Dilatation Of Ascending Aorta Research Articles

Predictors of Ascending Aorta Enlargement and Valvular Dysfunction Progression in Patients with Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) patients are at high risk of developing progressive aortic valve dysfunction and ascending aorta dilation. However, the progression of the disease is not well defined. We aimed to assess mid-long-term aorta dilation and valve dysfunction progression and their predictors. Patients were referred from cardiac outpatient clinics to the echocardiographic laboratories of 10 tertiary hospitals and followed clinically and by echocardiography for >5 years. Seven hundred and eighteen patients with BAV (median age 47.8 years [IQR 33–62], 69.2% male) were recruited. BAV without raphe was observed in 11.3%. After a median follow-up of 7.2 years [IQR5–8], mean aortic root growth rate was 0.23 ± 0.15 mm/year. On multivariate analysis, rapid aortic root dilation (>0.35 mm/year) was associated with male sex, hypertension, presence of raphe and aortic regurgitation. Annual ascending aorta growth rate was 0.43 ± 0.32 mm/year. Rapid ascending aorta dilation was related only to hypertension. Variables associated with aortic stenosis and regurgitation progression, adjusted by follow-up time, were presence of raphe, hypertension and dyslipidemia and basal valvular dysfunction, respectively. Intrinsic BAV characteristics and cardiovascular risk factors were associated with aorta dilation and valvular dysfunction progression, taking into account the inherent limitations of our study-design. Strict and early control of cardiovascular risk factors is mandatory in BAV patients.

Prognostic Implications of Bicuspid and Tricuspid Aortic Valve Phenotype on Progression of Moderate Aortic Stenosis and Ascending Aorta Dilatation

Studies on the impact of aortic valve anatomy (bicuspid aortic valve [BAV] or tricuspid aortic valve [TAV]) on the progression of moderate aortic stenosis (AS) and ascending aorta (AA) dilatation and its prognostic implications are limited. From 1991 to 2016, 288 asymptomatic patients with moderate AS detected during index echocardiography with at least 1 year of echocardiographic follow-up were retrospectively studied. Baseline clinical and echocardiographic characteristics were compared between patients with BAV (n=80) and patients with TAV (n=208). Co-primary outcomes were 1-year hemodynamic and anatomic progression of AS and AA dilatation. Secondary end points were the incidence of AA rapid progressors, all-cause mortality, aortic valve replacement, and congestive heart failure. Determinants of AS progression, AA diameters, AA dilatation, and prognostic outcomes were evaluated. Similar 1-year progression of the aortic valve peak velocity, Vmax (9 ± 18 vs 9 ± 23 cm/s), mean gradient (1.5 ± 2.3 vs 1.3 ± 3.2 mm Hg), and aortic valve area (AVA) (-0.04 ± 0.09 vs -0.05 ± 0.10 cm2) were noted for BAV and TAV groups, respectively. One-year progressions of AA were similar at Valsalva (0.11 ± 0.88 vs 0.14 ± 1.10 mm) and tubular levels (0.12 ± 0.68 vs 0.30 ± 1.51 mm) in BAV and TAV groups, respectively. A trend toward increased rapid AA progression in patients with BAV (31.3%) was observed compared with patients with TAV (14.8%, p=0.099). BAV was associated with progression of Vmax (β=0.17, p=0.036), the dimensionless index (β=-0.17, p=0.008), and AVA (β=-0.14, p=0.048), but not mean gradient after adjusting for age, baseline severity indexes, gender, hypertension, diabetes, and body surface area. Although BAV was a determinant of larger baseline AA diameter, there was no significant association between BAV and AA rapid progressors. Adjusted Kaplan-Meier curves demonstrated no differences in congestive heart failure, aortic valve replacement, or mortality between valve morphology. In conclusion, there was a similar 1-year disease progression in terms of AVA, Vmax, mean gradient, and AA diameters between patients with BAV and patients with TAV. BAV was associated with a significant increase in Vmax, dimensionless index, and AVA after adjusting for important confounders. Close and prolonged follow-up is warranted in both groups of patients.

Arterial Stiffness and Left Ventricular Myocardial Function in Children with a Well-Functioning Bicuspid Aortic Valve.

ResumoFundamento:A rigidez arterial é um importante preditor de aortopatia e remodelamento miocárdico em pacientes com válvula aórtica bicúspide, podendo estar aumentada na infância.Objetivo:Avaliar a rigidez arterial e a função miocárdica do ventrículo esquerdo em crianças com válvula aórtica bicúspide funcional.Métodos:Quarenta e quatro crianças com válvula aórtica bicúspide e 41 pares saudáveis com válvula aórtica tricúspide foram incluídos neste estudo caso-controle. Foram obtidos os diâmetros e os escores-z relacionados da raiz aórtica e da aorta ascendente. Quanto à função miocárdica do ventrículo esquerdo, juntamente com as velocidades de fluxo mitral e parâmetros do Modo M, as velocidades miocárdicas e os intervalos de tempo foram avaliados com Doppler tecidual. A análise da onda de pulso foi realizada por aparelho oscilométrico (Mobil-o-Graph). Um valor de p<0,05 foi considerado significativo.Resultados:O índice da massa ventricular esquerda, a velocidade A do fluxo mitral, o diâmetro e o escore z da aorta ascendente e o índice de desempenho miocárdico estavam significativamente maiores nos pacientes (p = 0,04, p = 0,02, p = 0,04, p <0,001 e p <0,001 respectivamente). O índice de desempenho miocárdico correlacionou-se positivamente com o diâmetro da aorta ascendente e a velocidade A (r=0,272; p=0,01, r=356; p=0,001, respectivamente). A análise multivariada revelou que o índice de desempenho miocárdico estava relacionado ao diâmetro da aorta ascendente (p = 0,01). O índice de aumento e a velocidade da onda de pulso foram semelhantes entre os grupos (p> 0,05).Conclusão:De acordo com a análise da onda de pulso oscilométrico, as crianças com válvula aórtica bicúspide funcional apresentam rigidez arterial semelhante a seus pares saudáveis. O diâmetro da aorta ascendente foi estabelecido como preditor independente da função miocárdica do ventrículo esquerdo. A rigidez arterial pode não ser um fator de risco grave em pacientes pediátricos sem dilatação acentuada da aorta ascendente.

Transcatheter aortic valve implantation for pure aortic regurgitation

Transcatheter aortic valve implantation (TAVI) has become an established alternative to surgery in patients with calcific aortic stenosis. Broad implementation of devices and increased experience have led operators to explore the feasibility of TAVI in off-label indication such as pure native aortic valve regurgitation. Given the technical issues related to the absence of leaflet calcification and aortic root or ascending aorta dilation, this procedure is typically performed in patients in whom surgical risk is deemed prohibitive. Although recently published data have shown encouraging results in patients treated with new generation prostheses, new iteration of transcatheter valves, specifically designed for the treatment of aortic regurgitation, is needed. Nowadays, with no dedicated system on the horizon and in order to guarantee the best results, efforts should be made to improve patient selection.

Abstract 130: Wnt16 Deficiency Worsens Angiotensin Ii - Induced Aneurysmal Remodeling Of Ascending Thoracic Aorta

Wnt16 controls bone strength via paracrine osteoblast-osteoclast remodeling interactions. Wnt16 mRNA is highly expressed in both aorta &amp; bone, &amp; immunofluorescence (IF) localized Wnt16 to vascular smooth muscle (VSM). Paracrine VSM - monocyte/macrophage (M/MAC) interactions control arterial remodeling, resembling osteoblast-osteoclast interactions in bone. We assessed the impact of Wnt16 deficiency on aneurysmal remodeling (6-7/group). Angiotensin II infusion for 4 weeks increased ascending thoracic aorta diameter by 60% (Holm-Sidak p = 1.5E-4, ANOVAp = 2.7E-6) in male LDLR-/- mice. Wnt16-/-;LDLR-/- cohorts exhibited worsened ascending aorta dilatation (by 20%; Holm-Sidak p = 0.03), indicating a protective role for Wnt16. Mass spectrometry of thoracic aorta proteins from Wnt16-/-;LDLR-/- vs. LDLR-/-mice revealed a 9-fold increase in MMP12 (p = 0.008; n=3/group) — a M/MAC protease key to aneurysmal remodeling. IF confirmed enhanced adventitial MMP12 in aortas of Wnt16-null mice. Treatment of M/MACs with Wnt16 (8 nM) down-regulated Mmp12 mRNA (78%; p &lt; 0.001), with increased IL10 (2-fold; p &lt; 0.05) &amp; Arg1 (6-fold; p =0.001). Hypomorphic alleles encoding contractile proteins predispose to hereditary thoracic aortic aneurysm; thus, we studied the impact of Wnt16 deficiency on the contractile phenotype. VSM from Wnt16-null thoracic aorta exhibited reductions in Myh11 (down 60%; p &lt; 0.05), Acta2 (by 35%, p &lt;0.05), &amp; the VSM transcriptional co-activator Myocardin ( by 65%; p = 0.0002), while Axin2 was increased 1.7-fold (p = 0.01). Acute siRNA-mediated knockdown of Wnt16 in VSM -M/MAC admixtures (95% VSM, 5% M/MAC) also downregulated contractile genes &amp; upregulated Mmp12 . This was phenocopied by siRNA targeting Taz/Wwtr1 — a transcriptional collaborator of Myocd we identified as exhibiting impaired nuclear localization in Wnt16-null VSM. In vivo dosing with Wnt16 (0.25 mg/kg/day, 2 days) upregulated aortic contractile gene expression 1.6- to 1.8-fold, with Mmp12 reduced 50% (p &lt; 0.05), as consistent with the reciprocal changes upon Wnt16 deficiency. Wnt16 limits thoracic aortic remodeling, preserves the VSM contractile phenotype, &amp; reduces Mmp12. Strategies that augment Wnt16 signaling may mitigate enlargement of thoracic aortic aneurysms.

Aortic root aortopathy in bicuspid aortic valve associated with high genetic risk

BackgroundThe bicuspid aortic valve (BAV) is prone to ascending aortic dilatation (AAD) involving both the tubular segment and the aortic root. The genetic factor was proposed as one of the most important mechanisms for AAD. We hypothesized that the rare genetic variants mainly contribute to the pathogenesis of aortic roots in affected individuals.MethodsThe diameter of aortic root or ascending aorta ≥ 40 mm was counted as AAD. The targeted next-generation sequencing of 13 BAV-associated genes were performed on a continuous cohort of 96 unrelated BAV patients. The rare variants with allele frequency < 0.05% were selected and analyzed. Variants frequency was compared against the Exome aggregation consortium database. The pathogenicity of the genetic variants was evaluated according to the American College of Medical Genetics and Genomics guidelines.ResultsA total of 27 rare nonsynonymous coding variants involving 9 genes were identified in 25 individuals. The burden analysis revealed that variants in GATA5, GATA6, and NOTCH1 were significantly associated with BAV. Eighty percent of the pathogenic variants were detected in root group. The detection rate of rare variants was higher in root dilatation group (71.4%) compared with normal aorta (29.0%) and tubular dilatation groups (29.6%) (P = 0.018). The rare variant was identified as the independent risk factor of root dilatation [P = 0.014, hazard ratio = 23.9, 95% confidence interval (1.9–302.9)].ConclusionsOur results presented a broad genetic spectrum in BAV patients. The rare variants of BAV genes contribute the most to the root phenotype among BAV patients.

Association of Regional Wall Shear Stress and Progressive Ascending Aorta Dilation in Bicuspid Aortic Valve

ObjectivesThe aim of this study was to evaluate the role of wall shear stress (WSS) as a predictor of ascending aorta (AAo) growth at 5 years or greater follow-up. BackgroundAortic 4-dimensional flow cardiac magnetic resonance (CMR) can quantify regions exposed to high WSS, a known stimulus for arterial wall dysfunction. However, its association with longitudinal changes in aortic dilation in patients with bicuspid aortic valve (BAV) is unknown. MethodsThis retrospective study identified 72 patients with BAV (age 45 ± 12 years) who underwent CMR for surveillance of aortic dilation at baseline and ≥5 years of follow-up. Four-dimensional flow CMR analysis included the calculation of WSS heat maps to compare regional WSS in individual patients with population averages of healthy age- and sex-matched subjects (database of 136 controls). The relative areas of the AAo and aorta (in %) exposed to elevated WSS (outside the 95% CI of healthy population averages) were quantified. ResultsAt a median follow-up duration of 6.0 years, the mean AAo growth rate was 0.24 ± 0.20 mm/y. The fraction of the AAo exposed to elevated WSS at baseline was increased for patients with higher growth rates (>0.24 mm/y, n = 32) compared with those with growth rates <0.24 mm/y (19.9% [IQR: 10.2%-25.5%] vs 5.7% [IQR: 1.5%-21.3%]; P = 0.008). Larger areas of elevated WSS in the AAo and entire aorta were associated with higher rates of AAo dilation >0.24 mm/y (odds ratio: 1.51; 95% CI: 1.05-2.17; P = 0.026 and odds ratio: 1.70; 95% CI: 1.01-3.15; P = 0.046, respectively). ConclusionsThe area of elevated AAo WSS as assessed by 4-dimensional flow CMR identified BAV patients with higher rates of aortic dilation and thus might determine which patients require closer follow-up.

Excess of visceral adipose tissue with or without aortic elongation leads to a steeper heart position.

The heart's position determined as the heart-aorta angle (HAA) has been demonstrated to associate with ascending aortic (AA) dilatation. Visceral adipose tissue (VAT) and aortic elongation may shift the heart to the steeper position. To investigate whether VAT and aortic length influence the HAA. We examined 346 consecutive patients (58.4% men; mean age = 67.0 ± 14.1 years) who underwent aortic computed tomography angiography (CTA). HAA was measured as the angle between the long axis of the heart and AA midline. The amount of VAT was measured at the level of middle L4 vertebra from a single axial CT slice. Aortic length was measured by combining four anatomical segments in different CTA images. The amount of VAT and aortic length were determined as mild with values in the lowest quartile and as excessive with values in the other three quartiles. A total of 191 patients (55.2%) had no history of aortic diseases, 134 (38.7%) displayed AA dilatation, 8 (2.3%) had abdominal aortic aneurysm (AAA), and 13 (3.8%) had both AA dilatation and AAA. There was a strong nonlinear regression between smaller HAA and VAT/height, and HAA and aortic length/height. Median HAA was 124.2° (interquartile range 119.0°-130.8°) in patients with a mild amount of VAT versus 120.5° (interquartile range 115.4°-124.7°) in patients with excessive VAT (P < 0.001). An excessive amount of VAT and aortic elongation led to a steeper heart position. These aspects may possess clinical value when evaluating aortic diseases in obese patients.

Sutureless aortic valve with supracoronary ascending aortic replacement as an alternative strategy for composite graft replacement in elderly patients.

Aortic valve disease is frequently associated with ascending aorta dilatation and can be treated either by separate replacement of the aortic valve and ascending aorta or by a composite valve graft. The type of surgery is depending on the exact location of the aortic dilatation and the concomitant valvular procedures required. The evidence for elective aortic surgery in elderly high-risk patients remains challenging and therefore alternative strategies could be warranted. We propose an alternative strategy for the treatment of ascending aortic aneurysm and aortic valve pathology with the use of a sutureless, collapsible, stent-mounted aortic valve prosthesis.

Bicuspid aortic valve fusion length correlates with maximum aortic diameter and heamodynamic abnormalities: a 4D flow CMR study

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Guala A. received funding from the Spanish Ministry of Science, Innovation and Universities. Background Bicuspid aortic valve (BAV), a congenital heart defect, is associated with ascending aorta dilation, possibly via alteration of aortic blood flow [1]. In BAV abnormal flow condition have been associated with aortic extracellular matrix dysregulation and elastic fiber degeneration [2]. Current morphological classification of BAV patients with aortic valve with a single fusion between two adjacent leaflets does not allow for risk stratification. Purpose This research work tested whether the extent of fusion between leaflets is related to AAo diameter and flow alterations. Methods Ninety BAV patients free from moderate and severe aortic valve disease and with no previous aortic or aortic valve surgery or replacement were prospectively enrolled. A comprehensive magnetic resonance protocol comprised a stack of double-oblique 2D balanced steady-state free-precession (bSSFP) cine CMR of the aortic valve, which was used to measure the length of the fusion between leaflets, a cine CMR at the level of the pulmonary bifurcation to assess aortic diameter and 4D flow MRI sequence to assess flow characteristics and regional stiffness [3]. Jet angle and flow radial displacement, quantifying the extent of flow eccentricity, and systolic flow reversal ratio (SFRR), assessing the relative amount of backward flow during systole, were computed at 8 equidistant planes in the ascending aorta and 4 equidistant planes in the aortic arch [4]. A two-tailed p-value &amp;lt; 0.05 was considered statistically significant. Results The length of leaflet fusion varied widely (median 7.7 mm, inter-quartile range [5.5; 10.2]), Table 1). In bivariate analysis, fusion length was also associated to ascending aortic diameter (R = 0.391, p &amp;lt; 0.001), age (R = 0.313, p = 0.005) and body surface area (R = 0.396, p &amp;lt; 0.001). It was also positively related to flow abnormalities: like displacement in the proximal and distal ascending aorta, jet angle in the mid ascending aorta, and SFRR in the ascending aorta and the aortic arch (see Figure 1). The association between fusion length and ascending aorta diameter persisted in multivariate analysis after correction for age (p = 0.006). Conclusions Bicuspid aortic valve fusion extent varies greatly and it is associated with aortic diameter, possibly through flow alterations. Prospective longitudinal studies are needed to establish whether fusion length may allow for risk stratification in bicuspid aortic valve patients.

Evaluation of Ascending Aortic Longitudinal Strain Via Two-Dimensional Speckle Tracking Echocardiography in Hypertensive Patients Complicated by Type A Aortic Dissection.

To explore the value of ascending aortic longitudinal strain (LS) in identification of hypertensive (HP) patients with a high risk of type A aortic dissection (AAD). Total 40 primary HP patients with AAD (group C), 80 selected age- and sex-matched primary HP patients (group A, normal-sized ascending aorta (AA), n=40; group B, dilated AA, n=40) and 40 healthy volunteers were enrolled in this study. Brachial blood pressures were measured, and the aortic stiffness index (β) determined by M-mode analysis was calculated as a conventional parameter of arterial stiffness. The LS of the anterior and posterior ascending aortic wall (AW-LS and PW-LS) were determined. Compared to the control group (34.21 ± 5.25%), the mean LS of AA in HP patients (group A 28.6 ± 5.95%; group B 23.64 ± 4.98%; group C 17.93 ± 3.96%; P < .001) were significantly reduced. Multivariate logistic regression analysis showed that the mean LS (OR 0.719, 95% CI 0.615-0.839, P < .001) and pulse pressure (PP) (OR 1.055, 95% CI 1.006-1.106, P=.028) were identified as independent predictors of AAD in HP patients. The AUC of mean LS combined with PP reached 0.926 (sensitivity, 95.0%; specificity, 82.5%), which was higher than the mean LS, PP, stiffness index, and ascending aortic diameter (AAd) separately. Besides, the AW-LS and PW-LS were negatively correlated with the AAd, stiffness index, stroke volume, systolic blood pressure, and PP, respectively (P < .001). The LS of AA evaluated by two-dimensional speckle tracking echocardiography decreased significantly along with the expansion of aortic lumen and the occurrence of AAD in HP patients. It is also an independent predictor of AAD in HP patients.

Ascending aorta dissection in a new classification system: Clinicopathological features of 62 cases

Herein we present a single institution 5-year experience with ascending aorta dissection biopsies depicting the clinicopathological features of 62 cases. To detect microscopic abnormalities in the aortic wall beside the dissection itself, we applied a new histopathological classification scheme from the consensus documents issued by The Society for Cardiovascular Pathology and The Association for the European Cardiovascular Pathology in 2015 and 2016. The most common finding was medial degeneration (MD) - 61 cases (98.4%); atherosclerosis (AS) was found in 19 aortae (30.6%), and chronic aortitis- giant cell pattern described in one aorta (1.6%). The medial degeneration constituents included mucoid matrix accumulation, smooth muscle cells and elastic fibers abnormalities, and medial fibrosis. The consensus document application led to increased MD reporting compared to older studies and to our previous experience, probably due to assessing more subtle and focal changes such as intralamellar fibrosis, intralamellar mucoid matrix accumulation, and loss of smooth muscle cell nuclei- these changes being also the most common MD abnormalities we are reporting. We have compared the results in patients with bicuspid (n = 7; 11.3%) versus tricuspid (n = 55; 88.7%) aortic valve, suggesting no significant differences except for translamellar fibrosis, which appeared to be more severe in the bicuspid valve group (p = 0.0397). The results might imply similar histopathological findings regardless of the aortic valve cuspidity in aortic dissection. These findings are in contrast to ascending aorta dilation (aneurysm), where more severe medial degeneration changes have been described in patients with the tricuspid aortic valve.

Combining 4D Flow MRI and Complex Networks Theory to Characterize the Hemodynamic Heterogeneity in Dilated and Non-dilated Human Ascending Aortas

Motivated by the evidence that the onset and progression of the aneurysm of the ascending aorta (AAo) is intertwined with an adverse hemodynamic environment, the present study characterized in vivo the hemodynamic spatiotemporal complexity and organization in human aortas, with and without dilated AAo, exploring the relations with clinically relevant hemodynamic and geometric parameters. The Complex Networks (CNs) theory was applied for the first time to 4D flow magnetic resonance imaging (MRI) velocity data of ten patients, five of them presenting with AAo dilation. The time-histories along the cardiac cycle of velocity-based quantities were used to build correlation-based CNs. The CNs approach succeeded in capturing large-scale coherent flow features, delimiting flow separation and recirculation regions. CNs metrics highlighted that an increasing AAo dilation (expressed in terms of the ratio between the maximum AAo and aortic root diameter) disrupts the correlation in forward flow reducing the correlation persistence length, while preserving the spatiotemporal homogeneity of secondary flows. The application of CNs to in vivo 4D MRI data holds promise for a mechanistic understanding of the spatiotemporal complexity and organization of aortic flows, opening possibilities for the integration of in vivo quantitative hemodynamic information into risk stratification and classification criteria.

A human importin-β-related disorder: Syndromic thoracic aortic aneurysm caused by bi-allelic loss-of-function variants in IPO8

Importin 8, encoded by IPO8, is a ubiquitously expressed member of the importin-β protein family that translocates cargo molecules such as proteins, RNAs, and ribonucleoprotein complexes into the nucleus in a RanGTP-dependent manner. Current knowledge of the cargoes of importin 8 is limited, but TGF-β signaling components such as SMAD1-4 have been suggested to be among them. Here, we report that bi-allelic loss-of-function variants in IPO8 cause a syndromic form of thoracic aortic aneurysm (TAA) with clinical overlap with Loeys-Dietz and Shprintzen-Goldberg syndromes. Seven individuals from six unrelated families showed a consistent phenotype with early-onset TAA, motor developmental delay, connective tissue findings, and craniofacial dysmorphic features. A C57BL/6N Ipo8 knockout mouse model recapitulates TAA development from 8-12weeks onward in both sexes but most prominently shows ascending aorta dilatation with a propensity for dissection in males. Compliance assays suggest augmented passive stiffness of the ascending aorta in male Ipo8-/- mice throughout life. Immunohistological investigation of mutant aortic walls reveals elastic fiber disorganization and fragmentation along with a signature of increased TGF-β signaling, as evidenced by nuclear pSmad2 accumulation. RT-qPCR assays of the aortic wall in male Ipo8-/- mice demonstrate decreased Smad6/7 and increased Mmp2 and Ccn2 (Ctgf) expression, reinforcing a role for dysregulation of the TGF-β signaling pathway in TAA development. Because importin 8 is the most downstream TGF-β-related effector implicated in TAA pathogenesis so far, it offers opportunities for future mechanistic studies and represents a candidate drug target for TAA.

Proteomic analysis of the ascending aorta in a hamster model of BAV disease

Bicuspid aortic valve (BAV) is the most prevalent human congenital cardiac malformation, which predisposes to ascending aortic dilatation (AD). Disease predisposition probably results from a congenital defect leading to anomalies in both, the morphology of the valve and the histology of the ascending aorta. Altered hemodynamics caused by the abnormal valve morphology would accelerate aortic media degeneration. AD in BAV patients results from medial smooth muscle cell (SMC) apoptosis probably caused by defective cell-matrix adhesion. Alterations of the TGFβ pathway seem to be central in disease initiation and progression, affecting extracellular matrix homeostasis. However, currently there are neither clear pathophysiological mechanisms nor effective biomarkers of disease predisposition or progression.The only spontaneous animal model of BAV disease consists of an inbred (T) strain of Syrian hamsters with a high (40%) incidence of BAV. Although AD has never been described in this model, animals of the T strain show significant SMC apoptosis and altered elastic lamina in the aortic media, irrespective of aortic valve morphology. We reasoned that analysing differentially expressed proteins in the aortic wall of animals with normal aortic valve (TAV) of the T strain compared to a control strain would inform about 1) the validity of the T strain as a model for BAV aortopathy predisposition; 2) the congenital origin of AD associated to BAV; 3) the proteins involved in AD etiology, independent of the effect of hemodynamics.To this aim, we compared the proteome of the ascending aorta of animals with TAV of the T strain (n=6) and a control outbred strain (n=6) by three independent experiments of quantitative proteomics (ESI-Quadrupole-Orbitrap LFQ). The analysis yielded expression data for over 1,954 proteins. Of these, 57 proteins (2.9%) showed concordant expression in at least two of the three experiments and were deregulated over 2.6-fold.Fourteen of these 57 proteins (24.6%) were previously proposed as AD biomarkers in patients. After database search, the 57 selected proteins were found to significantly interact (p<0.05 following FDR adjustment) within 16 molecular pathways and 27 biological processes on the STRING website. Most of these pathways and processes were relevant to AD pathophysiology, of note are the TGFβ non-canonical pathways (10/57; 17.5%; p=0.043), programmed cell death (14/57; 24.6%; p=3.5e-4), cell adhesion (15/57; 26.3%; p=2.4e-4), supramolecular fiber organization (9/57; 15.8%; p=3.8e-4) and stress fiber assembly (2/57; 3.5%; p=0.037).These results were obtained comparing the proteomes of aortas of individuals with TAV from an affected and a control strain. Thus, genetic rather than hemodynamic factors explain the structural abnormalities of the ascending aorta in this model. We propose that the T strain is an appropriate model for AD predisposition, as it replicates the ethiophysiological processes observed in patients. Deep study of our ascending aorta proteome analysis may uncover new molecular players and markers associated with aortopathy predisposition and progression.

Isolated ascending aorta dilatation is associated with increased risk of abdominal aortic aneurysm

BackgroundAbdominal aortic aneurysm (AAA) is an asymptomatic condition characterized by progressive dilatation of the aorta. The purpose of this study is to identify important 2D-TTE aortic indices associated with AAA as predictive tools for undiagnosed AAA.MethodsIn this retrospective study, we evaluated the size of the ascending aorta in patients without known valvular diseases or hemodynamic compromise as predictive tool for undiagnosed AAA. We studied the tubular ascending aorta of 170 patients by 2-dimensional transthoracic echocardiography (2D-TTE). Patients were further divided into two groups, 70 patients with AAA and 100 patients without AAA with normal imaging results.ResultsDilatation of tubular ascending aorta was measured in patients with AAA compared to the group with absent AAA (37.5 ± 4.8 mm vs. 31.2 ± 3.6 mm, p < 0.001, respectively) and confirmed by computed tomographic (CT) (35.6 ± 5.1 mm vs. 30.8 ± 3.7 mm, p < 0.001, respectively). An increase in tubular ascending aorta size was associated with the presence of AAA by both 2D-TTE and CT (r = 0.40, p < 0.001 and r = 0.37, p < 0.001, respectively). The tubular ascending aorta (D diameter) size of ≥33 mm or ≥ 19 mm/m2 presented with 2–4 times more risk of AAA presence (OR 4.68, CI 2.18–10.25, p = 0.001 or OR 2.63, CI 1.21–5.62, p = 0.02, respectively). In addition, multiple logistic regression analysis identified tubular ascending aorta (OR 1.46, p < 0.001), age (OR 1.09, p = 0.013), gender (OR 0.12, p = 0.002), and LVESD (OR 1.24, p = 0.009) as independent risk factors of AAA presence.ConclusionsAn increased tubular ascending aortic diameter, measured by 2D-TTE, is associated with the presence of AAA. Routine 2D-TTE screening for silent AAA by means of ascending aorta analysis, may appear useful especially in older patients with a dilated tubular ascending aorta (≥33 mm).

The relationship between famine exposure during early life and ascending aorta dilatation in adults.

The relationship between exposure to famine in early life and the risk of ascending aorta dilatation (AAD) in adulthood is still unclear; therefore, we aimed to examine the association in the Chinese population. We investigated the data of 2598 adults who were born between 1952 and 1964 in Guangdong, China. All enrolled subjects were categorised into five groups: not exposed to famine, exposed during fetal period, and exposed during early, mid or late childhood. AAD was assessed by cardiac ultrasound. Multivariate logistic regression and interaction tests were performed to estimate the OR and CI on the association between famine exposure and AAD. There were 2598 (943 male, mean age 58·3 ± 3·68 years) participants were enrolled, and 270 (10·4 %) subjects with AAD. We found that famine exposure (OR = 2·266, 95 % CI 1·477, 3·477,P = 0·013) was associated with elevated AAD after adjusting for multiple confounders. In addition, compared with the non-exposed group, the adjusted OR for famine exposure during fetal period, early, mid or late childhood were 1·374 (95 % CI 0·794, 2·364, P = 0·251), 1·976 (95 % CI 1·243, 3·181, P = 0·004), 1·929 (95 % CI 1·237, 3·058, P = 0·004) and 2·227 (95 % CI 1·433, 3·524, P < 0·001), respectively. Subgroup analysis showed that the effect of famine exposure on the association with AAD was more pronounced in female, current smokers, people with BMI ≥ 24 kg/m2 and hypertensive patients. We observed that exposure to famine during early life was linked to AAD in adulthood.

Prognostic role of the ascending aorta dilatation in patients with arterial hypertension.

Ascending aorta (ASC) dilatation (AAD) is a common finding in arterial hypertension, affecting about 15% of hypertensive patients. AAD is associated with an increase in cardiac and vascular hypertension-related organ damage, but its prognostic role is unknown. The aim of the study was to evaluate the prognostic value of AAD as predictor of cardiovascular events in essential hypertensive patients. Recruited patients underwent two-dimensional transthoracic echocardiography from 2007 to 2013 and followed-up for cardiovascular events until November 2018 by phone call and hospital information system check. ASC diameter and AAD were defined using both absolute and scaled definitions. Four hundred and twenty-three hypertensive patients were included in our study. During a median follow-up of 7.4 years (interquartile range 5.6-9.1 years), 52 events were observed. After adjusting for age, sex and BSA, both ASC diameter and AAD definition, according to ARGO-SIIA project, resulted associated with a greater risk of cardiovascular event (both P < 0.010), even after adjusting for major confounders (both P < 0.010). Moreover, we observed that the assessment of ASC improves risk stratification compared with pulse wave velocity alone, and that in absence of AAD, sinus of valsalva dilatation lost any prognostic value (P = 0.262). ASC diameter and AAD are both associated with a greater risk of cardiovascular events. ASC should be assessed to optimize risk stratification in hypertensive patients and its dilatation may be considered as a surrogate for vascular organ damage.

Monocyte-to-HDL-cholesterol ratio is associated with Ascending Aorta Dilatation in Patients with Bicuspid Aortic Valve.

The importance of monocyte count-to-HDL-cholesterol ratio (MHR) in cardio- vascular diseases has been shown in various studies. Ascending aortic dilatation (AAD) is a common complication in the patients with bicuspid aortic valve. In this study, we aimed to investigate the relationship between MHR and the presence of aortic dilatation in the patients with bicuspid aortic valve. The study population included totally 347 patients with bicuspid aortic valve.169 patients with aortic dilatation (ascending aorta diameter ≥ 4.0 cm) and 178 patients with no aortic dilatation. Echocardiographic and laboratory measurement was done and compared between groups. The mean age of the participants was 44.7 ± 15.4 years and average ascending aorta diameter was 3.2 ± 0.3 cm in dilatation negative group and 4.4 ± 0.4 cm in positive group. MHR was significantly increased in in patients with aortic dilatation. MHR and uric acid level was independently associated with the presence of aortic dilatation in the patients with bicuspid aortic valve. We found a significant relationship between MHR and aortic dilatation in the patients with bicuspid aortic valve.

How common is aortic dilatation?

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Aortic dilatation is most commonly associated with hypertension, bicuspid aortic valve and connective tissue diseases such as Marfan’s. It is a precursor to life threatening complications such as rupture or dissection of the aorta. The current ESC Guidelines recommend surgical intervention once the aortic diameter is &amp;gt;50 mm in patients with Marfan syndrome (Ic) and &amp;gt;55 mm in patients with a bicuspid or normal aortic valve morphology (IIb). There is currently a lack of literature on the prevalence of aortic dilatation in the general or even hospital population although there is historical data suggesting the incidence of thoracic aortic aneurysm to be 5.9 cases per 100,000. Purpose The aim is to investigate the prevalence of aortic dilatation by echocardiography in our hospital population which may help lay the foundation for population studies and identify prognostic factors which may determine the time of surgical intervention. Methods We carried out a retrospective survey using the digital echocardiogram archive and the electronic patient record system at our hospital. This survey covered the period between 1st October 2016 and 1st November 2018. For randomisation purposes, all transthoracic echocardiograms (TTE) performed on every Thursday during this period were included. All patients with an echocardiographic report of aortic root or ascending aorta dilatation were enrolled. Other information including echocardiographic dimensions along with demographics and past medical history was collected. Results During this 24-month period, we analysed a total of 3019 TTEs. 209 patients (6.9%) were reported to have aortic dilatation. 137 (66%) were male and the median age was 67 years. The mean height and weight were 169cm and 80kg, respectively. A bicuspid aortic valve was confirmed in 10 (4.8%) patients. 132 (63%) patients had a history of hypertension. On echocardiogram, 75 (36%) patients had septal hypertrophy and 26 (12.4%) had a dilated left ventricle. Conclusion Our findings are unique and for the first time, to our knowledge, we report the echocardiographic prevalence of aortic dilatation in the hospital population (6.9%). It is a staggering 40-fold increase when compared to the the prevalence of aortic aneurysm, the most likely end point of aortic dilatation. Based on our figures, there would be at least 400 patients with a dilated aorta in a year in our hospital alone. The prevalence of bicuspid aortic valve in our cohort (4.8%) was nearly three times higher than the general population where it is quoted as 1-2%. Our study also emphasised the established link between hypertension and aortic dilatation with an increased frequency in our cohort (63%) compared to the global prevalence (31%). Given the devastating sequelae of aortic dilatation and its increased prevalence in our patient population, it will be very important to keep these patients under routine surveillance and particularly those with hypertension.