu concentration (mean ± SD) was significantly lower in ANEURYSM (3.34 ± 0.16 µg/g) when compared to the CONTROL group tissues (4.33 ± 0.20 µg/g) (dry weight; mean ± SD; Student's t-test, P < 0.05). Over 46% of the Aneurysm patients were Maori and live in a geographically Cu-deficient NZ territory.CONCLUSIONSCu deficiency may play a role in the development or progression of non-syndromic ascending aortic aneurysms in NZ. Maori patients are more at risk as they commonly live in rural NZ, dependent on locally grown nutritional sources. Further studies are required to confirm this exciting finding and to establish cause and effect relationship.

Role of Oxidative Stress and Autophagy in Thoracic Aortic Aneurysms

Thoracic aortic aneurysms (TAA) pathogenesis and progression include many mechanisms. The authors investigated the role of autophagy, oxidative stress, and endothelial dysfunction in 36 TAA patients and 23 control patients. Univariable and multivariable analyses were performed. TAA patients displayed higher oxidative stress and endothelial dysfunction then control patients. Autophagy in the TAA group was reduced. The association of oxidative stress and autophagy with aortic disease supports the role of these processes in TAA. The authors demonstrate a putative role of Nox2 and autophagy dysregulation in human TAA. These findings could pinpoint novel treatment targets to prevent or limit TAA progression.

Characterization of Ascending Aortic Flow in Patients With Degenerative Aneurysms: A 4D Flow Magnetic Resonance Study.

Degenerative thoracic aortic aneurysm (TAA) patients are known to be at risk of life-threatening acute aortic events. Guidelines recommend preemptive surgery at diameters of greater than 55 mm, although many patients with small aneurysms show only mild growth rates and more than half of complications occur in aneurysms below this threshold. Thus, assessment of hemodynamics using 4-dimensional flow magnetic resonance has been of interest to obtain more insights in aneurysm development. Nonetheless, the role of aberrant flow patterns in TAA patients is not yet fully understood. A total of 25 TAA patients and 22 controls underwent time-resolved 3-dimensional phase contrast magnetic resonance imaging with 3-directional velocity encoding (ie, 4-dimensional flow magnetic resonance imaging). Hemodynamic parameters such as vorticity, helicity, and wall shear stress (WSS) were calculated from velocity data in 3 anatomical segments of the ascending aorta (root, proximal, and distal). Regional WSS distribution was assessed for the full cardiac cycle. Flow vorticity and helicity were significantly lower for TAA patients in all segments. The proximal ascending aorta showed a significant increase in peak WSS in the outer curvature in TAA patients, whereas WSS values at the inner curvature were significantly lower as compared with controls. Furthermore, positive WSS gradients from sinotubular junction to midascending aorta were most prominent in the outer curvature, whereas from midascending aorta to brachiocephalic trunk, the outer curvature showed negative WSS gradients in the TAA group. Controls solely showed a positive gradient at the inner curvature for both segments. Degenerative TAA patients show a decrease in flow vorticity and helicity, which is likely to cause perturbations in physiological flow patterns. The subsequent differing distribution of WSS might be a contributor to vessel wall remodeling and aneurysm formation.

Potential function of microRNAs in thoracic aortic aneurysm and thoracic aortic dissection pathogenesis.

Thoracic aortic aneurysm (TAA) and thoracic aortic dissection (TAD) are aortic diseases known as 'silent killers'. While TAA is characterized by an enlargement of at least half of the normal aortic diameter, TAD is characterized by progressive pseudo‑lumen formation, which results in the gradual separation of the aortic wall layers. In the present study, a total of 28 serum samples from nine patients with TAA, nine patients with TAD and ten healthy individuals were studied. The aim of the present study was to investigate the expression profiles of hsa‑microRNA(miR)‑143‑3p and hsa‑miR‑22‑3p in TAA and TAD in order to identify candidate miRNAs that are responsible for the pathogenesis of the diseases. Following the detection of target mRNAs from candidate miRNAs by bioinformatic tools, the expression profiles of target mRNAs were analyzed. A quantitative polymerase chain reaction was performed to detect Kirsten rat sarcoma viral oncogene homolog (KRAS), mitogen‑activated protein kinase (MAPK) 7, MAPK14 and transgelin (TAGLN) mRNA expression profiles. The results of the comparison with control group demonstrated that the increase in the expression levels of hsa‑miR‑143‑3p (P=0.017) and hsa‑miR‑22 (P=0.03) candidate miRNAs were statistically significant in the TAA group, but not in the TAD group. The expression of KRAS and MAPK7 mRNAs decreased in the two groups compared with the control group. The level of expression of MAPK14 decreased in the TAD group, but increased in the TAA group compared with the control group. TAGLN mRNA expression level increased in the two groups. The statistically significant difference in the expression of hsa‑miR‑143‑3p suggests that hsa‑miR‑143‑3p may be a potential biomarker for TAA, as the expression of the target mRNAs KRAS and MAPK7 decreased and the miRNA‑mRNA association was negatively correlated. These miRNAs and their associated genes may serve important functions in TAA formation, the altered expression of which may be important in the pathogenesis of TAA.

Serum matrix metalloproteinase-9 is a valuable biomarker for identification of abdominal and thoracic aortic aneurysm: a case-control study

BackgroundMatrix metalloproteinase-9 (MMP9) has been reported to play a key role in the pathogenesis of aortic aneurysm. However, few studies have assessed serum MMP9 levels in both abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA). In this study, we investigated the serum levels of MMP9 in aortic aneurysm to evaluate its predictive and diagnostic efficacy for AAA and TAA, and explored the association of MMP9 with circulating laboratory markers.MethodsA total of 296 subjects were enrolled, including 105 AAA patients, 79 TAA patients and 112 healthy controls. The levels of serum MMP9 were detected by enzyme-linked immunosorbent assay (ELISA).ResultsCompared to control group, both AAA and TAA patients had higher serum MMP9 levels in the overall comparison and subgroup analysis based on subjects aged<65 years, either male or female, hypertension, non-diabetes and non-hyperlipidemia (all P<0.05). Moreover, MMP9 levels were significantly higher in TAA group than those in AAA group in the total comparison, and this discrepancy was also found in the non-diabetes, non-hyperlipidemia and aortic diameter ≥ 5.5 cm subgroup analysis. Serum MMP9 levels were influenced by age and hypertension. There was a positive association of serum MMP9 with CRP (r = 0.33, P < 0.001) and Hcy (r = 0.199, P = 0.033). Multiple logistic analyses showed that serum MMP9 was an independent risk factor for AAA and TAA. Based on receiver operating characteristic (ROC) analysis, the area under the curve (AUC) of MMP9 for predicting TAA was 0.83 with 70% sensitivity and 91% specificity, while the AUC of MMP9 to detect AAA was 0.69 and the sensitivity and specificity were 50% and 88%.ConclusionsSerum MMP9 was closely related to the existence of aortic aneurysms and could be a valuable marker for the discrimination of aortic aneurysm, especially for TAA.

Microarray expression profile analysis of long non-coding RNAs in thoracic aortic aneurysm

Thoracic aortic aneurysm (TAA) is a highly lethal vascular disease. Long non-coding RNAs (lncRNAs) are newly discovered as a regulator of protein genes and play critical roles in cardiovascular physio-pathological processes. However, there were a few studies looking at lncRNAs in TAA. In this study, we profiled differential expression of lncRNAs between TAA (TAA group, N = 6) and normal thoracic aorta (control group, n = 6) by third-generation lncRNA microarray. We identified 1352 up-regulated and 1624 down-regulated lncRNAs with differential expression (log fold-change > 2.0, p < 0.01). Through nearby protein-coding gene associated with extracellular matrix (ECM) metabolism and vascular smooth muscle cell (VSMC) apoptosis, 12 up-regulated and 9 down-regulated lncRNAs were selected for further analysis. By calculating phastCons score of base, we identified 8 candidate lncRNAs (4 up-regulated and 4 down-regulated) with high conservation across species. By tissue specificity analysis, we found that 5 lncRNAs (HIF1A-AS1, RP11-465L10.10, LOC100506472, CTD-2184D3.5 and RP-399O19.5) were highly expressed in aortic tissues, suggested that they may be closely associated with TAA. Among them, 2 lncRNAs (RP11-465L10.10 and CTD-2184D3.5) with higher specificity in aorta (p < 0.01) were analyzed by bioinformatics. Further catRAPID analysis revealed a strong RNA-protein interaction between RP11-465L10.10 and myeloid zinc finger gene 1 (MZF1), a transcription factor of MMP9. However, no intense RNA-protein interactions were observed between CTD-2184D3.5 and transcript factors of MAPK6. In conclusions, our study showed differential expression profiles of lncRNAs in TAA and revealed the interaction between certain lncRNAs and coding genes. These data provides insights into new biomarker and therapeutic targets for TAA.

Regulation of membrane type-1 matrix metalloproteinase activity and intracellular localization in clinical thoracic aortic aneurysms

ObjectiveMembrane type-1 matrix metalloproteinase (MT1-MMP) is elevated during thoracic aortic aneurysm (TAA) development in mouse models, and plays an important role in the activation of matrix metalloproteinase (MMP)-2 and the release of matrix- bound transforming growth factor-β. In this study, we tested the hypothesis that MT1-MMP is subject to protein kinase C (PKC)–mediated regulation, which alters intracellular trafficking and activity with TAAs. MethodsLevels of MMP-2, native and phosphorylated MT1-MMP, and PKC-δ were measured in aortic tissue from patients with small TAAs (<5 cm; n = 8) and large TAAs (>6.5 cm; n = 8), and compared with values measured in normal controls (n = 8). Cellular localization of green fluorescent protein (GFP)-tagged MT1-MMP was assessed in aortic fibroblasts isolated from control and 4-week TAA mice. The effects of PKC-mediated phosphorylation on MT1-MMP cellular localization and function (active MMP-2 vs phospo-Smad2 abundance) were assessed after treatment with a PKC activator (phorbol-12-myristate-13-acetate [PMA], 100 nM) with and without a PKC-δ–specific inhibitor (röttlerin, 3 μM). ResultsCompared with controls, MT1-MMP abundance was increased in aortas from both TAA groups. Active MMP-2 was increased only in the large TAA group. The abundances of phosphorylated MT1-MMP and activated PKC-δ were enhanced in the small TAA group compared with the large TAA group. MT1-MMP was localized on the plasma membrane in aortic fibroblasts from control mice and in endosomes from TAA mice. Treatment with PMA induced MT1-MMP-GFP internalization, enhanced phospho-Smad2, and reduced MMP-2 activation, whereas röttlerin pretreatment inhibited these effects. ConclusionsPhosphorylation of MT1-MMP mediates its activity through directing cellular localization, shifting its role from MMP-2 activation to intracellular signaling. Thus, targeted inhibition of MT1-MMP may have therapeutic relevance as an approach to attenuating TAA development.

Endovascular Aortic Aneurysm and Dissection Repair (EVAR) in Iran: Descriptive Midterm Follow-up Results.

Background:Endovascular repair of aorta in comparison to open surgery has a low early operative mortality rate, but its long-term results are uncertain.Objectives:The current study describes for the first time our initial four-year experience of elective endovascular aortic repair (EVAR) at Tehran heart center, the first and a major referral heart center in Iran, as a pioneer of EVAR in Iran.Patients and Methods:A total of 51 patients (46 men) who had the diagnosis of either an abdominal aortic aneurysm (AAA) (n = 36), thoracic aortic aneurysm (TAA) (n = 7), or thoracic aortic dissection (TAD) (n = 8) who had undergone EVAR by Medtronic stent grafts by our team between December 2006 and June 2009 were reviewed.Results:The rate of in-hospital aneurysm-related deaths in the group with AAA stood at 2.8% (one case), while there was no in-hospital mortality in the other groups. All patients were followed up for 13-18 months. The cumulative death rate in follow-up was nine cases from the total 51 cases (18%), out of which six cases were in the AAA group (four patients due to non-cardiac causes and two patients due to aneurysm-related causes), one case in the TAA group (following a severe hemoptysis), and two cases in the TAD group (following an expansion of dissection from re-entrance). The major event-free survival rate was 80.7% for endovascular repair of AAA, 85.7% for endovascular repair of TAA, and 65.6% for endovascular repair of TAD.Conclusion:The endovascular stent-graft repair of the abdominal and thoracic aortic aneurysm and aortic dissection had high technical success rates in tandem with low-rate early mortality and morbidity, short hospital stay, and acceptable mid-term free symptom survival among Iranian patients.

Peripheral Blood Immunological Features Associated with Aortic Valve Disease and Ascending Throcic Aorta Aneurysm and Dilation

INTRODUCTION: Ascending thoracic aortic aneurysm (TAA) is a multi-factorial process in which histological modifications and immune-mediated inflammation are closely associated. The predominant role of a Th1-mediated response in influencing aortic wall remodeling, dilation, and aneurysm formation has been suggested by previous studies. Recently, the importance of chemokine receptors for Th1 cells recruitment into vascular inflammatory sites, as well as of the balance between pro- and anti-inflammatory T-cell subsets in influencing the severity of coronary artery disease, have been described.MATERIAL AND METHODS: We evaluated activation markers and chemokine receptors expression on peripheral T-cell and NK cell subsets of subject with aortic valve disease associated with ascending TAA (ascending aortic diameter &gt; 4 cm) and undergoing elective surgery for TAA (Group A), in comparison with patients with aortic valve disease without TAA (ascending aortic diameter &lt; 4 cm) (Group B). Peripheral blood samples from the two groups were also compared for intracellular T-lymphocyte cytokine production, frequency of regulatory T cells (Treg) and soluble levels of cytokine and chemokines. The aortic size index (ASI) was considered a parameter able to reflect aortic pathophysiological modifications leading to aortic dilation.RESULTS: The results demonstrated correlations between ASI values and CCR5 expression on CD3+, CD3+/CD8+, CD4+ and CD4+/CD28- T-cell subsets. In Group A the expression of CCR5 was higher on CD3+/CD8+, CD4+ and CD4+/CD28- T-cell subsets, when compared with Group B. CD4+ and CD4+/CD28- T-cells in Group A showed also a higher expression for the co-stimulatory molecule CD28 and the activation marker CD25, respectively. An increased expression of CXCR3 was found on CD4+, CD3+/CD8+ and CD3+/TCR+ T-cell subsets in Group A. A higher circulating fraction of NK cells, together with a higher NK cell positivity for CX3CR1, were observed in aneurysmatic patients. Intracellular cytokine analysis demonstrated a higher fraction of CD3+/CD4+ T-cells producing IL-17A and IL-10 in Group A, together with a higher intracellular content for IL-21. Finally, a higher soluble level of fractalkine (CX3CL1) has been detected in aneurysm group.CONCLUSION: Results indicate a higher activation state, migratory capacity and cytotoxic potential of peripheral blood NK and T-cell subsets in patients with aortic valve disease associated with ascending TAA, when compared with patients affected by aortic valve disease alone. These findings, together with the observed higher polarization towards a Th17 in patients with aortic aneurysm could suggest the involvement of autoimmune mechanisms leading to cellular loss, inflammation and fibrosis during ascending aortic wall dilation and aneurysmatic progression.Journal of Universal College of Medical Sciences Vol. 3, No. 1, 2015: 11-20

Ascending thoracic aortic aneurysms protect against myocardial infarctions.

There has been increasing evidence that ascending thoracic aortic aneurysms (TAAs) protect against atherosclerosis. However, there have been no studies examining the relationship between ascending TAAs and clinical endpoints of atherosclerosis, such as stroke or peripheral arterial disease. In this study, we aim to characterize the relationship between TAAs and a specific clinical endpoint of atherosclerosis, myocardial infarction (MI). We compared prevalence of coronary artery disease (CAD) and MIs in 487 patients who underwent surgical repair for ascending TAAs to 500 control patients who did not have an ascending TAA. Multivariate binary logistic regression was used to calculate the odds of having MI if a patient had an ascending TAA versus any of several MI risk factors. There was a significantly lower prevalence of CAD and MI in the ascending TAA group than in the control TAA group. The odds of having a MI if a patient had a MI risk factor were all > 1 (more likely to have a MI), with the lowest statistically significant odds ratio being 1.54 (age; p = 0.001) and the highest being 14.9 (family history of MI; p < 0.001). The odds ratio of having a MI if a patient had an ascending TAA, however, was near 0 at 0.05 (p < 0.001). This study provides evidence that ascending TAAs protect against MIs, adding further support to the hypothesis that ascending TAAs protect against atherosclerotic disease.

Low transcriptional activity haplotype of matrix metalloproteinase 1 is less frequent in bicuspid aortic valve patients

PurposeBicuspid aortic valve (BAV) is the most common congenital cardiac anomaly which affects 0.5–2% of the population. It can be associated with other cardiac congenital lesions such as aortic aneurysms or aortic coarctation. Some genetic abnormalities have been suggested as the underlying cause of BAV and aortic root dilatation, but no clear genetic substrate and no specific pathogenic gene variant have already been identified. Increased matrix metalloproteinase activity has been described in the aortic wall of thoracic aortic aneurysms (TAA). Methods87 patients with BAV and 77 controls with normal tricuspid aortic valve were prospectively assessed. We analysed three functional polymorphisms (−1607 1G/2G, −519 A/G, and −340 T/C) in the matrix metalloproteinase (MMP)-1 gene using polymerase chain reaction and restriction fragment length analysis. ResultsWe found a haplotype composed of the lower activity allele from each polymorphism (−1607 1G/−519 A/−340 C) significantly less frequent in BAV group (p=0.016; OR [95% CI]=0.37 [0.16–0.85]), association even more clear when we consider only men (p=0.0005, OR [95% CI]=0.24 [0.10–0.56]).We also found a borderline statistical significance in the distribution of the −1607 alleles, being 2G allele more frequent in patients with TAA (p=0.053). This association was stronger and statistically significant when we consider only men (p=0.013; OR [95% CI]=2.0 [1.16–3.50]). In addition, genotype −1607 2G2G, theoretically the more active transcriptionally, was also significantly more frequent in TAA group, independently of aortic valve morphology. ConclusionsOur study suggests that specific genotypes of MMP1 gene could be in part responsible of the complications of BAV pathology, like TAA.

High Prevalence of Abdominal Aortic Aneurysm in Patients with Chronic Low Back Pain

Low back pain (LBP) is one of the most common symptoms in outpatient clinics, and abdominal aortic aneurysm (AAA) is one of the causes of LBP. In the present study, we examined the prevalence of chronic LBP in patients with aortic aneurysm. The study included 23 patients with AAA and 23 patients with thoracic aortic aneurysm (TAA); all of them visited a regional center hospital in Akita, Japan. A total of 207 hypertension patients were also enrolled as a control. Chronic LBP was defined in patients who visited the orthopedic outpatient clinic for the LBP treatment for more than three months. The prevalence of chronic LBP in the AAA group (52.2%) was significantly higher than that in the TAA (17.4%, P < 0.05) or hypertension patients (11.6%, P < 0.01). The rate of a trigger point (TP) injection was significantly higher in the AAA group or the TAA group than that in hypertension patients (P < 0.01, P < 0.05), but there was no significant difference between the AAA and TAA groups. The TP injection represents an injection of local anesthesia to the low back muscles. We also evaluated the involvement of various factors in LBP caused by AAA, such as age, gender, blood pressure, the existence of dissection, and the maximum diameter of AAA, but none of them showed significant relationship to LBP. The prevalence of LBP is high in AAA patients, and doctors who treat chronic LBP should be aware of AAA as a potential cause of LBP.

Apoptotic Vascular Smooth Muscle Cell Depletion via BCL2 Family of Proteins in Human Ascending Aortic Aneurysm and Dissection

This study investigates the expression patterns of BCL2 (B-cell CLL/lymphoma2) family of proteins and the extent of vascular smooth muscle cell (VSMC) apoptosis in thoracic aortic aneurysms (TAA), type-A aortic dissections (TAD), and nondilated ascending aortic samples. Aortic wall specimens were obtained from patients undergoing surgical repair for TAA (n = 24), TAD (n = 20), and normal aortic tissues from organ donors (n = 6). The expression pattern of BCL2, BCL2L1 (BCL2-like1), BAK1 (BCL2-antagonist/killer1), and BAX (BCL2-associated X protein) proteins was investigated by immunohistochemistry. Furthermore, colocalization of alpha smooth muscle actin (ACTA2) and caspase3 (CASP3) in aortic VSMCs was analyzed by double-immunofluorescence staining. Onset of DNA fragmentation was measured by TUNEL assay. Apoptotic index was significantly increased in both TAD group (31.3 ± 17.2, P < 0.001) and TAA group (21.1 ± 12.7, P = 0.001) relative to control aortas (2.0 ± 1.2). Anti-CASP3 and ACTA2 double-immunostaining confirmed apoptosis in VSMCs in TAA and TAD groups but not in controls. Proapoptotic BAX expression was significantly elevated in VSMCs of TAA patients, compared with that of controls (OR = 20; P = 0.02; 95% CI, 16-250). In contrast, antiapoptotic BCL2L1 expression was higher in controls compared with that of TAA group (OR = 11.2; P = 0.049; 95% CI, 1.0-123.9). Furthermore, BAX/BCL2 ratio was significantly increased in both TAA (1.2 ± 0.7, P < 0.001) and TAD (0.6 ± 0.4, P = 0.05) groups relative to controls (0.2 ± 0.1, P < 0.001). Apoptotic VSMC depletion in human TAA/TAD is associated with disturbance of the balance between proapoptotic and antiapoptotic members of the BCL2 family proteins, which may have a role in the pathogenesis of vascular remodelling in aortic disease. In light of the future studies, targeting apoptotic pathways in TAA and TAD pathogenesis may provide therapeutic benefits to patients by slowing down the progression and even possibly preventing the TAD.

57 High-resolution genomic profiling of 533 B-cell lymphomas defines distinct tumor signatures, genomic aberrations correlated with outcome and pathogenetic subgroups

Bicuspid aortic valve (BAV) is the most common congenital cardiac anomaly which affects 0.5–2% of the population. It can be associated with other cardiac congenital lesions such as aortic aneurysms or aortic coarctation. Some genetic abnormalities have been suggested as the underlying cause of BAV and aortic root dilatation, but no clear genetic substrate and no specific pathogenic gene variant have already been identified. Increased matrix metalloproteinase activity has been described in the aortic wall of thoracic aortic aneurysms (TAA).87 patients with BAV and 77 controls with normal tricuspid aortic valve were prospectively assessed. We analysed three functional polymorphisms (− 1607 1G/2G, − 519 A/G, and − 340 T/C) in the matrix metalloproteinase (MMP)-1 gene using polymerase chain reaction and restriction fragment length analysis.We found a haplotype composed of the lower activity allele from each polymorphism (− 1607 1G/− 519 A/− 340 C) significantly less frequent in BAV group (p = 0.016; OR [95% CI] = 0.37 [0.16–0.85]), association even more clear when we consider only men (p = 0.0005, OR [95% CI] = 0.24 [0.10–0.56]).We also found a borderline statistical significance in the distribution of the − 1607 alleles, being 2G allele more frequent in patients with TAA (p = 0.053). This association was stronger and statistically significant when we consider only men (p = 0.013; OR [95% CI] = 2.0 [1.16–3.50]). In addition, genotype − 1607 2G2G, theoretically the more active transcriptionally, was also significantly more frequent in TAA group, independently of aortic valve morphology.Our study suggests that specific genotypes of MMP1 gene could be in part responsible of the complications of BAV pathology, like TAA.

Familial Thoracic Aortic Aneurysms and Dissections—Incidence, Modes of Inheritance, and Phenotypic Patterns

We examined the genetic nature and phenotypic features of thoracic aortic aneurysms (TAAs) and dissections in a large cohort of patients. Interviews were conducted with 520 patients with TAAs and their pedigrees were compiled to identify family members with aneurysms. Study patients were divided into three groups: 101 non-Marfan patients, in 88 pedigrees, had a family pattern for TAA (familial group), 369 had no family pattern (sporadic group), and 50 had Marfan syndrome (MFS). We determined incidence of familial clustering, age at presentation, rate of aneurysm growth, incidence of hypertension, correlation of aneurysm sites among kindred, and pedigree inheritance patterns. An inherited pattern for TAA was present in 21.5% of non-MFS patients. The predominant inheritance pattern was autosomal dominant (76.9%), with varying degrees of penetrance and expressivity. The familial TAA group was significantly younger than the sporadic group (p < 0.0001), but not as young as the MFS group (p < 0.0001) (mean ages, 58.2 versus 65.7 versus 27.4 years). Among all 197 probands and kindred with aneurysm, 131 (66.5%) had TAA, 49 (24.9%) had abdominal aortic aneurysm (AAA), and 17 (8.6%) had cerebral or other aneurysms. Ascending aneurysm paired most commonly with ascending, and descending with abdominal. Abdominal aortic aneurysms (AAAs) and hypertension were more often associated with descending than with ascending TAAs (p < 0.001). Aortic growth rate was highest for the familial group (0.21 cm/y), intermediate for the sporadic group (0.16 cm/y), and lowest for the Marfan group (0.1 cm/y; p < 0.01). TAAs are frequently familial diseases. The predominant mode of inheritance is autosomal dominant. Familial TAAs have a relatively early age of onset. Aneurysms in relatives may be seen in the thoracic aorta, the abdominal aorta, or the cerebral circulation. Screening of first-order relatives of probands with TAA is essential. Familial TAAs tend to grow at a higher rate, exemplifying a more aggressive clinical entity.

Impact of blood coagulation and fibrinolytic system changes on early and mid term clinical outcome in patients undergoing stent endografting surgery

Blood coagulation and fibrinolytic system changes after endovascular repair (EVAR) of aortic pathologies are of great interest. We have examined the risk for consumption coagulopathy and its clinical implications early, and at a mid-term follow-up, in a prospective study. From June 2002 to June 2004, 41 patients for abdominal aortic aneurysm (AAA), 16 for thoracic aortic aneurysm (TAA) and 13 for acute type-B dissection underwent EVAR. Plasminogen, fibrin degradation products (FDP) and D-dimer were monitored as markers of fibrinolysis. Platelet count, fibrinogen, antithrombin III and prothrombin were assayed as markers of coagulation. The aortic diameters were assessed by computed tomography (CT) scan. FDP and D-Dimer levels significantly increased, while plasminogen values significantly decreased, on postoperative day 1 and 5, coagulation parameters significantly decreased on postoperative day 1 and 5. All parameters recovered on the 1st month of follow-up, except fibrinogen levels that showed a significant increase on month 1 and 6. We did not observe clinical complications related to coagulative disorders. There was no correlation between the preoperative diameter and the coagulative and fibrinolysis variations in the AAA and TAA group. Type-B dissection patients showed a significant correlation between the preoperative presence of a large false lumen and a high level of fibrinolysis. EVAR leads to changes in coagulation and fibrinolysis, with characteristic developments. These latter have no clinical relevance and have no effect on early outcome and on mid-term follow-up.

Complications of endovascular repair of high-risk and emergent descending thoracic aortic aneurysms and dissections

Purpose The advent of endovascular prostheses to treat descending thoracic aortic lesions offers an alternative approach in patients who are poor candidates for surgery. The development of this approach includes complications that are common to the endovascular treatment of abdominal aortic aneurysms and some that are unique to thoracic endografting. Methods We conducted a retrospective review of 60 emergent and high-risk patients with thoracic aortic aneurysms (TAAs) and dissections treated with endovascular prostheses over 4 years under existing investigational protocols or on an emergent compassionate use basis. Results Fifty-nine of the 60 patients received treatment, with one access failure. Thirty-five patients received treatment of TAAs. Four of these procedures were performed emergently because of active hemorrhage. Twenty-four patients with aortic dissections (16 acute, 8 chronic) also received treatment. Eight of the patients with acute dissection had active hemorrhage at the time of treatment. Three devices were used: AneuRx (Medtronic; n = 31), Talent (Medtronic; n = 27), and Excluder (Gore; n = 1). Nineteen secondary endovascular procedures were performed in 14 patients. Most were secondary to endoleak (14 of 19), most commonly caused by modular separation of overlapping devices (n = 8). Other endoleaks included 4 proximal or distal type I leaks and 2 undefined endoleaks. The remaining secondary procedures were performed to treat recurrent dissection (n = 1), pseudoaneurysm enlargement (n = 3), and endovascular abdominal aortic aneurysm repair (n = 1). One patient underwent surgical repair of a retrograde ascending aortic dissection after endograft placement. Procedure-related mortality was 17% in the TAA group and 13% in the dissection group, including 2 acute retrograde dissections that resulted in death from cardiac tamponade. Overall mortality was 28% at 2-year follow-up. Conclusion Although significant morbidity and mortality remain, endovascular repair of descending TAAs and dissections in patients at high-risk patients can be accomplished with acceptable outcomes compared with traditional open repair. The major cause for repeat intervention in these patients was endoleak, most commonly caused by device separation. Improved understanding of these complications may result in a decrease in secondary procedures, morbidity, and mortality in these patients. The need for secondary interventions in a significant number of patients underscores the necessity for continued surveillance.